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37300913
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31958686
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36688857
|
Reduced memory precision in older age is associated with functional and structural differences in the angular gyrus.
|
A 7 Tesla fMRI investigation of human tinnitus percept in cortical and subcortical auditory areas.
|
Comparing the Results of Latissimus Dorsi Versus Teres Major Transfer in Children With Obstetric Brachial Plexus Injury and Residual Shoulder Sequelae.
|
Decreased fidelity of mnemonic representations plays a critical role in age-related episodic memory deficits, yet the brain mechanisms underlying such reductions remain unclear. Using functional and structural neuroimaging, we examined how changes in two key nodes of the posterior-medial network, the hippocampus and the angular gyrus (AG), might underpin loss of memory precision in older age. Healthy young and older adults completed a memory task that involved reconstructing object features on a continuous scale. Investigation of blood-oxygen-level-dependent (BOLD) activity during retrieval revealed an age-related reduction in activity reflecting successful recovery of object features in the hippocampus, whereas trial-wise modulation of BOLD signal by graded memory precision was diminished in the AG. Gray matter volume of the AG further predicted individual differences in memory precision in older age, beyond likelihood of successful retrieval. These findings provide converging evidence for a role of functional and structural integrity of the AG in constraining the fidelity of episodic remembering in older age, yielding new insights into parietal contributions to age-related episodic memory decline.</AbstractText
|
Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus.</AbstractText
|
Obstetric brachial plexus injury (OBPI) remains a fairly common problem in newborns despite the improved obstetric care. Children who do not show complete recovery often present with residual shoulder deformity of limited external rotation and abduction. Secondary interventions in the form of tendon transfer and soft tissue release are aimed at correcting the implicated muscular imbalance to restore shoulder function.</AbstractText The aim of this work was to compare the results of latissimus dorsi versus teres major tendon transfer in patients with OBPI with limited shoulder external rotation.</AbstractText This study included 40 patients admitted to El Hadara University Hospital with OBPI and limited shoulder abduction and external rotation aged between 1.5 and 4 years. Half of the patients had a latissimus dorsi transfer, and the other half, a teres major one. Children with limited preoperative passive external rotation in both groups required a subscapularis slide. Patients were evaluated preoperatively, at 6 months, and 12 months postoperatively using the Gilbert scale.</AbstractText Teres major tendon transfer showed better results in restoring limited shoulder abduction and external rotation than latissimus dorsi transfer. Limited shoulder internal rotation was the main complication occurring postoperatively. Loss of the last degree of internal rotation occurred in most patients who had subscapularis slide. Most patients regained functional midline abilities with physiotherapy and required no further interventions.</AbstractText Isolated teres major transfer has shown better results in improving the range of external rotation and abduction compared with isolated latissimus dorsi tendon transfer. Age of the patients did not affect the overall final improvement in shoulder range of motion. Limited internal rotation is the main complication postoperatively, which was prevalent in patients who required a subscapularis slide but was not statistically significant.</AbstractText
|
Reduced memory precision in older age is associated with functional and structural differences in the angular gyrus. Decreased fidelity of mnemonic representations plays a critical role in age-related episodic memory deficits, yet the brain mechanisms underlying such reductions remain unclear. Using functional and structural neuroimaging, we examined how changes in two key nodes of the posterior-medial network, the hippocampus and the angular gyrus (AG), might underpin loss of memory precision in older age. Healthy young and older adults completed a memory task that involved reconstructing object features on a continuous scale. Investigation of blood-oxygen-level-dependent (BOLD) activity during retrieval revealed an age-related reduction in activity reflecting successful recovery of object features in the hippocampus, whereas trial-wise modulation of BOLD signal by graded memory precision was diminished in the AG. Gray matter volume of the AG further predicted individual differences in memory precision in older age, beyond likelihood of successful retrieval. These findings provide converging evidence for a role of functional and structural integrity of the AG in constraining the fidelity of episodic remembering in older age, yielding new insights into parietal contributions to age-related episodic memory decline.</AbstractText
|
A 7 Tesla fMRI investigation of human tinnitus percept in cortical and subcortical auditory areas. Tinnitus is a clinical condition defined by hearing a sound in the absence of an objective source. Early experiments in animal models have suggested that tinnitus stems from an alteration of processing in the auditory system. However, translating these results to humans has proven challenging. One limiting factor has been the insufficient spatial resolution of non-invasive measurement techniques to investigate responses in subcortical auditory nuclei, like the inferior colliculus and the medial geniculate body (MGB). Here we employed ultra-high field functional magnetic resonance imaging (UHF-fMRI) at 7 Tesla to investigate the frequency-specific processing in sub-cortical and cortical regions in a cohort of six tinnitus patients and six hearing loss matched controls. We used task-based fMRI to perform tonotopic mapping and compared the magnitude and tuning of frequency-specific responses between the two groups. Additionally, we used resting-state fMRI to investigate the functional connectivity. Our results indicate frequency-unspecific reductions in the selectivity of frequency tuning that start at the level of the MGB and continue in the auditory cortex, as well as reduced thalamocortical and cortico-cortical connectivity with tinnitus. These findings suggest that tinnitus may be associated with reduced inhibition in the auditory pathway, potentially leading to increased neural noise and reduced functional connectivity. Moreover, these results indicate the relevance of high spatial resolution UHF-fMRI for the investigation of the role of sub-cortical auditory regions in tinnitus.</AbstractText
|
Comparing the Results of Latissimus Dorsi Versus Teres Major Transfer in Children With Obstetric Brachial Plexus Injury and Residual Shoulder Sequelae. Obstetric brachial plexus injury (OBPI) remains a fairly common problem in newborns despite the improved obstetric care. Children who do not show complete recovery often present with residual shoulder deformity of limited external rotation and abduction. Secondary interventions in the form of tendon transfer and soft tissue release are aimed at correcting the implicated muscular imbalance to restore shoulder function.</AbstractText The aim of this work was to compare the results of latissimus dorsi versus teres major tendon transfer in patients with OBPI with limited shoulder external rotation.</AbstractText This study included 40 patients admitted to El Hadara University Hospital with OBPI and limited shoulder abduction and external rotation aged between 1.5 and 4 years. Half of the patients had a latissimus dorsi transfer, and the other half, a teres major one. Children with limited preoperative passive external rotation in both groups required a subscapularis slide. Patients were evaluated preoperatively, at 6 months, and 12 months postoperatively using the Gilbert scale.</AbstractText Teres major tendon transfer showed better results in restoring limited shoulder abduction and external rotation than latissimus dorsi transfer. Limited shoulder internal rotation was the main complication occurring postoperatively. Loss of the last degree of internal rotation occurred in most patients who had subscapularis slide. Most patients regained functional midline abilities with physiotherapy and required no further interventions.</AbstractText Isolated teres major transfer has shown better results in improving the range of external rotation and abduction compared with isolated latissimus dorsi tendon transfer. Age of the patients did not affect the overall final improvement in shoulder range of motion. Limited internal rotation is the main complication postoperatively, which was prevalent in patients who required a subscapularis slide but was not statistically significant.</AbstractText
|
38186682
|
33853207
|
36810050
|
Liver decompensation after rapid weight loss from semaglutide in a patient with non-alcoholic steatohepatitis -associated cirrhosis.
|
Occult Hepatocellular Carcinoma Associated With Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients.
|
Genetic susceptibility and lifestyle modify the association of long-term air pollution exposure on major depressive disorder: a prospective study in UK Biobank.
|
There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonists such as semaglutide worldwide for weight loss and management of non-alcoholic steatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASH cirrhotic population. We report herein the first documented case of liver decompensation and need for liver transplant waitlisting in a patient with NASH-cirrhosis treated with semaglutide. Rapid weight loss led to the development of ascites and hepatic encephalopathy and an increase in the patients Model for Endstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritional supplementation was commenced and the semaglutide was stopped. Over the following months she regained her weight and her liver recompensated and her MELD-Na decreased to 13, allowing her to be delisted from the transplant waitlist. This case serves as a cautionary tale to clinicians using semaglutide in the cirrhotic population and highlights the need for more safety data in this patient group.</AbstractText
|
Transplant eligibility for hepatocellular carcinoma (HCC) is determined by the imaging identification of tumor burden within the Milan criteria. Transjugular intrahepatic portosystemic shunt(s) (TIPS) reduce portal hypertension but may impact HCC visualization. It was hypothesized that the presence of pretransplant TIPS would correlate with occult HCC and reduced survival. A single-center, retrospective, case control study was performed among liver transplant recipients with HCC (2000-2017). The primary endpoint was occult disease on explant pathology. Backward stepwise logistic regression was performed. The secondary endpoints disease-free survival (DFS) and overall survival (OS) were evaluated with Kaplan-Meier curves and Cox regression analysis. Of 640 patients, 40 had TIPS and more frequently exhibited occult disease (80.0% versus 43.1%; P < 0.001; odds ratio [OR], 4.16; P < 0.001). Portal vein thrombosis (PVT) similarly correlated with occult disease (OR, 1.97; P = 0.02). Explant tumor burden was equivalent between TIPS subgroups; accordingly, TIPS status was not independently associated with reduced DFS or OS. However, exceeding the Milan criteria was associated with reduced DFS (hazard ratio, 3.21; P = 0.001), and TIPS status in patients with a single suspected lesion (n = 316) independently correlated with explant tumor burdens beyond these criteria (OR, 13.47; P = 0.001). TIPS on pretransplant imaging are associated with occult HCC on explant pathology. Comparable occult disease findings in patients with PVT suggest that the mechanism may involve altered hepatic perfusion, obscuring imaging diagnosis. TIPS are not independently associated with reduced DFS or OS but are associated with exceeding the Milan criteria for patients with a single suspected lesion. The presence of TIPS may necessitate a higher index of suspicion for occult HCC.</AbstractText
|
Evidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations.</AbstractText This population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM<sub During a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM<sub Long-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health.</AbstractText
|
Liver decompensation after rapid weight loss from semaglutide in a patient with non-alcoholic steatohepatitis -associated cirrhosis. There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonists such as semaglutide worldwide for weight loss and management of non-alcoholic steatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASH cirrhotic population. We report herein the first documented case of liver decompensation and need for liver transplant waitlisting in a patient with NASH-cirrhosis treated with semaglutide. Rapid weight loss led to the development of ascites and hepatic encephalopathy and an increase in the patients Model for Endstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritional supplementation was commenced and the semaglutide was stopped. Over the following months she regained her weight and her liver recompensated and her MELD-Na decreased to 13, allowing her to be delisted from the transplant waitlist. This case serves as a cautionary tale to clinicians using semaglutide in the cirrhotic population and highlights the need for more safety data in this patient group.</AbstractText
|
Occult Hepatocellular Carcinoma Associated With Transjugular Intrahepatic Portosystemic Shunts in Liver Transplant Recipients. Transplant eligibility for hepatocellular carcinoma (HCC) is determined by the imaging identification of tumor burden within the Milan criteria. Transjugular intrahepatic portosystemic shunt(s) (TIPS) reduce portal hypertension but may impact HCC visualization. It was hypothesized that the presence of pretransplant TIPS would correlate with occult HCC and reduced survival. A single-center, retrospective, case control study was performed among liver transplant recipients with HCC (2000-2017). The primary endpoint was occult disease on explant pathology. Backward stepwise logistic regression was performed. The secondary endpoints disease-free survival (DFS) and overall survival (OS) were evaluated with Kaplan-Meier curves and Cox regression analysis. Of 640 patients, 40 had TIPS and more frequently exhibited occult disease (80.0% versus 43.1%; P < 0.001; odds ratio [OR], 4.16; P < 0.001). Portal vein thrombosis (PVT) similarly correlated with occult disease (OR, 1.97; P = 0.02). Explant tumor burden was equivalent between TIPS subgroups; accordingly, TIPS status was not independently associated with reduced DFS or OS. However, exceeding the Milan criteria was associated with reduced DFS (hazard ratio, 3.21; P = 0.001), and TIPS status in patients with a single suspected lesion (n = 316) independently correlated with explant tumor burdens beyond these criteria (OR, 13.47; P = 0.001). TIPS on pretransplant imaging are associated with occult HCC on explant pathology. Comparable occult disease findings in patients with PVT suggest that the mechanism may involve altered hepatic perfusion, obscuring imaging diagnosis. TIPS are not independently associated with reduced DFS or OS but are associated with exceeding the Milan criteria for patients with a single suspected lesion. The presence of TIPS may necessitate a higher index of suspicion for occult HCC.</AbstractText
|
Genetic susceptibility and lifestyle modify the association of long-term air pollution exposure on major depressive disorder: a prospective study in UK Biobank. Evidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations.</AbstractText This population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM<sub During a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM<sub Long-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health.</AbstractText
|
36086126
|
23302471
|
36110429
|
Rapid MR Scanner Independent B1 Field Measurement System for Phased Arrays.
|
Patient-induced susceptibility effect on geometric distortion of clinical brain MRI for radiation treatment planning on a 3T scanner.
|
Alzheimer's Disease Polygenic Risk Score Is Not Associated With Cognitive Decline Among Older Adults With Type 2 Diabetes.
|
This paper demonstrates a rapid B1 field benchtop measurement system that is independent of an MR scanner and network analyzer. This system can be used to obtain radiofrequency (B1 field) strength distribution plots of multiple 2D slices (with an extension to 3D) of a liquid cylindrical phantom for multi-element phased arrays used in MRI. The system can be used in three modes- element, phased array, and multiple fixed point pattern measurement. These modes are demonstrated for a 7T 1H eight-channel dipole array and a corn-syrup based phantom. The system can measure complex phase and amplitude measurements from up to 8 elements in the first mode one or 8 different phase settings in the second mode at a rate of approximately 37 positions per minute, allowing a full 2D B1 mapping for 1303 points in 33.05 minutes. The scan patterns obtained using this setup are compared to the ones obtained using an HP network analyzer and simulations. This work can be extended to measure the E field, SAR and upon increasing the speed of measurement, could be used for applications such as Transmit SENSE. Clinical Relevance- This work benefits a faster and more widely accessible measurement system for phased array antennas for MRI. As phased arrays are becoming very important in MRI, the ability to assess individual element performance more rapidly and B1 shimming performance is important to aid in their further development.</AbstractText
|
Concerns about the geometric accuracy of MRI in radiation therapy (RT) have been present since its invention. Although modern scanners typically have system levels of geometric accuracy that meet requirements of RT, subject-specific distortion is variable, and methods to in vivo assess and control patient-induced geometric distortion are not yet resolved. This study investigated the nature and magnitude of the subject-induced susceptibility effect on geometric distortions in clinical brain MRI, and tested the feasibility of in vivo quality control using field inhomogeneity mapping. For 19 consecutive patients scanned on a dedicated 3T MR scanner, B0 field inhomogeneity maps were acquired and analyzed to determine subject-induced distortions. For 3D T1 weighted images frequency-encoded with a bandwidth of 180 Hz/pixel, 86.9% of the estimated displacements were <0.5 mm, 97.4% <1 mm, and only 0.1% of displacements > 2 mm. The maximum displacement was <4 mm. The greatest distortions were observed at the interfaces with air at the sinuses. Displacements decayed to less than 1 mm over a distance of 8 mm. Metal surgical wires generated smaller distortions, with an averaged maximum displacement of 0.76 mm. Repeat acquisition of the field maps in 17 patients revealed a within-subject standard deviation of 0.25 ppm, equivalent to 0.22 mm displacement in the frequency-encoding direction in the 3D T1 weighted images. Susceptibility-induced voxel displacements in the brain are generally small, but should be monitored for precision RT. These effects are manageable at 3T and lower fields, and the methods applied can be used to monitor for potential local errors in individual patients, as well as to correct for local distortions as needed.</AbstractText
|
Multiple risk loci for late-onset Alzheimer's disease (LOAD) have been identified. Type 2 diabetes (T2D) is a risk factor for cognitive decline, dementia and Alzheimer's disease (AD). We investigated the association of polygenic risk score (PRS) for LOAD with overall cognitive functioning and longitudinal decline, among older adults with T2D.</AbstractText The study included 1046 Jewish participants from the Israel Diabetes and Cognitive Decline (IDCD) study, aged ≥ 65 years, diagnosed with T2D, and cognitively normal at baseline. The PRS included variants from 26 LOAD associated loci (at genome-wide significance level), and was calculated with and without <i The PRS was not significantly associated with overall functioning or decline in global cognition or any of the specific cognitive domains. Similarly, following correction for multiple testing, there was no association with Aβ burden and other brain imaging phenotypes.</AbstractText Our results suggest that the cumulative effect of LOAD susceptibility loci is not associated with a greater rate of cognitive decline in older adults with T2D, and other pathways may underlie this link.</AbstractText
|
Rapid MR Scanner Independent B1 Field Measurement System for Phased Arrays. This paper demonstrates a rapid B1 field benchtop measurement system that is independent of an MR scanner and network analyzer. This system can be used to obtain radiofrequency (B1 field) strength distribution plots of multiple 2D slices (with an extension to 3D) of a liquid cylindrical phantom for multi-element phased arrays used in MRI. The system can be used in three modes- element, phased array, and multiple fixed point pattern measurement. These modes are demonstrated for a 7T 1H eight-channel dipole array and a corn-syrup based phantom. The system can measure complex phase and amplitude measurements from up to 8 elements in the first mode one or 8 different phase settings in the second mode at a rate of approximately 37 positions per minute, allowing a full 2D B1 mapping for 1303 points in 33.05 minutes. The scan patterns obtained using this setup are compared to the ones obtained using an HP network analyzer and simulations. This work can be extended to measure the E field, SAR and upon increasing the speed of measurement, could be used for applications such as Transmit SENSE. Clinical Relevance- This work benefits a faster and more widely accessible measurement system for phased array antennas for MRI. As phased arrays are becoming very important in MRI, the ability to assess individual element performance more rapidly and B1 shimming performance is important to aid in their further development.</AbstractText
|
Patient-induced susceptibility effect on geometric distortion of clinical brain MRI for radiation treatment planning on a 3T scanner. Concerns about the geometric accuracy of MRI in radiation therapy (RT) have been present since its invention. Although modern scanners typically have system levels of geometric accuracy that meet requirements of RT, subject-specific distortion is variable, and methods to in vivo assess and control patient-induced geometric distortion are not yet resolved. This study investigated the nature and magnitude of the subject-induced susceptibility effect on geometric distortions in clinical brain MRI, and tested the feasibility of in vivo quality control using field inhomogeneity mapping. For 19 consecutive patients scanned on a dedicated 3T MR scanner, B0 field inhomogeneity maps were acquired and analyzed to determine subject-induced distortions. For 3D T1 weighted images frequency-encoded with a bandwidth of 180 Hz/pixel, 86.9% of the estimated displacements were <0.5 mm, 97.4% <1 mm, and only 0.1% of displacements > 2 mm. The maximum displacement was <4 mm. The greatest distortions were observed at the interfaces with air at the sinuses. Displacements decayed to less than 1 mm over a distance of 8 mm. Metal surgical wires generated smaller distortions, with an averaged maximum displacement of 0.76 mm. Repeat acquisition of the field maps in 17 patients revealed a within-subject standard deviation of 0.25 ppm, equivalent to 0.22 mm displacement in the frequency-encoding direction in the 3D T1 weighted images. Susceptibility-induced voxel displacements in the brain are generally small, but should be monitored for precision RT. These effects are manageable at 3T and lower fields, and the methods applied can be used to monitor for potential local errors in individual patients, as well as to correct for local distortions as needed.</AbstractText
|
Alzheimer's Disease Polygenic Risk Score Is Not Associated With Cognitive Decline Among Older Adults With Type 2 Diabetes. Multiple risk loci for late-onset Alzheimer's disease (LOAD) have been identified. Type 2 diabetes (T2D) is a risk factor for cognitive decline, dementia and Alzheimer's disease (AD). We investigated the association of polygenic risk score (PRS) for LOAD with overall cognitive functioning and longitudinal decline, among older adults with T2D.</AbstractText The study included 1046 Jewish participants from the Israel Diabetes and Cognitive Decline (IDCD) study, aged ≥ 65 years, diagnosed with T2D, and cognitively normal at baseline. The PRS included variants from 26 LOAD associated loci (at genome-wide significance level), and was calculated with and without <i The PRS was not significantly associated with overall functioning or decline in global cognition or any of the specific cognitive domains. Similarly, following correction for multiple testing, there was no association with Aβ burden and other brain imaging phenotypes.</AbstractText Our results suggest that the cumulative effect of LOAD susceptibility loci is not associated with a greater rate of cognitive decline in older adults with T2D, and other pathways may underlie this link.</AbstractText
|
34697990
|
26974435
|
35008842
|
Neural correlates of sex differences in communicative gestures and speech comprehension: A preliminary study.
|
Seeking Optimal Region-Of-Interest (ROI) Single-Value Summary Measures for fMRI Studies in Imaging Genetics.
|
Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders.
|
The goal of this study was to investigate whether the semantic processing of the audiovisual combination of communicative gestures with speech differs between men and women. We recorded event-related brain potentials in women and men during the presentation of communicative gestures that were either congruent or incongruent with the speech.Our results showed that incongruent gestures elicited an N400 effect over frontal sites compared to congruent ones in both groups. Moreover, the females showed an earlier N2 response to incongruent stimuli than congruent ones, while larger sustained negativity and late positivity in response to incongruent stimuli was observed only in males. These results suggest that women rapidly recognize and process audiovisual combinations of communicative gestures and speech (as early as 300 ms) whereas men analyze them at the later stages of the process.</AbstractText
|
A data-driven hypothesis-free genome-wide association (GWA) approach in imaging genetics studies allows screening the entire genome to discover novel genes that modulate brain structure, chemistry, and function. However, a whole brain voxel-wise analysis approach in such genome-wide based imaging genetic studies can be computationally intense and also likely has low statistical power since a stringent multiple comparisons correction is needed for searching over the entire genome and brain. In imaging genetics with functional magnetic resonance imaging (fMRI) phenotypes, since many experimental paradigms activate focal regions that can be pre-specified based on a priori knowledge, reducing the voxel-wise search to single-value summary measures within a priori ROIs could prove efficient and promising. The goal of this investigation is to evaluate the sensitivity and reliability of different single-value ROI summary measures and provide guidance in future work. Four different fMRI databases were tested and comparisons across different groups (patients with schizophrenia, their siblings, vs. normal control subjects; across genotype groups) were conducted. Our results show that four of these measures, particularly those that represent values from the top most-activated voxels within an ROI are more powerful at reliably detecting group differences and generating greater effect sizes than the others.</AbstractText
|
Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.</AbstractText
|
Neural correlates of sex differences in communicative gestures and speech comprehension: A preliminary study. The goal of this study was to investigate whether the semantic processing of the audiovisual combination of communicative gestures with speech differs between men and women. We recorded event-related brain potentials in women and men during the presentation of communicative gestures that were either congruent or incongruent with the speech.Our results showed that incongruent gestures elicited an N400 effect over frontal sites compared to congruent ones in both groups. Moreover, the females showed an earlier N2 response to incongruent stimuli than congruent ones, while larger sustained negativity and late positivity in response to incongruent stimuli was observed only in males. These results suggest that women rapidly recognize and process audiovisual combinations of communicative gestures and speech (as early as 300 ms) whereas men analyze them at the later stages of the process.</AbstractText
|
Seeking Optimal Region-Of-Interest (ROI) Single-Value Summary Measures for fMRI Studies in Imaging Genetics. A data-driven hypothesis-free genome-wide association (GWA) approach in imaging genetics studies allows screening the entire genome to discover novel genes that modulate brain structure, chemistry, and function. However, a whole brain voxel-wise analysis approach in such genome-wide based imaging genetic studies can be computationally intense and also likely has low statistical power since a stringent multiple comparisons correction is needed for searching over the entire genome and brain. In imaging genetics with functional magnetic resonance imaging (fMRI) phenotypes, since many experimental paradigms activate focal regions that can be pre-specified based on a priori knowledge, reducing the voxel-wise search to single-value summary measures within a priori ROIs could prove efficient and promising. The goal of this investigation is to evaluate the sensitivity and reliability of different single-value ROI summary measures and provide guidance in future work. Four different fMRI databases were tested and comparisons across different groups (patients with schizophrenia, their siblings, vs. normal control subjects; across genotype groups) were conducted. Our results show that four of these measures, particularly those that represent values from the top most-activated voxels within an ROI are more powerful at reliably detecting group differences and generating greater effect sizes than the others.</AbstractText
|
Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders. Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.</AbstractText
|
20657809
|
17654729
|
20488187
|
Dynamic Shimming of the Human Brain at 7 Tesla.
|
Cardiac MRI in mice at 9.4 Tesla with a transmit-receive surface coil and a cardiac-tailored intensity-correction algorithm.
|
Evidence for the possible existence of a second polarization-vision pathway in the locust brain.
|
Dynamic shim updating (DSU) of the zero- to second-order spherical harmonic field terms has previously been shown to improve the magnetic field homogeneity in the human brain at 4 Tesla. The increased magnetic field inhomogeneity at 7 Tesla can benefit from inclusion of third-order shims during DSU. However, pulsed higher-order shims can generate a multitude of temporally varying magnetic fields arising from eddy-currents that can strongly degrade the magnetic field homogeneity.The first realization of zero- to third-order DSU with full preemphasis and B(0) compensation enabled improved shimming of the human brain at 7 Tesla not only in comparison with global (i.e. static) shimming, but also when compared to state-of-the-art zero- to second-order DSU. Temporal shim-to-shim interactions were measured for each of the 16 zero- to third-order shim coils along 1D column projections on a spherical phantom. The decomposition into up to 3 exponentials allowed full preemphasis and B(0) compensation of all 16 shims covering 67 potential shim-to-shim interactions. Despite the significant improvements achievable with DSU, the magnetic field homogeneity is still not perfect even when updating all zero- through third-order shims. This is because DSU is still inherently limited by the shallowness of the low order spherical harmonic fields and their inability to compensate the higher-order inhomogeneities encountered in vivo. However, DSU maximizes the usefulness of conventional shim coil systems and provides magnetic field homogeneity that is adequate for a wide range of applications.</AbstractText
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To evaluate the use of a transmit-receive surface (TRS) coil and a cardiac-tailored intensity-correction algorithm for cardiac MRI in mice at 9.4 Tesla (9.4T).</AbstractText Fast low-angle shot (FLASH) cines, with and without delays alternating with nutations for tailored excitation (DANTE) tagging, were acquired in 13 mice. An intensity-correction algorithm was developed to compensate for the sensitivity profile of the surface coil, and was tailored to account for the unique distribution of noise and flow artifacts in cardiac MR images.</AbstractText Image quality was extremely high and allowed fine structures such as trabeculations, valve cusps, and coronary arteries to be clearly visualized. The tag lines created with the surface coil were also sharp and clearly visible. Application of the intensity-correction algorithm improved signal intensity, tissue contrast, and image quality even further. Importantly, the cardiac-tailored properties of the correction algorithm prevented noise and flow artifacts from being significantly amplified.</AbstractText The feasibility and value of cardiac MRI in mice with a TRS coil has been demonstrated. In addition, a cardiac-tailored intensity-correction algorithm has been developed and shown to improve image quality even further. The use of these techniques could produce significant potential benefits over a broad range of scanners, coil configurations, and field strengths.</AbstractText
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For spatial orientation and navigation, many insects derive compass information from the polarization pattern of the blue sky. The desert locust Schistocerca gregaria detects polarized light with a specialized dorsal rim area of its compound eye. In the locust brain, polarized-light signals are passed through the anterior optic tract and tubercle to the central complex which most likely serves as an internal sky compass. Here, we suggest that neurons of a second visual pathway, via the accessory medulla and posterior optic tubercle, also provide polarization information to the central complex. Intracellular recordings show that two types of neuron in this posterior pathway are sensitive to polarized light. One cell type connects the dorsal rim area of the medulla with the medulla and accessory medulla, and a second type connects the bilaterally paired posterior optic tubercles. Given the evidence for a role of the accessory medulla as the master clock controlling circadian changes in behavioral activity in flies and cockroaches, our data open the possibility that time-compensated polarized-light signals may reach the central complex via this pathway for time-compensated sky-compass navigation.</AbstractText
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Dynamic Shimming of the Human Brain at 7 Tesla. Dynamic shim updating (DSU) of the zero- to second-order spherical harmonic field terms has previously been shown to improve the magnetic field homogeneity in the human brain at 4 Tesla. The increased magnetic field inhomogeneity at 7 Tesla can benefit from inclusion of third-order shims during DSU. However, pulsed higher-order shims can generate a multitude of temporally varying magnetic fields arising from eddy-currents that can strongly degrade the magnetic field homogeneity.The first realization of zero- to third-order DSU with full preemphasis and B(0) compensation enabled improved shimming of the human brain at 7 Tesla not only in comparison with global (i.e. static) shimming, but also when compared to state-of-the-art zero- to second-order DSU. Temporal shim-to-shim interactions were measured for each of the 16 zero- to third-order shim coils along 1D column projections on a spherical phantom. The decomposition into up to 3 exponentials allowed full preemphasis and B(0) compensation of all 16 shims covering 67 potential shim-to-shim interactions. Despite the significant improvements achievable with DSU, the magnetic field homogeneity is still not perfect even when updating all zero- through third-order shims. This is because DSU is still inherently limited by the shallowness of the low order spherical harmonic fields and their inability to compensate the higher-order inhomogeneities encountered in vivo. However, DSU maximizes the usefulness of conventional shim coil systems and provides magnetic field homogeneity that is adequate for a wide range of applications.</AbstractText
|
Cardiac MRI in mice at 9.4 Tesla with a transmit-receive surface coil and a cardiac-tailored intensity-correction algorithm. To evaluate the use of a transmit-receive surface (TRS) coil and a cardiac-tailored intensity-correction algorithm for cardiac MRI in mice at 9.4 Tesla (9.4T).</AbstractText Fast low-angle shot (FLASH) cines, with and without delays alternating with nutations for tailored excitation (DANTE) tagging, were acquired in 13 mice. An intensity-correction algorithm was developed to compensate for the sensitivity profile of the surface coil, and was tailored to account for the unique distribution of noise and flow artifacts in cardiac MR images.</AbstractText Image quality was extremely high and allowed fine structures such as trabeculations, valve cusps, and coronary arteries to be clearly visualized. The tag lines created with the surface coil were also sharp and clearly visible. Application of the intensity-correction algorithm improved signal intensity, tissue contrast, and image quality even further. Importantly, the cardiac-tailored properties of the correction algorithm prevented noise and flow artifacts from being significantly amplified.</AbstractText The feasibility and value of cardiac MRI in mice with a TRS coil has been demonstrated. In addition, a cardiac-tailored intensity-correction algorithm has been developed and shown to improve image quality even further. The use of these techniques could produce significant potential benefits over a broad range of scanners, coil configurations, and field strengths.</AbstractText
|
Evidence for the possible existence of a second polarization-vision pathway in the locust brain. For spatial orientation and navigation, many insects derive compass information from the polarization pattern of the blue sky. The desert locust Schistocerca gregaria detects polarized light with a specialized dorsal rim area of its compound eye. In the locust brain, polarized-light signals are passed through the anterior optic tract and tubercle to the central complex which most likely serves as an internal sky compass. Here, we suggest that neurons of a second visual pathway, via the accessory medulla and posterior optic tubercle, also provide polarization information to the central complex. Intracellular recordings show that two types of neuron in this posterior pathway are sensitive to polarized light. One cell type connects the dorsal rim area of the medulla with the medulla and accessory medulla, and a second type connects the bilaterally paired posterior optic tubercles. Given the evidence for a role of the accessory medulla as the master clock controlling circadian changes in behavioral activity in flies and cockroaches, our data open the possibility that time-compensated polarized-light signals may reach the central complex via this pathway for time-compensated sky-compass navigation.</AbstractText
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38178693
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34589757
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38675647
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Comparison of head direction cell firing characteristics across thalamo-parahippocampal circuitry.
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The potential role of glial cells in driving the prion-like transcellular propagation of tau in tauopathies.
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Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile.
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Head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction, are widely thought to underlie an animal's sense of spatial orientation and have been identified in several limbic brain regions. Robust HD cell firing is observed throughout the thalamo-parahippocampal system, although recent studies report that parahippocampal HD cells exhibit distinct firing properties, including conjunctive aspects with other spatial parameters, which suggest they play a specialized role in spatial processing. Few studies, however, have quantified these apparent differences. Here, we performed a comparative assessment of HD cell firing characteristics across the anterior dorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal (MEC), and postrhinal (POR) cortices. We report that HD cells with a high degree of directional specificity were observed in all five brain regions, but ADN HD cells display greater sharpness and stability in their preferred directions, and greater anticipation of future headings compared to parahippocampal regions. Additional analysis indicated that POR HD cells were more coarsely modulated by other spatial parameters compared to PoS, PaS, and MEC. Finally, our analyses indicated that the sharpness of HD tuning decreased as a function of laminar position and conjunctive coding within the PoS, PaS, and MEC, with cells in the superficial layers along with conjunctive firing properties showing less robust directional tuning. The results are discussed in relation to theories of functional organization of HD cell tuning in thalamo-parahippocampal circuitry.</AbstractText
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Dementia is one of the leading causes of death worldwide, with tauopathies, a class of diseases defined by pathology associated with the microtubule-enriched protein, tau, as the major contributor. Although tauopathies, such as Alzheimer's disease and Frontotemporal dementia, are common amongst the ageing population, current effective treatment options are scarce, primarily due to the incomplete understanding of disease pathogenesis. The mechanisms via which aggregated forms of tau are able to propagate from one anatomical area to another to cause disease spread and progression is yet unknown. The prion-like hypothesis of tau propagation proposes that tau can propagate along neighbouring anatomical areas in a similar manner to prion proteins in prion diseases, such as Creutzfeldt-Jacob disease. This hypothesis has been supported by a plethora of studies that note the ability of tau to be actively secreted by neurons, propagated and internalised by neighbouring neuronal cells, causing disease spread. Surfacing research suggests a role of reactive astrocytes and microglia in early pre-clinical stages of tauopathy through their inflammatory actions. Furthermore, both glial types are able to internalise and secrete tau from the extracellular space, suggesting a potential role in tau propagation; although understanding the physiological mechanisms by which this can occur remains poorly understood. This review will discuss the current literature around the prion-like propagation of tau, with particular emphasis on glial-mediated neuroinflammation and the contribution it may play in this propagation process.</AbstractText
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This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (M<sub
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Comparison of head direction cell firing characteristics across thalamo-parahippocampal circuitry. Head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction, are widely thought to underlie an animal's sense of spatial orientation and have been identified in several limbic brain regions. Robust HD cell firing is observed throughout the thalamo-parahippocampal system, although recent studies report that parahippocampal HD cells exhibit distinct firing properties, including conjunctive aspects with other spatial parameters, which suggest they play a specialized role in spatial processing. Few studies, however, have quantified these apparent differences. Here, we performed a comparative assessment of HD cell firing characteristics across the anterior dorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal (MEC), and postrhinal (POR) cortices. We report that HD cells with a high degree of directional specificity were observed in all five brain regions, but ADN HD cells display greater sharpness and stability in their preferred directions, and greater anticipation of future headings compared to parahippocampal regions. Additional analysis indicated that POR HD cells were more coarsely modulated by other spatial parameters compared to PoS, PaS, and MEC. Finally, our analyses indicated that the sharpness of HD tuning decreased as a function of laminar position and conjunctive coding within the PoS, PaS, and MEC, with cells in the superficial layers along with conjunctive firing properties showing less robust directional tuning. The results are discussed in relation to theories of functional organization of HD cell tuning in thalamo-parahippocampal circuitry.</AbstractText
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The potential role of glial cells in driving the prion-like transcellular propagation of tau in tauopathies. Dementia is one of the leading causes of death worldwide, with tauopathies, a class of diseases defined by pathology associated with the microtubule-enriched protein, tau, as the major contributor. Although tauopathies, such as Alzheimer's disease and Frontotemporal dementia, are common amongst the ageing population, current effective treatment options are scarce, primarily due to the incomplete understanding of disease pathogenesis. The mechanisms via which aggregated forms of tau are able to propagate from one anatomical area to another to cause disease spread and progression is yet unknown. The prion-like hypothesis of tau propagation proposes that tau can propagate along neighbouring anatomical areas in a similar manner to prion proteins in prion diseases, such as Creutzfeldt-Jacob disease. This hypothesis has been supported by a plethora of studies that note the ability of tau to be actively secreted by neurons, propagated and internalised by neighbouring neuronal cells, causing disease spread. Surfacing research suggests a role of reactive astrocytes and microglia in early pre-clinical stages of tauopathy through their inflammatory actions. Furthermore, both glial types are able to internalise and secrete tau from the extracellular space, suggesting a potential role in tau propagation; although understanding the physiological mechanisms by which this can occur remains poorly understood. This review will discuss the current literature around the prion-like propagation of tau, with particular emphasis on glial-mediated neuroinflammation and the contribution it may play in this propagation process.</AbstractText
|
Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile. This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (M<sub
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37720236
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36944163
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37550815
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Exploring cognitive individuality and the underlying creativity in statistical learning and phase entrainment.
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Effects of Acute Stress on Rigid Learning, Flexible Learning, and Value-Based Decision-Making in Spatial Navigation.
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Supramaximal Resection for Glioblastoma: Redefining the Extent of Resection Criteria and Its Impact on Survival.
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Statistical learning starts at an early age and is intimately linked to brain development and the emergence of individuality. Through such a long period of statistical learning, the brain updates and constructs statistical models, with the model's individuality changing based on the type and degree of stimulation received. However, the detailed mechanisms underlying this process are unknown. This paper argues three main points of statistical learning, including 1) cognitive individuality based on "<i
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The current study investigated how stress affects value-based decision-making during spatial navigation and different types of learning underlying decisions. Eighty-two adult participants (42 females) first learned to find object locations in a virtual environment from a fixed starting location (rigid learning) and then to find the same objects from unpredictable starting locations (flexible learning). Participants then decided whether to reach goal objects from the fixed or unpredictable starting location. We found that stress impairs rigid learning in females, and it does not impair, and even improves, flexible learning when performance with rigid learning is controlled for. Critically, examining how earlier learning influences subsequent decision-making using computational models, we found that stress reduces memory integration, making participants more likely to focus on recent memory and less likely to integrate information from other sources. Collectively, our results show how stress impacts different memory systems and the communication between memory and decision-making.</AbstractText
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Glioblastomas (GBMs) are the most common and aggressive primary brain tumors, and despite advances in treatment, prognosis remains poor. The extent of resection has been widely recognized as a key factor affecting survival outcomes in GBM patients. The surgical principle of "maximal safe resection" has been widely applied to balance tumor removal and neurological function preservation. Historically, T1-contrast enhanced (T1CE) extent of resection has been the focus of research; however, the "supramaximal resection" concept has emerged, advocating for even greater tumor resection while maintaining neurological function. Recent studies have demonstrated potential survival benefits associated with resection beyond T1CE extent in GBMs. This review explores the developing consensus and newly established criteria for "supramaximal resection" in GBMs, with a focus on T2-extent of resection. Systematic reviews and meta-analyses on supramaximal resection are summarized, and the Response Assessment in Neuro-Oncology (RANO) resect group classification for extent of resection is introduced. The evolving understanding of the role of supramaximal resection in GBMs may lead to improved patient outcomes and more objective criteria for evaluating the extent of tumor resection.</AbstractText
|
Exploring cognitive individuality and the underlying creativity in statistical learning and phase entrainment. Statistical learning starts at an early age and is intimately linked to brain development and the emergence of individuality. Through such a long period of statistical learning, the brain updates and constructs statistical models, with the model's individuality changing based on the type and degree of stimulation received. However, the detailed mechanisms underlying this process are unknown. This paper argues three main points of statistical learning, including 1) cognitive individuality based on "<i
|
Effects of Acute Stress on Rigid Learning, Flexible Learning, and Value-Based Decision-Making in Spatial Navigation. The current study investigated how stress affects value-based decision-making during spatial navigation and different types of learning underlying decisions. Eighty-two adult participants (42 females) first learned to find object locations in a virtual environment from a fixed starting location (rigid learning) and then to find the same objects from unpredictable starting locations (flexible learning). Participants then decided whether to reach goal objects from the fixed or unpredictable starting location. We found that stress impairs rigid learning in females, and it does not impair, and even improves, flexible learning when performance with rigid learning is controlled for. Critically, examining how earlier learning influences subsequent decision-making using computational models, we found that stress reduces memory integration, making participants more likely to focus on recent memory and less likely to integrate information from other sources. Collectively, our results show how stress impacts different memory systems and the communication between memory and decision-making.</AbstractText
|
Supramaximal Resection for Glioblastoma: Redefining the Extent of Resection Criteria and Its Impact on Survival. Glioblastomas (GBMs) are the most common and aggressive primary brain tumors, and despite advances in treatment, prognosis remains poor. The extent of resection has been widely recognized as a key factor affecting survival outcomes in GBM patients. The surgical principle of "maximal safe resection" has been widely applied to balance tumor removal and neurological function preservation. Historically, T1-contrast enhanced (T1CE) extent of resection has been the focus of research; however, the "supramaximal resection" concept has emerged, advocating for even greater tumor resection while maintaining neurological function. Recent studies have demonstrated potential survival benefits associated with resection beyond T1CE extent in GBMs. This review explores the developing consensus and newly established criteria for "supramaximal resection" in GBMs, with a focus on T2-extent of resection. Systematic reviews and meta-analyses on supramaximal resection are summarized, and the Response Assessment in Neuro-Oncology (RANO) resect group classification for extent of resection is introduced. The evolving understanding of the role of supramaximal resection in GBMs may lead to improved patient outcomes and more objective criteria for evaluating the extent of tumor resection.</AbstractText
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37517356
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34290601
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36349505
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Increased neural variability in adolescents with ADHD symptomatology: Evidence from a single-trial EEG study.
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Evidence for a Specific Association Between Sustained Attention and Gait Speed in Middle-to-Older-Aged Adults.
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Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.
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Increased intrasubject variability of reaction time (RT) refers to inconsistency in an individual's speed of responding to a task. This increased variability has been suggested as a fundamental feature of attention deficit hyperactivity disorder (ADHD), however, its neural sources are still unclear. In this study, we aimed to examine whether such inconsistency at the behavioral level would be accompanied by inconsistency at the neural level; and whether different types of neural and behavioral variability would be related to ADHD symptomatology. We recorded electroencephalogram (EEG) data from 62 adolescents, who were part of a prospective longitudinal study on the development of ADHD. We examined trial-by-trial neural variability in response to visual stimuli in two cognitive tasks. Adolescents with high ADHD symptomatology exhibited an increased neural variability before the presentation of the stimulus, but when presented with a visual stimulus, this variability decreased to a level that was similar to that exhibited by participants with low ADHD symptomatology. In contrast with our prediction, neural variability was unrelated to the magnitude of behavioral variability. Our findings suggest that adolescents with higher symptoms are characterized by increased neural variability before the stimulation, which might reflect a difficulty in alertness to the forthcoming stimulus; but this increased neural variability does not seem to account for their RT variability.</AbstractText
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Although cognitive decline has previously been associated with mobility limitations and frailty, the relationship between sustained attention and gait speed is incompletely characterized. To better quantify the specificity of the sustained attention and gait speed association, we examined the extent to which this relationship is unique rather than accounted for by executive functioning and physical health characteristics. 58 middle-to-older-aged community-dwelling adults without overt evidence of cognitive impairment (45-90 years old; 21 females) participated in the study. Each participant completed a 4-meter gait speed assessment and validated neuropsychological tests to examine various domains of executive functioning including working memory (i.e., Digit Span), inhibitory control (i.e., D-KEFS Color-Word Interference), and task switching (i.e., D-KEFS Number/Letter Switching). Multiple physical and vascular risk factors were also evaluated. Sustained attention was assessed using the gradual onset continuous performance task (gradCPT), a well-validated go/no-go sustained attention task. A series of linear regression models were used to examine how different aspects of cognition, including sustained attention and traditional measures of executive functioning, related to gait speed while controlling for a variety of physical and vascular risk factors. Among all predictors, gradCPT accuracy explained the most variance in gait speed (<i
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Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89-43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R<sup
|
Increased neural variability in adolescents with ADHD symptomatology: Evidence from a single-trial EEG study. Increased intrasubject variability of reaction time (RT) refers to inconsistency in an individual's speed of responding to a task. This increased variability has been suggested as a fundamental feature of attention deficit hyperactivity disorder (ADHD), however, its neural sources are still unclear. In this study, we aimed to examine whether such inconsistency at the behavioral level would be accompanied by inconsistency at the neural level; and whether different types of neural and behavioral variability would be related to ADHD symptomatology. We recorded electroencephalogram (EEG) data from 62 adolescents, who were part of a prospective longitudinal study on the development of ADHD. We examined trial-by-trial neural variability in response to visual stimuli in two cognitive tasks. Adolescents with high ADHD symptomatology exhibited an increased neural variability before the presentation of the stimulus, but when presented with a visual stimulus, this variability decreased to a level that was similar to that exhibited by participants with low ADHD symptomatology. In contrast with our prediction, neural variability was unrelated to the magnitude of behavioral variability. Our findings suggest that adolescents with higher symptoms are characterized by increased neural variability before the stimulation, which might reflect a difficulty in alertness to the forthcoming stimulus; but this increased neural variability does not seem to account for their RT variability.</AbstractText
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Evidence for a Specific Association Between Sustained Attention and Gait Speed in Middle-to-Older-Aged Adults. Although cognitive decline has previously been associated with mobility limitations and frailty, the relationship between sustained attention and gait speed is incompletely characterized. To better quantify the specificity of the sustained attention and gait speed association, we examined the extent to which this relationship is unique rather than accounted for by executive functioning and physical health characteristics. 58 middle-to-older-aged community-dwelling adults without overt evidence of cognitive impairment (45-90 years old; 21 females) participated in the study. Each participant completed a 4-meter gait speed assessment and validated neuropsychological tests to examine various domains of executive functioning including working memory (i.e., Digit Span), inhibitory control (i.e., D-KEFS Color-Word Interference), and task switching (i.e., D-KEFS Number/Letter Switching). Multiple physical and vascular risk factors were also evaluated. Sustained attention was assessed using the gradual onset continuous performance task (gradCPT), a well-validated go/no-go sustained attention task. A series of linear regression models were used to examine how different aspects of cognition, including sustained attention and traditional measures of executive functioning, related to gait speed while controlling for a variety of physical and vascular risk factors. Among all predictors, gradCPT accuracy explained the most variance in gait speed (<i
|
Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome. Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89-43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R<sup
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32169824
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19478285
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32549629
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Fenfluramine acts as a positive modulator of sigma-1 receptors.
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Antidepressant-induced jitteriness/anxiety syndrome: systematic review.
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Common, Difficult Questions about Providing Nutrition at End of Life: Bedside Application of Catholic Moral Teaching.
|
Adjunctive fenfluramine hydrochloride, classically described as acting pharmacologically through a serotonergic mechanism, has demonstrated a unique and robust clinical response profile with regard to its magnitude, consistency, and durability of effect on seizure activity in patients with pharmacoresistant Dravet syndrome. Recent findings also support long-term improvements in executive functions (behavior, emotion, cognition) in these patients. The observed clinical profile is inconsistent with serotonergic activity alone, as other serotonergic medications have not been demonstrated to have these clinical effects. This study investigated a potential role for σ<sub Radioligand binding assays tested the affinity of fenfluramine for 47 receptors associated with seizures in the literature, including σ receptors. Cellular function assays tested fenfluramine and norfenfluramine (its major metabolite) activity at various receptors, including adrenergic, muscarinic, and serotonergic receptors. The σ<sub Fenfluramine and norfenfluramine bound ≥30% to β<sub Fenfluramine demonstrated modulatory activity at σ<sub
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Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking.</AbstractText To review systematically all evidence relating to jitteriness/anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions.</AbstractText A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.</AbstractText Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome.</AbstractText Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.</AbstractText
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There is much confusion surrounding how to interpret provision of artificial nutrition and hydration (ANH) at the bedside in complicated clinical circumstances. The specific scenario that prompted these questions was a request by a patient and her family to remove a feeding tube that had become, in the patient's eyes and opinion, disproportionately burdensome in her particular set of clinical circumstances. This clinically relevant article can be viewed as a bedside interpretation of Catholic bioethical teachings on provision of ANH to the dying patient. Please note that this article does not address specific ethical issues that pertain to persistent vegetative state, which is beyond the scope of this particular discussion.</AbstractText
|
Fenfluramine acts as a positive modulator of sigma-1 receptors. Adjunctive fenfluramine hydrochloride, classically described as acting pharmacologically through a serotonergic mechanism, has demonstrated a unique and robust clinical response profile with regard to its magnitude, consistency, and durability of effect on seizure activity in patients with pharmacoresistant Dravet syndrome. Recent findings also support long-term improvements in executive functions (behavior, emotion, cognition) in these patients. The observed clinical profile is inconsistent with serotonergic activity alone, as other serotonergic medications have not been demonstrated to have these clinical effects. This study investigated a potential role for σ<sub Radioligand binding assays tested the affinity of fenfluramine for 47 receptors associated with seizures in the literature, including σ receptors. Cellular function assays tested fenfluramine and norfenfluramine (its major metabolite) activity at various receptors, including adrenergic, muscarinic, and serotonergic receptors. The σ<sub Fenfluramine and norfenfluramine bound ≥30% to β<sub Fenfluramine demonstrated modulatory activity at σ<sub
|
Antidepressant-induced jitteriness/anxiety syndrome: systematic review. Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking.</AbstractText To review systematically all evidence relating to jitteriness/anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions.</AbstractText A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.</AbstractText Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome.</AbstractText Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.</AbstractText
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Common, Difficult Questions about Providing Nutrition at End of Life: Bedside Application of Catholic Moral Teaching. There is much confusion surrounding how to interpret provision of artificial nutrition and hydration (ANH) at the bedside in complicated clinical circumstances. The specific scenario that prompted these questions was a request by a patient and her family to remove a feeding tube that had become, in the patient's eyes and opinion, disproportionately burdensome in her particular set of clinical circumstances. This clinically relevant article can be viewed as a bedside interpretation of Catholic bioethical teachings on provision of ANH to the dying patient. Please note that this article does not address specific ethical issues that pertain to persistent vegetative state, which is beyond the scope of this particular discussion.</AbstractText
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28067751
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25713746
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27432000
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Efficacy of clozapine on dopamine supersensitivity psychosis in schizophrenia.
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Uncommon applications of deep brain stimulation in hyperkinetic movement disorders.
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Evolution of language: Lessons from the genome.
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Although the effectiveness of clozapine (CLZ) for patients with treatment-resistant schizophrenia (TRS) has been well established, its active mechanism has not been completely clarified. Several clinical studies showed that neuroleptic-induced dopamine supersensitivity psychosis (DSP) could be involved in the etiology of TRS. We preliminarily explored the possible beneficial effect of CLZ for dopamine supersensitivity schizophrenia. The present study is a case series. We followed 15 patients with DSP for about 2.5 years from the introduction of CLZ and compared the prevalence of episodes (particularly, rebound psychosis, tolerance to antipsychotic effects, or tardive dyskinesia) between the period before and during CLZ treatment. Our observation over 2.5 years following the introduction of CLZ showed that 13 of the 15 DSP patients presented no further DSP episodes. One patient showed continued tardive dyskinesia, which had already existed in the preperiod, and the other patient presented with rebound psychosis that appeared immediately after discontinuation of CLZ. The results of the present study indicated that DSP in schizophrenic patients treated with general antipsychotics disappeared over the subsequent 2.5 years under CLZ treatment, suggesting that the agent ameliorates the dopamine supersensitivity state induced by previous antipsychotic treatment.</AbstractText
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In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study.</AbstractText A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus.</AbstractText We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi) DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies.</AbstractText Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.</AbstractText
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The post-genomic era is an exciting time for researchers interested in the biology of speech and language. Substantive advances in molecular methodologies have opened up entire vistas of investigation that were not previously possible, or in some cases even imagined. Speculations concerning the origins of human cognitive traits are being transformed into empirically addressable questions, generating specific hypotheses that can be explicitly tested using data collected from both the natural world and experimental settings. In this article, I discuss a number of promising lines of research in this area. For example, the field has begun to identify genes implicated in speech and language skills, including not just disorders but also the normal range of abilities. Such genes provide powerful entry points for gaining insights into neural bases and evolutionary origins, using sophisticated experimental tools from molecular neuroscience and developmental neurobiology. At the same time, sequencing of ancient hominin genomes is giving us an unprecedented view of the molecular genetic changes that have occurred during the evolution of our species. Synthesis of data from these complementary sources offers an opportunity to robustly evaluate alternative accounts of language evolution. Of course, this endeavour remains challenging on many fronts, as I also highlight in the article. Nonetheless, such an integrated approach holds great potential for untangling the complexities of the capacities that make us human.</AbstractText
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Efficacy of clozapine on dopamine supersensitivity psychosis in schizophrenia. Although the effectiveness of clozapine (CLZ) for patients with treatment-resistant schizophrenia (TRS) has been well established, its active mechanism has not been completely clarified. Several clinical studies showed that neuroleptic-induced dopamine supersensitivity psychosis (DSP) could be involved in the etiology of TRS. We preliminarily explored the possible beneficial effect of CLZ for dopamine supersensitivity schizophrenia. The present study is a case series. We followed 15 patients with DSP for about 2.5 years from the introduction of CLZ and compared the prevalence of episodes (particularly, rebound psychosis, tolerance to antipsychotic effects, or tardive dyskinesia) between the period before and during CLZ treatment. Our observation over 2.5 years following the introduction of CLZ showed that 13 of the 15 DSP patients presented no further DSP episodes. One patient showed continued tardive dyskinesia, which had already existed in the preperiod, and the other patient presented with rebound psychosis that appeared immediately after discontinuation of CLZ. The results of the present study indicated that DSP in schizophrenic patients treated with general antipsychotics disappeared over the subsequent 2.5 years under CLZ treatment, suggesting that the agent ameliorates the dopamine supersensitivity state induced by previous antipsychotic treatment.</AbstractText
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Uncommon applications of deep brain stimulation in hyperkinetic movement disorders. In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study.</AbstractText A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus.</AbstractText We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi) DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies.</AbstractText Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.</AbstractText
|
Evolution of language: Lessons from the genome. The post-genomic era is an exciting time for researchers interested in the biology of speech and language. Substantive advances in molecular methodologies have opened up entire vistas of investigation that were not previously possible, or in some cases even imagined. Speculations concerning the origins of human cognitive traits are being transformed into empirically addressable questions, generating specific hypotheses that can be explicitly tested using data collected from both the natural world and experimental settings. In this article, I discuss a number of promising lines of research in this area. For example, the field has begun to identify genes implicated in speech and language skills, including not just disorders but also the normal range of abilities. Such genes provide powerful entry points for gaining insights into neural bases and evolutionary origins, using sophisticated experimental tools from molecular neuroscience and developmental neurobiology. At the same time, sequencing of ancient hominin genomes is giving us an unprecedented view of the molecular genetic changes that have occurred during the evolution of our species. Synthesis of data from these complementary sources offers an opportunity to robustly evaluate alternative accounts of language evolution. Of course, this endeavour remains challenging on many fronts, as I also highlight in the article. Nonetheless, such an integrated approach holds great potential for untangling the complexities of the capacities that make us human.</AbstractText
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39121824
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32546134
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38260411
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Response to iron supplementation is similar between boys and girls with pediatric sleep movement disorders.
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Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database.
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Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells.
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This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD).</AbstractText Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I).</AbstractText In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes.</AbstractText The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes.</AbstractText
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Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants' classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants' classes with movement disorders.</AbstractText Using VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders' reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders.</AbstractText Out of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62-11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38-1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants.</AbstractText A potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone. Clinicians should beware of these adverse effects and monitor early warning signs carefully. However, this observational study must be interpreted as an exploratory analysis, and these results should be refined by future epidemiological studies.</AbstractText
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Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells - the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.</AbstractText
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Response to iron supplementation is similar between boys and girls with pediatric sleep movement disorders. This study aims to investigate sex differences in response to iron supplementation in children and adolescents suffering from sleep-related movement disorders such as Restless Legs Syndrome (RLS), Periodic Limb Movement Disorder (PLMD), and Restless Sleep Disorder (RSD).</AbstractText Data were retrieved and reanalyzed from previous studies involving children with RLS, PLMD, or RSD. The analysis included 54 patients treated with intravenous (IV) ferric carboxymaltose (FCM) and 31 patients treated with oral ferrous sulfate (FS). Demographic, biological, and clinical parameters were compared between sexes. Clinical outcomes were measured using the Clinical Global Impression rating scales for severity (CGI-S) and improvement (CGI-I).</AbstractText In the group treated with IV FCM, no significant differences were found between males and females in demographic (age), biological (ferritin, iron, total iron-binding capacity, transferrin), or clinical parameters (CGI-S and CGI-I). However, among adolescents, females showed significantly better clinical improvement (CGI-I) compared to males (t-value 2.428, p < 0.024). In the group treated with oral FS, no significant sex differences were observed in any parameters. Side effects were reported by a small number of patients, with no significant difference between sexes.</AbstractText The findings indicate no major significant sex-based differences in response to iron supplementation for treating sleep-related movement disorders in children and adolescents, despite distinct hormonal and physiological differences in iron metabolism. Both boys and girls benefit similarly from iron treatment during this developmental stage, suggesting that a standardized approach to iron supplementation may be effective. However, individual assessment and monitoring remain crucial to ensure optimal outcomes.</AbstractText
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Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database. Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants' classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants' classes with movement disorders.</AbstractText Using VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders' reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders.</AbstractText Out of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62-11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38-1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants.</AbstractText A potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone. Clinicians should beware of these adverse effects and monitor early warning signs carefully. However, this observational study must be interpreted as an exploratory analysis, and these results should be refined by future epidemiological studies.</AbstractText
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Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells. Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells - the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.</AbstractText
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30910630
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32630166
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31170963
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Altered functional connectivity in patients with subcortical ischemic vascular disease: A resting-state fMRI study.
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Function-Based Tractography of the Language Network Correlates with Aphasia in Patients with Language-Eloquent Glioblastoma.
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Central nervous system vasculopathy caused by Fabry disease: a case report.
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Patients with subcortical ischemic vascular disease (SIVD) may hold a high risk of cognitive impairment (CI) by affecting the functional connectivity (FC) of resting-state networks (RSNs). Current studies have mainly focused on the patients with CI but have ignored the prodromal stage when people suffered subcortical vascular damage, but without CI. Independent component analysis (ICA) of rs-fMRI could detect altered FC in RSNs at the early stage of the disease. 81 SIVD patients with CI (SVCI = 29) and without CI (pre-SVCI = 25), and 27 normal controls (NCs) were scanned with rs-fMRI, analyzed by ICA and assessed by neuropsychological examinations. We found significantly altered FC within the RSNs of sensorimotor network (SMN), posterior default mode networks (pDMN), right frontoparietal network (rFPN) and language network (LN) (P < 0.05, AlphaSim corrected). The pre-SVCI group showed significantly increased FC in brain regions of the multiple RSNs when compared with the other two groups. The mean values extracted from the right inferior frontal gyrus (IFG.R) and the left posterior cingulate gyrus (PCG.L) were significantly correlated with clock drawing test (CDT). The right precentral/postcentral gyrus (PreCG.R/PoCG.R) and the right supramarginal gyrus (SMG.R) were positively correlated with Stroop-1 Test. We concluded the FC in RSNs had already been changed at the early stage of the disease as the maladaptive response or compensatory reallocation of the cognitive resources. The ICA of rs-fMRI can be applied as a potential approach to identify the underlying mechanisms of SIVD.</AbstractText
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To date, the structural characteristics that distinguish language-involved from non-involved cortical areas are largely unclear. Particularly in patients suffering from language-eloquent brain tumors, reliable mapping of the cortico-subcortical language network is of high clinical importance to prepare and guide safe tumor resection. To investigate differences in structural characteristics between language-positive and language-negative areas, 20 patients (mean age: 63.2 ± 12.9 years, 16 males) diagnosed with language-eloquent left-hemispheric glioblastoma multiforme (GBM) underwent preoperative language mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT). The number of language-positive and language-negative points as well as the gray matter intensity (GMI), normalized volumes of U-fibers, interhemispheric fibers, and fibers projecting to the cerebellum were assessed and compared between language-positive and language-negative nTMS mappings and set in correlation with aphasia grades. We found significantly lower GMI for language-positive nTMS points (5.7 ± 1.7 versus 7.1 ± 1.6, <i
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Fabry disease is rare, and the diagnosis is often delayed. Here, we describe a case of Fabry disease resulting in vasculopathy of the central nervous system. Magnetic resonance (MR) black-blood sequence (three-dimensional T1 volumetric isotropic turbo spin echo acquisition), with the unique advantage of imaging the vascular wall, facilitated a clear identification of the vasculopathy.</AbstractText A 27-year-old man visited our hospital for the treatment of " double vision 6d." After a series of examinations, the patient was diagnosed with Fabry disease, which caused vasculopathy of the central nervous system. Subsequently, the patient was treated with corticosteroids and his symptoms were attenuated. Two months after the initial treatment, the initial lesion in the vascular vessel disappeared, however, a new lesion appeared. Similarly, four months after the initial treatment, although the previous lesion disappeared, a new lesion appeared.</AbstractText This case highlights that clinicians should use MR black-blood sequence scan in a timely manner in case of young patients with migratory lesions of brain. In case of detection of a vascular lesion in combination with other systemic lesions, the possibility of Fabry disease should be considered.</AbstractText
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Altered functional connectivity in patients with subcortical ischemic vascular disease: A resting-state fMRI study. Patients with subcortical ischemic vascular disease (SIVD) may hold a high risk of cognitive impairment (CI) by affecting the functional connectivity (FC) of resting-state networks (RSNs). Current studies have mainly focused on the patients with CI but have ignored the prodromal stage when people suffered subcortical vascular damage, but without CI. Independent component analysis (ICA) of rs-fMRI could detect altered FC in RSNs at the early stage of the disease. 81 SIVD patients with CI (SVCI = 29) and without CI (pre-SVCI = 25), and 27 normal controls (NCs) were scanned with rs-fMRI, analyzed by ICA and assessed by neuropsychological examinations. We found significantly altered FC within the RSNs of sensorimotor network (SMN), posterior default mode networks (pDMN), right frontoparietal network (rFPN) and language network (LN) (P < 0.05, AlphaSim corrected). The pre-SVCI group showed significantly increased FC in brain regions of the multiple RSNs when compared with the other two groups. The mean values extracted from the right inferior frontal gyrus (IFG.R) and the left posterior cingulate gyrus (PCG.L) were significantly correlated with clock drawing test (CDT). The right precentral/postcentral gyrus (PreCG.R/PoCG.R) and the right supramarginal gyrus (SMG.R) were positively correlated with Stroop-1 Test. We concluded the FC in RSNs had already been changed at the early stage of the disease as the maladaptive response or compensatory reallocation of the cognitive resources. The ICA of rs-fMRI can be applied as a potential approach to identify the underlying mechanisms of SIVD.</AbstractText
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Function-Based Tractography of the Language Network Correlates with Aphasia in Patients with Language-Eloquent Glioblastoma. To date, the structural characteristics that distinguish language-involved from non-involved cortical areas are largely unclear. Particularly in patients suffering from language-eloquent brain tumors, reliable mapping of the cortico-subcortical language network is of high clinical importance to prepare and guide safe tumor resection. To investigate differences in structural characteristics between language-positive and language-negative areas, 20 patients (mean age: 63.2 ± 12.9 years, 16 males) diagnosed with language-eloquent left-hemispheric glioblastoma multiforme (GBM) underwent preoperative language mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT). The number of language-positive and language-negative points as well as the gray matter intensity (GMI), normalized volumes of U-fibers, interhemispheric fibers, and fibers projecting to the cerebellum were assessed and compared between language-positive and language-negative nTMS mappings and set in correlation with aphasia grades. We found significantly lower GMI for language-positive nTMS points (5.7 ± 1.7 versus 7.1 ± 1.6, <i
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Central nervous system vasculopathy caused by Fabry disease: a case report. Fabry disease is rare, and the diagnosis is often delayed. Here, we describe a case of Fabry disease resulting in vasculopathy of the central nervous system. Magnetic resonance (MR) black-blood sequence (three-dimensional T1 volumetric isotropic turbo spin echo acquisition), with the unique advantage of imaging the vascular wall, facilitated a clear identification of the vasculopathy.</AbstractText A 27-year-old man visited our hospital for the treatment of " double vision 6d." After a series of examinations, the patient was diagnosed with Fabry disease, which caused vasculopathy of the central nervous system. Subsequently, the patient was treated with corticosteroids and his symptoms were attenuated. Two months after the initial treatment, the initial lesion in the vascular vessel disappeared, however, a new lesion appeared. Similarly, four months after the initial treatment, although the previous lesion disappeared, a new lesion appeared.</AbstractText This case highlights that clinicians should use MR black-blood sequence scan in a timely manner in case of young patients with migratory lesions of brain. In case of detection of a vascular lesion in combination with other systemic lesions, the possibility of Fabry disease should be considered.</AbstractText
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18352792
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15480126
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17631868
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Allergic reaction to a bovine dural substitute following spinal cord untethering. Case report.
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The "human tail": a rare cause of tethered cord: a case report.
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Increased expression of 5-HT6 receptors in the nucleus accumbens blocks the rewarding but not psychomotor activating properties of cocaine.
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Bovine tissues are now routinely used for dural closure in cranial and spinal surgery. The authors report the case of an 18-year-old woman with a history of myelomeningocele who had symptoms of tethered cord syndrome and presented to a regional hospital. At that hospital she underwent a cord untethering procedure. The spinal dura was closed with Durepair, a dural substitute derived from fetal bovine skin. Her postoperative course was complicated by a cerebrospinal fluid leak that was surgically repaired. Following this, she developed erythroderma, intermittent fevers, eosinophilia, and marked elevation in serum immunoglobulin E. She was then transferred to the authors' institution. A skin antigen test to beef was administered, which revealed a positive reaction. A radioallergosorbent test to beef also yielded positive results. She was taken to the operating room for removal of the bovine graft due to concern for an allergic reaction to the graft. The graft material showed evidence of eosinophilic infiltration. Her clinical symptoms and laboratory values all improved after surgery. To the authors' knowledge this is the first reported case of an allergic reaction to bovine-based dural substitutes.</AbstractText
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Observational case report.</AbstractText To report a case of dorsal cutaneous appendage or the so-called human tail that was the cause of tethered cord syndrome.</AbstractText The dorsal cutaneous appendage, or so-called human tail, is often considered to be a cutaneous marker of underlying occult spinal dysraphism. In such cases, there is usually a separate underlying tethering lesion. There have been only three case reports in the literature where this appendage itself was the tethering lesion. The fourth such case is being reported.</AbstractText An 11-month-old male child was brought for consultation for a "tail-like" structure in the low back since birth. Examination revealed a subtle thinning of the right lower extremity and a caudal appendage in the lower lumbar region. Plain radiographs revealed spina bifida at S1. MRI revealed a transitional lipoma at L5-S1 with a terminal syrinx.</AbstractText During surgery, a fibrous tract was seen extending from the base of the appendage through the defect in the bone and dura. The tract ended in the transitional lipoma of the cord at L5-S1. Sectioning of the tract and debulking of the transitional lipoma was done. After surgery, there was no change in the neurologic status of the patient.</AbstractText This case illustrates that the so-called "human tail" or the dorsal cutaneous appendage is not just a marker of underlying occult spinal dysraphism. In rare cases, the appendage itself can be the tethering lesion. In every case of dorsal cutaneous appendage, the surgeon should diligently search for the intraspinal extension of the lesion even if such an extension is not revealed by the MRI.</AbstractText
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Repeated exposure to cocaine produces enduring forms of drug experience-dependent behavioral plasticity, including conditioned place preference (CPP) and psychomotor sensitization, a progressive and persistent increase in cocaine's psychomotor activating effects. Although serotonin-6 receptors (5-HT6Rs) are abundantly expressed in the brain regions thought to underlie these phenomena, such as the nucleus accumbens (NAc), surprisingly little is known about the role of 5-HT6Rs in the rewarding and psychomotor activating effects of cocaine.</AbstractText Viral-mediated gene transfer was used to selectively increase 5-HT6R expression in the NAc of rats. The effects of 5-HT6R overexpression and the selective 5-HT6R antagonist Ro4368554 on CPP and psychomotor sensitization were examined.</AbstractText Increased expression of 5-HT6Rs in the NAc blocks a CPP to cocaine but has no effect on either the acute locomotor response to cocaine or on the development of cocaine-induced locomotor sensitization. Furthermore, antagonism of 5-HT6Rs facilitates the acquisition of a CPP to cocaine but has no effect on cocaine-induced stereotypy.</AbstractText These results demonstrate that 5-HT6Rs in the NAc can selectively modulate drug reward, possibly through facilitation of reward learning.</AbstractText
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Allergic reaction to a bovine dural substitute following spinal cord untethering. Case report. Bovine tissues are now routinely used for dural closure in cranial and spinal surgery. The authors report the case of an 18-year-old woman with a history of myelomeningocele who had symptoms of tethered cord syndrome and presented to a regional hospital. At that hospital she underwent a cord untethering procedure. The spinal dura was closed with Durepair, a dural substitute derived from fetal bovine skin. Her postoperative course was complicated by a cerebrospinal fluid leak that was surgically repaired. Following this, she developed erythroderma, intermittent fevers, eosinophilia, and marked elevation in serum immunoglobulin E. She was then transferred to the authors' institution. A skin antigen test to beef was administered, which revealed a positive reaction. A radioallergosorbent test to beef also yielded positive results. She was taken to the operating room for removal of the bovine graft due to concern for an allergic reaction to the graft. The graft material showed evidence of eosinophilic infiltration. Her clinical symptoms and laboratory values all improved after surgery. To the authors' knowledge this is the first reported case of an allergic reaction to bovine-based dural substitutes.</AbstractText
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The "human tail": a rare cause of tethered cord: a case report. Observational case report.</AbstractText To report a case of dorsal cutaneous appendage or the so-called human tail that was the cause of tethered cord syndrome.</AbstractText The dorsal cutaneous appendage, or so-called human tail, is often considered to be a cutaneous marker of underlying occult spinal dysraphism. In such cases, there is usually a separate underlying tethering lesion. There have been only three case reports in the literature where this appendage itself was the tethering lesion. The fourth such case is being reported.</AbstractText An 11-month-old male child was brought for consultation for a "tail-like" structure in the low back since birth. Examination revealed a subtle thinning of the right lower extremity and a caudal appendage in the lower lumbar region. Plain radiographs revealed spina bifida at S1. MRI revealed a transitional lipoma at L5-S1 with a terminal syrinx.</AbstractText During surgery, a fibrous tract was seen extending from the base of the appendage through the defect in the bone and dura. The tract ended in the transitional lipoma of the cord at L5-S1. Sectioning of the tract and debulking of the transitional lipoma was done. After surgery, there was no change in the neurologic status of the patient.</AbstractText This case illustrates that the so-called "human tail" or the dorsal cutaneous appendage is not just a marker of underlying occult spinal dysraphism. In rare cases, the appendage itself can be the tethering lesion. In every case of dorsal cutaneous appendage, the surgeon should diligently search for the intraspinal extension of the lesion even if such an extension is not revealed by the MRI.</AbstractText
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Increased expression of 5-HT6 receptors in the nucleus accumbens blocks the rewarding but not psychomotor activating properties of cocaine. Repeated exposure to cocaine produces enduring forms of drug experience-dependent behavioral plasticity, including conditioned place preference (CPP) and psychomotor sensitization, a progressive and persistent increase in cocaine's psychomotor activating effects. Although serotonin-6 receptors (5-HT6Rs) are abundantly expressed in the brain regions thought to underlie these phenomena, such as the nucleus accumbens (NAc), surprisingly little is known about the role of 5-HT6Rs in the rewarding and psychomotor activating effects of cocaine.</AbstractText Viral-mediated gene transfer was used to selectively increase 5-HT6R expression in the NAc of rats. The effects of 5-HT6R overexpression and the selective 5-HT6R antagonist Ro4368554 on CPP and psychomotor sensitization were examined.</AbstractText Increased expression of 5-HT6Rs in the NAc blocks a CPP to cocaine but has no effect on either the acute locomotor response to cocaine or on the development of cocaine-induced locomotor sensitization. Furthermore, antagonism of 5-HT6Rs facilitates the acquisition of a CPP to cocaine but has no effect on cocaine-induced stereotypy.</AbstractText These results demonstrate that 5-HT6Rs in the NAc can selectively modulate drug reward, possibly through facilitation of reward learning.</AbstractText
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39826672
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32082109
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40636238
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Neurobiology of L-proline: From molecules to behavior.
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Asthmatic Airway Vagal Hypertonia Involves Chloride Dyshomeostasis of Preganglionic Neurons in Rats.
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(18)FDG PET/CT is Sensitive but not Specific for Malignancy: Two Cases of Disseminated Tuberculosis Mimicking Metastatic Cancer on Imaging and Clinical Presentation.
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L-proline is an amino acid with a unique cyclic structure, involvement in various physiological processes, such as protein synthesis, collagen production, and neurotransmission. This review explores the complex roles of proline in the central nervous system (CNS), where it contributes to both excitatory and inhibitory neurotransmission. Additionally, L-proline has distinct metabolic functions attributed to its structural properties. The concentration-dependent effects of L-proline indicate its importance in CNS function, with potential implications for health and disease. Studies in animal models suggest that L-proline influences cognitive function and behavior, with dysregulated levels linked to learning and memory deficits. Furthermore, this review addresses the neuropathological consequences of hyperprolinemia, a metabolic disorder marked by elevated L-proline levels in the CNS and examines the potential role of L-proline in neurological and psychiatric disorders. In sum, this work provides a comprehensive perspective on the neurobiological importance of L-proline, underscoring its involvement in neurotransmission, behavioral modulation, and disease pathology.</AbstractText
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Airway vagal hypertonia is closely related to the severity of asthma; however, the mechanisms of its genesis are unclear. This study aims to prove that asthmatic airway vagal hypertonia involves neuronal Cl<sup
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<sup We report a case series of two young patients with exclusive extrapulmonary disseminated tuberculosis that mimicked a neoplastic process both clinically and on <sup These cases underscore the importance of considering disseminated tuberculosis as a differential diagnosis during oncologic evaluations, especially in patients from endemic regions, and highlight the potential psychological impact of prematurely labelling a condition as cancer.</AbstractText Extrapulmonary tuberculosis can mimic metastatic malignancies.Imaging does not replace pathology, which remains the gold standard for accurately diagnosing multiorgan involvement.Prematurely announcing a diagnosis of cancer before final confirmation can have significant psychological consequences.</AbstractText
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Neurobiology of L-proline: From molecules to behavior. L-proline is an amino acid with a unique cyclic structure, involvement in various physiological processes, such as protein synthesis, collagen production, and neurotransmission. This review explores the complex roles of proline in the central nervous system (CNS), where it contributes to both excitatory and inhibitory neurotransmission. Additionally, L-proline has distinct metabolic functions attributed to its structural properties. The concentration-dependent effects of L-proline indicate its importance in CNS function, with potential implications for health and disease. Studies in animal models suggest that L-proline influences cognitive function and behavior, with dysregulated levels linked to learning and memory deficits. Furthermore, this review addresses the neuropathological consequences of hyperprolinemia, a metabolic disorder marked by elevated L-proline levels in the CNS and examines the potential role of L-proline in neurological and psychiatric disorders. In sum, this work provides a comprehensive perspective on the neurobiological importance of L-proline, underscoring its involvement in neurotransmission, behavioral modulation, and disease pathology.</AbstractText
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Asthmatic Airway Vagal Hypertonia Involves Chloride Dyshomeostasis of Preganglionic Neurons in Rats. Airway vagal hypertonia is closely related to the severity of asthma; however, the mechanisms of its genesis are unclear. This study aims to prove that asthmatic airway vagal hypertonia involves neuronal Cl<sup
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(18)FDG PET/CT is Sensitive but not Specific for Malignancy: Two Cases of Disseminated Tuberculosis Mimicking Metastatic Cancer on Imaging and Clinical Presentation. <sup We report a case series of two young patients with exclusive extrapulmonary disseminated tuberculosis that mimicked a neoplastic process both clinically and on <sup These cases underscore the importance of considering disseminated tuberculosis as a differential diagnosis during oncologic evaluations, especially in patients from endemic regions, and highlight the potential psychological impact of prematurely labelling a condition as cancer.</AbstractText Extrapulmonary tuberculosis can mimic metastatic malignancies.Imaging does not replace pathology, which remains the gold standard for accurately diagnosing multiorgan involvement.Prematurely announcing a diagnosis of cancer before final confirmation can have significant psychological consequences.</AbstractText
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40484186
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19706341
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40713993
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Investigating zinc's role in mitigating blood lead levels' toxicity on gut microbiota diversity: NHANES 2007-2010.
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Cadmium and mitochondria.
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Synthesis of CaCO(3) microspheres modified by glycine and ethylene glycol for adsorption removal of Cd(II).
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Zinc serves as a cofactor for numerous vital processes across species. Microorganisms that make up the gut microbiome rely on these zinc-dependent mechanisms to perform essential functions, contributing to a diverse and stable microbial environment. Environmental contaminants, such as lead, has been shown to disrupt diversity and stability. The purpose of this study was to determine whether zinc serves as an effect modifier against elevated blood lead levels (BLL) on gut microbiota diversity.</AbstractText The 2007-2008 and 2009-2010 NHANES datasets were utilized to conduct a cross-sectional complex survey analysis aimed at determining whether zinc intake acts as a protective factor against changes in microbiome diversity associated with BLL, using enterolactone (ENL) as a biomarker. A multiple linear regression was conducted to evaluate whether an interaction between BLL and zinc intake could predict ENL. The model included fiber intake and BMI as covariates.</AbstractText BMI and fiber intake were identified as covariates. Fiber intake was a confounding variable in the relationship between zinc and ENL levels. Lead was found to decrease ENL levels (p = 0.002). The interaction between zinc and BLL was marginally significant (p = 0.089).</AbstractText This study suggests that lead's impact on gut microbial diversity may depend on zinc status. These findings emphasize the importance of accounting for dietary confounders, such as fiber intake, to improve model accuracy and interpretation. While additional research is needed to confirm zinc's potential protective role, public health strategies encouraging adequate zinc and fiber intake may in part help support microbial resilience and reduce lead's effects on the gut microbiota.</AbstractText
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The heavy metal cadmium (Cd) a pollutant associated with several modern industrial processes, is absorbed in significant quantities from cigarette smoke, water, food and air contaminations. It is known to have numerous undesirable effects on health in both experimental animals and humans, targeting kidney, liver and vascular system. The molecular mechanism accounting for most of the biological effects of Cd are not well-understood and the toxicity targets are largely unidentified. The present review focuses on important recent advances about the effects of cadmium on mitochondria of mammalian cells. Mitochondria are the proverbial powerhouses of the cell, running the fundamental biochemical processes that produce energy from nutrients using oxygen. They are among the key intracellular targets for different stressors including Cd. This review provides new additional informations on the cellular and molecular aspects of the interaction between Cd and cells, emphasizing alterations of mitochondria as important events in Cd cytotoxicity, thus representing an important basis for understanding the mechanisms of cadmium effect on the cells.</AbstractText
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Calcium carbonate (CaCO<sub
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Investigating zinc's role in mitigating blood lead levels' toxicity on gut microbiota diversity: NHANES 2007-2010. Zinc serves as a cofactor for numerous vital processes across species. Microorganisms that make up the gut microbiome rely on these zinc-dependent mechanisms to perform essential functions, contributing to a diverse and stable microbial environment. Environmental contaminants, such as lead, has been shown to disrupt diversity and stability. The purpose of this study was to determine whether zinc serves as an effect modifier against elevated blood lead levels (BLL) on gut microbiota diversity.</AbstractText The 2007-2008 and 2009-2010 NHANES datasets were utilized to conduct a cross-sectional complex survey analysis aimed at determining whether zinc intake acts as a protective factor against changes in microbiome diversity associated with BLL, using enterolactone (ENL) as a biomarker. A multiple linear regression was conducted to evaluate whether an interaction between BLL and zinc intake could predict ENL. The model included fiber intake and BMI as covariates.</AbstractText BMI and fiber intake were identified as covariates. Fiber intake was a confounding variable in the relationship between zinc and ENL levels. Lead was found to decrease ENL levels (p = 0.002). The interaction between zinc and BLL was marginally significant (p = 0.089).</AbstractText This study suggests that lead's impact on gut microbial diversity may depend on zinc status. These findings emphasize the importance of accounting for dietary confounders, such as fiber intake, to improve model accuracy and interpretation. While additional research is needed to confirm zinc's potential protective role, public health strategies encouraging adequate zinc and fiber intake may in part help support microbial resilience and reduce lead's effects on the gut microbiota.</AbstractText
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Cadmium and mitochondria. The heavy metal cadmium (Cd) a pollutant associated with several modern industrial processes, is absorbed in significant quantities from cigarette smoke, water, food and air contaminations. It is known to have numerous undesirable effects on health in both experimental animals and humans, targeting kidney, liver and vascular system. The molecular mechanism accounting for most of the biological effects of Cd are not well-understood and the toxicity targets are largely unidentified. The present review focuses on important recent advances about the effects of cadmium on mitochondria of mammalian cells. Mitochondria are the proverbial powerhouses of the cell, running the fundamental biochemical processes that produce energy from nutrients using oxygen. They are among the key intracellular targets for different stressors including Cd. This review provides new additional informations on the cellular and molecular aspects of the interaction between Cd and cells, emphasizing alterations of mitochondria as important events in Cd cytotoxicity, thus representing an important basis for understanding the mechanisms of cadmium effect on the cells.</AbstractText
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Synthesis of CaCO(3) microspheres modified by glycine and ethylene glycol for adsorption removal of Cd(II). Calcium carbonate (CaCO<sub
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39128907
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26784969
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39398064
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A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.
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Diffusion magnetic resonance imaging study of schizophrenia in the context of abnormal neurodevelopment using multiple site data in a Chinese Han population.
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Unveiling the therapeutic potentialities and chemical characterization of methanolic Merremia vitifolia (Burm.f) Hallier f. stem extract: A Multi-faceted investigation via in vitro, in vivo, and in silico approaches.
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The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.</AbstractText
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Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention.</AbstractText
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Current study focused on <i
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A worldwide study of white matter microstructural alterations in people living with Parkinson's disease. The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.</AbstractText
|
Diffusion magnetic resonance imaging study of schizophrenia in the context of abnormal neurodevelopment using multiple site data in a Chinese Han population. Schizophrenia has increasingly been considered a neurodevelopmental disorder, and the advancement of neuroimaging techniques and associated computational methods has enabled quantitative re-examination of this important theory on the pathogenesis of the disease. Inspired by previous findings from neonatal brains, we proposed that an increase in diffusion magnetic resonance imaging (dMRI) mean diffusivity (MD) should be observed in the cerebral cortex of schizophrenia patients compared with healthy controls, corresponding to lower tissue complexity and potentially a failure to reach cortical maturation. We tested this hypothesis using dMRI data from a Chinese Han population comprising patients from four different hospital sites. Utilizing data-driven methods based on the state-of-the-art tensor-based registration algorithm, significantly increased MD measurements were consistently observed in the cortex of schizophrenia patients across all four sites, despite differences in psychopathology, exposure to antipsychotic medication and scanners used for image acquisition. Specifically, we found increased MD in the limbic system of the schizophrenic brain, mainly involving the bilateral insular and prefrontal cortices. In light of the existing literature, we speculate that this may represent a neuroanatomical signature of the disorder, reflecting microstructural deficits due to developmental abnormalities. Our findings not only provide strong support to the abnormal neurodevelopment theory of schizophrenia, but also highlight an important neuroimaging endophenotype for monitoring the developmental trajectory of high-risk subjects of the disease, thereby facilitating early detection and prevention.</AbstractText
|
Unveiling the therapeutic potentialities and chemical characterization of methanolic Merremia vitifolia (Burm.f) Hallier f. stem extract: A Multi-faceted investigation via in vitro, in vivo, and in silico approaches. Current study focused on <i
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40268049
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21153847
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40507093
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Protein oxidation in non-exercising healthy adults under varying dietary conditions: Physiological determinants, effects on fuel partitioning, and implications for body weight regulation.
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Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature.
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In Preclinical Epilepsy, GLUT1 and GFAP Dysregulation in Cells Surrounding the Third Ventricle, Including Tanycytes, Is Differentially Restored with Ketogenic Diet Treatment.
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Protein oxidation (PROTOX) typically accounts for the smallest fraction of daily energy expenditure (24hEE) in humans compared to carbohydrate and lipid oxidation. However, inter-individual differences in PROTOX may explain differences in fuel partitioning and body weight change. We aimed to elucidate the physiological determinants of PROTOX under controlled 24-h dietary conditions, including eucaloric feeding, fasting, and overfeeding diets with variable protein content.</AbstractText Eighty-six weight-stable healthy volunteers with normal glucose regulation (67 M/19F; age: 37 ± 10 years; BMI: 26.7 ± 4.5 kg/m<sup PROTOX during energy balance (mean ± SD: 372 ± 78 kcal/day) was positively associated with protein intake (r = 0.39, p < 0.001), fat free mass (r = 0.35, p < 0.001), but not with fat mass (p = 0.24). Higher PROTOX was associated with higher 24-h urinary norepinephrine (partial r = 0.27, p = 0.01), but not epinephrine (p = 0.48), excretion rates. During normal-protein diets, higher PROTOX was associated with lower lipid oxidation, but showed no association with carbohydrate oxidation. Inter-individual variability in PROTOX did not predict changes in weight or body composition over two years.</AbstractText Dietary protein content, lean body mass, and sympathetic nervous system activity are key determinants of PROTOX. Although PROTOX did not predict free-living weight gain, increased PROTOX is associated with decreased lipid oxidation, underscoring its role in fuel partitioning and whole-body energy and substrate balance.</AbstractText
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Age at menarche is closely related to scoliosis progression during adolescence. Current data concerning the timing of menarche between scoliotic and non-scoliotic girls in the literature are conflicting, with inconclusive results. The aim of this study was to investigate the distribution difference of age at menarche for adolescent idiopathic scoliosis (AIS) girls and normal control population and to subsequently elucidate the menarche age difference through literature reviewing. Moreover, menarche age of AIS girls with Cobb angle <40°, 40-60°, >60° were compared to estimate its association with curve severity. Menstrual status data were available for 6,376 healthy female adolescents and 2,196 AIS girls. We notice that less than 10% of healthy Chinese girls experienced onset of menses before 11.38 years, and approximately 90% of healthy Chinese girls were menstruating by 13.88 years, with a median age of 12.63 years. As for AIS girls, less than 10% started to menstruate before 11.27 years, and approximately 90% were menstruating by 14.38 years, with a median age of 12.83 years. Average menarche age in AIS (12.83 ± 1.22 years) was significantly later than that of normal control girls (12.63 ± 0.98 years) (p < 0.001). Age at menarche for AIS affected girls was significantly greater than that of normal control girls at 75%, 90% of whom had attained menarche (p = 0.001, p < 0.001). Proportion of girls starting to menstruate after 14 years was significantly higher in AIS population compared with normal controls (16.3 vs. 8.1%, p < 0.001). In addition, AIS girls with Cobb angle >60° experienced onset of menses at an average age of 13.25 years, which was significantly later than AIS girls with Cobb angle <40° (12.81 years, p < 0.05) and marginally significantly later than AIS girls with Cobb angle between 40 and 60° (12.86 years, p = 0.053). In conclusion, a tendency of delayed onset of menarche was observed in Chinese idiopathic scoliotic girls in this large sample study, especially for girls with Cobb angle >60°, which is supported by multiple previously established positive linkages on AIS etiology studies. Accordingly it is believed that late menarche may contribute importantly to abnormal pubertal growth and subsequently modulate curve behavior in AIS.</AbstractText
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<b
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Protein oxidation in non-exercising healthy adults under varying dietary conditions: Physiological determinants, effects on fuel partitioning, and implications for body weight regulation. Protein oxidation (PROTOX) typically accounts for the smallest fraction of daily energy expenditure (24hEE) in humans compared to carbohydrate and lipid oxidation. However, inter-individual differences in PROTOX may explain differences in fuel partitioning and body weight change. We aimed to elucidate the physiological determinants of PROTOX under controlled 24-h dietary conditions, including eucaloric feeding, fasting, and overfeeding diets with variable protein content.</AbstractText Eighty-six weight-stable healthy volunteers with normal glucose regulation (67 M/19F; age: 37 ± 10 years; BMI: 26.7 ± 4.5 kg/m<sup PROTOX during energy balance (mean ± SD: 372 ± 78 kcal/day) was positively associated with protein intake (r = 0.39, p < 0.001), fat free mass (r = 0.35, p < 0.001), but not with fat mass (p = 0.24). Higher PROTOX was associated with higher 24-h urinary norepinephrine (partial r = 0.27, p = 0.01), but not epinephrine (p = 0.48), excretion rates. During normal-protein diets, higher PROTOX was associated with lower lipid oxidation, but showed no association with carbohydrate oxidation. Inter-individual variability in PROTOX did not predict changes in weight or body composition over two years.</AbstractText Dietary protein content, lean body mass, and sympathetic nervous system activity are key determinants of PROTOX. Although PROTOX did not predict free-living weight gain, increased PROTOX is associated with decreased lipid oxidation, underscoring its role in fuel partitioning and whole-body energy and substrate balance.</AbstractText
|
Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature. Age at menarche is closely related to scoliosis progression during adolescence. Current data concerning the timing of menarche between scoliotic and non-scoliotic girls in the literature are conflicting, with inconclusive results. The aim of this study was to investigate the distribution difference of age at menarche for adolescent idiopathic scoliosis (AIS) girls and normal control population and to subsequently elucidate the menarche age difference through literature reviewing. Moreover, menarche age of AIS girls with Cobb angle <40°, 40-60°, >60° were compared to estimate its association with curve severity. Menstrual status data were available for 6,376 healthy female adolescents and 2,196 AIS girls. We notice that less than 10% of healthy Chinese girls experienced onset of menses before 11.38 years, and approximately 90% of healthy Chinese girls were menstruating by 13.88 years, with a median age of 12.63 years. As for AIS girls, less than 10% started to menstruate before 11.27 years, and approximately 90% were menstruating by 14.38 years, with a median age of 12.83 years. Average menarche age in AIS (12.83 ± 1.22 years) was significantly later than that of normal control girls (12.63 ± 0.98 years) (p < 0.001). Age at menarche for AIS affected girls was significantly greater than that of normal control girls at 75%, 90% of whom had attained menarche (p = 0.001, p < 0.001). Proportion of girls starting to menstruate after 14 years was significantly higher in AIS population compared with normal controls (16.3 vs. 8.1%, p < 0.001). In addition, AIS girls with Cobb angle >60° experienced onset of menses at an average age of 13.25 years, which was significantly later than AIS girls with Cobb angle <40° (12.81 years, p < 0.05) and marginally significantly later than AIS girls with Cobb angle between 40 and 60° (12.86 years, p = 0.053). In conclusion, a tendency of delayed onset of menarche was observed in Chinese idiopathic scoliotic girls in this large sample study, especially for girls with Cobb angle >60°, which is supported by multiple previously established positive linkages on AIS etiology studies. Accordingly it is believed that late menarche may contribute importantly to abnormal pubertal growth and subsequently modulate curve behavior in AIS.</AbstractText
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In Preclinical Epilepsy, GLUT1 and GFAP Dysregulation in Cells Surrounding the Third Ventricle, Including Tanycytes, Is Differentially Restored with Ketogenic Diet Treatment. <b
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15171772
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12206847
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15662200
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Objective changes in brow position, superior palpebral crease, peak angle of the eyebrow, and jowl surface area after volumetric radiofrequency treatments to half of the face.
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The cryobiology of cryosurgical injury.
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Blind source separation and the analysis of microarray data.
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Radiofrequency application through a proprietary device has recently been used for facial tissue tightening. Uniform volumetric heating of the dermis is created by passage of electrical current, while protection of the epidermis is maintained by concurrent cryogen cooling.</AbstractText To objectively quantify the effectiveness of volumetric radiofrequency application on the face, we treated 10 patients on the left side of the face with radiofrequency and evaluated the changes in brow position, superior palpebral crease, angle of the eyebrow, and jowl surface area.</AbstractText Uniform treatments were applied at 134 J/cm(2) to the left side of the forehead and 1 cm past midline, at 115 J/cm(2) to the left side of temple and cheeks, and at 97 J/cm(2) to the left side of the jaw line and inferior postauricular surface. Patients were evaluated at monthly intervals up to 3 months with digital photography. Morphologic changes were evaluated with the "measuring tool" and "angle tool" of the Mirror Suite imaging system for aligned frontal-view photographs (for eyebrow position, superior palpebral crease elevation, and eyebrow angle changes) and the "outline tool" for aligned oblique-view photographs (for jowl surface area changes).</AbstractText At the end of 3 months on the side that was treated, patients exhibited on average 4.3 mm of brow elevation and 1.9 mm of superior palpebral crease elevation along the midpupillary line and an average of 2.4 mm of brow elevation along the lateral canthal line. There was no significant improvement of brow elevation along the lateral canthal line on the contralateral side. The peak angle of the ipsilateral eyebrow became slightly more acute by an average of 4.5 degrees after treatments. Moreover, the jowls on the lower part of the face, displayed a mean decrease of 22.6% in surface area after treatments. The nontreated side displayed a lack of eyebrow angle and jowl surface area changes.</AbstractText The application of radiofrequency to the face provides quantifiable changes. The brow along the midpupillary line is elevated to a greater degree than the lateral brow. This is consistent with acute angle changes seen in the eyebrow. Improvements in the lower part of the face with radiofrequency application can be quantified by demonstrating a decrease jowl surface. Moreover, these measurement techniques can be useful tools for evaluating other treatment parameters with radiofrequency application.</AbstractText
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Cryosurgery, or tissue destruction by controlled freezing, has been investigated as a possible alternative to surgical intervention in the treatment of many diseases. This technique, which is under the larger category of thermal therapy, has its origins in the 1800s when advanced carcinomas of the breast and uterine cervix were treated with iced saline solutions. Since those early times, this technique has been used routinely to treat malignancies on the surface of the body (ie, dermatologic tumors) and has gained some acceptance as a clinical tool for the management of internal malignancies, including carcinoma of the prostate and kidney. The main advantages of the technique are the potential for less invasiveness and lower morbidity compared with surgical excision. The study of the destructive process of freezing is the focus of this article and is divided into 2 main areas: (1) understanding the mechanism by which freezing destroys tissue, and (2) understanding the thermal history that causes tissue destruction. The term "thermal history," as used in this article, will mean the time-temperature history experienced by the tissue during a thermal insult.</AbstractText
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We develop an approach for the exploratory analysis of gene expression data, based upon blind source separation techniques. This approach exploits higher-order statistics to identify a linear model for (logarithms of) expression profiles, described as linear combinations of "independent sources." As a result, it yields "elementary expression patterns" (the "sources"), which may be interpreted as potential regulation pathways. Further analysis of the so-obtained sources show that they are generally characterized by a small number of specific coexpressed or antiexpressed genes. In addition, the projections of the expression profiles onto the estimated sources often provides significant clustering of conditions. The algorithm relies on a large number of runs of "independent component analysis" with random initializations, followed by a search of "consensus sources." It then provides estimates for independent sources, together with an assessment of their robustness. The results obtained on two datasets (namely, breast cancer data and Bacillus subtilis sulfur metabolism data) show that some of the obtained gene families correspond to well known families of coregulated genes, which validates the proposed approach.</AbstractText
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Objective changes in brow position, superior palpebral crease, peak angle of the eyebrow, and jowl surface area after volumetric radiofrequency treatments to half of the face. Radiofrequency application through a proprietary device has recently been used for facial tissue tightening. Uniform volumetric heating of the dermis is created by passage of electrical current, while protection of the epidermis is maintained by concurrent cryogen cooling.</AbstractText To objectively quantify the effectiveness of volumetric radiofrequency application on the face, we treated 10 patients on the left side of the face with radiofrequency and evaluated the changes in brow position, superior palpebral crease, angle of the eyebrow, and jowl surface area.</AbstractText Uniform treatments were applied at 134 J/cm(2) to the left side of the forehead and 1 cm past midline, at 115 J/cm(2) to the left side of temple and cheeks, and at 97 J/cm(2) to the left side of the jaw line and inferior postauricular surface. Patients were evaluated at monthly intervals up to 3 months with digital photography. Morphologic changes were evaluated with the "measuring tool" and "angle tool" of the Mirror Suite imaging system for aligned frontal-view photographs (for eyebrow position, superior palpebral crease elevation, and eyebrow angle changes) and the "outline tool" for aligned oblique-view photographs (for jowl surface area changes).</AbstractText At the end of 3 months on the side that was treated, patients exhibited on average 4.3 mm of brow elevation and 1.9 mm of superior palpebral crease elevation along the midpupillary line and an average of 2.4 mm of brow elevation along the lateral canthal line. There was no significant improvement of brow elevation along the lateral canthal line on the contralateral side. The peak angle of the ipsilateral eyebrow became slightly more acute by an average of 4.5 degrees after treatments. Moreover, the jowls on the lower part of the face, displayed a mean decrease of 22.6% in surface area after treatments. The nontreated side displayed a lack of eyebrow angle and jowl surface area changes.</AbstractText The application of radiofrequency to the face provides quantifiable changes. The brow along the midpupillary line is elevated to a greater degree than the lateral brow. This is consistent with acute angle changes seen in the eyebrow. Improvements in the lower part of the face with radiofrequency application can be quantified by demonstrating a decrease jowl surface. Moreover, these measurement techniques can be useful tools for evaluating other treatment parameters with radiofrequency application.</AbstractText
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The cryobiology of cryosurgical injury. Cryosurgery, or tissue destruction by controlled freezing, has been investigated as a possible alternative to surgical intervention in the treatment of many diseases. This technique, which is under the larger category of thermal therapy, has its origins in the 1800s when advanced carcinomas of the breast and uterine cervix were treated with iced saline solutions. Since those early times, this technique has been used routinely to treat malignancies on the surface of the body (ie, dermatologic tumors) and has gained some acceptance as a clinical tool for the management of internal malignancies, including carcinoma of the prostate and kidney. The main advantages of the technique are the potential for less invasiveness and lower morbidity compared with surgical excision. The study of the destructive process of freezing is the focus of this article and is divided into 2 main areas: (1) understanding the mechanism by which freezing destroys tissue, and (2) understanding the thermal history that causes tissue destruction. The term "thermal history," as used in this article, will mean the time-temperature history experienced by the tissue during a thermal insult.</AbstractText
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Blind source separation and the analysis of microarray data. We develop an approach for the exploratory analysis of gene expression data, based upon blind source separation techniques. This approach exploits higher-order statistics to identify a linear model for (logarithms of) expression profiles, described as linear combinations of "independent sources." As a result, it yields "elementary expression patterns" (the "sources"), which may be interpreted as potential regulation pathways. Further analysis of the so-obtained sources show that they are generally characterized by a small number of specific coexpressed or antiexpressed genes. In addition, the projections of the expression profiles onto the estimated sources often provides significant clustering of conditions. The algorithm relies on a large number of runs of "independent component analysis" with random initializations, followed by a search of "consensus sources." It then provides estimates for independent sources, together with an assessment of their robustness. The results obtained on two datasets (namely, breast cancer data and Bacillus subtilis sulfur metabolism data) show that some of the obtained gene families correspond to well known families of coregulated genes, which validates the proposed approach.</AbstractText
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40462968
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32092432
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39662178
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Aperiodic neural timescales in prefrontal cortex dilate with increased task abstraction.
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Magnitude and timing of major white matter tract maturation from infancy through adolescence with NODDI.
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Accelerated biological aging increases the risk of short- and long-term stroke prognosis in patients with ischemic stroke or TIA.
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Navigating everyday environments requires that the brain perform information processing at multiple different timescales. For example, while watching a movie we use sensory information from every video frame to construct the current movie scene, which itself is continuously integrated into the narrative arc of the film. This critical function is supported by sensory inputs propagating from dynamic sensory cortices to association cortices, where neural activity remains more stable over time. The hierarchical organization of cortex is therefore reflected in a gradient of neural timescales. While this propagation of inputs up the cortical hierarchy is facilitated by both rhythmic (oscillatory) and non-rhythmic (aperiodic) neural activity, traditional measures of oscillations are often confounded by the influence of aperiodic signals. The reverse is also true: traditional measures of aperiodic neural timescales are influenced by oscillations. This makes it difficult to distinguish between oscillatory and timescale effects in cognition. Here, we analyzed electroencephalography (EEG) data from participants performing a cognitive control task that manipulated the amount of task-relevant contextual information, called task abstraction. Critically, we separated aperiodic neural timescales from the confounding influence of oscillatory power. We hypothesized that neural timescales would increase during the task, and more so in high-abstraction conditions. We found that task abstraction dilated the aperiodic neural timescale, as estimated from the autocorrelation function, over prefrontal cortical regions. Our findings suggests that neural timescales are a dynamic feature of the cerebral cortex that change to meet task demands.</AbstractText
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White matter maturation is a nonlinear and heterogeneous phenomenon characterized by axonal packing, increased axon caliber, and a prolonged period of myelination. While current in vivo diffusion MRI (dMRI) methods, like diffusion tensor imaging (DTI), have successfully characterized the gross structure of major white matter tracts, these measures lack the specificity required to unravel the distinct processes that contribute to microstructural development. Neurite orientation dispersion and density imaging (NODDI) is a dMRI approach that probes tissue compartments and provides biologically meaningful measures that quantify neurite density index (NDI) and orientation dispersion index (ODI). The purpose of this study was to characterize the magnitude and timing of major white matter tract maturation with NODDI from infancy through adolescence in a cross-sectional cohort of 104 subjects (0.6-18.8 years). To probe the regional nature of white matter development, we use an along-tract approach that partitions tracts to enable more fine-grained analysis. Major white matter tracts showed exponential age-related changes in NDI with distinct maturational patterns. Overall, analyses revealed callosal fibers developed before association fibers. Our along-tract analyses elucidate spatially varying patterns of maturation with NDI that are distinct from those obtained with DTI. ODI was not significantly associated with age in the majority of tracts. Our results support the conclusion that white matter tract maturation is heterochronous process and, furthermore, we demonstrate regional variability in the developmental timing within major white matter tracts. Together, these results help to disentangle the distinct processes that contribute to and more specifically define the time course of white matter maturation.</AbstractText
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Biological age (BA), an integrated measure of physiological aging, has a clear link to stroke. There is a paucity of long-term longitudinal studies about the association between accelerated biological age and stroke prognosis in patients with previous strokes, and the differences in the predictive ability of various BA indicators calculated from clinical biochemistry biomarkers for future stroke outcomes are still unknown. To evaluate the role of three accelerated BA indicators for short- and long-term prognosis of patients with ischemic stroke or transient ischemic attack (TIA), and to identify the most appropriate predictor.</AbstractText This study included 7396 patients from the Third China National Stroke Registry (CNSR-III), a prospective national registry of patients with acute ischemic stroke or TIA between August 2015 and March 2018 in China. We constructed accelerated BA using three widely recognized algorithms: PhenoAge, Klemera-Doubal, and HD method. To ascertain the association of accelerated BA with the risk of short- and long-term stroke outcomes, a Cox or logistic regression model was conducted for the analysis. The net reclassification index and integrated discrimination improvement were used to evaluate the added model improvement ability of BA acceleration.</AbstractText Compared to those with the lowest of PhenoAge acceleration, patients with the highest were more likely to have a higher risk of stroke (HR 1.98, 95% CI 1.49-2.63, P < 0.001), ischemic stroke (HR 1.88, 95% CI 1.41-2.53, P < 0.001), composite vascular events (HR 2.03, 95% CI 1.53-2.68, P < 0.001), all-cause death (HR 7.02, 95% CI 3.41-14.47, P < 0.001) and the modified Rankin scale of 3-6 (OR 2.55, 95% CI 2.05-3.16, P < 0.001) at three months, and the association observed within one year and five years was similar to that within three months. The risk of all stroke outcomes for HDAge was consistent with PhenoAge acceleration, but KDMAge acceleration was the same, except for stroke within one year (HR 1.24, 95% CI 1.00-1.53, P = 0.053). PhenoAge acceleration provided a better improvement in the model's predictive ability for stroke prognosis, compared to BA determined by other algorithms.</AbstractText In this prospective cohort study, BA acceleration, particularly PhenoAge, may help identify stroke patients with risks of short- and long-term poor outcomes, potentially enabling subclinical prevention and early intervention.</AbstractText This work was supported by grants from Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-029), the National Natural Science Foundation of China (U20A20358), Beijing Hospitals Authority Clinical Medicine Development of special funding support (ZLRK202312), the National Key R&D Program of China (No. 2022YFC3602500, 2022YFC3602505), Outstanding Young Talents Project of Capital Medical University (A2105), and Beijing High-Level Public Health Technical Personnel Construction Project (Discipline leader -03-12).</AbstractText
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Aperiodic neural timescales in prefrontal cortex dilate with increased task abstraction. Navigating everyday environments requires that the brain perform information processing at multiple different timescales. For example, while watching a movie we use sensory information from every video frame to construct the current movie scene, which itself is continuously integrated into the narrative arc of the film. This critical function is supported by sensory inputs propagating from dynamic sensory cortices to association cortices, where neural activity remains more stable over time. The hierarchical organization of cortex is therefore reflected in a gradient of neural timescales. While this propagation of inputs up the cortical hierarchy is facilitated by both rhythmic (oscillatory) and non-rhythmic (aperiodic) neural activity, traditional measures of oscillations are often confounded by the influence of aperiodic signals. The reverse is also true: traditional measures of aperiodic neural timescales are influenced by oscillations. This makes it difficult to distinguish between oscillatory and timescale effects in cognition. Here, we analyzed electroencephalography (EEG) data from participants performing a cognitive control task that manipulated the amount of task-relevant contextual information, called task abstraction. Critically, we separated aperiodic neural timescales from the confounding influence of oscillatory power. We hypothesized that neural timescales would increase during the task, and more so in high-abstraction conditions. We found that task abstraction dilated the aperiodic neural timescale, as estimated from the autocorrelation function, over prefrontal cortical regions. Our findings suggests that neural timescales are a dynamic feature of the cerebral cortex that change to meet task demands.</AbstractText
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Magnitude and timing of major white matter tract maturation from infancy through adolescence with NODDI. White matter maturation is a nonlinear and heterogeneous phenomenon characterized by axonal packing, increased axon caliber, and a prolonged period of myelination. While current in vivo diffusion MRI (dMRI) methods, like diffusion tensor imaging (DTI), have successfully characterized the gross structure of major white matter tracts, these measures lack the specificity required to unravel the distinct processes that contribute to microstructural development. Neurite orientation dispersion and density imaging (NODDI) is a dMRI approach that probes tissue compartments and provides biologically meaningful measures that quantify neurite density index (NDI) and orientation dispersion index (ODI). The purpose of this study was to characterize the magnitude and timing of major white matter tract maturation with NODDI from infancy through adolescence in a cross-sectional cohort of 104 subjects (0.6-18.8 years). To probe the regional nature of white matter development, we use an along-tract approach that partitions tracts to enable more fine-grained analysis. Major white matter tracts showed exponential age-related changes in NDI with distinct maturational patterns. Overall, analyses revealed callosal fibers developed before association fibers. Our along-tract analyses elucidate spatially varying patterns of maturation with NDI that are distinct from those obtained with DTI. ODI was not significantly associated with age in the majority of tracts. Our results support the conclusion that white matter tract maturation is heterochronous process and, furthermore, we demonstrate regional variability in the developmental timing within major white matter tracts. Together, these results help to disentangle the distinct processes that contribute to and more specifically define the time course of white matter maturation.</AbstractText
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Accelerated biological aging increases the risk of short- and long-term stroke prognosis in patients with ischemic stroke or TIA. Biological age (BA), an integrated measure of physiological aging, has a clear link to stroke. There is a paucity of long-term longitudinal studies about the association between accelerated biological age and stroke prognosis in patients with previous strokes, and the differences in the predictive ability of various BA indicators calculated from clinical biochemistry biomarkers for future stroke outcomes are still unknown. To evaluate the role of three accelerated BA indicators for short- and long-term prognosis of patients with ischemic stroke or transient ischemic attack (TIA), and to identify the most appropriate predictor.</AbstractText This study included 7396 patients from the Third China National Stroke Registry (CNSR-III), a prospective national registry of patients with acute ischemic stroke or TIA between August 2015 and March 2018 in China. We constructed accelerated BA using three widely recognized algorithms: PhenoAge, Klemera-Doubal, and HD method. To ascertain the association of accelerated BA with the risk of short- and long-term stroke outcomes, a Cox or logistic regression model was conducted for the analysis. The net reclassification index and integrated discrimination improvement were used to evaluate the added model improvement ability of BA acceleration.</AbstractText Compared to those with the lowest of PhenoAge acceleration, patients with the highest were more likely to have a higher risk of stroke (HR 1.98, 95% CI 1.49-2.63, P < 0.001), ischemic stroke (HR 1.88, 95% CI 1.41-2.53, P < 0.001), composite vascular events (HR 2.03, 95% CI 1.53-2.68, P < 0.001), all-cause death (HR 7.02, 95% CI 3.41-14.47, P < 0.001) and the modified Rankin scale of 3-6 (OR 2.55, 95% CI 2.05-3.16, P < 0.001) at three months, and the association observed within one year and five years was similar to that within three months. The risk of all stroke outcomes for HDAge was consistent with PhenoAge acceleration, but KDMAge acceleration was the same, except for stroke within one year (HR 1.24, 95% CI 1.00-1.53, P = 0.053). PhenoAge acceleration provided a better improvement in the model's predictive ability for stroke prognosis, compared to BA determined by other algorithms.</AbstractText In this prospective cohort study, BA acceleration, particularly PhenoAge, may help identify stroke patients with risks of short- and long-term poor outcomes, potentially enabling subclinical prevention and early intervention.</AbstractText This work was supported by grants from Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-029), the National Natural Science Foundation of China (U20A20358), Beijing Hospitals Authority Clinical Medicine Development of special funding support (ZLRK202312), the National Key R&D Program of China (No. 2022YFC3602500, 2022YFC3602505), Outstanding Young Talents Project of Capital Medical University (A2105), and Beijing High-Level Public Health Technical Personnel Construction Project (Discipline leader -03-12).</AbstractText
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33483282
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22317837
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34720862
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Vestibular evoked myogenic potentials.
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Short-term audiologic effect of intratympanic gadolinium contrast agent application in patients with Ménière's disease.
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White Matter Integrity and Nicotine Dependence: Evaluating Vertical and Horizontal Pleiotropy.
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Vestibular Evoked Myogenic Potentials (VEMP) are commonly recorded in patients experiencing vertigo or chronic instability. This test evaluates the patient's otolith function and is often combined with both Videonystagmography and Video Head Impulse Test. VEMP is a simple, reproducible test, in the absence of any pre-existing conductive hearing loss. Cervical VEMP explore both saccular function and the inferior vestibular nerve, whereas ocular VEMP assess utricular function and the superior vestibular nerve. In combination with previously described tests, VEMP allows characterization of vertigo and provides support for the diagnosis of superior semicircular canal dehiscence syndrome, Menière's disease, vestibular neuritis, vestibular schwannoma or idiopathic bilateral vestibulopathy. A good knowledge of these electrophysiological tests is essential in order to precisely assess the presence or absence of vestibular function impairment. We describe the test recording technique and the most common pitfalls in interpretation of the results. We then outline the results observed in various diseases impacting vestibular function.</AbstractText
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The aim of this study was to assess whether gadolinium-based contrast agent influences short-term hearing function in patients with Ménière's disease undergoing intratympanically enhanced inner-ear magnetic resonance imaging.</AbstractText This is a prospective cohort study.</AbstractText This study was conducted a tertiary referral university hospital, ENT department.</AbstractText In this study, 21 adult patients with definite, unilateral Ménière's disease were included. According to the criteria of the Committee on Hearing and Equilibrium, all patients were in stage 1 or 2 of the disease, with largely preserved hearing function.</AbstractText All patients underwent clinical and audiologic testing before and 24 hours after intratympanic application of gadolinium-based contrast agent. The effects of the contrast medium on the hearing function were assessed by analysis of frequency thresholds, pure-tone average from 500 Hz to 3 kHz, and speech audiometry.</AbstractText Pure-tone average and single-frequency thresholds in audiometry showed no statistically significant difference after the application of intratympanic gadolinium-based contrast agent. Furthermore, speech audiometry scores remained stable after the application of the contrast agent.</AbstractText This study did not demonstrate clinically significant short-term effects of intratympanic application of gadolinium-based contrast agent on hearing function in patients with Ménière's disease in initial stages.</AbstractText
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Tobacco smoking is an addictive behavior that supports nicotine dependence and is an independent risk factor for cancer and other illnesses. Its neurogenetic mechanisms are not fully understood but may act through alterations in the cerebral white matter (WM). We hypothesized that the vertical pleiotropic pathways, where genetic variants influence a trait that in turn influences another trait, link genetic factors, integrity of cerebral WM, and nicotine addiction. We tested this hypothesis using individual genetic factors, WM integrity measured by fractional anisotropy (FA), and nicotine dependence-related smoking phenotypes, including smoking status (SS) and cigarettes per day (CPDs), in a large epidemiological sample collected by the UK Biobank. We performed a genome-wide association study (GWAS) to identify previously reported loci associated with smoking behavior. Smoking was found to be associated with reduced WM integrity in multiple brain regions. We then evaluated two competing vertical pathways: Genes → WM integrity → Smoking versus Genes → Smoking → WM integrity and a horizontal pleiotropy pathway where genetic factors independently affect both smoking and WM integrity. The causal pathway analysis identified 272 pleiotropic single-nucleotide polymorphisms (SNPs) whose effects on SS were mediated by FA, as well as 22 pleiotropic SNPs whose effects on FA were mediated by CPD. These SNPs were mainly located in important susceptibility genes for smoking-induced diseases <i
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Vestibular evoked myogenic potentials. Vestibular Evoked Myogenic Potentials (VEMP) are commonly recorded in patients experiencing vertigo or chronic instability. This test evaluates the patient's otolith function and is often combined with both Videonystagmography and Video Head Impulse Test. VEMP is a simple, reproducible test, in the absence of any pre-existing conductive hearing loss. Cervical VEMP explore both saccular function and the inferior vestibular nerve, whereas ocular VEMP assess utricular function and the superior vestibular nerve. In combination with previously described tests, VEMP allows characterization of vertigo and provides support for the diagnosis of superior semicircular canal dehiscence syndrome, Menière's disease, vestibular neuritis, vestibular schwannoma or idiopathic bilateral vestibulopathy. A good knowledge of these electrophysiological tests is essential in order to precisely assess the presence or absence of vestibular function impairment. We describe the test recording technique and the most common pitfalls in interpretation of the results. We then outline the results observed in various diseases impacting vestibular function.</AbstractText
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Short-term audiologic effect of intratympanic gadolinium contrast agent application in patients with Ménière's disease. The aim of this study was to assess whether gadolinium-based contrast agent influences short-term hearing function in patients with Ménière's disease undergoing intratympanically enhanced inner-ear magnetic resonance imaging.</AbstractText This is a prospective cohort study.</AbstractText This study was conducted a tertiary referral university hospital, ENT department.</AbstractText In this study, 21 adult patients with definite, unilateral Ménière's disease were included. According to the criteria of the Committee on Hearing and Equilibrium, all patients were in stage 1 or 2 of the disease, with largely preserved hearing function.</AbstractText All patients underwent clinical and audiologic testing before and 24 hours after intratympanic application of gadolinium-based contrast agent. The effects of the contrast medium on the hearing function were assessed by analysis of frequency thresholds, pure-tone average from 500 Hz to 3 kHz, and speech audiometry.</AbstractText Pure-tone average and single-frequency thresholds in audiometry showed no statistically significant difference after the application of intratympanic gadolinium-based contrast agent. Furthermore, speech audiometry scores remained stable after the application of the contrast agent.</AbstractText This study did not demonstrate clinically significant short-term effects of intratympanic application of gadolinium-based contrast agent on hearing function in patients with Ménière's disease in initial stages.</AbstractText
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White Matter Integrity and Nicotine Dependence: Evaluating Vertical and Horizontal Pleiotropy. Tobacco smoking is an addictive behavior that supports nicotine dependence and is an independent risk factor for cancer and other illnesses. Its neurogenetic mechanisms are not fully understood but may act through alterations in the cerebral white matter (WM). We hypothesized that the vertical pleiotropic pathways, where genetic variants influence a trait that in turn influences another trait, link genetic factors, integrity of cerebral WM, and nicotine addiction. We tested this hypothesis using individual genetic factors, WM integrity measured by fractional anisotropy (FA), and nicotine dependence-related smoking phenotypes, including smoking status (SS) and cigarettes per day (CPDs), in a large epidemiological sample collected by the UK Biobank. We performed a genome-wide association study (GWAS) to identify previously reported loci associated with smoking behavior. Smoking was found to be associated with reduced WM integrity in multiple brain regions. We then evaluated two competing vertical pathways: Genes → WM integrity → Smoking versus Genes → Smoking → WM integrity and a horizontal pleiotropy pathway where genetic factors independently affect both smoking and WM integrity. The causal pathway analysis identified 272 pleiotropic single-nucleotide polymorphisms (SNPs) whose effects on SS were mediated by FA, as well as 22 pleiotropic SNPs whose effects on FA were mediated by CPD. These SNPs were mainly located in important susceptibility genes for smoking-induced diseases <i
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34520095
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26762877
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34680578
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Neuroimaging measures of iron and gliosis explain memory performance in aging.
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T1 Mapping: Basic Techniques and Clinical Applications.
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Stereotactic Arrhythmia Radioablation as a Novel Treatment Approach for Cardiac Arrhythmias: Facts and Limitations.
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Evidence from animal and histological studies has indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo. The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multicompartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age-related increases in iron content (R2*) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low-moderate iron (hippocampus, caudate) and to all diffusion metrics in regions with moderate-high iron (putamen, globus pallidus). This pattern is consistent with different stages of iron-related gliosis, ranging from astrogliosis that may influence intracellular diffusion to microglial proliferation and increased vascular permeability that may influence all sources of diffusion. Further, hippocampal restricted diffusion was significantly related to memory performance, with a third of this effect related to iron content; consistent with the hypothesis that higher iron-related astrogliosis in the hippocampus is associated with poorer memory performance. These results demonstrate the sensitivity of MRI to iron-related gliosis and extend our understanding of its impact on cognition by showing that this relationship also explains individual differences in memory performance.</AbstractText
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In cardiac magnetic resonance (CMR) imaging, the T1 relaxation time for the 1H magnetization in myocardial tissue may represent a valuable biomarker for a variety of pathological conditions. This possibility has driven the growing interest in quantifying T1, rather than just relying on its effect on image contrast. The techniques have advanced to where pixel-level myocardial T1 mapping has become a routine component of CMR examinations. Combined with the use of contrast agents, T1 mapping has led an expansive investigation of interstitial remodeling in ischemic and nonischemic heart disease. The purpose of this review was to introduce the reader to the physical principles of T1 mapping, the imaging techniques developed for T1 mapping, the pathophysiological markers accessible by T1 mapping, and its clinical uses.</AbstractText
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Stereotactic ablative radiotherapy (SABR) is highly focused radiation therapy that targets well-demarcated, limited-volume malignant or benign tumors with high accuracy and precision using image guidance. Stereotactic arrhythmia radioablation (STAR) applies SABR to treat cardiac arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF), and has recently been a focus in research. Clinical studies have demonstrated electrophysiologic conduction blockade and histologic fibrosis after STAR, which provides a proof of principle for its potential for treating arrhythmias. This review will present the basic STAR principles, available clinical study outcomes, and how the technique has evolved since the first pre-clinical study. In addition to the clinical workflow, focus will be given on the process for stereotactic radiotherapy Quality Assurance (QA) tests, as well as the need for establishing a standardized QA protocol. Future implications and potential courses of research will also be discussed.</AbstractText
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Neuroimaging measures of iron and gliosis explain memory performance in aging. Evidence from animal and histological studies has indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo. The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multicompartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age-related increases in iron content (R2*) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low-moderate iron (hippocampus, caudate) and to all diffusion metrics in regions with moderate-high iron (putamen, globus pallidus). This pattern is consistent with different stages of iron-related gliosis, ranging from astrogliosis that may influence intracellular diffusion to microglial proliferation and increased vascular permeability that may influence all sources of diffusion. Further, hippocampal restricted diffusion was significantly related to memory performance, with a third of this effect related to iron content; consistent with the hypothesis that higher iron-related astrogliosis in the hippocampus is associated with poorer memory performance. These results demonstrate the sensitivity of MRI to iron-related gliosis and extend our understanding of its impact on cognition by showing that this relationship also explains individual differences in memory performance.</AbstractText
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T1 Mapping: Basic Techniques and Clinical Applications. In cardiac magnetic resonance (CMR) imaging, the T1 relaxation time for the 1H magnetization in myocardial tissue may represent a valuable biomarker for a variety of pathological conditions. This possibility has driven the growing interest in quantifying T1, rather than just relying on its effect on image contrast. The techniques have advanced to where pixel-level myocardial T1 mapping has become a routine component of CMR examinations. Combined with the use of contrast agents, T1 mapping has led an expansive investigation of interstitial remodeling in ischemic and nonischemic heart disease. The purpose of this review was to introduce the reader to the physical principles of T1 mapping, the imaging techniques developed for T1 mapping, the pathophysiological markers accessible by T1 mapping, and its clinical uses.</AbstractText
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Stereotactic Arrhythmia Radioablation as a Novel Treatment Approach for Cardiac Arrhythmias: Facts and Limitations. Stereotactic ablative radiotherapy (SABR) is highly focused radiation therapy that targets well-demarcated, limited-volume malignant or benign tumors with high accuracy and precision using image guidance. Stereotactic arrhythmia radioablation (STAR) applies SABR to treat cardiac arrhythmias, including ventricular tachycardia (VT) and atrial fibrillation (AF), and has recently been a focus in research. Clinical studies have demonstrated electrophysiologic conduction blockade and histologic fibrosis after STAR, which provides a proof of principle for its potential for treating arrhythmias. This review will present the basic STAR principles, available clinical study outcomes, and how the technique has evolved since the first pre-clinical study. In addition to the clinical workflow, focus will be given on the process for stereotactic radiotherapy Quality Assurance (QA) tests, as well as the need for establishing a standardized QA protocol. Future implications and potential courses of research will also be discussed.</AbstractText
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40566853
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38643018
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40060569
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The Role of Cannabis Policies and Perceptions of Penalties on the Association Between Adolescent Social Bonds and Cannabis Use.
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Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?
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Heart Scar-In-A-Dish: Tissue Culture Platform to Study Myocardial Infarct Healing In Vitro.
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Recent shifts in cannabis policies have led to lowered risk perceptions, less disapproval of use, and an increase in use among adolescents. This increase in usage is problematic as heavy cannabis use during adolescence can hinder brain development and increase the likelihood of mental health disorders. As such, it is crucial to understand the factors safeguarding adolescents from cannabis use. Research suggests that social bonds and legal consequences may be protective factors against adolescent cannabis use. However, it remains uncertain whether increased accessibility of cannabis undermines the effectiveness of these protective factors.</AbstractText The current study uses data from the 2023 National Survey on Drug Use and Health to investigate the impact of state-level medical cannabis policies and perceptions of state-level cannabis possession penalties on past year cannabis use, as well as whether these variables moderate the association between social bonds (attachment, commitment, involvement) and past year cannabis use among adolescents.</AbstractText The results indicate that medical cannabis policies are positively and significantly associated with past year cannabis use, while perception of serious criminal justice penalties for cannabis possession is negatively and significantly associated with past year cannabis use. Additionally, the effects of attachment and involvement differ by medical cannabis policy status, but there was no evidence that perception of penalties moderated the association between social bonds and cannabis use.</AbstractText The results of the current study reveal a need for more education among adolescents on both the health consequences and criminal penalties for cannabis use.</AbstractText
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Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. βFSIQ = -1.9, SEFSIQ = 0.3, PFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%-43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. rrb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. βFSIQ = 0.9, SEFSIQ = 0.3, PFSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.</AbstractText
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Myocardial Infarction (MI) is a major contributor to morbidity and mortality, wherein blood flow is blocked to a portion of the left ventricle and leads to myocardial necrosis and scar formation. Cardiac remodeling in response to MI is a major determinant of patient prognosis, so many therapies are under development to improve infarct healing. Part of this development involves in vitro therapy screening which can be accelerated by engineered heart tissues (EHTs). Unfortunately, EHTs often over-simplify the infarcted tissue microarchitecture by neglecting spatial variation found in infarcted ventricles. MI results in a spatially heterogeneous environment with an infarct zone composed mostly of extracellular matrix (ECM) and cardiac fibroblasts, contrasted with a remote (non-infarct) zone composed mostly of cardiomyocytes, and a border zone transitioning in between. The heterogeneous structure is accompanied by heterogeneous mechanics where the passive infarct zone is cyclically stretched under tension as the remote zone cyclically contracts with every heartbeat. We present an in vitro 3-dimensional tissue culture platform focused on mimicking the heterogeneous mechanical environment of post-infarct myocardium. Herein, EHTs were subjected to a cryowound injury to induce localized cell death in a central portion of beating tissues composed of neonatal rat cardiomyocytes and cardiac fibroblasts. After injury, the remote zone continued to contract (i.e., negative strains) while the wounded zone was cyclically stretched (i.e., positive tensile strains) with intermediate strains in the border zone. We also observed increased tissue stiffnesses in the wounded zone and border zone following injury, while the remote zone did not show the same stiffening. Collectively, this work establishes a novel in vitro platform for characterizing myocardial wound remodeling with both spatial and temporal resolution, contributing to a deeper understanding of MI and offering insights for potential therapeutic approaches.</AbstractText
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The Role of Cannabis Policies and Perceptions of Penalties on the Association Between Adolescent Social Bonds and Cannabis Use. Recent shifts in cannabis policies have led to lowered risk perceptions, less disapproval of use, and an increase in use among adolescents. This increase in usage is problematic as heavy cannabis use during adolescence can hinder brain development and increase the likelihood of mental health disorders. As such, it is crucial to understand the factors safeguarding adolescents from cannabis use. Research suggests that social bonds and legal consequences may be protective factors against adolescent cannabis use. However, it remains uncertain whether increased accessibility of cannabis undermines the effectiveness of these protective factors.</AbstractText The current study uses data from the 2023 National Survey on Drug Use and Health to investigate the impact of state-level medical cannabis policies and perceptions of state-level cannabis possession penalties on past year cannabis use, as well as whether these variables moderate the association between social bonds (attachment, commitment, involvement) and past year cannabis use among adolescents.</AbstractText The results indicate that medical cannabis policies are positively and significantly associated with past year cannabis use, while perception of serious criminal justice penalties for cannabis possession is negatively and significantly associated with past year cannabis use. Additionally, the effects of attachment and involvement differ by medical cannabis policy status, but there was no evidence that perception of penalties moderated the association between social bonds and cannabis use.</AbstractText The results of the current study reveal a need for more education among adolescents on both the health consequences and criminal penalties for cannabis use.</AbstractText
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Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline? Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. βFSIQ = -1.9, SEFSIQ = 0.3, PFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%-43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. rrb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. βFSIQ = 0.9, SEFSIQ = 0.3, PFSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.</AbstractText
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Heart Scar-In-A-Dish: Tissue Culture Platform to Study Myocardial Infarct Healing In Vitro. Myocardial Infarction (MI) is a major contributor to morbidity and mortality, wherein blood flow is blocked to a portion of the left ventricle and leads to myocardial necrosis and scar formation. Cardiac remodeling in response to MI is a major determinant of patient prognosis, so many therapies are under development to improve infarct healing. Part of this development involves in vitro therapy screening which can be accelerated by engineered heart tissues (EHTs). Unfortunately, EHTs often over-simplify the infarcted tissue microarchitecture by neglecting spatial variation found in infarcted ventricles. MI results in a spatially heterogeneous environment with an infarct zone composed mostly of extracellular matrix (ECM) and cardiac fibroblasts, contrasted with a remote (non-infarct) zone composed mostly of cardiomyocytes, and a border zone transitioning in between. The heterogeneous structure is accompanied by heterogeneous mechanics where the passive infarct zone is cyclically stretched under tension as the remote zone cyclically contracts with every heartbeat. We present an in vitro 3-dimensional tissue culture platform focused on mimicking the heterogeneous mechanical environment of post-infarct myocardium. Herein, EHTs were subjected to a cryowound injury to induce localized cell death in a central portion of beating tissues composed of neonatal rat cardiomyocytes and cardiac fibroblasts. After injury, the remote zone continued to contract (i.e., negative strains) while the wounded zone was cyclically stretched (i.e., positive tensile strains) with intermediate strains in the border zone. We also observed increased tissue stiffnesses in the wounded zone and border zone following injury, while the remote zone did not show the same stiffening. Collectively, this work establishes a novel in vitro platform for characterizing myocardial wound remodeling with both spatial and temporal resolution, contributing to a deeper understanding of MI and offering insights for potential therapeutic approaches.</AbstractText
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40204432
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26157000
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40097702
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Takeaways from the First Year of Open Peer Review at JNeurosci.
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Deep Neural Networks Reveal a Gradient in the Complexity of Neural Representations across the Ventral Stream.
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Hybrid manganite-graphene sensor for magnetic field magnitude and direction measurement.
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<i
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Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream.</AbstractText
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In this work, we present a novel hybrid magnetic sensor that combines the unique properties of manganite and graphene to measure both the magnitude and direction of a magnetic field. The sensor consists of a nanostructured manganite film to detect the magnetic field strength and a graphene layer to determine the angle between the magnetic field and the sensor plane. This dual sensor approach increases sensitivity over a wide range of magnetic field strengths and provides directional information, making it ideal for applications such as object positioning and navigation. The sensor design, based on a voltage divider configuration, has been optimized to achieve high sensitivity. Experimental results in pulsed magnetic fields up to 21 T demonstrated the increased sensitivity offered by the graphene-manganite combination. In addition, a measurement system for recording and processing data was developed that enables real-time measurement of the magnetic field magnitude and its orientation.</AbstractText
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Takeaways from the First Year of Open Peer Review at JNeurosci. <i
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Deep Neural Networks Reveal a Gradient in the Complexity of Neural Representations across the Ventral Stream. Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream.</AbstractText
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Hybrid manganite-graphene sensor for magnetic field magnitude and direction measurement. In this work, we present a novel hybrid magnetic sensor that combines the unique properties of manganite and graphene to measure both the magnitude and direction of a magnetic field. The sensor consists of a nanostructured manganite film to detect the magnetic field strength and a graphene layer to determine the angle between the magnetic field and the sensor plane. This dual sensor approach increases sensitivity over a wide range of magnetic field strengths and provides directional information, making it ideal for applications such as object positioning and navigation. The sensor design, based on a voltage divider configuration, has been optimized to achieve high sensitivity. Experimental results in pulsed magnetic fields up to 21 T demonstrated the increased sensitivity offered by the graphene-manganite combination. In addition, a measurement system for recording and processing data was developed that enables real-time measurement of the magnetic field magnitude and its orientation.</AbstractText
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40425313
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30819546
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40572187
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Rod Inputs Arrive at Horizontal Cell Somas in Mouse Retina Solely via Rod-Cone Coupling.
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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration.
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Diagnostic Utility of (18)F-FDG PET/CT in Infective Endocarditis.
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Rod and cone photoreceptor cells selectively contact different compartments of axon-bearing retinal horizontal cells in the mammalian retina. Cones synapse exclusively on the soma whereas rods synapse exclusively on a large axon terminal compartment. The possibility that rod signals can travel down the axon from terminal to soma has been proposed as a means of producing spectrally opponent interactions between rods and cones, but there is conflicting data about whether this actually occurs. The spectral overlap between rods and cones in mouse makes it difficult to stimulate rod and cone pigments separately. We therefore used optogenetic techniques to analyze photoreceptor inputs into horizontal somas by selectively expressing channelrhodopsin in rods and/or cones. Optogenetic stimulation of rods and cones both evoked large fast inward currents in horizontal cell somas. Cone-driven responses were abolished by eliminating synaptic release in a cone-specific knock-out of the exocytotic calcium sensor, synaptotagmin 1 (Syt1). However, rod-driven responses in horizontal somas were unchanged after eliminating synaptic release from rods but abolished by eliminating release from both rods and cones. This suggests that release from cones is required for transmission of rod signals to horizontal cell somas. Rods and cones are coupled by Cx36 gap junctions, and we found that selective elimination of Cx36 from rods also abolished rod-driven optogenetic responses in horizontal cell somas. Together, these results show that rod signals reach the somas of B-type horizontal cells exclusively via gap junctions with cones and not by transmission down the axon from the axon terminal.</AbstractText
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Neurons exhibit a limited ability of repair. Given that mechanical forces affect neuronal outgrowth, it is important to investigate whether mechanosensitive ion channels may regulate axon regeneration. Here, we show that DmPiezo, a Ca<sup
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Infective endocarditis (IE) as a diagnosis remains challenging, particularly in prosthetic valve endocarditis (PVE). This study evaluates the diagnostic utility of <sup
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Rod Inputs Arrive at Horizontal Cell Somas in Mouse Retina Solely via Rod-Cone Coupling. Rod and cone photoreceptor cells selectively contact different compartments of axon-bearing retinal horizontal cells in the mammalian retina. Cones synapse exclusively on the soma whereas rods synapse exclusively on a large axon terminal compartment. The possibility that rod signals can travel down the axon from terminal to soma has been proposed as a means of producing spectrally opponent interactions between rods and cones, but there is conflicting data about whether this actually occurs. The spectral overlap between rods and cones in mouse makes it difficult to stimulate rod and cone pigments separately. We therefore used optogenetic techniques to analyze photoreceptor inputs into horizontal somas by selectively expressing channelrhodopsin in rods and/or cones. Optogenetic stimulation of rods and cones both evoked large fast inward currents in horizontal cell somas. Cone-driven responses were abolished by eliminating synaptic release in a cone-specific knock-out of the exocytotic calcium sensor, synaptotagmin 1 (Syt1). However, rod-driven responses in horizontal somas were unchanged after eliminating synaptic release from rods but abolished by eliminating release from both rods and cones. This suggests that release from cones is required for transmission of rod signals to horizontal cell somas. Rods and cones are coupled by Cx36 gap junctions, and we found that selective elimination of Cx36 from rods also abolished rod-driven optogenetic responses in horizontal cell somas. Together, these results show that rod signals reach the somas of B-type horizontal cells exclusively via gap junctions with cones and not by transmission down the axon from the axon terminal.</AbstractText
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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration. Neurons exhibit a limited ability of repair. Given that mechanical forces affect neuronal outgrowth, it is important to investigate whether mechanosensitive ion channels may regulate axon regeneration. Here, we show that DmPiezo, a Ca<sup
|
Diagnostic Utility of (18)F-FDG PET/CT in Infective Endocarditis. Infective endocarditis (IE) as a diagnosis remains challenging, particularly in prosthetic valve endocarditis (PVE). This study evaluates the diagnostic utility of <sup
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21280904
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19767295
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21134399
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Optoelectrophysiological stimulation of the human eye using fundus-controlled silent substitution technique.
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Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism.
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A method to solubilise protein aggregates for immunoassay quantification which overcomes the neurofilament "hook" effect.
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We design, characterize, and apply a novel optoelectrophysiological setup for a fundus-controlled silent substitution technique that accounts for interindividual variability in retina morphology and simultaneously monitors the stimulation site under investigation. We connect a digital color liquid crystal on silicon projector, an electron-multiplying imager, and a light-emitting diode to a fundus camera. The temporal and spatial characterization reveal a maximal contrast loss of 7% for the highest stimulation frequency (30 Hz) and maximum cutoff spatial frequencies of ∼120 cycles∕deg. Two silent substitution flash sequences are applied to modulate selective activity in the short-wavelength-sensitive cone (S-cone) and combined long- and middle-wavelength-sensitive cone (LM-cone) pathways. Simultaneously, the visual evoked potentials are recorded. The data are compared to the grand average responses from a previous study that employed standard computer-screen presentation and showed very good latency matches. All the volunteers in the present examination exhibit differences between the S-cone and LM-cone evoked potentials (parameters mean values: peak-to-peak amplitude, N1 latency, and P1 latency for S-cone∕LM-cone responses: 8 μV∕15 μV, 113 ms∕89 ms, 170 ms∕143 ms). We demonstrate that the developed optoelectrophysiological setup simultaneously provides imaging, functional stimulation, and electrophysiological investigation of the retina.</AbstractText
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The cone cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. This channel is composed of two structurally related subunits, CNGA3 and CNGB3; CNGA3 is the ion-conducting subunit, whereas CNGB3 is a modulatory subunit. Mutations in both subunits are associated with achromatopsia and progressive cone dystrophy, with mutations in CNGB3 alone accounting for 50% of all known cases of achromatopsia. However, the molecular mechanisms underlying cone diseases that result from CNGB3 deficiency are unknown. This study investigated the role of CNGB3 in cones, using CNGB3(-/-) mice. Cone dysfunction was apparent at the earliest time point examined (post-natal day 30) in CNGB3(-/-) mice. When compared with wild-type (WT) controls: photopic electroretingraphic (ERG) responses were decreased by approximately 75%, whereas scotopic ERG responses were unchanged; visual acuity was decreased by approximately 20%, whereas contrast sensitivity was unchanged; cone density was reduced by approximately 40%; photoreceptor apoptosis was detected; and outer segment disorganization was observed in some cones. Notably, CNGA3 protein and mRNA levels were significantly decreased in CNGB3(-/-) mice; in contrast, mRNA levels of S-opsin, Gnat2 and Pde6c were unchanged, relative to WT mice. Hence, we show that loss of CNGB3 reduces biosynthesis of CNGA3 and impairs cone CNG channel function. We suggest that down-regulation of CNGA3 contributes to the pathogenic mechanism by which CNGB3 mutations lead to human cone disease.</AbstractText
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Neurofilament (Nf) aggregates are a common pathological feature of neurodegenerative disorders. Although Nf levels have been investigated as a potential disease biomarker, Nf aggregates may mask Nf epitopes, preventing accurate quantification by immunoassay. Using the SOD1(G93A) mouse model of amyotrophic lateral sclerosis, we developed a method to disrupt Nf aggregates, allowing optimal immunoassay performance.</AbstractText Phosphorylated (NfH(SMI35)) and hyperphosphorylated (NfH(SMI34)) Nf levels in plasma from 120-day SOD1(G93A) mice were quantified using an in-house ELISA modified for use with small volumes. Different pre-analytical methods were tested for their ability to solubilize Nf aggregates and immunoblotting was used for qualitative analysis.</AbstractText A 'hook effect' was observed for serially diluted plasma samples quantified using an ELISA originally developed for CSF samples. Immunoblotting confirmed the existence of high molecular-weight NfH aggregates in plasma and the resolving effect of timed urea on these aggregates. Thermostatic (pre-thawing) and chemical (calcium chelators, urea) pre-analytical processing of samples had variable success in disrupting NfH aggregates. Timed urea-calcium chelator incubation yielded the most consistent plasma NfH levels. A one hour sample pre-incubation with 0.5M urea in Barbitone-EDTA buffer at room temperature resolved the "hook effect" without compromising the ELISA. In SOD1(G93A) mice, median levels of NfH(SMI34) were over 10-fold and NfH(SMI35) levels 5-fold greater than controls.</AbstractText NfH aggregates can be solubilised and the "hook effect" abolished by a one-hour sample pre-incubation in a urea-calcium chelator-enriched buffer. This method is applicable for quantification of NfH phosphoforms in experimental and disease settings where Nf aggregate formation occurs.</AbstractText
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Optoelectrophysiological stimulation of the human eye using fundus-controlled silent substitution technique. We design, characterize, and apply a novel optoelectrophysiological setup for a fundus-controlled silent substitution technique that accounts for interindividual variability in retina morphology and simultaneously monitors the stimulation site under investigation. We connect a digital color liquid crystal on silicon projector, an electron-multiplying imager, and a light-emitting diode to a fundus camera. The temporal and spatial characterization reveal a maximal contrast loss of 7% for the highest stimulation frequency (30 Hz) and maximum cutoff spatial frequencies of ∼120 cycles∕deg. Two silent substitution flash sequences are applied to modulate selective activity in the short-wavelength-sensitive cone (S-cone) and combined long- and middle-wavelength-sensitive cone (LM-cone) pathways. Simultaneously, the visual evoked potentials are recorded. The data are compared to the grand average responses from a previous study that employed standard computer-screen presentation and showed very good latency matches. All the volunteers in the present examination exhibit differences between the S-cone and LM-cone evoked potentials (parameters mean values: peak-to-peak amplitude, N1 latency, and P1 latency for S-cone∕LM-cone responses: 8 μV∕15 μV, 113 ms∕89 ms, 170 ms∕143 ms). We demonstrate that the developed optoelectrophysiological setup simultaneously provides imaging, functional stimulation, and electrophysiological investigation of the retina.</AbstractText
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Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism. The cone cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. This channel is composed of two structurally related subunits, CNGA3 and CNGB3; CNGA3 is the ion-conducting subunit, whereas CNGB3 is a modulatory subunit. Mutations in both subunits are associated with achromatopsia and progressive cone dystrophy, with mutations in CNGB3 alone accounting for 50% of all known cases of achromatopsia. However, the molecular mechanisms underlying cone diseases that result from CNGB3 deficiency are unknown. This study investigated the role of CNGB3 in cones, using CNGB3(-/-) mice. Cone dysfunction was apparent at the earliest time point examined (post-natal day 30) in CNGB3(-/-) mice. When compared with wild-type (WT) controls: photopic electroretingraphic (ERG) responses were decreased by approximately 75%, whereas scotopic ERG responses were unchanged; visual acuity was decreased by approximately 20%, whereas contrast sensitivity was unchanged; cone density was reduced by approximately 40%; photoreceptor apoptosis was detected; and outer segment disorganization was observed in some cones. Notably, CNGA3 protein and mRNA levels were significantly decreased in CNGB3(-/-) mice; in contrast, mRNA levels of S-opsin, Gnat2 and Pde6c were unchanged, relative to WT mice. Hence, we show that loss of CNGB3 reduces biosynthesis of CNGA3 and impairs cone CNG channel function. We suggest that down-regulation of CNGA3 contributes to the pathogenic mechanism by which CNGB3 mutations lead to human cone disease.</AbstractText
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A method to solubilise protein aggregates for immunoassay quantification which overcomes the neurofilament "hook" effect. Neurofilament (Nf) aggregates are a common pathological feature of neurodegenerative disorders. Although Nf levels have been investigated as a potential disease biomarker, Nf aggregates may mask Nf epitopes, preventing accurate quantification by immunoassay. Using the SOD1(G93A) mouse model of amyotrophic lateral sclerosis, we developed a method to disrupt Nf aggregates, allowing optimal immunoassay performance.</AbstractText Phosphorylated (NfH(SMI35)) and hyperphosphorylated (NfH(SMI34)) Nf levels in plasma from 120-day SOD1(G93A) mice were quantified using an in-house ELISA modified for use with small volumes. Different pre-analytical methods were tested for their ability to solubilize Nf aggregates and immunoblotting was used for qualitative analysis.</AbstractText A 'hook effect' was observed for serially diluted plasma samples quantified using an ELISA originally developed for CSF samples. Immunoblotting confirmed the existence of high molecular-weight NfH aggregates in plasma and the resolving effect of timed urea on these aggregates. Thermostatic (pre-thawing) and chemical (calcium chelators, urea) pre-analytical processing of samples had variable success in disrupting NfH aggregates. Timed urea-calcium chelator incubation yielded the most consistent plasma NfH levels. A one hour sample pre-incubation with 0.5M urea in Barbitone-EDTA buffer at room temperature resolved the "hook effect" without compromising the ELISA. In SOD1(G93A) mice, median levels of NfH(SMI34) were over 10-fold and NfH(SMI35) levels 5-fold greater than controls.</AbstractText NfH aggregates can be solubilised and the "hook effect" abolished by a one-hour sample pre-incubation in a urea-calcium chelator-enriched buffer. This method is applicable for quantification of NfH phosphoforms in experimental and disease settings where Nf aggregate formation occurs.</AbstractText
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39630731
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20143387
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38444736
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Liver/spleen magnetic resonance elastography and T1/T2 mapping in chronic liver disease: a prospective study.
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Distortion correction for diffusion-weighted MRI tractography and fMRI in the temporal lobes.
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Pax2-cre-mediated deletion of Lgl1 causes abnormal development of the midbrain.
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This study aims to compare liver and spleen stiffness measurements using magnetic resonance elastography with T1 and T2 relaxation times in patients with chronic liver disease.</AbstractText A total of 75 chronic liver disease patients and 25 healthy volunteers underwent MR. Patients with significant liver fat and iron accumulation were excluded. Student's t-test was employed to compare magnetic resonance elastography and T1/T2 values. Pearson's correlation test was used to assess the relationship between magnetic resonance elastography and T1/T2 values.</AbstractText Liver magnetic resonance elastography showed a significant moderate positive correlation with liver T1 mapping (r=0.51, p<0.001) and liver T2 mapping (r=0.30, p=0.009) in patients. Spleen magnetic resonance elastography exhibited a significant moderate positive correlation with spleen T2 mapping (r=0.37, p=0.001). However, there was no significant correlation between spleen magnetic resonance elastography and spleen T1 mapping in patients. Spleen magnetic resonance elastography was moderately positively correlated with liver magnetic resonance elastography (r=0.30, p=0.01), and spleen volume showed positive correlations with spleen magnetic resonance elastography, spleen T1 mapping, and spleen T2 mapping. Cut-off values for liver magnetic resonance elastography, liver T1 mapping, and liver T2 mapping in patient and control groups were 2.6 kPa (AUC=0.97), 619 ms (AUC=0.90), and 52.5 ms (AUC=0.62), respectively.</AbstractText Relaxation methods offer noninvasive imaging without additional equipment. Liver T1 mapping may serve as an alternative to magnetic resonance elastography for chronic liver patient follow-up, while spleen T1 mapping is not reliable.</AbstractText
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Single shot echo-planar imaging (EPI) sequences are currently the most commonly used sequences for diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) as they allow relatively high signal to noise with rapid acquisition time. A major drawback of EPI is the substantial geometric distortion and signal loss that can occur due to magnetic field inhomogeneities close to air-tissue boundaries. If DWI-based tractography and fMRI are to be applied to these regions, then the distortions must be accurately corrected to achieve meaningful results. We describe robust acquisition and processing methods for correcting such distortions in spin echo (SE) EPI using a variant of the reversed direction k space traversal method with a number of novel additions. We demonstrate that dual direction k space traversal with maintained diffusion-encoding gradient strength and direction results in correction of the great majority of eddy current-associated distortions in DWI, in addition to those created by variations in magnetic susceptibility. We also provide examples to demonstrate that the presence of severe distortions cannot be ignored if meaningful tractography results are desired. The distortion correction routine was applied to SE-EPI fMRI acquisitions and allowed detection of activation in the temporal lobe that had been previously found using PET but not conventional fMRI.</AbstractText
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Lgl1 protein plays a critical role in neurodevelopment, including hippocampus, olfactory bulb, and Purkinje cell. However, the specific mechanism of LGL1 function in the midbrain remains elusive. In this study, we generated Lgl1 conditional knockout mice using Pax2-Cre, which is expressed in the midbrain, and examined the functions of Lgl1 in the midbrain. Histological analysis exhibited abnormal midbrain development characterized by enlarged ventricular aqueduct and thinning tectum cortex. Lgl1 deletion caused excessive proliferation and heightened apoptosis of neural progenitor cells in the tectum of LP cko mice. BrdU labeling studies demonstrated abnormal neuronal migration. Immunofluorescence analysis of Nestin demonstrated an irregular and clustered distribution of glial cell fibers, with the adhesion junction marker N-cadherin employed for immunofluorescent labeling, unveiling abnormal epithelial connections within the tectum of LP cko mice. The current findings suggest that the deletion of Lgl1 leads to the disruption of the expression pattern of N-cadherin, resulting in abnormal development of the midbrain.</AbstractText
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Liver/spleen magnetic resonance elastography and T1/T2 mapping in chronic liver disease: a prospective study. This study aims to compare liver and spleen stiffness measurements using magnetic resonance elastography with T1 and T2 relaxation times in patients with chronic liver disease.</AbstractText A total of 75 chronic liver disease patients and 25 healthy volunteers underwent MR. Patients with significant liver fat and iron accumulation were excluded. Student's t-test was employed to compare magnetic resonance elastography and T1/T2 values. Pearson's correlation test was used to assess the relationship between magnetic resonance elastography and T1/T2 values.</AbstractText Liver magnetic resonance elastography showed a significant moderate positive correlation with liver T1 mapping (r=0.51, p<0.001) and liver T2 mapping (r=0.30, p=0.009) in patients. Spleen magnetic resonance elastography exhibited a significant moderate positive correlation with spleen T2 mapping (r=0.37, p=0.001). However, there was no significant correlation between spleen magnetic resonance elastography and spleen T1 mapping in patients. Spleen magnetic resonance elastography was moderately positively correlated with liver magnetic resonance elastography (r=0.30, p=0.01), and spleen volume showed positive correlations with spleen magnetic resonance elastography, spleen T1 mapping, and spleen T2 mapping. Cut-off values for liver magnetic resonance elastography, liver T1 mapping, and liver T2 mapping in patient and control groups were 2.6 kPa (AUC=0.97), 619 ms (AUC=0.90), and 52.5 ms (AUC=0.62), respectively.</AbstractText Relaxation methods offer noninvasive imaging without additional equipment. Liver T1 mapping may serve as an alternative to magnetic resonance elastography for chronic liver patient follow-up, while spleen T1 mapping is not reliable.</AbstractText
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Distortion correction for diffusion-weighted MRI tractography and fMRI in the temporal lobes. Single shot echo-planar imaging (EPI) sequences are currently the most commonly used sequences for diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) as they allow relatively high signal to noise with rapid acquisition time. A major drawback of EPI is the substantial geometric distortion and signal loss that can occur due to magnetic field inhomogeneities close to air-tissue boundaries. If DWI-based tractography and fMRI are to be applied to these regions, then the distortions must be accurately corrected to achieve meaningful results. We describe robust acquisition and processing methods for correcting such distortions in spin echo (SE) EPI using a variant of the reversed direction k space traversal method with a number of novel additions. We demonstrate that dual direction k space traversal with maintained diffusion-encoding gradient strength and direction results in correction of the great majority of eddy current-associated distortions in DWI, in addition to those created by variations in magnetic susceptibility. We also provide examples to demonstrate that the presence of severe distortions cannot be ignored if meaningful tractography results are desired. The distortion correction routine was applied to SE-EPI fMRI acquisitions and allowed detection of activation in the temporal lobe that had been previously found using PET but not conventional fMRI.</AbstractText
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Pax2-cre-mediated deletion of Lgl1 causes abnormal development of the midbrain. Lgl1 protein plays a critical role in neurodevelopment, including hippocampus, olfactory bulb, and Purkinje cell. However, the specific mechanism of LGL1 function in the midbrain remains elusive. In this study, we generated Lgl1 conditional knockout mice using Pax2-Cre, which is expressed in the midbrain, and examined the functions of Lgl1 in the midbrain. Histological analysis exhibited abnormal midbrain development characterized by enlarged ventricular aqueduct and thinning tectum cortex. Lgl1 deletion caused excessive proliferation and heightened apoptosis of neural progenitor cells in the tectum of LP cko mice. BrdU labeling studies demonstrated abnormal neuronal migration. Immunofluorescence analysis of Nestin demonstrated an irregular and clustered distribution of glial cell fibers, with the adhesion junction marker N-cadherin employed for immunofluorescent labeling, unveiling abnormal epithelial connections within the tectum of LP cko mice. The current findings suggest that the deletion of Lgl1 leads to the disruption of the expression pattern of N-cadherin, resulting in abnormal development of the midbrain.</AbstractText
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34872157
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36029548
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34622945
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Conflict monitoring and attentional adjustment during binocular rivalry.
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The importance of resource allocation for the interplay between automatic and cognitive control in response inhibition - An EEG source localization study.
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The effects of obstetric emergency team training on patient outcome: A systematic review and meta-analysis.
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To make sense of ambiguous and, at times, fragmentary sensory input, the brain must rely on a process of active interpretation. At any given moment, only one of several possible perceptual representations prevails in our conscious experience. Our hypothesis is that the competition between alternative representations induces a pattern of neural activation resembling cognitive conflict, eventually leading to fluctuations between different perceptual outcomes in the case of steep competition. To test this hypothesis, we probed changes in perceptual awareness between competing images using binocular rivalry. We drew our predictions from the conflict monitoring theory, which holds that cognitive control is invoked by the detection of conflict during information processing. Our results show that fronto-medial theta oscillations (5-7 Hz), an established electroencephalography (EEG) marker of conflict, increases right before perceptual alternations and decreases thereafter, suggesting that conflict monitoring occurs during perceptual competition. Furthermore, to investigate conflict resolution via attentional engagement, we looked for a neural marker of perceptual switches as by parieto-occipital alpha oscillations (8-12 Hz). The power of parieto-occipital alpha displayed an inverse pattern to that of fronto-medial theta, reflecting periods of high interocular inhibition during stable perception, and low inhibition around moments of perceptual change. Our findings aim to elucidate the relationship between conflict monitoring mechanisms and perceptual awareness.</AbstractText
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Goal-directed behavior often requires the inhibition of prepotent automatic responses. Response inhibition encompasses several top-down cognitive operations embedded in a neural network extending from fronto-cortical regions to subcortical nuclei. Yet, it has remained unclear whether the early allocation of cognitive resources also modulates response inhibition performance and neural structures involved in this process. To investigate this question, we used a Simon Nogo task, which was designed to manipulate the relationship between automaticity and cognitive control during response inhibition, and combined it with an electroencephalogram (EEG) and source localization approach. We showed that the early allocation of cognitive resources, as reflected by the P2 amplitude, might be a critical determinant in the interplay between automaticity and cognitive control in response inhibition. Specifically, the obtained results demonstrated that individual variations in cognitive resource allocation modulated the need for conflict monitoring and engagement in cognitive control processes, as reflected by N2 and P3b amplitudes, respectively. Importantly, larger P2 amplitudes were associated with higher activation in cortical regions encompassing the temporo-parietal junction (TPJ). This stresses the importance of this cortical region for the encoding of relevant stimulus information to resolve conflicting contexts in response inhibition. The increased cognitive control in more automatic contexts was also reflected by higher activation of the superior and medial frontal cortices. These findings provide a new perspective on response inhibition, suggesting that early resource allocation is a central modulator of the interaction between automaticity and cognitive control.</AbstractText
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Little is known about the optimal simulation-based team training in obstetric emergencies. We aimed to review how simulation-based team training affects patient outcomes in obstetric emergencies.</AbstractText Search Strategy: MEDLINE, Embase, Cochrane Library, and Cochrane Central Register of Controlled Trials were searched up to and including May 15, 2021.</AbstractText randomized controlled trials (RCTs) and cohort studies on obstetric teams in high-resource settings comparing the effect of simulation-based obstetric emergency team training with no training on the risk of Apgar scores less than 7 at 5 min, neonatal hypoxic ischemic encephalopathy, severe postpartum hemorrhage, blood transfusion of four or more units, and delay of emergency cesarean section by more than 30 min.</AbstractText The included studies were assessed using PRISMA, EPCO, and GRADE.</AbstractText We found 21 studies, four RCTs and 17 cohort studies, evaluating patient outcomes after obstetric team training compared with no training. Annual obstetric emergency team training may reduce brachial plexus injury (six cohort studies: odds ratio [OR] 0.47, 95% CI 0.33-0.68; one RCT: OR 1.30, 95 CI% 0.39-4.33, low certainty evidence) and suggest a positive effect; but it was not significant on Apgar score below 7 at 5 min (three cohort studies: OR 0.77, 95% CI 0.51-1.19; two RCT: OR 0.87, 95% CI 0.72-1.05, moderate certainty evidence). The effect was unclear for hypoxic ischemic encephalopathy, umbilical prolapse, decision to birth interval in emergency cesarean section, and for severe postpartum hemorrhage. Studies with in situ multi-professional simulation-based training demonstrated the best effect.</AbstractText Emerging evidence suggests an effect of obstetric team training on obstetric outcomes, but conflicting results call for controlled trials targeted to identify the optimal methodology for effective team training.</AbstractText
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Conflict monitoring and attentional adjustment during binocular rivalry. To make sense of ambiguous and, at times, fragmentary sensory input, the brain must rely on a process of active interpretation. At any given moment, only one of several possible perceptual representations prevails in our conscious experience. Our hypothesis is that the competition between alternative representations induces a pattern of neural activation resembling cognitive conflict, eventually leading to fluctuations between different perceptual outcomes in the case of steep competition. To test this hypothesis, we probed changes in perceptual awareness between competing images using binocular rivalry. We drew our predictions from the conflict monitoring theory, which holds that cognitive control is invoked by the detection of conflict during information processing. Our results show that fronto-medial theta oscillations (5-7 Hz), an established electroencephalography (EEG) marker of conflict, increases right before perceptual alternations and decreases thereafter, suggesting that conflict monitoring occurs during perceptual competition. Furthermore, to investigate conflict resolution via attentional engagement, we looked for a neural marker of perceptual switches as by parieto-occipital alpha oscillations (8-12 Hz). The power of parieto-occipital alpha displayed an inverse pattern to that of fronto-medial theta, reflecting periods of high interocular inhibition during stable perception, and low inhibition around moments of perceptual change. Our findings aim to elucidate the relationship between conflict monitoring mechanisms and perceptual awareness.</AbstractText
|
The importance of resource allocation for the interplay between automatic and cognitive control in response inhibition - An EEG source localization study. Goal-directed behavior often requires the inhibition of prepotent automatic responses. Response inhibition encompasses several top-down cognitive operations embedded in a neural network extending from fronto-cortical regions to subcortical nuclei. Yet, it has remained unclear whether the early allocation of cognitive resources also modulates response inhibition performance and neural structures involved in this process. To investigate this question, we used a Simon Nogo task, which was designed to manipulate the relationship between automaticity and cognitive control during response inhibition, and combined it with an electroencephalogram (EEG) and source localization approach. We showed that the early allocation of cognitive resources, as reflected by the P2 amplitude, might be a critical determinant in the interplay between automaticity and cognitive control in response inhibition. Specifically, the obtained results demonstrated that individual variations in cognitive resource allocation modulated the need for conflict monitoring and engagement in cognitive control processes, as reflected by N2 and P3b amplitudes, respectively. Importantly, larger P2 amplitudes were associated with higher activation in cortical regions encompassing the temporo-parietal junction (TPJ). This stresses the importance of this cortical region for the encoding of relevant stimulus information to resolve conflicting contexts in response inhibition. The increased cognitive control in more automatic contexts was also reflected by higher activation of the superior and medial frontal cortices. These findings provide a new perspective on response inhibition, suggesting that early resource allocation is a central modulator of the interaction between automaticity and cognitive control.</AbstractText
|
The effects of obstetric emergency team training on patient outcome: A systematic review and meta-analysis. Little is known about the optimal simulation-based team training in obstetric emergencies. We aimed to review how simulation-based team training affects patient outcomes in obstetric emergencies.</AbstractText Search Strategy: MEDLINE, Embase, Cochrane Library, and Cochrane Central Register of Controlled Trials were searched up to and including May 15, 2021.</AbstractText randomized controlled trials (RCTs) and cohort studies on obstetric teams in high-resource settings comparing the effect of simulation-based obstetric emergency team training with no training on the risk of Apgar scores less than 7 at 5 min, neonatal hypoxic ischemic encephalopathy, severe postpartum hemorrhage, blood transfusion of four or more units, and delay of emergency cesarean section by more than 30 min.</AbstractText The included studies were assessed using PRISMA, EPCO, and GRADE.</AbstractText We found 21 studies, four RCTs and 17 cohort studies, evaluating patient outcomes after obstetric team training compared with no training. Annual obstetric emergency team training may reduce brachial plexus injury (six cohort studies: odds ratio [OR] 0.47, 95% CI 0.33-0.68; one RCT: OR 1.30, 95 CI% 0.39-4.33, low certainty evidence) and suggest a positive effect; but it was not significant on Apgar score below 7 at 5 min (three cohort studies: OR 0.77, 95% CI 0.51-1.19; two RCT: OR 0.87, 95% CI 0.72-1.05, moderate certainty evidence). The effect was unclear for hypoxic ischemic encephalopathy, umbilical prolapse, decision to birth interval in emergency cesarean section, and for severe postpartum hemorrhage. Studies with in situ multi-professional simulation-based training demonstrated the best effect.</AbstractText Emerging evidence suggests an effect of obstetric team training on obstetric outcomes, but conflicting results call for controlled trials targeted to identify the optimal methodology for effective team training.</AbstractText
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20562657
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11164022
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11201083
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A neuroimaging study of conflict during word recognition.
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Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework.
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Early loss of dendritic spines in murine scrapie revealed by confocal analysis.
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Using functional magnetic resonance imaging the neural activity associated with error commission and conflict monitoring in a lexical decision task was assessed. In a cohort of 20 native speakers of Spanish conflict was introduced by presenting words with high and low lexical frequency and pseudo-words with high and low syllabic frequency for the first syllable. Erroneous versus correct responses showed activation in the frontomedial and left inferior frontal cortex. A similar pattern was found for correctly classified words of low versus high lexical frequency and for correctly classified pseudo-words of high versus low syllabic frequency. Conflict-related activations for language materials largely overlapped with error-induced activations. The effect of syllabic frequency underscores the role of sublexical processing in visual word recognition and supports the view that the initial syllable mediates between the letter and word level.</AbstractText
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This introductory chapter attempts to clarify the philosophical, empirical, and theoretical bases on which a cognitive neuroscience approach to consciousness can be founded. We isolate three major empirical observations that any theory of consciousness should incorporate, namely (1) a considerable amount of processing is possible without consciousness, (2) attention is a prerequisite of consciousness, and (3) consciousness is required for some specific cognitive tasks, including those that require durable information maintenance, novel combinations of operations, or the spontaneous generation of intentional behavior. We then propose a theoretical framework that synthesizes those facts: the hypothesis of a global neuronal workspace. This framework postulates that, at any given time, many modular cerebral networks are active in parallel and process information in an unconscious manner. An information becomes conscious, however, if the neural population that represents it is mobilized by top-down attentional amplification into a brain-scale state of coherent activity that involves many neurons distributed throughout the brain. The long-distance connectivity of these 'workspace neurons' can, when they are active for a minimal duration, make the information available to a variety of processes including perceptual categorization, long-term memorization, evaluation, and intentional action. We postulate that this global availability of information through the workspace is what we subjectively experience as a conscious state. A complete theory of consciousness should explain why some cognitive and cerebral representations can be permanently or temporarily inaccessible to consciousness, what is the range of possible conscious contents, how they map onto specific cerebral circuits, and whether a generic neuronal mechanism underlies all of them. We confront the workspace model with those issues and identify novel experimental predictions. Neurophysiological, anatomical, and brain-imaging data strongly argue for a major role of prefrontal cortex, anterior cingulate, and the areas that connect to them, in creating the postulated brain-scale workspace.</AbstractText
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Confocal analysis of dye-filled neurons has revealed a significant early loss of dendritic spines in a murine scrapie model in which neuron loss occurs in the hippocampus. An 18% loss of spines was found at 109 days, > 50 days before neuron loss occurs, and by 126 days a 51% spine loss was found. Spine loss is concurrent with synapse loss, axon terminal degeneration and a decrease in long term potentiation in this model. Preceding these changes is the deposition of disease specific PrP at 70 days, which may initiate the damage to dendritic spines and the subsequent degeneration of synapses. We suggest that these changes underlie the development of clinical disease in the transmissible spongiform encephalopathies.</AbstractText
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A neuroimaging study of conflict during word recognition. Using functional magnetic resonance imaging the neural activity associated with error commission and conflict monitoring in a lexical decision task was assessed. In a cohort of 20 native speakers of Spanish conflict was introduced by presenting words with high and low lexical frequency and pseudo-words with high and low syllabic frequency for the first syllable. Erroneous versus correct responses showed activation in the frontomedial and left inferior frontal cortex. A similar pattern was found for correctly classified words of low versus high lexical frequency and for correctly classified pseudo-words of high versus low syllabic frequency. Conflict-related activations for language materials largely overlapped with error-induced activations. The effect of syllabic frequency underscores the role of sublexical processing in visual word recognition and supports the view that the initial syllable mediates between the letter and word level.</AbstractText
|
Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. This introductory chapter attempts to clarify the philosophical, empirical, and theoretical bases on which a cognitive neuroscience approach to consciousness can be founded. We isolate three major empirical observations that any theory of consciousness should incorporate, namely (1) a considerable amount of processing is possible without consciousness, (2) attention is a prerequisite of consciousness, and (3) consciousness is required for some specific cognitive tasks, including those that require durable information maintenance, novel combinations of operations, or the spontaneous generation of intentional behavior. We then propose a theoretical framework that synthesizes those facts: the hypothesis of a global neuronal workspace. This framework postulates that, at any given time, many modular cerebral networks are active in parallel and process information in an unconscious manner. An information becomes conscious, however, if the neural population that represents it is mobilized by top-down attentional amplification into a brain-scale state of coherent activity that involves many neurons distributed throughout the brain. The long-distance connectivity of these 'workspace neurons' can, when they are active for a minimal duration, make the information available to a variety of processes including perceptual categorization, long-term memorization, evaluation, and intentional action. We postulate that this global availability of information through the workspace is what we subjectively experience as a conscious state. A complete theory of consciousness should explain why some cognitive and cerebral representations can be permanently or temporarily inaccessible to consciousness, what is the range of possible conscious contents, how they map onto specific cerebral circuits, and whether a generic neuronal mechanism underlies all of them. We confront the workspace model with those issues and identify novel experimental predictions. Neurophysiological, anatomical, and brain-imaging data strongly argue for a major role of prefrontal cortex, anterior cingulate, and the areas that connect to them, in creating the postulated brain-scale workspace.</AbstractText
|
Early loss of dendritic spines in murine scrapie revealed by confocal analysis. Confocal analysis of dye-filled neurons has revealed a significant early loss of dendritic spines in a murine scrapie model in which neuron loss occurs in the hippocampus. An 18% loss of spines was found at 109 days, > 50 days before neuron loss occurs, and by 126 days a 51% spine loss was found. Spine loss is concurrent with synapse loss, axon terminal degeneration and a decrease in long term potentiation in this model. Preceding these changes is the deposition of disease specific PrP at 70 days, which may initiate the damage to dendritic spines and the subsequent degeneration of synapses. We suggest that these changes underlie the development of clinical disease in the transmissible spongiform encephalopathies.</AbstractText
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37705463
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33808956
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38663879
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Racial Identity Attitudes and Vicarious Traumatization from Undue Police Violence on Anticipatory Traumatic Reaction Among Black Americans.
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Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection.
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MEF2C contributes to axonal branching by regulating Kif2c transcription.
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Although the viral nature of videos that capture violent and racialized policing of Black Americans in the United States can increase awareness, exposure to race-based violence can result in vicarious traumatization, particularly among Black Americans. The relationship between anticipatory traumatic reactions (ATRs) and racial identity attitudes is not clearly addressed in the extant body of literature. The current study addresses this research disparity by first analyzing group mean differences among Black Americans (<i
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We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [<sup
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Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.</AbstractText
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Racial Identity Attitudes and Vicarious Traumatization from Undue Police Violence on Anticipatory Traumatic Reaction Among Black Americans. Although the viral nature of videos that capture violent and racialized policing of Black Americans in the United States can increase awareness, exposure to race-based violence can result in vicarious traumatization, particularly among Black Americans. The relationship between anticipatory traumatic reactions (ATRs) and racial identity attitudes is not clearly addressed in the extant body of literature. The current study addresses this research disparity by first analyzing group mean differences among Black Americans (<i
|
Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection. We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [<sup
|
MEF2C contributes to axonal branching by regulating Kif2c transcription. Neurons are post-mitotic cells, with microtubules playing crucial roles in axonal transport and growth. Kinesin family member 2c (KIF2C), a member of the Kinesin-13 family, possesses the ability to depolymerize microtubules and is involved in remodelling the microtubule lattice. Myocyte enhancer factor 2c (MEF2C) was initially identified as a regulator of muscle differentiation but has recently been associated with neurological abnormalities such as severe cognitive impairment, stereotyping, epilepsy and brain malformations when mutated or deleted. However, further investigation is required to determine which target genes MEF2C acts upon to influence neuronal function as a transcription regulator. Our data demonstrate that knockdown of both Mef2c and Kif2c significantly impacts spinal motor neuron development and behaviour in zebrafish. Luciferase reporter assays and chromosome immunoprecipitation assays, along with down/upregulated expression analysis, revealed that MFE2C functions as a novel transcription regulator for the Kif2c gene. Additionally, the knockdown of either Mef2c or Kif2c expression in E18 cortical neurons substantially reduces the number of primary neurites and axonal branches during neuronal development in vitro without affecting neurite length. Finally, depletion of Kif2c eliminated the effects of overexpression of Mef2c on the neurite branching. Based on these findings, we provided novel evidence demonstrating that MEF2C regulates the transcription of the Kif2c gene thereby influencing the axonal branching.</AbstractText
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21463649
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15107475
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22936905
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Does conventional anti-bipolar and antidepressant drug therapy reduce NMDA-mediated neuronal excitation by downregulating astrocytic GluK2 function?
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Presynaptic kainate receptor facilitation of glutamate release involves protein kinase A in the rat hippocampus.
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Emotional and cognitive processing of narratives and individual appraisal styles: recruitment of cognitive control networks vs. modulation of deactivations.
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Chronic treatment with anti-bipolar drugs (lithium, carbamazepine, and valproic acid) down-regulates mRNA and protein expression of kainate receptor GluK2 in mouse brain and cultured astrocytes. It also abolishes glutamate-mediated, Ca(2+)-dependent ERK(1/2) phosphorylation in the astrocytes. Chronic treatment with the SSRI fluoxetine enhances astrocytic GluK2 expression, but increases mRNA editing, abolishing glutamate-mediated ERK(1/2) phosphorylation and [Ca(2+)](i) increase, which are shown to be GluK2-mediated. Neither drug group affects Glu4/Glu5 expression necessary for GluK2's ionotropic effect. Consistent with a metabotropic effect, the PKC inhibitor GF 109203X and the IP(3) inhibitor xestospongin C abolish glutamate stimulation in cultured astrocytes. In CA1/CA3 pyramidal cells in hippocampal slices, activation of extrasynaptic GluK2 receptors, presumably including astrocytic, metabotropic GluK2 receptors, causes long-lasting inhibition of slow neuronal afterhyperpolarization mediated by Ca(2+)-dependent K(+) flux. This may be secondary to the induced astrocytic [Ca(2+)](i) increase, causing release of 'gliotransmitter' glutamate. Neuronal NMDA receptors respond to astrocytic glutamate release with enhancement of excitatory glutamatergic activity. Since reduction of NMDA receptor activity is known to have antidepressant effect in bipolar depression and major depression, these observations suggest that the inactivation of astrocytic GluK2 activity by antidepressant/anti-bipolar therapy ameliorates depression by inhibiting astrocytic glutamate release. A resultant strengthening of neuronal afterhyperpolarization may cause reduced NMDA-mediated activity.</AbstractText
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We have explored the mechanisms involved in the facilitation of glutamate release mediated by the activation of kainate receptors in the rat hippocampus using isolated nerve terminal (synaptosome) and slice preparations. In hippocampal nerve terminals, kainate (KA) produced an increase of glutamate release at concentrations of agonist ranging from 10 to 1000 microm. In hippocampal slices, KA at low nanomolar concentrations (20-50 nm) also produced an increase of evoked excitatory postsynaptic currents (eEPSCs) at mossy fibre-CA3 synapses. In both, synaptosomes and slices, the effect of KA was antagonized by CNQX, and persisted after pretreatment with a cocktail of antagonists for other receptors whose activation could potentially have produced facilitation of release. These data indicate that the facilitation of glutamate release observed is mediated by the activation of presynaptic glutamate receptors of the kainate type. Mechanistically, the observed effects of KA appear to be the same in synaptosomal and slice preparations. Thus, the effect of KA on glutamate release and mossy fibre-CA3 synaptic transmission was occluded by the stimulation of adenylyl cyclase by forskolin and suppressed by the inhibition of protein kinase A by H-89 or Rp-Br-cAMP. We conclude that kainate receptors present at presynaptic terminals in the rat hippocampus mediate the facilitation of glutamate release through a mechanism involving the activation of an adenylyl cyclase-second messenger cAMP-protein kinase A signalling cascade.</AbstractText
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Research in psychotherapy has shown that the frequency of use of specific classes of words (such as terms with emotional valence) in descriptions of scenes of affective relevance is a possible indicator of psychological affective functioning. Using functional magnetic resonance imaging (MRI), we investigated the neural correlates of these linguistic markers in narrative texts depicting core aspects of emotional experience in human interaction, and their modulation by individual differences in the propensity to use these markers. Emotional words activated both lateral and medial aspects of the prefrontal cortex, as in previous studies of instructed emotion regulation and in consistence with recruitment of effortful control processes. However, individual differences in the spontaneous use of emotional terms in characterizing the stimulus material were prevalently associated with modulation of the signal in the perigenual cortex, in the retrosplenial cortex and precuneus, and the anterior insula/ventrolateral prefrontal cortex. Modulation of signal by the presence of these textual markers or individual differences mostly involved areas deactivated by the main task, thus further differentiating neural correlates of these appraisal styles from those associated with effortful control. These findings are discussed in the context of reports in the literature of modulations of deactivations, which suggest their importance in orienting attention and generation of response in the presence of emotional information. These findings suggest that deactivations may play a functional role in emotional appraisal and may contribute to characterizing different appraisal styles.</AbstractText
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Does conventional anti-bipolar and antidepressant drug therapy reduce NMDA-mediated neuronal excitation by downregulating astrocytic GluK2 function? Chronic treatment with anti-bipolar drugs (lithium, carbamazepine, and valproic acid) down-regulates mRNA and protein expression of kainate receptor GluK2 in mouse brain and cultured astrocytes. It also abolishes glutamate-mediated, Ca(2+)-dependent ERK(1/2) phosphorylation in the astrocytes. Chronic treatment with the SSRI fluoxetine enhances astrocytic GluK2 expression, but increases mRNA editing, abolishing glutamate-mediated ERK(1/2) phosphorylation and [Ca(2+)](i) increase, which are shown to be GluK2-mediated. Neither drug group affects Glu4/Glu5 expression necessary for GluK2's ionotropic effect. Consistent with a metabotropic effect, the PKC inhibitor GF 109203X and the IP(3) inhibitor xestospongin C abolish glutamate stimulation in cultured astrocytes. In CA1/CA3 pyramidal cells in hippocampal slices, activation of extrasynaptic GluK2 receptors, presumably including astrocytic, metabotropic GluK2 receptors, causes long-lasting inhibition of slow neuronal afterhyperpolarization mediated by Ca(2+)-dependent K(+) flux. This may be secondary to the induced astrocytic [Ca(2+)](i) increase, causing release of 'gliotransmitter' glutamate. Neuronal NMDA receptors respond to astrocytic glutamate release with enhancement of excitatory glutamatergic activity. Since reduction of NMDA receptor activity is known to have antidepressant effect in bipolar depression and major depression, these observations suggest that the inactivation of astrocytic GluK2 activity by antidepressant/anti-bipolar therapy ameliorates depression by inhibiting astrocytic glutamate release. A resultant strengthening of neuronal afterhyperpolarization may cause reduced NMDA-mediated activity.</AbstractText
|
Presynaptic kainate receptor facilitation of glutamate release involves protein kinase A in the rat hippocampus. We have explored the mechanisms involved in the facilitation of glutamate release mediated by the activation of kainate receptors in the rat hippocampus using isolated nerve terminal (synaptosome) and slice preparations. In hippocampal nerve terminals, kainate (KA) produced an increase of glutamate release at concentrations of agonist ranging from 10 to 1000 microm. In hippocampal slices, KA at low nanomolar concentrations (20-50 nm) also produced an increase of evoked excitatory postsynaptic currents (eEPSCs) at mossy fibre-CA3 synapses. In both, synaptosomes and slices, the effect of KA was antagonized by CNQX, and persisted after pretreatment with a cocktail of antagonists for other receptors whose activation could potentially have produced facilitation of release. These data indicate that the facilitation of glutamate release observed is mediated by the activation of presynaptic glutamate receptors of the kainate type. Mechanistically, the observed effects of KA appear to be the same in synaptosomal and slice preparations. Thus, the effect of KA on glutamate release and mossy fibre-CA3 synaptic transmission was occluded by the stimulation of adenylyl cyclase by forskolin and suppressed by the inhibition of protein kinase A by H-89 or Rp-Br-cAMP. We conclude that kainate receptors present at presynaptic terminals in the rat hippocampus mediate the facilitation of glutamate release through a mechanism involving the activation of an adenylyl cyclase-second messenger cAMP-protein kinase A signalling cascade.</AbstractText
|
Emotional and cognitive processing of narratives and individual appraisal styles: recruitment of cognitive control networks vs. modulation of deactivations. Research in psychotherapy has shown that the frequency of use of specific classes of words (such as terms with emotional valence) in descriptions of scenes of affective relevance is a possible indicator of psychological affective functioning. Using functional magnetic resonance imaging (MRI), we investigated the neural correlates of these linguistic markers in narrative texts depicting core aspects of emotional experience in human interaction, and their modulation by individual differences in the propensity to use these markers. Emotional words activated both lateral and medial aspects of the prefrontal cortex, as in previous studies of instructed emotion regulation and in consistence with recruitment of effortful control processes. However, individual differences in the spontaneous use of emotional terms in characterizing the stimulus material were prevalently associated with modulation of the signal in the perigenual cortex, in the retrosplenial cortex and precuneus, and the anterior insula/ventrolateral prefrontal cortex. Modulation of signal by the presence of these textual markers or individual differences mostly involved areas deactivated by the main task, thus further differentiating neural correlates of these appraisal styles from those associated with effortful control. These findings are discussed in the context of reports in the literature of modulations of deactivations, which suggest their importance in orienting attention and generation of response in the presence of emotional information. These findings suggest that deactivations may play a functional role in emotional appraisal and may contribute to characterizing different appraisal styles.</AbstractText
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36622542
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23703378
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37258297
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Machine learning based model to diagnose obstructive coronary artery disease using calcium scoring, PET imaging, and clinical data.
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Improved accuracy of myocardial perfusion SPECT for detection of coronary artery disease by machine learning in a large population.
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Deviation From Normative Whole Brain and Deep Gray Matter Growth in Children With MOGAD, MS, and Monophasic Seronegative Demyelination.
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Accurate risk stratification in patients with suspected stable coronary artery disease is essential for choosing an appropriate treatment strategy. Our aim was to develop and validate a machine learning (ML) based model to diagnose obstructive CAD (oCAD).</AbstractText We retrospectively have included 1007 patients without a prior history of CAD who underwent CT-based calcium scoring (CACS) and a Rubidium-82 PET scan. The entire dataset was split 4:1 into a training and test dataset. An ML model was developed on the training set using fivefold stratified cross-validation. The test dataset was used to compare the performance of expert readers to the model. The primary endpoint was oCAD on invasive coronary angiography (ICA).</AbstractText ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.94) for the training dataset and 0.89 (95% CI 0.84-0.93) for the test dataset. The ML model showed no significant differences as compared to the expert readers (p ≥ 0.03) in accuracy (89% vs. 88%), sensitivity (68% vs. 69%), and specificity (92% vs. 90%).</AbstractText The ML model resulted in a similar diagnostic performance as compared to expert readers, and may be deployed as a risk stratification tool for obstructive CAD. This study showed that utilization of ML is promising in the diagnosis of obstructive CAD.</AbstractText
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We aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features with machine learning (ML) algorithms.</AbstractText 1,181 rest (201)Tl/stress (99m)Tc-sestamibi dual-isotope MPS studies [713 consecutive cases with correlating invasive coronary angiography (ICA) and suspected coronary artery disease (CAD) and 468 with low likelihood (LLk) of CAD <5%] were considered. Cases with stenosis <70% by ICA and LLk of CAD were considered normal. Total stress perfusion deficit (TPD) for supine/prone data, stress/rest perfusion change, and transient ischemic dilatation were derived by automated perfusion quantification software and were combined with age, sex, and post-electrocardiogram CAD probability by a boosted ensemble ML algorithm (LogitBoost). The diagnostic accuracy of the model for prediction of obstructive CAD ≥70% was compared to standard prone/supine quantification and to visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. Tenfold stratified cross-validation was performed.</AbstractText The diagnostic accuracy of ML (87.3% ± 2.1%) was similar to Expert 1 (86.0% ± 2.1%), but superior to combined supine/prone TPD (82.8% ± 2.2%) and Expert 2 (82.1% ± 2.2%) (P < .01). The receiver operator characteristic areas under curve for ML algorithm (0.94 ± 0.01) were higher than those for TPD and both visual readers (P < .001). The sensitivity of ML algorithm (78.9% ± 4.2%) was similar to TPD (75.6% ± 4.4%) and Expert 1 (76.3% ± 4.3%), but higher than that of Expert 2 (71.1% ± 4.6%), (P < .01). The specificity of ML algorithm (92.1% ± 2.2%) was similar to Expert 1 (91.4% ± 2.2%) and Expert 2 (88.3% ± 2.5%), but higher than TPD (86.8% ± 2.6%), (P < .01).</AbstractText ML significantly improves diagnostic performance of MPS by computational integration of quantitative perfusion and clinical data to the level rivaling expert analysis.</AbstractText
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Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination.</AbstractText We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized <i We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed (<i The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time.</AbstractText
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Machine learning based model to diagnose obstructive coronary artery disease using calcium scoring, PET imaging, and clinical data. Accurate risk stratification in patients with suspected stable coronary artery disease is essential for choosing an appropriate treatment strategy. Our aim was to develop and validate a machine learning (ML) based model to diagnose obstructive CAD (oCAD).</AbstractText We retrospectively have included 1007 patients without a prior history of CAD who underwent CT-based calcium scoring (CACS) and a Rubidium-82 PET scan. The entire dataset was split 4:1 into a training and test dataset. An ML model was developed on the training set using fivefold stratified cross-validation. The test dataset was used to compare the performance of expert readers to the model. The primary endpoint was oCAD on invasive coronary angiography (ICA).</AbstractText ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.94) for the training dataset and 0.89 (95% CI 0.84-0.93) for the test dataset. The ML model showed no significant differences as compared to the expert readers (p ≥ 0.03) in accuracy (89% vs. 88%), sensitivity (68% vs. 69%), and specificity (92% vs. 90%).</AbstractText The ML model resulted in a similar diagnostic performance as compared to expert readers, and may be deployed as a risk stratification tool for obstructive CAD. This study showed that utilization of ML is promising in the diagnosis of obstructive CAD.</AbstractText
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Improved accuracy of myocardial perfusion SPECT for detection of coronary artery disease by machine learning in a large population. We aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features with machine learning (ML) algorithms.</AbstractText 1,181 rest (201)Tl/stress (99m)Tc-sestamibi dual-isotope MPS studies [713 consecutive cases with correlating invasive coronary angiography (ICA) and suspected coronary artery disease (CAD) and 468 with low likelihood (LLk) of CAD <5%] were considered. Cases with stenosis <70% by ICA and LLk of CAD were considered normal. Total stress perfusion deficit (TPD) for supine/prone data, stress/rest perfusion change, and transient ischemic dilatation were derived by automated perfusion quantification software and were combined with age, sex, and post-electrocardiogram CAD probability by a boosted ensemble ML algorithm (LogitBoost). The diagnostic accuracy of the model for prediction of obstructive CAD ≥70% was compared to standard prone/supine quantification and to visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. Tenfold stratified cross-validation was performed.</AbstractText The diagnostic accuracy of ML (87.3% ± 2.1%) was similar to Expert 1 (86.0% ± 2.1%), but superior to combined supine/prone TPD (82.8% ± 2.2%) and Expert 2 (82.1% ± 2.2%) (P < .01). The receiver operator characteristic areas under curve for ML algorithm (0.94 ± 0.01) were higher than those for TPD and both visual readers (P < .001). The sensitivity of ML algorithm (78.9% ± 4.2%) was similar to TPD (75.6% ± 4.4%) and Expert 1 (76.3% ± 4.3%), but higher than that of Expert 2 (71.1% ± 4.6%), (P < .01). The specificity of ML algorithm (92.1% ± 2.2%) was similar to Expert 1 (91.4% ± 2.2%) and Expert 2 (88.3% ± 2.5%), but higher than TPD (86.8% ± 2.6%), (P < .01).</AbstractText ML significantly improves diagnostic performance of MPS by computational integration of quantitative perfusion and clinical data to the level rivaling expert analysis.</AbstractText
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Deviation From Normative Whole Brain and Deep Gray Matter Growth in Children With MOGAD, MS, and Monophasic Seronegative Demyelination. Pediatric-acquired demyelination of the CNS associated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG; MOG antibody-associated disease [MOGAD]) occurs as a monophasic or relapsing disease and with variable but often extensive T2 lesions in the brain. The impact of MOGAD on brain growth during maturation is unknown. We quantified the effect of pediatric MOGAD on brain growth trajectories and compared this with the growth trajectories of age-matched and sex-matched healthy children and children with multiple sclerosis (MS, a chronic relapsing disease known to lead to failure of normal brain growth and to loss of brain volume) and monophasic seronegative demyelination.</AbstractText We included children enrolled at incident attack in the prospective longitudinal Canadian Pediatric Demyelinating Disease Study who were recruited at the 3 largest enrollment sites, underwent research brain MRI scans, and were tested for serum MOG-IgG. Children seropositive for MOG-IgG were diagnosed with MOGAD. MS was diagnosed per the 2017 McDonald criteria. Monophasic seronegative demyelination was confirmed in children with no clinical or MRI evidence of recurrent demyelination and negative results for MOG-IgG and aquaporin-4-IgG. Whole and regional brain volumes were computed through symmetric nonlinear registration to templates. We computed age-normalized and sex-normalized <i We assessed brain volumes of 46 children with MOGAD, 26 with MS, and 51 with monophasic seronegative demyelinating syndrome. Children with MOGAD exhibited delayed (<i The onset of MOGAD during childhood adversely affects the expected trajectory of growth of deep gray matter structures, with accelerated changes in the months after an acute attack. Further studies are required to better determine the relative impact of monophasic vs relapsing MOGAD and whether relapsing MOGAD with attacks isolated to the optic nerves or spinal cord affects brain volume over time.</AbstractText
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34967377
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32424881
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33533500
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Primary pharyngeal synovial sarcoma in a pediatric patient: A case report.
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Prediction Model for Intermediate-Stage Hepatocellular Carcinoma Response to Transarterial Chemoembolization.
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Electromagnetic simulation of a 16-channel head transceiver at 7 T using circuit-spatial optimization.
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Synovial sarcoma is a rare malignant tumor that typically originates from the soft tissue of the extremities. The occurrence of primary pharyngeal synovial sarcoma is even rarer, and few studies have reported its radiological features. Here, we report a case of pediatric primary pharyngeal synovial sarcoma and describe the conventional and advanced magnetic resonance imaging (MRI) findings with pathologic correlation.</AbstractText An 11-year-old girl presented to the otolaryngologic clinic with dysphagia.</AbstractText Laryngoscopy revealed a large mass in the oropharynx. MRI revealed a well-defined soft tissue mass with a maximal diameter of approximately 5 cm originating from the submucosal space of the oropharynx. The mass was primarily solid and showed homogeneous contrast-enhancement. The mass was hypointense on T1-weighted images and hyperintense on T2-weighted images. The mass showed a homogeneously low apparent diffusion coefficient value on diffusion-weighted imaging, which indicated high tumor cellularity. Dynamic contrast-enhanced MRI revealed a hypovascular tumor with low values of the volume transfer constant between the extracellular extravascular space and blood plasma and blood plasma volume per unit tissue volume. Amide proton transfer-weighted MRI revealed a relatively high amide proton transfer signal in the tumor, indicating a high protein/peptide component. The patient underwent partial surgical resection of the tumor, and the diagnosis of biphasic synovial sarcoma was confirmed on postoperative pathological examination.</AbstractText The patient was started on chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide.</AbstractText The tumor did not respond to the 3 cycles of the chemotherapy. Thus, the patient underwent second surgery and subsequent radiation therapy. The patient is now under ifosfamide/carboplatin/etoposide chemotherapy.</AbstractText Synovial sarcoma should be considered in the differential diagnosis of pediatric oropharyngeal submucosal tumors. Multimodal MRI may aid diagnosis, although the final diagnosis should be based on the postoperative pathological examination findings.</AbstractText
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The outcome of intermediate-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is greatly heterogeneous. Current means for predicting HCC response to TACE are lacking.</AbstractText To investigate whether the combination of parameters derived from amide proton transfer (APT) and intravoxel incoherent motion (IVIM) imaging, and morphological characteristics of tumor can establish a better prediction model than the univariant model for HCC response to TACE.</AbstractText Prospective.</AbstractText 56 patients with intermediate-stage HCC (50 males and six females).</AbstractText 3.0T; T<sub Pretreatment APT signal intensities (SIs), apparent diffusion coefficient (ADC), true molecular diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) for tumor, peritumoral, and normal tissues were measured. Follow-up MRI scanning was performed, and the patients were classified as responders or nonresponders based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.</AbstractText The imaging parameters were compared among the three tissues and between the two groups using analysis of variance (ANOVA) or two-sample t-test. The prediction model's variables were derived from univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to explore the predictive performance.</AbstractText Based on the logistic regression analysis results, we established a prediction model that integrated the APT SI and D values in the tumor tissue and the tumor size. ROC analyses revealed that the model was better able to predict tumor response to TACE (area under the ROC curve = 0.851) than the individual parameters on their own.</AbstractText A prediction model incorporating pretreatment APT SI, D in the tumor tissue and tumor size may be useful for predicting the response of intermediate-stage HCC to TACE.</AbstractText 1 TECHNICAL EFFICACY: Stage 1 J. MAGN. RESON. IMAGING 2020;52:1657-1667.</AbstractText
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With increased interest in parallel transmission in ultrahigh-field MRI, methods are needed to correctly calculate the S-parameters and complex field maps of the parallel transmission coil. We present S-parameters paired with spatial field optimization to fully simulate a double-row 16-element transceiver array for brain MRI at 7 T.</AbstractText We implemented a closed-form equation of the coil S-parameters and overall spatial <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" As performed with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" This co-simulation methodology accurately simulates the transceiver, predicting consistent S-parameters, component values, and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
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Primary pharyngeal synovial sarcoma in a pediatric patient: A case report. Synovial sarcoma is a rare malignant tumor that typically originates from the soft tissue of the extremities. The occurrence of primary pharyngeal synovial sarcoma is even rarer, and few studies have reported its radiological features. Here, we report a case of pediatric primary pharyngeal synovial sarcoma and describe the conventional and advanced magnetic resonance imaging (MRI) findings with pathologic correlation.</AbstractText An 11-year-old girl presented to the otolaryngologic clinic with dysphagia.</AbstractText Laryngoscopy revealed a large mass in the oropharynx. MRI revealed a well-defined soft tissue mass with a maximal diameter of approximately 5 cm originating from the submucosal space of the oropharynx. The mass was primarily solid and showed homogeneous contrast-enhancement. The mass was hypointense on T1-weighted images and hyperintense on T2-weighted images. The mass showed a homogeneously low apparent diffusion coefficient value on diffusion-weighted imaging, which indicated high tumor cellularity. Dynamic contrast-enhanced MRI revealed a hypovascular tumor with low values of the volume transfer constant between the extracellular extravascular space and blood plasma and blood plasma volume per unit tissue volume. Amide proton transfer-weighted MRI revealed a relatively high amide proton transfer signal in the tumor, indicating a high protein/peptide component. The patient underwent partial surgical resection of the tumor, and the diagnosis of biphasic synovial sarcoma was confirmed on postoperative pathological examination.</AbstractText The patient was started on chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide.</AbstractText The tumor did not respond to the 3 cycles of the chemotherapy. Thus, the patient underwent second surgery and subsequent radiation therapy. The patient is now under ifosfamide/carboplatin/etoposide chemotherapy.</AbstractText Synovial sarcoma should be considered in the differential diagnosis of pediatric oropharyngeal submucosal tumors. Multimodal MRI may aid diagnosis, although the final diagnosis should be based on the postoperative pathological examination findings.</AbstractText
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Prediction Model for Intermediate-Stage Hepatocellular Carcinoma Response to Transarterial Chemoembolization. The outcome of intermediate-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is greatly heterogeneous. Current means for predicting HCC response to TACE are lacking.</AbstractText To investigate whether the combination of parameters derived from amide proton transfer (APT) and intravoxel incoherent motion (IVIM) imaging, and morphological characteristics of tumor can establish a better prediction model than the univariant model for HCC response to TACE.</AbstractText Prospective.</AbstractText 56 patients with intermediate-stage HCC (50 males and six females).</AbstractText 3.0T; T<sub Pretreatment APT signal intensities (SIs), apparent diffusion coefficient (ADC), true molecular diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) for tumor, peritumoral, and normal tissues were measured. Follow-up MRI scanning was performed, and the patients were classified as responders or nonresponders based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.</AbstractText The imaging parameters were compared among the three tissues and between the two groups using analysis of variance (ANOVA) or two-sample t-test. The prediction model's variables were derived from univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to explore the predictive performance.</AbstractText Based on the logistic regression analysis results, we established a prediction model that integrated the APT SI and D values in the tumor tissue and the tumor size. ROC analyses revealed that the model was better able to predict tumor response to TACE (area under the ROC curve = 0.851) than the individual parameters on their own.</AbstractText A prediction model incorporating pretreatment APT SI, D in the tumor tissue and tumor size may be useful for predicting the response of intermediate-stage HCC to TACE.</AbstractText 1 TECHNICAL EFFICACY: Stage 1 J. MAGN. RESON. IMAGING 2020;52:1657-1667.</AbstractText
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Electromagnetic simulation of a 16-channel head transceiver at 7 T using circuit-spatial optimization. With increased interest in parallel transmission in ultrahigh-field MRI, methods are needed to correctly calculate the S-parameters and complex field maps of the parallel transmission coil. We present S-parameters paired with spatial field optimization to fully simulate a double-row 16-element transceiver array for brain MRI at 7 T.</AbstractText We implemented a closed-form equation of the coil S-parameters and overall spatial <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" As performed with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" This co-simulation methodology accurately simulates the transceiver, predicting consistent S-parameters, component values, and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"
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39097805
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36031929
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38925210
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The effect of reconstruction algorithms on semi-quantitative measurements in (18)F-FDG PET/CT imaging.
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Technical note: Characterization of novel iterative reconstructed cone beam CT images for dose tracking and adaptive radiotherapy on L-shape linacs.
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Sense of agency in schizophrenia: A reconciliation of conflicting findings through a theory-driven literature review.
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This study was carried out to understand whether Q.Clear and ordered subset expectation maximization (OSEM), reconstruction algorithms used in fluorine-18-fluorodeoxyglucose (<sup Raw PET data of 264 patients who were referred to <sup β350+ToF yielded higher measurement results than all other variables for all of the lesion SUVmax, lesion SUVmean, L/AP SUVmax, and L/AP SUVmean parameters. OSEM+ToF and OSEM+TOF+PSF algorithms yielded higher mean and median SUVmax values for the reference structures (liver and mediastinum) and for lesions SUVmax and SUVmean values were statistically significantly lower than the β350+ToF method. The method with the lowest mean value for the L/Liver SUVmax variable was OSEM+ToF 4iter16ss (mean=1.76), while the method with the highest mean value was β350+ToF (mean=2.26). β350+ToF was the reconstruction method with the highest ratios for L/AP SUVmax and SUVmean for both lesions below and above 1 cm. β350+ToF algorithm had also statistically significantly higher results for these variables compared to all other parameters in malignant lesions.</AbstractText When comparing <sup
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Cone-beam computed tomography (CBCT) allows for patient setup and positioning, and potentially dose verification or adaptive replanning prior to each treatment delivery. Poor CBCT image quality due to scatter artifacts and patient motion has been a major limiting factor. A new image reconstruction algorithm was recently clinically implemented for improving image quality through iterative reconstruction (iCBCT).</AbstractText This study aims to characterize iCBCT image quality, establish image value (HU)-to-relative electron density (RED) calibration curves for dose calculation, and assess the dosimetric accuracy for different anatomical sites.</AbstractText Both conventional CBCT and iCBCT scans were acquired from a Varian TrueBeam On-Board Imager system. A Catphan 604 phantom was scanned to compare image quality between the traditional Feldkamp-Davis-Kress (FDK) and novel iterative reconstruction techniques. Computerized Imaging Reference Systems (CIRS) electron density phantom was used to construct site-specific HU-RED curves corresponding to various scan settings. The CIRS Dynamic Thorax phantom, Rando pelvis phantom, and BrainLab head phantom were used for assessing dosimetric accuracy calculated on iCBCT images, compared to that on traditional FDK-based CBCT images. All phantoms were scanned on a computed tomography (CT) to obtain baseline HU values for comparison.</AbstractText Test results obtained from Catphan showed statistically significant improvement with iCBCT, compared to FDK CBCT. Average HU differences from the baseline CT values were improved to within ±30 HU for iCBCT, compared to FDK CBCT for phantom studies. Dose calculated on iCBCT for both phantoms and patient cases directly using baseline HU-RED calibration from CT showed 0.5%-2.0% accuracy from the baseline dose calculated on CT, which is comparable to doses calculated using site-specific HU-RED calibration curves.</AbstractText iCBCT provides improved image quality, improved HU accuracy compared to CT baseline, and has potential to provide online dose verification as part of the adaptive radiotherapy workflow directly using the baseline HU-RED calibration curve from CT.</AbstractText
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The sense of agency is the experience of being the author of self-generated actions and their outcomes. Both clinical manifestations and experimental evidence suggest that the agency experience and the mechanisms underlying agency attribution may be dysfunctional in schizophrenia. Yet, studies investigating the sense of agency in these patients show seemingly conflicting results: some indicated under-attribution of self-agency (coherently with certain positive symptoms), while others suggested over-attribution of self-agency. In this review, we assess whether recent theoretical frameworks can reconcile these divergent results. We examine whether the identification of agency abnormalities in schizophrenia might depend on the measure of self-agency considered (depending on the specific task requirements) and the available agency-related cues. We conclude that all these aspects are relevant to predict and characterize the type of agency misattribution that schizophrenia patients might show. We argue that one particular model, based on the predictive coding theory, can reconcile the interpretation of the multifarious phenomenology of agency manifestations in schizophrenia, paving the way for testing agency disorders in novel ways.</AbstractText
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The effect of reconstruction algorithms on semi-quantitative measurements in (18)F-FDG PET/CT imaging. This study was carried out to understand whether Q.Clear and ordered subset expectation maximization (OSEM), reconstruction algorithms used in fluorine-18-fluorodeoxyglucose (<sup Raw PET data of 264 patients who were referred to <sup β350+ToF yielded higher measurement results than all other variables for all of the lesion SUVmax, lesion SUVmean, L/AP SUVmax, and L/AP SUVmean parameters. OSEM+ToF and OSEM+TOF+PSF algorithms yielded higher mean and median SUVmax values for the reference structures (liver and mediastinum) and for lesions SUVmax and SUVmean values were statistically significantly lower than the β350+ToF method. The method with the lowest mean value for the L/Liver SUVmax variable was OSEM+ToF 4iter16ss (mean=1.76), while the method with the highest mean value was β350+ToF (mean=2.26). β350+ToF was the reconstruction method with the highest ratios for L/AP SUVmax and SUVmean for both lesions below and above 1 cm. β350+ToF algorithm had also statistically significantly higher results for these variables compared to all other parameters in malignant lesions.</AbstractText When comparing <sup
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Technical note: Characterization of novel iterative reconstructed cone beam CT images for dose tracking and adaptive radiotherapy on L-shape linacs. Cone-beam computed tomography (CBCT) allows for patient setup and positioning, and potentially dose verification or adaptive replanning prior to each treatment delivery. Poor CBCT image quality due to scatter artifacts and patient motion has been a major limiting factor. A new image reconstruction algorithm was recently clinically implemented for improving image quality through iterative reconstruction (iCBCT).</AbstractText This study aims to characterize iCBCT image quality, establish image value (HU)-to-relative electron density (RED) calibration curves for dose calculation, and assess the dosimetric accuracy for different anatomical sites.</AbstractText Both conventional CBCT and iCBCT scans were acquired from a Varian TrueBeam On-Board Imager system. A Catphan 604 phantom was scanned to compare image quality between the traditional Feldkamp-Davis-Kress (FDK) and novel iterative reconstruction techniques. Computerized Imaging Reference Systems (CIRS) electron density phantom was used to construct site-specific HU-RED curves corresponding to various scan settings. The CIRS Dynamic Thorax phantom, Rando pelvis phantom, and BrainLab head phantom were used for assessing dosimetric accuracy calculated on iCBCT images, compared to that on traditional FDK-based CBCT images. All phantoms were scanned on a computed tomography (CT) to obtain baseline HU values for comparison.</AbstractText Test results obtained from Catphan showed statistically significant improvement with iCBCT, compared to FDK CBCT. Average HU differences from the baseline CT values were improved to within ±30 HU for iCBCT, compared to FDK CBCT for phantom studies. Dose calculated on iCBCT for both phantoms and patient cases directly using baseline HU-RED calibration from CT showed 0.5%-2.0% accuracy from the baseline dose calculated on CT, which is comparable to doses calculated using site-specific HU-RED calibration curves.</AbstractText iCBCT provides improved image quality, improved HU accuracy compared to CT baseline, and has potential to provide online dose verification as part of the adaptive radiotherapy workflow directly using the baseline HU-RED calibration curve from CT.</AbstractText
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Sense of agency in schizophrenia: A reconciliation of conflicting findings through a theory-driven literature review. The sense of agency is the experience of being the author of self-generated actions and their outcomes. Both clinical manifestations and experimental evidence suggest that the agency experience and the mechanisms underlying agency attribution may be dysfunctional in schizophrenia. Yet, studies investigating the sense of agency in these patients show seemingly conflicting results: some indicated under-attribution of self-agency (coherently with certain positive symptoms), while others suggested over-attribution of self-agency. In this review, we assess whether recent theoretical frameworks can reconcile these divergent results. We examine whether the identification of agency abnormalities in schizophrenia might depend on the measure of self-agency considered (depending on the specific task requirements) and the available agency-related cues. We conclude that all these aspects are relevant to predict and characterize the type of agency misattribution that schizophrenia patients might show. We argue that one particular model, based on the predictive coding theory, can reconcile the interpretation of the multifarious phenomenology of agency manifestations in schizophrenia, paving the way for testing agency disorders in novel ways.</AbstractText
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39997048
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37425525
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39878398
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The Critical Role of Penicillin in Syphilis Treatment and Emerging Resistance Challenges.
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A Rare Case of Neurosyphilis Manifesting as Psychosis in an HIV-Negative Patient.
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Riga-Fede Disease in a Child With Neuropsychomotor Impairment: A Case Report.
|
Syphilis, a global healthcare burden, is a sexually transmitted infection caused by the spirochete <i
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Neurosyphilis is a rare disease now, given the availability of antibiotics to treat syphilis. Patients with neurosyphilis could present with psychiatric symptoms. We present a rare case of neurosyphilis with only psychiatric symptoms. The patient was a 49-year-old male who presented with self-neglect and was not interacting with others. Treponema antibodies were positive, and rapid plasma reagin (RPR) was 1:512 with a positive venereal disease research laboratory test (VDRL) in the cerebrospinal fluid. The patient was treated with an IV penicillin regimen for neurosyphilis and improved remarkably with a return to baseline on follow-up.</AbstractText
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Riga-Fede disease (RFD) is a rare, benign condition marked by traumatic ulceration on the tongue's ventral side in infants. It arises from friction between the tongue and lower incisors during sucking, potentially worsening into a keratinized lesion if the cause is not addressed. This report details the case of a 1-year-6-month-old male with hydrocephalus, cleft palate, corpus callosum dysgenesis, neuropsychomotor developmental delay, and tracheostomy and gastrostomy needs. He presented to the Hospital for Rehabilitation of Craniofacial Anomalies of Bauru with a persistent tongue lesion. Clinical examination showed a yellowish-white lesion with defined edges, closely associated with teeth 71 and 81. A biopsy under general anesthesia confirmed RFD. Initial treatment involved smoothing the incisors and applying fluoride varnish to reduce sensitivity. Due to the child's repetitive tongue movements, the lesion persisted. Consequently, low-level laser therapy was introduced weekly, leading to substantial improvement. The laser's anti-inflammatory and tissue repair properties demonstrated effectiveness. This case underscores the importance of tailoring treatment to the individual clinical circumstances of each patient.</AbstractText
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The Critical Role of Penicillin in Syphilis Treatment and Emerging Resistance Challenges. Syphilis, a global healthcare burden, is a sexually transmitted infection caused by the spirochete <i
|
A Rare Case of Neurosyphilis Manifesting as Psychosis in an HIV-Negative Patient. Neurosyphilis is a rare disease now, given the availability of antibiotics to treat syphilis. Patients with neurosyphilis could present with psychiatric symptoms. We present a rare case of neurosyphilis with only psychiatric symptoms. The patient was a 49-year-old male who presented with self-neglect and was not interacting with others. Treponema antibodies were positive, and rapid plasma reagin (RPR) was 1:512 with a positive venereal disease research laboratory test (VDRL) in the cerebrospinal fluid. The patient was treated with an IV penicillin regimen for neurosyphilis and improved remarkably with a return to baseline on follow-up.</AbstractText
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Riga-Fede Disease in a Child With Neuropsychomotor Impairment: A Case Report. Riga-Fede disease (RFD) is a rare, benign condition marked by traumatic ulceration on the tongue's ventral side in infants. It arises from friction between the tongue and lower incisors during sucking, potentially worsening into a keratinized lesion if the cause is not addressed. This report details the case of a 1-year-6-month-old male with hydrocephalus, cleft palate, corpus callosum dysgenesis, neuropsychomotor developmental delay, and tracheostomy and gastrostomy needs. He presented to the Hospital for Rehabilitation of Craniofacial Anomalies of Bauru with a persistent tongue lesion. Clinical examination showed a yellowish-white lesion with defined edges, closely associated with teeth 71 and 81. A biopsy under general anesthesia confirmed RFD. Initial treatment involved smoothing the incisors and applying fluoride varnish to reduce sensitivity. Due to the child's repetitive tongue movements, the lesion persisted. Consequently, low-level laser therapy was introduced weekly, leading to substantial improvement. The laser's anti-inflammatory and tissue repair properties demonstrated effectiveness. This case underscores the importance of tailoring treatment to the individual clinical circumstances of each patient.</AbstractText
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27130564
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24046740
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27574308
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Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study.
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tDCS over the left inferior frontal cortex improves speech production in aphasia.
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Repetition suppression: a means to index neural representations using BOLD?
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Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.</AbstractText
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In this study, we investigated the combined effect of transcranial direct current stimulation (tDCS) and an intensive Conversational therapy treatment on discourse skills in 12 persons with chronic aphasia. Six short video clips depicting everyday life contexts were prepared. Three videoclips were used to elicit spontaneous conversation during treatment. The remaining three were presented only before and after the therapy. Participants were prompted to talk about the contents of each videoclip while stimulated with tDCS (20 min 1 mA) over the left hemisphere in three conditions: anodic tDCS over the Broca's area, anodic tDCS over the Wernicke's area, and a sham condition. Each experimental condition was performed for 10 consecutive daily sessions with 14 days of intersession interval. After stimulation over Broca's area, the participants produced more Content Units, verbs and sentences than in the remaining two conditions. Importantly, this improvement was still detectable 1 month after the end of treatment and its effects were generalized also to the three videoclips that had been administered at the beginning and at the end of the therapy sessions. In conclusion, anodic tDCS applied over the left Broca's area together with an intensive "Conversational Therapy" treatment improves informative speech in persons with chronic aphasia. We believe that positive tDCS effects may be further extended to other language domains, such as the recovery of speech production.</AbstractText
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Understanding how the human brain gives rise to complex cognitive processes remains one of the biggest challenges of contemporary neuroscience. While invasive recording in animal models can provide insight into neural processes that are conserved across species, our understanding of cognition more broadly relies upon investigation of the human brain itself. There is therefore an imperative to establish non-invasive tools that allow human brain activity to be measured at high spatial and temporal resolution. In recent years, various attempts have been made to refine the coarse signal available in functional magnetic resonance imaging (fMRI), providing a means to investigate neural activity at the meso-scale, i.e. at the level of neural populations. The most widely used techniques include repetition suppression and multivariate pattern analysis. Human neuroscience can now use these techniques to investigate how representations are encoded across neural populations and transformed by relevant computations. Here, we review the physiological basis, applications and limitations of fMRI repetition suppression with a brief comparison to multivariate techniques. By doing so, we show how fMRI repetition suppression holds promise as a tool to reveal complex neural mechanisms that underlie human cognitive function.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.</AbstractText
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Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study. Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.</AbstractText
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tDCS over the left inferior frontal cortex improves speech production in aphasia. In this study, we investigated the combined effect of transcranial direct current stimulation (tDCS) and an intensive Conversational therapy treatment on discourse skills in 12 persons with chronic aphasia. Six short video clips depicting everyday life contexts were prepared. Three videoclips were used to elicit spontaneous conversation during treatment. The remaining three were presented only before and after the therapy. Participants were prompted to talk about the contents of each videoclip while stimulated with tDCS (20 min 1 mA) over the left hemisphere in three conditions: anodic tDCS over the Broca's area, anodic tDCS over the Wernicke's area, and a sham condition. Each experimental condition was performed for 10 consecutive daily sessions with 14 days of intersession interval. After stimulation over Broca's area, the participants produced more Content Units, verbs and sentences than in the remaining two conditions. Importantly, this improvement was still detectable 1 month after the end of treatment and its effects were generalized also to the three videoclips that had been administered at the beginning and at the end of the therapy sessions. In conclusion, anodic tDCS applied over the left Broca's area together with an intensive "Conversational Therapy" treatment improves informative speech in persons with chronic aphasia. We believe that positive tDCS effects may be further extended to other language domains, such as the recovery of speech production.</AbstractText
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Repetition suppression: a means to index neural representations using BOLD? Understanding how the human brain gives rise to complex cognitive processes remains one of the biggest challenges of contemporary neuroscience. While invasive recording in animal models can provide insight into neural processes that are conserved across species, our understanding of cognition more broadly relies upon investigation of the human brain itself. There is therefore an imperative to establish non-invasive tools that allow human brain activity to be measured at high spatial and temporal resolution. In recent years, various attempts have been made to refine the coarse signal available in functional magnetic resonance imaging (fMRI), providing a means to investigate neural activity at the meso-scale, i.e. at the level of neural populations. The most widely used techniques include repetition suppression and multivariate pattern analysis. Human neuroscience can now use these techniques to investigate how representations are encoded across neural populations and transformed by relevant computations. Here, we review the physiological basis, applications and limitations of fMRI repetition suppression with a brief comparison to multivariate techniques. By doing so, we show how fMRI repetition suppression holds promise as a tool to reveal complex neural mechanisms that underlie human cognitive function.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.</AbstractText
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36495178
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29470968
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38024664
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Measuring capillary flow dynamics using interlaced two-photon volumetric scanning.
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Multiple Sclerosis: Mechanisms and Immunotherapy.
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Fabrication and Characterization of a Polydopamine-Modified Bacterial Cellulose and Sugarcane Filter Cake-Derived Hydroxyapatite Composite Scaffold.
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Two photon microscopy and optical coherence tomography (OCT) are two standard methods for measuring flow speeds of red blood cells in microvessels, particularly in animal models. However, traditional two photon microscopy lacks the depth of field to adequately capture the full volumetric complexity of the cerebral microvasculature and OCT lacks the specificity offered by fluorescent labeling. In addition, the traditional raster scanning technique utilized in both modalities requires a balance of image frame rate and field of view, which severely limits the study of RBC velocities in the microvascular network. Here, we overcome this by using a custom two photon system with an axicon based Bessel beam to obtain volumetric images of the microvascular network with fluorescent specificity. We combine this with a novel scan pattern that generates pairs of frames with short time delay sufficient for tracking red blood cell flow in capillaries. We track RBC flow speeds in 10 or more capillaries simultaneously at 1 Hz in a 237 µm × 237 µm × 120 µm volume and quantified both their spatial and temporal variability in speed. We also demonstrate the ability to track flow speed changes around stalls in capillary flow and measure to 300 µm in depth.</AbstractText
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Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system. However, most drugs for relapsing MS are not effective in treating progressive disease. Progressive MS features a compartmentalized immune response in the central nervous system, involving microglia cells and astrocytes, as well as immune-independent processes that drive axonal dysfunction. Major challenges for MS research involve understanding the mechanisms of disease progression, developing treatment for progressive MS, and determining the degree to which progressive disease can be prevented by early treatment. Key priorities for MS research include developing biomarkers, personalized medicine and advanced imaging, and a better understanding of the microbiome. With a better understanding of the genetic and epidemiological aspects of this disease, approaches to prevent MS are now also being considered.</AbstractText
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The search for environmentally friendly and sustainable sources of raw materials has been ongoing for quite a while, and currently, the utilization and applications of agro-industrial biomass residues in biomedicine are being researched. In this study, a polydopamine (PDA)-modified bacterial cellulose (BC) and hydroxyapatite (HA) composite scaffold was fabricated using the freeze-drying method. The as-prepared hydroxyapatite was synthesized via the chemical precipitation method using sugarcane filter cake as a calcium source, as reported in a previous study. X-ray diffraction analysis revealed a carbonated phase of the prepared hydroxyapatite, similar to that of the natural bone mineral. Wide-angle X-ray scattering analysis revealed the successful fabrication of BC/HA composite scaffolds, while X-ray photoelectron spectroscopy suggested that PDA was deposited on the surface of the BC/HA composite scaffolds. In vitro cell viability assays indicated that BC/HA and PDA-modified composite scaffolds did not induce cytotoxicity and were biocompatible with MC3T3-E1 preosteoblasts. PDA-modified composite scaffolds showed enhanced protein adsorption capacity in vitro compared to the unmodified scaffolds. On a concluding note, these results demonstrate that agro-industrial biomass residues have the potential to be used in biomedical applications and that PDA-modified BC/HA composite scaffolds are a promising biomaterial for bone tissue engineering.</AbstractText
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Measuring capillary flow dynamics using interlaced two-photon volumetric scanning. Two photon microscopy and optical coherence tomography (OCT) are two standard methods for measuring flow speeds of red blood cells in microvessels, particularly in animal models. However, traditional two photon microscopy lacks the depth of field to adequately capture the full volumetric complexity of the cerebral microvasculature and OCT lacks the specificity offered by fluorescent labeling. In addition, the traditional raster scanning technique utilized in both modalities requires a balance of image frame rate and field of view, which severely limits the study of RBC velocities in the microvascular network. Here, we overcome this by using a custom two photon system with an axicon based Bessel beam to obtain volumetric images of the microvascular network with fluorescent specificity. We combine this with a novel scan pattern that generates pairs of frames with short time delay sufficient for tracking red blood cell flow in capillaries. We track RBC flow speeds in 10 or more capillaries simultaneously at 1 Hz in a 237 µm × 237 µm × 120 µm volume and quantified both their spatial and temporal variability in speed. We also demonstrate the ability to track flow speed changes around stalls in capillary flow and measure to 300 µm in depth.</AbstractText
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Multiple Sclerosis: Mechanisms and Immunotherapy. Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system. However, most drugs for relapsing MS are not effective in treating progressive disease. Progressive MS features a compartmentalized immune response in the central nervous system, involving microglia cells and astrocytes, as well as immune-independent processes that drive axonal dysfunction. Major challenges for MS research involve understanding the mechanisms of disease progression, developing treatment for progressive MS, and determining the degree to which progressive disease can be prevented by early treatment. Key priorities for MS research include developing biomarkers, personalized medicine and advanced imaging, and a better understanding of the microbiome. With a better understanding of the genetic and epidemiological aspects of this disease, approaches to prevent MS are now also being considered.</AbstractText
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Fabrication and Characterization of a Polydopamine-Modified Bacterial Cellulose and Sugarcane Filter Cake-Derived Hydroxyapatite Composite Scaffold. The search for environmentally friendly and sustainable sources of raw materials has been ongoing for quite a while, and currently, the utilization and applications of agro-industrial biomass residues in biomedicine are being researched. In this study, a polydopamine (PDA)-modified bacterial cellulose (BC) and hydroxyapatite (HA) composite scaffold was fabricated using the freeze-drying method. The as-prepared hydroxyapatite was synthesized via the chemical precipitation method using sugarcane filter cake as a calcium source, as reported in a previous study. X-ray diffraction analysis revealed a carbonated phase of the prepared hydroxyapatite, similar to that of the natural bone mineral. Wide-angle X-ray scattering analysis revealed the successful fabrication of BC/HA composite scaffolds, while X-ray photoelectron spectroscopy suggested that PDA was deposited on the surface of the BC/HA composite scaffolds. In vitro cell viability assays indicated that BC/HA and PDA-modified composite scaffolds did not induce cytotoxicity and were biocompatible with MC3T3-E1 preosteoblasts. PDA-modified composite scaffolds showed enhanced protein adsorption capacity in vitro compared to the unmodified scaffolds. On a concluding note, these results demonstrate that agro-industrial biomass residues have the potential to be used in biomedical applications and that PDA-modified BC/HA composite scaffolds are a promising biomaterial for bone tissue engineering.</AbstractText
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24399974
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20139014
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40585536
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Connectivity, pharmacology, and computation: toward a mechanistic understanding of neural system dysfunction in schizophrenia.
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Spontaneous brain activity and EEG microstates. A novel EEG/fMRI analysis approach to explore resting-state networks.
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Sleep disturbance as a mediator of the relationship between perceived stress and demoralization in hemodialysis patients: a structural equation modeling analysis.
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Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks. Functional neuroimaging tools have evolved sufficiently to reliably detect system-level disturbances in neural networks. This review focuses on recent findings in schizophrenia and bipolar illness using resting-state neuroimaging, an advantageous approach for biomarker development given its ease of data collection and lack of task-based confounds. These benefits notwithstanding, neuroimaging does not yet allow the evaluation of individual neurons within local circuits, where pharmacological treatments ultimately exert their effects. This limitation constitutes an important obstacle in translating findings from animal research to humans and from healthy humans to patient populations. Integrating new neuroscientific tools may help to bridge some of these gaps. We specifically discuss two complementary approaches. The first is pharmacological manipulations in healthy volunteers, which transiently mimic some cardinal features of psychiatric conditions. We specifically focus on recent neuroimaging studies using the NMDA receptor antagonist, ketamine, to probe glutamate synaptic dysfunction associated with schizophrenia. Second, we discuss the combination of human pharmacological imaging with biophysically informed computational models developed to guide the interpretation of functional imaging studies and to inform the development of pathophysiologic hypotheses. To illustrate this approach, we review clinical investigations in addition to recent findings of how computational modeling has guided inferences drawn from our studies involving ketamine administration to healthy subjects. Thus, this review asserts that linking experimental studies in humans with computational models will advance to effort to bridge cellular, systems, and clinical neuroscience approaches to psychiatric disorders.</AbstractText
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The brain is active even in the absence of explicit input or output as demonstrated from electrophysiological as well as imaging studies. Using a combined approach we measured spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal along with electroencephalography (EEG) in eleven healthy subjects during relaxed wakefulness (eyes closed). In contrast to other studies which used the EEG frequency information to guide the functional MRI (fMRI) analysis, we opted for transient EEG events, which identify and quantify brain electric microstates as time epochs with quasi-stable field topography. We then used this microstate information as regressors for the BOLD fluctuations. Single trial EEGs were segmented with a specific module of the LORETA (low resolution electromagnetic tomography) software package in which microstates are represented as normalized vectors constituted by scalp electric potentials, i.e., the related 3-dimensional distribution of cortical current density in the brain. Using the occurrence and the duration of each microstate, we modeled the hemodynamic response function (HRF) which revealed BOLD activation in all subjects. The BOLD activation patterns resembled well known resting-state networks (RSNs) such as the default mode network. Furthermore we "cross validated" the data performing a BOLD independent component analysis (ICA) and computing the correlation between each ICs and the EEG microstates across all subjects. This study shows for the first time that the information contained within EEG microstates on a millisecond timescale is able to elicit BOLD activation patterns consistent with well known RSNs, opening new avenues for multimodal imaging data processing.</AbstractText
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Demoralization describes a state of existential distress, isolation, impotence, hopelessness, helplessness, and loss of purpose and meaning in life. Demoralization is associated with suicidal thoughts, which could lead to a desire for hastened death. Perceived stress could be viewed as the sense of imbalance between the stressors experienced by an individual in daily life and his or her coping capability. Many studies have tested the relationships between perceived stress, sleep disturbance, and demoralization; however, the mechanism of sleep disturbance has not been fully evaluated.</AbstractText To verify the relationship between perceived stress and demoralization and explore the mediating effect of sleep disturbance on the relationship between perceived stress and demoralization in hemodialysis patients.</AbstractText A cross-sectional questionnaire survey using convenience sampling from July to August 2022, 547 hemodialysis patients from ten hospitals filled out the Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI), Demoralization Scale (DS), and general information questionnaire. The data were analyzed using SPSS 26.0, and path analysis and structural equation modeling were used to explore the relationships among perceived stress, sleep disturbance, and demoralization.</AbstractText Perceived stress was significantly and positively associated with demoralization (<i Perceived stress affects demoralization among hemodialysis patients, and sleep disturbance is a mediator in the relationship. Perceived stress in hemodialysis patients should be measured and effectively managed to improve positive effects on demoralization. It is necessary for medical staff to consider implementing perceived stress interventions with an emphasis on construction of sleep strategies to assist hemodialysis patients improve their demoralization.</AbstractText
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Connectivity, pharmacology, and computation: toward a mechanistic understanding of neural system dysfunction in schizophrenia. Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks. Functional neuroimaging tools have evolved sufficiently to reliably detect system-level disturbances in neural networks. This review focuses on recent findings in schizophrenia and bipolar illness using resting-state neuroimaging, an advantageous approach for biomarker development given its ease of data collection and lack of task-based confounds. These benefits notwithstanding, neuroimaging does not yet allow the evaluation of individual neurons within local circuits, where pharmacological treatments ultimately exert their effects. This limitation constitutes an important obstacle in translating findings from animal research to humans and from healthy humans to patient populations. Integrating new neuroscientific tools may help to bridge some of these gaps. We specifically discuss two complementary approaches. The first is pharmacological manipulations in healthy volunteers, which transiently mimic some cardinal features of psychiatric conditions. We specifically focus on recent neuroimaging studies using the NMDA receptor antagonist, ketamine, to probe glutamate synaptic dysfunction associated with schizophrenia. Second, we discuss the combination of human pharmacological imaging with biophysically informed computational models developed to guide the interpretation of functional imaging studies and to inform the development of pathophysiologic hypotheses. To illustrate this approach, we review clinical investigations in addition to recent findings of how computational modeling has guided inferences drawn from our studies involving ketamine administration to healthy subjects. Thus, this review asserts that linking experimental studies in humans with computational models will advance to effort to bridge cellular, systems, and clinical neuroscience approaches to psychiatric disorders.</AbstractText
|
Spontaneous brain activity and EEG microstates. A novel EEG/fMRI analysis approach to explore resting-state networks. The brain is active even in the absence of explicit input or output as demonstrated from electrophysiological as well as imaging studies. Using a combined approach we measured spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal along with electroencephalography (EEG) in eleven healthy subjects during relaxed wakefulness (eyes closed). In contrast to other studies which used the EEG frequency information to guide the functional MRI (fMRI) analysis, we opted for transient EEG events, which identify and quantify brain electric microstates as time epochs with quasi-stable field topography. We then used this microstate information as regressors for the BOLD fluctuations. Single trial EEGs were segmented with a specific module of the LORETA (low resolution electromagnetic tomography) software package in which microstates are represented as normalized vectors constituted by scalp electric potentials, i.e., the related 3-dimensional distribution of cortical current density in the brain. Using the occurrence and the duration of each microstate, we modeled the hemodynamic response function (HRF) which revealed BOLD activation in all subjects. The BOLD activation patterns resembled well known resting-state networks (RSNs) such as the default mode network. Furthermore we "cross validated" the data performing a BOLD independent component analysis (ICA) and computing the correlation between each ICs and the EEG microstates across all subjects. This study shows for the first time that the information contained within EEG microstates on a millisecond timescale is able to elicit BOLD activation patterns consistent with well known RSNs, opening new avenues for multimodal imaging data processing.</AbstractText
|
Sleep disturbance as a mediator of the relationship between perceived stress and demoralization in hemodialysis patients: a structural equation modeling analysis. Demoralization describes a state of existential distress, isolation, impotence, hopelessness, helplessness, and loss of purpose and meaning in life. Demoralization is associated with suicidal thoughts, which could lead to a desire for hastened death. Perceived stress could be viewed as the sense of imbalance between the stressors experienced by an individual in daily life and his or her coping capability. Many studies have tested the relationships between perceived stress, sleep disturbance, and demoralization; however, the mechanism of sleep disturbance has not been fully evaluated.</AbstractText To verify the relationship between perceived stress and demoralization and explore the mediating effect of sleep disturbance on the relationship between perceived stress and demoralization in hemodialysis patients.</AbstractText A cross-sectional questionnaire survey using convenience sampling from July to August 2022, 547 hemodialysis patients from ten hospitals filled out the Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI), Demoralization Scale (DS), and general information questionnaire. The data were analyzed using SPSS 26.0, and path analysis and structural equation modeling were used to explore the relationships among perceived stress, sleep disturbance, and demoralization.</AbstractText Perceived stress was significantly and positively associated with demoralization (<i Perceived stress affects demoralization among hemodialysis patients, and sleep disturbance is a mediator in the relationship. Perceived stress in hemodialysis patients should be measured and effectively managed to improve positive effects on demoralization. It is necessary for medical staff to consider implementing perceived stress interventions with an emphasis on construction of sleep strategies to assist hemodialysis patients improve their demoralization.</AbstractText
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39081795
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37759406
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38513522
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Adrenocortical and autonomic cross-system regulation in youth: A meta-analysis.
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Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury.
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'Snakes and ladders' in paleoanthropology: From cognitive surprise to skillfulness a million years ago.
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Childhood and adolescence are salient periods for the development of adrenocortical and autonomic arms of the stress response system (SRS), setting the stage for subsequent health and adaptive functioning. Although adrenocortical and autonomic systems theoretically function in highly coordinated ways, the strength of the relationship between these systems remains unclear. We leveraged a multivariate mixed effects meta-analytic approach to assess associations between adrenocortical, sympathetic, and parasympathetic functioning at rest and reactivity during stress-inducing tasks across 52 studies (N = 7,671; 5-20 years old). Results suggested a modest positive relation between adrenocortical and sympathetic systems as well as between adrenocortical and parasympathetic systems. Moderation analyses indicated the strength of associations varied as a function of several methodological and sociodemographic characteristics. Environmental effects on cross-system regulation were less clear, perhaps due to underrepresentation of adverse-exposed youth in the included studies. Collectively, our findings call for greater methodological attention to the dynamical, non-linear nature of cross-system functioning, as well as the role of experience in their organization across development.</AbstractText
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Traumatic brain injury (TBI) is a devastating neurological disorder caused by a physical impact to the brain that promotes diffuse damage and chronic neurodegeneration. Key mechanisms believed to support secondary brain injury include mitochondrial dysfunction and chronic neuroinflammation. Microglia and brain-infiltrating macrophages are responsible for neuroinflammatory cytokine and reactive oxygen species (ROS) production after TBI. Their production is associated with loss of homeostatic microglial functions such as immunosurveillance, phagocytosis, and immune resolution. Beyond providing energy support, mitochondrial metabolic pathways reprogram the pro- and anti-inflammatory machinery in immune cells, providing a critical immunometabolic axis capable of regulating immunologic response to noxious stimuli. In the brain, the capacity to adapt to different environmental stimuli derives, in part, from microglia's ability to recognize and respond to changes in extracellular and intracellular metabolite levels. This capacity is met by an equally plastic metabolism, capable of altering immune function. Microglial pro-inflammatory activation is associated with decreased mitochondrial respiration, whereas anti-inflammatory microglial polarization is supported by increased oxidative metabolism. These metabolic adaptations contribute to neuroimmune responses, placing mitochondria as a central regulator of post-traumatic neuroinflammation. Although it is established that profound neurometabolic changes occur following TBI, key questions related to metabolic shifts in microglia remain unresolved. These include (a) the nature of microglial mitochondrial dysfunction after TBI, (b) the hierarchical positions of different metabolic pathways such as glycolysis, pentose phosphate pathway, glutaminolysis, and lipid oxidation during secondary injury and recovery, and (c) how immunometabolism alters microglial phenotypes, culminating in chronic non-resolving neuroinflammation. In this basic neurochemistry review article, we describe the contributions of immunometabolism to TBI, detail primary evidence of mitochondrial dysfunction and metabolic impairments in microglia and macrophages, discuss how major metabolic pathways contribute to post-traumatic neuroinflammation, and set out future directions toward advancing immunometabolic phenotyping in TBI.</AbstractText
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A paradigmatic account may suffice to explain behavioral evolution in early Homo. We propose a parsimonious account that (1) could explain a particular, frequently-encountered, archeological outcome of behavior in early Homo - namely, the fashioning of a Paleolithic stone 'handaxe' - from a biological theoretic perspective informed by the free energy principle (FEP); and that (2) regards instances of the outcome as postdictive or retrodictive, circumstantial corroboration. Our proposal considers humankind evolving as a self-organizing biological ecosystem at a geological time-scale. We offer a narrative treatment of this self-organization in terms of the FEP. Specifically, we indicate how 'cognitive surprises' could underwrite an evolving propensity in early Homo to express sporadic unorthodox or anomalous behavior. This co-evolutionary propensity has left us a legacy of Paleolithic artifacts that is reminiscent of a 'snakes and ladders' board game of appearances, disappearances, and reappearances of particular archeological traces of Paleolithic behavior. When detected in the Early and Middle Pleistocene record, anthropologists and archeologists often imagine evidence of unusual or novel behavior in terms of early humankind ascending the rungs of a figurative phylogenetic 'ladder' - as if these corresponded to progressive evolution of cognitive abilities that enabled incremental achievements of increasingly innovative technical prowess, culminating in the cognitive ascendancy of Homo sapiens. The conjecture overlooks a plausible likelihood that behavior by an individual who was atypical among her conspecifics could have been disregarded in a community of Hominina (for definition see Appendix 1) that failed to recognize, imagine, or articulate potential advantages of adopting hitherto unorthodox behavior. Such failure, as well as diverse fortuitous demographic accidents, would cause exceptional personal behavior to be ignored and hence unremembered. It could disappear by a pitfall, down a 'snake', as it were, in the figurative evolutionary board game; thereby causing a discontinuity in the evolution of human behavior that presents like an evolutionary puzzle. The puzzle discomforts some paleoanthropologists trained in the natural and life sciences. They often dismiss it, explaining it away with such self-justifying conjectures as that, maybe, separate paleospecies of Homo differentially possessed different cognitive abilities, which, supposedly, could account for the presence or absence in the Pleistocene archeological record of traces of this or that behavioral outcome or skill. We argue that an alternative perspective - that inherits from the FEP and an individual's 'active inference' about its surroundings and of its own responses - affords a prosaic, deflationary, and parsimonious way to account for appearances, disappearances, and reappearances of particular behavioral outcomes and skills of early humankind.</AbstractText
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Adrenocortical and autonomic cross-system regulation in youth: A meta-analysis. Childhood and adolescence are salient periods for the development of adrenocortical and autonomic arms of the stress response system (SRS), setting the stage for subsequent health and adaptive functioning. Although adrenocortical and autonomic systems theoretically function in highly coordinated ways, the strength of the relationship between these systems remains unclear. We leveraged a multivariate mixed effects meta-analytic approach to assess associations between adrenocortical, sympathetic, and parasympathetic functioning at rest and reactivity during stress-inducing tasks across 52 studies (N = 7,671; 5-20 years old). Results suggested a modest positive relation between adrenocortical and sympathetic systems as well as between adrenocortical and parasympathetic systems. Moderation analyses indicated the strength of associations varied as a function of several methodological and sociodemographic characteristics. Environmental effects on cross-system regulation were less clear, perhaps due to underrepresentation of adverse-exposed youth in the included studies. Collectively, our findings call for greater methodological attention to the dynamical, non-linear nature of cross-system functioning, as well as the role of experience in their organization across development.</AbstractText
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Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury. Traumatic brain injury (TBI) is a devastating neurological disorder caused by a physical impact to the brain that promotes diffuse damage and chronic neurodegeneration. Key mechanisms believed to support secondary brain injury include mitochondrial dysfunction and chronic neuroinflammation. Microglia and brain-infiltrating macrophages are responsible for neuroinflammatory cytokine and reactive oxygen species (ROS) production after TBI. Their production is associated with loss of homeostatic microglial functions such as immunosurveillance, phagocytosis, and immune resolution. Beyond providing energy support, mitochondrial metabolic pathways reprogram the pro- and anti-inflammatory machinery in immune cells, providing a critical immunometabolic axis capable of regulating immunologic response to noxious stimuli. In the brain, the capacity to adapt to different environmental stimuli derives, in part, from microglia's ability to recognize and respond to changes in extracellular and intracellular metabolite levels. This capacity is met by an equally plastic metabolism, capable of altering immune function. Microglial pro-inflammatory activation is associated with decreased mitochondrial respiration, whereas anti-inflammatory microglial polarization is supported by increased oxidative metabolism. These metabolic adaptations contribute to neuroimmune responses, placing mitochondria as a central regulator of post-traumatic neuroinflammation. Although it is established that profound neurometabolic changes occur following TBI, key questions related to metabolic shifts in microglia remain unresolved. These include (a) the nature of microglial mitochondrial dysfunction after TBI, (b) the hierarchical positions of different metabolic pathways such as glycolysis, pentose phosphate pathway, glutaminolysis, and lipid oxidation during secondary injury and recovery, and (c) how immunometabolism alters microglial phenotypes, culminating in chronic non-resolving neuroinflammation. In this basic neurochemistry review article, we describe the contributions of immunometabolism to TBI, detail primary evidence of mitochondrial dysfunction and metabolic impairments in microglia and macrophages, discuss how major metabolic pathways contribute to post-traumatic neuroinflammation, and set out future directions toward advancing immunometabolic phenotyping in TBI.</AbstractText
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'Snakes and ladders' in paleoanthropology: From cognitive surprise to skillfulness a million years ago. A paradigmatic account may suffice to explain behavioral evolution in early Homo. We propose a parsimonious account that (1) could explain a particular, frequently-encountered, archeological outcome of behavior in early Homo - namely, the fashioning of a Paleolithic stone 'handaxe' - from a biological theoretic perspective informed by the free energy principle (FEP); and that (2) regards instances of the outcome as postdictive or retrodictive, circumstantial corroboration. Our proposal considers humankind evolving as a self-organizing biological ecosystem at a geological time-scale. We offer a narrative treatment of this self-organization in terms of the FEP. Specifically, we indicate how 'cognitive surprises' could underwrite an evolving propensity in early Homo to express sporadic unorthodox or anomalous behavior. This co-evolutionary propensity has left us a legacy of Paleolithic artifacts that is reminiscent of a 'snakes and ladders' board game of appearances, disappearances, and reappearances of particular archeological traces of Paleolithic behavior. When detected in the Early and Middle Pleistocene record, anthropologists and archeologists often imagine evidence of unusual or novel behavior in terms of early humankind ascending the rungs of a figurative phylogenetic 'ladder' - as if these corresponded to progressive evolution of cognitive abilities that enabled incremental achievements of increasingly innovative technical prowess, culminating in the cognitive ascendancy of Homo sapiens. The conjecture overlooks a plausible likelihood that behavior by an individual who was atypical among her conspecifics could have been disregarded in a community of Hominina (for definition see Appendix 1) that failed to recognize, imagine, or articulate potential advantages of adopting hitherto unorthodox behavior. Such failure, as well as diverse fortuitous demographic accidents, would cause exceptional personal behavior to be ignored and hence unremembered. It could disappear by a pitfall, down a 'snake', as it were, in the figurative evolutionary board game; thereby causing a discontinuity in the evolution of human behavior that presents like an evolutionary puzzle. The puzzle discomforts some paleoanthropologists trained in the natural and life sciences. They often dismiss it, explaining it away with such self-justifying conjectures as that, maybe, separate paleospecies of Homo differentially possessed different cognitive abilities, which, supposedly, could account for the presence or absence in the Pleistocene archeological record of traces of this or that behavioral outcome or skill. We argue that an alternative perspective - that inherits from the FEP and an individual's 'active inference' about its surroundings and of its own responses - affords a prosaic, deflationary, and parsimonious way to account for appearances, disappearances, and reappearances of particular behavioral outcomes and skills of early humankind.</AbstractText
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35445831
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30319552
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35940423
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Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation.
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The Anti-tumoral Properties of Orexin/Hypocretin Hypothalamic Neuropeptides: An Unexpected Therapeutic Role.
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Structural and functional network mechanisms of rescuing cognitive control in aging.
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Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease is considered to be the result of the selective disruption of neuronal cells in the lateral hypothalamus expressing the neuropeptide hypocretin, which controls the sleep-wake cycle. Diagnosis and management of narcolepsy represent still a substantial medical challenge due to the large heterogeneity in the clinical manifestation of the disease as well as to the lack of understanding of the underlying pathophysiological mechanisms. However, significant advances have been made in the last years, thus opening new perspective in the field. This review describes the current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management. Recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are also highlighted.</AbstractText
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Orexins (OxA and OxB) also termed hypocretins are hypothalamic neuropeptides involved in central nervous system (CNS) to control the sleep/wake process which is mediated by two G protein-coupled receptor subtypes, OX1R, and OX2R. Beside these central effects, orexins also play a role in various peripheral organs such as the intestine, pancreas, adrenal glands, kidney, adipose tissue and reproductive tract.In the past few years, an unexpected anti-tumoral role of orexins mediated by a new signaling pathway involving the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIM) in both orexin receptors subtypes, the recruitment of the phosphotyrosine phosphatase SHP2 and the induction of mitochondrial apoptosis has been elucidated. In the present review, we will discuss the anti-tumoral effect of orexin/OXR system in colon, pancreas, prostate and other cancers, and its interest as a possible therapeutic target.</AbstractText
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Age-related declines in cognitive control, an ability critical in most daily tasks, threaten individual independence. We previously showed in both older and younger adults that transcranial alternating current stimulation (tACS) can improve cognitive control, with effects observed across neural regions distant from the stimulated site and frequencies outside the stimulated range. Here, we assess network-level changes in neural activity that extend beyond the stimulated site and evaluate anatomical pathways that subserve these effects. We investigated the potential to rescue cognitive control in aging using prefrontal (F3-F4) theta (6 Hz) or control (1 Hz) tACS while older adults engaged in a cognitive control video game intervention on three consecutive days. Functional connectivity was assessed with EEG by measuring daily changes in frontal-posterior phase-locking values (PLV) from the tACS-free baseline. Structural connectivity was measured using MRI diffusion tractography data collected at baseline. Theta tACS improved multitasking performance, and individual gains reflected a dissociation in daily PLV changes, where theta tACS strengthened PLV and control tACS reduced PLV. Strengthened alpha-beta PLV in the theta tACS group correlated positively with inferior longitudinal fasciculus and corpus callosum body integrity, and further explained multitasking gains. These results demonstrate that theta tACS can improve cognitive control in aging by strengthening functional connectivity, particularly in higher frequency bands. However, the extent of functional connectivity gains is limited by the integrity of structural white matter tracts. Given that advanced age is associated with decreased white matter integrity, results suggest that the deployment of tACS as a therapeutic is best prior to advanced age.</AbstractText
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Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation. Narcolepsy is a rare chronic neurological disorder characterized by an irresistible excessive daytime sleepiness and cataplexy. The disease is considered to be the result of the selective disruption of neuronal cells in the lateral hypothalamus expressing the neuropeptide hypocretin, which controls the sleep-wake cycle. Diagnosis and management of narcolepsy represent still a substantial medical challenge due to the large heterogeneity in the clinical manifestation of the disease as well as to the lack of understanding of the underlying pathophysiological mechanisms. However, significant advances have been made in the last years, thus opening new perspective in the field. This review describes the current knowledge of clinical presentation and pathology of narcolepsy as well as the existing diagnostic criteria and therapeutic intervention for the disease management. Recent evidence on the potential immune-mediated mechanisms that may underpin the disease establishment and progression are also highlighted.</AbstractText
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The Anti-tumoral Properties of Orexin/Hypocretin Hypothalamic Neuropeptides: An Unexpected Therapeutic Role. Orexins (OxA and OxB) also termed hypocretins are hypothalamic neuropeptides involved in central nervous system (CNS) to control the sleep/wake process which is mediated by two G protein-coupled receptor subtypes, OX1R, and OX2R. Beside these central effects, orexins also play a role in various peripheral organs such as the intestine, pancreas, adrenal glands, kidney, adipose tissue and reproductive tract.In the past few years, an unexpected anti-tumoral role of orexins mediated by a new signaling pathway involving the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIM) in both orexin receptors subtypes, the recruitment of the phosphotyrosine phosphatase SHP2 and the induction of mitochondrial apoptosis has been elucidated. In the present review, we will discuss the anti-tumoral effect of orexin/OXR system in colon, pancreas, prostate and other cancers, and its interest as a possible therapeutic target.</AbstractText
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Structural and functional network mechanisms of rescuing cognitive control in aging. Age-related declines in cognitive control, an ability critical in most daily tasks, threaten individual independence. We previously showed in both older and younger adults that transcranial alternating current stimulation (tACS) can improve cognitive control, with effects observed across neural regions distant from the stimulated site and frequencies outside the stimulated range. Here, we assess network-level changes in neural activity that extend beyond the stimulated site and evaluate anatomical pathways that subserve these effects. We investigated the potential to rescue cognitive control in aging using prefrontal (F3-F4) theta (6 Hz) or control (1 Hz) tACS while older adults engaged in a cognitive control video game intervention on three consecutive days. Functional connectivity was assessed with EEG by measuring daily changes in frontal-posterior phase-locking values (PLV) from the tACS-free baseline. Structural connectivity was measured using MRI diffusion tractography data collected at baseline. Theta tACS improved multitasking performance, and individual gains reflected a dissociation in daily PLV changes, where theta tACS strengthened PLV and control tACS reduced PLV. Strengthened alpha-beta PLV in the theta tACS group correlated positively with inferior longitudinal fasciculus and corpus callosum body integrity, and further explained multitasking gains. These results demonstrate that theta tACS can improve cognitive control in aging by strengthening functional connectivity, particularly in higher frequency bands. However, the extent of functional connectivity gains is limited by the integrity of structural white matter tracts. Given that advanced age is associated with decreased white matter integrity, results suggest that the deployment of tACS as a therapeutic is best prior to advanced age.</AbstractText
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37457651
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20054397
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37964406
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HIV-1 envelope protein gp120 modulation of glutamate effects on cortical neuronal synapses: implications for HIV-1-associated neuropathogenesis.
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High-performance genetically targetable optical neural silencing by light-driven proton pumps.
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An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery.
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Despite the introduction of combined antiretroviral therapy (cART) HIV-1 virus persists in the brain in a latent or restricted manner and viral proteins, such as gp120, continue to play a significant disease-inciting role. Gp120 is known to interact with <i
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The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.</AbstractText
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Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.</AbstractText
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HIV-1 envelope protein gp120 modulation of glutamate effects on cortical neuronal synapses: implications for HIV-1-associated neuropathogenesis. Despite the introduction of combined antiretroviral therapy (cART) HIV-1 virus persists in the brain in a latent or restricted manner and viral proteins, such as gp120, continue to play a significant disease-inciting role. Gp120 is known to interact with <i
|
High-performance genetically targetable optical neural silencing by light-driven proton pumps. The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.</AbstractText
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An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery. Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.</AbstractText
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34287663
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29668721
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35047805
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Assessment of myelination in infants and young children by T1 relaxation time measurements using the magnetization-prepared 2 rapid acquisition gradient echoes sequence.
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Ultra-high field MRI of human hippocampi: Morphological and multiparametric differentiation of hippocampal sclerosis subtypes.
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Assessing the development status of intraoperative fluorescence imaging for perfusion assessments, using the IDEAL framework.
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Axonal myelination is an important maturation process in the developing brain. Increasing myelin content correlates with the longitudinal relaxation rate (R1=1/T1) in magnetic resonance imaging (MRI).</AbstractText By using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) on a 3-T MRI system, we provide R1 values and myelination rates for infants and young children.</AbstractText Average R1 values in white and grey matter regions in 94 children without pathological MRI findings (age range: 3 months to 6 years) were measured and fitted by a saturating-exponential growth model. For comparison, R1 values of 36 children with different brain pathologies are presented. The findings were related to a qualitative evaluation using T2, magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and MP2RAGE.</AbstractText R1 changes rapidly in the first 16 months of life, then much slower thereafter. R1 is highest in pre-myelinated structures in the youngest subjects, such as the posterior limb of the internal capsule (0.74-0.76±0.04 s<sup MP2RAGE permits a quantitative R1 mapping method with an examination time of approximately 6 min. The age-dependent R1 values for children without MRI-identified brain pathologies are well described by a saturating-exponential function with time constants depending on the investigated brain region. This model can serve as a reference for this age group and to search for indications of subtle pathologies. Moreover, the MP2RAGE sequence can also be used for the qualitative assessment of myelinated structures.</AbstractText
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The aim of the present study is to differentiate subtypes of hippocampal sclerosis (HS) using ex vivo ultra-high field magnetic resonance imaging (MRI). Included were 14 surgically resected hippocampi of patients with medically intractable temporal lobe epilepsy. The resected hippocampi were histologically categorized into subtypes of hippocampal sclerosis (HS type 1 (n = 10), HS type 2 (n = 2) and no-HS (n = 2)) and subsequently scanned on a preclinical 7T MRI acquiring T2-weighted morphology, relaxometry and diffusion tensor imaging. On the morphological images, the pyramidal cell layer (PCL) of the hippocampus was segmented and the following parameters were derived: T2 signal intensity, T1-, T2- and T2*-relaxation times, apparent diffusion coefficient (ADC), fractional anisotropy (FA) and mean diffusivity (MD). Furthermore, the area of the PCL was determined, as well as the parameter product which refers to the widths of the PCL parallel and perpendicular to the stratum moleculare. Spearman correlation coefficient was used to demonstrate relationships between MR-parameters and type of sclerosis. In comparison to no-HS specimens, the PCL was significantly narrower in HS type 1 and HS type 2 hippocampi. This narrowing affected the entire cornu ammonis sector (CA) 1 in HS type 1, while it was limited to the upper half of CA1 in direction to CA2 in HS type 2. The parameter product median increased from 0.43 to 1.67 and 2.91 mm2 for HS type 1, HS type 2 and no-HS, respectively. Correlation coefficients were significant for the PCL parameters product (0.73), area (0.71), T2*-time (-0.67), FA (0.65) and ADC (0.55). Our initial results suggest that HS type 1, HS type 2 and no-HS subtypes can be distinguished from each other using ex vivo UHF MRI based on T2-weighted morphologic images and the assessment of the parameter product. Upon clinical translation, UHF-MRI may provide a promising technique for the preoperative differentiation of HS subtypes in patients.</AbstractText
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Intraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: assessing tissue perfusion; identifying/localizing cancer; mapping lymphatic systems; and visualizing anatomy. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging for perfusion assessments using the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework, which was designed for describing the stages of innovation in surgery and other interventional procedures.</AbstractText Narrative literature review with analysis of IDEAL stage of each field of study.</AbstractText All publications on intraoperative fluorescence imaging for perfusion assessments reported in PubMed through 2019 were identified for six surgical procedures: coronary artery bypass grafting (CABG), upper gastrointestinal (GI) surgery, colorectal surgery, solid organ transplantation, reconstructive surgery, and cerebral aneurysm surgery.</AbstractText The IDEAL stage of research evidence was determined for each specialty field using a previously described approach.</AbstractText 196 articles (15 003 cases) were selected for analysis. Current status of research evidence was determined to be IDEAL Stage 2a for upper GI and transplantation surgery, IDEAL 2b for CABG, colorectal and cerebral aneurysm surgery, and IDEAL Stage 3 for reconstructive surgery. Using the technique resulted in a high (up to 50%) rate of revisions among surgical procedures, but its efficacy improving postoperative outcomes has not yet been demonstrated by randomized controlled trials in any discipline. Only one possible adverse reaction to intravenous indocyanine green was reported.</AbstractText Using fluorescence imaging intraoperatively to assess perfusion is feasible and appears useful for surgical decision making across a range of disciplines. Identifying the IDEAL stage of current research knowledge aids in planning further studies to establish the potential for patient benefit.</AbstractText
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Assessment of myelination in infants and young children by T1 relaxation time measurements using the magnetization-prepared 2 rapid acquisition gradient echoes sequence. Axonal myelination is an important maturation process in the developing brain. Increasing myelin content correlates with the longitudinal relaxation rate (R1=1/T1) in magnetic resonance imaging (MRI).</AbstractText By using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) on a 3-T MRI system, we provide R1 values and myelination rates for infants and young children.</AbstractText Average R1 values in white and grey matter regions in 94 children without pathological MRI findings (age range: 3 months to 6 years) were measured and fitted by a saturating-exponential growth model. For comparison, R1 values of 36 children with different brain pathologies are presented. The findings were related to a qualitative evaluation using T2, magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and MP2RAGE.</AbstractText R1 changes rapidly in the first 16 months of life, then much slower thereafter. R1 is highest in pre-myelinated structures in the youngest subjects, such as the posterior limb of the internal capsule (0.74-0.76±0.04 s<sup MP2RAGE permits a quantitative R1 mapping method with an examination time of approximately 6 min. The age-dependent R1 values for children without MRI-identified brain pathologies are well described by a saturating-exponential function with time constants depending on the investigated brain region. This model can serve as a reference for this age group and to search for indications of subtle pathologies. Moreover, the MP2RAGE sequence can also be used for the qualitative assessment of myelinated structures.</AbstractText
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Ultra-high field MRI of human hippocampi: Morphological and multiparametric differentiation of hippocampal sclerosis subtypes. The aim of the present study is to differentiate subtypes of hippocampal sclerosis (HS) using ex vivo ultra-high field magnetic resonance imaging (MRI). Included were 14 surgically resected hippocampi of patients with medically intractable temporal lobe epilepsy. The resected hippocampi were histologically categorized into subtypes of hippocampal sclerosis (HS type 1 (n = 10), HS type 2 (n = 2) and no-HS (n = 2)) and subsequently scanned on a preclinical 7T MRI acquiring T2-weighted morphology, relaxometry and diffusion tensor imaging. On the morphological images, the pyramidal cell layer (PCL) of the hippocampus was segmented and the following parameters were derived: T2 signal intensity, T1-, T2- and T2*-relaxation times, apparent diffusion coefficient (ADC), fractional anisotropy (FA) and mean diffusivity (MD). Furthermore, the area of the PCL was determined, as well as the parameter product which refers to the widths of the PCL parallel and perpendicular to the stratum moleculare. Spearman correlation coefficient was used to demonstrate relationships between MR-parameters and type of sclerosis. In comparison to no-HS specimens, the PCL was significantly narrower in HS type 1 and HS type 2 hippocampi. This narrowing affected the entire cornu ammonis sector (CA) 1 in HS type 1, while it was limited to the upper half of CA1 in direction to CA2 in HS type 2. The parameter product median increased from 0.43 to 1.67 and 2.91 mm2 for HS type 1, HS type 2 and no-HS, respectively. Correlation coefficients were significant for the PCL parameters product (0.73), area (0.71), T2*-time (-0.67), FA (0.65) and ADC (0.55). Our initial results suggest that HS type 1, HS type 2 and no-HS subtypes can be distinguished from each other using ex vivo UHF MRI based on T2-weighted morphologic images and the assessment of the parameter product. Upon clinical translation, UHF-MRI may provide a promising technique for the preoperative differentiation of HS subtypes in patients.</AbstractText
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Assessing the development status of intraoperative fluorescence imaging for perfusion assessments, using the IDEAL framework. Intraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: assessing tissue perfusion; identifying/localizing cancer; mapping lymphatic systems; and visualizing anatomy. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging for perfusion assessments using the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework, which was designed for describing the stages of innovation in surgery and other interventional procedures.</AbstractText Narrative literature review with analysis of IDEAL stage of each field of study.</AbstractText All publications on intraoperative fluorescence imaging for perfusion assessments reported in PubMed through 2019 were identified for six surgical procedures: coronary artery bypass grafting (CABG), upper gastrointestinal (GI) surgery, colorectal surgery, solid organ transplantation, reconstructive surgery, and cerebral aneurysm surgery.</AbstractText The IDEAL stage of research evidence was determined for each specialty field using a previously described approach.</AbstractText 196 articles (15 003 cases) were selected for analysis. Current status of research evidence was determined to be IDEAL Stage 2a for upper GI and transplantation surgery, IDEAL 2b for CABG, colorectal and cerebral aneurysm surgery, and IDEAL Stage 3 for reconstructive surgery. Using the technique resulted in a high (up to 50%) rate of revisions among surgical procedures, but its efficacy improving postoperative outcomes has not yet been demonstrated by randomized controlled trials in any discipline. Only one possible adverse reaction to intravenous indocyanine green was reported.</AbstractText Using fluorescence imaging intraoperatively to assess perfusion is feasible and appears useful for surgical decision making across a range of disciplines. Identifying the IDEAL stage of current research knowledge aids in planning further studies to establish the potential for patient benefit.</AbstractText
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34535274
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29293892
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33989345
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Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study.
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Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy.
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Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis.
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Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients.</AbstractText We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery.</AbstractText There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml<sup Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.</AbstractText
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Alzheimer's disease and progressive supranuclear palsy (PSP) represent neurodegenerative tauopathies with predominantly cortical versus subcortical disease burden. In Alzheimer's disease, neuropathology and atrophy preferentially affect 'hub' brain regions that are densely connected. It was unclear whether hubs are differentially affected by neurodegeneration because they are more likely to receive pathological proteins that propagate trans-neuronally, in a prion-like manner, or whether they are selectively vulnerable due to a lack of local trophic factors, higher metabolic demands, or differential gene expression. We assessed the relationship between tau burden and brain functional connectivity, by combining in vivo PET imaging using the ligand AV-1451, and graph theoretic measures of resting state functional MRI in 17 patients with Alzheimer's disease, 17 patients with PSP, and 12 controls. Strongly connected nodes displayed more tau pathology in Alzheimer's disease, independently of intrinsic connectivity network, validating the predictions of theories of trans-neuronal spread but not supporting a role for metabolic demands or deficient trophic support in tau accumulation. This was not a compensatory phenomenon, as the functional consequence of increasing tau burden in Alzheimer's disease was a progressive weakening of the connectivity of these same nodes, reducing weighted degree and local efficiency and resulting in weaker 'small-world' properties. Conversely, in PSP, unlike in Alzheimer's disease, those nodes that accrued pathological tau were those that displayed graph metric properties associated with increased metabolic demand and a lack of trophic support rather than strong functional connectivity. Together, these findings go some way towards explaining why Alzheimer's disease affects large scale connectivity networks throughout cortex while neuropathology in PSP is concentrated in a small number of subcortical structures. Further, we demonstrate that in PSP increasing tau burden in midbrain and deep nuclei was associated with strengthened cortico-cortical functional connectivity. Disrupted cortico-subcortical and cortico-brainstem interactions meant that information transfer took less direct paths, passing through a larger number of cortical nodes, reducing closeness centrality and eigenvector centrality in PSP, while increasing weighted degree, clustering, betweenness centrality and local efficiency. Our results have wide-ranging implications, from the validation of models of tau trafficking in humans to understanding the relationship between regional tau burden and brain functional reorganization.</AbstractText
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Mycobacterium tuberculosis (Mtb) has complex and dynamic interactions with the human host, and subpopulations of Mtb that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn2+) availability as a likely driver of bacterial phenotypic heterogeneity in vivo. Zn2+ sequestration is part of "nutritional immunity", where the immune system limits micronutrients to control pathogen growth, but this defense mechanism seems to be ineffective in controlling Mtb infection. Nonetheless, Zn2+-limitation is an environmental cue sensed by Mtb, as calprotectin triggers the zinc uptake regulator (Zur) regulon response in vitro and co-localizes with Zn2+-limited Mtb in vivo. Prolonged Zn2+ limitation leads to numerous physiological changes in vitro, including differential expression of certain antigens, alterations in lipid metabolism and distinct cell surface morphology. Furthermore, Mtb enduring limited Zn2+ employ defensive measures to fight oxidative stress, by increasing expression of proteins involved in DNA repair and antioxidant activity, including well described virulence factors KatG and AhpC, along with altered utilization of redox cofactors. Here, we propose a model in which prolonged Zn2+ limitation defines a population of Mtb with anticipatory adaptations against impending immune attack, based on the evidence that Zn2+-limited Mtb are more resistant to oxidative stress and exhibit increased survival and induce more severe pulmonary granulomas in mice. Considering that extracellular Mtb may transit through the Zn2+-limited caseum before infecting naïve immune cells or upon host-to-host transmission, the resulting phenotypic heterogeneity driven by varied Zn2+ availability likely plays a key role during early interactions with host cells.</AbstractText
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Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study. Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients.</AbstractText We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery.</AbstractText There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml<sup Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.</AbstractText
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Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy. Alzheimer's disease and progressive supranuclear palsy (PSP) represent neurodegenerative tauopathies with predominantly cortical versus subcortical disease burden. In Alzheimer's disease, neuropathology and atrophy preferentially affect 'hub' brain regions that are densely connected. It was unclear whether hubs are differentially affected by neurodegeneration because they are more likely to receive pathological proteins that propagate trans-neuronally, in a prion-like manner, or whether they are selectively vulnerable due to a lack of local trophic factors, higher metabolic demands, or differential gene expression. We assessed the relationship between tau burden and brain functional connectivity, by combining in vivo PET imaging using the ligand AV-1451, and graph theoretic measures of resting state functional MRI in 17 patients with Alzheimer's disease, 17 patients with PSP, and 12 controls. Strongly connected nodes displayed more tau pathology in Alzheimer's disease, independently of intrinsic connectivity network, validating the predictions of theories of trans-neuronal spread but not supporting a role for metabolic demands or deficient trophic support in tau accumulation. This was not a compensatory phenomenon, as the functional consequence of increasing tau burden in Alzheimer's disease was a progressive weakening of the connectivity of these same nodes, reducing weighted degree and local efficiency and resulting in weaker 'small-world' properties. Conversely, in PSP, unlike in Alzheimer's disease, those nodes that accrued pathological tau were those that displayed graph metric properties associated with increased metabolic demand and a lack of trophic support rather than strong functional connectivity. Together, these findings go some way towards explaining why Alzheimer's disease affects large scale connectivity networks throughout cortex while neuropathology in PSP is concentrated in a small number of subcortical structures. Further, we demonstrate that in PSP increasing tau burden in midbrain and deep nuclei was associated with strengthened cortico-cortical functional connectivity. Disrupted cortico-subcortical and cortico-brainstem interactions meant that information transfer took less direct paths, passing through a larger number of cortical nodes, reducing closeness centrality and eigenvector centrality in PSP, while increasing weighted degree, clustering, betweenness centrality and local efficiency. Our results have wide-ranging implications, from the validation of models of tau trafficking in humans to understanding the relationship between regional tau burden and brain functional reorganization.</AbstractText
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Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis. Mycobacterium tuberculosis (Mtb) has complex and dynamic interactions with the human host, and subpopulations of Mtb that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn2+) availability as a likely driver of bacterial phenotypic heterogeneity in vivo. Zn2+ sequestration is part of "nutritional immunity", where the immune system limits micronutrients to control pathogen growth, but this defense mechanism seems to be ineffective in controlling Mtb infection. Nonetheless, Zn2+-limitation is an environmental cue sensed by Mtb, as calprotectin triggers the zinc uptake regulator (Zur) regulon response in vitro and co-localizes with Zn2+-limited Mtb in vivo. Prolonged Zn2+ limitation leads to numerous physiological changes in vitro, including differential expression of certain antigens, alterations in lipid metabolism and distinct cell surface morphology. Furthermore, Mtb enduring limited Zn2+ employ defensive measures to fight oxidative stress, by increasing expression of proteins involved in DNA repair and antioxidant activity, including well described virulence factors KatG and AhpC, along with altered utilization of redox cofactors. Here, we propose a model in which prolonged Zn2+ limitation defines a population of Mtb with anticipatory adaptations against impending immune attack, based on the evidence that Zn2+-limited Mtb are more resistant to oxidative stress and exhibit increased survival and induce more severe pulmonary granulomas in mice. Considering that extracellular Mtb may transit through the Zn2+-limited caseum before infecting naïve immune cells or upon host-to-host transmission, the resulting phenotypic heterogeneity driven by varied Zn2+ availability likely plays a key role during early interactions with host cells.</AbstractText
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40774517
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31172280
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40690758
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Baseline glutamate-glutamine complex levels modulate antidepressant response to rTMS in major depressive disorder: Insights from magnetic resonance spectroscopy.
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Intra- and inter-resting-state networks abnormalities in overactive bladder syndrome patients: an independent component analysis of resting-state fMRI.
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Facilitators and Barriers to Implementing AI in Routine Medical Imaging: Systematic Review and Qualitative Analysis.
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Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but its neurometabolic effects remain unknown. This study examined whether rTMS outcomes depend on baseline medial prefrontal cortex (mPFC) glutamate-glutamine complex (Glx) levels and aimed to identify clinically translatable imaging biomarkers.</AbstractText Seventy-six MDD patients and 44 healthy controls (HC) were enrolled. 39 patients underwent 20-session rTMS treatments and were divided into high Glx (hGlx, N = 20) and low Glx (lGlx, N = 19) subgroups based on the median baseline Glx levels of all patients in the MDD group (N = 76). Metabolite concentrations (GABA, Glx, Glx/GABA) changes within the mPFC were quantified via magnetic resonance spectroscopy. Baseline subgroup differences and their associations with treatment outcomes investigated. Diffusion MRI metrics were extracted from the corpus callosum (CC) for correlation analysis, including fractional anisotropy, radial diffusivity (RD), mean diffusivity (MD), and axial diffusivity (AD).</AbstractText After rTMS treatment, both Glx subgroups regained significant Glx-GABA coupling, mirroring the HC pattern. In the hGlx subgroup, baseline mPFC Glx, GABA, and Glx/GABA predicted improvements in Montgomery-Åsberg Depression Rating Scale and Hamilton Depression Rating Scale factor scores. Notably, hGlx patients exhibited higher CC RD and MD values, with mPFC Glx levels correlating specifically with the splenium of CC MD and AD.</AbstractText Subgroup analyses demonstrated baseline mPFC excitatory neurotransmission modulates rTMS efficacy. Higher Glx concentrations may synergize with adjacent white matter integrity to restore excitatory-inhibitory balance, supporting higher mPFC Glx as a predictive biomarker for rTMS outcomes.</AbstractText
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This study aims to determine whether intra-network and inter-network brain connectivities are altered using an independent component analysis (ICA).</AbstractText Resting-state functional MRI (rs-fMRI) data were acquired from 26 patients with OAB and 28 healthy controls (HC). Eleven resting-state networks (RSNs) were identified via ICA. General linear model (GLM) was used to compare intra-network FC and inter-network FC of RSNs between the two groups. Pearson correlation analyses were performed to investigate the relationship between the identified RSNs and clinical variables.</AbstractText Compared with HC, the OAB group showed abnormal FC within the sensorimotor-related network (SMN), the dorsal attention network (DAN), the dorsal visual network (dVN), and the left frontoparietal network (LFPN). With respect to inter-network interactions, decreased FC was detected between the SMN and the anterior default mode network (aDMN).</AbstractText This study demonstrated that abnormal FC between RSNs may reflect the altered resting state of the brain-bladder network. The findings of this study provide complementary evidence that can help further understand the neural substrates of the overactive bladder.</AbstractText
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Artificial intelligence (AI) is rapidly advancing in health care, particularly in medical imaging, offering potential for improved efficiency and reduced workload. However, there is little systematic evidence on process factors for successful AI technology implementation into clinical workflows.</AbstractText This study aimed to systematically assess and synthesize the facilitators and barriers to AI implementation reported in studies evaluating AI solutions in routine medical imaging.</AbstractText We conducted a systematic review of 6 medical databases. Using a qualitative content analysis, we extracted the reported facilitators and barriers, outcomes, and moderators in the implementation process of AI. Two reviewers analyzed and categorized the data separately. We then used epistemic network analysis to explore their relationships across different stages of AI implementation.</AbstractText Our search yielded 13,756 records. After screening, we included 38 original studies in our final review. We identified 12 key dimensions and 37 subthemes that influence the implementation of AI in health care workflows. Key dimensions included evaluation of AI use and fit into workflow, with frequency depending considerably on the stage of the implementation process. In total, 20 themes were mentioned as both facilitators and barriers to AI implementation. Studies often focused predominantly on performance metrics over the experiences or outcomes of clinicians.</AbstractText This systematic review provides a thorough synthesis of facilitators and barriers to successful AI implementation in medical imaging. Our study highlights the usefulness of AI technologies in clinical care and the fit of their integration into routine clinical workflows. Most studies did not directly report facilitators and barriers to AI implementation, underscoring the importance of comprehensive reporting to foster knowledge sharing. Our findings reveal a predominant focus on technological aspects of AI adoption in clinical work, highlighting the need for holistic, human-centric consideration to fully leverage the potential of AI in health care.</AbstractText PROSPERO CRD42022303439; https://www.crd.york.ac.uk/PROSPERO/view/CRD42022303439.</AbstractText RR2-10.2196/40485.</AbstractText
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Baseline glutamate-glutamine complex levels modulate antidepressant response to rTMS in major depressive disorder: Insights from magnetic resonance spectroscopy. Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but its neurometabolic effects remain unknown. This study examined whether rTMS outcomes depend on baseline medial prefrontal cortex (mPFC) glutamate-glutamine complex (Glx) levels and aimed to identify clinically translatable imaging biomarkers.</AbstractText Seventy-six MDD patients and 44 healthy controls (HC) were enrolled. 39 patients underwent 20-session rTMS treatments and were divided into high Glx (hGlx, N = 20) and low Glx (lGlx, N = 19) subgroups based on the median baseline Glx levels of all patients in the MDD group (N = 76). Metabolite concentrations (GABA, Glx, Glx/GABA) changes within the mPFC were quantified via magnetic resonance spectroscopy. Baseline subgroup differences and their associations with treatment outcomes investigated. Diffusion MRI metrics were extracted from the corpus callosum (CC) for correlation analysis, including fractional anisotropy, radial diffusivity (RD), mean diffusivity (MD), and axial diffusivity (AD).</AbstractText After rTMS treatment, both Glx subgroups regained significant Glx-GABA coupling, mirroring the HC pattern. In the hGlx subgroup, baseline mPFC Glx, GABA, and Glx/GABA predicted improvements in Montgomery-Åsberg Depression Rating Scale and Hamilton Depression Rating Scale factor scores. Notably, hGlx patients exhibited higher CC RD and MD values, with mPFC Glx levels correlating specifically with the splenium of CC MD and AD.</AbstractText Subgroup analyses demonstrated baseline mPFC excitatory neurotransmission modulates rTMS efficacy. Higher Glx concentrations may synergize with adjacent white matter integrity to restore excitatory-inhibitory balance, supporting higher mPFC Glx as a predictive biomarker for rTMS outcomes.</AbstractText
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Intra- and inter-resting-state networks abnormalities in overactive bladder syndrome patients: an independent component analysis of resting-state fMRI. This study aims to determine whether intra-network and inter-network brain connectivities are altered using an independent component analysis (ICA).</AbstractText Resting-state functional MRI (rs-fMRI) data were acquired from 26 patients with OAB and 28 healthy controls (HC). Eleven resting-state networks (RSNs) were identified via ICA. General linear model (GLM) was used to compare intra-network FC and inter-network FC of RSNs between the two groups. Pearson correlation analyses were performed to investigate the relationship between the identified RSNs and clinical variables.</AbstractText Compared with HC, the OAB group showed abnormal FC within the sensorimotor-related network (SMN), the dorsal attention network (DAN), the dorsal visual network (dVN), and the left frontoparietal network (LFPN). With respect to inter-network interactions, decreased FC was detected between the SMN and the anterior default mode network (aDMN).</AbstractText This study demonstrated that abnormal FC between RSNs may reflect the altered resting state of the brain-bladder network. The findings of this study provide complementary evidence that can help further understand the neural substrates of the overactive bladder.</AbstractText
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Facilitators and Barriers to Implementing AI in Routine Medical Imaging: Systematic Review and Qualitative Analysis. Artificial intelligence (AI) is rapidly advancing in health care, particularly in medical imaging, offering potential for improved efficiency and reduced workload. However, there is little systematic evidence on process factors for successful AI technology implementation into clinical workflows.</AbstractText This study aimed to systematically assess and synthesize the facilitators and barriers to AI implementation reported in studies evaluating AI solutions in routine medical imaging.</AbstractText We conducted a systematic review of 6 medical databases. Using a qualitative content analysis, we extracted the reported facilitators and barriers, outcomes, and moderators in the implementation process of AI. Two reviewers analyzed and categorized the data separately. We then used epistemic network analysis to explore their relationships across different stages of AI implementation.</AbstractText Our search yielded 13,756 records. After screening, we included 38 original studies in our final review. We identified 12 key dimensions and 37 subthemes that influence the implementation of AI in health care workflows. Key dimensions included evaluation of AI use and fit into workflow, with frequency depending considerably on the stage of the implementation process. In total, 20 themes were mentioned as both facilitators and barriers to AI implementation. Studies often focused predominantly on performance metrics over the experiences or outcomes of clinicians.</AbstractText This systematic review provides a thorough synthesis of facilitators and barriers to successful AI implementation in medical imaging. Our study highlights the usefulness of AI technologies in clinical care and the fit of their integration into routine clinical workflows. Most studies did not directly report facilitators and barriers to AI implementation, underscoring the importance of comprehensive reporting to foster knowledge sharing. Our findings reveal a predominant focus on technological aspects of AI adoption in clinical work, highlighting the need for holistic, human-centric consideration to fully leverage the potential of AI in health care.</AbstractText PROSPERO CRD42022303439; https://www.crd.york.ac.uk/PROSPERO/view/CRD42022303439.</AbstractText RR2-10.2196/40485.</AbstractText
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26162578
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21987483
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27114033
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Chemical shift MRI can aid in the diagnosis of indeterminate skeletal lesions of the spine.
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Quantitative characterization of bone marrow edema pattern in rheumatoid arthritis using 3 Tesla MRI.
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Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.
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To evaluate the role of chemical shift MRI in the characterisation of indeterminate skeletal lesions of the spine as benign or malignant.</AbstractText Fifty-five patients (mean age 54.7 years) with 57 indeterminate skeletal lesions of the spine were included in this retrospective study. In addition to conventional MRI at 3 T which included at least sagittal T1WI and T2WI/STIR sequences, patients underwent chemical shift MRI. A cut-off value with a signal drop-out of 20 % was used to differentiate benign lesions from malignant lesions (signal drop-out <20 % being malignant).</AbstractText There were 45 benign lesions and 12 malignant lesions. Chemical shift imaging correctly diagnosed 33 of 45 lesions as benign and 11 of 12 lesions as malignant. In contrast, there were 12 false positive cases and 1 false negative case based on chemical shift MRI. This yielded a sensitivity of 91.7 %, a specificity of 73.3 %, a negative predictive value of 97.1 %, a positive predictive value of 47.8 % and a diagnostic accuracy of 82.5 %.</AbstractText Chemical shift MRI can aid in the characterisation of indeterminate skeletal lesions of the spine in view of its high sensitivity in diagnosing malignant lesions. Chemical shift MRI can potentially avoid biopsy in a considerable percentage of patients with benign skeletal lesions of the spine.</AbstractText • Differentiating benign from malignant skeletal lesions of the spine can be challenging. • Utility of chemical shift MRI in characterising indeterminate spinal lesion is unreported. • This study demonstrates sensitivity 91.7 %, specificity 73.3 %, diagnostic accuracy 82.5 % for CSI. • CSI is useful in differentiating benign from malignant skeletal spine lesions. • Biopsy can potentially be avoided in some patients with benign skeletal lesions.</AbstractText
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To develop imaging techniques that provide quantitative characterization of bone marrow edema pattern (BME) in wrist joints of patients with rheumatoid arthritis (RA), including volume, signal intensity changes, and perfusion properties.</AbstractText Fourteen RA patients and three controls were scanned using 3 Tesla MR. BME was semi-automatically segmented in water images obtained from iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) sequences. BME perfusion parameters (enhancement and slope) were evaluated using three-dimensional (3D) dynamic enhanced MRI (DCE-MRI). Experimental reproducibility, inter- and intra-observer reproducibility of BME quantification were evaluated using root mean square coefficients of variation (RMS-CV) and intraclass correlation (ICC).</AbstractText The RMS-CV for BME volume quantification with repeated scans were 6.9%. The inter-observer ICC was 0.993 and RMS CV was 5.2%. The intra-observer ICC was 0.998 and RMS CV was 2.3%. Both maximum enhancement and slope during DCE-MRI were significantly higher in BME than in normal bone marrow (P < 0.001). No significant correlation was found between BME quantification and clinical evaluations.</AbstractText A highly reproducible semi-automatic method for quantifying BME lesion burden in RA was developed, which may enhance our capability of predicting disease progression and monitoring treatment response.</AbstractText
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Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency.</AbstractText
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Chemical shift MRI can aid in the diagnosis of indeterminate skeletal lesions of the spine. To evaluate the role of chemical shift MRI in the characterisation of indeterminate skeletal lesions of the spine as benign or malignant.</AbstractText Fifty-five patients (mean age 54.7 years) with 57 indeterminate skeletal lesions of the spine were included in this retrospective study. In addition to conventional MRI at 3 T which included at least sagittal T1WI and T2WI/STIR sequences, patients underwent chemical shift MRI. A cut-off value with a signal drop-out of 20 % was used to differentiate benign lesions from malignant lesions (signal drop-out <20 % being malignant).</AbstractText There were 45 benign lesions and 12 malignant lesions. Chemical shift imaging correctly diagnosed 33 of 45 lesions as benign and 11 of 12 lesions as malignant. In contrast, there were 12 false positive cases and 1 false negative case based on chemical shift MRI. This yielded a sensitivity of 91.7 %, a specificity of 73.3 %, a negative predictive value of 97.1 %, a positive predictive value of 47.8 % and a diagnostic accuracy of 82.5 %.</AbstractText Chemical shift MRI can aid in the characterisation of indeterminate skeletal lesions of the spine in view of its high sensitivity in diagnosing malignant lesions. Chemical shift MRI can potentially avoid biopsy in a considerable percentage of patients with benign skeletal lesions of the spine.</AbstractText • Differentiating benign from malignant skeletal lesions of the spine can be challenging. • Utility of chemical shift MRI in characterising indeterminate spinal lesion is unreported. • This study demonstrates sensitivity 91.7 %, specificity 73.3 %, diagnostic accuracy 82.5 % for CSI. • CSI is useful in differentiating benign from malignant skeletal spine lesions. • Biopsy can potentially be avoided in some patients with benign skeletal lesions.</AbstractText
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Quantitative characterization of bone marrow edema pattern in rheumatoid arthritis using 3 Tesla MRI. To develop imaging techniques that provide quantitative characterization of bone marrow edema pattern (BME) in wrist joints of patients with rheumatoid arthritis (RA), including volume, signal intensity changes, and perfusion properties.</AbstractText Fourteen RA patients and three controls were scanned using 3 Tesla MR. BME was semi-automatically segmented in water images obtained from iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) sequences. BME perfusion parameters (enhancement and slope) were evaluated using three-dimensional (3D) dynamic enhanced MRI (DCE-MRI). Experimental reproducibility, inter- and intra-observer reproducibility of BME quantification were evaluated using root mean square coefficients of variation (RMS-CV) and intraclass correlation (ICC).</AbstractText The RMS-CV for BME volume quantification with repeated scans were 6.9%. The inter-observer ICC was 0.993 and RMS CV was 5.2%. The intra-observer ICC was 0.998 and RMS CV was 2.3%. Both maximum enhancement and slope during DCE-MRI were significantly higher in BME than in normal bone marrow (P < 0.001). No significant correlation was found between BME quantification and clinical evaluations.</AbstractText A highly reproducible semi-automatic method for quantifying BME lesion burden in RA was developed, which may enhance our capability of predicting disease progression and monitoring treatment response.</AbstractText
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Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation. Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency.</AbstractText
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32705997
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26051422
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32823180
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An optically transparent multi-electrode array for combined electrophysiology and optophysiology at the mesoscopic scale.
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Cortical Feedback Decorrelates Olfactory Bulb Output in Awake Mice.
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Brain connectivity and socioeconomic status at birth and externalizing symptoms at age 2 years.
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A number of tissue penetrating opto-electrodes to simultaneously record and optogenetically influence brain activity have been developed. For experiments at the surface of the brain, such as electrocorticogram (ECoG) recordings and surface optogenetics, fewer devices have been described and no device has found widespread adoption for neuroscientific experiments. One issue slowing adoption is the complexity and fragility of existing devices, typically based on transparent electrode materials like graphene and indium-tin oxide (ITO). We focused here on improving existing processes based on metal traces and polyimide (PI), which produce more robust and cost-effective devices, to develop a multi-electrode array for optophysiology.</AbstractText The most widely used substrate material for surface electrodes, PI, has seen little use for optophysiologicalμECoG/ECoG arrays. This is due to its lack of transparency at optogenetically relevant short wavelengths. Here we use very thin layers of PI in combination with chrome-gold-platinum electrodes to achieve the necessary substrate transparency and high mechanical flexibility in a device that still rejects light artifacts well.</AbstractText The manufactured surface arrays have a thickness of only 6.5 µm, resulting in 80% transparency for blue light. We demonstrate immunity against opto-electric artifacts, long term stability and biocompatibility as well as suitability for optical voltage imaging. The biocompatible arrays are capable of recording stable ECoGs over months without any measurable degradation and can be used to map the tonotopic organization of the curved rodent auditory cortex.</AbstractText Our novel probes combine proven materials and processing steps to create optically near-transparent electrode arrays with superior longevity. In contrast to previous opto-electrodes, our probes are simple to manufacture, robust, offer long-term stability, and are a practical engineering solution for optophysiological experiments not requiring transparency of the electrode sites themselves.</AbstractText
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The olfactory bulb receives rich glutamatergic projections from the piriform cortex. However, the dynamics and importance of these feedback signals remain unknown. Here, we use multiphoton calcium imaging to monitor cortical feedback in the olfactory bulb of awake mice and further probe its impact on the bulb output. Responses of feedback boutons were sparse, odor specific, and often outlasted stimuli by several seconds. Odor presentation either enhanced or suppressed the activity of boutons. However, any given bouton responded with stereotypic polarity across multiple odors, preferring either enhancement or suppression. Feedback representations were locally diverse and differed in dynamics across bulb layers. Inactivation of piriform cortex increased odor responsiveness and pairwise similarity of mitral cells but had little impact on tufted cells. We propose that cortical feedback differentially impacts these two output channels of the bulb by specifically decorrelating mitral cell responses to enable odor separation.</AbstractText
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Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to whole-brain functional connectivity of five brain regions representing functional networks implicated in psychiatric illnesses and affected by socioeconomic disadvantage: striatum, medial prefrontal cortex (mPFC), ventrolateral prefrontal cortex (vlPFC), and dorsal anterior cingulate cortex. Lower SES was associated with differences in striatum and vlPFC connectivity. Striatum connectivity with frontopolar and medial PFC mediated the relationship between SES and behavioral inhibition at age 2 measured by the Infant-Toddler Social Emotional Assessment (n = 46). Striatum-frontopolar connectivity mediated the relationship between SES and externalizing symptoms. These results, convergent across three SES metrics, suggest that neurodevelopmental trajectories linking SES and mental illness may begin as early as birth.</AbstractText
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An optically transparent multi-electrode array for combined electrophysiology and optophysiology at the mesoscopic scale. A number of tissue penetrating opto-electrodes to simultaneously record and optogenetically influence brain activity have been developed. For experiments at the surface of the brain, such as electrocorticogram (ECoG) recordings and surface optogenetics, fewer devices have been described and no device has found widespread adoption for neuroscientific experiments. One issue slowing adoption is the complexity and fragility of existing devices, typically based on transparent electrode materials like graphene and indium-tin oxide (ITO). We focused here on improving existing processes based on metal traces and polyimide (PI), which produce more robust and cost-effective devices, to develop a multi-electrode array for optophysiology.</AbstractText The most widely used substrate material for surface electrodes, PI, has seen little use for optophysiologicalμECoG/ECoG arrays. This is due to its lack of transparency at optogenetically relevant short wavelengths. Here we use very thin layers of PI in combination with chrome-gold-platinum electrodes to achieve the necessary substrate transparency and high mechanical flexibility in a device that still rejects light artifacts well.</AbstractText The manufactured surface arrays have a thickness of only 6.5 µm, resulting in 80% transparency for blue light. We demonstrate immunity against opto-electric artifacts, long term stability and biocompatibility as well as suitability for optical voltage imaging. The biocompatible arrays are capable of recording stable ECoGs over months without any measurable degradation and can be used to map the tonotopic organization of the curved rodent auditory cortex.</AbstractText Our novel probes combine proven materials and processing steps to create optically near-transparent electrode arrays with superior longevity. In contrast to previous opto-electrodes, our probes are simple to manufacture, robust, offer long-term stability, and are a practical engineering solution for optophysiological experiments not requiring transparency of the electrode sites themselves.</AbstractText
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Cortical Feedback Decorrelates Olfactory Bulb Output in Awake Mice. The olfactory bulb receives rich glutamatergic projections from the piriform cortex. However, the dynamics and importance of these feedback signals remain unknown. Here, we use multiphoton calcium imaging to monitor cortical feedback in the olfactory bulb of awake mice and further probe its impact on the bulb output. Responses of feedback boutons were sparse, odor specific, and often outlasted stimuli by several seconds. Odor presentation either enhanced or suppressed the activity of boutons. However, any given bouton responded with stereotypic polarity across multiple odors, preferring either enhancement or suppression. Feedback representations were locally diverse and differed in dynamics across bulb layers. Inactivation of piriform cortex increased odor responsiveness and pairwise similarity of mitral cells but had little impact on tufted cells. We propose that cortical feedback differentially impacts these two output channels of the bulb by specifically decorrelating mitral cell responses to enable odor separation.</AbstractText
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Brain connectivity and socioeconomic status at birth and externalizing symptoms at age 2 years. Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to whole-brain functional connectivity of five brain regions representing functional networks implicated in psychiatric illnesses and affected by socioeconomic disadvantage: striatum, medial prefrontal cortex (mPFC), ventrolateral prefrontal cortex (vlPFC), and dorsal anterior cingulate cortex. Lower SES was associated with differences in striatum and vlPFC connectivity. Striatum connectivity with frontopolar and medial PFC mediated the relationship between SES and behavioral inhibition at age 2 measured by the Infant-Toddler Social Emotional Assessment (n = 46). Striatum-frontopolar connectivity mediated the relationship between SES and externalizing symptoms. These results, convergent across three SES metrics, suggest that neurodevelopmental trajectories linking SES and mental illness may begin as early as birth.</AbstractText
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39112741
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25246569
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39525629
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Scoring story recall for individual differences research: Central details, peripheral details, and automated scoring.
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Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans.
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Dopamine internalization via Uptake(2) and stimulation of intracellular D(5)-receptor-dependent calcium mobilization and CDP-diacylglycerol signaling.
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Story recall is an episodic memory paradigm that is popular among researchers interested in the effects of aging, disease, and/or injury on memory functioning; it is less popular among individual-differences researchers studying neurotypical young adults. One reason differential psychologists may favor other episodic memory paradigms is that the prospect of scoring story recall is daunting, as it typically requires manually scoring hundreds or thousands of freely recalled narratives. In this study, I investigated two questions related to scoring story recall for individual differences research. First, whether there is anything to gain by scoring story recall for memory of central and peripheral details or if a single score is sufficient. Second, I investigated whether scoring can be automated using computational methods - namely, BERTScore and GPT-4. A total of 235 individuals participated in this study. At the latent variable level, central and peripheral factors were highly correlated (r = .99), and the two factors correlated with external factors (viz., fluid intelligence, crystallized intelligence, and working memory capacity) similarly. Regarding automated scoring, both BERTScore and GPT-4 derived scores were strongly correlated with manually derived scores (r ≥ .97); additionally, factors estimated from the various scoring methods all showed a similar pattern of correlations with the external factors. Thus, differential psychologists may be able to streamline scoring by disregarding detail type and by using automated approaches. Further research is needed, particularly of the automated approaches, as both BERTScore and GPT-4 derived scores were occasionally leptokurtic while manual scores were not.</AbstractText
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Recent models of episodic memory propose a division of labor among medial temporal lobe cortices comprising the parahippocampal gyrus. Specifically, perirhinal and lateral entorhinal cortices are thought to comprise an object/item information pathway, whereas parahippocampal and medial entorhinal cortices are thought to comprise a spatial/contextual information pathway. Although several studies in human subjects have demonstrated a perirhinal/parahippocampal division, such a division among subregions of the human entorhinal cortex has been elusive. Other recent work has implicated pattern separation computations in the dentate gyrus and CA3 subregions of the hippocampus as a mechanism supporting the resolution of mnemonic interference. However, the nature of contributions of medial temporal lobe cortices to downstream hippocampal computations is largely unknown. We used high-resolution fMRI during a task selectively taxing mnemonic discrimination of object identity or spatial location, designed to differentially engage the two information pathways in the medial temporal lobes. Consistent with animal models, we demonstrate novel evidence for a domain-selective dissociation between lateral and medial entorhinal cortex in humans, and between perirhinal and parahippocampal cortex as a function of information content. Conversely, hippocampal dentate gyrus/CA3 demonstrated signals consistent with resolution of mnemonic interference across domains. These results provide insight into the information processing capacities and hierarchical interference resolution throughout the human medial temporal lobe.</AbstractText
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Dopamine stimulates CDP-diacylglycerol biosynthesis through D<sub
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Scoring story recall for individual differences research: Central details, peripheral details, and automated scoring. Story recall is an episodic memory paradigm that is popular among researchers interested in the effects of aging, disease, and/or injury on memory functioning; it is less popular among individual-differences researchers studying neurotypical young adults. One reason differential psychologists may favor other episodic memory paradigms is that the prospect of scoring story recall is daunting, as it typically requires manually scoring hundreds or thousands of freely recalled narratives. In this study, I investigated two questions related to scoring story recall for individual differences research. First, whether there is anything to gain by scoring story recall for memory of central and peripheral details or if a single score is sufficient. Second, I investigated whether scoring can be automated using computational methods - namely, BERTScore and GPT-4. A total of 235 individuals participated in this study. At the latent variable level, central and peripheral factors were highly correlated (r = .99), and the two factors correlated with external factors (viz., fluid intelligence, crystallized intelligence, and working memory capacity) similarly. Regarding automated scoring, both BERTScore and GPT-4 derived scores were strongly correlated with manually derived scores (r ≥ .97); additionally, factors estimated from the various scoring methods all showed a similar pattern of correlations with the external factors. Thus, differential psychologists may be able to streamline scoring by disregarding detail type and by using automated approaches. Further research is needed, particularly of the automated approaches, as both BERTScore and GPT-4 derived scores were occasionally leptokurtic while manual scores were not.</AbstractText
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Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans. Recent models of episodic memory propose a division of labor among medial temporal lobe cortices comprising the parahippocampal gyrus. Specifically, perirhinal and lateral entorhinal cortices are thought to comprise an object/item information pathway, whereas parahippocampal and medial entorhinal cortices are thought to comprise a spatial/contextual information pathway. Although several studies in human subjects have demonstrated a perirhinal/parahippocampal division, such a division among subregions of the human entorhinal cortex has been elusive. Other recent work has implicated pattern separation computations in the dentate gyrus and CA3 subregions of the hippocampus as a mechanism supporting the resolution of mnemonic interference. However, the nature of contributions of medial temporal lobe cortices to downstream hippocampal computations is largely unknown. We used high-resolution fMRI during a task selectively taxing mnemonic discrimination of object identity or spatial location, designed to differentially engage the two information pathways in the medial temporal lobes. Consistent with animal models, we demonstrate novel evidence for a domain-selective dissociation between lateral and medial entorhinal cortex in humans, and between perirhinal and parahippocampal cortex as a function of information content. Conversely, hippocampal dentate gyrus/CA3 demonstrated signals consistent with resolution of mnemonic interference across domains. These results provide insight into the information processing capacities and hierarchical interference resolution throughout the human medial temporal lobe.</AbstractText
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Dopamine internalization via Uptake(2) and stimulation of intracellular D(5)-receptor-dependent calcium mobilization and CDP-diacylglycerol signaling. Dopamine stimulates CDP-diacylglycerol biosynthesis through D<sub
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38281087
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35842345
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37897926
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A quantum-based oversampling method for classification of highly imbalanced and overlapped data.
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AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review.
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Design, synthesis and preclinical evaluation of muscarine receptor antagonists via a scaffold-hopping approach.
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Data imbalance is a challenging problem in classification tasks, and when combined with class overlapping, it further deteriorates classification performance. However, existing studies have rarely addressed both issues simultaneously. In this article, we propose a novel quantum-based oversampling method (QOSM) to effectively tackle data imbalance and class overlapping, thereby improving classification performance. QOSM utilizes the quantum potential theory to calculate the potential energy of each sample and selects the sample with the lowest potential as the center of each cover generated by a constructive covering algorithm. This approach optimizes cover center selection and better captures the distribution of the original samples, particularly in the overlapping regions. In addition, oversampling is performed on the samples of the minority class covers to mitigate the imbalance ratio (IR). We evaluated QOSM using three traditional classifiers (support vector machines [SVM], k-nearest neighbor [KNN], and naive Bayes [NB] classifier) on 10 publicly available KEEL data sets characterized by high IRs and varying degrees of overlap. Experimental results demonstrate that QOSM significantly improves classification accuracy compared to approaches that do not address class imbalance and overlapping. Moreover, QOSM consistently outperforms existing oversampling methods tested. With its compatibility with different classifiers, QOSM exhibits promising potential to improve the classification performance of highly imbalanced and overlapped data.</AbstractText
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Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of the US and global populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus. Limited guidance is available to clinicians on appropriate clinical evaluation in lean individuals with NAFLD, such as for inherited/genetic disorders, lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now provide more robust evidence to define the epidemiology, natural history, prognosis, and mortality of lean individuals with NAFLD. Multiple studies have found that NAFLD among lean individuals is associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD. This American Gastroenterological Association Clinical Practice Update provides Best Practice Advice to assist clinicians in evidence-based approaches to the diagnosis, staging, and management of NAFLD in lean individuals.</AbstractText This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Lean NAFLD should be diagnosed in individuals with NAFLD and body mass index <25 kg/m<sup
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Our research group recently identified a rearrangement product of pirenzepine as starting point for a comprehensive rational drug design approach towards orthosteric muscarinic acetylcholine receptor ligands. Chemical reduction and bioscaffold hop lead to the development of sixteen promising compounds featuring either a benzimidazole or carbamate moiety, all exhibiting comparable pharmacophoric characteristics. The synthesized compounds were characterized by NMR, HR-MS, and RP-HPLC techniques. Subsequent evaluation encompassed binding affinity assessment on CHO-hM<sub
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A quantum-based oversampling method for classification of highly imbalanced and overlapped data. Data imbalance is a challenging problem in classification tasks, and when combined with class overlapping, it further deteriorates classification performance. However, existing studies have rarely addressed both issues simultaneously. In this article, we propose a novel quantum-based oversampling method (QOSM) to effectively tackle data imbalance and class overlapping, thereby improving classification performance. QOSM utilizes the quantum potential theory to calculate the potential energy of each sample and selects the sample with the lowest potential as the center of each cover generated by a constructive covering algorithm. This approach optimizes cover center selection and better captures the distribution of the original samples, particularly in the overlapping regions. In addition, oversampling is performed on the samples of the minority class covers to mitigate the imbalance ratio (IR). We evaluated QOSM using three traditional classifiers (support vector machines [SVM], k-nearest neighbor [KNN], and naive Bayes [NB] classifier) on 10 publicly available KEEL data sets characterized by high IRs and varying degrees of overlap. Experimental results demonstrate that QOSM significantly improves classification accuracy compared to approaches that do not address class imbalance and overlapping. Moreover, QOSM consistently outperforms existing oversampling methods tested. With its compatibility with different classifiers, QOSM exhibits promising potential to improve the classification performance of highly imbalanced and overlapped data.</AbstractText
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AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review. Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of the US and global populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus. Limited guidance is available to clinicians on appropriate clinical evaluation in lean individuals with NAFLD, such as for inherited/genetic disorders, lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now provide more robust evidence to define the epidemiology, natural history, prognosis, and mortality of lean individuals with NAFLD. Multiple studies have found that NAFLD among lean individuals is associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD. This American Gastroenterological Association Clinical Practice Update provides Best Practice Advice to assist clinicians in evidence-based approaches to the diagnosis, staging, and management of NAFLD in lean individuals.</AbstractText This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Lean NAFLD should be diagnosed in individuals with NAFLD and body mass index <25 kg/m<sup
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Design, synthesis and preclinical evaluation of muscarine receptor antagonists via a scaffold-hopping approach. Our research group recently identified a rearrangement product of pirenzepine as starting point for a comprehensive rational drug design approach towards orthosteric muscarinic acetylcholine receptor ligands. Chemical reduction and bioscaffold hop lead to the development of sixteen promising compounds featuring either a benzimidazole or carbamate moiety, all exhibiting comparable pharmacophoric characteristics. The synthesized compounds were characterized by NMR, HR-MS, and RP-HPLC techniques. Subsequent evaluation encompassed binding affinity assessment on CHO-hM<sub
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39466847
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33220651
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39080439
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Object color knowledge representation occurs in the macaque brain despite the absence of a developed language system.
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Altering access to autobiographical episodes with prior semantic knowledge.
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The Derlin-1-Stat5b axis maintains homeostasis of adult hippocampal neurogenesis.
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Animals guide their behaviors through internal representations of the world in the brain. We aimed to understand how the macaque brain stores such general world knowledge, focusing on object color knowledge. Three functional magnetic resonance imaging (fMRI) experiments were conducted in macaque monkeys: viewing chromatic and achromatic gratings, viewing grayscale images of their familiar fruits and vegetables (e.g., grayscale strawberry), and viewing true- and false-colored objects (e.g., red strawberry and green strawberry). We observed robust object knowledge representations in the color patches, especially the one located around TEO: the activity patterns could classify grayscale pictures of objects based on their memory color and response patterns in these regions could translate between chromatic grating viewing and grayscale object viewing (e.g., red grating-grayscale images of strawberry), such that classifiers trained by viewing chromatic gratings could successfully classify grayscale object images according to their memory colors. Our results showed direct positive evidence of object color memory in macaque monkeys. These results indicate the perceptually grounded knowledge representation as a conservative memory mechanism and open a new avenue to study this particular (semantic) memory representation with macaque models.</AbstractText
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Within autobiographical knowledge, semantic and episodic memory are traditionally considered separate, but newer models place them along a continuum, which raises the possibility of an intermediate form of knowledge - personal semantics. This study tested how different types of semantics - general semantics and two forms of personal semantics - impact access to personal episodic memories. In two experiments, participants made a series of true/false judgments about a prime statement, which reflected a general semantic fact, a context-dependent (e.g., repeated event) or context-independent (e.g., trait), personal semantic fact and then retrieved a specific past episodic memory. There was a significantly stronger priming effect for accessing specific episodic memories after judging personal semantic facts versus general facts. We also found that context-dependent and -independent personal semantic facts had separable priming effects on episodic memory. These findings support a continuum model of memory and verifies that there are multiple forms of personal knowledge.</AbstractText
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Adult neural stem cells (NSCs) in the hippocampal dentate gyrus continuously proliferate and generate new neurons throughout life. Although various functions of organelles are closely related to the regulation of adult neurogenesis, the role of endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER-associated degradation component, spatiotemporally maintains adult hippocampal neurogenesis through a mechanism distinct from its established role as an ER quality controller. Derlin-1 deficiency in the mouse central nervous system leads to the ectopic localization of newborn neurons and impairs NSC transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1-deficient mice exhibit phenotypes of increased seizure susceptibility and cognitive dysfunction. Reduced Stat5b expression is responsible for adult neurogenesis defects in Derlin-1-deficient NSCs. Inhibition of histone deacetylase activity effectively induces Stat5b expression and restores abnormal adult neurogenesis, resulting in improved seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice. Our findings indicate that the Derlin-1-Stat5b axis is indispensable for the homeostasis of adult hippocampal neurogenesis.</AbstractText
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Object color knowledge representation occurs in the macaque brain despite the absence of a developed language system. Animals guide their behaviors through internal representations of the world in the brain. We aimed to understand how the macaque brain stores such general world knowledge, focusing on object color knowledge. Three functional magnetic resonance imaging (fMRI) experiments were conducted in macaque monkeys: viewing chromatic and achromatic gratings, viewing grayscale images of their familiar fruits and vegetables (e.g., grayscale strawberry), and viewing true- and false-colored objects (e.g., red strawberry and green strawberry). We observed robust object knowledge representations in the color patches, especially the one located around TEO: the activity patterns could classify grayscale pictures of objects based on their memory color and response patterns in these regions could translate between chromatic grating viewing and grayscale object viewing (e.g., red grating-grayscale images of strawberry), such that classifiers trained by viewing chromatic gratings could successfully classify grayscale object images according to their memory colors. Our results showed direct positive evidence of object color memory in macaque monkeys. These results indicate the perceptually grounded knowledge representation as a conservative memory mechanism and open a new avenue to study this particular (semantic) memory representation with macaque models.</AbstractText
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Altering access to autobiographical episodes with prior semantic knowledge. Within autobiographical knowledge, semantic and episodic memory are traditionally considered separate, but newer models place them along a continuum, which raises the possibility of an intermediate form of knowledge - personal semantics. This study tested how different types of semantics - general semantics and two forms of personal semantics - impact access to personal episodic memories. In two experiments, participants made a series of true/false judgments about a prime statement, which reflected a general semantic fact, a context-dependent (e.g., repeated event) or context-independent (e.g., trait), personal semantic fact and then retrieved a specific past episodic memory. There was a significantly stronger priming effect for accessing specific episodic memories after judging personal semantic facts versus general facts. We also found that context-dependent and -independent personal semantic facts had separable priming effects on episodic memory. These findings support a continuum model of memory and verifies that there are multiple forms of personal knowledge.</AbstractText
|
The Derlin-1-Stat5b axis maintains homeostasis of adult hippocampal neurogenesis. Adult neural stem cells (NSCs) in the hippocampal dentate gyrus continuously proliferate and generate new neurons throughout life. Although various functions of organelles are closely related to the regulation of adult neurogenesis, the role of endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER-associated degradation component, spatiotemporally maintains adult hippocampal neurogenesis through a mechanism distinct from its established role as an ER quality controller. Derlin-1 deficiency in the mouse central nervous system leads to the ectopic localization of newborn neurons and impairs NSC transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1-deficient mice exhibit phenotypes of increased seizure susceptibility and cognitive dysfunction. Reduced Stat5b expression is responsible for adult neurogenesis defects in Derlin-1-deficient NSCs. Inhibition of histone deacetylase activity effectively induces Stat5b expression and restores abnormal adult neurogenesis, resulting in improved seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice. Our findings indicate that the Derlin-1-Stat5b axis is indispensable for the homeostasis of adult hippocampal neurogenesis.</AbstractText
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18447674
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23932444
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18296757
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Combination of myxopapillary ependymoma and fatty filum in a child with tethered cord syndrome. Case report.
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Early identification of tethered cord syndrome: a clinical challenge.
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Validation of calculations for electrons modulated with conventional photon multileaf collimators.
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The authors present a case of a child with a tethered spinal cord associated with a myxopapillary ependymoma. This 16-month-old boy presented to the authors' institution with developmental delays in standing and walking. Magnetic resonance (MR) imaging demonstrated a fatty terminal filum and tethered cord. The child underwent surgical exploration of the spine with resection of the fatty filum tissue and release of the cord. Histological analysis of the fatty filum suggested the presence of a coexisting myxopapillary ependymoma. The child made a good recovery with no evidence of tumor recurrence after 4-years of follow-up with serial MR imaging. This unusual combination has not previously been reported in children, and to the authors' knowledge there is only one reported case in an adult. The likelihood of a common pathophysiological process in these conditions is also discussed.</AbstractText
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Tethered cord syndrome (TCS) is a progressive clinical condition that arises from excessive spinal cord tension. The clinical signs and symptoms of TCS may be cutaneous, neurologic, musculoskeletal, genitourinary, and/or gastrointestinal. Patients also may be asymptomatic, which does not exclude the diagnosis of TCS. Although the exact etiology is unknown, early identification and lifelong surveillance or surgical treatment is an essential component of patient management. In this article we review the pathophysiology, various etiologies, clinical presentation, and long-term sequelae of TCS. This information will help pediatric nurse practitioners identify TCS early and anticipate the patient's needs and management requirements.</AbstractText
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Treating shallow tumors with a homogeneous dose while simultaneously minimizing the dose to distal critical organs remains a challenge in radiotherapy. One promising approach is modulated electron radiotherapy (MERT). Due to the scattering properties of electron beams, the commercially provided secondary and tertiary photon collimation systems are not conducive for electron beam delivery when standard source-to-surface distances are used. Also, commercial treatment planning systems may not accurately model electron-beam dose distributions when collimated without the standard applicators. However, by using the photon multileaf collimators (MLCs) to create segments to modulate electron beams, the quality of superficial tumor dose distributions may improve substantially. The purpose of this study is to develop and evaluate calculations for the narrow segments needed to modulate megavoltage electron beams using photon beam multileaf collimators. Modulated electron radiotherapy (MERT) will be performed with a conventional linear accelerator equipped with a 120 leaf MLC for 6-20 MeV electron beam energies. To provide a sharp penumbra, segments were delivered with short SSDs (70-85 cm). Segment widths (SW) ranging from 1 to 10 cm were configured for delivery and planning, using BEAMnrc Monte Carlo (MC) code, and the DOSXYZnrc MC dose calculations. Calculations were performed with voxel size of 0.2 x 0.2 x 0.1 cm3. Dosimetry validation was performed using radiographic film and micro- or parallel-plate chambers. Calculated and measured data were compared using technical computing software. Beam sharpness (penumbra) degraded with decreasing incident beam energy and field size (FS), and increasing SSD. A 70 cm SSD was found to be optimal. The PDD decreased significantly with decreasing FS. The comparisons demonstrated excellent agreement for calculations and measurements within 3%, 1 mm. This study shows that accurate calculations for MERT as delivered with existing photon MLC are feasible and allows the opportunity to take advantage of the dynamic leaf motion capabilities and control systems, to provide conformal dose distributions.</AbstractText
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Combination of myxopapillary ependymoma and fatty filum in a child with tethered cord syndrome. Case report. The authors present a case of a child with a tethered spinal cord associated with a myxopapillary ependymoma. This 16-month-old boy presented to the authors' institution with developmental delays in standing and walking. Magnetic resonance (MR) imaging demonstrated a fatty terminal filum and tethered cord. The child underwent surgical exploration of the spine with resection of the fatty filum tissue and release of the cord. Histological analysis of the fatty filum suggested the presence of a coexisting myxopapillary ependymoma. The child made a good recovery with no evidence of tumor recurrence after 4-years of follow-up with serial MR imaging. This unusual combination has not previously been reported in children, and to the authors' knowledge there is only one reported case in an adult. The likelihood of a common pathophysiological process in these conditions is also discussed.</AbstractText
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Early identification of tethered cord syndrome: a clinical challenge. Tethered cord syndrome (TCS) is a progressive clinical condition that arises from excessive spinal cord tension. The clinical signs and symptoms of TCS may be cutaneous, neurologic, musculoskeletal, genitourinary, and/or gastrointestinal. Patients also may be asymptomatic, which does not exclude the diagnosis of TCS. Although the exact etiology is unknown, early identification and lifelong surveillance or surgical treatment is an essential component of patient management. In this article we review the pathophysiology, various etiologies, clinical presentation, and long-term sequelae of TCS. This information will help pediatric nurse practitioners identify TCS early and anticipate the patient's needs and management requirements.</AbstractText
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Validation of calculations for electrons modulated with conventional photon multileaf collimators. Treating shallow tumors with a homogeneous dose while simultaneously minimizing the dose to distal critical organs remains a challenge in radiotherapy. One promising approach is modulated electron radiotherapy (MERT). Due to the scattering properties of electron beams, the commercially provided secondary and tertiary photon collimation systems are not conducive for electron beam delivery when standard source-to-surface distances are used. Also, commercial treatment planning systems may not accurately model electron-beam dose distributions when collimated without the standard applicators. However, by using the photon multileaf collimators (MLCs) to create segments to modulate electron beams, the quality of superficial tumor dose distributions may improve substantially. The purpose of this study is to develop and evaluate calculations for the narrow segments needed to modulate megavoltage electron beams using photon beam multileaf collimators. Modulated electron radiotherapy (MERT) will be performed with a conventional linear accelerator equipped with a 120 leaf MLC for 6-20 MeV electron beam energies. To provide a sharp penumbra, segments were delivered with short SSDs (70-85 cm). Segment widths (SW) ranging from 1 to 10 cm were configured for delivery and planning, using BEAMnrc Monte Carlo (MC) code, and the DOSXYZnrc MC dose calculations. Calculations were performed with voxel size of 0.2 x 0.2 x 0.1 cm3. Dosimetry validation was performed using radiographic film and micro- or parallel-plate chambers. Calculated and measured data were compared using technical computing software. Beam sharpness (penumbra) degraded with decreasing incident beam energy and field size (FS), and increasing SSD. A 70 cm SSD was found to be optimal. The PDD decreased significantly with decreasing FS. The comparisons demonstrated excellent agreement for calculations and measurements within 3%, 1 mm. This study shows that accurate calculations for MERT as delivered with existing photon MLC are feasible and allows the opportunity to take advantage of the dynamic leaf motion capabilities and control systems, to provide conformal dose distributions.</AbstractText
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37955408
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36483824
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39371600
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Interleukin-10 promoter polymorphisms and haplotypes in patients with Guillain-Barré syndrome.
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Multiple cranial nerve palsies with small angle exotropia following COVID-19 mRNA vaccination in an adolescent: A case report.
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Electrical stimulation: a potential alternative to positively impact cerebral health?
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Interleukin-10 (IL-10) is a multifunctional cytokine that exerts both pro- and anti-inflammatory effects on the immune system as well as in the pathogenesis of Guillain-Barré syndrome (GBS). We investigated whether the three common polymorphisms -1082 G/A(rs1800896), -819 C/T(rs1800871), and -592 C/A(rs1800872) in the promoter region of IL-10 have any influence on the susceptibility, severity, and clinical outcome of GBS.</AbstractText IL-10 promoter polymorphisms were investigated in 152 patients with GBS and 152 healthy controls from Bangladesh using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and allele-specific oligonucleotide-PCR (ASO-PCR). Haplotype patterns and frequencies were analyzed using Heatmaply R-package, chi-square, and Fisher's exact test. The serum level of IL-10 was measured through enzyme-linked immunosorbent assays. p-values < 0.05 were considered statistically significant.</AbstractText IL-10 promoter polymorphisms -1082 G/A, -819 C/T, and -592 C/A were not associated with GBS susceptibility. The homozygous -819 TT genotype showed a tendency with susceptibility (p = 0.029; pc = 0.08) and was prevalent in axonal variants of GBS compared to demyelinating subtypes and controls (p = 0.042, OR = 8.67, 95% CI = 1.03-72.97; pc = 0.123 and p = 0.005, OR = 4.2, 95% CI = 1.55-11.40; pc = 0.015, respectively). Haplotype analysis revealed 19 patterns of genotypes and high IL-10 expression haplotype combinations (GCC/GTA, GCC/ATA, and GCC/GCA) may have influence on disease severity (p = 0.026; pc = 0.078). Serum expression of IL-10 was elevated in GBS patients ([GBS, 12.16 ± 45.71] vs. [HC, 0.65 ± 5.17] pg/mL; p = 0.0027) and varied with disease severity ([severe-GBS, 15.25 ± 51.72] vs. [mild-GBS, 3.59 ± 19.79] pg/mL, p = 0.046).</AbstractText The -819 TT genotypes influence axonal GBS, and high frequency of IL-10 expression haplotype combination with elevated serum IL-10 may play an important role in disease severity.</AbstractText
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Several vaccines against the severe acute respiratory syndrome coronavirus 2 have been approved and widely distributed, raising public concerns regarding the side effects of immunization, as the incidence of ease. Although many adverse events following the coronavirus disease 2019 (COVID-19) vaccine have been reported, neurological complications are relatively uncommon. Herein, we report a rare case of multiple cranial palsies following COVID-19 vaccination in an adolescent patient.</AbstractText A previously healthy, 14-year-old Asian girl with facial palsy presented to the emergency department with inability to close the right eye or wrinkle right side of the forehead, and pain in the right cheek. She had received second dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech) 18 days before onset of symptoms. She was diagnosed with Bell's palsy and prescribed a steroid (1 mg/kg/day methylprednisolone) based on symptoms and magnetic resonance imaging findings. However, the next day, all sense of taste was lost with inability to swallow solid food; the gag reflex was absent. Horizontal diplopia was also present. Due to worsening of her condition, she was given high-dose steroids (1 g/day methylprednisolone) for 3 days and then discharged with oral steroids. Improvement in the symptoms was noted 4 days post steroid treatment completion. At the most recent follow-up, her general condition was good with no symptoms except diplopia; ocular motility disturbances were noted. Hence, prism glasses were prescribed for diplopia relief.</AbstractText Small-angle exotropia was observed in the facial, trigeminal, and glossopharyngeal nerve palsies, in our patient. The etiology of this adverse effect following vaccination was thought to be immunological.</AbstractText
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An increasing body of evidence confirms the effectiveness of physical exercise (PE) in promoting brain health by preventing age-related cognitive decline and reducing the risk of neurodegenerative diseases. The benefits of PE are attributed to neuroplasticity processes which have been reported to enhance cerebral health. However, moderate to high-intensity PE is necessary to induce these responses and these intensities cannot always be achieved especially by people with physical limitations. As a countermeasure, electrical stimulation (ES) offers several benefits, particularly for improving physical functions, for various neurological diseases. This review aims to provide an overview of key mechanisms that could contribute to the enhancement in brain health in response to ES-induced exercise, including increases in cerebral blood flow, neuronal activity, and humoral pathways. This narrative review also focuses on the effects of ES protocols, applied to both humans and animals, on cognition. Despite a certain paucity of research when compared to the more classical aerobic exercise, it seems that ES could be of interest for improving cerebral health, particularly in people who have difficulty engaging in voluntary exercise.</AbstractText
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Interleukin-10 promoter polymorphisms and haplotypes in patients with Guillain-Barré syndrome. Interleukin-10 (IL-10) is a multifunctional cytokine that exerts both pro- and anti-inflammatory effects on the immune system as well as in the pathogenesis of Guillain-Barré syndrome (GBS). We investigated whether the three common polymorphisms -1082 G/A(rs1800896), -819 C/T(rs1800871), and -592 C/A(rs1800872) in the promoter region of IL-10 have any influence on the susceptibility, severity, and clinical outcome of GBS.</AbstractText IL-10 promoter polymorphisms were investigated in 152 patients with GBS and 152 healthy controls from Bangladesh using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), and allele-specific oligonucleotide-PCR (ASO-PCR). Haplotype patterns and frequencies were analyzed using Heatmaply R-package, chi-square, and Fisher's exact test. The serum level of IL-10 was measured through enzyme-linked immunosorbent assays. p-values < 0.05 were considered statistically significant.</AbstractText IL-10 promoter polymorphisms -1082 G/A, -819 C/T, and -592 C/A were not associated with GBS susceptibility. The homozygous -819 TT genotype showed a tendency with susceptibility (p = 0.029; pc = 0.08) and was prevalent in axonal variants of GBS compared to demyelinating subtypes and controls (p = 0.042, OR = 8.67, 95% CI = 1.03-72.97; pc = 0.123 and p = 0.005, OR = 4.2, 95% CI = 1.55-11.40; pc = 0.015, respectively). Haplotype analysis revealed 19 patterns of genotypes and high IL-10 expression haplotype combinations (GCC/GTA, GCC/ATA, and GCC/GCA) may have influence on disease severity (p = 0.026; pc = 0.078). Serum expression of IL-10 was elevated in GBS patients ([GBS, 12.16 ± 45.71] vs. [HC, 0.65 ± 5.17] pg/mL; p = 0.0027) and varied with disease severity ([severe-GBS, 15.25 ± 51.72] vs. [mild-GBS, 3.59 ± 19.79] pg/mL, p = 0.046).</AbstractText The -819 TT genotypes influence axonal GBS, and high frequency of IL-10 expression haplotype combination with elevated serum IL-10 may play an important role in disease severity.</AbstractText
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Multiple cranial nerve palsies with small angle exotropia following COVID-19 mRNA vaccination in an adolescent: A case report. Several vaccines against the severe acute respiratory syndrome coronavirus 2 have been approved and widely distributed, raising public concerns regarding the side effects of immunization, as the incidence of ease. Although many adverse events following the coronavirus disease 2019 (COVID-19) vaccine have been reported, neurological complications are relatively uncommon. Herein, we report a rare case of multiple cranial palsies following COVID-19 vaccination in an adolescent patient.</AbstractText A previously healthy, 14-year-old Asian girl with facial palsy presented to the emergency department with inability to close the right eye or wrinkle right side of the forehead, and pain in the right cheek. She had received second dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech) 18 days before onset of symptoms. She was diagnosed with Bell's palsy and prescribed a steroid (1 mg/kg/day methylprednisolone) based on symptoms and magnetic resonance imaging findings. However, the next day, all sense of taste was lost with inability to swallow solid food; the gag reflex was absent. Horizontal diplopia was also present. Due to worsening of her condition, she was given high-dose steroids (1 g/day methylprednisolone) for 3 days and then discharged with oral steroids. Improvement in the symptoms was noted 4 days post steroid treatment completion. At the most recent follow-up, her general condition was good with no symptoms except diplopia; ocular motility disturbances were noted. Hence, prism glasses were prescribed for diplopia relief.</AbstractText Small-angle exotropia was observed in the facial, trigeminal, and glossopharyngeal nerve palsies, in our patient. The etiology of this adverse effect following vaccination was thought to be immunological.</AbstractText
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Electrical stimulation: a potential alternative to positively impact cerebral health? An increasing body of evidence confirms the effectiveness of physical exercise (PE) in promoting brain health by preventing age-related cognitive decline and reducing the risk of neurodegenerative diseases. The benefits of PE are attributed to neuroplasticity processes which have been reported to enhance cerebral health. However, moderate to high-intensity PE is necessary to induce these responses and these intensities cannot always be achieved especially by people with physical limitations. As a countermeasure, electrical stimulation (ES) offers several benefits, particularly for improving physical functions, for various neurological diseases. This review aims to provide an overview of key mechanisms that could contribute to the enhancement in brain health in response to ES-induced exercise, including increases in cerebral blood flow, neuronal activity, and humoral pathways. This narrative review also focuses on the effects of ES protocols, applied to both humans and animals, on cognition. Despite a certain paucity of research when compared to the more classical aerobic exercise, it seems that ES could be of interest for improving cerebral health, particularly in people who have difficulty engaging in voluntary exercise.</AbstractText
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40449343
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37716988
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39028358
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Heightened effector immune cell infiltration of the hippocampus concurrently with brain ventricular volume expansion in aged APP/PS1 mice.
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Systematic characterization of a non-transgenic Aβ(1-42) amyloidosis model: synaptic plasticity and memory deficits in female and male mice.
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The Use of fMRI Regional Analysis to Automatically Detect ADHD Through a 3D CNN-Based Approach.
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Alzheimer's disease (AD) is the most common form of dementia for which the role of neuroinflammation is becoming more realized. Recent studies have shown that immune cells infiltrate the hippocampus and the cortex of AD patients as well as mouse models of the disease. In this study, we employed T2-weighted magnetic resonance imaging (MRI) to view changes in ventricular volume in addition to spectral flow cytometric assessment of the hippocampus infiltrating immune profile in the aged APP/PS1 mice. Aged APP/PS1 mice present with increased size of lateral, dorsal, and ventral ventricles plus increased numbers of hippocampus infiltrating effector immune cell subsets, including CD8 T cells expressing IFNγ, granzyme B, and perforin along with other cell types such as γδ T cells, neutrophils, and NK cells. The concurrent increase in effector cell types with ventricular enlargement expands the putative mechanism of brain atrophy in the APP/PS1 mouse model to include cytolytic functions of these aforementioned immune cell subsets.</AbstractText
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The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ accumulation and dyshomeostasis have shown a key role in AD onset, leading to excitatory/inhibitory imbalance, the impairments of synaptic plasticity and oscillatory activity, and memory deficits. Despite the higher prevalence of Alzheimer's disease (AD) in women compared to men, the possible sex difference is scarcely explored and the information from amyloidosis transgenic mice models is contradictory. Thus, given the lack of data regarding the early stages of amyloidosis in female mice, the aim of this study was to systematically characterize the effect of an intracerebroventricular (icv.) injection of Aβ<sub To do so, we evaluated long term potentiation (LTP) with ex vivo electrophysiological recordings as well as encoding and retrieval of spatial (working, short- and long-term) and exploratory habituation memories using Barnes maze and object location, or open field habituation tasks, respectively.</AbstractText Aβ<sub In conclusion, our results provide further evidence on the shifting of LTP/LTD threshold due to a single icv. Aβ<sub This study focuses on investigating how amyloid-β (Aβ), a key toxic protein in Alzheimer's disease (AD), impacts memory and functioning of the synapses in both male and female mice.Our primary objective was to comprehensively understand the impact of Aβ<sub
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Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a reduced attention span, hyperactivity, and impulsive behaviors, which typically manifest during childhood. This study employs functional magnetic resonance imaging (fMRI) to use spontaneous brain activity for classifying individuals with ADHD, focusing on a 3D convolutional neural network (CNN) architecture to facilitate the design of decision support systems. We developed a novel deep learning model based on 3D CNNs using the ADHD-200 database, which comprises datasets from NeuroImage (NI), New York University (NYU), and Peking University (PU). We used fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) data in three dimensions and performed a fivefold cross-validation to address the dataset imbalance. We aimed to verify the efficacy of our proposed 3D CNN by contrasting it with a fully connected neural network (FCNN) architecture. The 3D CNN achieved accuracy rates of 76.19% (NI), 69.92% (NYU), and 70.77% (PU) for fALFF data. The FCNN model yielded lower accuracy rates across all datasets. For generalizability, we trained on NI and NYU datasets and tested on PU. The 3D CNN achieved 69.48% accuracy on fALFF outperforming the FCNN. Our results demonstrate that using 3D CNNs for classifying fALFF data is an effective approach for diagnosing ADHD. Also, FCNN confirmed the efficiency of the designed model.</AbstractText
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Heightened effector immune cell infiltration of the hippocampus concurrently with brain ventricular volume expansion in aged APP/PS1 mice. Alzheimer's disease (AD) is the most common form of dementia for which the role of neuroinflammation is becoming more realized. Recent studies have shown that immune cells infiltrate the hippocampus and the cortex of AD patients as well as mouse models of the disease. In this study, we employed T2-weighted magnetic resonance imaging (MRI) to view changes in ventricular volume in addition to spectral flow cytometric assessment of the hippocampus infiltrating immune profile in the aged APP/PS1 mice. Aged APP/PS1 mice present with increased size of lateral, dorsal, and ventral ventricles plus increased numbers of hippocampus infiltrating effector immune cell subsets, including CD8 T cells expressing IFNγ, granzyme B, and perforin along with other cell types such as γδ T cells, neutrophils, and NK cells. The concurrent increase in effector cell types with ventricular enlargement expands the putative mechanism of brain atrophy in the APP/PS1 mouse model to include cytolytic functions of these aforementioned immune cell subsets.</AbstractText
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Systematic characterization of a non-transgenic Aβ(1-42) amyloidosis model: synaptic plasticity and memory deficits in female and male mice. The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ accumulation and dyshomeostasis have shown a key role in AD onset, leading to excitatory/inhibitory imbalance, the impairments of synaptic plasticity and oscillatory activity, and memory deficits. Despite the higher prevalence of Alzheimer's disease (AD) in women compared to men, the possible sex difference is scarcely explored and the information from amyloidosis transgenic mice models is contradictory. Thus, given the lack of data regarding the early stages of amyloidosis in female mice, the aim of this study was to systematically characterize the effect of an intracerebroventricular (icv.) injection of Aβ<sub To do so, we evaluated long term potentiation (LTP) with ex vivo electrophysiological recordings as well as encoding and retrieval of spatial (working, short- and long-term) and exploratory habituation memories using Barnes maze and object location, or open field habituation tasks, respectively.</AbstractText Aβ<sub In conclusion, our results provide further evidence on the shifting of LTP/LTD threshold due to a single icv. Aβ<sub This study focuses on investigating how amyloid-β (Aβ), a key toxic protein in Alzheimer's disease (AD), impacts memory and functioning of the synapses in both male and female mice.Our primary objective was to comprehensively understand the impact of Aβ<sub
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The Use of fMRI Regional Analysis to Automatically Detect ADHD Through a 3D CNN-Based Approach. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a reduced attention span, hyperactivity, and impulsive behaviors, which typically manifest during childhood. This study employs functional magnetic resonance imaging (fMRI) to use spontaneous brain activity for classifying individuals with ADHD, focusing on a 3D convolutional neural network (CNN) architecture to facilitate the design of decision support systems. We developed a novel deep learning model based on 3D CNNs using the ADHD-200 database, which comprises datasets from NeuroImage (NI), New York University (NYU), and Peking University (PU). We used fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) data in three dimensions and performed a fivefold cross-validation to address the dataset imbalance. We aimed to verify the efficacy of our proposed 3D CNN by contrasting it with a fully connected neural network (FCNN) architecture. The 3D CNN achieved accuracy rates of 76.19% (NI), 69.92% (NYU), and 70.77% (PU) for fALFF data. The FCNN model yielded lower accuracy rates across all datasets. For generalizability, we trained on NI and NYU datasets and tested on PU. The 3D CNN achieved 69.48% accuracy on fALFF outperforming the FCNN. Our results demonstrate that using 3D CNNs for classifying fALFF data is an effective approach for diagnosing ADHD. Also, FCNN confirmed the efficiency of the designed model.</AbstractText
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22699023
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18567609
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24238156
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Direct current stimulation (tDCS) reveals parietal asymmetry in local/global and salience-based selection.
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Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography.
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Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors.
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Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in processing object's global form versus local parts. However the attentional mechanisms subtending visual selection of different levels of information are poorly understood. The classical left hemisphere/local-right hemisphere/global dichotomy has been recently challenged by studies linking the asymmetry of activation in the posterior parietal cortex (PPC) with the relative salience of the stimulus rather than with the local/global level. The present study aimed to assess hemispheric asymmetry in local-global and salience-based selection in hierarchical stimuli by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the PPC of both the hemispheres. Our data revealed that tDCS did affect the selection of the target on the basis of its relative salience in a manner that depended on the tDCS polarity applied to the two hemispheres. This result is in line with previous findings that the left PPC is critically involved in attention for low-salience stimuli in the presence of high-salience distractor information, while right PPC is involved in attending to more salient stimuli. Hemispheric asymmetries were also found in local/global selection. Overall the results suggest that neural activation in the PPC is related to both the salience and the level of stimulus representations mediating responses to hierarchical stimuli. The comparison of the results from Experiments 1 and 2 in local/global-based selection suggests that the effect of stimulation could be completely opposite depending on subtle differences in demands of attentional control (sustained attention vs task switching).</AbstractText
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The characterization of the topological architecture of complex networks underlying the structural and functional organization of the brain is a basic challenge in neuroscience. However, direct evidence for anatomical connectivity networks in the human brain remains scarce. Here, we utilized diffusion tensor imaging deterministic tractography to construct a macroscale anatomical network capturing the underlying common connectivity pattern of human cerebral cortex in a large sample of subjects (80 young adults) and further quantitatively analyzed its topological properties with graph theoretical approaches. The cerebral cortex was divided into 78 cortical regions, each representing a network node, and 2 cortical regions were considered connected if the probability of fiber connections exceeded a statistical criterion. The topological parameters of the established cortical network (binarized) resemble that of a "small-world" architecture characterized by an exponentially truncated power-law distribution. These characteristics imply high resilience to localized damage. Furthermore, this cortical network was characterized by major hub regions in association cortices that were connected by bridge connections following long-range white matter pathways. Our results are compatible with previous structural and functional brain networks studies and provide insight into the organizational principles of human brain anatomical networks that underlie functional states.</AbstractText
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The possible connection between psoriasis with cardiovascular disease and associated risk factors has been implied, but inconsistent results have been reported.</AbstractText We sought to create an overview and statistical summary of the previous literature with elucidating subgroup analysis.</AbstractText This was a meta-analysis of observational studies using random effect statistics. A systematic search of observational studies of psoriasis as study variable and cardiovascular disease and associated risk factors as outcome, published before October 25, 2012, was conducted.</AbstractText Of 835 references in the original search, 75 relevant articles were identified. We included 503,686 cases and 29,686,694 controls. Psoriasis was associated with cardiovascular disease in total (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.2-1.7), ischemic heart disease (OR 1.5; 95% CI 1.2-1.9), peripheral vascular disease (OR 1.5; 95% CI 1.2-1.8), atherosclerosis (OR 1.1; 95% CI 1.1-1.2), diabetes (OR 1.9; 95% CI 1.5-2.5), hypertension (OR 1.8; 95% CI 1.6-2.0), dyslipidemia (OR 1.5; 95% CI 1.4-1.7), obesity by body mass index (OR 1.8; 95% CI 1.4-2.2), obesity by abdominal fat (OR 1.6; 95% CI 1.2-2.3), and the metabolic syndrome (OR 1.8; 95% CI 1.2-2.8), but not associated with cerebrovascular disease (OR 1.1; 95% CI 0.9-1.3) and cardiovascular mortality (OR 0.9; 95% CI 0.4-2.2). The strongest associations were seen in hospital-based studies and psoriatic arthritis. Population-based studies did not show significant associations, with the exception of dyslipidemia.</AbstractText The heterogeneity of the studies makes clinical interpretation challenging.</AbstractText In aggregate, psoriasis was associated with ischemic heart disease and cardiovascular risk factors. The association was only significant for hospital-based studies, except for dyslipidemia, which was also significant in population-based studies.</AbstractText
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Direct current stimulation (tDCS) reveals parietal asymmetry in local/global and salience-based selection. Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in processing object's global form versus local parts. However the attentional mechanisms subtending visual selection of different levels of information are poorly understood. The classical left hemisphere/local-right hemisphere/global dichotomy has been recently challenged by studies linking the asymmetry of activation in the posterior parietal cortex (PPC) with the relative salience of the stimulus rather than with the local/global level. The present study aimed to assess hemispheric asymmetry in local-global and salience-based selection in hierarchical stimuli by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the PPC of both the hemispheres. Our data revealed that tDCS did affect the selection of the target on the basis of its relative salience in a manner that depended on the tDCS polarity applied to the two hemispheres. This result is in line with previous findings that the left PPC is critically involved in attention for low-salience stimuli in the presence of high-salience distractor information, while right PPC is involved in attending to more salient stimuli. Hemispheric asymmetries were also found in local/global selection. Overall the results suggest that neural activation in the PPC is related to both the salience and the level of stimulus representations mediating responses to hierarchical stimuli. The comparison of the results from Experiments 1 and 2 in local/global-based selection suggests that the effect of stimulation could be completely opposite depending on subtle differences in demands of attentional control (sustained attention vs task switching).</AbstractText
|
Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography. The characterization of the topological architecture of complex networks underlying the structural and functional organization of the brain is a basic challenge in neuroscience. However, direct evidence for anatomical connectivity networks in the human brain remains scarce. Here, we utilized diffusion tensor imaging deterministic tractography to construct a macroscale anatomical network capturing the underlying common connectivity pattern of human cerebral cortex in a large sample of subjects (80 young adults) and further quantitatively analyzed its topological properties with graph theoretical approaches. The cerebral cortex was divided into 78 cortical regions, each representing a network node, and 2 cortical regions were considered connected if the probability of fiber connections exceeded a statistical criterion. The topological parameters of the established cortical network (binarized) resemble that of a "small-world" architecture characterized by an exponentially truncated power-law distribution. These characteristics imply high resilience to localized damage. Furthermore, this cortical network was characterized by major hub regions in association cortices that were connected by bridge connections following long-range white matter pathways. Our results are compatible with previous structural and functional brain networks studies and provide insight into the organizational principles of human brain anatomical networks that underlie functional states.</AbstractText
|
Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. The possible connection between psoriasis with cardiovascular disease and associated risk factors has been implied, but inconsistent results have been reported.</AbstractText We sought to create an overview and statistical summary of the previous literature with elucidating subgroup analysis.</AbstractText This was a meta-analysis of observational studies using random effect statistics. A systematic search of observational studies of psoriasis as study variable and cardiovascular disease and associated risk factors as outcome, published before October 25, 2012, was conducted.</AbstractText Of 835 references in the original search, 75 relevant articles were identified. We included 503,686 cases and 29,686,694 controls. Psoriasis was associated with cardiovascular disease in total (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.2-1.7), ischemic heart disease (OR 1.5; 95% CI 1.2-1.9), peripheral vascular disease (OR 1.5; 95% CI 1.2-1.8), atherosclerosis (OR 1.1; 95% CI 1.1-1.2), diabetes (OR 1.9; 95% CI 1.5-2.5), hypertension (OR 1.8; 95% CI 1.6-2.0), dyslipidemia (OR 1.5; 95% CI 1.4-1.7), obesity by body mass index (OR 1.8; 95% CI 1.4-2.2), obesity by abdominal fat (OR 1.6; 95% CI 1.2-2.3), and the metabolic syndrome (OR 1.8; 95% CI 1.2-2.8), but not associated with cerebrovascular disease (OR 1.1; 95% CI 0.9-1.3) and cardiovascular mortality (OR 0.9; 95% CI 0.4-2.2). The strongest associations were seen in hospital-based studies and psoriatic arthritis. Population-based studies did not show significant associations, with the exception of dyslipidemia.</AbstractText The heterogeneity of the studies makes clinical interpretation challenging.</AbstractText In aggregate, psoriasis was associated with ischemic heart disease and cardiovascular risk factors. The association was only significant for hospital-based studies, except for dyslipidemia, which was also significant in population-based studies.</AbstractText
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12390981
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29249925
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11859299
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Changes of non-affected upper limb cortical representation in paraplegic patients as assessed by fMRI.
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Determining Excitatory and Inhibitory Neuronal Activity from Multimodal fMRI Data Using a Generative Hemodynamic Model.
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Cardiac MRI: comparison between single-shot fast spin echo and conventional spin echo sequences in the morphological evaluation of the ventricles.
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Peripheral and central nervous system lesions can induce reorganization within central somatosensory and motor body representations. We report changes in brain activation patterns during movements of non-affected body parts in paraplegic patients with spinal cord injury (SCI). Nine SCI patients and 12 healthy controls underwent blood oxygen level dependent signal functional MRI during sequential finger-to-thumb opposition, flexion and extension of wrist and of elbow, and horizontal movements of the tongue. Single subject and group analyses were performed, and the activation volumes, maximum t values and centres of gravity were calculated. The somatotopical upper limb and tongue representations in the contralateral primary motor cortex (M1) in the SCI patients were preserved without any shift of activation towards the deefferented and deafferented M1 foot area. During finger movements, however, the SCI patients showed an increased volume in M1 activation. Increased activation was also found in non-primary motor and parietal areas, as well as in the cerebellum during movements of the fingers, wrist and elbow, whereas no changes were present during tongue movements. These results document that, in paraplegic patients, the representation of the non-impaired upper limb muscles is modified, though without any topographical reorganization in M1. The extensive changes in primary and non-primary motor areas, and in subcortical regions demonstrate that even distant neuronal damage has impact upon the activation of the whole sensorimotor system.</AbstractText
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Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory and inhibitory (E-I) balance between active neuronal populations. Typical BOLD responses exhibit transients, such as the early-overshoot and post-stimulus undershoot, that can be linked to transients in neuronal activity, but they can also result from vascular uncoupling between cerebral blood flow (CBF) and venous cerebral blood volume (venous CBV). Recently, we have proposed a novel generative hemodynamic model of the BOLD signal within the dynamic causal modeling framework, inspired by physiological observations, called P-DCM (Havlicek et al., 2015). We demonstrated the generative model's ability to more accurately model commonly observed neuronal and vascular transients in single regions but also effective connectivity between multiple brain areas (Havlicek et al., 2017b). In this paper, we additionally demonstrate the versatility of the generative model to jointly explain dynamic relationships between neuronal and hemodynamic physiological variables underlying the BOLD signal using multi-modal data. For this purpose, we utilized three distinct data-sets of experimentally induced responses in the primary visual areas measured in human, cat, and monkey brain, respectively: (1) CBF and BOLD responses; (2) CBF, total CBV, and BOLD responses (Jin and Kim, 2008); and (3) positive and negative neuronal and BOLD responses (Shmuel et al., 2006). By fitting the generative model to the three multi-modal experimental data-sets, we showed that the presence or absence of dynamic features in the BOLD signal is not an unambiguous indication of presence or absence of those features on the neuronal level. Nevertheless, the generative model that takes into account the dynamics of the physiological mechanisms underlying the BOLD response allowed dissociating neuronal from vascular transients and deducing excitatory and inhibitory neuronal activity time-courses from BOLD data alone and from multi-modal data.</AbstractText
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Black blood single shot FSE sequences (Nffse) employ 180 degrees RF refocalisation pulses preceded by an inversion RF double pulse associated to presaturation pulses. The latter produce signal void of the external volume, and possible reduction of the field of view without wrap-around artifacts along the phase coding direction. The aim of our study was to compare the diagnostic possibilities of the Nffse sequences with those of conventional SE study of cardiac morphology.</AbstractText Twenty-five patients (19 males and 9 females with age ranging from 20 to 54 years) presented findings suggesting right ventricular arrhythmogenic dysplasia. MR examinations were performed with a 1,5 T unit (GE Signa Horizon Echospeed 8.3, Milwaukee, USA) and Torso Phased Array coil positioned at thoracic level. The morphologic study was performed with SE multiphase-multislice ECG-gated sequences (TR: R-R, TE: 30 ms, FOV 320X250, matrix 160X256, slice thickness 10 mm, acquisition time about 5 minutes) and Single-Shot FSE Half Fourier sequences (TR: R-R, TE: 30 ms, flip angle 120 degrees, ETL 30-40, FOV 360X180, Phase FOV 0,5, VBW 64 MHz, slice tickness 10 mm, acquisition time about 10-12 seconds), by imaging along the long and short axis. The study was completed with Fast Gradient Echo sequences (TR: 9ms, TE: 8,2ms, flip angle 25 degrees, VBW 15,63 MHz, FOV 320X250, 10 mm slice thickness, matrix 128X256), subsequently assessed by cine-MR. In order to compare both sequences, two experienced radiologists performed an analysis of quantitative parameters (signal intensity ratio between fat and muscular interventricular septum) and qualitative parameters (double blind evaluation for the presence of cardiac and respiratory artifacts).</AbstractText The signal intensity ratio for the Nffse sequence images was 4.63 +/- 1.56 on the long axis and 7.69 +/- 2.46 on the short axis, whereas it was 3.17 +/- 0.64 on the long axis and 3,50 +/- 0,75 on the axis one for SE images, with a statistically significant difference (p<0,001 and p<0.002 for the long and short axis, respectively). The two radiologists evaluation of the magnitude of artifacts on the SE and Nffse images was similar only as regards the images with significant artefacts alone. Nffse images consistently afforded a detailed evaluation of the right ventricular wall, although blurring artifacts were more common than with good quality SE images. Presence of fatty infiltration of the right ventricle wall was observed in 5 out of 25 patients. In the remaining 20 patients no fatty substitution of the muscular wall of the right ventricle was observed.</AbstractText The Nffse sequences provide a number of gated multiphase-multislice images, similar to that obtained by conventional SE sequences, in one breath-hold time interval. Due to high intrinsic contrast and reduction of motion artifacts, the Nffse sequences allow a good evaluation of the ventricular morphology and subepicardial and paracardiac adipose tissue. Image quality can be suboptimal due to blurring artifacts. Therefore Nffse sequences can be advantageously employed to image patients with suspected right ventricular arrhythmogenic dysplasia, whenever conventional SE images exhibit substandard quality.</AbstractText
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Changes of non-affected upper limb cortical representation in paraplegic patients as assessed by fMRI. Peripheral and central nervous system lesions can induce reorganization within central somatosensory and motor body representations. We report changes in brain activation patterns during movements of non-affected body parts in paraplegic patients with spinal cord injury (SCI). Nine SCI patients and 12 healthy controls underwent blood oxygen level dependent signal functional MRI during sequential finger-to-thumb opposition, flexion and extension of wrist and of elbow, and horizontal movements of the tongue. Single subject and group analyses were performed, and the activation volumes, maximum t values and centres of gravity were calculated. The somatotopical upper limb and tongue representations in the contralateral primary motor cortex (M1) in the SCI patients were preserved without any shift of activation towards the deefferented and deafferented M1 foot area. During finger movements, however, the SCI patients showed an increased volume in M1 activation. Increased activation was also found in non-primary motor and parietal areas, as well as in the cerebellum during movements of the fingers, wrist and elbow, whereas no changes were present during tongue movements. These results document that, in paraplegic patients, the representation of the non-impaired upper limb muscles is modified, though without any topographical reorganization in M1. The extensive changes in primary and non-primary motor areas, and in subcortical regions demonstrate that even distant neuronal damage has impact upon the activation of the whole sensorimotor system.</AbstractText
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Determining Excitatory and Inhibitory Neuronal Activity from Multimodal fMRI Data Using a Generative Hemodynamic Model. Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory and inhibitory (E-I) balance between active neuronal populations. Typical BOLD responses exhibit transients, such as the early-overshoot and post-stimulus undershoot, that can be linked to transients in neuronal activity, but they can also result from vascular uncoupling between cerebral blood flow (CBF) and venous cerebral blood volume (venous CBV). Recently, we have proposed a novel generative hemodynamic model of the BOLD signal within the dynamic causal modeling framework, inspired by physiological observations, called P-DCM (Havlicek et al., 2015). We demonstrated the generative model's ability to more accurately model commonly observed neuronal and vascular transients in single regions but also effective connectivity between multiple brain areas (Havlicek et al., 2017b). In this paper, we additionally demonstrate the versatility of the generative model to jointly explain dynamic relationships between neuronal and hemodynamic physiological variables underlying the BOLD signal using multi-modal data. For this purpose, we utilized three distinct data-sets of experimentally induced responses in the primary visual areas measured in human, cat, and monkey brain, respectively: (1) CBF and BOLD responses; (2) CBF, total CBV, and BOLD responses (Jin and Kim, 2008); and (3) positive and negative neuronal and BOLD responses (Shmuel et al., 2006). By fitting the generative model to the three multi-modal experimental data-sets, we showed that the presence or absence of dynamic features in the BOLD signal is not an unambiguous indication of presence or absence of those features on the neuronal level. Nevertheless, the generative model that takes into account the dynamics of the physiological mechanisms underlying the BOLD response allowed dissociating neuronal from vascular transients and deducing excitatory and inhibitory neuronal activity time-courses from BOLD data alone and from multi-modal data.</AbstractText
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Cardiac MRI: comparison between single-shot fast spin echo and conventional spin echo sequences in the morphological evaluation of the ventricles. Black blood single shot FSE sequences (Nffse) employ 180 degrees RF refocalisation pulses preceded by an inversion RF double pulse associated to presaturation pulses. The latter produce signal void of the external volume, and possible reduction of the field of view without wrap-around artifacts along the phase coding direction. The aim of our study was to compare the diagnostic possibilities of the Nffse sequences with those of conventional SE study of cardiac morphology.</AbstractText Twenty-five patients (19 males and 9 females with age ranging from 20 to 54 years) presented findings suggesting right ventricular arrhythmogenic dysplasia. MR examinations were performed with a 1,5 T unit (GE Signa Horizon Echospeed 8.3, Milwaukee, USA) and Torso Phased Array coil positioned at thoracic level. The morphologic study was performed with SE multiphase-multislice ECG-gated sequences (TR: R-R, TE: 30 ms, FOV 320X250, matrix 160X256, slice thickness 10 mm, acquisition time about 5 minutes) and Single-Shot FSE Half Fourier sequences (TR: R-R, TE: 30 ms, flip angle 120 degrees, ETL 30-40, FOV 360X180, Phase FOV 0,5, VBW 64 MHz, slice tickness 10 mm, acquisition time about 10-12 seconds), by imaging along the long and short axis. The study was completed with Fast Gradient Echo sequences (TR: 9ms, TE: 8,2ms, flip angle 25 degrees, VBW 15,63 MHz, FOV 320X250, 10 mm slice thickness, matrix 128X256), subsequently assessed by cine-MR. In order to compare both sequences, two experienced radiologists performed an analysis of quantitative parameters (signal intensity ratio between fat and muscular interventricular septum) and qualitative parameters (double blind evaluation for the presence of cardiac and respiratory artifacts).</AbstractText The signal intensity ratio for the Nffse sequence images was 4.63 +/- 1.56 on the long axis and 7.69 +/- 2.46 on the short axis, whereas it was 3.17 +/- 0.64 on the long axis and 3,50 +/- 0,75 on the axis one for SE images, with a statistically significant difference (p<0,001 and p<0.002 for the long and short axis, respectively). The two radiologists evaluation of the magnitude of artifacts on the SE and Nffse images was similar only as regards the images with significant artefacts alone. Nffse images consistently afforded a detailed evaluation of the right ventricular wall, although blurring artifacts were more common than with good quality SE images. Presence of fatty infiltration of the right ventricle wall was observed in 5 out of 25 patients. In the remaining 20 patients no fatty substitution of the muscular wall of the right ventricle was observed.</AbstractText The Nffse sequences provide a number of gated multiphase-multislice images, similar to that obtained by conventional SE sequences, in one breath-hold time interval. Due to high intrinsic contrast and reduction of motion artifacts, the Nffse sequences allow a good evaluation of the ventricular morphology and subepicardial and paracardiac adipose tissue. Image quality can be suboptimal due to blurring artifacts. Therefore Nffse sequences can be advantageously employed to image patients with suspected right ventricular arrhythmogenic dysplasia, whenever conventional SE images exhibit substandard quality.</AbstractText
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39980738
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39629040
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40662273
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Navigating neural pathways: how stimulation polarity shapes deep brain stimulation efficacy.
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Deciphering pain: molecular mechanisms and neurochemical pathways-challenges and future opportunities.
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Mannose Oligosaccharide-Conjugated In Situ Pore-Forming Injectable Hydrogels for Rheumatoid Arthritis Treatment by Reprogramming Macrophage Extracellular Vesicles.
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This scientific commentary refers to 'Neural pathway activation in the subthalamic region depends on stimulation polarity' by Borgheai <i
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This review delves into the intricate biological underpinnings of pain perception. It encompasses nociceptive signaling pathways, the molecular mechanisms involved, and the subjective experience of discomfort in humans. The initial focus is on nociceptor transduction, where specialized neurons transform noxious stimuli into electrical impulses. Subsequently, the review explores the central nervous system, elucidating how these signals are processed and modulated by critical elements such as ion channels, receptors, and neurotransmitters (e.g., substance P, glutamate, GABA). Shifting gears toward chronic pain, the review examines the concept of neuroplasticity, highlighting its potential to induce maladaptive responses through alterations in neural networks. The burgeoning field of pain genomics, alongside established genetic research, offers valuable insights that could pave the way for a framework of personalized pain management strategies. Finally, the review emphasizes the significance of these molecular insights in facilitating accurate therapeutic interventions. The overarching objective is to establish an integrative framework for precision medicine in pain management by incorporating this information alongside biopsychosocial models. This framework serves to translate the heterogeneous landscape of pain mechanisms into a coherent roadmap for the development of effective therapies.</AbstractText
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Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes severe cartilage erosion in joints. Current treatments are limited in accessing a 3D platform that not only supports chondrocyte recovery and new cartilage matrix formation but also effectively modulates the inflammatory environment, particularly through macrophage regulation and extracellular vesicle (EV)-mediated functions. Here, an injectable hydrogel is developed incorporating mannose oligosaccharide (MOS)-modified chondroitin sulfate and hyaluronic. This hydrogel forms a porous structure in situ, supporting cell adhesion and matrix production. The MOS groups grafted onto the hydrogel bind to CD206 receptors of macrophages, selectively recruiting and regulating M2 macrophages over an extended period. These macrophages, in turn, release EVs with potent anti-inflammatory properties, which support new cartilage formation and preservation. This innovative approach addresses a critical gap in RA treatment, offering a novel, cost-effective, and efficient tissue-engineering solution with the potential to significantly improve patient outcomes and quality of life.</AbstractText
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Navigating neural pathways: how stimulation polarity shapes deep brain stimulation efficacy. This scientific commentary refers to 'Neural pathway activation in the subthalamic region depends on stimulation polarity' by Borgheai <i
|
Deciphering pain: molecular mechanisms and neurochemical pathways-challenges and future opportunities. This review delves into the intricate biological underpinnings of pain perception. It encompasses nociceptive signaling pathways, the molecular mechanisms involved, and the subjective experience of discomfort in humans. The initial focus is on nociceptor transduction, where specialized neurons transform noxious stimuli into electrical impulses. Subsequently, the review explores the central nervous system, elucidating how these signals are processed and modulated by critical elements such as ion channels, receptors, and neurotransmitters (e.g., substance P, glutamate, GABA). Shifting gears toward chronic pain, the review examines the concept of neuroplasticity, highlighting its potential to induce maladaptive responses through alterations in neural networks. The burgeoning field of pain genomics, alongside established genetic research, offers valuable insights that could pave the way for a framework of personalized pain management strategies. Finally, the review emphasizes the significance of these molecular insights in facilitating accurate therapeutic interventions. The overarching objective is to establish an integrative framework for precision medicine in pain management by incorporating this information alongside biopsychosocial models. This framework serves to translate the heterogeneous landscape of pain mechanisms into a coherent roadmap for the development of effective therapies.</AbstractText
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Mannose Oligosaccharide-Conjugated In Situ Pore-Forming Injectable Hydrogels for Rheumatoid Arthritis Treatment by Reprogramming Macrophage Extracellular Vesicles. Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes severe cartilage erosion in joints. Current treatments are limited in accessing a 3D platform that not only supports chondrocyte recovery and new cartilage matrix formation but also effectively modulates the inflammatory environment, particularly through macrophage regulation and extracellular vesicle (EV)-mediated functions. Here, an injectable hydrogel is developed incorporating mannose oligosaccharide (MOS)-modified chondroitin sulfate and hyaluronic. This hydrogel forms a porous structure in situ, supporting cell adhesion and matrix production. The MOS groups grafted onto the hydrogel bind to CD206 receptors of macrophages, selectively recruiting and regulating M2 macrophages over an extended period. These macrophages, in turn, release EVs with potent anti-inflammatory properties, which support new cartilage formation and preservation. This innovative approach addresses a critical gap in RA treatment, offering a novel, cost-effective, and efficient tissue-engineering solution with the potential to significantly improve patient outcomes and quality of life.</AbstractText
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32611113
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28473644
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33266296
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Synchronization of extreme rainfall during the Australian summer monsoon: Complex network perspectives.
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Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.
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Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of the CD44 Gene.
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Monsoon rains are an important fresh water supply for agricultural activity, while extreme rainfalls during a monsoon season frequently cause flash floods. In this study, a nonlinear causation measure of event synchronization is used to set complex networks of extreme rainfall during the Australian summer monsoon (ASM) development between 1st November and 1st March. We adopted Tropical Rainfall Measuring Mission-based satellite rain rate estimates from 1998 to 2015. Examining several standard network centrality measures, such as degree and local clustering, we revealed the multiscale nature of ASM development, which previously was only studied by weather analysis methods. The land-sea contrast in surface heating critical for ASM is depicted clearly by the degree centrality. In addition, both the clustering coefficient and the community structure show critical change in spatial pattern matching with the climatological average onset time of the ASM during late December. The former is likely related to the interaction between synoptic forcing and mesoscale convection during monsoon onset, resulting in characteristic changes in the rainfall field. One of the network communities also extends spatially during the onset, revealing critical information from the near-equatorial region to ASM and would be applicable to monitor monsoon development. Results from this study further support that network measures as defined by a single parameter of rainfall have enormous potential for monsoon onset prediction.</AbstractText
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Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation.<b
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Splicing reporter minigenes are used in cell-based in vitro splicing studies. Exon skippable antisense oligonucleotide (ASO) has been identified using minigene splicing assays, but these assays include a time- and cost-consuming step of reverse transcription PCR amplification. To make in vitro splicing assay easier, a ready-made minigene (FMv2) amenable to quantitative splicing analysis by fluorescence microscopy was constructed. FMv2 was designed to encode two fluorescence proteins namely, mCherry, a transfection marker and split eGFP, a marker of splicing reaction. The split eGFP was intervened by an artificial intron containing a multicloning site sequence. Expectedly, FMv2 transfected HeLa cells produced not only red mCherry but also green eGFP signals. Transfection of FMv2<i
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Synchronization of extreme rainfall during the Australian summer monsoon: Complex network perspectives. Monsoon rains are an important fresh water supply for agricultural activity, while extreme rainfalls during a monsoon season frequently cause flash floods. In this study, a nonlinear causation measure of event synchronization is used to set complex networks of extreme rainfall during the Australian summer monsoon (ASM) development between 1st November and 1st March. We adopted Tropical Rainfall Measuring Mission-based satellite rain rate estimates from 1998 to 2015. Examining several standard network centrality measures, such as degree and local clustering, we revealed the multiscale nature of ASM development, which previously was only studied by weather analysis methods. The land-sea contrast in surface heating critical for ASM is depicted clearly by the degree centrality. In addition, both the clustering coefficient and the community structure show critical change in spatial pattern matching with the climatological average onset time of the ASM during late December. The former is likely related to the interaction between synoptic forcing and mesoscale convection during monsoon onset, resulting in characteristic changes in the rainfall field. One of the network communities also extends spatially during the onset, revealing critical information from the near-equatorial region to ASM and would be applicable to monitor monsoon development. Results from this study further support that network measures as defined by a single parameter of rainfall have enormous potential for monsoon onset prediction.</AbstractText
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Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan. Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation.<b
|
Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of the CD44 Gene. Splicing reporter minigenes are used in cell-based in vitro splicing studies. Exon skippable antisense oligonucleotide (ASO) has been identified using minigene splicing assays, but these assays include a time- and cost-consuming step of reverse transcription PCR amplification. To make in vitro splicing assay easier, a ready-made minigene (FMv2) amenable to quantitative splicing analysis by fluorescence microscopy was constructed. FMv2 was designed to encode two fluorescence proteins namely, mCherry, a transfection marker and split eGFP, a marker of splicing reaction. The split eGFP was intervened by an artificial intron containing a multicloning site sequence. Expectedly, FMv2 transfected HeLa cells produced not only red mCherry but also green eGFP signals. Transfection of FMv2<i
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40492100
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32638873
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40388021
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Genetic and environmental effects on weight gain from young adulthood to old age and its association with body mass index at early young adulthood: an individual-based pooled analysis of 16 twin cohorts.
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[Health of adolescents in the 1997/1998 birth cohort in São Luís, Maranhão State, Brazil].
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Differential response by tandem leaders and followers to landmark-rich and landmark-poor environments.
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Genetic factors contribute to weight gain, but how these effects change over adulthood is still unknown. We studied the impact of genetics on BMI change from young adulthood to old age and its relationship with BMI in early young adulthood.</AbstractText Data from 16 longitudinal twin cohorts, including 111,370 adults (56% women) and 55,657 complete twin pairs (42% monozygotic), were pooled. The data were divided into three stages (young adulthood-early middle age, late middle age, and old age). BMI change was calculated using linear mixed effects and delta slope methods. Genetic and environmental contributions to these changes and their correlations with baseline BMI were estimated through structural equation modeling.</AbstractText The average BMI increase per year was 0.18 kg/m<sup Genetics influence BMI change across adulthood, with their impact varying by age and sex. Environmental factors are the main drivers of adult BMI change, highlighting the role of modifiable factors in long-term weight regulation.</AbstractText
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The study aimed to estimate the prevalence of health indicators among adolescents in São Luís, Maranhão State, Brazil, in 2016. The analysis included sociodemographic conditions, life habits, body composition, sleep quality, physical activity, cognitive performance, and suicide risk in 2,515 adolescents 18 to 19 years of age. The adolescents belonged to the 1997/1998 birth cohort or were included retrospectively using the SINASC (Brazilian Information System on Live Births) database. The adolescents were mainly from economic class C (50.1%), 69.5% were in school, 40.3% were working, and 25.2% were neither studying nor working; 60.3% had been robbed, and 48.7% had parents who were separated or divorced; 19.4% showed harmful or excessive alcohol consumption or probable addiction, 19.1% had used or were using illicit drugs, 53.7% reported poor sleep quality, 40.8% reported frequent headaches, 34.3% reported more than five hours of daily screen time, and 4.1% showed high suicide risk. Prevalence of high blood pressure was 12%, and 6% were obese. Girls were more physically inactive (80.7%) and showed greater percentage of high (15.8%) and very high body fat (21.5%), while boys showed greater prevalence of high blood pressure (21.2%) and lower prevalence of physical inactivity (40.9%). High prevalence rates of health risk factors increase the adolescents' vulnerability, exposing these individuals earlier to factors leading to diseases and other health problems.</AbstractText
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When animals use the same route repeatedly, they have the opportunity to update information that might help them to navigate more quickly and more accurately. Here we analyse ants involved in tandem running, in which the leader has evaluated a new nest and decided to recruit to it while the follower has chosen to be led and shown the route. We used a motorised gantry equipped with a camera to track the movements of tandem members on their tandem and return trips in a landmark-rich and a landmark-poor environment. Although the amount of visual navigational information did not affect the movements of leaders or followers on their tandem trip, the paths of followers were significantly more tortuous and their speeds significantly slower than those of leaders on their return trips in the landmark-poor environment. By contrast, there were no such differences between the followers and leaders on their return trips in the landmark-rich environment even though the return paths of followers in the landmark-rich environment were significantly more tortuous than that of leaders in the landmark-poor environment. Indeed, in the landmark-rich environment, the majority of the leaders' return paths had loops while most were straight in the landmark-poor environment. Thus, the availability of more information when many landmarks are present may induce tandem leaders to make the loops, typically associated with the paths of tandem followers. This suggests knowledgeable individuals slow down to update navigational information and has implications for the formation of leader oligarchies in tandem running.</AbstractText
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Genetic and environmental effects on weight gain from young adulthood to old age and its association with body mass index at early young adulthood: an individual-based pooled analysis of 16 twin cohorts. Genetic factors contribute to weight gain, but how these effects change over adulthood is still unknown. We studied the impact of genetics on BMI change from young adulthood to old age and its relationship with BMI in early young adulthood.</AbstractText Data from 16 longitudinal twin cohorts, including 111,370 adults (56% women) and 55,657 complete twin pairs (42% monozygotic), were pooled. The data were divided into three stages (young adulthood-early middle age, late middle age, and old age). BMI change was calculated using linear mixed effects and delta slope methods. Genetic and environmental contributions to these changes and their correlations with baseline BMI were estimated through structural equation modeling.</AbstractText The average BMI increase per year was 0.18 kg/m<sup Genetics influence BMI change across adulthood, with their impact varying by age and sex. Environmental factors are the main drivers of adult BMI change, highlighting the role of modifiable factors in long-term weight regulation.</AbstractText
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[Health of adolescents in the 1997/1998 birth cohort in São Luís, Maranhão State, Brazil]. The study aimed to estimate the prevalence of health indicators among adolescents in São Luís, Maranhão State, Brazil, in 2016. The analysis included sociodemographic conditions, life habits, body composition, sleep quality, physical activity, cognitive performance, and suicide risk in 2,515 adolescents 18 to 19 years of age. The adolescents belonged to the 1997/1998 birth cohort or were included retrospectively using the SINASC (Brazilian Information System on Live Births) database. The adolescents were mainly from economic class C (50.1%), 69.5% were in school, 40.3% were working, and 25.2% were neither studying nor working; 60.3% had been robbed, and 48.7% had parents who were separated or divorced; 19.4% showed harmful or excessive alcohol consumption or probable addiction, 19.1% had used or were using illicit drugs, 53.7% reported poor sleep quality, 40.8% reported frequent headaches, 34.3% reported more than five hours of daily screen time, and 4.1% showed high suicide risk. Prevalence of high blood pressure was 12%, and 6% were obese. Girls were more physically inactive (80.7%) and showed greater percentage of high (15.8%) and very high body fat (21.5%), while boys showed greater prevalence of high blood pressure (21.2%) and lower prevalence of physical inactivity (40.9%). High prevalence rates of health risk factors increase the adolescents' vulnerability, exposing these individuals earlier to factors leading to diseases and other health problems.</AbstractText
|
Differential response by tandem leaders and followers to landmark-rich and landmark-poor environments. When animals use the same route repeatedly, they have the opportunity to update information that might help them to navigate more quickly and more accurately. Here we analyse ants involved in tandem running, in which the leader has evaluated a new nest and decided to recruit to it while the follower has chosen to be led and shown the route. We used a motorised gantry equipped with a camera to track the movements of tandem members on their tandem and return trips in a landmark-rich and a landmark-poor environment. Although the amount of visual navigational information did not affect the movements of leaders or followers on their tandem trip, the paths of followers were significantly more tortuous and their speeds significantly slower than those of leaders on their return trips in the landmark-poor environment. By contrast, there were no such differences between the followers and leaders on their return trips in the landmark-rich environment even though the return paths of followers in the landmark-rich environment were significantly more tortuous than that of leaders in the landmark-poor environment. Indeed, in the landmark-rich environment, the majority of the leaders' return paths had loops while most were straight in the landmark-poor environment. Thus, the availability of more information when many landmarks are present may induce tandem leaders to make the loops, typically associated with the paths of tandem followers. This suggests knowledgeable individuals slow down to update navigational information and has implications for the formation of leader oligarchies in tandem running.</AbstractText
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34924093
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24759798
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37928304
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Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing.
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Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders.
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Retroperitoneal capillary arteriovenous malformation mimicking a malignant neoplasm.
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Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (<i
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Brain neuroimaging has been widely used to investigate the bran signature of chronic orofacial pain, including trigeminal neuropathic pain (TNP) and pain related to temporomandibular joint disorders (TMD). We here systematically reviewed the neuroimaging literature regarding the functional and structural changes in the brain of TNP and TMD pain patients, using a computerized search of journal articles via PubMed. Ten TNP studies and 14 TMD studies were reviewed. Study quality and risk of bias were assessed based on the criteria of patient selection, the history of medication, the use of standardized pain/psychological assessments, and the model and statistics of imaging analyses. Qualitative meta-analysis was performed by examining the brain regions which showed significant changes in either brain functions (including the blood-oxygen-level dependent signal, cerebral blood flow and the magnetic resonance spectroscopy signal) or brain structure (including gray matter and white matter anatomy). We hypothesized that the neuroimaging findings would display a common pattern as well as distinct patterns of brain signature in the disorders. This major hypothesis was supported by the following findings: (1) TNP and TMD patients showed consistent functional/structural changes in the thalamus and the primary somatosensory cortex, indicating the thalamocortical pathway as the major site of plasticity. (2) The TNP patients showed more alterations at the thalamocortical pathway, and the two disorders showed distinct patterns of thalamic and insular connectivity. Additionally, functional and structural changes were frequently reported in the prefrontal cortex and the basal ganglia, suggesting the role of cognitive modulation and reward processing in chronic orofacial pain. The findings highlight the potential for brain neuroimaging as an investigating tool for understanding chronic orofacial pain.</AbstractText
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Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations.</AbstractText A 72-year-old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27-mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast-enhanced computed tomography revealed a heterogeneously enhanced tumor with well-defined borders. Dynamic contrast-enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling-in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation.</AbstractText Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.</AbstractText
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Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing. Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (<i
|
Brain signature of chronic orofacial pain: a systematic review and meta-analysis on neuroimaging research of trigeminal neuropathic pain and temporomandibular joint disorders. Brain neuroimaging has been widely used to investigate the bran signature of chronic orofacial pain, including trigeminal neuropathic pain (TNP) and pain related to temporomandibular joint disorders (TMD). We here systematically reviewed the neuroimaging literature regarding the functional and structural changes in the brain of TNP and TMD pain patients, using a computerized search of journal articles via PubMed. Ten TNP studies and 14 TMD studies were reviewed. Study quality and risk of bias were assessed based on the criteria of patient selection, the history of medication, the use of standardized pain/psychological assessments, and the model and statistics of imaging analyses. Qualitative meta-analysis was performed by examining the brain regions which showed significant changes in either brain functions (including the blood-oxygen-level dependent signal, cerebral blood flow and the magnetic resonance spectroscopy signal) or brain structure (including gray matter and white matter anatomy). We hypothesized that the neuroimaging findings would display a common pattern as well as distinct patterns of brain signature in the disorders. This major hypothesis was supported by the following findings: (1) TNP and TMD patients showed consistent functional/structural changes in the thalamus and the primary somatosensory cortex, indicating the thalamocortical pathway as the major site of plasticity. (2) The TNP patients showed more alterations at the thalamocortical pathway, and the two disorders showed distinct patterns of thalamic and insular connectivity. Additionally, functional and structural changes were frequently reported in the prefrontal cortex and the basal ganglia, suggesting the role of cognitive modulation and reward processing in chronic orofacial pain. The findings highlight the potential for brain neuroimaging as an investigating tool for understanding chronic orofacial pain.</AbstractText
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Retroperitoneal capillary arteriovenous malformation mimicking a malignant neoplasm. Retroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations.</AbstractText A 72-year-old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27-mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast-enhanced computed tomography revealed a heterogeneously enhanced tumor with well-defined borders. Dynamic contrast-enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling-in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation.</AbstractText Herein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.</AbstractText
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38988761
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36012029
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38684900
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Therapeutic Efficacy of Mirogabalin in managing Trigeminal Neuralgia.
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"No One Truly Understands What We Go through and How to Treat It": Lived Experiences with Medical Providers among Patients with Orofacial Pain.
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A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.
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Trigeminal neuralgia presents significant challenges in management, often requiring alternative pharmacotherapy due to resistance or side effects to first-line medications like carbamazepine. This case series investigates the efficacy and safety of mirogabalin, a novel α2δ ligand, in six trigeminal neuralgia patients. Mirogabalin demonstrated varying degrees of pain reduction, with an average Numerical Rating Scale improvement rate of 43.1%. Side effects were generally mild, with drowsiness and dizziness being the most common. Despite limited efficacy in some cases, mirogabalin shows promise as a potential treatment option for trigeminal neuralgia, warranting further investigation. <b
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Orofacial pain affects 10-15% of adults, yet treatments are limited. The gaps in care are frustrating for both patients and providers and can negatively impact patient-provider interactions. These interactions are key because they impact patient-reported outcomes and satisfaction with care.</AbstractText Our study aims to understand the nuanced experiences with medical providers among patients with orofacial pain.</AbstractText In a cross-sectional survey, 260 patients provided written responses describing their experiences with medical providers. Using an inductive-deductive approach to thematic analysis, we identified themes and subthemes and organized them into four domains based on the Patient-Centered Model of Communication.</AbstractText Patients reported feeling hopeless about treatment options, frustrated with lack of provider knowledge, disappointed in ineffective care, and stigmatized and dismissed by providers. Patients also said they learned to advocate for their health, were grateful for effective care, and felt lucky when providers listened and showed compassion. Patients identified key barriers that interfere with care (e.g., insurance, transportation, limited providers, lack of team coordination).</AbstractText Findings can help inform training programs and psychoeducation that target patient-provider communication to improve patient-reported outcomes, the quality of care delivered, and health care utilization and costs.</AbstractText
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Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees. Ultrarare DNA variants near the repeat expansion indicate a common distant founder event in Sweden. Intranuclear ZFHX3-p62-ubiquitin aggregates were abundant in SCA4 basis pontis neurons. In fibroblasts and induced pluripotent stem cells, the GGC expansion led to increased ZFHX3 protein levels and abnormal autophagy, which were normalized with small interfering RNA-mediated ZFHX3 knockdown in both cell types. Improving autophagy points to a therapeutic avenue for this novel polyG disease. The coding GGC-repeat expansion in an extremely G+C-rich region was not detectable by short-read whole-exome sequencing, which demonstrates the power of LR-GS for variant discovery.</AbstractText
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Therapeutic Efficacy of Mirogabalin in managing Trigeminal Neuralgia. Trigeminal neuralgia presents significant challenges in management, often requiring alternative pharmacotherapy due to resistance or side effects to first-line medications like carbamazepine. This case series investigates the efficacy and safety of mirogabalin, a novel α2δ ligand, in six trigeminal neuralgia patients. Mirogabalin demonstrated varying degrees of pain reduction, with an average Numerical Rating Scale improvement rate of 43.1%. Side effects were generally mild, with drowsiness and dizziness being the most common. Despite limited efficacy in some cases, mirogabalin shows promise as a potential treatment option for trigeminal neuralgia, warranting further investigation. <b
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"No One Truly Understands What We Go through and How to Treat It": Lived Experiences with Medical Providers among Patients with Orofacial Pain. Orofacial pain affects 10-15% of adults, yet treatments are limited. The gaps in care are frustrating for both patients and providers and can negatively impact patient-provider interactions. These interactions are key because they impact patient-reported outcomes and satisfaction with care.</AbstractText Our study aims to understand the nuanced experiences with medical providers among patients with orofacial pain.</AbstractText In a cross-sectional survey, 260 patients provided written responses describing their experiences with medical providers. Using an inductive-deductive approach to thematic analysis, we identified themes and subthemes and organized them into four domains based on the Patient-Centered Model of Communication.</AbstractText Patients reported feeling hopeless about treatment options, frustrated with lack of provider knowledge, disappointed in ineffective care, and stigmatized and dismissed by providers. Patients also said they learned to advocate for their health, were grateful for effective care, and felt lucky when providers listened and showed compassion. Patients identified key barriers that interfere with care (e.g., insurance, transportation, limited providers, lack of team coordination).</AbstractText Findings can help inform training programs and psychoeducation that target patient-provider communication to improve patient-reported outcomes, the quality of care delivered, and health care utilization and costs.</AbstractText
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A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy. Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees. Ultrarare DNA variants near the repeat expansion indicate a common distant founder event in Sweden. Intranuclear ZFHX3-p62-ubiquitin aggregates were abundant in SCA4 basis pontis neurons. In fibroblasts and induced pluripotent stem cells, the GGC expansion led to increased ZFHX3 protein levels and abnormal autophagy, which were normalized with small interfering RNA-mediated ZFHX3 knockdown in both cell types. Improving autophagy points to a therapeutic avenue for this novel polyG disease. The coding GGC-repeat expansion in an extremely G+C-rich region was not detectable by short-read whole-exome sequencing, which demonstrates the power of LR-GS for variant discovery.</AbstractText
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40236719
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12670672
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40552686
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Explicit Motor Imaging Abilities Are Similar in Complex Regional Pain Syndrome, Chronic Limb Pain and Healthy Individuals: A Cross-Sectional Study.
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The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study.
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Comparing Folic Acid Interventions and Arsenic Reduction Strategies for Neural Tube Defect Prevention in Bangladesh: A Systematic Review and Decision Analysis.
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Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by peripheral, central sensory and motor dysfunction. Implicit motor imagery is known to be impaired in CRPS patients, but evidence for explicit motor imagery is still lacking. Using a self-rated questionnaire, this study aims to compare explicit motor imagery abilities between individuals with CRPS, with chronic limb pain (CLP), and healthy controls, and to also examine differences between affected and unaffected limbs. We hypothesize that both CRPS and CLP patients will show a decrease in motor imagery abilities compared to healthy controls and in their affected limb compared to their own contralateral, unaffected side.</AbstractText In this single-center observational study, 123 participants were recruited (CRPS = 40, chronic limb pain, CLP = 40, and healthy individuals = 43). Participants completed the Movement Imagery Questionnaire-Revised Second (MIQ-RS) once for each side of the body. The total MIQ<i A high degree of heterogeneity was observed in the explicit motor imagery scores and subscores, regardless of whether the participants were healthy or individuals with chronic pain. The MIQ<i Individuals with CRPS and chronic limb pain displayed preserved explicit motor imagery abilities, notably on the pain side. The preservation of these abilities supports the recommendation of mental imagery therapy to improve motor function and relieve pain in chronic pain patients.</AbstractText
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To compare the effects of two free radical scavengers, dimethylsulfoxide 50% (DMSO) and N-acetylcysteine (NAC), for treatment of complex regional pain syndrome I (CRPS I), a randomized, double-dummy controlled, double-blind trial was conducted. Two outpatient clinics of two university hospitals in The Netherlands participated in the study and 146 patients, were included over a period of 24 months. Patients were randomized into two treatment groups, one was instructed to apply DMSO 50% five times daily to the affected extremity, the second was treated with NAC 600mg effervescent tablets three times daily, both combined with placebo. Interventions were accompanied by pain medication, occupational therapy for upper extremity CRPS I and physical therapy for lower extremity CRPS I in specific circumstances. Treatment was given for 17 weeks, with a possibility to continue or switch medication after this period, up to 1 year following the onset of treatment. An impairment level sum score was the primary outcome measure. Upper and lower extremity skills and functions, and general health status were also evaluated. Overall, no significant differences were found between NAC and DMSO after 17 and 52 weeks on impairment level and general health status. Significant differences were found for subscores of lower extremity function, in favor of DMSO-treatment. Subgroup analysis showed more favorable results for DMSO for warm CRPS I and significantly better performance of NAC for patients with a cold CRPS I. Results tended to be negatively influenced if the duration of the complaint was longer. Treatment with DMSO and NAC are generally equally effective in treatment of CRPS I. Strong indications exist for differences in effects for subgroups of patients with warm or cold CRPS I: for warm CRPS I, DMSO-treatment appears more favorable, while for cold CRPS I, NAC-treatment appears to be more effective.</AbstractText
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Maternal intake of folic acid prevents most cases of neural tube defects (NTDs), and arsenic exposure may increase NTD risk. In Bangladesh, where arsenic exposures are high, understanding the potential impacts of arsenic reduction and folic acid-based interventions can guide decision-making.</AbstractText We conducted a systematic review and meta-analysis to estimate the prevalence of NTDs in Bangladesh. We searched PubMed, Embase, Web of Science, Global Health, and Bangladesh Journals Online and extracted data using standardized forms. We used forest plots and random effects models to estimate the prevalence of all NTDs and spina bifida. Decision analysis used assumptions from the literature to compare expected NTD prevalence under strategies incorporating combinations of folic acid supplementation, fortification, and arsenic filters. Sensitivity analyses aimed to quantify the influence of adherence to supplements on estimates.</AbstractText Eleven studies were included. Prevalences of NTD and spina bifida were 27.4 and 11.2 per 10,000 births, respectively; however, when estimated from population red blood cell folate concentrations, NTD prevalence was higher in both high arsenic exposure (drinking water ≥ 50 μg/L) and lower arsenic exposure groups (34.3 and 25.3 per 10,000 births, respectively). Folic acid fortification reduced the prevalence of NTDs to 11.1 and 9.1 per 10,000 births among high exposure and low exposure groups, respectively. Arsenic filters provided little marginal benefit. Benefits of supplements equaled those of fortification when adherence to supplements exceeded 90%.</AbstractText Bangladesh has high rates of NTDs and high arsenic exposures. Folic acid fortification is projected to be the most effective strategy for NTD prevention.</AbstractText
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Explicit Motor Imaging Abilities Are Similar in Complex Regional Pain Syndrome, Chronic Limb Pain and Healthy Individuals: A Cross-Sectional Study. Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by peripheral, central sensory and motor dysfunction. Implicit motor imagery is known to be impaired in CRPS patients, but evidence for explicit motor imagery is still lacking. Using a self-rated questionnaire, this study aims to compare explicit motor imagery abilities between individuals with CRPS, with chronic limb pain (CLP), and healthy controls, and to also examine differences between affected and unaffected limbs. We hypothesize that both CRPS and CLP patients will show a decrease in motor imagery abilities compared to healthy controls and in their affected limb compared to their own contralateral, unaffected side.</AbstractText In this single-center observational study, 123 participants were recruited (CRPS = 40, chronic limb pain, CLP = 40, and healthy individuals = 43). Participants completed the Movement Imagery Questionnaire-Revised Second (MIQ-RS) once for each side of the body. The total MIQ<i A high degree of heterogeneity was observed in the explicit motor imagery scores and subscores, regardless of whether the participants were healthy or individuals with chronic pain. The MIQ<i Individuals with CRPS and chronic limb pain displayed preserved explicit motor imagery abilities, notably on the pain side. The preservation of these abilities supports the recommendation of mental imagery therapy to improve motor function and relieve pain in chronic pain patients.</AbstractText
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The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study. To compare the effects of two free radical scavengers, dimethylsulfoxide 50% (DMSO) and N-acetylcysteine (NAC), for treatment of complex regional pain syndrome I (CRPS I), a randomized, double-dummy controlled, double-blind trial was conducted. Two outpatient clinics of two university hospitals in The Netherlands participated in the study and 146 patients, were included over a period of 24 months. Patients were randomized into two treatment groups, one was instructed to apply DMSO 50% five times daily to the affected extremity, the second was treated with NAC 600mg effervescent tablets three times daily, both combined with placebo. Interventions were accompanied by pain medication, occupational therapy for upper extremity CRPS I and physical therapy for lower extremity CRPS I in specific circumstances. Treatment was given for 17 weeks, with a possibility to continue or switch medication after this period, up to 1 year following the onset of treatment. An impairment level sum score was the primary outcome measure. Upper and lower extremity skills and functions, and general health status were also evaluated. Overall, no significant differences were found between NAC and DMSO after 17 and 52 weeks on impairment level and general health status. Significant differences were found for subscores of lower extremity function, in favor of DMSO-treatment. Subgroup analysis showed more favorable results for DMSO for warm CRPS I and significantly better performance of NAC for patients with a cold CRPS I. Results tended to be negatively influenced if the duration of the complaint was longer. Treatment with DMSO and NAC are generally equally effective in treatment of CRPS I. Strong indications exist for differences in effects for subgroups of patients with warm or cold CRPS I: for warm CRPS I, DMSO-treatment appears more favorable, while for cold CRPS I, NAC-treatment appears to be more effective.</AbstractText
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Comparing Folic Acid Interventions and Arsenic Reduction Strategies for Neural Tube Defect Prevention in Bangladesh: A Systematic Review and Decision Analysis. Maternal intake of folic acid prevents most cases of neural tube defects (NTDs), and arsenic exposure may increase NTD risk. In Bangladesh, where arsenic exposures are high, understanding the potential impacts of arsenic reduction and folic acid-based interventions can guide decision-making.</AbstractText We conducted a systematic review and meta-analysis to estimate the prevalence of NTDs in Bangladesh. We searched PubMed, Embase, Web of Science, Global Health, and Bangladesh Journals Online and extracted data using standardized forms. We used forest plots and random effects models to estimate the prevalence of all NTDs and spina bifida. Decision analysis used assumptions from the literature to compare expected NTD prevalence under strategies incorporating combinations of folic acid supplementation, fortification, and arsenic filters. Sensitivity analyses aimed to quantify the influence of adherence to supplements on estimates.</AbstractText Eleven studies were included. Prevalences of NTD and spina bifida were 27.4 and 11.2 per 10,000 births, respectively; however, when estimated from population red blood cell folate concentrations, NTD prevalence was higher in both high arsenic exposure (drinking water ≥ 50 μg/L) and lower arsenic exposure groups (34.3 and 25.3 per 10,000 births, respectively). Folic acid fortification reduced the prevalence of NTDs to 11.1 and 9.1 per 10,000 births among high exposure and low exposure groups, respectively. Arsenic filters provided little marginal benefit. Benefits of supplements equaled those of fortification when adherence to supplements exceeded 90%.</AbstractText Bangladesh has high rates of NTDs and high arsenic exposures. Folic acid fortification is projected to be the most effective strategy for NTD prevention.</AbstractText
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40325749
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38969091
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39925712
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Multifactorial balance rehabilitation in diabetic neuropathy elders: Randomized controlled trial.
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Targeting neuroinflammation in distal symmetrical polyneuropathy in diabetes.
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Realistic extension of partial-body pediatric CT for whole-body organ dose estimation in radiotherapy patients.
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Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, particularly affecting the elderly and increasing their risk of falls due to impaired balance. This study investigates the effect of a multifactorial balance rehabilitation program on postural stability, fall risk, and quality of life in elderly individuals with DPN.</AbstractText In a randomized controlled trial, 150 elderly participants (aged 60-80) diagnosed with DPN were enrolled. Comprehensive demographic data were collected, diabetic foot assessments were performed, and key outcome measures included postural sway parameters, fall risk, and quality of life. Participants were randomly assigned to two groups: the study group underwent a 12-week multifactorial balance rehabilitation program (3-5 days a week), while the control group received standard medical care and advice.</AbstractText The study identified statistically significant improvements in postural sway parameters (AP sway Z = -3.16, ML sway Z = -2.20, COP length Z = -6.27, COP area Z = -2.25), a substantial reduction in fall risk (F (1, 134) = 263.42), and enhanced quality of life, as measured by physical health domain of WHOQOL-BREF (D1F (1, 134) = 3.94) and MDQoL 17 (F (1, 134) = 7.67), among the study group participants (p < .05).</AbstractText Following the 12-week multifactorial balance rehabilitation program, participants in the study group demonstrated notable improvements in postural stability, reduced risk of falls, and improved quality of life compared to the control group.</AbstractText
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Diabetic distal symmetric polyneuropathy is the most common type of peripheral neuropathy complication of diabetes mellitus. Neuroinflammation is emerging as an important contributor to diabetes-induced neuropathy. Long-term hyperglycemia results in increased production of advanced glycation end products (AGEs). AGEs interact with their receptors to activate intracellular signaling, leading to the release of various inflammatory cytokines. Increased release of inflammatory cytokines is associated with diabetes, diabetic neuropathy, and neuropathic pain. Thus, anti-inflammatory intervention is a potential therapy for diabetic distal symmetric polyneuropathy. Further characterization of inflammatory mechanisms might identify novel therapeutic targets to mitigate diabetic neuropathy.</AbstractText
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While modern radiotherapy treatments can deliver a localized radiation dose to the tumor, healthy tissues at distance are inevitably exposed to scatter radiation that has been linked to late health effects such as second cancers. Quantifying the radiation dose received by tissues beyond the target is critical for research on such late health effects. However, the typical radiotherapy planning CT only covers part of the body near the target and the organs of interest for late effects research are not always included. Therefore, the purpose of this study was to develop a method for extending a partial-body pediatric CT scan for estimating organ doses beyond the original CT scan range. Our method uses a library of CT images for 359 pediatric patients from which a candidate patient is selected for providing surrogate anatomy. The most appropriate surrogate patient images to use for the extension are determined based on patient demographic information pulled from the image metadata. Image registration is performed through comparison of the patients' skeletons. The images showing closest similarity are adapted by a transformation method and appended to the original partial-body CT and a new structure file containing organ contours is written; we refer to this extended CT scan with organ contours as the Anatomical Predictive Extension (APE). To test the APE method, three patients with nearly full-body anatomy were extracted from the library, and a continuous subset of the images was removed to simulate a partial-body CT. The APE method was then applied to the partial-body CT to create extended anatomies, with the original images serving as ground truth. Radiotherapy plans were simulated using the Monte Carlo code XVMC on both the original and APE anatomies, with the original serving as ground truth. Three pediatric radiotherapy cases were considered for performance testing: (1) head CT for a simulated brain tumor extended to chest; (2) superior chest CT for simulated Hodgkin's lymphoma extended to inferior chest; (3) pelvic CT for Wilms tumor extended to superior chest. Three geometric metrics (Dice similarity coefficient, overlap fraction, and volume similarity) were calculated to quantify the differences between the original patient and the extended anatomies. In all cases, calculated organ doses showed good agreement between the original and APE anatomies. The average absolute relative dose difference across all organs considered for the three cases was 11%, 12% and 15%, respectively. The APE method is useful for estimating radiation doses to peripheral organs in support of research on late effects following radiotherapy.</AbstractText
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Multifactorial balance rehabilitation in diabetic neuropathy elders: Randomized controlled trial. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes, particularly affecting the elderly and increasing their risk of falls due to impaired balance. This study investigates the effect of a multifactorial balance rehabilitation program on postural stability, fall risk, and quality of life in elderly individuals with DPN.</AbstractText In a randomized controlled trial, 150 elderly participants (aged 60-80) diagnosed with DPN were enrolled. Comprehensive demographic data were collected, diabetic foot assessments were performed, and key outcome measures included postural sway parameters, fall risk, and quality of life. Participants were randomly assigned to two groups: the study group underwent a 12-week multifactorial balance rehabilitation program (3-5 days a week), while the control group received standard medical care and advice.</AbstractText The study identified statistically significant improvements in postural sway parameters (AP sway Z = -3.16, ML sway Z = -2.20, COP length Z = -6.27, COP area Z = -2.25), a substantial reduction in fall risk (F (1, 134) = 263.42), and enhanced quality of life, as measured by physical health domain of WHOQOL-BREF (D1F (1, 134) = 3.94) and MDQoL 17 (F (1, 134) = 7.67), among the study group participants (p < .05).</AbstractText Following the 12-week multifactorial balance rehabilitation program, participants in the study group demonstrated notable improvements in postural stability, reduced risk of falls, and improved quality of life compared to the control group.</AbstractText
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Targeting neuroinflammation in distal symmetrical polyneuropathy in diabetes. Diabetic distal symmetric polyneuropathy is the most common type of peripheral neuropathy complication of diabetes mellitus. Neuroinflammation is emerging as an important contributor to diabetes-induced neuropathy. Long-term hyperglycemia results in increased production of advanced glycation end products (AGEs). AGEs interact with their receptors to activate intracellular signaling, leading to the release of various inflammatory cytokines. Increased release of inflammatory cytokines is associated with diabetes, diabetic neuropathy, and neuropathic pain. Thus, anti-inflammatory intervention is a potential therapy for diabetic distal symmetric polyneuropathy. Further characterization of inflammatory mechanisms might identify novel therapeutic targets to mitigate diabetic neuropathy.</AbstractText
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Realistic extension of partial-body pediatric CT for whole-body organ dose estimation in radiotherapy patients. While modern radiotherapy treatments can deliver a localized radiation dose to the tumor, healthy tissues at distance are inevitably exposed to scatter radiation that has been linked to late health effects such as second cancers. Quantifying the radiation dose received by tissues beyond the target is critical for research on such late health effects. However, the typical radiotherapy planning CT only covers part of the body near the target and the organs of interest for late effects research are not always included. Therefore, the purpose of this study was to develop a method for extending a partial-body pediatric CT scan for estimating organ doses beyond the original CT scan range. Our method uses a library of CT images for 359 pediatric patients from which a candidate patient is selected for providing surrogate anatomy. The most appropriate surrogate patient images to use for the extension are determined based on patient demographic information pulled from the image metadata. Image registration is performed through comparison of the patients' skeletons. The images showing closest similarity are adapted by a transformation method and appended to the original partial-body CT and a new structure file containing organ contours is written; we refer to this extended CT scan with organ contours as the Anatomical Predictive Extension (APE). To test the APE method, three patients with nearly full-body anatomy were extracted from the library, and a continuous subset of the images was removed to simulate a partial-body CT. The APE method was then applied to the partial-body CT to create extended anatomies, with the original images serving as ground truth. Radiotherapy plans were simulated using the Monte Carlo code XVMC on both the original and APE anatomies, with the original serving as ground truth. Three pediatric radiotherapy cases were considered for performance testing: (1) head CT for a simulated brain tumor extended to chest; (2) superior chest CT for simulated Hodgkin's lymphoma extended to inferior chest; (3) pelvic CT for Wilms tumor extended to superior chest. Three geometric metrics (Dice similarity coefficient, overlap fraction, and volume similarity) were calculated to quantify the differences between the original patient and the extended anatomies. In all cases, calculated organ doses showed good agreement between the original and APE anatomies. The average absolute relative dose difference across all organs considered for the three cases was 11%, 12% and 15%, respectively. The APE method is useful for estimating radiation doses to peripheral organs in support of research on late effects following radiotherapy.</AbstractText
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33347884
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32913951
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32457424
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Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research.
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A retrospective review of changes and challenges in the use of antiseizure medicines in Dravet syndrome in Norway.
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Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms.
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The therapeutic potential of cannabidiol (CBD) in seizure disorders has been known for many years, but it is only in the last decade that major progress has been made in characterizing its preclinical and clinical properties as an antiseizure medication. The mechanisms responsible for protection against seizures are not fully understood, but they are likely to be multifactorial and to include, among others, antagonism of G protein-coupled receptor, desensitization of transient receptor potential vanilloid type 1 channels, potentiation of adenosine-mediated signaling, and enhancement of GABAergic transmission. CBD has a low and highly variable oral bioavailability, and can be a victim and perpetrator of many drug-drug interactions. A pharmaceutical-grade formulation of purified CBD derived from Cannabis sativa has been evaluated in several randomized placebo-controlled adjunctive-therapy trials, which resulted in its regulatory approval for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Interpretation of results of these trials, however, has been complicated by the occurrence of an interaction with clobazam, which leads to a prominent increase in the plasma concentration of the active metabolite N-desmethylclobazam in CBD-treated patients. Despite impressive advances, significant gaps in knowledge still remain. Areas that require further investigation include the mechanisms underlying the antiseizure activity of CBD in different syndromes, its pharmacokinetic profile in infants and children, potential relationships between plasma drug concentration and clinical response, interactions with other co-administered medications, potential efficacy in other epilepsy syndromes, and magnitude of antiseizure effects independent from interactions with clobazam. This article is part of the special issue on 'Cannabinoids'.</AbstractText
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Dravet syndrome is a developmental and epileptic encephalopathy characterized by severe and drug-resistant seizures in early childhood, followed by developmental delay. The purpose of this study was to investigate aspects of pharmacological treatment of Norwegian patients with Dravet syndrome, focusing on the use of antiseizure medicines (ASMs) and identifying treatment challenges.</AbstractText Patients were identified through medical registries at the National Center for Epilepsy in Norway and National Center for Rare Epilepsy Related Disorders during 2008-2018. Additional clinical data were obtained from medical records and laboratory request forms.</AbstractText We identified 53 patients with Dravet syndrome, 30/23 males/females, aged 2-50 years. The majority of patients with known seizure frequency experienced frequent seizures, 80% (n = 35/44). Only two patients were seizure-free. Valproate (n = 48), clobazam (n = 45), levetiracetam (n = 30), and stiripentol (n = 38) were most commonly used, previous or current use. More than one-third (n = 20) had tried sodium channel blockers (including lamotrigine), but these drugs were used less during the last decade. Polytherapy was common, 81% (n = 43) used two or more ASMs, and eight of these patients used 4-5 drugs (15%). Several challenges were identified: high seizure frequency, comorbidities, treatment changes with a wide range of ASMs, common use of oral gastro-tubes, extensive polypharmacy, and drug interactions.</AbstractText The use of ASMs has changed over the last decade, in accordance with updated international recommendations. Various treatment challenges were identified. This vulnerable group of patients needs close follow-up for an optimal treatment outcome.</AbstractText
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A third of patients receiving Interferon-α (IFN-α) treatment for Hepatitis-C develop major depressive disorder (MDD). Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the "inflammatory theory" of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-α and anti-TNF enhance/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0 ± 10.5 years, 21 male) initiating IFN-α treatment for Hepatitis-C and 30 (mean 50.4 ± 15.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-α (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-α significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (p < 0.001) but not 4-h after first dose (p > 0.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (P = 0.015) and 12 weeks (p = 0.018). In support of our a-priori hypothesis, both IFN-α and anti-TNF significantly modulated amygdala reactivity with IFN-α acutely enhancing right amygdala responses to sad (compared with neutral) faces (p = 0.032) and anti-TNF conversely decreasing right amygdala reactivity (across emotional valence) (p = 0.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (R<sup
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Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research. The therapeutic potential of cannabidiol (CBD) in seizure disorders has been known for many years, but it is only in the last decade that major progress has been made in characterizing its preclinical and clinical properties as an antiseizure medication. The mechanisms responsible for protection against seizures are not fully understood, but they are likely to be multifactorial and to include, among others, antagonism of G protein-coupled receptor, desensitization of transient receptor potential vanilloid type 1 channels, potentiation of adenosine-mediated signaling, and enhancement of GABAergic transmission. CBD has a low and highly variable oral bioavailability, and can be a victim and perpetrator of many drug-drug interactions. A pharmaceutical-grade formulation of purified CBD derived from Cannabis sativa has been evaluated in several randomized placebo-controlled adjunctive-therapy trials, which resulted in its regulatory approval for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Interpretation of results of these trials, however, has been complicated by the occurrence of an interaction with clobazam, which leads to a prominent increase in the plasma concentration of the active metabolite N-desmethylclobazam in CBD-treated patients. Despite impressive advances, significant gaps in knowledge still remain. Areas that require further investigation include the mechanisms underlying the antiseizure activity of CBD in different syndromes, its pharmacokinetic profile in infants and children, potential relationships between plasma drug concentration and clinical response, interactions with other co-administered medications, potential efficacy in other epilepsy syndromes, and magnitude of antiseizure effects independent from interactions with clobazam. This article is part of the special issue on 'Cannabinoids'.</AbstractText
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A retrospective review of changes and challenges in the use of antiseizure medicines in Dravet syndrome in Norway. Dravet syndrome is a developmental and epileptic encephalopathy characterized by severe and drug-resistant seizures in early childhood, followed by developmental delay. The purpose of this study was to investigate aspects of pharmacological treatment of Norwegian patients with Dravet syndrome, focusing on the use of antiseizure medicines (ASMs) and identifying treatment challenges.</AbstractText Patients were identified through medical registries at the National Center for Epilepsy in Norway and National Center for Rare Epilepsy Related Disorders during 2008-2018. Additional clinical data were obtained from medical records and laboratory request forms.</AbstractText We identified 53 patients with Dravet syndrome, 30/23 males/females, aged 2-50 years. The majority of patients with known seizure frequency experienced frequent seizures, 80% (n = 35/44). Only two patients were seizure-free. Valproate (n = 48), clobazam (n = 45), levetiracetam (n = 30), and stiripentol (n = 38) were most commonly used, previous or current use. More than one-third (n = 20) had tried sodium channel blockers (including lamotrigine), but these drugs were used less during the last decade. Polytherapy was common, 81% (n = 43) used two or more ASMs, and eight of these patients used 4-5 drugs (15%). Several challenges were identified: high seizure frequency, comorbidities, treatment changes with a wide range of ASMs, common use of oral gastro-tubes, extensive polypharmacy, and drug interactions.</AbstractText The use of ASMs has changed over the last decade, in accordance with updated international recommendations. Various treatment challenges were identified. This vulnerable group of patients needs close follow-up for an optimal treatment outcome.</AbstractText
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Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms. A third of patients receiving Interferon-α (IFN-α) treatment for Hepatitis-C develop major depressive disorder (MDD). Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the "inflammatory theory" of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-α and anti-TNF enhance/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0 ± 10.5 years, 21 male) initiating IFN-α treatment for Hepatitis-C and 30 (mean 50.4 ± 15.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-α (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-α significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (p < 0.001) but not 4-h after first dose (p > 0.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (P = 0.015) and 12 weeks (p = 0.018). In support of our a-priori hypothesis, both IFN-α and anti-TNF significantly modulated amygdala reactivity with IFN-α acutely enhancing right amygdala responses to sad (compared with neutral) faces (p = 0.032) and anti-TNF conversely decreasing right amygdala reactivity (across emotional valence) (p = 0.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (R<sup
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40592466
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40125393
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40646014
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The Impact of Parafunctional Habits on Orthodontic Malocclusions in Children With Cerebral Palsy.
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The effect of Kinesio Taping on motor function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials.
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Congo red fluorescence enhances digital pathology workflow in cardiac amyloidosis.
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This study aimed to investigate the correlation between orthodontic malocclusion and parafunctional habits, including atypical swallowing, mouth breathing and drooling, in children with cerebral palsy (CP).</AbstractText Fifty-one children with CP (ages 6-14) from the Spastic Children Foundation were assessed. Drooling, lip incompetence and malocclusion were evaluated using the Balasco and Ballard methods, Angle Classification and WHO standards. Soft tissue relations, facial type, profile and face ratios were examined via extraoral assessment and photo analysis. Fisher's exact test was used for statistical analysis.</AbstractText Among the children, 47% had lip incompetence, 57% exhibited mouth breathing, 63% had atypical swallowing and 66% showed increased overjet. Malocclusion findings included 45% with Class II molar relationships and 66% with parafunctional habits. A significant relationship was found between parafunctional habits and orthodontic malocclusion (p < 0.05).</AbstractText A high prevalence of parafunctional habits was observed in children with CP, significantly correlating with orthodontic issues. Early preventive and interceptive orthodontic treatment before the growth phase is essential to improve swallowing, chewing, respiratory function and nutritional intake, ultimately enhancing overall quality of life.</AbstractText Parafunctional habits are highly prevalent in children with cerebral palsy. These habits are significantly associated with the development of malocclusion and craniofacial morphology. Complex tongue thrust, mouth breathing and severe drooling are strongly linked to skeletal and dental anomalies. Early multidisciplinary follow-up and preventive orthodontic approaches can reduce long-term complications. Swallowing patterns, respiratory types and oral motor functions should be evaluated together in clinical assessment and treatment planning.</AbstractText
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Kinesio taping (KT) is a well-known rehabilitation therapy technique used for treating children with cerebral palsy. However, no meta-analysis of kinesio taping has been conducted specifically for this purpose. This systematic review and meta-analysis aim to explore the effectiveness of kinesio taping in enhancing gross motor function, balance ability, and gait in children with cerebral palsy.</AbstractText A comprehensive database search was conducted using PubMed, Embase, the Cochrane Library, Web of Science, Cnki, Wan Fang, VIP, and the Physiotherapy Evidence Database (PEDro) to identify randomized controlled trials (RCTs) investigating the impact of kinesio taping (KT) on cerebral palsy. RCTs published until May 31, 2024, that met our predetermined inclusion and exclusion criteria were included. Data extraction, literature review, and assessment of the methodological quality of the trials were performed. The meta-analysis was conducted using StataSE version 16.</AbstractText The primary outcome was Gross Motor Function Measure, Berg Balance Scale, Muscle Tension-Heel-Ear Test. The secondary outcomes were step frequency, step speed, step length. Our meta-analysis includes 378 children from 10 RCTs incorporated. Main result the Gross Motor Function Measure (GMFM D) (SMD = 1.00, 95%CI = 0.24-1.77, <i To some extent, compared to the control group, the addition of kinesio taping improved motor dysfunction in children with cerebral palsy during rehabilitation.</AbstractText https://www.crd.york.ac.uk/PROSPERO/search, identifier: CRD42024528254.</AbstractText
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Despite advances in non-invasive methods, endomyocardial biopsy (EMB) remains essential for definitive diagnosis of amyloidosis in many cases. Traditionally, Congo red birefringence (CRB) has been crucial for identifying amyloid deposits but is challenging to capture digitally. Emerging fluorescent Congo red imaging (CRF) overcomes this problem and holds promise in image analysis and AI applications. The diagnostic performance of CRF on virtual slides was evaluated in a cohort of EMB and autopsy cases. The feasibility of developing AI algorithms applicable to centers lacking a fluorescence scanner was investigated leveraging a computational pipeline that enables fluorescence outcome visualization in brightfield. The study analyzed 43 digital myocardial slides stained with Congo Red, acquired using a fluorescent Texas Red filter. Among these, 28 (65%) were diagnosed with amyloidosis, with complete diagnostic agreement with original diagnosis. AI achieved an AUC-ROC of 0.87, 0.86 and 0.79 on the training, validation and test set, respectively, in tile-level classification for amyloidosis positivity and IoU and Dice scores indicating partial but reasonable overlap between predictions and ground truth in amyloid segmentation. The study underscores CRF's transformative impact on virtual slides and AI integration for diagnosing cardiac amyloidosis, showcasing high reliability and diagnostic accuracy. These advancements promise a more quantitative and precise approach, facilitating the histological study of the disease in the digital transition era of pathology labs.</AbstractText
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The Impact of Parafunctional Habits on Orthodontic Malocclusions in Children With Cerebral Palsy. This study aimed to investigate the correlation between orthodontic malocclusion and parafunctional habits, including atypical swallowing, mouth breathing and drooling, in children with cerebral palsy (CP).</AbstractText Fifty-one children with CP (ages 6-14) from the Spastic Children Foundation were assessed. Drooling, lip incompetence and malocclusion were evaluated using the Balasco and Ballard methods, Angle Classification and WHO standards. Soft tissue relations, facial type, profile and face ratios were examined via extraoral assessment and photo analysis. Fisher's exact test was used for statistical analysis.</AbstractText Among the children, 47% had lip incompetence, 57% exhibited mouth breathing, 63% had atypical swallowing and 66% showed increased overjet. Malocclusion findings included 45% with Class II molar relationships and 66% with parafunctional habits. A significant relationship was found between parafunctional habits and orthodontic malocclusion (p < 0.05).</AbstractText A high prevalence of parafunctional habits was observed in children with CP, significantly correlating with orthodontic issues. Early preventive and interceptive orthodontic treatment before the growth phase is essential to improve swallowing, chewing, respiratory function and nutritional intake, ultimately enhancing overall quality of life.</AbstractText Parafunctional habits are highly prevalent in children with cerebral palsy. These habits are significantly associated with the development of malocclusion and craniofacial morphology. Complex tongue thrust, mouth breathing and severe drooling are strongly linked to skeletal and dental anomalies. Early multidisciplinary follow-up and preventive orthodontic approaches can reduce long-term complications. Swallowing patterns, respiratory types and oral motor functions should be evaluated together in clinical assessment and treatment planning.</AbstractText
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The effect of Kinesio Taping on motor function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials. Kinesio taping (KT) is a well-known rehabilitation therapy technique used for treating children with cerebral palsy. However, no meta-analysis of kinesio taping has been conducted specifically for this purpose. This systematic review and meta-analysis aim to explore the effectiveness of kinesio taping in enhancing gross motor function, balance ability, and gait in children with cerebral palsy.</AbstractText A comprehensive database search was conducted using PubMed, Embase, the Cochrane Library, Web of Science, Cnki, Wan Fang, VIP, and the Physiotherapy Evidence Database (PEDro) to identify randomized controlled trials (RCTs) investigating the impact of kinesio taping (KT) on cerebral palsy. RCTs published until May 31, 2024, that met our predetermined inclusion and exclusion criteria were included. Data extraction, literature review, and assessment of the methodological quality of the trials were performed. The meta-analysis was conducted using StataSE version 16.</AbstractText The primary outcome was Gross Motor Function Measure, Berg Balance Scale, Muscle Tension-Heel-Ear Test. The secondary outcomes were step frequency, step speed, step length. Our meta-analysis includes 378 children from 10 RCTs incorporated. Main result the Gross Motor Function Measure (GMFM D) (SMD = 1.00, 95%CI = 0.24-1.77, <i To some extent, compared to the control group, the addition of kinesio taping improved motor dysfunction in children with cerebral palsy during rehabilitation.</AbstractText https://www.crd.york.ac.uk/PROSPERO/search, identifier: CRD42024528254.</AbstractText
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Congo red fluorescence enhances digital pathology workflow in cardiac amyloidosis. Despite advances in non-invasive methods, endomyocardial biopsy (EMB) remains essential for definitive diagnosis of amyloidosis in many cases. Traditionally, Congo red birefringence (CRB) has been crucial for identifying amyloid deposits but is challenging to capture digitally. Emerging fluorescent Congo red imaging (CRF) overcomes this problem and holds promise in image analysis and AI applications. The diagnostic performance of CRF on virtual slides was evaluated in a cohort of EMB and autopsy cases. The feasibility of developing AI algorithms applicable to centers lacking a fluorescence scanner was investigated leveraging a computational pipeline that enables fluorescence outcome visualization in brightfield. The study analyzed 43 digital myocardial slides stained with Congo Red, acquired using a fluorescent Texas Red filter. Among these, 28 (65%) were diagnosed with amyloidosis, with complete diagnostic agreement with original diagnosis. AI achieved an AUC-ROC of 0.87, 0.86 and 0.79 on the training, validation and test set, respectively, in tile-level classification for amyloidosis positivity and IoU and Dice scores indicating partial but reasonable overlap between predictions and ground truth in amyloid segmentation. The study underscores CRF's transformative impact on virtual slides and AI integration for diagnosing cardiac amyloidosis, showcasing high reliability and diagnostic accuracy. These advancements promise a more quantitative and precise approach, facilitating the histological study of the disease in the digital transition era of pathology labs.</AbstractText
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39651269
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30233328
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39380831
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ALS molecular subtypes are a combination of cellular, genetic, and pathological features learned by deep multiomics classifiers.
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Chemogenetic Recruitment of Specific Interneurons Suppresses Seizure Activity.
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Silicone granuloma with intact breast implants: A case report.
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Amyotrophic Lateral Sclerosis (ALS) is a complex syndrome with multiple genetic causes and wide variation in disease presentation. Despite this general heterogeneity, several common factors have been identified. For example, nearly all patients show pathological accumulations of phosphorylated TDP-43 protein in affected regions of the motor cortex and spinal cord. Moreover, large patient cohort studies have revealed that most patient samples can be grouped into a small number of ALS subtypes, as defined by their transcriptomic profiles. These ALS molecular subtypes can be grouped by whether postmortem motor cortex samples display signatures of: mitochondrial dysfunction and oxidative stress (ALS-Ox), microglial activation and neuroinflammation (ALS-Glia), or dense TDP-43 pathology and associated transposable element de-silencing (ALS-TE). In this study, we have built a deep layer ALS neural network classifier (DANcer) that has learned to accurately assign patient samples to these ALS subtypes, and which can be run on either bulk or single-cell datasets. Upon applying this classifier to an expanded ALS patient cohort from the NYGC ALS Consortium, we show that ALS Molecular Subtypes are robust across clinical centers, with no new subtypes appearing in a cohort that has quadrupled in size. Signatures from two of these molecular subtypes strongly correlate with disease duration: ALS-TE signatures in cortex and ALS-Glia signatures in spinal cord, revealing molecular correlates of clinical features. Finally, we use single nucleus RNA sequencing to reveal the cell type-specific contributions to ALS subtype, as determined by our single-cell classifier (scDANCer). Single-cell transcriptomes reveal that ALS molecular subtypes are recapitulated in neurons and glia, with both ALS-wide shared alterations in each cell type as well as ALS subtype-specific alterations. In summary, ALS molecular subtypes: (1) are robust across large cohorts of sporadic and familial ALS patient samples, (2) represent a combination of cellular, genetic, and pathological features, and (3) correlate with clinical features of ALS.</AbstractText
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Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant side-effects and even paradoxical responses due to the broad nature of their action. Recently developed chemogenetic techniques provide the opportunity to pharmacologically recruit endogenous inhibitory mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics to assess the potential of suppressing epileptiform activity by enhancing the synaptic output from three major interneuron populations in the rodent hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) expressing interneurons. To target different neuronal populations, promoter-specific cre-recombinase mice were combined with viral-mediated delivery of chemogenetic constructs. Targeted electrophysiological recordings were then conducted in an <i
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Silicone granuloma formation is a potential complication of silicone implant rupture. Breast magnetic resonance imaging (MRI) is a useful diagnostic tool to assess implant integrity and complications; however, there can be overlap in the enhancement pattern of silicone granuloma and malignancy. We present the case of an 85 year old with suspicious axillary masses on clinical exam for which MRI was recommended. MRI demonstrated enhancing masses in the right axilla that were suspicious for malignancy and biopsy was ultimately performed. This case discusses the use of inversion recovery sequences on MRI, as well as ultrasound, to differentiate malignancy from silicone granuloma formation to prevent unnecessary biopsies.</AbstractText
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ALS molecular subtypes are a combination of cellular, genetic, and pathological features learned by deep multiomics classifiers. Amyotrophic Lateral Sclerosis (ALS) is a complex syndrome with multiple genetic causes and wide variation in disease presentation. Despite this general heterogeneity, several common factors have been identified. For example, nearly all patients show pathological accumulations of phosphorylated TDP-43 protein in affected regions of the motor cortex and spinal cord. Moreover, large patient cohort studies have revealed that most patient samples can be grouped into a small number of ALS subtypes, as defined by their transcriptomic profiles. These ALS molecular subtypes can be grouped by whether postmortem motor cortex samples display signatures of: mitochondrial dysfunction and oxidative stress (ALS-Ox), microglial activation and neuroinflammation (ALS-Glia), or dense TDP-43 pathology and associated transposable element de-silencing (ALS-TE). In this study, we have built a deep layer ALS neural network classifier (DANcer) that has learned to accurately assign patient samples to these ALS subtypes, and which can be run on either bulk or single-cell datasets. Upon applying this classifier to an expanded ALS patient cohort from the NYGC ALS Consortium, we show that ALS Molecular Subtypes are robust across clinical centers, with no new subtypes appearing in a cohort that has quadrupled in size. Signatures from two of these molecular subtypes strongly correlate with disease duration: ALS-TE signatures in cortex and ALS-Glia signatures in spinal cord, revealing molecular correlates of clinical features. Finally, we use single nucleus RNA sequencing to reveal the cell type-specific contributions to ALS subtype, as determined by our single-cell classifier (scDANCer). Single-cell transcriptomes reveal that ALS molecular subtypes are recapitulated in neurons and glia, with both ALS-wide shared alterations in each cell type as well as ALS subtype-specific alterations. In summary, ALS molecular subtypes: (1) are robust across large cohorts of sporadic and familial ALS patient samples, (2) represent a combination of cellular, genetic, and pathological features, and (3) correlate with clinical features of ALS.</AbstractText
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Chemogenetic Recruitment of Specific Interneurons Suppresses Seizure Activity. Current anti-epileptic medications that boost synaptic inhibition are effective in reducing several types of epileptic seizure activity. Nevertheless, these drugs can generate significant side-effects and even paradoxical responses due to the broad nature of their action. Recently developed chemogenetic techniques provide the opportunity to pharmacologically recruit endogenous inhibitory mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics to assess the potential of suppressing epileptiform activity by enhancing the synaptic output from three major interneuron populations in the rodent hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) expressing interneurons. To target different neuronal populations, promoter-specific cre-recombinase mice were combined with viral-mediated delivery of chemogenetic constructs. Targeted electrophysiological recordings were then conducted in an <i
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Silicone granuloma with intact breast implants: A case report. Silicone granuloma formation is a potential complication of silicone implant rupture. Breast magnetic resonance imaging (MRI) is a useful diagnostic tool to assess implant integrity and complications; however, there can be overlap in the enhancement pattern of silicone granuloma and malignancy. We present the case of an 85 year old with suspicious axillary masses on clinical exam for which MRI was recommended. MRI demonstrated enhancing masses in the right axilla that were suspicious for malignancy and biopsy was ultimately performed. This case discusses the use of inversion recovery sequences on MRI, as well as ultrasound, to differentiate malignancy from silicone granuloma formation to prevent unnecessary biopsies.</AbstractText
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39978238
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35020015
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40428097
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An algorithmic approach to MR characterization of focal liver lesions in adults without cirrhosis.
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Diagnostic performance of MRI in detecting locally recurrent soft tissue sarcoma: systematic review and meta-analysis.
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Cervical Cancer Detection Using Deep Neural Network and Hybrid Waterwheel Plant Optimization Algorithm.
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Diagnosing both known and incidental liver lesions in the non-cirrhotic liver on MRI can be challenging. The radiologist can often narrow the diagnosis toward a diagnostic category using various sequences. Using an organized framework to guide the reader's differential diagnosis can be helpful. We present a sequential approach to the diagnosis of focal liver lesions, by first assessing background liver parenchymal signal intensity, then comparing the T1-weighted signal intensity of the reference organ(s), followed by comparing the T2-weighted signal intensity characteristics of lesion to fluid/spleen, and finally confirming using additional sequences including dynamic contrast-enhanced imaging, hepatobiliary imaging, diffusion weighted imaging, as well as clinical and laboratory testing and additional modalities. Using this stepwise framework can sequentially guide the reader toward a diagnosis.</AbstractText
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To systematically review the diagnostic criteria and performance of MRI in detecting locally recurrent soft tissue sarcoma.</AbstractText Medline and Embase were searched for original studies on the diagnostic performance of MRI detecting locally recurrent soft tissue sarcoma. Study quality was assessed using QUADAS-2. Sensitivity and specificity were pooled using a bivariate random-effects model.</AbstractText Ten studies were included. There was a high risk of bias with respect to patient selection in 2 studies and a high risk of bias with respect to flow and timing in 8 studies. The presence of a mass yielded a pooled sensitivity of 80.9% and a pooled specificity of 77.0%. Hyperintensity at T2-weighted imaging yielded a pooled sensitivity of 82.4% and a pooled specificity of 11.0%. Hypo- or isointensity at T1-weighted imaging yielded a pooled sensitivity of 82.0% and a pooled specificity of 14.3%. Contrast enhancement images yielded a pooled sensitivity of 95.9% and a pooled specificity of 12.3%. Low signal mass on the apparent diffusion coefficient (ADC) map yielded a pooled sensitivity of 67.5% and a pooled specificity of 95.3%. Early and rapid arterial phase enhancement at dynamic contrast-enhanced (DCE) MRI yielded a pooled sensitivity of 91.3% and a pooled specificity of 84.7%.</AbstractText The presence of a mass appears a useful criterion to diagnose locally recurrent soft tissue sarcoma. Signal characteristics at standard T2- and T1-weighted imaging and contrast enhancement seem less useful because they lack specificity. Functional MRI techniques, including DWI with ADC mapping and DCE, may help to make a correct diagnosis.</AbstractText • The presence of a mass at MRI appears useful to diagnose locally recurrent soft tissue sarcoma, because both sensitivity and specificity are fairly high. • Signal characteristics at standard T2- and T1-weighted sequences and contrast enhancement suffer from poor specificity. • DWI with ADC mapping and DCE may help to make a correct diagnosis, but further research is needed to better understand the value of these functional MRI techniques.</AbstractText
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More than 85% of the world's cervical cancer fatalities occur in less-developed nations, causing early mortality among women. In this paper, we propose a novel approach for the early classification of cervical cancer based on a new feature selection algorithm and classification method. The new feature selection algorithm is based on a hybrid of the Waterwheel Plant Algorithm and Particle Swarm Optimization algorithms, and bWWPAPSO denotes it. Meanwhile, the new classification method is based on optimizing the parameters of a multilayer perceptron neural network (WWPAPSO+MLP). A publicly available dataset is employed to verify the effectiveness of the proposed approach. Due to this dataset's imbalance and missing values, it is preprocessed and balanced using SMOTETomek, where undersampling and oversampling were utilized. The usefulness of class imbalance and feature selection based on the classifier's specificity, sensitivity, and accuracy has been demonstrated by way of a comparative study of the proposed methodology that has been carried out. WWPAPSO+MLP achieves superior performance, with an accuracy of 97.3% and a sensitivity of 98.8%. On the other hand, several statistical tests were conducted, including the Wilcoxon signed rank test and analysis of variance (ANOVA) to confirm the effectiveness and superiority of the proposed approach.</AbstractText
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An algorithmic approach to MR characterization of focal liver lesions in adults without cirrhosis. Diagnosing both known and incidental liver lesions in the non-cirrhotic liver on MRI can be challenging. The radiologist can often narrow the diagnosis toward a diagnostic category using various sequences. Using an organized framework to guide the reader's differential diagnosis can be helpful. We present a sequential approach to the diagnosis of focal liver lesions, by first assessing background liver parenchymal signal intensity, then comparing the T1-weighted signal intensity of the reference organ(s), followed by comparing the T2-weighted signal intensity characteristics of lesion to fluid/spleen, and finally confirming using additional sequences including dynamic contrast-enhanced imaging, hepatobiliary imaging, diffusion weighted imaging, as well as clinical and laboratory testing and additional modalities. Using this stepwise framework can sequentially guide the reader toward a diagnosis.</AbstractText
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Diagnostic performance of MRI in detecting locally recurrent soft tissue sarcoma: systematic review and meta-analysis. To systematically review the diagnostic criteria and performance of MRI in detecting locally recurrent soft tissue sarcoma.</AbstractText Medline and Embase were searched for original studies on the diagnostic performance of MRI detecting locally recurrent soft tissue sarcoma. Study quality was assessed using QUADAS-2. Sensitivity and specificity were pooled using a bivariate random-effects model.</AbstractText Ten studies were included. There was a high risk of bias with respect to patient selection in 2 studies and a high risk of bias with respect to flow and timing in 8 studies. The presence of a mass yielded a pooled sensitivity of 80.9% and a pooled specificity of 77.0%. Hyperintensity at T2-weighted imaging yielded a pooled sensitivity of 82.4% and a pooled specificity of 11.0%. Hypo- or isointensity at T1-weighted imaging yielded a pooled sensitivity of 82.0% and a pooled specificity of 14.3%. Contrast enhancement images yielded a pooled sensitivity of 95.9% and a pooled specificity of 12.3%. Low signal mass on the apparent diffusion coefficient (ADC) map yielded a pooled sensitivity of 67.5% and a pooled specificity of 95.3%. Early and rapid arterial phase enhancement at dynamic contrast-enhanced (DCE) MRI yielded a pooled sensitivity of 91.3% and a pooled specificity of 84.7%.</AbstractText The presence of a mass appears a useful criterion to diagnose locally recurrent soft tissue sarcoma. Signal characteristics at standard T2- and T1-weighted imaging and contrast enhancement seem less useful because they lack specificity. Functional MRI techniques, including DWI with ADC mapping and DCE, may help to make a correct diagnosis.</AbstractText • The presence of a mass at MRI appears useful to diagnose locally recurrent soft tissue sarcoma, because both sensitivity and specificity are fairly high. • Signal characteristics at standard T2- and T1-weighted sequences and contrast enhancement suffer from poor specificity. • DWI with ADC mapping and DCE may help to make a correct diagnosis, but further research is needed to better understand the value of these functional MRI techniques.</AbstractText
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Cervical Cancer Detection Using Deep Neural Network and Hybrid Waterwheel Plant Optimization Algorithm. More than 85% of the world's cervical cancer fatalities occur in less-developed nations, causing early mortality among women. In this paper, we propose a novel approach for the early classification of cervical cancer based on a new feature selection algorithm and classification method. The new feature selection algorithm is based on a hybrid of the Waterwheel Plant Algorithm and Particle Swarm Optimization algorithms, and bWWPAPSO denotes it. Meanwhile, the new classification method is based on optimizing the parameters of a multilayer perceptron neural network (WWPAPSO+MLP). A publicly available dataset is employed to verify the effectiveness of the proposed approach. Due to this dataset's imbalance and missing values, it is preprocessed and balanced using SMOTETomek, where undersampling and oversampling were utilized. The usefulness of class imbalance and feature selection based on the classifier's specificity, sensitivity, and accuracy has been demonstrated by way of a comparative study of the proposed methodology that has been carried out. WWPAPSO+MLP achieves superior performance, with an accuracy of 97.3% and a sensitivity of 98.8%. On the other hand, several statistical tests were conducted, including the Wilcoxon signed rank test and analysis of variance (ANOVA) to confirm the effectiveness and superiority of the proposed approach.</AbstractText
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39849075
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36395107
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39853946
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Comparative proteomic analysis of astrocytoma tissues from patients with and without seizures.
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Cbln1 regulates axon growth and guidance in multiple neural regions.
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Photooxidation Cross-Linked, Glutaraldehyde Cross-Linked, or Enzyme and Hydrostatic Pressure Processed Decellularized Biomaterials for Cardiovascular Repair Do Not Affect Host Response in a Rat Right Ventricular Outflow Flow Tract Reconstruction (RVOT) Model.
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Astrocytoma is a common type of glioma and a frequent cause of brain tumour-related epilepsy. Although the link between glioma and epilepsy is well established, the precise mechanisms underlying epileptogenesis in astrocytoma remain poorly understood. In this study, we performed proteomic analysis of astrocytoma tissue from patients with and without seizures using mass spectrometry-based techniques. We detected 131 differentially expressed proteins (42 upregulated and 89 downregulated). Proteins upregulated in patients with seizures were mostly related to an increase in energy metabolism. Moreover, glial fibrillary acidic protein, which is involved in maintaining normal axonal structures, was abnormally highly expressed in patients with seizures. Proteins downregulated in patients with seizures included those involved in trans-synaptic signalling and gamma-aminobutyric acid synaptic transmission. Interestingly, comparison of protein expression profiles from our cohort with those from a previous study of patients with epilepsy due to other causes showed that the collapsin response mediator protein family of axonal growth regulators was highly expressed only in patients with seizures due to astrocytomas. Further studies of the proteins identified here are required to determine their potential as biomarkers and therapeutic targets.</AbstractText
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The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon development have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS) by experiments using mouse and chick embryos. Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here, we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.</AbstractText
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Cardiovascular diseases (CVDs) were responsible for approximately 19 million deaths in 2020, marking an increase of 18.7% since 2010. Biological decellularized patches are common therapeutic solutions for CVD such as cardiac and valve defects. The preparation of biomaterials for cardiac patches involves two main processing methods: glutaraldehyde or photooxidation cross-linking (fixation) and noncross-linked (nonfixation) processing. Despite the variety of products available in the market, cardiac patches still suffer from significant limitations, failing to adequately mimic the properties of biological tissue and restore its function. This study assesses the impact of different processing methodologies on the biological and biomechanical outcomes of three commercially available cardiac patches (CorPatch, CardioCel, PhotoFix) and one newly developed decellularized cardiac patch (Adeka) when implanted as right ventricular outflow tract (RVOT) repair material on a rat model. Four different patches for cardiovascular repair were selected based on their processing approaches and included: photooxidation crosslinked (PhotoFix), glutaraldehyde crosslinked (CardioCel), noncross-linked small intestine submucosa (CorPatch) or enzyme, and hydrostatic pressure (Adeka) processed decellularized biomaterials. Structure and function were characterized prior to implantation via thickness mapping, cross-section morphology, 2D surface topography, 3D volume microstructure, biaxial testing, uniaxial tensile testing, ball burst, and suture retention. Their host-biomaterials response was assessed in vivo using a relevant model for cardiovascular repair: a rat (RVOT) reconstruction with 8 and 16-week timepoints. Topological analysis showed that the crosslinked cardiac patches had a more homogeneous thickness distribution when compared to the noncrosslinked patches. This agreed with histological evaluation, where cross-linking processed materials better preserved collagen content than noncrosslinked patches who were also more delaminated. Biaxial data demonstrated that all patches, except CorPatch, recapitulated the anisotropic behavior of healthy left ventricle tissue. The Adeka patch in-plane mechanics at 16 weeks was the one who better resembled the mechanics of healthy cardiac tissue. All patches showed appropriate biocompatibility and function at 8- and 16-week timepoints for RVOT patching. This included echocardiographic assessment, biomechanics, macrophage infiltration and polarization, and angiogenesis. Consistently with a more porous laminae structure, explants histology showed higher cell infiltration in non-crosslinked Adeka when compared to the crosslinked PhotoFix. Overall, both in vitro and in vivo tests indicate that the material processing does not impact the function, biomechanical performance, and the host response of the patches that can be considered as equally effective as materials based cardiac repair solutions.</AbstractText
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Comparative proteomic analysis of astrocytoma tissues from patients with and without seizures. Astrocytoma is a common type of glioma and a frequent cause of brain tumour-related epilepsy. Although the link between glioma and epilepsy is well established, the precise mechanisms underlying epileptogenesis in astrocytoma remain poorly understood. In this study, we performed proteomic analysis of astrocytoma tissue from patients with and without seizures using mass spectrometry-based techniques. We detected 131 differentially expressed proteins (42 upregulated and 89 downregulated). Proteins upregulated in patients with seizures were mostly related to an increase in energy metabolism. Moreover, glial fibrillary acidic protein, which is involved in maintaining normal axonal structures, was abnormally highly expressed in patients with seizures. Proteins downregulated in patients with seizures included those involved in trans-synaptic signalling and gamma-aminobutyric acid synaptic transmission. Interestingly, comparison of protein expression profiles from our cohort with those from a previous study of patients with epilepsy due to other causes showed that the collapsin response mediator protein family of axonal growth regulators was highly expressed only in patients with seizures due to astrocytomas. Further studies of the proteins identified here are required to determine their potential as biomarkers and therapeutic targets.</AbstractText
|
Cbln1 regulates axon growth and guidance in multiple neural regions. The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon development have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS) by experiments using mouse and chick embryos. Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here, we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.</AbstractText
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Photooxidation Cross-Linked, Glutaraldehyde Cross-Linked, or Enzyme and Hydrostatic Pressure Processed Decellularized Biomaterials for Cardiovascular Repair Do Not Affect Host Response in a Rat Right Ventricular Outflow Flow Tract Reconstruction (RVOT) Model. Cardiovascular diseases (CVDs) were responsible for approximately 19 million deaths in 2020, marking an increase of 18.7% since 2010. Biological decellularized patches are common therapeutic solutions for CVD such as cardiac and valve defects. The preparation of biomaterials for cardiac patches involves two main processing methods: glutaraldehyde or photooxidation cross-linking (fixation) and noncross-linked (nonfixation) processing. Despite the variety of products available in the market, cardiac patches still suffer from significant limitations, failing to adequately mimic the properties of biological tissue and restore its function. This study assesses the impact of different processing methodologies on the biological and biomechanical outcomes of three commercially available cardiac patches (CorPatch, CardioCel, PhotoFix) and one newly developed decellularized cardiac patch (Adeka) when implanted as right ventricular outflow tract (RVOT) repair material on a rat model. Four different patches for cardiovascular repair were selected based on their processing approaches and included: photooxidation crosslinked (PhotoFix), glutaraldehyde crosslinked (CardioCel), noncross-linked small intestine submucosa (CorPatch) or enzyme, and hydrostatic pressure (Adeka) processed decellularized biomaterials. Structure and function were characterized prior to implantation via thickness mapping, cross-section morphology, 2D surface topography, 3D volume microstructure, biaxial testing, uniaxial tensile testing, ball burst, and suture retention. Their host-biomaterials response was assessed in vivo using a relevant model for cardiovascular repair: a rat (RVOT) reconstruction with 8 and 16-week timepoints. Topological analysis showed that the crosslinked cardiac patches had a more homogeneous thickness distribution when compared to the noncrosslinked patches. This agreed with histological evaluation, where cross-linking processed materials better preserved collagen content than noncrosslinked patches who were also more delaminated. Biaxial data demonstrated that all patches, except CorPatch, recapitulated the anisotropic behavior of healthy left ventricle tissue. The Adeka patch in-plane mechanics at 16 weeks was the one who better resembled the mechanics of healthy cardiac tissue. All patches showed appropriate biocompatibility and function at 8- and 16-week timepoints for RVOT patching. This included echocardiographic assessment, biomechanics, macrophage infiltration and polarization, and angiogenesis. Consistently with a more porous laminae structure, explants histology showed higher cell infiltration in non-crosslinked Adeka when compared to the crosslinked PhotoFix. Overall, both in vitro and in vivo tests indicate that the material processing does not impact the function, biomechanical performance, and the host response of the patches that can be considered as equally effective as materials based cardiac repair solutions.</AbstractText
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40000056
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39190141
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40186816
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Mucosal angioleiomyoma: mucoscopic findings adding value to diagnosis.
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Diagnostic accuracy of arterial spin labeling MR imaging in detecting cerebral arteriovenous malformations: a systematic review and meta-analysis.
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Racism in Education among Black Youth in Canada and its Association with Depression, Anxiety, Stress, and Post-Traumatic Stress Disorder.
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This article presents a female patient in her 40s who presented with a tender violaceous bump on her upper right lip. Our primary differential diagnosis was an arteriovenous malformation. Punch biopsy revealed the lesion to be an angioleiomyoma (ALM). The punch biopsy was sufficient for the complete removal of the lesion, and the lesion did not recur to date. There were no complications. We discuss the dermatoscopic description of an ALM and its clinical picture.</AbstractText
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Diagnostic accuracy of arteriovenous malformations (AVMs) is imperative for delineating management. The current standard is digital subtraction angiography (DSA). Arterial spin labeling (ASL) is an understudied noninvasive, non-contrast technique that allows angioarchitecture visualization and additionally quantifies cortical and AVM cerebral blood flow and hemodynamics. This meta-analysis aims to compare ASL and DSA imaging in detecting and characterizing cerebral AVMs. EMBASE, Medline, Scopus, and Cochrane databases were queried from inception to July 2022 for reports of AVMs evaluated by DSA and ASL imaging. Fourteen studies with 278 patients evaluated using DSA and ASL imaging prior to intervention were included; pCASL in 11 studies (n = 239, 85.37%) and PASL in three studies (n = 41, 14.64%). The overall AVM detection rate on ASL was 99% (CI 97-100%); subgroup analysis revealed no difference between pCASL vs. PASL (99%; CI 96-100% vs. 100%; CI 95-100% respectively, p = 0.42). The correlation value comparing ASL and DSA nidus size was 0.99. DSA and ASL intermodality agreement Cohen's k factor for Spetzler Martin Grading (SMG) was reported at a median of 0.98 (IQR 0.73-0.1), with a 1.0 agreement on SMG classification. A median of 25 arteries were detected by DSA (IQR 14.5-27), vs. 25 by ASL (IQR 14.5-27.5) at a median 0.92 k factor. ASL provides angioarchitectural visualization noninferior to DSA and additionally quantifies CBF. Our study suggests that ASL should be considered in the detection of AVMs, especially in patients with contrast contraindications or apprehension towards an invasive assessment.</AbstractText
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Racial discrimination in educational settings remains a significant barrier to equitable learning environments and is toxic for the mental health of Black youth in Canada. This study employed a mixed-methods multi-study approach to document the rates, dynamics, and mental health impacts of racial discrimination in education experienced by Black youths aged 14 to 24. Quantitative data were collected from two large samples (N = 558 and N = 914) to measure racial discrimination in education, stress, anxiety, depression, and post-traumatic stress disorder (PTSD). Additionally, qualitative data from semi-structured interviews with 32 youths provided deeper insights into their racial discrimination's experiences in educational settings. Over 40% of participants reported racial discrimination in education, which was significantly associated to elevated symptoms of anxiety, depression, stress, and PTSD. In both quantitative datasets, experience of racial discrimination in education moderated the association between resilience and internalized mental health problems (β = .53, p = .037, β = .34, p = .015, respectively). Racial discrimination in education lowers the protective role of resilience against internalized mental health problems. Thematic analysis of qualitative data uncovered key themes, including pervasive assumptions of low academic potential for Black students by authority figures, lack of appropriate intervention by educators and administrators when racial discrimination occurred, and ongoing enablement of a racist environment within schools. These findings underscore a critical need for systemic reform in Canadian schools and universities to prevent racism and address its mental health impacts. Implementing culturally responsive policies and antiracist interventions can foster safer, more inclusive educational environments, supporting well-being and academic success of Black Canadians youth.</AbstractText
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Mucosal angioleiomyoma: mucoscopic findings adding value to diagnosis. This article presents a female patient in her 40s who presented with a tender violaceous bump on her upper right lip. Our primary differential diagnosis was an arteriovenous malformation. Punch biopsy revealed the lesion to be an angioleiomyoma (ALM). The punch biopsy was sufficient for the complete removal of the lesion, and the lesion did not recur to date. There were no complications. We discuss the dermatoscopic description of an ALM and its clinical picture.</AbstractText
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Diagnostic accuracy of arterial spin labeling MR imaging in detecting cerebral arteriovenous malformations: a systematic review and meta-analysis. Diagnostic accuracy of arteriovenous malformations (AVMs) is imperative for delineating management. The current standard is digital subtraction angiography (DSA). Arterial spin labeling (ASL) is an understudied noninvasive, non-contrast technique that allows angioarchitecture visualization and additionally quantifies cortical and AVM cerebral blood flow and hemodynamics. This meta-analysis aims to compare ASL and DSA imaging in detecting and characterizing cerebral AVMs. EMBASE, Medline, Scopus, and Cochrane databases were queried from inception to July 2022 for reports of AVMs evaluated by DSA and ASL imaging. Fourteen studies with 278 patients evaluated using DSA and ASL imaging prior to intervention were included; pCASL in 11 studies (n = 239, 85.37%) and PASL in three studies (n = 41, 14.64%). The overall AVM detection rate on ASL was 99% (CI 97-100%); subgroup analysis revealed no difference between pCASL vs. PASL (99%; CI 96-100% vs. 100%; CI 95-100% respectively, p = 0.42). The correlation value comparing ASL and DSA nidus size was 0.99. DSA and ASL intermodality agreement Cohen's k factor for Spetzler Martin Grading (SMG) was reported at a median of 0.98 (IQR 0.73-0.1), with a 1.0 agreement on SMG classification. A median of 25 arteries were detected by DSA (IQR 14.5-27), vs. 25 by ASL (IQR 14.5-27.5) at a median 0.92 k factor. ASL provides angioarchitectural visualization noninferior to DSA and additionally quantifies CBF. Our study suggests that ASL should be considered in the detection of AVMs, especially in patients with contrast contraindications or apprehension towards an invasive assessment.</AbstractText
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Racism in Education among Black Youth in Canada and its Association with Depression, Anxiety, Stress, and Post-Traumatic Stress Disorder. Racial discrimination in educational settings remains a significant barrier to equitable learning environments and is toxic for the mental health of Black youth in Canada. This study employed a mixed-methods multi-study approach to document the rates, dynamics, and mental health impacts of racial discrimination in education experienced by Black youths aged 14 to 24. Quantitative data were collected from two large samples (N = 558 and N = 914) to measure racial discrimination in education, stress, anxiety, depression, and post-traumatic stress disorder (PTSD). Additionally, qualitative data from semi-structured interviews with 32 youths provided deeper insights into their racial discrimination's experiences in educational settings. Over 40% of participants reported racial discrimination in education, which was significantly associated to elevated symptoms of anxiety, depression, stress, and PTSD. In both quantitative datasets, experience of racial discrimination in education moderated the association between resilience and internalized mental health problems (β = .53, p = .037, β = .34, p = .015, respectively). Racial discrimination in education lowers the protective role of resilience against internalized mental health problems. Thematic analysis of qualitative data uncovered key themes, including pervasive assumptions of low academic potential for Black students by authority figures, lack of appropriate intervention by educators and administrators when racial discrimination occurred, and ongoing enablement of a racist environment within schools. These findings underscore a critical need for systemic reform in Canadian schools and universities to prevent racism and address its mental health impacts. Implementing culturally responsive policies and antiracist interventions can foster safer, more inclusive educational environments, supporting well-being and academic success of Black Canadians youth.</AbstractText
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40780548
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40597855
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40725175
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Tenecteplase in Practice: A Rural Tele-Stroke Network's Experience.
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Symptom burden profiles and influencing factors in convalescent stroke patients: a latent profile analysis.
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Tumor-Associated Macrophages and Collagen Remodeling in Mammary Carcinomas: A Comparative Analysis in Dogs and Humans.
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Alteplase (tPA) and Tenecteplase (TNK) are both FDA-approved thrombolytic agents for acute ischemic stroke (AIS) treatment. While TNK showed efficacy and safety in the randomized clinical trials, its real-world utilization and effectiveness in rural populations remain key areas for post-approval evaluation. In August 2023 our academic institution, serving as a statewide telestroke network hub, implemented a system-wide transition from tPA to TNK. This study explores the real-world experience of this transition within a telestroke network in rural South Carolina.</AbstractText This retrospective study analyzed data from the Medical University of South Carolina (MUSC) Telestroke Network (1 Hub, 16 spoke centers) on patients with confirmed AIS who received thrombolytics between 2022 and 2024. We compared outcomes between patients treated with tPA or TNK and performed subgroup analyses for LVO and spoke center patients. The analysis focused on safety, efficiency metrics, and functional outcomes. Categorical and continuous variables were assessed using Fisher's exact and Wilcoxon rank-sum tests (p<0.05).</AbstractText Among 1644 patients with discharge diagnosis of AIS, 302 (18%) received thrombolytics: TNK (n=144, 47.7%) and tPA (n=158, 52.3%). Median door-to-needle times were similar (TNK 45 min vs. tPA 42 min, p=0.6). No statistical differences were observed in symptomatic hemorrhage (4.2% vs. 1.9%, p=0.32), discharge NIHSS, or hospital length of stay. Outcomes at spoke centers were comparable. In LVO transferred patients and treated at the hub, TNK was associated with fewer mechanical thrombectomy passes (median 1 vs. 2, p=0.046) and higher rates of functional independence at discharge (mRS ≤3: 75.4% vs. 54.4%, p=0.02).</AbstractText The system-wide transition to TNK resulted in similar safety profiles and treatment times, with notable improvements in procedural efficiency and functional outcomes for patients with LVO. These findings support the broader adoption of TNK as a viable alternative to tPA in acute ischemic stroke management, particularly in telestroke networks and rural communities where staffing and infrastructure may be constrained.</AbstractText
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With advancements in acute stroke treatments, more patients receive timely interventions and survive. However, during the recovery phase, stroke patients often experience a range of coexisting symptoms, which contribute to significant physical and psychological distress and hinder rehabilitation outcomes, thereby exacerbating their symptom burden. Addressing the symptom burden and implementing precise management strategies are therefore essential to improve the quality of life and rehabilitation outcomes of convalescent stroke patients. This study aimed to identify the symptom burden profiles of convalescent stroke patients and explore the factors influencing these profiles.</AbstractText This was a cross-sectional study. A total of 330 convalescent stroke patients who were hospitalized in a tertiary hospital in Guangdong Province were selected as survey subjects. A demographic and clinical characteristics questionnaire, the Symptom Experience Scale for Stroke Survivors, the Fear of Progression Questionnaire-Short Form, and the Acceptance of Illness Scale were used for the investigation. Latent profile analysis of symptom burden in convalescent stroke patients was conducted, and the factors influencing the latent profiles were explored by unordered logistic regression analysis.</AbstractText The symptoms of convalescent stroke patients are complex, with the top five common symptoms being: fatigue (88.2%), moodiness (79.4%), unilateral limb weakness (79.1%), slower response (70.0%), and uncoordinated movement (68.8%). Symptom burden of convalescent stroke patients was divided into three categories: low symptom burden group (40.7%), moderate symptom burden group (36.8%), and high symptom burden - somatic discomfort group (22.5%). The unordered logistic regression analysis indicated that age, daily caregiver status, self-care ability, fear of disease progression, and illness acceptance were influential factors across different potential categories.</AbstractText There was heterogeneity in symptom burden among convalescent stroke patients. Clinicians should tailor interventions to the distinct symptom profiles and influencing factors of stroke patients in the recovery period. Targeted interventions should focus on elderly patients and those who experience fear of disease progression, as this may be an effective approach to alleviate symptoms in the moderate symptom burden group and the high symptom burden - somatic discomfort group.</AbstractText
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The tumor microenvironment (TME) plays a central role in cancer progression, with tumor-associated macrophages (TAMs) and extracellular matrix (ECM) components such as collagen being key modulators of invasiveness and immune regulation. Although macrophage infiltration and ECM remodeling are well-documented individually, their coordinated contribution to mammary carcinoma aggressiveness remains underexplored, particularly in comparative oncology models. This study analyzed 117 mammary carcinoma samples-59 from dogs and 58 from women-using immunohistochemistry, immunofluorescence, and second-harmonic-generation (SHG) microscopy. We quantified TAM density and phenotype (CD206, iNOS, and S100A8/A9), assessed collagen fiber organization, and examined correlations with clinical-pathological variables and overall survival. Increased TAM infiltration was associated with a higher histological grade, aggressive molecular subtypes, enhanced cell proliferation, and shortened survival in dogs. High TAM density also correlated with decreased collagen fiber length and increased alignment, suggesting active immune-matrix remodeling in aggressive tumors. Macrophage phenotyping revealed heterogeneous populations, with CD206<sup
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Tenecteplase in Practice: A Rural Tele-Stroke Network's Experience. Alteplase (tPA) and Tenecteplase (TNK) are both FDA-approved thrombolytic agents for acute ischemic stroke (AIS) treatment. While TNK showed efficacy and safety in the randomized clinical trials, its real-world utilization and effectiveness in rural populations remain key areas for post-approval evaluation. In August 2023 our academic institution, serving as a statewide telestroke network hub, implemented a system-wide transition from tPA to TNK. This study explores the real-world experience of this transition within a telestroke network in rural South Carolina.</AbstractText This retrospective study analyzed data from the Medical University of South Carolina (MUSC) Telestroke Network (1 Hub, 16 spoke centers) on patients with confirmed AIS who received thrombolytics between 2022 and 2024. We compared outcomes between patients treated with tPA or TNK and performed subgroup analyses for LVO and spoke center patients. The analysis focused on safety, efficiency metrics, and functional outcomes. Categorical and continuous variables were assessed using Fisher's exact and Wilcoxon rank-sum tests (p<0.05).</AbstractText Among 1644 patients with discharge diagnosis of AIS, 302 (18%) received thrombolytics: TNK (n=144, 47.7%) and tPA (n=158, 52.3%). Median door-to-needle times were similar (TNK 45 min vs. tPA 42 min, p=0.6). No statistical differences were observed in symptomatic hemorrhage (4.2% vs. 1.9%, p=0.32), discharge NIHSS, or hospital length of stay. Outcomes at spoke centers were comparable. In LVO transferred patients and treated at the hub, TNK was associated with fewer mechanical thrombectomy passes (median 1 vs. 2, p=0.046) and higher rates of functional independence at discharge (mRS ≤3: 75.4% vs. 54.4%, p=0.02).</AbstractText The system-wide transition to TNK resulted in similar safety profiles and treatment times, with notable improvements in procedural efficiency and functional outcomes for patients with LVO. These findings support the broader adoption of TNK as a viable alternative to tPA in acute ischemic stroke management, particularly in telestroke networks and rural communities where staffing and infrastructure may be constrained.</AbstractText
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Symptom burden profiles and influencing factors in convalescent stroke patients: a latent profile analysis. With advancements in acute stroke treatments, more patients receive timely interventions and survive. However, during the recovery phase, stroke patients often experience a range of coexisting symptoms, which contribute to significant physical and psychological distress and hinder rehabilitation outcomes, thereby exacerbating their symptom burden. Addressing the symptom burden and implementing precise management strategies are therefore essential to improve the quality of life and rehabilitation outcomes of convalescent stroke patients. This study aimed to identify the symptom burden profiles of convalescent stroke patients and explore the factors influencing these profiles.</AbstractText This was a cross-sectional study. A total of 330 convalescent stroke patients who were hospitalized in a tertiary hospital in Guangdong Province were selected as survey subjects. A demographic and clinical characteristics questionnaire, the Symptom Experience Scale for Stroke Survivors, the Fear of Progression Questionnaire-Short Form, and the Acceptance of Illness Scale were used for the investigation. Latent profile analysis of symptom burden in convalescent stroke patients was conducted, and the factors influencing the latent profiles were explored by unordered logistic regression analysis.</AbstractText The symptoms of convalescent stroke patients are complex, with the top five common symptoms being: fatigue (88.2%), moodiness (79.4%), unilateral limb weakness (79.1%), slower response (70.0%), and uncoordinated movement (68.8%). Symptom burden of convalescent stroke patients was divided into three categories: low symptom burden group (40.7%), moderate symptom burden group (36.8%), and high symptom burden - somatic discomfort group (22.5%). The unordered logistic regression analysis indicated that age, daily caregiver status, self-care ability, fear of disease progression, and illness acceptance were influential factors across different potential categories.</AbstractText There was heterogeneity in symptom burden among convalescent stroke patients. Clinicians should tailor interventions to the distinct symptom profiles and influencing factors of stroke patients in the recovery period. Targeted interventions should focus on elderly patients and those who experience fear of disease progression, as this may be an effective approach to alleviate symptoms in the moderate symptom burden group and the high symptom burden - somatic discomfort group.</AbstractText
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Tumor-Associated Macrophages and Collagen Remodeling in Mammary Carcinomas: A Comparative Analysis in Dogs and Humans. The tumor microenvironment (TME) plays a central role in cancer progression, with tumor-associated macrophages (TAMs) and extracellular matrix (ECM) components such as collagen being key modulators of invasiveness and immune regulation. Although macrophage infiltration and ECM remodeling are well-documented individually, their coordinated contribution to mammary carcinoma aggressiveness remains underexplored, particularly in comparative oncology models. This study analyzed 117 mammary carcinoma samples-59 from dogs and 58 from women-using immunohistochemistry, immunofluorescence, and second-harmonic-generation (SHG) microscopy. We quantified TAM density and phenotype (CD206, iNOS, and S100A8/A9), assessed collagen fiber organization, and examined correlations with clinical-pathological variables and overall survival. Increased TAM infiltration was associated with a higher histological grade, aggressive molecular subtypes, enhanced cell proliferation, and shortened survival in dogs. High TAM density also correlated with decreased collagen fiber length and increased alignment, suggesting active immune-matrix remodeling in aggressive tumors. Macrophage phenotyping revealed heterogeneous populations, with CD206<sup
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40146982
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21914216
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40776321
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Stress and Hypertension Among African American Female Family Caregivers of Persons Living With Alzheimer Disease and Related Dementias: Protocol for a Pilot Internet-Based Randomized Controlled Trial.
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Improved responsiveness and reduced sample size requirements of PROMIS physical function scales with item response theory.
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Decoding Sepsis: A Technical Blueprint for an Algorithm-Driven System Architecture.
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Caregivers of persons with Alzheimer disease and related dementias (ADRD) neglect their health, including by ignoring stress levels. African American women are vulnerable and susceptible to hypertension. Chronic caregiving stress and hypertension place them at high risk for cardiovascular disease. Addressing stress reactivity or resilience is vital in lessening their caregiving stress, enhancing their quality of life (QOL), and fostering healthy blood pressure (BP) self-care behaviors.</AbstractText This pilot study aims to investigate the feasibility and acceptability of implementing the Mindfulness in Motion (MIM) plus the Dietary Approaches to Stop Hypertension (DASH) intervention in this population and to evaluate its effect on ADRD caregivers' stress and QOL. Additionally, it explores the mediation of stress reactivity or resilience between interventions and self-care behaviors.</AbstractText A small randomized controlled trial pilot study will recruit 28 African American or Black female caregivers aged 40 years diagnosed with hypertension and on an antihypertensive medication. Participants will be randomly assigned to either the MIM DASH or the Alzheimer's Association caregiver training group (attention control). Trained facilitators will deliver both interventions over 8 weeks through 1-hour, group, internet-based sessions, via video or telephone. After completion, both groups will receive coaching calls over 9 months, beginning with 8 weekly calls followed by 4 monthly calls to encourage use of the educational materials. Primary outcome measures include feasibility (recruitment and retention) and acceptability (attendance). Secondary measures assess caregiver stress (Perceived Stress Scale), QOL, and self-care behaviors (Food Frequency Questionnaire and self-reported physical activity). Data collection occurs at baseline, 3 months, and 9 months. Quantitative data will be analyzed using descriptive statistics, CIs, and mediation models.</AbstractText This study was approved by the institutional review board in April 2022 and funded in May 2022. The first data were collected in January 2023, and the last data were collected in September 2024. The completion of all aims' data analysis is anticipated in spring 2025. The participants' mean age was 62.4 (SD 7.98) years, with a mean baseline systolic BP of 128 (SD 19) mm Hg and diastolic BP of 79 (SD 10) mm Hg. Participants reported that MIM DASH was acceptable (at a mean score of 59.08, SD 7.38, compared to 60.83, SD 5.56 for caregiver training). Regarding feasibility, as reflected in attendance, MIM DASH participants had a mean attendance of 6.3 (SD 2.3) sessions, and the caregiver training group had 4.9 (SD 2.9) sessions.</AbstractText This study's findings demonstrate the feasibility of conducting an internet-based intervention (MIM DASH) for African American women with hypertension who also care for families living with ADRD. These results will inform the design of a larger randomized controlled trial to evaluate the intervention's efficacy and scalability further.</AbstractText ClinicalTrials.gov NCT05721482; https://clinicaltrials.gov/study/NCT05721482.</AbstractText DERR1-10.2196/66975.</AbstractText
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The Health Assessment Questionnaire Disability Index (HAQ) and the SF-36 PF-10, among other instruments, yield sensitive and valid Disability (Physical Function) endpoints. Modern techniques, such as Item Response Theory (IRT), now enable development of more precise instruments using improved items. The NIH Patient Reported Outcomes Measurement Information System (PROMIS) is charged with developing improved IRT-based tools. We compared the ability to detect change in physical function using original (Legacy) instruments with Item-Improved and PROMIS IRT-based instruments.</AbstractText We studied two Legacy (original) Physical Function/Disability instruments (HAQ, PF-10), their item-improved derivatives (Item-Improved HAQ and PF-10), and the IRT-based PROMIS Physical Function 10- (PROMIS PF 10) and 20-item (PROMIS PF 20) instruments. We compared sensitivity to detect 12-month changes in physical function in 451 rheumatoid arthritis (RA) patients and assessed relative responsiveness using P-values, effect sizes (ES), and sample size requirements.</AbstractText The study sample was 81% female, 87% Caucasian, 65 years of age, had 14 years of education, and had moderate baseline disability. All instruments were sensitive to detecting change (< 0.05) in physical function over one year. The most responsive instruments in these patients were the Item-Improved HAQ and the PROMIS PF 20. IRT-improved instruments could detect a 1.2% difference with 80% power, while reference instruments could detect only a 2.3% difference (P < 0.01). The best IRT-based instruments required only one-quarter of the sample sizes of the Legacy (PF-10) comparator (95 versus 427). The HAQ outperformed the PF-10 in more impaired populations; the reverse was true in more normal populations. Considering especially the range of severity measured, the PROMIS PF 20 appears the most responsive instrument.</AbstractText Physical Function scales using item improved or IRT-based items can result in greater responsiveness and precision across a broader range of physical function. This can reduce sample size requirements and thus study costs.</AbstractText
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This paper presents a scalable, serverless machine learning operations (ML Ops) architecture for near real-time sepsis detection in Emergency Department (ED) waiting rooms. Built on Amazon Web Services (AWS) cloud environment, the system processes HL7 messages via MuleSoft, using Lambda for data handling, and SageMaker for model deployment. Data is stored in Aurora PostgreSQL and visualized in on-premise Tableau™. With 99.7% of HL7 messages successfully processed, the system shows strong performance, though occasional downtime, code set mismatches, and peak execution times reveal areas for optimization.</AbstractText
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Stress and Hypertension Among African American Female Family Caregivers of Persons Living With Alzheimer Disease and Related Dementias: Protocol for a Pilot Internet-Based Randomized Controlled Trial. Caregivers of persons with Alzheimer disease and related dementias (ADRD) neglect their health, including by ignoring stress levels. African American women are vulnerable and susceptible to hypertension. Chronic caregiving stress and hypertension place them at high risk for cardiovascular disease. Addressing stress reactivity or resilience is vital in lessening their caregiving stress, enhancing their quality of life (QOL), and fostering healthy blood pressure (BP) self-care behaviors.</AbstractText This pilot study aims to investigate the feasibility and acceptability of implementing the Mindfulness in Motion (MIM) plus the Dietary Approaches to Stop Hypertension (DASH) intervention in this population and to evaluate its effect on ADRD caregivers' stress and QOL. Additionally, it explores the mediation of stress reactivity or resilience between interventions and self-care behaviors.</AbstractText A small randomized controlled trial pilot study will recruit 28 African American or Black female caregivers aged 40 years diagnosed with hypertension and on an antihypertensive medication. Participants will be randomly assigned to either the MIM DASH or the Alzheimer's Association caregiver training group (attention control). Trained facilitators will deliver both interventions over 8 weeks through 1-hour, group, internet-based sessions, via video or telephone. After completion, both groups will receive coaching calls over 9 months, beginning with 8 weekly calls followed by 4 monthly calls to encourage use of the educational materials. Primary outcome measures include feasibility (recruitment and retention) and acceptability (attendance). Secondary measures assess caregiver stress (Perceived Stress Scale), QOL, and self-care behaviors (Food Frequency Questionnaire and self-reported physical activity). Data collection occurs at baseline, 3 months, and 9 months. Quantitative data will be analyzed using descriptive statistics, CIs, and mediation models.</AbstractText This study was approved by the institutional review board in April 2022 and funded in May 2022. The first data were collected in January 2023, and the last data were collected in September 2024. The completion of all aims' data analysis is anticipated in spring 2025. The participants' mean age was 62.4 (SD 7.98) years, with a mean baseline systolic BP of 128 (SD 19) mm Hg and diastolic BP of 79 (SD 10) mm Hg. Participants reported that MIM DASH was acceptable (at a mean score of 59.08, SD 7.38, compared to 60.83, SD 5.56 for caregiver training). Regarding feasibility, as reflected in attendance, MIM DASH participants had a mean attendance of 6.3 (SD 2.3) sessions, and the caregiver training group had 4.9 (SD 2.9) sessions.</AbstractText This study's findings demonstrate the feasibility of conducting an internet-based intervention (MIM DASH) for African American women with hypertension who also care for families living with ADRD. These results will inform the design of a larger randomized controlled trial to evaluate the intervention's efficacy and scalability further.</AbstractText ClinicalTrials.gov NCT05721482; https://clinicaltrials.gov/study/NCT05721482.</AbstractText DERR1-10.2196/66975.</AbstractText
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Improved responsiveness and reduced sample size requirements of PROMIS physical function scales with item response theory. The Health Assessment Questionnaire Disability Index (HAQ) and the SF-36 PF-10, among other instruments, yield sensitive and valid Disability (Physical Function) endpoints. Modern techniques, such as Item Response Theory (IRT), now enable development of more precise instruments using improved items. The NIH Patient Reported Outcomes Measurement Information System (PROMIS) is charged with developing improved IRT-based tools. We compared the ability to detect change in physical function using original (Legacy) instruments with Item-Improved and PROMIS IRT-based instruments.</AbstractText We studied two Legacy (original) Physical Function/Disability instruments (HAQ, PF-10), their item-improved derivatives (Item-Improved HAQ and PF-10), and the IRT-based PROMIS Physical Function 10- (PROMIS PF 10) and 20-item (PROMIS PF 20) instruments. We compared sensitivity to detect 12-month changes in physical function in 451 rheumatoid arthritis (RA) patients and assessed relative responsiveness using P-values, effect sizes (ES), and sample size requirements.</AbstractText The study sample was 81% female, 87% Caucasian, 65 years of age, had 14 years of education, and had moderate baseline disability. All instruments were sensitive to detecting change (< 0.05) in physical function over one year. The most responsive instruments in these patients were the Item-Improved HAQ and the PROMIS PF 20. IRT-improved instruments could detect a 1.2% difference with 80% power, while reference instruments could detect only a 2.3% difference (P < 0.01). The best IRT-based instruments required only one-quarter of the sample sizes of the Legacy (PF-10) comparator (95 versus 427). The HAQ outperformed the PF-10 in more impaired populations; the reverse was true in more normal populations. Considering especially the range of severity measured, the PROMIS PF 20 appears the most responsive instrument.</AbstractText Physical Function scales using item improved or IRT-based items can result in greater responsiveness and precision across a broader range of physical function. This can reduce sample size requirements and thus study costs.</AbstractText
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Decoding Sepsis: A Technical Blueprint for an Algorithm-Driven System Architecture. This paper presents a scalable, serverless machine learning operations (ML Ops) architecture for near real-time sepsis detection in Emergency Department (ED) waiting rooms. Built on Amazon Web Services (AWS) cloud environment, the system processes HL7 messages via MuleSoft, using Lambda for data handling, and SageMaker for model deployment. Data is stored in Aurora PostgreSQL and visualized in on-premise Tableau™. With 99.7% of HL7 messages successfully processed, the system shows strong performance, though occasional downtime, code set mismatches, and peak execution times reveal areas for optimization.</AbstractText
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32818621
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23136412
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33011115
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Cortical beta oscillations reflect the contextual gating of visual action feedback.
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Conceptual object representations in human anterior temporal cortex.
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Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping.
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In sensorimotor integration, the brain needs to decide how its predictions should accommodate novel evidence by 'gating' sensory data depending on the current context. Here, we examined the oscillatory correlates of this process by recording magnetoencephalography (MEG) data during a new task requiring action under intersensory conflict. We used virtual reality to decouple visual (virtual) and proprioceptive (real) hand postures during a task in which the phase of grasping movements tracked a target (in either modality). Thus, we rendered visual information either task-relevant or a (to-be-ignored) distractor. Under visuo-proprioceptive incongruence, occipital beta power decreased (relative to congruence) when vision was task-relevant but increased when it had to be ignored. Dynamic causal modeling (DCM) revealed that this interaction was best explained by diametrical, task-dependent changes in visual gain. These results suggest a crucial role for beta oscillations in the contextual gating (i.e., gain or precision control) of visual vs proprioceptive action feedback, depending on current behavioral demands.</AbstractText
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Interaction with everyday objects requires the representation of conceptual object properties, such as where and how an object is used. What are the neural mechanisms that support this knowledge? While research on semantic dementia has provided evidence for a critical role of the anterior temporal lobes (ATLs) in object knowledge, fMRI studies using univariate analysis have primarily implicated regions outside the ATL. In the present human fMRI study we used multivoxel pattern analysis to test whether activity patterns in ATLs carry information about conceptual object properties. Participants viewed objects that differed on two dimensions: where the object is typically found (in the kitchen or the garage) and how the object is commonly used (with a rotate or a squeeze movement). Anatomical region-of-interest analyses covering the ventral visual stream revealed that information about the location and action dimensions increased from posterior to anterior ventral temporal cortex, peaking in the temporal pole. Whole-brain multivoxel searchlight analysis confirmed these results, revealing highly significant and regionally specific information about the location and action dimensions in the anterior temporal lobes bilaterally. In contrast to conceptual object properties, perceptual and low-level visual properties of the objects were reflected in activity patterns in posterior lateral occipitotemporal cortex and occipital cortex, respectively. These results provide fMRI evidence that object representations in the anterior temporal lobes are abstracted away from perceptual properties, categorizing objects in semantically meaningful groups to support conceptual object knowledge.</AbstractText
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The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD).</AbstractText VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD.</AbstractText One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps.</AbstractText In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%).</AbstractText VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.</AbstractText
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Cortical beta oscillations reflect the contextual gating of visual action feedback. In sensorimotor integration, the brain needs to decide how its predictions should accommodate novel evidence by 'gating' sensory data depending on the current context. Here, we examined the oscillatory correlates of this process by recording magnetoencephalography (MEG) data during a new task requiring action under intersensory conflict. We used virtual reality to decouple visual (virtual) and proprioceptive (real) hand postures during a task in which the phase of grasping movements tracked a target (in either modality). Thus, we rendered visual information either task-relevant or a (to-be-ignored) distractor. Under visuo-proprioceptive incongruence, occipital beta power decreased (relative to congruence) when vision was task-relevant but increased when it had to be ignored. Dynamic causal modeling (DCM) revealed that this interaction was best explained by diametrical, task-dependent changes in visual gain. These results suggest a crucial role for beta oscillations in the contextual gating (i.e., gain or precision control) of visual vs proprioceptive action feedback, depending on current behavioral demands.</AbstractText
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Conceptual object representations in human anterior temporal cortex. Interaction with everyday objects requires the representation of conceptual object properties, such as where and how an object is used. What are the neural mechanisms that support this knowledge? While research on semantic dementia has provided evidence for a critical role of the anterior temporal lobes (ATLs) in object knowledge, fMRI studies using univariate analysis have primarily implicated regions outside the ATL. In the present human fMRI study we used multivoxel pattern analysis to test whether activity patterns in ATLs carry information about conceptual object properties. Participants viewed objects that differed on two dimensions: where the object is typically found (in the kitchen or the garage) and how the object is commonly used (with a rotate or a squeeze movement). Anatomical region-of-interest analyses covering the ventral visual stream revealed that information about the location and action dimensions increased from posterior to anterior ventral temporal cortex, peaking in the temporal pole. Whole-brain multivoxel searchlight analysis confirmed these results, revealing highly significant and regionally specific information about the location and action dimensions in the anterior temporal lobes bilaterally. In contrast to conceptual object properties, perceptual and low-level visual properties of the objects were reflected in activity patterns in posterior lateral occipitotemporal cortex and occipital cortex, respectively. These results provide fMRI evidence that object representations in the anterior temporal lobes are abstracted away from perceptual properties, categorizing objects in semantically meaningful groups to support conceptual object knowledge.</AbstractText
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Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping. The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD).</AbstractText VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD.</AbstractText One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps.</AbstractText In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%).</AbstractText VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.</AbstractText
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39911382
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34569714
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40731382
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Knockdown of PDPN in astrocytes reduces hippocampal inflammation in T2DM mice.
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Dementia in Africa: Current evidence, knowledge gaps, and future directions.
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Comparison of SEEK(flex)/videolaryngoscopy and fibreoptic bronchoscope for awake tracheal intubation: a randomized clinical trial.
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Individuals with type 2 diabetes mellitus (T2DM) are at-risk for developing vascular dementia (VaD). Hyperglycemia leads to the activation of astrocytes. These activated cells produce proinflammatory mediators like cytokines or chemokines, that cause cerebrovascular damage. Previous sequencing showed <i Firstly, we will validate the expression of the <i After the validation of transcriptome sequencing, the <i In summary, this study demonstrates that <i
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In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.</AbstractText
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Fibreoptic bronchoscope (FOB) is considered complex to learn and operate, and it remains controversial whether videolaryngoscopy can be used as an alternative to FOB for awake tracheal intubation (ATI).</AbstractText The Objective is to compare the effectiveness of Safe Easy Endotracheal kit-flexible (SEEK<sup We conducted a pragmatic, multicentre, non-blinded, randomized, parallel-group clinical trial in Shanghai and Putian, China. Between January 2023 and June 2024, patients aged 18-80 years who required ATI and were able to adapt to videolaryngoscopy were enrolled. We randomly assigned 148 patients who received ATI to two groups in a 1:1 ratio: SEEK<sup Successful intubation at the first attempt was achieved in 69 cases (93%) using SEEK<sup SEEK<sup ChiCTR2300067555, 01/11/2023.</AbstractText
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Knockdown of PDPN in astrocytes reduces hippocampal inflammation in T2DM mice. Individuals with type 2 diabetes mellitus (T2DM) are at-risk for developing vascular dementia (VaD). Hyperglycemia leads to the activation of astrocytes. These activated cells produce proinflammatory mediators like cytokines or chemokines, that cause cerebrovascular damage. Previous sequencing showed <i Firstly, we will validate the expression of the <i After the validation of transcriptome sequencing, the <i In summary, this study demonstrates that <i
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Dementia in Africa: Current evidence, knowledge gaps, and future directions. In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.</AbstractText
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Comparison of SEEK(flex)/videolaryngoscopy and fibreoptic bronchoscope for awake tracheal intubation: a randomized clinical trial. Fibreoptic bronchoscope (FOB) is considered complex to learn and operate, and it remains controversial whether videolaryngoscopy can be used as an alternative to FOB for awake tracheal intubation (ATI).</AbstractText The Objective is to compare the effectiveness of Safe Easy Endotracheal kit-flexible (SEEK<sup We conducted a pragmatic, multicentre, non-blinded, randomized, parallel-group clinical trial in Shanghai and Putian, China. Between January 2023 and June 2024, patients aged 18-80 years who required ATI and were able to adapt to videolaryngoscopy were enrolled. We randomly assigned 148 patients who received ATI to two groups in a 1:1 ratio: SEEK<sup Successful intubation at the first attempt was achieved in 69 cases (93%) using SEEK<sup SEEK<sup ChiCTR2300067555, 01/11/2023.</AbstractText
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23222106
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2795099
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22560215
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Neuroborreliosis presenting as acute disseminated encephalomyelitis.
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Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years.
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The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling.
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We report a case of a 5-year-old boy with acute disseminated encephalomyelitis as the initial presentation of neuroborreliosis. Parents report an upper-airway infection a few days before the development of acute encephalopathy, mild facial palsy, and seizures. The patient needed mechanical ventilation for 10 days, and after extubation, he presented hypotonia, ataxia, dysarthria, as well as weak gag and cough reflexes. Brain magnetic resonance imaging showed hyperintense lesions on T2- and fluid-attenuated inversion recovery sequences on the right subcortical occipital and parietal region, left posterior arm of the internal capsule, and in the medulla oblongata. Borrelia burgdorferi was identified in the plasma and cerebrospinal fluid by polymerase chain reaction and in the plasma by Western blotting. He was treated with ceftriaxone, methylprednisolone, and human immunoglobulin. Recovery was partial.</AbstractText
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In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5-27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an "immunological scar syndrome". Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis.</AbstractText
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The endoplasmic reticulum (ER) is a critical site of protein, lipid, and glucose metabolism, lipoprotein secretion, and calcium homeostasis. Many of the sensing, metabolizing, and signaling mechanisms for these pathways exist within or on the ER membrane domain. Here, we review the cellular functions of ER, how perturbation of ER homeostasis contributes to metabolic dysregulation and potential causative mechanisms of ER stress in obesity, with a particular focus on lipids, metabolic adaptations of ER, and the maintenance of its membrane homeostasis. We also suggest a conceptual framework of metabolic roundabout to integrate key mechanisms of insulin resistance and metabolic diseases.</AbstractText
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Neuroborreliosis presenting as acute disseminated encephalomyelitis. We report a case of a 5-year-old boy with acute disseminated encephalomyelitis as the initial presentation of neuroborreliosis. Parents report an upper-airway infection a few days before the development of acute encephalopathy, mild facial palsy, and seizures. The patient needed mechanical ventilation for 10 days, and after extubation, he presented hypotonia, ataxia, dysarthria, as well as weak gag and cough reflexes. Brain magnetic resonance imaging showed hyperintense lesions on T2- and fluid-attenuated inversion recovery sequences on the right subcortical occipital and parietal region, left posterior arm of the internal capsule, and in the medulla oblongata. Borrelia burgdorferi was identified in the plasma and cerebrospinal fluid by polymerase chain reaction and in the plasma by Western blotting. He was treated with ceftriaxone, methylprednisolone, and human immunoglobulin. Recovery was partial.</AbstractText
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Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years. In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5-27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an "immunological scar syndrome". Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis.</AbstractText
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The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. The endoplasmic reticulum (ER) is a critical site of protein, lipid, and glucose metabolism, lipoprotein secretion, and calcium homeostasis. Many of the sensing, metabolizing, and signaling mechanisms for these pathways exist within or on the ER membrane domain. Here, we review the cellular functions of ER, how perturbation of ER homeostasis contributes to metabolic dysregulation and potential causative mechanisms of ER stress in obesity, with a particular focus on lipids, metabolic adaptations of ER, and the maintenance of its membrane homeostasis. We also suggest a conceptual framework of metabolic roundabout to integrate key mechanisms of insulin resistance and metabolic diseases.</AbstractText
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40138108
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23108489
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40637428
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The Role of Nitric Oxide and Endothelial Hyperpolarization in Relaxation of Mesenteric Arteries of Rats with Metabolic Syndrome.
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Pregnancy in congenital myasthenic syndrome.
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External Ventricular Drain Placement Using Active Augmented Reality Guidance: A Proof of Concept of a Clinically Integrable System.
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Changes in the relative contribution of endothelium-produced vasodilators to the modulation of mesenteric artery reactivity were studied in Wistar rats treated with 20% fructose for 16 and 32 weeks. Rats that consumed fructose developed symptoms of metabolic syndrome. Acetylcholine-induced relaxation of phenylephrine-precontracted mesenteric arteries was reduced in rats with metabolic syndrome. The NO-mediated component of acetylcholine-induced relaxation was reduced in these rats. At the same time, arterial relaxation mediated by endothelium-dependent hyperpolarization was increased. Endothelium-independent relaxation of mesenteric arteries to sodium nitroprusside in rats with metabolic syndrome was the same as in the arteries of control rats. These results suggest that the increased contraction of mesenteric arteries caused by phenylephrine in rats with metabolic syndrome is due to decreased NO production by the endothelium. Endothelium-dependent hyperpolarization appears to partially compensates for this dysfunction.</AbstractText
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Some case reports have suggested possible worsening of the clinical condition of patients with congenital myasthenic syndromes (CMS) during pregnancy. However, this risk has not yet been quantified in a significant number of patients. Using a standardized report form, we reviewed the gynecological and obstetrical medical history of all patients with CMS listed in the French Registry. The data were reviewed with the assistance of the patients to insure accuracy. We report on 17 pregnancies in eight patients with CMS with mutations in CHRNA1, CHRNE, CHRND, GFPT1, COLQ, or DOK7. Symptoms worsened for six patients during at least one of their pregnancies, and one patient required hospitalization in an intensive care unit during the post-partum period. One patient never recovered to the level of her pre-pregnancy clinical condition. Only one caesarean section was performed. The outcome for children was excellent, with the exceptions of a pulmonary artery atresia in the offspring of a mother on pyridostigmin and a newborn with a severe neonatal congenital myasthenic syndrome (an autosomic dominant slow channel transmission). Our study argues in favor of frequent clinical worsening of symptoms during pregnancy in patients with CMS. These patients should be closely followed by neurologists during the course of pregnancy. However, the overall clinical prognosis is good since the vast majority of patients recovered their pre-pregnancy clinical status six months after the delivery.</AbstractText
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Suboptimal placement occurs in 26% of external ventricular drain (EVD) procedures performed using traditional freehand methods. We developed a low-cost augmented reality stereotactic navigation system aimed at improving accuracy and safety of the procedure, which is readily compatible with existing Picture Archiving and Communication Systems and automated image segmentation algorithms.</AbstractText The system integrates cloud storage, image segmentation, trajectory planning, point-based image-to-patient registration, and real-time 3-dimensional guidance superimposed over the surgical field. As a proof of concept, 15 neurosurgeons, neurosurgical residents, and physician assistants used anatomical landmark-based registration to conduct 29 EVD placements on anatomical phantoms with small ventricles within a simulated surgical environment. From postoperative computed tomography, placement accuracy was assessed using the Kakarla grading scale, along with the distance to target and angular deviation.</AbstractText Twenty EVDs (69.0%; 95% CI, 52.1%-85.8%) were graded as optimal Kakarla 1 placements, 4 (13.8%; 95% CI, 1.2%-26.3%) as suboptimal Kakarla 2 placements, and 5 (17.2%; 95% CI, 3.5%-31.0%) as suboptimal Kakarla 3 placements. The mean distance to target was 9.49 mm (SD, 4.64 mm), and the mean angular deviation was 9.20° (SD, 6.35°). The mean workflow time was 22 minutes 45 seconds (SD, 11 minutes 38 seconds), and the system demonstrated a fiducial registration error of 4.00 mm (SD, 1.16 mm). Challenges related to human-computer interaction were identified, suggesting further refinement is needed to optimize usability.</AbstractText While the accuracy, user interface, and procedural time of the system require further refinement for clinical implementation, this proof of concept demonstrates the clinical and technical feasibility of an end-to-end 3-dimensional augmented reality system with the potential to enhance the safety and accuracy of EVD placements.</AbstractText
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The Role of Nitric Oxide and Endothelial Hyperpolarization in Relaxation of Mesenteric Arteries of Rats with Metabolic Syndrome. Changes in the relative contribution of endothelium-produced vasodilators to the modulation of mesenteric artery reactivity were studied in Wistar rats treated with 20% fructose for 16 and 32 weeks. Rats that consumed fructose developed symptoms of metabolic syndrome. Acetylcholine-induced relaxation of phenylephrine-precontracted mesenteric arteries was reduced in rats with metabolic syndrome. The NO-mediated component of acetylcholine-induced relaxation was reduced in these rats. At the same time, arterial relaxation mediated by endothelium-dependent hyperpolarization was increased. Endothelium-independent relaxation of mesenteric arteries to sodium nitroprusside in rats with metabolic syndrome was the same as in the arteries of control rats. These results suggest that the increased contraction of mesenteric arteries caused by phenylephrine in rats with metabolic syndrome is due to decreased NO production by the endothelium. Endothelium-dependent hyperpolarization appears to partially compensates for this dysfunction.</AbstractText
|
Pregnancy in congenital myasthenic syndrome. Some case reports have suggested possible worsening of the clinical condition of patients with congenital myasthenic syndromes (CMS) during pregnancy. However, this risk has not yet been quantified in a significant number of patients. Using a standardized report form, we reviewed the gynecological and obstetrical medical history of all patients with CMS listed in the French Registry. The data were reviewed with the assistance of the patients to insure accuracy. We report on 17 pregnancies in eight patients with CMS with mutations in CHRNA1, CHRNE, CHRND, GFPT1, COLQ, or DOK7. Symptoms worsened for six patients during at least one of their pregnancies, and one patient required hospitalization in an intensive care unit during the post-partum period. One patient never recovered to the level of her pre-pregnancy clinical condition. Only one caesarean section was performed. The outcome for children was excellent, with the exceptions of a pulmonary artery atresia in the offspring of a mother on pyridostigmin and a newborn with a severe neonatal congenital myasthenic syndrome (an autosomic dominant slow channel transmission). Our study argues in favor of frequent clinical worsening of symptoms during pregnancy in patients with CMS. These patients should be closely followed by neurologists during the course of pregnancy. However, the overall clinical prognosis is good since the vast majority of patients recovered their pre-pregnancy clinical status six months after the delivery.</AbstractText
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External Ventricular Drain Placement Using Active Augmented Reality Guidance: A Proof of Concept of a Clinically Integrable System. Suboptimal placement occurs in 26% of external ventricular drain (EVD) procedures performed using traditional freehand methods. We developed a low-cost augmented reality stereotactic navigation system aimed at improving accuracy and safety of the procedure, which is readily compatible with existing Picture Archiving and Communication Systems and automated image segmentation algorithms.</AbstractText The system integrates cloud storage, image segmentation, trajectory planning, point-based image-to-patient registration, and real-time 3-dimensional guidance superimposed over the surgical field. As a proof of concept, 15 neurosurgeons, neurosurgical residents, and physician assistants used anatomical landmark-based registration to conduct 29 EVD placements on anatomical phantoms with small ventricles within a simulated surgical environment. From postoperative computed tomography, placement accuracy was assessed using the Kakarla grading scale, along with the distance to target and angular deviation.</AbstractText Twenty EVDs (69.0%; 95% CI, 52.1%-85.8%) were graded as optimal Kakarla 1 placements, 4 (13.8%; 95% CI, 1.2%-26.3%) as suboptimal Kakarla 2 placements, and 5 (17.2%; 95% CI, 3.5%-31.0%) as suboptimal Kakarla 3 placements. The mean distance to target was 9.49 mm (SD, 4.64 mm), and the mean angular deviation was 9.20° (SD, 6.35°). The mean workflow time was 22 minutes 45 seconds (SD, 11 minutes 38 seconds), and the system demonstrated a fiducial registration error of 4.00 mm (SD, 1.16 mm). Challenges related to human-computer interaction were identified, suggesting further refinement is needed to optimize usability.</AbstractText While the accuracy, user interface, and procedural time of the system require further refinement for clinical implementation, this proof of concept demonstrates the clinical and technical feasibility of an end-to-end 3-dimensional augmented reality system with the potential to enhance the safety and accuracy of EVD placements.</AbstractText
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21469799
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30932661
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20825464
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Field-induced phase transitions of repulsive spin-1 bosons in optical lattices.
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Chiral Phonon Transport Induced by Topological Magnons.
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Sleep and daily functioning during androgen deprivation therapy for prostate cancer.
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We study the phase diagram of repulsively interacting spin-1 bosons in optical lattices at unit filling, showing that an externally induced quadratic Zeeman effect may lead to a rich physics characterized by various phases and phase transitions. We find that the main properties of the system may be described by an effective field model, which provides the precise location of the phase boundaries for any dimension, in excellent agreement with our numerical calculations for one-dimensional (1D) systems. Thus, our work provides a quantitative guide for the experimental analysis of various types of field-induced quantum phase transitions in spin-1 lattice bosons. These transitions, which are precluded in spin-1/2 systems, may be realized by using an externally modified quadratic Zeeman coupling, similar to recent experiments with spinor condensates in the continuum.</AbstractText
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The plethora of recent discoveries in the field of topological electronic insulators has inspired a search for boson systems with similar properties. There are predictions that ferromagnets on a two-dimensional honeycomb lattice may host chiral edge magnons. In such systems, we theoretically study how magnons and phonons couple. We find topological magnon polarons around the avoided crossings between phonons and topological magnons. Exploiting this feature along with our finding of Rayleigh-like edge phonons in armchair ribbons, we demonstrate the existence of chiral edge modes with a phononic character. We predict that these modes mediate a chirality in the coherent phonon response and suggest measuring this effect via elastic transducers. These findings reveal a possible approach towards heat management in future devices.</AbstractText
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A limited body of evidence suggests that sleep problems are common in prostate cancer patients undergoing androgen deprivation therapy, yet little is known about sleep characteristics and the effects of poor sleep on daily functioning in this population. This study assessed sleep in 60 prostate cancer patients taking androgen deprivation therapy with wrist actigraphy and daily diaries for 7 days. The Epworth Sleepiness Scale and the general version of the Functional Assessment of Cancer Therapy scale were also administered. On average, total sleep time was 5.9 (SD = 1.4) h, and sleep efficiency was 75% (SD = 12.0) as assessed by actigraphy. There was generally poor concordance between actigraphy and daily diary for most sleep metrics. Subjects reported awakening, on average, 2.7 times per night, most commonly for nocturia and hot flashes. Assessment of daily functioning showed that participants had mild daytime sleepiness, which was predicted by total sleep time (F(1,47) = 4.5, P= 0.04) General quality of life was not impaired. This study supports more research on the predictors of poor sleep in order to identify effective interventions.</AbstractText
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Field-induced phase transitions of repulsive spin-1 bosons in optical lattices. We study the phase diagram of repulsively interacting spin-1 bosons in optical lattices at unit filling, showing that an externally induced quadratic Zeeman effect may lead to a rich physics characterized by various phases and phase transitions. We find that the main properties of the system may be described by an effective field model, which provides the precise location of the phase boundaries for any dimension, in excellent agreement with our numerical calculations for one-dimensional (1D) systems. Thus, our work provides a quantitative guide for the experimental analysis of various types of field-induced quantum phase transitions in spin-1 lattice bosons. These transitions, which are precluded in spin-1/2 systems, may be realized by using an externally modified quadratic Zeeman coupling, similar to recent experiments with spinor condensates in the continuum.</AbstractText
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Chiral Phonon Transport Induced by Topological Magnons. The plethora of recent discoveries in the field of topological electronic insulators has inspired a search for boson systems with similar properties. There are predictions that ferromagnets on a two-dimensional honeycomb lattice may host chiral edge magnons. In such systems, we theoretically study how magnons and phonons couple. We find topological magnon polarons around the avoided crossings between phonons and topological magnons. Exploiting this feature along with our finding of Rayleigh-like edge phonons in armchair ribbons, we demonstrate the existence of chiral edge modes with a phononic character. We predict that these modes mediate a chirality in the coherent phonon response and suggest measuring this effect via elastic transducers. These findings reveal a possible approach towards heat management in future devices.</AbstractText
|
Sleep and daily functioning during androgen deprivation therapy for prostate cancer. A limited body of evidence suggests that sleep problems are common in prostate cancer patients undergoing androgen deprivation therapy, yet little is known about sleep characteristics and the effects of poor sleep on daily functioning in this population. This study assessed sleep in 60 prostate cancer patients taking androgen deprivation therapy with wrist actigraphy and daily diaries for 7 days. The Epworth Sleepiness Scale and the general version of the Functional Assessment of Cancer Therapy scale were also administered. On average, total sleep time was 5.9 (SD = 1.4) h, and sleep efficiency was 75% (SD = 12.0) as assessed by actigraphy. There was generally poor concordance between actigraphy and daily diary for most sleep metrics. Subjects reported awakening, on average, 2.7 times per night, most commonly for nocturia and hot flashes. Assessment of daily functioning showed that participants had mild daytime sleepiness, which was predicted by total sleep time (F(1,47) = 4.5, P= 0.04) General quality of life was not impaired. This study supports more research on the predictors of poor sleep in order to identify effective interventions.</AbstractText
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40768537
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33757602
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26173003
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Exploring influences of health and wellbeing in Sydney's apartment living: A qualitative study of residents' perceptions.
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Feasibility and acceptability of an online mindfulness-based group intervention for adults with tic disorders.
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Cryptochromes and Hormone Signal Transduction under Near-Zero Magnetic Fields: New Clues to Magnetic Field Effects in a Rice Planthopper.
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In Australia, and internationally, a shift is occurring towards high-density apartment living with initiatives and research showing an increased interest in the relations between health, wellbeing and apartment buildings. This study explores the complex associations between residents' perceptions of their health and wellbeing and the apartment buildings where they live within the context of Sydney, Australia, as the case study. It challenges the fragmented approach previously used to study healthy apartment living and their underlying assumptions that do not account for a coupled human-environment systems view of health and wellbeing concerning apartment living. Qualitative research was used, which included in-depth, semi-structured interviews with 17 residents living in different apartment buildings, supplemented by fieldwork and narrated photographs. Using a structured iterative thematic analysis process, 20 areas of health and wellbeing influence (themes) were identified and further categorised using synthetic thinking into diverse, context-dependent, multilevel, and pervading influences. The findings from this exploratory study suggest a complex view of health and wellbeing by residents of apartment buildings and provide novel and important insights that have not been previously reported in such breadth.</AbstractText
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Preliminary research suggests that a mindfulness-based treatment approach may be beneficial for adults with tic disorders. In the present study, we report on the feasibility, acceptability, safety, and symptomatic effect of a novel online mindfulness-based group intervention for adults with Tourette syndrome or persistent tic disorder. Data from this study will directly inform the conduct of a funded randomized controlled trial comparing the efficacy of this intervention to another active psychological intervention.</AbstractText One cohort of adults with Tourette syndrome participated in an 8-week online mindfulness-based group intervention. Measures of feasibility, acceptability, and safety were administered throughout and at posttreatment. Self-reported measures of mindfulness and clinician-rated measures of tic severity and impairment were administered at baseline and posttreatment.</AbstractText Data on refusal, dropout rate, attendance, participant satisfaction, and safety suggest that this is a feasible and acceptable intervention. However, participant adherence to home practice was lower than anticipated. Mindfulness, tic severity, and tic-related impairment only modestly improved from baseline to posttreatment. Qualitative analysis of participant feedback revealed aspects of the intervention that were most helpful and also areas for improvement.</AbstractText Data suggest that although this is a feasible and acceptable intervention, it should be modified to enhance participant adherence, more successfully engage the target mechanism, and optimize outcomes.</AbstractText Clinicaltrials.gov registration # NCT03525626 . Registered on 24 April 2018.</AbstractText
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Although there are considerable reports of magnetic field effects (MFE) on organisms, very little is known so far about the MFE-related signal transduction pathways. Here we establish a manipulative near-zero magnetic field (NZMF) to investigate the potential signal transduction pathways involved in MFE. We show that exposure of migratory white-backed planthopper, Sogatella furcifera, to the NZMF results in delayed egg and nymphal development, increased frequency of brachypterous females, and reduced longevity of macropterous female adults. To understand the changes in gene expression underlying these phenotypes, we examined the temporal patterns of gene expression of (i) CRY1 and CRY2 as putative magnetosensors, (ii) JHAMT, FAMeT and JHEH in the juvenile hormone pathway, (iii) CYP307A1 in the ecdysone pathway, and (iv) reproduction-related Vitellogenin (Vg). The significantly altered gene expression of CRY1 and CRY2 under the NZMF suggest their developmental stage-specific patterns and potential upstream location in magnetic response. Gene expression patterns of JHAMT, JHEH and CYP307A1 were consistent with the NZMF-triggered delay in nymphal development, higher proportion of brachypterous female adults, and the shortened longevity of macropterous female adults, which show feasible links between hormone signal transduction and phenotypic MFE. By conducting manipulative NZMF experiments, our study suggests an important role of the geomagnetic field (GMF) in modulating development and physiology of insects, provides new insights into the complexity of MFE-magnetosensitivity interactions, and represents an initial but crucial step forward in understanding the molecular basis of cryptochromes and hormone signal transduction involved in MFE.</AbstractText
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Exploring influences of health and wellbeing in Sydney's apartment living: A qualitative study of residents' perceptions. In Australia, and internationally, a shift is occurring towards high-density apartment living with initiatives and research showing an increased interest in the relations between health, wellbeing and apartment buildings. This study explores the complex associations between residents' perceptions of their health and wellbeing and the apartment buildings where they live within the context of Sydney, Australia, as the case study. It challenges the fragmented approach previously used to study healthy apartment living and their underlying assumptions that do not account for a coupled human-environment systems view of health and wellbeing concerning apartment living. Qualitative research was used, which included in-depth, semi-structured interviews with 17 residents living in different apartment buildings, supplemented by fieldwork and narrated photographs. Using a structured iterative thematic analysis process, 20 areas of health and wellbeing influence (themes) were identified and further categorised using synthetic thinking into diverse, context-dependent, multilevel, and pervading influences. The findings from this exploratory study suggest a complex view of health and wellbeing by residents of apartment buildings and provide novel and important insights that have not been previously reported in such breadth.</AbstractText
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Feasibility and acceptability of an online mindfulness-based group intervention for adults with tic disorders. Preliminary research suggests that a mindfulness-based treatment approach may be beneficial for adults with tic disorders. In the present study, we report on the feasibility, acceptability, safety, and symptomatic effect of a novel online mindfulness-based group intervention for adults with Tourette syndrome or persistent tic disorder. Data from this study will directly inform the conduct of a funded randomized controlled trial comparing the efficacy of this intervention to another active psychological intervention.</AbstractText One cohort of adults with Tourette syndrome participated in an 8-week online mindfulness-based group intervention. Measures of feasibility, acceptability, and safety were administered throughout and at posttreatment. Self-reported measures of mindfulness and clinician-rated measures of tic severity and impairment were administered at baseline and posttreatment.</AbstractText Data on refusal, dropout rate, attendance, participant satisfaction, and safety suggest that this is a feasible and acceptable intervention. However, participant adherence to home practice was lower than anticipated. Mindfulness, tic severity, and tic-related impairment only modestly improved from baseline to posttreatment. Qualitative analysis of participant feedback revealed aspects of the intervention that were most helpful and also areas for improvement.</AbstractText Data suggest that although this is a feasible and acceptable intervention, it should be modified to enhance participant adherence, more successfully engage the target mechanism, and optimize outcomes.</AbstractText Clinicaltrials.gov registration # NCT03525626 . Registered on 24 April 2018.</AbstractText
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Cryptochromes and Hormone Signal Transduction under Near-Zero Magnetic Fields: New Clues to Magnetic Field Effects in a Rice Planthopper. Although there are considerable reports of magnetic field effects (MFE) on organisms, very little is known so far about the MFE-related signal transduction pathways. Here we establish a manipulative near-zero magnetic field (NZMF) to investigate the potential signal transduction pathways involved in MFE. We show that exposure of migratory white-backed planthopper, Sogatella furcifera, to the NZMF results in delayed egg and nymphal development, increased frequency of brachypterous females, and reduced longevity of macropterous female adults. To understand the changes in gene expression underlying these phenotypes, we examined the temporal patterns of gene expression of (i) CRY1 and CRY2 as putative magnetosensors, (ii) JHAMT, FAMeT and JHEH in the juvenile hormone pathway, (iii) CYP307A1 in the ecdysone pathway, and (iv) reproduction-related Vitellogenin (Vg). The significantly altered gene expression of CRY1 and CRY2 under the NZMF suggest their developmental stage-specific patterns and potential upstream location in magnetic response. Gene expression patterns of JHAMT, JHEH and CYP307A1 were consistent with the NZMF-triggered delay in nymphal development, higher proportion of brachypterous female adults, and the shortened longevity of macropterous female adults, which show feasible links between hormone signal transduction and phenotypic MFE. By conducting manipulative NZMF experiments, our study suggests an important role of the geomagnetic field (GMF) in modulating development and physiology of insects, provides new insights into the complexity of MFE-magnetosensitivity interactions, and represents an initial but crucial step forward in understanding the molecular basis of cryptochromes and hormone signal transduction involved in MFE.</AbstractText
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32926243
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31411808
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32191935
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Associated analysis of PER1/TUBB2B with endometrial cancer development caused by circadian rhythm disorders.
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D-Ser2-oxyntomodulin ameliorated Aβ31-35-induced circadian rhythm disorder in mice.
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Artificial intelligence in glioma imaging: challenges and advances.
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Endometrial cancer (EC) is one of the most common gynecologic malignancies, and the incidence rate of night shift among women workers is higher than that in the general population. Circadian rhythm disorder, mainly rhythm gene, is related to various tumor onset, including EC. This study described the sleep/night-shift features of EC patients, explored the mechanism of the circadian clock gene PER and investigated prognostic and functional values of Per1 caused by night shift. A total of 619 subjects were enrolled and divided into two groups according to night-shift duties (rhythm group and control group), analyzed for clinical risk factors and night shift features of endometrial carcinoma. Then samples were randomly selected for sequencing and western blot were performed, and the function of overexpressed PER1 in ishikawa cells was explored. We noticed that severer EC patients experienced night-shift more frequently and with longer durations. A total of 58,174 differentially expressed genes were discovered, mainly rhythm genes and related to up and downstream regulatory genes. Western blot showed that the rhythm group had elevated protein expression of BCAS4, TUBB2B and RSPO4, and decreased expression of PER1 and PER2 in night-shift. In TCGA-EC datasets, PER1 was decreased in the EC patients with a significantly positive correlation with PER2, and higher PER1 expression indicated longer survival, opposite to TUBB2B. The research of overexpressing PER1 gene in EC ishikawa cells found that PER1 can promote apoptosis, expression of TNF-a, IL-6 and PD-1/PD-L1, inhibit the tumor invasion and expression of TUBB2B gene. Together, EC severity was associated with night-shift and rhythm disorders. The rhythm relating factors PER1, TUBB2B and tumor immune factors may regulate the mechanisms of EC onset and progression.</AbstractText
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The occurrence of circadian rhythm disorder in patients with Alzheimer's disease (AD) is closely related to the abnormal deposition of amyloid-β (Aβ), and d-Ser2-oxyntomodulin (Oxy) is a protease-resistant oxyntomodulin analogue that has been shown to exert neuroprotective effects.</AbstractText This study aimed to explore whether Oxy, a new GLP-1R/GCGR dual receptor agonist, can improve the Aβ-induced disrupted circadian rhythm and the role of GLP-1R.</AbstractText A mouse wheel-running experiment was performed to explore the circadian rhythm, and western blotting and real-time PCR were performed to assess the expression of the circadian clock genes Bmal1 and Per2. Furthermore, a lentivirus encoding an shGLP-1R-GFP-PURO was used to interfere with GLP-1R gene expression and so explore the role of GLP-1R.</AbstractText The present study has confirmed that Oxy could restore Aβ31-35-induced circadian rhythm disorders and improve the abnormal expression of Bmal1 and Per2. After interfering the GLP-1R gene, we found that Oxy could not improve the Aβ31-35-induced circadian rhythm disorder and abnormal expression of clock genes.</AbstractText This study demonstrated that Oxy could improve Aβ31-35-induced circadian rhythm disorders, and GLP-1R plays a critical role. This study thus describes a novel target that may be potentially used in the treatment of AD.</AbstractText
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Primary brain tumors including gliomas continue to pose significant management challenges to clinicians. While the presentation, the pathology, and the clinical course of these lesions are variable, the initial investigations are usually similar. Patients who are suspected to have a brain tumor will be assessed with computed tomography (CT) and magnetic resonance imaging (MRI). The imaging findings are used by neurosurgeons to determine the feasibility of surgical resection and plan such an undertaking. Imaging studies are also an indispensable tool in tracking tumor progression or its response to treatment. As these imaging studies are non-invasive, relatively cheap and accessible to patients, there have been many efforts over the past two decades to increase the amount of clinically-relevant information that can be extracted from brain imaging. Most recently, artificial intelligence (AI) techniques have been employed to segment and characterize brain tumors, as well as to detect progression or treatment-response. However, the clinical utility of such endeavours remains limited due to challenges in data collection and annotation, model training, and the reliability of AI-generated information. We provide a review of recent advances in addressing the above challenges. First, to overcome the challenge of data paucity, different image imputation and synthesis techniques along with annotation collection efforts are summarized. Next, various training strategies are presented to meet multiple desiderata, such as model performance, generalization ability, data privacy protection, and learning with sparse annotations. Finally, standardized performance evaluation and model interpretability methods have been reviewed. We believe that these technical approaches will facilitate the development of a fully-functional AI tool in the clinical care of patients with gliomas.</AbstractText
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Associated analysis of PER1/TUBB2B with endometrial cancer development caused by circadian rhythm disorders. Endometrial cancer (EC) is one of the most common gynecologic malignancies, and the incidence rate of night shift among women workers is higher than that in the general population. Circadian rhythm disorder, mainly rhythm gene, is related to various tumor onset, including EC. This study described the sleep/night-shift features of EC patients, explored the mechanism of the circadian clock gene PER and investigated prognostic and functional values of Per1 caused by night shift. A total of 619 subjects were enrolled and divided into two groups according to night-shift duties (rhythm group and control group), analyzed for clinical risk factors and night shift features of endometrial carcinoma. Then samples were randomly selected for sequencing and western blot were performed, and the function of overexpressed PER1 in ishikawa cells was explored. We noticed that severer EC patients experienced night-shift more frequently and with longer durations. A total of 58,174 differentially expressed genes were discovered, mainly rhythm genes and related to up and downstream regulatory genes. Western blot showed that the rhythm group had elevated protein expression of BCAS4, TUBB2B and RSPO4, and decreased expression of PER1 and PER2 in night-shift. In TCGA-EC datasets, PER1 was decreased in the EC patients with a significantly positive correlation with PER2, and higher PER1 expression indicated longer survival, opposite to TUBB2B. The research of overexpressing PER1 gene in EC ishikawa cells found that PER1 can promote apoptosis, expression of TNF-a, IL-6 and PD-1/PD-L1, inhibit the tumor invasion and expression of TUBB2B gene. Together, EC severity was associated with night-shift and rhythm disorders. The rhythm relating factors PER1, TUBB2B and tumor immune factors may regulate the mechanisms of EC onset and progression.</AbstractText
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D-Ser2-oxyntomodulin ameliorated Aβ31-35-induced circadian rhythm disorder in mice. The occurrence of circadian rhythm disorder in patients with Alzheimer's disease (AD) is closely related to the abnormal deposition of amyloid-β (Aβ), and d-Ser2-oxyntomodulin (Oxy) is a protease-resistant oxyntomodulin analogue that has been shown to exert neuroprotective effects.</AbstractText This study aimed to explore whether Oxy, a new GLP-1R/GCGR dual receptor agonist, can improve the Aβ-induced disrupted circadian rhythm and the role of GLP-1R.</AbstractText A mouse wheel-running experiment was performed to explore the circadian rhythm, and western blotting and real-time PCR were performed to assess the expression of the circadian clock genes Bmal1 and Per2. Furthermore, a lentivirus encoding an shGLP-1R-GFP-PURO was used to interfere with GLP-1R gene expression and so explore the role of GLP-1R.</AbstractText The present study has confirmed that Oxy could restore Aβ31-35-induced circadian rhythm disorders and improve the abnormal expression of Bmal1 and Per2. After interfering the GLP-1R gene, we found that Oxy could not improve the Aβ31-35-induced circadian rhythm disorder and abnormal expression of clock genes.</AbstractText This study demonstrated that Oxy could improve Aβ31-35-induced circadian rhythm disorders, and GLP-1R plays a critical role. This study thus describes a novel target that may be potentially used in the treatment of AD.</AbstractText
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Artificial intelligence in glioma imaging: challenges and advances. Primary brain tumors including gliomas continue to pose significant management challenges to clinicians. While the presentation, the pathology, and the clinical course of these lesions are variable, the initial investigations are usually similar. Patients who are suspected to have a brain tumor will be assessed with computed tomography (CT) and magnetic resonance imaging (MRI). The imaging findings are used by neurosurgeons to determine the feasibility of surgical resection and plan such an undertaking. Imaging studies are also an indispensable tool in tracking tumor progression or its response to treatment. As these imaging studies are non-invasive, relatively cheap and accessible to patients, there have been many efforts over the past two decades to increase the amount of clinically-relevant information that can be extracted from brain imaging. Most recently, artificial intelligence (AI) techniques have been employed to segment and characterize brain tumors, as well as to detect progression or treatment-response. However, the clinical utility of such endeavours remains limited due to challenges in data collection and annotation, model training, and the reliability of AI-generated information. We provide a review of recent advances in addressing the above challenges. First, to overcome the challenge of data paucity, different image imputation and synthesis techniques along with annotation collection efforts are summarized. Next, various training strategies are presented to meet multiple desiderata, such as model performance, generalization ability, data privacy protection, and learning with sparse annotations. Finally, standardized performance evaluation and model interpretability methods have been reviewed. We believe that these technical approaches will facilitate the development of a fully-functional AI tool in the clinical care of patients with gliomas.</AbstractText
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18365529
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18429018
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17536227
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MR imaging, proton MR spectroscopy, ultrasonographic, histologic findings in patients with chronic lymphedema.
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Generalized k-space decomposition with chemical shift correction for non-Cartesian water-fat imaging.
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Change in stroke incidence from a population-based intervention trial in three urban communities in China.
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Lymphedema is a progressive disease with multiple alterations occurring in the dermis. We undertook this study using high-frequency ultrasonography (US), magnetic resonance imaging, proton MR spectroscopy and histology to examine structural changes occurring in the subcutaneous tissue and precisely describe the nature of intralobular changes in chronic lymphedema. Four cutaneous and subcutaneous tissue biopsies from patients with chronic lymphedema during lymphonodal transplantation were studied. We performed US with a 13.5 MHz transducer, TSE T1 and TSE T2 magnetic resonance images with and without fat-suppression, MR Chemical Shift Imaging Spectroscopy and histological evaluation on these biopsies. We found that normal subcutaneous septa are seen as hyperechogenic lines in US and hyposignal lines in MRI and that hyperechogenic subcutis in US can be due to interlobular and intralobular water accumulation and/or to interlobular and intralobular fibrosis. Our study also confirms the usefulness of MR spectroscopy to assess water or fat content of soft tissue. Thus, multiple imaging modalities may be necessary to precisely delineate the nature of tissue alterations in chronic lymphedema.</AbstractText
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Chemical-shift artifacts associated with non-Cartesian imaging are more complex to model and less clinically acceptable than the bulk fat shift that occurs with conventional spin-warp Cartesian imaging. A novel k-space based iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) approach is introduced that decomposes multiple species while simultaneously correcting distortion of off-resonant species. The new signal model accounts for the additional phase accumulated by off-resonant spins at each point in the k-space acquisition trajectory. This phase can then be corrected by adjusting the decomposition matrix for each k-space point during the final IDEAL processing step with little increase in reconstruction time. The technique is demonstrated with water-fat decomposition using projection reconstruction (PR)/radial, spiral, and Cartesian spin-warp imaging of phantoms and human subjects, in each case achieving substantial correction of chemical-shift artifacts. Simulations of the point-spread-function (PSF) for off-resonant spins are examined to show the nature of the chemical-shift distortion for each acquisition. Also introduced is an approach to improve the signal model for species which have multiple resonant peaks. Many chemical species, including fat, have multiple resonant peaks, although such species are often approximated as a single peak. The improved multipeak decomposition is demonstrated with water-fat imaging, showing a substantial improvement in water-fat separation.</AbstractText
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Stroke has been the main cause of death in most urban residents in China since the 1990s. A community-based intervention trial carried out in China aimed to reduce the incidence and mortality of stroke. In 1991, two well-matched communities each with approximately 50,000 people were selected as intervention or control communities in the urban areas of Beijing, Shanghai and Changsha. Regular health education and health promotion activities were carried out between 1991 and 2000 in the intervention communities but no special action was taken in the control communities. Both fatal and nonfatal stroke cases were meticulously registered during the study in the two communities to assess the effect of long-term intervention. The trend in stroke incidence and the effect of intervention on stroke incidence were analyzed using a Poisson regression model adjusted for age, sex, year and city. Between 1991 and 2000, 2,273 first-ever stroke cases were registered in the intervention communities and 3,015 in the control communities. Geographic variation and changes in the incidence of stroke and its subtypes were found among these 3 cities. Through 10 years of intervention, incidence risks of all, ischemic and hemorrhagic strokes decreased by 11.4% (relative risk 0.8959; 95% confidence interval, CI, 0.8483-0.9460; p < 0.0001), 13.2% (relative risk 0.8676; 95% CI 0.8054-0.9345; p = 0.0002) and 7.2% (relative risk 0.9283; 95% CI 0.8517-1.0117; p = 0.0899), respectively, in the intervention compared with control communities. Accordingly, comprehensive community-based intervention measures could effectively reduce the incidence of stroke in the population.</AbstractText
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MR imaging, proton MR spectroscopy, ultrasonographic, histologic findings in patients with chronic lymphedema. Lymphedema is a progressive disease with multiple alterations occurring in the dermis. We undertook this study using high-frequency ultrasonography (US), magnetic resonance imaging, proton MR spectroscopy and histology to examine structural changes occurring in the subcutaneous tissue and precisely describe the nature of intralobular changes in chronic lymphedema. Four cutaneous and subcutaneous tissue biopsies from patients with chronic lymphedema during lymphonodal transplantation were studied. We performed US with a 13.5 MHz transducer, TSE T1 and TSE T2 magnetic resonance images with and without fat-suppression, MR Chemical Shift Imaging Spectroscopy and histological evaluation on these biopsies. We found that normal subcutaneous septa are seen as hyperechogenic lines in US and hyposignal lines in MRI and that hyperechogenic subcutis in US can be due to interlobular and intralobular water accumulation and/or to interlobular and intralobular fibrosis. Our study also confirms the usefulness of MR spectroscopy to assess water or fat content of soft tissue. Thus, multiple imaging modalities may be necessary to precisely delineate the nature of tissue alterations in chronic lymphedema.</AbstractText
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Generalized k-space decomposition with chemical shift correction for non-Cartesian water-fat imaging. Chemical-shift artifacts associated with non-Cartesian imaging are more complex to model and less clinically acceptable than the bulk fat shift that occurs with conventional spin-warp Cartesian imaging. A novel k-space based iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) approach is introduced that decomposes multiple species while simultaneously correcting distortion of off-resonant species. The new signal model accounts for the additional phase accumulated by off-resonant spins at each point in the k-space acquisition trajectory. This phase can then be corrected by adjusting the decomposition matrix for each k-space point during the final IDEAL processing step with little increase in reconstruction time. The technique is demonstrated with water-fat decomposition using projection reconstruction (PR)/radial, spiral, and Cartesian spin-warp imaging of phantoms and human subjects, in each case achieving substantial correction of chemical-shift artifacts. Simulations of the point-spread-function (PSF) for off-resonant spins are examined to show the nature of the chemical-shift distortion for each acquisition. Also introduced is an approach to improve the signal model for species which have multiple resonant peaks. Many chemical species, including fat, have multiple resonant peaks, although such species are often approximated as a single peak. The improved multipeak decomposition is demonstrated with water-fat imaging, showing a substantial improvement in water-fat separation.</AbstractText
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Change in stroke incidence from a population-based intervention trial in three urban communities in China. Stroke has been the main cause of death in most urban residents in China since the 1990s. A community-based intervention trial carried out in China aimed to reduce the incidence and mortality of stroke. In 1991, two well-matched communities each with approximately 50,000 people were selected as intervention or control communities in the urban areas of Beijing, Shanghai and Changsha. Regular health education and health promotion activities were carried out between 1991 and 2000 in the intervention communities but no special action was taken in the control communities. Both fatal and nonfatal stroke cases were meticulously registered during the study in the two communities to assess the effect of long-term intervention. The trend in stroke incidence and the effect of intervention on stroke incidence were analyzed using a Poisson regression model adjusted for age, sex, year and city. Between 1991 and 2000, 2,273 first-ever stroke cases were registered in the intervention communities and 3,015 in the control communities. Geographic variation and changes in the incidence of stroke and its subtypes were found among these 3 cities. Through 10 years of intervention, incidence risks of all, ischemic and hemorrhagic strokes decreased by 11.4% (relative risk 0.8959; 95% confidence interval, CI, 0.8483-0.9460; p < 0.0001), 13.2% (relative risk 0.8676; 95% CI 0.8054-0.9345; p = 0.0002) and 7.2% (relative risk 0.9283; 95% CI 0.8517-1.0117; p = 0.0899), respectively, in the intervention compared with control communities. Accordingly, comprehensive community-based intervention measures could effectively reduce the incidence of stroke in the population.</AbstractText
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39950182
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29567077
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40720330
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Distal Nerve Transfer for Opponensplasty in the Setting of High Median Nerve Injury: A Case Series.
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Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of melatonin.
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The power of protective factors to mitigate LGBTQ+ suicide risk: Improving positive aspects of one's identity in a vacuum is not enough.
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<b
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Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive loss of lung function due to tissue scarring. A variety of pro-inflammatory and pro-fibrogenic factors including interleukin‑17A, transforming growth factor β, Wnt/β‑catenin, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factors, endotelin‑1, renin angiotensin system and impaired caveolin‑1 function are involved in the IPF pathogenesis. Current therapies for IPF have some limitations and this highlights the need for effective therapeutic agents to treat this fatal disease. Melatonin and its metabolites are broad-spectrum antioxidants that not only remove reactive oxygen and nitrogen species by radical scavenging but also up-regulate the expression and activity of endogenous antioxidants. Via these actions, melatonin and its metabolites modulate a variety of molecular pathways in different pathophysiological conditions. Herein, we review the signaling pathways involved in the pathophysiology of IPF and the potentially protective effects of melatonin on these pathways.</AbstractText
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The goal of the present study was to determine whether positive components of lesbian, gay, bisexual, transgender, queer/questioning, and related (LGBTQ+) identity mitigate suicide risk. A sample of 260 LGBTQ+ participants completed assessments of adverse childhood experiences (ACEs), positive LGBTQ+ identity (authenticity, community, self-awareness, intimacy, social justice), outness, and self-acceptance of sexuality. Bivariate analyses indicated that ACEs were positively associated with both suicidal ideation (SI) and suicide attempts (SA). Authenticity was negatively correlated with SI, whereas a sense of community negatively correlated with SA. A multinomial logistic regression was conducted with all variables of interest entered as independent variables and suicide continuum group as the dependent variable (SI, SA, and no history of SI or SA). Compared to those with no history, individuals in the SI group reported greater ACEs and psychosocial distress. Compared to the SI group, the SA group reported significantly greater ACEs (but not distress) and a lower sense of community. Surprisingly, they also reported greater authenticity. Adding the interaction term between community and authenticity significantly improved model fit. Examination of the interaction slopes indicated that the odds of reporting an SA decreased as both authenticity and community increased. These findings suggest that fostering a sense of community may mitigate suicide risk for LGBTQ+ individuals and that authenticity in the absence of community support may increase this risk. LGBTQ+ community engagement is likely an important avenue for suicide prevention efforts. Additional findings pertaining to social desirability are also discussed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).</AbstractText
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Distal Nerve Transfer for Opponensplasty in the Setting of High Median Nerve Injury: A Case Series. <b
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Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of melatonin. Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive loss of lung function due to tissue scarring. A variety of pro-inflammatory and pro-fibrogenic factors including interleukin‑17A, transforming growth factor β, Wnt/β‑catenin, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factors, endotelin‑1, renin angiotensin system and impaired caveolin‑1 function are involved in the IPF pathogenesis. Current therapies for IPF have some limitations and this highlights the need for effective therapeutic agents to treat this fatal disease. Melatonin and its metabolites are broad-spectrum antioxidants that not only remove reactive oxygen and nitrogen species by radical scavenging but also up-regulate the expression and activity of endogenous antioxidants. Via these actions, melatonin and its metabolites modulate a variety of molecular pathways in different pathophysiological conditions. Herein, we review the signaling pathways involved in the pathophysiology of IPF and the potentially protective effects of melatonin on these pathways.</AbstractText
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The power of protective factors to mitigate LGBTQ+ suicide risk: Improving positive aspects of one's identity in a vacuum is not enough. The goal of the present study was to determine whether positive components of lesbian, gay, bisexual, transgender, queer/questioning, and related (LGBTQ+) identity mitigate suicide risk. A sample of 260 LGBTQ+ participants completed assessments of adverse childhood experiences (ACEs), positive LGBTQ+ identity (authenticity, community, self-awareness, intimacy, social justice), outness, and self-acceptance of sexuality. Bivariate analyses indicated that ACEs were positively associated with both suicidal ideation (SI) and suicide attempts (SA). Authenticity was negatively correlated with SI, whereas a sense of community negatively correlated with SA. A multinomial logistic regression was conducted with all variables of interest entered as independent variables and suicide continuum group as the dependent variable (SI, SA, and no history of SI or SA). Compared to those with no history, individuals in the SI group reported greater ACEs and psychosocial distress. Compared to the SI group, the SA group reported significantly greater ACEs (but not distress) and a lower sense of community. Surprisingly, they also reported greater authenticity. Adding the interaction term between community and authenticity significantly improved model fit. Examination of the interaction slopes indicated that the odds of reporting an SA decreased as both authenticity and community increased. These findings suggest that fostering a sense of community may mitigate suicide risk for LGBTQ+ individuals and that authenticity in the absence of community support may increase this risk. LGBTQ+ community engagement is likely an important avenue for suicide prevention efforts. Additional findings pertaining to social desirability are also discussed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).</AbstractText
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40291083
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32955013
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40051716
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Enhancing ad hoc team performance with emotional intelligence.
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Efficacy of a patient decision aid for improving person-centered decision-making by older adults with obstructive sleep apnea.
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Study of Eye Movements Abnormalities in Epilepsy.
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Ad hoc teams in healthcare systems are beneficial from an organizational lens. Despite the benefits of ad hoc teams, clinical faculty have reported concerns due to a short time to coalesce prior to taking care of complex patients in areas such as the intensive care unit, trauma bay, or operating room. Evidence around ad hoc teams is scarce, so we extrapolated key findings from adjacent literature to establish a foundation for ad hoc team members' individual readiness. We propose that it is critical for team members to be individually prepared, and we borrow from literature focused on building emotionally intelligent (EI) teams. Thus, all team members should develop their EI to ensure that they will demonstrate self-awareness, empathy, transparency, adaptability, and collaboration. If each team member shows up with a high level of EI, the team should be able to read the situation, anticipate the needs of other team members, and adapt as needed, ensuring a positive outcome for the patient and team.</AbstractText
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Person-centered obstructive sleep apnea (OSA) care is a collaborative approach that is respectful of an individual's health priorities. Informed decision-making is essential to person-centered care, especially as patients age. In a feasibility study, we evaluated the effects of a new decision aid (Decide2Rest) on OSA treatment decision-making in older adults.</AbstractText Patients (aged ≥ 60 years) with newly diagnosed OSA were recruited from two health care systems and randomized either to Decide2Rest or to a control program. Postintervention outcomes included 1) Decisional Conflict Scale (0-100, where 0 = low and 100 = high conflict), which measures perceptions of uncertainty, whether decisions reflect what matters most to patients, and whether patients feel supported in decision-making; 2) Preparation for Decision-Making scale (0-100, where 0 = least and 100 most prepared); and 3) OSA knowledge (0-100, where 0 = poor and 100 = outstanding). Multivariable linear regression models examined relationships between Decide2Rest and outcomes (Decisional Conflict Scale, Preparation for Decision-Making, OSA knowledge).</AbstractText Seventy-three patients were randomized to Decide2Rest (n = 36; mean age, 69 years; 72% male) vs control (n = 37; mean age, 69 years; 70% male). Results from the regressions, controlling for study site, indicate that the Decide2Rest program resulted in less decisional conflict (20.5 vs 32.7 on the Decisional Conflict Scale; P = .014), more preparedness for decision-making (87.8 vs 66.2 on the Preparation for Decision-Making scale; P < .001), and greater OSA knowledge (75.1 vs 65.3 OSA knowledge score; P = .04) scores than in the control group.</AbstractText The Decide2Rest program promotes person-centered OSA decision-making for older patients with newly diagnosed OSA. Future studies are needed to optimize implementation of the program.</AbstractText Registry: ClinicalTrials.gov, Name: Improving Older Adults' Decision-Making for OSAT (eDecide2Rest); URL: https://clinicaltrials.gov/ct2/show/NCT03138993; Identifier: NCT03138993.</AbstractText
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Idiopathic epilepsy (IE), is a group of epileptic syndromes with no structural brain lesion, but with microstructural changes in neuronal networks leading to neuropsychological consequences. Therefore, the assessment of saccadic eye movements can provide insight into the integrity of cerebral networks as it involves large cortical and subcortical brain areas and circuitries. Describe saccadic eye movement abnormalities in patients with IE and correlate them with disease characteristics and antiseizure medication. Case-control study including IE patients followed in the Neurology Department of Razi University Hospital and healthy controls matched. Participants underwent a recording of saccadic eye movements. Pursuit, prosaccade, and anti-saccade tasks were performed. 115 patients and 98 matched healthy controls were included. The gender ratio (male to female) was 0.6. The mean age at onset was 16.3 ± 12 years. Diagnosed epileptic syndromes were juvenile myoclonic epilepsy (JME), epilepsy with generalized tonic-clonic seizures, childhood absence epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, and rolandic epilepsy. Saccadic eye movements were impaired in 52.2% of our patients and significantly more altered in those with JME (<i
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Enhancing ad hoc team performance with emotional intelligence. Ad hoc teams in healthcare systems are beneficial from an organizational lens. Despite the benefits of ad hoc teams, clinical faculty have reported concerns due to a short time to coalesce prior to taking care of complex patients in areas such as the intensive care unit, trauma bay, or operating room. Evidence around ad hoc teams is scarce, so we extrapolated key findings from adjacent literature to establish a foundation for ad hoc team members' individual readiness. We propose that it is critical for team members to be individually prepared, and we borrow from literature focused on building emotionally intelligent (EI) teams. Thus, all team members should develop their EI to ensure that they will demonstrate self-awareness, empathy, transparency, adaptability, and collaboration. If each team member shows up with a high level of EI, the team should be able to read the situation, anticipate the needs of other team members, and adapt as needed, ensuring a positive outcome for the patient and team.</AbstractText
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Efficacy of a patient decision aid for improving person-centered decision-making by older adults with obstructive sleep apnea. Person-centered obstructive sleep apnea (OSA) care is a collaborative approach that is respectful of an individual's health priorities. Informed decision-making is essential to person-centered care, especially as patients age. In a feasibility study, we evaluated the effects of a new decision aid (Decide2Rest) on OSA treatment decision-making in older adults.</AbstractText Patients (aged ≥ 60 years) with newly diagnosed OSA were recruited from two health care systems and randomized either to Decide2Rest or to a control program. Postintervention outcomes included 1) Decisional Conflict Scale (0-100, where 0 = low and 100 = high conflict), which measures perceptions of uncertainty, whether decisions reflect what matters most to patients, and whether patients feel supported in decision-making; 2) Preparation for Decision-Making scale (0-100, where 0 = least and 100 most prepared); and 3) OSA knowledge (0-100, where 0 = poor and 100 = outstanding). Multivariable linear regression models examined relationships between Decide2Rest and outcomes (Decisional Conflict Scale, Preparation for Decision-Making, OSA knowledge).</AbstractText Seventy-three patients were randomized to Decide2Rest (n = 36; mean age, 69 years; 72% male) vs control (n = 37; mean age, 69 years; 70% male). Results from the regressions, controlling for study site, indicate that the Decide2Rest program resulted in less decisional conflict (20.5 vs 32.7 on the Decisional Conflict Scale; P = .014), more preparedness for decision-making (87.8 vs 66.2 on the Preparation for Decision-Making scale; P < .001), and greater OSA knowledge (75.1 vs 65.3 OSA knowledge score; P = .04) scores than in the control group.</AbstractText The Decide2Rest program promotes person-centered OSA decision-making for older patients with newly diagnosed OSA. Future studies are needed to optimize implementation of the program.</AbstractText Registry: ClinicalTrials.gov, Name: Improving Older Adults' Decision-Making for OSAT (eDecide2Rest); URL: https://clinicaltrials.gov/ct2/show/NCT03138993; Identifier: NCT03138993.</AbstractText
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Study of Eye Movements Abnormalities in Epilepsy. Idiopathic epilepsy (IE), is a group of epileptic syndromes with no structural brain lesion, but with microstructural changes in neuronal networks leading to neuropsychological consequences. Therefore, the assessment of saccadic eye movements can provide insight into the integrity of cerebral networks as it involves large cortical and subcortical brain areas and circuitries. Describe saccadic eye movement abnormalities in patients with IE and correlate them with disease characteristics and antiseizure medication. Case-control study including IE patients followed in the Neurology Department of Razi University Hospital and healthy controls matched. Participants underwent a recording of saccadic eye movements. Pursuit, prosaccade, and anti-saccade tasks were performed. 115 patients and 98 matched healthy controls were included. The gender ratio (male to female) was 0.6. The mean age at onset was 16.3 ± 12 years. Diagnosed epileptic syndromes were juvenile myoclonic epilepsy (JME), epilepsy with generalized tonic-clonic seizures, childhood absence epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, and rolandic epilepsy. Saccadic eye movements were impaired in 52.2% of our patients and significantly more altered in those with JME (<i
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40392186
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37108127
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40084496
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Young Adults Are Impacted by the Spatial Context of Visual Cues to Perform Walking Turns.
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Inhibitory Synaptic Influences on Developmental Motor Disorders.
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Dystrophin isoform deficiency and upper-limb and respiratory function in Duchenne muscular dystrophy.
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Walking turns require coordinated axial segment rotations combined with step placement modifications. Visual information can inform this coordination and is used in three stages of processing: to <i
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During development, GABA and glycine play major trophic and synaptic roles in the establishment of the neuromotor system. In this review, we summarise the formation, function and maturation of GABAergic and glycinergic synapses within neuromotor circuits during development. We take special care to discuss the differences in limb and respiratory neuromotor control. We then investigate the influences that GABAergic and glycinergic neurotransmission has on two major developmental neuromotor disorders: Rett syndrome and spastic cerebral palsy. We present these two syndromes in order to contrast the approaches to disease mechanism and therapy. While both conditions have motor dysfunctions at their core, one condition Rett syndrome, despite having myriad symptoms, has scientists focused on the breathing abnormalities and their alleviation-to great clinical advances. By contrast, cerebral palsy remains a scientific quagmire or poor definitions, no widely adopted model and a lack of therapeutic focus. We conclude that the sheer abundance of diversity of inhibitory neurotransmitter targets should provide hope for intractable conditions, particularly those that exhibit broad spectra of dysfunction-such as spastic cerebral palsy and Rett syndrome.</AbstractText
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To investigate the associations between mutations expected to differentially affect Dp140 expression and long-term trajectories of respiratory and upper-limb motor outcomes in Duchenne muscular dystrophy (DMD).</AbstractText In a retrospective analysis of population-based longitudinal data from three real-world and natural history data sources, individuals with DMD aged 5 years to 18 years were subdivided according to the predicted effects of the participants' DMD mutation on dystrophin isoform expression (group 1, Dp427 absent, Dp140/Dp71 present; group 2, Dp427/Dp140 absent, Dp71 present).</AbstractText A total of 459 participants were studied, with upper-limb outcomes assessed in 71 (27 in group 1 and 44 in group 2) and forced vital capacity percentage predicted (%pred) assessed in 434 (224 in group 1 and 210 in group 2). Mean grip strength %pred was on average 7.1 percentage points lower in group 2 than in group 1 (p = 0.03). Mean pinch strength %pred was on average 9.2 percentage points lower in group 2 than in group 1 (p = 0.04). Mean forced vital capacity %pred was on average 4.3 percentage points lower in group 2 than in group 1 (p = 0.01).</AbstractText In individuals with DMD, DMD mutations predicted to affect Dp140 expression were associated with more severe trajectories of respiratory and upper-limb motor outcomes.</AbstractText
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Young Adults Are Impacted by the Spatial Context of Visual Cues to Perform Walking Turns. Walking turns require coordinated axial segment rotations combined with step placement modifications. Visual information can inform this coordination and is used in three stages of processing: to <i
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Inhibitory Synaptic Influences on Developmental Motor Disorders. During development, GABA and glycine play major trophic and synaptic roles in the establishment of the neuromotor system. In this review, we summarise the formation, function and maturation of GABAergic and glycinergic synapses within neuromotor circuits during development. We take special care to discuss the differences in limb and respiratory neuromotor control. We then investigate the influences that GABAergic and glycinergic neurotransmission has on two major developmental neuromotor disorders: Rett syndrome and spastic cerebral palsy. We present these two syndromes in order to contrast the approaches to disease mechanism and therapy. While both conditions have motor dysfunctions at their core, one condition Rett syndrome, despite having myriad symptoms, has scientists focused on the breathing abnormalities and their alleviation-to great clinical advances. By contrast, cerebral palsy remains a scientific quagmire or poor definitions, no widely adopted model and a lack of therapeutic focus. We conclude that the sheer abundance of diversity of inhibitory neurotransmitter targets should provide hope for intractable conditions, particularly those that exhibit broad spectra of dysfunction-such as spastic cerebral palsy and Rett syndrome.</AbstractText
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Dystrophin isoform deficiency and upper-limb and respiratory function in Duchenne muscular dystrophy. To investigate the associations between mutations expected to differentially affect Dp140 expression and long-term trajectories of respiratory and upper-limb motor outcomes in Duchenne muscular dystrophy (DMD).</AbstractText In a retrospective analysis of population-based longitudinal data from three real-world and natural history data sources, individuals with DMD aged 5 years to 18 years were subdivided according to the predicted effects of the participants' DMD mutation on dystrophin isoform expression (group 1, Dp427 absent, Dp140/Dp71 present; group 2, Dp427/Dp140 absent, Dp71 present).</AbstractText A total of 459 participants were studied, with upper-limb outcomes assessed in 71 (27 in group 1 and 44 in group 2) and forced vital capacity percentage predicted (%pred) assessed in 434 (224 in group 1 and 210 in group 2). Mean grip strength %pred was on average 7.1 percentage points lower in group 2 than in group 1 (p = 0.03). Mean pinch strength %pred was on average 9.2 percentage points lower in group 2 than in group 1 (p = 0.04). Mean forced vital capacity %pred was on average 4.3 percentage points lower in group 2 than in group 1 (p = 0.01).</AbstractText In individuals with DMD, DMD mutations predicted to affect Dp140 expression were associated with more severe trajectories of respiratory and upper-limb motor outcomes.</AbstractText
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32093482
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31076535
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33168794
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Brain Network Dynamics Correlate with Personality Traits.
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Abnormal thalamocortical network dynamics in migraine.
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Methyl-CpG-binding protein 2 gene mutations and its association with epilepsy: a single centre study from the Indian subcontinent.
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Identifying the neural substrates underlying the personality traits is a topic of great interest. On the other hand, it is now established that the brain is a dynamic networked system that can be studied by using functional connectivity techniques. However, much of the current understanding of personality-related differences in functional connectivity has been obtained through the stationary analysis, which does not capture the complex dynamical properties of brain networks. In this study, we aimed at evaluating the feasibility of using dynamic network measures to predict personality traits. Using the electro-encephalography (EEG)/magneto-encephalography (MEG) source connectivity method combined with a sliding window approach, dynamic functional brain networks were reconstructed from two datasets: (1) resting-state EEG data acquired from 56 subjects; (2) resting-state MEG data provided from the Human Connectome Project. Then, several dynamic functional connectivity metrics were evaluated. Similar observations were obtained by the two modalities (EEG and MEG) according to the neuroticism, which showed a negative correlation with the dynamic variability of resting-state brain networks. In particular, a significant relationship between this personality trait and the dynamic variability of the temporal lobe regions was observed. Results also revealed that extraversion and openness are positively correlated with the dynamics of the brain networks. These findings highlight the importance of tracking the dynamics of functional brain networks to improve our understanding about the neural substrates of personality.</AbstractText
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To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.</AbstractText We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.</AbstractText Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.</AbstractText Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.</AbstractText
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Rett syndrome (RTT) is an X-linked disorder caused by mutations in <i
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Brain Network Dynamics Correlate with Personality Traits. Identifying the neural substrates underlying the personality traits is a topic of great interest. On the other hand, it is now established that the brain is a dynamic networked system that can be studied by using functional connectivity techniques. However, much of the current understanding of personality-related differences in functional connectivity has been obtained through the stationary analysis, which does not capture the complex dynamical properties of brain networks. In this study, we aimed at evaluating the feasibility of using dynamic network measures to predict personality traits. Using the electro-encephalography (EEG)/magneto-encephalography (MEG) source connectivity method combined with a sliding window approach, dynamic functional brain networks were reconstructed from two datasets: (1) resting-state EEG data acquired from 56 subjects; (2) resting-state MEG data provided from the Human Connectome Project. Then, several dynamic functional connectivity metrics were evaluated. Similar observations were obtained by the two modalities (EEG and MEG) according to the neuroticism, which showed a negative correlation with the dynamic variability of resting-state brain networks. In particular, a significant relationship between this personality trait and the dynamic variability of the temporal lobe regions was observed. Results also revealed that extraversion and openness are positively correlated with the dynamics of the brain networks. These findings highlight the importance of tracking the dynamics of functional brain networks to improve our understanding about the neural substrates of personality.</AbstractText
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Abnormal thalamocortical network dynamics in migraine. To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.</AbstractText We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.</AbstractText Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.</AbstractText Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.</AbstractText
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Methyl-CpG-binding protein 2 gene mutations and its association with epilepsy: a single centre study from the Indian subcontinent. Rett syndrome (RTT) is an X-linked disorder caused by mutations in <i
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22162059
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21322385
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34184781
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Multiple sclerosis normal-appearing white matter: pathology-imaging correlations.
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Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs.
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Genome-Wide Association Study Identifies Risk Loci for Cluster Headache.
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The study was undertaken to determine the pathologic basis of subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple sclerosis brains.</AbstractText Brain tissues were obtained through a rapid postmortem protocol that included in situ magnetic resonance imaging (MRI). Four types of MRI-defined regions of interest (ROIs) were analyzed: (1) regions that were abnormal on all images (T2T1MTR lesions); (2) NAWM regions with slightly abnormal MTR located close to white matter lesions (sa-WM Close); (3) NAWM regions with slightly abnormal MTR located far from lesions (sa-WM Far); and (4) NAWM regions with normal MTR (NAWM). Immunohistochemical analysis for each ROI comprised immunostaining for myelin, axonal markers, activated microglia/macrophages, astrocytes, plasma proteins, and blood vessels.</AbstractText Forty-eight ROIs from 4 secondary progressive MS brains were analyzed. sa-WM Close ROIs were associated with significantly more axonal swellings. There were more enlarged major histocompatibility complex II(+) microglia and macrophages detected in sa-WM Far, sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI measures were moderately correlated with myelin density, axonal area, and axonal counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI measures in nonlesional white matter (WM) were correlated with activated microglia, but not with axonal or myelin integrity.</AbstractText The pathologic substrates for MRI abnormalities in NAWM vary based on distance from focal WM lesions. Close to WM lesions, axonal pathology and microglial activation may explain subtle MRI changes. Distant from lesions, microglial activation associated with proximity to cortical lesions might underlie MRI abnormalities.</AbstractText
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Cerebrovascular accidents, or strokes, and gliomas are common intraaxial brain lesions in dogs. An accurate differentiation of these two lesions is necessary for prognosis and treatment decisions. The magnetic resonance (MR) imaging characteristics of 21 dogs with a presumed cerebrovascular accident and 17 with a glioma were compared. MR imaging findings were reviewed retrospectively by three observers unaware of the final diagnosis. Statistically significant differences between the appearance of gliomas and cerebrovascular accidents were identified based on lesion location, size, mass effect, perilesional edema, and appearance of the apparent diffusion coefficient map. Gliomas were predominantly located in the cerebrum (76%) compared with presumed cerebrovascular accidents that were located mainly in the cerebellum, thalamus, caudate nucleus, midbrain, and brainstem (76%). Gliomas were significantly larger compared with presumed cerebrovascular accidents and more commonly associated with mass effect and perilesional edema. Wedge-shaped lesions were seen only in 19% of presumed cerebrovascular accidents. Between the three observers, 10-47% of the presumed cerebrovascular accidents were misdiagnosed as gliomas, and 0-12% of the gliomas were misdiagnosed as cerebrovascular accidents. Diffusion weighted imaging increased the accuracy of the diagnosis for both lesions. Agreement between observers was moderate (kappa = 0.48, P < 0.01).</AbstractText
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This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways.</AbstractText We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed.</AbstractText Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 × 10<sup We identified and replicated several genome-wide significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021;90:193-202.</AbstractText
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Multiple sclerosis normal-appearing white matter: pathology-imaging correlations. The study was undertaken to determine the pathologic basis of subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple sclerosis brains.</AbstractText Brain tissues were obtained through a rapid postmortem protocol that included in situ magnetic resonance imaging (MRI). Four types of MRI-defined regions of interest (ROIs) were analyzed: (1) regions that were abnormal on all images (T2T1MTR lesions); (2) NAWM regions with slightly abnormal MTR located close to white matter lesions (sa-WM Close); (3) NAWM regions with slightly abnormal MTR located far from lesions (sa-WM Far); and (4) NAWM regions with normal MTR (NAWM). Immunohistochemical analysis for each ROI comprised immunostaining for myelin, axonal markers, activated microglia/macrophages, astrocytes, plasma proteins, and blood vessels.</AbstractText Forty-eight ROIs from 4 secondary progressive MS brains were analyzed. sa-WM Close ROIs were associated with significantly more axonal swellings. There were more enlarged major histocompatibility complex II(+) microglia and macrophages detected in sa-WM Far, sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI measures were moderately correlated with myelin density, axonal area, and axonal counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI measures in nonlesional white matter (WM) were correlated with activated microglia, but not with axonal or myelin integrity.</AbstractText The pathologic substrates for MRI abnormalities in NAWM vary based on distance from focal WM lesions. Close to WM lesions, axonal pathology and microglial activation may explain subtle MRI changes. Distant from lesions, microglial activation associated with proximity to cortical lesions might underlie MRI abnormalities.</AbstractText
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Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs. Cerebrovascular accidents, or strokes, and gliomas are common intraaxial brain lesions in dogs. An accurate differentiation of these two lesions is necessary for prognosis and treatment decisions. The magnetic resonance (MR) imaging characteristics of 21 dogs with a presumed cerebrovascular accident and 17 with a glioma were compared. MR imaging findings were reviewed retrospectively by three observers unaware of the final diagnosis. Statistically significant differences between the appearance of gliomas and cerebrovascular accidents were identified based on lesion location, size, mass effect, perilesional edema, and appearance of the apparent diffusion coefficient map. Gliomas were predominantly located in the cerebrum (76%) compared with presumed cerebrovascular accidents that were located mainly in the cerebellum, thalamus, caudate nucleus, midbrain, and brainstem (76%). Gliomas were significantly larger compared with presumed cerebrovascular accidents and more commonly associated with mass effect and perilesional edema. Wedge-shaped lesions were seen only in 19% of presumed cerebrovascular accidents. Between the three observers, 10-47% of the presumed cerebrovascular accidents were misdiagnosed as gliomas, and 0-12% of the gliomas were misdiagnosed as cerebrovascular accidents. Diffusion weighted imaging increased the accuracy of the diagnosis for both lesions. Agreement between observers was moderate (kappa = 0.48, P < 0.01).</AbstractText
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Genome-Wide Association Study Identifies Risk Loci for Cluster Headache. This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways.</AbstractText We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed.</AbstractText Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 × 10<sup We identified and replicated several genome-wide significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021;90:193-202.</AbstractText
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26265200
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18601309
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26110112
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Probing the Role of Side-Chain Interconnecting Groups in the Structural Hydrophobicity of Comblike Fluorinated Polystyrene by Solid-State NMR Spectroscopy.
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A 140 GHz prepolarizer for dissolution dynamic nuclear polarization.
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Disruption of caudate working memory activation in chronic blast-related traumatic brain injury.
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In order to probe the role of side-chain interconnecting groups (-O-, -S-, and -SO2- linkages between the polystyrene (PST) main chain and fluorooctyl side chain) in the hydrophobicity of the comblike fluorinated polystyrenes, the molecular motion and structure of polymers are explored using the spin-lattice relaxation times (T1 and T1ρ) by solid-state (1)H and (19)F nuclear magnetic resonance spectroscopy. The chain-end motions of the polystyrene main chain and the fluorooctyl side chain are homogeneous, regardless of the interconnecting groups, which means that the chain-end motions of the main chain and the side chain maintain consistency, and these are irrelevant to each other. However, the local dynamic of the main chain shows the structural heterogeneity composed of the mobile and rigid regions, attributed to the rigidity of the side chain. The mobile dynamic portions of the main chain for PST-O and PST-S increase, and their rigid dynamic portions decrease as the temperature increases, whereas the ratio of structural heterogeneity for PST-SO2 is maintained despite increasing temperature. The activation energies (Ea) corresponding to the local motion of fluorooctyl side chains for PST-O and PST-S are drastically increased on the fast motion side compared to the slow motion side, suggesting the motional transformation of side chains for PST-O and PST-S from the small local motion into the large-scale movements related to a cooperative segmental motion when heated. Also, the local motion of the fluorooctyl side chain for PST-SO2 has similar Ea values on both sides, indicating that the relaxation time of PST-SO2 does not change with temperature. Therefore, PST-SO2 is structurally more stable than PST-O or PST-S, which can be attributed to the densely packed fluorooctyl side chain structure caused by the large dipole moment of the sulfone interconnecting group.</AbstractText
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Apart from their very classical use to build polarized targets for particle physics, the methods of dynamic nuclear polarization (DNP) have more recently found application for sensitivity enhancement in high-resolution NMR, both in the solid and in the liquid state. It is often thought that the possible signal enhancement in such applications deteriorates when the DNP is performed at higher fields. We show that for a dissolution-DNP method that uses conventional (2,2,6,6-tetramethylpiperidine 1-oxyl) radicals as the paramagnetic agent, this is not the case for fields up to 5 T.</AbstractText
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Mild to moderate traumatic brain injury (TBI) due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes). Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI) study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female) who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females) with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females) and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females) without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate). Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results could not be attributed to caudate atrophy or the presence of PTSD symptoms. Our results point to a specific vulnerability of the caudate to blast injury. Changes in activation during the Sternberg Item Recognition Task, and potentially other tasks that recruit the caudate, may serve as biomarkers for blast TBI.</AbstractText
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Probing the Role of Side-Chain Interconnecting Groups in the Structural Hydrophobicity of Comblike Fluorinated Polystyrene by Solid-State NMR Spectroscopy. In order to probe the role of side-chain interconnecting groups (-O-, -S-, and -SO2- linkages between the polystyrene (PST) main chain and fluorooctyl side chain) in the hydrophobicity of the comblike fluorinated polystyrenes, the molecular motion and structure of polymers are explored using the spin-lattice relaxation times (T1 and T1ρ) by solid-state (1)H and (19)F nuclear magnetic resonance spectroscopy. The chain-end motions of the polystyrene main chain and the fluorooctyl side chain are homogeneous, regardless of the interconnecting groups, which means that the chain-end motions of the main chain and the side chain maintain consistency, and these are irrelevant to each other. However, the local dynamic of the main chain shows the structural heterogeneity composed of the mobile and rigid regions, attributed to the rigidity of the side chain. The mobile dynamic portions of the main chain for PST-O and PST-S increase, and their rigid dynamic portions decrease as the temperature increases, whereas the ratio of structural heterogeneity for PST-SO2 is maintained despite increasing temperature. The activation energies (Ea) corresponding to the local motion of fluorooctyl side chains for PST-O and PST-S are drastically increased on the fast motion side compared to the slow motion side, suggesting the motional transformation of side chains for PST-O and PST-S from the small local motion into the large-scale movements related to a cooperative segmental motion when heated. Also, the local motion of the fluorooctyl side chain for PST-SO2 has similar Ea values on both sides, indicating that the relaxation time of PST-SO2 does not change with temperature. Therefore, PST-SO2 is structurally more stable than PST-O or PST-S, which can be attributed to the densely packed fluorooctyl side chain structure caused by the large dipole moment of the sulfone interconnecting group.</AbstractText
|
A 140 GHz prepolarizer for dissolution dynamic nuclear polarization. Apart from their very classical use to build polarized targets for particle physics, the methods of dynamic nuclear polarization (DNP) have more recently found application for sensitivity enhancement in high-resolution NMR, both in the solid and in the liquid state. It is often thought that the possible signal enhancement in such applications deteriorates when the DNP is performed at higher fields. We show that for a dissolution-DNP method that uses conventional (2,2,6,6-tetramethylpiperidine 1-oxyl) radicals as the paramagnetic agent, this is not the case for fields up to 5 T.</AbstractText
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Disruption of caudate working memory activation in chronic blast-related traumatic brain injury. Mild to moderate traumatic brain injury (TBI) due to blast exposure is frequently diagnosed in veterans returning from the wars in Iraq and Afghanistan. However, it is unclear whether neural damage resulting from blast TBI differs from that found in TBI due to blunt-force trauma (e.g., falls and motor vehicle crashes). Little is also known about the effects of blast TBI on neural networks, particularly over the long term. Because impairment in working memory has been linked to blunt-force TBI, the present functional magnetic resonance imaging (fMRI) study sought to investigate whether brain activation in response to a working memory task would discriminate blunt-force from blast TBI. Twenty-five veterans (mean age = 29.8 years, standard deviation = 6.01 years, 1 female) who incurred TBI due to blast an average of 4.2 years prior to enrollment and 25 civilians (mean age = 27.4 years, standard deviation = 6.68 years, 4 females) with TBI due to blunt-force trauma performed the Sternberg Item Recognition Task while undergoing fMRI. The task involved encoding 1, 3, or 5 items in working memory. A group of 25 veterans (mean age = 29.9 years, standard deviation = 5.53 years, 0 females) and a group of 25 civilians (mean age = 27.3 years, standard deviation = 5.81 years, 0 females) without history of TBI underwent identical imaging procedures and served as controls. Results indicated that the civilian TBI group and both control groups demonstrated a monotonic relationship between working memory set size and activation in the right caudate during encoding, whereas the blast TBI group did not (p < 0.05, corrected for multiple comparisons using False Discovery Rate). Blast TBI was also associated with worse performance on the Sternberg Item Recognition Task relative to the other groups, although no other group differences were found on neuropsychological measures of episodic memory, inhibition, and general processing speed. These results could not be attributed to caudate atrophy or the presence of PTSD symptoms. Our results point to a specific vulnerability of the caudate to blast injury. Changes in activation during the Sternberg Item Recognition Task, and potentially other tasks that recruit the caudate, may serve as biomarkers for blast TBI.</AbstractText
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18715754
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12143363
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19041611
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Impact of protein kinase C activation on epileptiform activity in the hippocampal slice.
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Effects of chronic epilepsy on declarative memory systems.
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"You just have to make the pain go away"--children's experiences of pain management.
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There is evidence suggesting that protein kinase C (PKC) activation can prevent the enhanced network excitability associated with status epilepticus and group I metabotropic glutamate receptor (mGluR)-induced epileptogenesis. However, we observed no suppression of mGluR-induced burst prolongation in the guinea pig hippocampal slice when applied in the presence of the PKC activator phorbol-12,13-dibutyrate (PDBu). Furthermore, PDBu alone converted picrotoxin-induced interictal bursts into ictal-length discharges ranging from 2 to 6s in length. This effect could not be elicited by the inactive analog 4-alpha-PDBu and was suppressed with the PKC inhibitor chelerythrine, indicating PKC dependence. PKC activation can enhance neurotransmitter release, and both glutamate and acetylcholine are capable of eliciting similar prolonged synchronized discharges. However, neither mGluR1 nor NMDA receptor antagonist suppressed PDBu-driven burst prolongation, suggesting that increased glutamate release alone is unlikely to account for the PKC-induced expression of ictaform discharges. Similarly, atropine, a broad-spectrum muscarinic receptor antagonist, had no effect on PKC-induced burst prolongation. By contrast, AMPA/kainate receptor antagonist abolished PKC-induced burst prolongation, and mGluR5 antagonist significantly blunted the maximum burst length induced by PKC. These data suggest that PKC-induced prolongation of epileptiform bursts is dependent on changes specific to mGluR5 and AMPA/kainate receptors and not mediated simply by a generalized increase in transmitter release.</AbstractText
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Memory is systematically affected by temporal lobe epilepsy. Since surgery is a promising alternative to pharmacological treatment the questions which memory system is affected and what the long-term prognosis of memory is are more relevant than ever. We address these issues by cross-sectional and longitudinal analysis of memory performance in large series of patients with temporal lobe epilepsy (TLE). The findings indicate that episodic memory rather than semantic memory is impaired in TLE, in particular in TLE with mesial temporal pathology. With the exception that mesial functions appear increasingly affected by chronic non-mesial TLE, memory decline in TLE is not different from that observed in healthy control subjects. However, since patients perform poorer than controls at any age, normal senescence brings patients to mnesic disability at a younger age. Semantic memory seems unaffected by this process but early cortical lesions appear to interfere with knowledge acquisition. Longitudinal data come to a different conclusion regarding the contribution of epilepsy/seizures to memory decline. Conservative treatment is associated with significant decline in figural memory and 37% of the patients experience some memory decline in the long run. Surgery partly anticipates the decline observed with conservative treatment, but losses are most marked after left temporal lobe surgery. After surgery, quite stable memory or even late recovery from surgery is indicated. Leaving aside the surgical intervention, the data provide evidence that the longitudinal memory outcome in TLE is determined by seizure control, seizure severity, mental reserve capacities, and the retest interval. Thus early and efficient seizure control and the prevention of any cerebral damage from the beginning of epilepsy are demanded.</AbstractText
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This paper reports a study of the descriptions young children use and their expectations for pain management interventions experienced during hospitalization. The alleviation of children's pain has been investigated through the eyes of health care providers and parents, but the children's own perspective has largely been ignored. To date, there is a growing tendency to listen to the children when making final decisions on treatment in child health care. The evidence shows that children should be regarded as experts on their pain to maximize the options for pain management and to provide high-quality care. Forty-four children who were inpatients in four pediatric units in a university hospital participated in the study. The data were collected by means of a qualitative interview with the children until theoretic saturation was reached. The data analysis was based on inductive content analysis. The findings indicate that the children used multiple strategies while trying to deal with their pains during hospitalization and expected professional competence from health care professionals. Moreover, the children valued the care and attention provided by significant others. When managing pain in hospitalized children with a wide diversity of sources, the complexity of pain as a physiologic, psychologic, social, and cultural phenomenon must not be overlooked.</AbstractText
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Impact of protein kinase C activation on epileptiform activity in the hippocampal slice. There is evidence suggesting that protein kinase C (PKC) activation can prevent the enhanced network excitability associated with status epilepticus and group I metabotropic glutamate receptor (mGluR)-induced epileptogenesis. However, we observed no suppression of mGluR-induced burst prolongation in the guinea pig hippocampal slice when applied in the presence of the PKC activator phorbol-12,13-dibutyrate (PDBu). Furthermore, PDBu alone converted picrotoxin-induced interictal bursts into ictal-length discharges ranging from 2 to 6s in length. This effect could not be elicited by the inactive analog 4-alpha-PDBu and was suppressed with the PKC inhibitor chelerythrine, indicating PKC dependence. PKC activation can enhance neurotransmitter release, and both glutamate and acetylcholine are capable of eliciting similar prolonged synchronized discharges. However, neither mGluR1 nor NMDA receptor antagonist suppressed PDBu-driven burst prolongation, suggesting that increased glutamate release alone is unlikely to account for the PKC-induced expression of ictaform discharges. Similarly, atropine, a broad-spectrum muscarinic receptor antagonist, had no effect on PKC-induced burst prolongation. By contrast, AMPA/kainate receptor antagonist abolished PKC-induced burst prolongation, and mGluR5 antagonist significantly blunted the maximum burst length induced by PKC. These data suggest that PKC-induced prolongation of epileptiform bursts is dependent on changes specific to mGluR5 and AMPA/kainate receptors and not mediated simply by a generalized increase in transmitter release.</AbstractText
|
Effects of chronic epilepsy on declarative memory systems. Memory is systematically affected by temporal lobe epilepsy. Since surgery is a promising alternative to pharmacological treatment the questions which memory system is affected and what the long-term prognosis of memory is are more relevant than ever. We address these issues by cross-sectional and longitudinal analysis of memory performance in large series of patients with temporal lobe epilepsy (TLE). The findings indicate that episodic memory rather than semantic memory is impaired in TLE, in particular in TLE with mesial temporal pathology. With the exception that mesial functions appear increasingly affected by chronic non-mesial TLE, memory decline in TLE is not different from that observed in healthy control subjects. However, since patients perform poorer than controls at any age, normal senescence brings patients to mnesic disability at a younger age. Semantic memory seems unaffected by this process but early cortical lesions appear to interfere with knowledge acquisition. Longitudinal data come to a different conclusion regarding the contribution of epilepsy/seizures to memory decline. Conservative treatment is associated with significant decline in figural memory and 37% of the patients experience some memory decline in the long run. Surgery partly anticipates the decline observed with conservative treatment, but losses are most marked after left temporal lobe surgery. After surgery, quite stable memory or even late recovery from surgery is indicated. Leaving aside the surgical intervention, the data provide evidence that the longitudinal memory outcome in TLE is determined by seizure control, seizure severity, mental reserve capacities, and the retest interval. Thus early and efficient seizure control and the prevention of any cerebral damage from the beginning of epilepsy are demanded.</AbstractText
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"You just have to make the pain go away"--children's experiences of pain management. This paper reports a study of the descriptions young children use and their expectations for pain management interventions experienced during hospitalization. The alleviation of children's pain has been investigated through the eyes of health care providers and parents, but the children's own perspective has largely been ignored. To date, there is a growing tendency to listen to the children when making final decisions on treatment in child health care. The evidence shows that children should be regarded as experts on their pain to maximize the options for pain management and to provide high-quality care. Forty-four children who were inpatients in four pediatric units in a university hospital participated in the study. The data were collected by means of a qualitative interview with the children until theoretic saturation was reached. The data analysis was based on inductive content analysis. The findings indicate that the children used multiple strategies while trying to deal with their pains during hospitalization and expected professional competence from health care professionals. Moreover, the children valued the care and attention provided by significant others. When managing pain in hospitalized children with a wide diversity of sources, the complexity of pain as a physiologic, psychologic, social, and cultural phenomenon must not be overlooked.</AbstractText
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40376890
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38517752
|
40759726
|
Unraveling the Relation of Parkinson's Disease and Metabolites: A Combined Analysis of Stool and Plasma Metabolites Based on Untargeted Metabolomics Technology.
|
Structural mechanisms for VMAT2 inhibition by tetrabenazine.
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Internet of things enabled deep learning monitoring system for realtime performance metrics and athlete feedback in college sports.
|
Metabolomics technology has been widely utilized to uncover the action mechanisms of Parkinson's Disease (PD) and to identify PD-related biomarkers. In this study, we compared plasma and fecal metabolite levels between PD patients and their healthy spouses (HS), aiming to identify the associations of differential metabolites with intestinal inflammation, intestinal barrier function, and clinical characteristics of PD.</AbstractText Untargeted metabolomics techniques were used to characterize plasma and fecal metabolite profiles. We identified metabolites with elevated plasma levels in PD patients, while no significant differences were observed in fecal samples. Partial correlation analysis was employed to investigate the associations between these metabolites, markers of intestinal inflammation (calprotectin and lactoferrin), markers of intestinal permeability (α-1-antitrypsin and zonulin), and clinical characteristics of PD patients.</AbstractText The study identified ten metabolites that were significantly elevated in the plasma of PD patients compared to HS (p < 0.05), while their fecal concentrations did not differ significantly. Correlation analysis revealed that elevated levels of differential metabolites in the plasma of PD patients were associated with increased intestinal permeability and inflammation. Furthermore, five metabolites, including 3,4-Dihydroxyphenylglycol O-sulfate and Propyl gallate, were linked to PD symptoms. Receiver Operating Characteristic (ROC) curves demonstrated that these metabolites could effectively distinguish between PD patients and HS, with an area under the curve (AUC) of 0.94, indicating excellent predictive performance.</AbstractText This study identified significant metabolite alterations in PD patients and revealed their associations with intestinal barrier dysfunction and clinical characteristics of the disease.</AbstractText
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The vesicular monoamine transporter 2 (VMAT2) is a proton-dependent antiporter responsible for loading monoamine neurotransmitters into synaptic vesicles. Dysregulation of VMAT2 can lead to several neuropsychiatric disorders including Parkinson's disease and schizophrenia. Furthermore, drugs such as amphetamine and MDMA are known to act on VMAT2, exemplifying its role in the mechanisms of actions for drugs of abuse. Despite VMAT2's importance, there remains a critical lack of mechanistic understanding, largely driven by a lack of structural information. Here, we report a 3.1 Å resolution cryo-electron microscopy (cryo-EM) structure of VMAT2 complexed with tetrabenazine (TBZ), a non-competitive inhibitor used in the treatment of Huntington's chorea. We find TBZ interacts with residues in a central binding site, locking VMAT2 in an occluded conformation and providing a mechanistic basis for non-competitive inhibition. We further identify residues critical for cytosolic and lumenal gating, including a cluster of hydrophobic residues which are involved in a lumenal gating strategy. Our structure also highlights three distinct polar networks that may determine VMAT2 conformational dynamics and play a role in proton transduction. The structure elucidates mechanisms of VMAT2 inhibition and transport, providing insights into VMAT2 architecture, function, and the design of small-molecule therapeutics.</AbstractText
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This study presents an Internet of Things (IoT)-enabled Deep Learning Monitoring (IoT-E-DLM) model for real-time Athletic Performance (AP) tracking and feedback in collegiate sports. The proposed work integrates advanced wearable sensor technologies with a hybrid neural network combining Temporal Convolutional Networks, Bidirectional Long Short-Term Memory (TCN + BiLSTM) + Attention mechanisms. It is designed to overcome key challenges in processing heterogeneous, high-frequency sensor data and delivering low-latency, sport-specific feedback. The system deployed edge computing for real-time local processing and cloud setup for high-complexity analytics, achieving a balance between responsiveness and accuracy. Extensive research was tested with 147 student-athletes across numerous sports, including track and field, basketball, soccer, and swimming, over 12 months at Shangqiu University. The proposed model achieved a prediction accuracy of 93.45% with an average processing latency of 12.34 ms, outperforming conventional and state-of-the-art approaches. The system also demonstrated efficient resource usage (CPU: 68.34%, GPU: 72.56%), high data capture reliability (98.37%), and precise temporal synchronization. These results confirm the model's effectiveness in enabling real-time performance monitoring and feedback delivery, establishing a robust groundwork for future developments in Artificial Intelligence (AI)-driven sports analytics.</AbstractText
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Unraveling the Relation of Parkinson's Disease and Metabolites: A Combined Analysis of Stool and Plasma Metabolites Based on Untargeted Metabolomics Technology. Metabolomics technology has been widely utilized to uncover the action mechanisms of Parkinson's Disease (PD) and to identify PD-related biomarkers. In this study, we compared plasma and fecal metabolite levels between PD patients and their healthy spouses (HS), aiming to identify the associations of differential metabolites with intestinal inflammation, intestinal barrier function, and clinical characteristics of PD.</AbstractText Untargeted metabolomics techniques were used to characterize plasma and fecal metabolite profiles. We identified metabolites with elevated plasma levels in PD patients, while no significant differences were observed in fecal samples. Partial correlation analysis was employed to investigate the associations between these metabolites, markers of intestinal inflammation (calprotectin and lactoferrin), markers of intestinal permeability (α-1-antitrypsin and zonulin), and clinical characteristics of PD patients.</AbstractText The study identified ten metabolites that were significantly elevated in the plasma of PD patients compared to HS (p < 0.05), while their fecal concentrations did not differ significantly. Correlation analysis revealed that elevated levels of differential metabolites in the plasma of PD patients were associated with increased intestinal permeability and inflammation. Furthermore, five metabolites, including 3,4-Dihydroxyphenylglycol O-sulfate and Propyl gallate, were linked to PD symptoms. Receiver Operating Characteristic (ROC) curves demonstrated that these metabolites could effectively distinguish between PD patients and HS, with an area under the curve (AUC) of 0.94, indicating excellent predictive performance.</AbstractText This study identified significant metabolite alterations in PD patients and revealed their associations with intestinal barrier dysfunction and clinical characteristics of the disease.</AbstractText
|
Structural mechanisms for VMAT2 inhibition by tetrabenazine. The vesicular monoamine transporter 2 (VMAT2) is a proton-dependent antiporter responsible for loading monoamine neurotransmitters into synaptic vesicles. Dysregulation of VMAT2 can lead to several neuropsychiatric disorders including Parkinson's disease and schizophrenia. Furthermore, drugs such as amphetamine and MDMA are known to act on VMAT2, exemplifying its role in the mechanisms of actions for drugs of abuse. Despite VMAT2's importance, there remains a critical lack of mechanistic understanding, largely driven by a lack of structural information. Here, we report a 3.1 Å resolution cryo-electron microscopy (cryo-EM) structure of VMAT2 complexed with tetrabenazine (TBZ), a non-competitive inhibitor used in the treatment of Huntington's chorea. We find TBZ interacts with residues in a central binding site, locking VMAT2 in an occluded conformation and providing a mechanistic basis for non-competitive inhibition. We further identify residues critical for cytosolic and lumenal gating, including a cluster of hydrophobic residues which are involved in a lumenal gating strategy. Our structure also highlights three distinct polar networks that may determine VMAT2 conformational dynamics and play a role in proton transduction. The structure elucidates mechanisms of VMAT2 inhibition and transport, providing insights into VMAT2 architecture, function, and the design of small-molecule therapeutics.</AbstractText
|
Internet of things enabled deep learning monitoring system for realtime performance metrics and athlete feedback in college sports. This study presents an Internet of Things (IoT)-enabled Deep Learning Monitoring (IoT-E-DLM) model for real-time Athletic Performance (AP) tracking and feedback in collegiate sports. The proposed work integrates advanced wearable sensor technologies with a hybrid neural network combining Temporal Convolutional Networks, Bidirectional Long Short-Term Memory (TCN + BiLSTM) + Attention mechanisms. It is designed to overcome key challenges in processing heterogeneous, high-frequency sensor data and delivering low-latency, sport-specific feedback. The system deployed edge computing for real-time local processing and cloud setup for high-complexity analytics, achieving a balance between responsiveness and accuracy. Extensive research was tested with 147 student-athletes across numerous sports, including track and field, basketball, soccer, and swimming, over 12 months at Shangqiu University. The proposed model achieved a prediction accuracy of 93.45% with an average processing latency of 12.34 ms, outperforming conventional and state-of-the-art approaches. The system also demonstrated efficient resource usage (CPU: 68.34%, GPU: 72.56%), high data capture reliability (98.37%), and precise temporal synchronization. These results confirm the model's effectiveness in enabling real-time performance monitoring and feedback delivery, establishing a robust groundwork for future developments in Artificial Intelligence (AI)-driven sports analytics.</AbstractText
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36105590
|
24373885
|
36272786
|
Neural dynamics of illusory tactile pulling sensations.
|
The what, when, where, and how of visual word recognition.
|
Buffer gas cooled ice chemistry. I. Buffer gas cell and mm-wave spectrometer.
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Directional tactile pulling sensations are integral to everyday life, but their neural mechanisms remain unknown. Prior accounts hold that primary somatosensory (SI) activity is sufficient to generate pulling sensations, with alternative proposals suggesting that amodal frontal or parietal regions may be critical. We combined high-density EEG with asymmetric vibration, which creates an illusory pulling sensation, thereby unconfounding pulling sensations from unrelated sensorimotor processes. Oddballs that created opposite direction pulls to common stimuli were compared to the same oddballs after neutral common stimuli (symmetric vibration) and to neutral oddballs. We found evidence against the sensory-frontal N140 and in favor of the midline P200 tracking the emergence of pulling sensations, specifically contralateral parietal lobe activity 264-320ms, centered on the intraparietal sulcus. This suggests that SI is not sufficient to generate pulling sensations, which instead depend on the parietal association cortex, and may reflect the extraction of orientation information and related spatial processing.</AbstractText
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A long-standing debate in reading research is whether printed words are perceived in a feedforward manner on the basis of orthographic information, with other representations such as semantics and phonology activated subsequently, or whether the system is fully interactive and feedback from these representations shapes early visual word recognition. We review recent evidence from behavioral, functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and biologically plausible connectionist modeling approaches, focusing on how each approach provides insight into the temporal flow of information in the lexical system. We conclude that, consistent with interactive accounts, higher-order linguistic representations modulate early orthographic processing. We also discuss how biologically plausible interactive frameworks and coordinated empirical and computational work can advance theories of visual word recognition and other domains (e.g., object recognition).</AbstractText
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A new instrument is described that will employ buffer gas cooling with mm-wave rotational spectroscopy (60-90 GHz) to probe molecules desorbed from astrochemical ices prepared in an ultrahigh vacuum environment. Here the design and performance of the buffer gas cell, mm-wave spectrometer and data acquisition system are reported, while application to molecules desorbed from ice surfaces will be described in a future publication. The effective temperature of the neon-cooled buffer gas cell is determined by monitoring a range of rotational lines of propyl cyanide introduced into the cell. Its number density is estimated from comparison to room temperature measurements and the effective collision cross section with neon is estimated by monitoring the free induction decay (FID) lifetimes. The spectrometer and data acquisition system described are capable of acquiring and time-domain averaging the FIDs at 10 Gs/s, 10 bit vertical resolution and 98% duty cycle.</AbstractText
|
Neural dynamics of illusory tactile pulling sensations. Directional tactile pulling sensations are integral to everyday life, but their neural mechanisms remain unknown. Prior accounts hold that primary somatosensory (SI) activity is sufficient to generate pulling sensations, with alternative proposals suggesting that amodal frontal or parietal regions may be critical. We combined high-density EEG with asymmetric vibration, which creates an illusory pulling sensation, thereby unconfounding pulling sensations from unrelated sensorimotor processes. Oddballs that created opposite direction pulls to common stimuli were compared to the same oddballs after neutral common stimuli (symmetric vibration) and to neutral oddballs. We found evidence against the sensory-frontal N140 and in favor of the midline P200 tracking the emergence of pulling sensations, specifically contralateral parietal lobe activity 264-320ms, centered on the intraparietal sulcus. This suggests that SI is not sufficient to generate pulling sensations, which instead depend on the parietal association cortex, and may reflect the extraction of orientation information and related spatial processing.</AbstractText
|
The what, when, where, and how of visual word recognition. A long-standing debate in reading research is whether printed words are perceived in a feedforward manner on the basis of orthographic information, with other representations such as semantics and phonology activated subsequently, or whether the system is fully interactive and feedback from these representations shapes early visual word recognition. We review recent evidence from behavioral, functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and biologically plausible connectionist modeling approaches, focusing on how each approach provides insight into the temporal flow of information in the lexical system. We conclude that, consistent with interactive accounts, higher-order linguistic representations modulate early orthographic processing. We also discuss how biologically plausible interactive frameworks and coordinated empirical and computational work can advance theories of visual word recognition and other domains (e.g., object recognition).</AbstractText
|
Buffer gas cooled ice chemistry. I. Buffer gas cell and mm-wave spectrometer. A new instrument is described that will employ buffer gas cooling with mm-wave rotational spectroscopy (60-90 GHz) to probe molecules desorbed from astrochemical ices prepared in an ultrahigh vacuum environment. Here the design and performance of the buffer gas cell, mm-wave spectrometer and data acquisition system are reported, while application to molecules desorbed from ice surfaces will be described in a future publication. The effective temperature of the neon-cooled buffer gas cell is determined by monitoring a range of rotational lines of propyl cyanide introduced into the cell. Its number density is estimated from comparison to room temperature measurements and the effective collision cross section with neon is estimated by monitoring the free induction decay (FID) lifetimes. The spectrometer and data acquisition system described are capable of acquiring and time-domain averaging the FIDs at 10 Gs/s, 10 bit vertical resolution and 98% duty cycle.</AbstractText
|
40783750
|
27050242
|
40667175
|
Investigating the prevalence of medication near-misses and reporting intention among nurses in tertiary hospitals from China.
|
Technical Actions, Heart Rate, and Locomotor Activity in 7v7 and 8v8 Games for Female Youth Soccer Players.
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Competition between tool and hand motion impairs movement planning in limb apraxia.
|
Globally, medication near-misses are a public health issue as they often have serious consequences for patients and healthcare systems. Currently, few studies have investigated nurses' intention to report medication near-misses. Therefore, this study aims to examine the incidence of medication near-misses and factors influencing reporting intention among nurses in tertiary hospitals in Shandong Province, to fill the research gap in this area.</AbstractText A descriptive cross-sectional design.</AbstractText Between March 2021 and December 2021, 2625 nurses in seven tertiary hospitals from Shandong Province, China were enrolled in the study, using convenience sampling. Information about medication near-misses, reporting intention and barriers was collected using self-reported questionnaire, subscales of the Adverse Event Reporting Intention Questionnaire, and Medication Near-Miss Reporting Barriers Scale. This study explored the association between potential determinants from the perspective of nurses and managers using generalized linear model.</AbstractText About 25.3% of nurses experienced medication near-misses, with a mean reporting intention score of 5.44 (standardized deviation=1.13). The main approach for reporting medication near-misses was verbal language (80.6%). Higher professional title (χ2=13.770, P = 0.003), lower educational level (χ2=6.722, P = 0.035), fewer weekly work hours (χ2=3.947, P = 0.047), no previous medication near-misses experience (χ2=46.517, P < 0.001), and not having siblings (χ2=4.150, P = 0.042) nurses showed a higher level of reporting intention. The manager's negative response (χ2=7.059, P = 0.008) and complex reporting system (χ2=17.120, P < 0.001) were associated with lower levels of reporting intention, primarily influenced by departmental categories (χ2=22.306, P = 0.002).</AbstractText The results of this study show that nurses' medication near-misses reporting rate is relatively low, but their intention to report is relatively strong. Meanwhile, nurses' intention to report medication near-misses is influenced by multiple factors. This suggests that nursing managers should develop management strategies for near-miss events and actively provide training to enhance clinical nurses' willingness to report such events.</AbstractText
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Ørntoft, C, Larsen, MN, Andersen, TB, Rasmussen, LS, Póvoas, SCA, Randers, MB, and Krustrup, P. Technical actions, heart rate, and locomotor activity in 7v7 and 8v8 games for female youth soccer players. J Strength Cond Res 30(12): 3298-3303, 2016-The purpose of this study was to evaluate technical performance, heart rate (HR), and activity profile in 7v7 and 8v8 soccer games for 9- to 10-year-old girls (U11). A total of 24 female youth players participated in the study, all playing 20-minute 7v7 and 8v8 games with 160 and 223 m per player, respectively. Technical actions, HR, and activity profile were measured during the games using video filming, HR monitors, and 5-Hz Global positioning system (GPS) units. The number of technical actions was higher in 7v7 than in 8v8 games (34 ± 19 vs. 28 ± 14; p = 0.03; d = 0.37), as was the number of successful actions (25 ± 16 vs. 20 ± 12; p = 0.01; d = 0.35), with no difference in success rate for technical actions (70 ± 13 vs. 69 ± 14%; p = 0.63; d = 0.07). No differences were found between 7v7 and 8v8 in total distance covered (1,574 ± 251 and 1,622 ± 281 m; p = 0.66; d = 0.18), peak speed (19.5 ± 2.6 and 20.7 ± 1.5 km·h; p = 0.16; d = 0.56), mean HR values (85 ± 5 and 86 ± 6%HRpeak; p = 0.85; d = 0.18), and time of >90% HRpeak (37 ± 16 and 35 ± 14% of playing time; p = 0.70; d = 0.13). Distance covered at the highest running speeds of >16 km·h was lower in 7v7 than in 8v8 games (34 ± 24 vs. 63 ± 34 m; p = 0.018; d = 0.98), as was the number of entries into this speed zone (8 ± 5 vs. 13 ± 7; p = 0.006; d = 0.82). In conclusion, more technical actions and successful actions were observed in 7v7 than in 8v8 games, but players covered more ground with high-speed running in 8v8 games. This study also revealed that HR values were high in both game formats for U11 adolescent female players, with no difference between formats.</AbstractText
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Tool use is a complex motor planning problem. Prior research suggests that planning to use tools involves resolving competition between different tool-related action representations. We therefore reasoned that competition may also be exacerbated with tools for which the motions of the tool and the hand are incongruent (e.g., pinching the fingers to open a clothespin). If this hypothesis is correct, we should observe marked deficits in planning the use of incongruent as compared to congruent tools in individuals with limb apraxia following left-hemisphere stroke (LCVA), a disorder associated with abnormal action competition. We asked 34 individuals with chronic LCVA (14 females) and 16 matched neurotypical controls (8 females) to use novel tools in which the correspondence between the motions of the hand and tool-tip were either congruent or incongruent. Individuals with LCVA also completed background assessments to quantify apraxia severity. We observed increased planning time for incongruent as compared to congruent tools as a function of apraxia severity. Further analysis revealed that this impairment predominantly occurred early in the task when the tools were first introduced. Lesion-symptom mapping analyses revealed that lesions to posterior temporal and inferior parietal areas were associated with impaired planning for incongruent tools. A second experiment on the same individuals with LCVA revealed that the ability to gesture the use of conventional tools was impaired for tools rated as more incongruent by a normative sample. These findings suggest that tool-hand incongruence evokes action competition and influences the tool-use difficulties experienced by people with apraxia.</AbstractText
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Investigating the prevalence of medication near-misses and reporting intention among nurses in tertiary hospitals from China. Globally, medication near-misses are a public health issue as they often have serious consequences for patients and healthcare systems. Currently, few studies have investigated nurses' intention to report medication near-misses. Therefore, this study aims to examine the incidence of medication near-misses and factors influencing reporting intention among nurses in tertiary hospitals in Shandong Province, to fill the research gap in this area.</AbstractText A descriptive cross-sectional design.</AbstractText Between March 2021 and December 2021, 2625 nurses in seven tertiary hospitals from Shandong Province, China were enrolled in the study, using convenience sampling. Information about medication near-misses, reporting intention and barriers was collected using self-reported questionnaire, subscales of the Adverse Event Reporting Intention Questionnaire, and Medication Near-Miss Reporting Barriers Scale. This study explored the association between potential determinants from the perspective of nurses and managers using generalized linear model.</AbstractText About 25.3% of nurses experienced medication near-misses, with a mean reporting intention score of 5.44 (standardized deviation=1.13). The main approach for reporting medication near-misses was verbal language (80.6%). Higher professional title (χ2=13.770, P = 0.003), lower educational level (χ2=6.722, P = 0.035), fewer weekly work hours (χ2=3.947, P = 0.047), no previous medication near-misses experience (χ2=46.517, P < 0.001), and not having siblings (χ2=4.150, P = 0.042) nurses showed a higher level of reporting intention. The manager's negative response (χ2=7.059, P = 0.008) and complex reporting system (χ2=17.120, P < 0.001) were associated with lower levels of reporting intention, primarily influenced by departmental categories (χ2=22.306, P = 0.002).</AbstractText The results of this study show that nurses' medication near-misses reporting rate is relatively low, but their intention to report is relatively strong. Meanwhile, nurses' intention to report medication near-misses is influenced by multiple factors. This suggests that nursing managers should develop management strategies for near-miss events and actively provide training to enhance clinical nurses' willingness to report such events.</AbstractText
|
Technical Actions, Heart Rate, and Locomotor Activity in 7v7 and 8v8 Games for Female Youth Soccer Players. Ørntoft, C, Larsen, MN, Andersen, TB, Rasmussen, LS, Póvoas, SCA, Randers, MB, and Krustrup, P. Technical actions, heart rate, and locomotor activity in 7v7 and 8v8 games for female youth soccer players. J Strength Cond Res 30(12): 3298-3303, 2016-The purpose of this study was to evaluate technical performance, heart rate (HR), and activity profile in 7v7 and 8v8 soccer games for 9- to 10-year-old girls (U11). A total of 24 female youth players participated in the study, all playing 20-minute 7v7 and 8v8 games with 160 and 223 m per player, respectively. Technical actions, HR, and activity profile were measured during the games using video filming, HR monitors, and 5-Hz Global positioning system (GPS) units. The number of technical actions was higher in 7v7 than in 8v8 games (34 ± 19 vs. 28 ± 14; p = 0.03; d = 0.37), as was the number of successful actions (25 ± 16 vs. 20 ± 12; p = 0.01; d = 0.35), with no difference in success rate for technical actions (70 ± 13 vs. 69 ± 14%; p = 0.63; d = 0.07). No differences were found between 7v7 and 8v8 in total distance covered (1,574 ± 251 and 1,622 ± 281 m; p = 0.66; d = 0.18), peak speed (19.5 ± 2.6 and 20.7 ± 1.5 km·h; p = 0.16; d = 0.56), mean HR values (85 ± 5 and 86 ± 6%HRpeak; p = 0.85; d = 0.18), and time of >90% HRpeak (37 ± 16 and 35 ± 14% of playing time; p = 0.70; d = 0.13). Distance covered at the highest running speeds of >16 km·h was lower in 7v7 than in 8v8 games (34 ± 24 vs. 63 ± 34 m; p = 0.018; d = 0.98), as was the number of entries into this speed zone (8 ± 5 vs. 13 ± 7; p = 0.006; d = 0.82). In conclusion, more technical actions and successful actions were observed in 7v7 than in 8v8 games, but players covered more ground with high-speed running in 8v8 games. This study also revealed that HR values were high in both game formats for U11 adolescent female players, with no difference between formats.</AbstractText
|
Competition between tool and hand motion impairs movement planning in limb apraxia. Tool use is a complex motor planning problem. Prior research suggests that planning to use tools involves resolving competition between different tool-related action representations. We therefore reasoned that competition may also be exacerbated with tools for which the motions of the tool and the hand are incongruent (e.g., pinching the fingers to open a clothespin). If this hypothesis is correct, we should observe marked deficits in planning the use of incongruent as compared to congruent tools in individuals with limb apraxia following left-hemisphere stroke (LCVA), a disorder associated with abnormal action competition. We asked 34 individuals with chronic LCVA (14 females) and 16 matched neurotypical controls (8 females) to use novel tools in which the correspondence between the motions of the hand and tool-tip were either congruent or incongruent. Individuals with LCVA also completed background assessments to quantify apraxia severity. We observed increased planning time for incongruent as compared to congruent tools as a function of apraxia severity. Further analysis revealed that this impairment predominantly occurred early in the task when the tools were first introduced. Lesion-symptom mapping analyses revealed that lesions to posterior temporal and inferior parietal areas were associated with impaired planning for incongruent tools. A second experiment on the same individuals with LCVA revealed that the ability to gesture the use of conventional tools was impaired for tools rated as more incongruent by a normative sample. These findings suggest that tool-hand incongruence evokes action competition and influences the tool-use difficulties experienced by people with apraxia.</AbstractText
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33609568
|
21490129
|
33928578
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A comprehensive review of studies using the Affective Neuroscience Personality Scales in the psychological and psychiatric sciences.
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Drug wanting: behavioral sensitization and relapse to drug-seeking behavior.
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MRI-Visible Nanovehicle for Efficient siRNA Delivery.
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Jaak Panksepp's Affective Neuroscience Theory (ANT) belongs to the most prominent emotion theories in the psychological and psychiatric sciences. ANT proposes the existence of seven primary emotional systems deeply anchored in the mammalian brain. These emotional/motivational systems have been shaped by evolutionary processes and function as tools for survival in mammalian species. The systems are called SEEKING, LUST, CARE, and PLAY, as well as ANGER, FEAR, and SADNESS. Panksepp carved out these emotional systems via means of deep brain stimulation, brain lesion and pharmacological manipulation studies. Davis et al. (2003) designed the Affective Neuroscience Personality Scales (ANPS) against the background of findings from ANT. This self-report inventory is meant to enable researchers to assess individual differences in primary emotional systems. Seventeen years have passed since the first version of the ANPS has been published. Therefore, we now provide a comprehensive overview on studies using the ANPS including work from personality science, psychiatry and the neurosciences.</AbstractText
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Repeated exposure to drugs of abuse enhances the motor-stimulant response to these drugs, a phenomenon termed behavioral sensitization. Animals that are extinguished from self-administration training readily relapse to drug, conditioned cue, or stress priming. The involvement of sensitization in reinstated drug-seeking behavior remains controversial. This review describes sensitization and reinstated drug seeking as behavioral events, and the neural circuitry, neurochemistry, and neuropharmacology underlying both behavioral models will be described, compared, and contrasted. It seems that although sensitization and reinstatement involve overlapping circuitry and neurotransmitter and receptor systems, the role of sensitization in reinstatement remains ill-defined. Nevertheless, it is argued that sensitization remains a useful model for determining the neural basis of addiction, and an example is provided in which data from sensitization studies led to potential pharmacotherapies that have been tested in animal models of relapse and in human addicts.</AbstractText
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Visualizing siRNA delivery through medical imaging methods has drawn much attentions in recent gene therapy studies. Among them, iron oxide-based magnetic resonance imaging (MRI) is regarded as one of the most promising imaging modalities for its high spatial resolution as well as deep penetration and real-time properties. In this chapter, a detailed protocol of an amphiphilic superparamagnetic iron oxide (SPIO) nanovehicle-based siRNA delivery is described, mainly focusing on SPIO/siRNA complexes formation and characterization, in vitro and in vivo siRNA delivery, MRI study of the delivery and transfection efficiency evaluation.</AbstractText
|
A comprehensive review of studies using the Affective Neuroscience Personality Scales in the psychological and psychiatric sciences. Jaak Panksepp's Affective Neuroscience Theory (ANT) belongs to the most prominent emotion theories in the psychological and psychiatric sciences. ANT proposes the existence of seven primary emotional systems deeply anchored in the mammalian brain. These emotional/motivational systems have been shaped by evolutionary processes and function as tools for survival in mammalian species. The systems are called SEEKING, LUST, CARE, and PLAY, as well as ANGER, FEAR, and SADNESS. Panksepp carved out these emotional systems via means of deep brain stimulation, brain lesion and pharmacological manipulation studies. Davis et al. (2003) designed the Affective Neuroscience Personality Scales (ANPS) against the background of findings from ANT. This self-report inventory is meant to enable researchers to assess individual differences in primary emotional systems. Seventeen years have passed since the first version of the ANPS has been published. Therefore, we now provide a comprehensive overview on studies using the ANPS including work from personality science, psychiatry and the neurosciences.</AbstractText
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Drug wanting: behavioral sensitization and relapse to drug-seeking behavior. Repeated exposure to drugs of abuse enhances the motor-stimulant response to these drugs, a phenomenon termed behavioral sensitization. Animals that are extinguished from self-administration training readily relapse to drug, conditioned cue, or stress priming. The involvement of sensitization in reinstated drug-seeking behavior remains controversial. This review describes sensitization and reinstated drug seeking as behavioral events, and the neural circuitry, neurochemistry, and neuropharmacology underlying both behavioral models will be described, compared, and contrasted. It seems that although sensitization and reinstatement involve overlapping circuitry and neurotransmitter and receptor systems, the role of sensitization in reinstatement remains ill-defined. Nevertheless, it is argued that sensitization remains a useful model for determining the neural basis of addiction, and an example is provided in which data from sensitization studies led to potential pharmacotherapies that have been tested in animal models of relapse and in human addicts.</AbstractText
|
MRI-Visible Nanovehicle for Efficient siRNA Delivery. Visualizing siRNA delivery through medical imaging methods has drawn much attentions in recent gene therapy studies. Among them, iron oxide-based magnetic resonance imaging (MRI) is regarded as one of the most promising imaging modalities for its high spatial resolution as well as deep penetration and real-time properties. In this chapter, a detailed protocol of an amphiphilic superparamagnetic iron oxide (SPIO) nanovehicle-based siRNA delivery is described, mainly focusing on SPIO/siRNA complexes formation and characterization, in vitro and in vivo siRNA delivery, MRI study of the delivery and transfection efficiency evaluation.</AbstractText
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40757977
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34457043
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40612388
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Andrographolide attenuates oxidative stress and apoptosis in osteoporosis rats via MEK/ERK and Beclin-1/ATG-5-mediated autophagy pathway.
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Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer.
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An integrative approach prioritizes the orphan GPR61 genomic region in tissue-specific regulation of chronotype.
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To explore how andrographolide (AG) activates autophagy and reduces oxidative stress in osteoporosis.</AbstractText An ovariectomized rat (OVX) model was created in vivo. Osteoblasts were obtained from rat skulls in vitro, and an oxidative stress model was induced by H2O2. Masson staining and micro-CT were utilized to assess pathological damage to bone tissue following treatment with AG, 3-MA, or silencing the ATG-5 gene. The kit detected changes in oxidative stress-related indices, flow cytometry detected apoptosis, alkaline phosphatase and Alizarin Red S staining assessed osteogenic differentiation ability, and Western blot detected changes in osteogenic differentiation-related indices and autophagy-related indices.</AbstractText AG therapy clearly reduced pathological damage and inhibited oxidative stress in OVX rats. AG also significantly boosted osteoblast viability, reduced apoptosis, and facilitated osteoblast differentiation. Furthermore, AG treatment substantially elevated the expression of Runx, OPG, BMP-2, as well as autophagy-related proteins MEK, ERK, ATG-5, Beclin-1, and LC3.</AbstractText These findings indicate that AG possesses antioxidant and anti-osteoporosis properties, and that its mechanism may be linked to the MEK/ERK and Beclin-1/ATG-5-mediated autophagy pathways. These results establish the groundwork for the development of AG as an osteoporosis treatment, as well as new directions and therapeutic targets for the intervention of oxidative stress and autophagy-related disorders.</AbstractText
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Gastric cancer is a common malignancy worldwide. However, the molecular mechanisms underlying this malignancy remain unclear and there are a lack of effective drugs. The present study aimed to investigate the antitumor effect of Dihydroartemisinin (DHA) or inhibition of Tankyrases (TNKS), and determine the underlying molecular mechanisms of gastric cancer. Immunohistochemistry and immunofluorescence analyses were performed to detect the expression levels of TNKS, epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related proteins in gastric cancer tissues and adjacent normal tissues. The Cell Counting Kit-8 assay was performed to assess the viability of HGC-27 and AGS cells following treatment with different concentrations of HLY78 (a Wnt activator) or DHA. Following treatment with HLY78, DHA or small interfering (si)-TNKS1/si-TNKS2, colony formation and migratory abilities were assessed via the colony formation, wound healing and Transwell assays. Furthermore, western blot and immunofluorescence analyses were performed to detect the expression levels of TNKS, EMT- and Wnt/β-catenin-related proteins. The results demonstrated that the expression levels of TNKS, AXI2, β-catenin, N-cadherin and Vimentin were upregulated, whereas E-cadherin expression was downregulated in gastric cancer tissues compared with normal tissues. Furthermore, HLY78 and DHA suppressed the viability of HGC-27 and AGS cells, in a concentration-independent manner. Notably, TNKS knockdown or treatment with DHA suppressed colony formation, migration, TNKS expression, EMT and the Wnt/β-catenin pathway. Opposing effects were observed following treatment with HLY78, which were ameliorated following co-treatment with DHA. Taken together, these results suggest that DHA or inhibition of TNKS can suppress the proliferation and migration of gastric cancer cells, which is partly associated with inactivation of the Wnt/β-catenin pathway and EMT process.</AbstractText
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Chronotype, a manifestation of circadian rhythms, affects morning or evening preferences and ease of getting up. This study explores the genetic basis of morning chronotype and ease of getting up, focusing on the G-protein-coupled receptor locus, GPR61.</AbstractText We analyzed the genetic correlation between chronotype and ease of getting up using linkage disequilibrium score regression with summary statistics from the UK Biobank (<i We identified a strong genetic correlation (Rg = 0.80, <i Our findings reveal pleiotropic genetic factors influencing chronotype and ease of getting up, emphasizing <i
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Andrographolide attenuates oxidative stress and apoptosis in osteoporosis rats via MEK/ERK and Beclin-1/ATG-5-mediated autophagy pathway. To explore how andrographolide (AG) activates autophagy and reduces oxidative stress in osteoporosis.</AbstractText An ovariectomized rat (OVX) model was created in vivo. Osteoblasts were obtained from rat skulls in vitro, and an oxidative stress model was induced by H2O2. Masson staining and micro-CT were utilized to assess pathological damage to bone tissue following treatment with AG, 3-MA, or silencing the ATG-5 gene. The kit detected changes in oxidative stress-related indices, flow cytometry detected apoptosis, alkaline phosphatase and Alizarin Red S staining assessed osteogenic differentiation ability, and Western blot detected changes in osteogenic differentiation-related indices and autophagy-related indices.</AbstractText AG therapy clearly reduced pathological damage and inhibited oxidative stress in OVX rats. AG also significantly boosted osteoblast viability, reduced apoptosis, and facilitated osteoblast differentiation. Furthermore, AG treatment substantially elevated the expression of Runx, OPG, BMP-2, as well as autophagy-related proteins MEK, ERK, ATG-5, Beclin-1, and LC3.</AbstractText These findings indicate that AG possesses antioxidant and anti-osteoporosis properties, and that its mechanism may be linked to the MEK/ERK and Beclin-1/ATG-5-mediated autophagy pathways. These results establish the groundwork for the development of AG as an osteoporosis treatment, as well as new directions and therapeutic targets for the intervention of oxidative stress and autophagy-related disorders.</AbstractText
|
Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer. Gastric cancer is a common malignancy worldwide. However, the molecular mechanisms underlying this malignancy remain unclear and there are a lack of effective drugs. The present study aimed to investigate the antitumor effect of Dihydroartemisinin (DHA) or inhibition of Tankyrases (TNKS), and determine the underlying molecular mechanisms of gastric cancer. Immunohistochemistry and immunofluorescence analyses were performed to detect the expression levels of TNKS, epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related proteins in gastric cancer tissues and adjacent normal tissues. The Cell Counting Kit-8 assay was performed to assess the viability of HGC-27 and AGS cells following treatment with different concentrations of HLY78 (a Wnt activator) or DHA. Following treatment with HLY78, DHA or small interfering (si)-TNKS1/si-TNKS2, colony formation and migratory abilities were assessed via the colony formation, wound healing and Transwell assays. Furthermore, western blot and immunofluorescence analyses were performed to detect the expression levels of TNKS, EMT- and Wnt/β-catenin-related proteins. The results demonstrated that the expression levels of TNKS, AXI2, β-catenin, N-cadherin and Vimentin were upregulated, whereas E-cadherin expression was downregulated in gastric cancer tissues compared with normal tissues. Furthermore, HLY78 and DHA suppressed the viability of HGC-27 and AGS cells, in a concentration-independent manner. Notably, TNKS knockdown or treatment with DHA suppressed colony formation, migration, TNKS expression, EMT and the Wnt/β-catenin pathway. Opposing effects were observed following treatment with HLY78, which were ameliorated following co-treatment with DHA. Taken together, these results suggest that DHA or inhibition of TNKS can suppress the proliferation and migration of gastric cancer cells, which is partly associated with inactivation of the Wnt/β-catenin pathway and EMT process.</AbstractText
|
An integrative approach prioritizes the orphan GPR61 genomic region in tissue-specific regulation of chronotype. Chronotype, a manifestation of circadian rhythms, affects morning or evening preferences and ease of getting up. This study explores the genetic basis of morning chronotype and ease of getting up, focusing on the G-protein-coupled receptor locus, GPR61.</AbstractText We analyzed the genetic correlation between chronotype and ease of getting up using linkage disequilibrium score regression with summary statistics from the UK Biobank (<i We identified a strong genetic correlation (Rg = 0.80, <i Our findings reveal pleiotropic genetic factors influencing chronotype and ease of getting up, emphasizing <i
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32526385
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27434134
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32066314
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ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies.
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Overview of quantitative susceptibility mapping.
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Below-the-Ankle Arrival Time as a Novel Limb Tissue Perfusion Index: Two-dimensional Perfusion Angiography Evaluation.
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Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.</AbstractText
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Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and represents an important parameter in the field of MRI. With the recently introduced method of quantitative susceptibility mapping (QSM) and its conceptual extension to susceptibility tensor imaging (STI), the non-invasive assessment of this important physical quantity has become possible with MRI. Both methods solve the ill-posed inverse problem to determine the magnetic susceptibility from local magnetic fields. Whilst QSM allows the extraction of the spatial distribution of the bulk magnetic susceptibility from a single measurement, STI enables the quantification of magnetic susceptibility anisotropy, but requires multiple measurements with different orientations of the object relative to the main static magnetic field. In this review, we briefly recapitulate the fundamental theoretical foundation of QSM and STI, as well as computational strategies for the characterization of magnetic susceptibility with MRI phase data. In the second part, we provide an overview of current methodological and clinical applications of QSM with a focus on brain imaging. Copyright © 2016 John Wiley & Sons, Ltd.</AbstractText
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<b
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ExploreASL: An image processing pipeline for multi-center ASL perfusion MRI studies. Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.</AbstractText
|
Overview of quantitative susceptibility mapping. Magnetic susceptibility describes the magnetizability of a material to an applied magnetic field and represents an important parameter in the field of MRI. With the recently introduced method of quantitative susceptibility mapping (QSM) and its conceptual extension to susceptibility tensor imaging (STI), the non-invasive assessment of this important physical quantity has become possible with MRI. Both methods solve the ill-posed inverse problem to determine the magnetic susceptibility from local magnetic fields. Whilst QSM allows the extraction of the spatial distribution of the bulk magnetic susceptibility from a single measurement, STI enables the quantification of magnetic susceptibility anisotropy, but requires multiple measurements with different orientations of the object relative to the main static magnetic field. In this review, we briefly recapitulate the fundamental theoretical foundation of QSM and STI, as well as computational strategies for the characterization of magnetic susceptibility with MRI phase data. In the second part, we provide an overview of current methodological and clinical applications of QSM with a focus on brain imaging. Copyright © 2016 John Wiley & Sons, Ltd.</AbstractText
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Below-the-Ankle Arrival Time as a Novel Limb Tissue Perfusion Index: Two-dimensional Perfusion Angiography Evaluation. <b
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24478658
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16776594
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25315462
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Composition of agarose substrate affects behavioral output of Drosophila larvae.
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Complete functional characterization of sensory neurons by system identification.
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Unexpected crosslinking and diglycation as advanced glycation end-products from glyoxal.
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In the last decade the Drosophila larva has evolved into a simple model organism offering the opportunity to integrate molecular genetics with systems neuroscience. This led to a detailed understanding of the neuronal networks for a number of sensory functions and behaviors including olfaction, vision, gustation and learning and memory. Typically, behavioral assays in use exploit simple Petri dish setups with either agarose or agar as a substrate. However, neither the quality nor the concentration of the substrate is generally standardized across these experiments and there is no data available on how larval behavior is affected by such different substrates. Here, we have investigated the effects of different agarose concentrations on several larval behaviors. We demonstrate that agarose concentration is an important parameter, which affects all behaviors tested: preference, feeding, learning and locomotion. Larvae can discriminate between different agarose concentrations, they feed differently on them, they can learn to associate an agarose concentration with an odor stimulus and change locomotion on a substrate of higher agarose concentration. Additionally, we have investigated the effect of agarose concentration on three quinine based behaviors: preference, feeding and learning. We show that in all cases examined the behavioral output changes in an agarose concentration-dependent manner. Our results suggest that comparisons between experiments performed on substrates differing in agarose concentration should be done with caution. It should be taken into consideration that the agarose concentration can affect the behavioral output and thereby the experimental outcomes per se potentially due to the initiation of an escape response or changes in foraging behavior on more rigid substrates.</AbstractText
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System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.</AbstractText
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Glyoxal-derived advanced glycation end-products (AGEs) are formed in physiological systems affecting protein/peptide function and structure. These AGEs are generated during aging and chronic diseases such as diabetes and are considered arginine glycating agents. Thus, the study of glyoxal-derived AGEs in lysine residues and amino acid competition is addressed here using acetylated and non-acetylated undecapeptides, with one arginine and one lysine residue available for glycation. Tandem mass spectrometry results from a Fourier transform ion cyclotron resonance mass spectrometer showed glycated species at both the arginine and lysine residues. One species with the mass addition of 116.01096 Da is formed at the arginine residue. A possible structure is proposed to explain this finding (Nδ-[2-(dihydroxymethyl)-2H,3aH,4H,6aH-[1,3]dioxolo[5,6-d]imidazolin-5-yl]-L-ornithine-derived AGE). The second species corresponded to intramolecular crosslink involving the lysine residue and its presence is checked with ion-mobility mass spectrometry.</AbstractText
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Composition of agarose substrate affects behavioral output of Drosophila larvae. In the last decade the Drosophila larva has evolved into a simple model organism offering the opportunity to integrate molecular genetics with systems neuroscience. This led to a detailed understanding of the neuronal networks for a number of sensory functions and behaviors including olfaction, vision, gustation and learning and memory. Typically, behavioral assays in use exploit simple Petri dish setups with either agarose or agar as a substrate. However, neither the quality nor the concentration of the substrate is generally standardized across these experiments and there is no data available on how larval behavior is affected by such different substrates. Here, we have investigated the effects of different agarose concentrations on several larval behaviors. We demonstrate that agarose concentration is an important parameter, which affects all behaviors tested: preference, feeding, learning and locomotion. Larvae can discriminate between different agarose concentrations, they feed differently on them, they can learn to associate an agarose concentration with an odor stimulus and change locomotion on a substrate of higher agarose concentration. Additionally, we have investigated the effect of agarose concentration on three quinine based behaviors: preference, feeding and learning. We show that in all cases examined the behavioral output changes in an agarose concentration-dependent manner. Our results suggest that comparisons between experiments performed on substrates differing in agarose concentration should be done with caution. It should be taken into consideration that the agarose concentration can affect the behavioral output and thereby the experimental outcomes per se potentially due to the initiation of an escape response or changes in foraging behavior on more rigid substrates.</AbstractText
|
Complete functional characterization of sensory neurons by system identification. System identification is a growing approach to sensory neurophysiology that facilitates the development of quantitative functional models of sensory processing. This approach provides a clear set of guidelines for combining experimental data with other knowledge about sensory function to obtain a description that optimally predicts the way that neurons process sensory information. This prediction paradigm provides an objective method for evaluating and comparing computational models. In this chapter we review many of the system identification algorithms that have been used in sensory neurophysiology, and we show how they can be viewed as variants of a single statistical inference problem. We then review many of the practical issues that arise when applying these methods to neurophysiological experiments: stimulus selection, behavioral control, model visualization, and validation. Finally we discuss several problems to which system identification has been applied recently, including one important long-term goal of sensory neuroscience: developing models of sensory systems that accurately predict neuronal responses under completely natural conditions.</AbstractText
|
Unexpected crosslinking and diglycation as advanced glycation end-products from glyoxal. Glyoxal-derived advanced glycation end-products (AGEs) are formed in physiological systems affecting protein/peptide function and structure. These AGEs are generated during aging and chronic diseases such as diabetes and are considered arginine glycating agents. Thus, the study of glyoxal-derived AGEs in lysine residues and amino acid competition is addressed here using acetylated and non-acetylated undecapeptides, with one arginine and one lysine residue available for glycation. Tandem mass spectrometry results from a Fourier transform ion cyclotron resonance mass spectrometer showed glycated species at both the arginine and lysine residues. One species with the mass addition of 116.01096 Da is formed at the arginine residue. A possible structure is proposed to explain this finding (Nδ-[2-(dihydroxymethyl)-2H,3aH,4H,6aH-[1,3]dioxolo[5,6-d]imidazolin-5-yl]-L-ornithine-derived AGE). The second species corresponded to intramolecular crosslink involving the lysine residue and its presence is checked with ion-mobility mass spectrometry.</AbstractText
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35953417
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28715780
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35659297
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Pretreatment electroencephalographic features in patients with childhood absence epilepsy.
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Use of perampanel in children and adolescents with Lennox-Gastaut Syndrome.
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Pediatric lumbar disc herniation: a report of two cases and review of the literature.
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To analyze the ictal and interictal electroencephalographic (EEG) features in newly diagnosed childhood absence epilepsy (CAE) and determine the association between seizure onset topography, interictal focal spike-wave discharges (FSWDs) and accompanying clinical features of absence seizures.</AbstractText The authors searched the EEG database for a definite diagnosis of CAE according to ILAE 2017 criteria. Video-EEGs of untreated pediatric patients during sleep and wakefulness were evaluated retrospectively.</AbstractText The study included 47 patients (25 males, 22 females). Interictal FSWDs were observed in 49% of patients with CAE during wakefulness and in 85.1% during sleep (p = 0.001). Interictal FSWDs were most frequently observed in the frontal regions (awake: 34%; asleep: 74.5%), followed by the posterior temporoparietooccipital region (awake: 21.2%; asleep: 36.1%), and the centrotemporal region (awake: 6.4%; asleep: 8.5%). Eleven patients (23.4%) had polyspikes during sleep. Both bilateral symmetric and asymmetric seizure onset were noted in 32%, whereas focal seizure onset was observed in 14.9% of the patients. Absence seizures with and without motor components were seen in 72.3% and 61.7% of patients, respectively, and in 33% of patients both occurred. There were no associations between the existence of interictal FSWDs, focal/asymmetric seizure onset, and absence seizures with and/or without motor components.</AbstractText Asymmetric and/or focal seizure onset, interictal FSWDs, and absence seizures with motor components are commonly observed in drug-naive CAE. This study found no association between seizure onset topography, interictal FSWDs, and semiological features of absence seizures.</AbstractText
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Report the use of perampanel treatment in children with Lennox-Gastaut syndrome (LGS).</AbstractText We conducted a prospective study of 13 LGS patients (seven male; mean age, 12.8years) treated with adjunctive perampanel therapy. Perampanel was initiated at 2mg/day and titrated to a median maximum dose of 6mg/day.</AbstractText After a mean follow-up duration of 10.8months (range, 1-24months), nine patients (69.2%) were responders (≥50% reduction in total seizure frequency) and nine (69.2%) were rated by their physician as "much improved" or "very much improved". Four patients (30.8%) discontinued perampanel due to the lack of efficacy (n=2) and seizure aggravation (n=2). No patients discontinued due to other adverse events (AEs). AEs were reported for six patients (46.2%) and comprised decreased activity/social interaction (n=3), behavior disturbance with agitation (n=2), and/or fatigue (n=2). All AEs became manageable after perampanel dosing was decreased. Improvements in cognitive function and/or behavior were reported for seven patients (53.8%). Introduction of perampanel allowed the dose reduction and/or discontinuation of other treatments in seven patients (53.8%).</AbstractText Perampanel was efficacious and generally well tolerated as an adjunctive treatment for seizures associated with LGS, supporting further research in this area.</AbstractText
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Lumbar disc herniation (LDH) is not a common condition in children. Most reports on pediatric LDH concern the outcomes of surgeries performed in children in whom nonsurgical treatment failed while the outcome of nonsurgical treatment of LDH in children was rarely reported.</AbstractText Case 1: a 10-year-old girl presented with back pain and sciatica in her left leg for over 3 months. The physical examination revealed exacerbation of back pain by waist extension or flexion, and a positive Lasegue's sign was revealed in her left leg. Magnetic resonance imaging (MRI) revealed lumbar disc herniation at the L5/S1 level. She was diagnosed with LDH. After receiving nonsurgical treatment of traditional Chinese medicine (TCM) for 30 days, the girl had mild low back pain and sciatica and the symptoms had resolved completely at the 3-month follow-up. There was no recurrence within the following 2 years. MRI performed 30 months later revealed that the herniated disc did not shrink significantly. However, she was totally asymptomatic at the follow-up performed 30 months later. Case 2: a 13-year-old boy presented with sciatica in his left leg for over 3 months. The physical examination revealed that Lasegue's sign was positive in the left leg, the level of muscle strength in the left ankle plantar flexors was grade 4. MRI revealed a lumbar disc herniation at the L5/S1 level. He was diagnosed with LDH. The boy underwent 2 weeks of TCM treatment, and exhibited a favorable outcome: only mild pain was noticed in his left buttocks after walking for more than 15 min. He was asymptomatic at the 3-month follow-up and there was no recurrence within the next 3 years. MRI scan performed at 40 months later showed no significant resorption of the herniated disc. However, he was totally asymptomatic at the follow-up performed 40 months later.</AbstractText For the nonsurgical treatment of pediatric LDH, resorption of herniated discs is not necessary for favorable long-term outcomes, and children with symptomatic LDH may become asymptomatic without resorption.</AbstractText
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Pretreatment electroencephalographic features in patients with childhood absence epilepsy. To analyze the ictal and interictal electroencephalographic (EEG) features in newly diagnosed childhood absence epilepsy (CAE) and determine the association between seizure onset topography, interictal focal spike-wave discharges (FSWDs) and accompanying clinical features of absence seizures.</AbstractText The authors searched the EEG database for a definite diagnosis of CAE according to ILAE 2017 criteria. Video-EEGs of untreated pediatric patients during sleep and wakefulness were evaluated retrospectively.</AbstractText The study included 47 patients (25 males, 22 females). Interictal FSWDs were observed in 49% of patients with CAE during wakefulness and in 85.1% during sleep (p = 0.001). Interictal FSWDs were most frequently observed in the frontal regions (awake: 34%; asleep: 74.5%), followed by the posterior temporoparietooccipital region (awake: 21.2%; asleep: 36.1%), and the centrotemporal region (awake: 6.4%; asleep: 8.5%). Eleven patients (23.4%) had polyspikes during sleep. Both bilateral symmetric and asymmetric seizure onset were noted in 32%, whereas focal seizure onset was observed in 14.9% of the patients. Absence seizures with and without motor components were seen in 72.3% and 61.7% of patients, respectively, and in 33% of patients both occurred. There were no associations between the existence of interictal FSWDs, focal/asymmetric seizure onset, and absence seizures with and/or without motor components.</AbstractText Asymmetric and/or focal seizure onset, interictal FSWDs, and absence seizures with motor components are commonly observed in drug-naive CAE. This study found no association between seizure onset topography, interictal FSWDs, and semiological features of absence seizures.</AbstractText
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Use of perampanel in children and adolescents with Lennox-Gastaut Syndrome. Report the use of perampanel treatment in children with Lennox-Gastaut syndrome (LGS).</AbstractText We conducted a prospective study of 13 LGS patients (seven male; mean age, 12.8years) treated with adjunctive perampanel therapy. Perampanel was initiated at 2mg/day and titrated to a median maximum dose of 6mg/day.</AbstractText After a mean follow-up duration of 10.8months (range, 1-24months), nine patients (69.2%) were responders (≥50% reduction in total seizure frequency) and nine (69.2%) were rated by their physician as "much improved" or "very much improved". Four patients (30.8%) discontinued perampanel due to the lack of efficacy (n=2) and seizure aggravation (n=2). No patients discontinued due to other adverse events (AEs). AEs were reported for six patients (46.2%) and comprised decreased activity/social interaction (n=3), behavior disturbance with agitation (n=2), and/or fatigue (n=2). All AEs became manageable after perampanel dosing was decreased. Improvements in cognitive function and/or behavior were reported for seven patients (53.8%). Introduction of perampanel allowed the dose reduction and/or discontinuation of other treatments in seven patients (53.8%).</AbstractText Perampanel was efficacious and generally well tolerated as an adjunctive treatment for seizures associated with LGS, supporting further research in this area.</AbstractText
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Pediatric lumbar disc herniation: a report of two cases and review of the literature. Lumbar disc herniation (LDH) is not a common condition in children. Most reports on pediatric LDH concern the outcomes of surgeries performed in children in whom nonsurgical treatment failed while the outcome of nonsurgical treatment of LDH in children was rarely reported.</AbstractText Case 1: a 10-year-old girl presented with back pain and sciatica in her left leg for over 3 months. The physical examination revealed exacerbation of back pain by waist extension or flexion, and a positive Lasegue's sign was revealed in her left leg. Magnetic resonance imaging (MRI) revealed lumbar disc herniation at the L5/S1 level. She was diagnosed with LDH. After receiving nonsurgical treatment of traditional Chinese medicine (TCM) for 30 days, the girl had mild low back pain and sciatica and the symptoms had resolved completely at the 3-month follow-up. There was no recurrence within the following 2 years. MRI performed 30 months later revealed that the herniated disc did not shrink significantly. However, she was totally asymptomatic at the follow-up performed 30 months later. Case 2: a 13-year-old boy presented with sciatica in his left leg for over 3 months. The physical examination revealed that Lasegue's sign was positive in the left leg, the level of muscle strength in the left ankle plantar flexors was grade 4. MRI revealed a lumbar disc herniation at the L5/S1 level. He was diagnosed with LDH. The boy underwent 2 weeks of TCM treatment, and exhibited a favorable outcome: only mild pain was noticed in his left buttocks after walking for more than 15 min. He was asymptomatic at the 3-month follow-up and there was no recurrence within the next 3 years. MRI scan performed at 40 months later showed no significant resorption of the herniated disc. However, he was totally asymptomatic at the follow-up performed 40 months later.</AbstractText For the nonsurgical treatment of pediatric LDH, resorption of herniated discs is not necessary for favorable long-term outcomes, and children with symptomatic LDH may become asymptomatic without resorption.</AbstractText
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30583064
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37252737
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30745830
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Age-related microstructural and physiological changes in normal brain measured by MRI γ-metrics derived from anomalous diffusion signal representation.
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Longitudinal Associations of Clinical and Biochemical Head Injury Biomarkers With Head Impact Exposure in Adolescent Football Players.
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Melatonin Stimulates STAR Expression and Progesterone Production via Activation of the PI3K/AKT Pathway in Bovine Theca Cells.
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Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline. In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20-77 years) using 3.0T and 12 b-values up to 5000 s/mm<sup
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Consequences of subconcussive head impacts have been recognized, yet most studies to date have included small samples from a single site, used a unimodal approach, and lacked repeated testing.</AbstractText To examine time-course changes in clinical (near point of convergence [NPC]) and brain-injury blood biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], and neurofilament light [NF-L]) in adolescent football players and to test whether changes in the outcomes were associated with playing position, impact kinematics, and/or brain tissue strain.</AbstractText This multisite, prospective cohort study included male high school football players aged 13 to 18 years at 4 high schools in the Midwest during the 2021 high school football season (preseason [July] and August 2 to November 19).</AbstractText A single football season.</AbstractText The main outcomes were NPC (a clinical oculomotor test) and serum levels of GFAP, UCH-L1, and NF-L. Participants' head impact exposure (frequency and peak linear and rotational accelerations) was tracked using instrumented mouthguards, and maximum principal strain was computed to reflect brain tissue strain. Players' neurological function was assessed at 5 time points (preseason, post-training camp, 2 in season, and postseason).</AbstractText Ninety-nine male players contributed to the time-course analysis (mean [SD] age, 15.8 [1.1] years), but data from 6 players (6.1%) were excluded from the association analysis due to issues related to mouthguards. Thus, 93 players yielded 9498 head impacts in a season (mean [SD], 102 [113] impacts per player). There were time-course elevations in NPC and GFAP, UCH-L1, and NF-L levels. Compared with baseline, the NPC exhibited a significant elevation over time and peaked at postseason (2.21 cm; 95% CI, 1.80-2.63 cm; P < .001). Levels of GFAP and UCH-L1 increased by 25.6 pg/mL (95% CI, 17.6-33.6 pg/mL; P < .001) and 188.5 pg/mL (95% CI, 145.6-231.4 pg/mL; P < .001), respectively, later in the season. Levels of NF-L were elevated after the training camp (0.78 pg/mL; 95% CI, 0.14-1.41 pg/mL; P = .011) and midseason (0.55 pg/mL; 95% CI, 0.13-0.99 pg/mL; P = .006) but normalized by the end of the season. Changes in UCH-L1 levels were associated with maximum principal strain later in the season (0.052 pg/mL; 95% CI, 0.015-0.088 pg/mL; P = .007) and postseason (0.069 pg/mL; 95% CI, 0.031-0.106 pg/mL; P < .001).</AbstractText The study data suggest that adolescent football players exhibited impairments in oculomotor function and elevations in blood biomarker levels associated with astrocyte activation and neuronal injury throughout a season. Several years of follow-up are needed to examine the long-term effects of subconcussive head impacts in adolescent football players.</AbstractText
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Melatonin is present in mammalian follicular fluid and plays an important role in regulating steroidogenesis in follicular cells. In this study, we report the effect of melatonin on steroidogenesis in the theca interna (TI) in small bovine follicles and theca cells (TCs) cultured in vitro. Treatment with melatonin significantly increased the expression of steroidogenic acute regulatory protein (STAR) and the production of progesterone in both TI and in TCs. Melatonin stimulated the phosphorylation of AKT but not ERK1/2, and the addition of luzindole (a nonspecific MT1 and MT2 inhibitor) or 4P-PDOT (specific MT2 inhibitor) reduced melatonin-induced STAR expression, progesterone secretion, and PI3K/AKT pathway activation. The effect of melatonin on the TI in follicles was more obvious than on the TCs in vitro. Results indicate that melatonin stimulates the steroidogenesis of TCs mainly via the activation of the PI3K/AKT pathway by MT1 and MT2.</AbstractText
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Age-related microstructural and physiological changes in normal brain measured by MRI γ-metrics derived from anomalous diffusion signal representation. Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline. In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20-77 years) using 3.0T and 12 b-values up to 5000 s/mm<sup
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Longitudinal Associations of Clinical and Biochemical Head Injury Biomarkers With Head Impact Exposure in Adolescent Football Players. Consequences of subconcussive head impacts have been recognized, yet most studies to date have included small samples from a single site, used a unimodal approach, and lacked repeated testing.</AbstractText To examine time-course changes in clinical (near point of convergence [NPC]) and brain-injury blood biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], and neurofilament light [NF-L]) in adolescent football players and to test whether changes in the outcomes were associated with playing position, impact kinematics, and/or brain tissue strain.</AbstractText This multisite, prospective cohort study included male high school football players aged 13 to 18 years at 4 high schools in the Midwest during the 2021 high school football season (preseason [July] and August 2 to November 19).</AbstractText A single football season.</AbstractText The main outcomes were NPC (a clinical oculomotor test) and serum levels of GFAP, UCH-L1, and NF-L. Participants' head impact exposure (frequency and peak linear and rotational accelerations) was tracked using instrumented mouthguards, and maximum principal strain was computed to reflect brain tissue strain. Players' neurological function was assessed at 5 time points (preseason, post-training camp, 2 in season, and postseason).</AbstractText Ninety-nine male players contributed to the time-course analysis (mean [SD] age, 15.8 [1.1] years), but data from 6 players (6.1%) were excluded from the association analysis due to issues related to mouthguards. Thus, 93 players yielded 9498 head impacts in a season (mean [SD], 102 [113] impacts per player). There were time-course elevations in NPC and GFAP, UCH-L1, and NF-L levels. Compared with baseline, the NPC exhibited a significant elevation over time and peaked at postseason (2.21 cm; 95% CI, 1.80-2.63 cm; P < .001). Levels of GFAP and UCH-L1 increased by 25.6 pg/mL (95% CI, 17.6-33.6 pg/mL; P < .001) and 188.5 pg/mL (95% CI, 145.6-231.4 pg/mL; P < .001), respectively, later in the season. Levels of NF-L were elevated after the training camp (0.78 pg/mL; 95% CI, 0.14-1.41 pg/mL; P = .011) and midseason (0.55 pg/mL; 95% CI, 0.13-0.99 pg/mL; P = .006) but normalized by the end of the season. Changes in UCH-L1 levels were associated with maximum principal strain later in the season (0.052 pg/mL; 95% CI, 0.015-0.088 pg/mL; P = .007) and postseason (0.069 pg/mL; 95% CI, 0.031-0.106 pg/mL; P < .001).</AbstractText The study data suggest that adolescent football players exhibited impairments in oculomotor function and elevations in blood biomarker levels associated with astrocyte activation and neuronal injury throughout a season. Several years of follow-up are needed to examine the long-term effects of subconcussive head impacts in adolescent football players.</AbstractText
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Melatonin Stimulates STAR Expression and Progesterone Production via Activation of the PI3K/AKT Pathway in Bovine Theca Cells. Melatonin is present in mammalian follicular fluid and plays an important role in regulating steroidogenesis in follicular cells. In this study, we report the effect of melatonin on steroidogenesis in the theca interna (TI) in small bovine follicles and theca cells (TCs) cultured in vitro. Treatment with melatonin significantly increased the expression of steroidogenic acute regulatory protein (STAR) and the production of progesterone in both TI and in TCs. Melatonin stimulated the phosphorylation of AKT but not ERK1/2, and the addition of luzindole (a nonspecific MT1 and MT2 inhibitor) or 4P-PDOT (specific MT2 inhibitor) reduced melatonin-induced STAR expression, progesterone secretion, and PI3K/AKT pathway activation. The effect of melatonin on the TI in follicles was more obvious than on the TCs in vitro. Results indicate that melatonin stimulates the steroidogenesis of TCs mainly via the activation of the PI3K/AKT pathway by MT1 and MT2.</AbstractText
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22432451
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15662424
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21576110
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The ubiquity of small-world networks.
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Evolutionary dynamics on graphs.
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Lesion evidence for the critical role of the intraparietal sulcus in spatial attention.
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Small-world networks, according to Watts and Strogatz, are a class of networks that are "highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs." These characteristics result in networks with unique properties of regional specialization with efficient information transfer. Social networks are intuitive examples of this organization, in which cliques or clusters of friends being interconnected but each person is really only five or six people away from anyone else. Although this qualitative definition has prevailed in network science theory, in application, the standard quantitative application is to compare path length (a surrogate measure of distributed processing) and clustering (a surrogate measure of regional specialization) to an equivalent random network. It is demonstrated here that comparing network clustering to that of a random network can result in aberrant findings and that networks once thought to exhibit small-world properties may not. We propose a new small-world metric, ω (omega), which compares network clustering to an equivalent lattice network and path length to a random network, as Watts and Strogatz originally described. Example networks are presented that would be interpreted as small-world when clustering is compared to a random network but are not small-world according to ω. These findings have important implications in network science because small-world networks have unique topological properties, and it is critical to accurately distinguish them from networks without simultaneous high clustering and short path length.</AbstractText
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Evolutionary dynamics have been traditionally studied in the context of homogeneous or spatially extended populations. Here we generalize population structure by arranging individuals on a graph. Each vertex represents an individual. The weighted edges denote reproductive rates which govern how often individuals place offspring into adjacent vertices. The homogeneous population, described by the Moran process, is the special case of a fully connected graph with evenly weighted edges. Spatial structures are described by graphs where vertices are connected with their nearest neighbours. We also explore evolution on random and scale-free networks. We determine the fixation probability of mutants, and characterize those graphs for which fixation behaviour is identical to that of a homogeneous population. Furthermore, some graphs act as suppressors and others as amplifiers of selection. It is even possible to find graphs that guarantee the fixation of any advantageous mutant. We also study frequency-dependent selection and show that the outcome of evolutionary games can depend entirely on the structure of the underlying graph. Evolutionary graph theory has many fascinating applications ranging from ecology to multi-cellular organization and economics.</AbstractText
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Based on lesion mapping studies, the inferior parietal lobule and temporoparietal junction are considered the critical parietal regions for spatial-attentional deficits. Lesion evidence for a key role of the intraparietal sulcus, a region featuring prominently in non-human primate studies and human functional imaging studies of the intact brain, is still lacking, probably due to the exceptional nature of isolated intraparietal sulcus lesions. We combined behavioural testing and functional imaging in two patients with a focal intraparietal sulcus lesion sparing the inferior parietal lobule and temporoparietal junction to examine the critical contribution of the intraparietal sulcus to spatial attention. Case H.H. had a focal ischaemic lesion (1.8 cm3) that was confined to the posterior segment of the left intraparietal sulcus, whereas Case N.V. had a partially reversible lesion of the middle segment of the right intraparietal sulcus extending into the superior parietal lobule (13.8 cm3). The performance of these cases was contrasted with five cases with a classical inferior parietal lesion, as well as with a group of 31 age-matched controls. In the behavioural study, the patients performed an orientation discrimination task on a peripheral target (eccentricity 7.6°) that was preceded by a central spatial cue. We manipulated both the cue validity (17% trials with an invalid spatial cue) and the presence of a competing distracter in the visual field contralateral to the target (17% double stimulation trials). The ability of the patients with an intraparietal sulcus lesion to reorient their spatial focus of attention and to select between competing stimuli was impaired for contralesional targets compared with controls, similarly to what we saw in the inferior parietal group. Furthermore, we could observe that the deficit in Case N.V. resolved with regression of the lesion. To further evaluate the correspondence between spatial-attentional deficits and the intraparietal sulcus lesions, we ascertained the functional integrity of the inferior parietal lobule and temporoparietal junction in Case H.H. using event-related functional magnetic resonance imaging with the same task as in the behavioural study. The intraparietal sulcus lesion of this patient did not affect the task-related activation of the inferior parietal lobule or temporoparietal junction. Additionally, a resting-state functional magnetic resonance imaging study in Case H.H. and 62 controls revealed that the lesion in Case H.H. did not affect the topology of the ventral attention network nor the strength of its main inter- and intrahemispheric connections. Our findings demonstrate that the human superior parietal cortex critically contributes to spatially selective attention.</AbstractText
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The ubiquity of small-world networks. Small-world networks, according to Watts and Strogatz, are a class of networks that are "highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs." These characteristics result in networks with unique properties of regional specialization with efficient information transfer. Social networks are intuitive examples of this organization, in which cliques or clusters of friends being interconnected but each person is really only five or six people away from anyone else. Although this qualitative definition has prevailed in network science theory, in application, the standard quantitative application is to compare path length (a surrogate measure of distributed processing) and clustering (a surrogate measure of regional specialization) to an equivalent random network. It is demonstrated here that comparing network clustering to that of a random network can result in aberrant findings and that networks once thought to exhibit small-world properties may not. We propose a new small-world metric, ω (omega), which compares network clustering to an equivalent lattice network and path length to a random network, as Watts and Strogatz originally described. Example networks are presented that would be interpreted as small-world when clustering is compared to a random network but are not small-world according to ω. These findings have important implications in network science because small-world networks have unique topological properties, and it is critical to accurately distinguish them from networks without simultaneous high clustering and short path length.</AbstractText
|
Evolutionary dynamics on graphs. Evolutionary dynamics have been traditionally studied in the context of homogeneous or spatially extended populations. Here we generalize population structure by arranging individuals on a graph. Each vertex represents an individual. The weighted edges denote reproductive rates which govern how often individuals place offspring into adjacent vertices. The homogeneous population, described by the Moran process, is the special case of a fully connected graph with evenly weighted edges. Spatial structures are described by graphs where vertices are connected with their nearest neighbours. We also explore evolution on random and scale-free networks. We determine the fixation probability of mutants, and characterize those graphs for which fixation behaviour is identical to that of a homogeneous population. Furthermore, some graphs act as suppressors and others as amplifiers of selection. It is even possible to find graphs that guarantee the fixation of any advantageous mutant. We also study frequency-dependent selection and show that the outcome of evolutionary games can depend entirely on the structure of the underlying graph. Evolutionary graph theory has many fascinating applications ranging from ecology to multi-cellular organization and economics.</AbstractText
|
Lesion evidence for the critical role of the intraparietal sulcus in spatial attention. Based on lesion mapping studies, the inferior parietal lobule and temporoparietal junction are considered the critical parietal regions for spatial-attentional deficits. Lesion evidence for a key role of the intraparietal sulcus, a region featuring prominently in non-human primate studies and human functional imaging studies of the intact brain, is still lacking, probably due to the exceptional nature of isolated intraparietal sulcus lesions. We combined behavioural testing and functional imaging in two patients with a focal intraparietal sulcus lesion sparing the inferior parietal lobule and temporoparietal junction to examine the critical contribution of the intraparietal sulcus to spatial attention. Case H.H. had a focal ischaemic lesion (1.8 cm3) that was confined to the posterior segment of the left intraparietal sulcus, whereas Case N.V. had a partially reversible lesion of the middle segment of the right intraparietal sulcus extending into the superior parietal lobule (13.8 cm3). The performance of these cases was contrasted with five cases with a classical inferior parietal lesion, as well as with a group of 31 age-matched controls. In the behavioural study, the patients performed an orientation discrimination task on a peripheral target (eccentricity 7.6°) that was preceded by a central spatial cue. We manipulated both the cue validity (17% trials with an invalid spatial cue) and the presence of a competing distracter in the visual field contralateral to the target (17% double stimulation trials). The ability of the patients with an intraparietal sulcus lesion to reorient their spatial focus of attention and to select between competing stimuli was impaired for contralesional targets compared with controls, similarly to what we saw in the inferior parietal group. Furthermore, we could observe that the deficit in Case N.V. resolved with regression of the lesion. To further evaluate the correspondence between spatial-attentional deficits and the intraparietal sulcus lesions, we ascertained the functional integrity of the inferior parietal lobule and temporoparietal junction in Case H.H. using event-related functional magnetic resonance imaging with the same task as in the behavioural study. The intraparietal sulcus lesion of this patient did not affect the task-related activation of the inferior parietal lobule or temporoparietal junction. Additionally, a resting-state functional magnetic resonance imaging study in Case H.H. and 62 controls revealed that the lesion in Case H.H. did not affect the topology of the ventral attention network nor the strength of its main inter- and intrahemispheric connections. Our findings demonstrate that the human superior parietal cortex critically contributes to spatially selective attention.</AbstractText
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40208971
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31488341
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40209163
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A neuroimmune circuit mediates cancer cachexia-associated apathy.
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Altered amygdala subregion-related circuits in treatment-naïve post-traumatic stress disorder comorbid with major depressive disorder.
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Comparing MEG and EEG measurement set-ups for a brain-computer interface based on selective auditory attention.
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Cachexia, a severe wasting syndrome associated with inflammatory conditions, often leads to multiorgan failure and death. Patients with cachexia experience extreme fatigue, apathy, and clinical depression, yet the biological mechanisms underlying these behavioral symptoms and their relationship to the disease remain unclear. In a mouse cancer model, cachexia specifically induced increased effort-sensitivity, apathy-like symptoms through a cytokine-sensing brainstem-to-basal ganglia circuit. This neural circuit detects elevated interleukin-6 (IL-6) at cachexia onset and translates inflammatory signals into decreased mesolimbic dopamine, thereby increasing effort sensitivity. We alleviated these apathy-like symptoms by targeting key circuit nodes: administering an anti-IL-6 antibody treatment, ablating cytokine sensing in the brainstem, and optogenetically or pharmacologically boosting mesolimbic dopamine. Our findings uncovered a central neural circuit that senses systemic inflammation and orchestrates behavioral changes, providing mechanistic insights into the connection between chronic inflammation and depressive symptoms.</AbstractText
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Individuals with both post-traumatic stress disorder and major depressive disorder (PTSD+MDD) often show greater social and occupational impairment and poorer treatment response than individuals with PTSD alone. Increasing evidence reveals that the amygdala, a brain region implicated in the pathophysiology of both of these conditions, is a complex of structurally and functionally heterogeneous nuclei. Quantifying the functional connectivity of two key amygdala subregions, the basolateral (BLA) and centromedial (CMA), in PTSD+MDD and PTSD-alone could advance our understanding of the neurocircuitry of these conditions. 18 patients with PTSD+MDD, 28 with PTSD-alone, and 50 trauma exposed healthy controls (TEHC), all from a cohort who survived the same large earthquake in China, underwent resting-state functional magnetic resonance imaging. Bilateral BLA and CMA functional connectivity (FC) maps were created using a seed-based approach for each participant. The analysis of covariance of FC was used to determine between-group differences. A significant interaction between amygdala subregion and diagnostic group suggested that differences in connectivity patterns between the two seeds were mediated by diagnosis. Post-hoc analyses revealed that PTSD+MDD patients showed weaker connectivity between right BLA and (a) left anterior cingulate cortex/supplementary motor area, and (b) bilateral putamen/pallidum, compared with PTSD-alone patients. Higher CMA connectivities left ACC/SMA were also observed in PTSD+MDD compared with PTSD-alone. An inverse relationship between the connectivity of right BLA with right putamen/pallidum and MDD symptoms was found in PTSD+MDD. These findings indicate a relationship between the neural pathophysiology of PTSD+MDD compared with PTSD-alone and TEHC and may inform future clinical interventions.</AbstractText
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Auditory attention modulates auditory evoked responses to target vs. non-target sounds in electro- and magnetoencephalographic (EEG/MEG) recordings. Employing whole-scalp MEG recordings and offline classification algorithms has been shown to enable high accuracy in tracking the target of auditory attention. Here, we investigated the decrease in accuracy when moving from the whole-scalp MEG to lower channel count EEG recordings and when training the classifier only from the initial or middle part of the recording instead of extracting training trials throughout the recording. To this end, we recorded simultaneous MEG (306 channels) and EEG (64 channels) in 18 healthy volunteers while presented with concurrent streams of spoken "Yes"/"No" words and instructed to attend to one of them. We then trained support vector machine classifiers to predict the target of attention from unaveraged trials of MEG/EEG. Classifiers were trained on 204 MEG gradiometers or on EEG with 64, 30, nine or three channels with trials extracted randomly across or only from the beginning of the recording. The highest classification accuracy, 73.2% on average across the participants for one-second trials, was obtained with MEG when the training trials were randomly extracted throughout the recording. With EEG, the accuracy was 69%, 69%, 66%, and 61% when using 64, 30, nine, and three channels, respectively. When training the classifiers with the same amount of data but extracted only from the beginning of the recording, the accuracy dropped by 11%-units on average, causing the result from the three-channel EEG to fall below the chance level. The combination of five consecutive trials partially compensated for this drop such that it was one to 5%-units. Although moving from whole-scalp MEG to EEG reduces classification accuracy, usable auditory-attention-based brain-computer interfaces can be implemented with a small set of optimally placed EEG channels.</AbstractText
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A neuroimmune circuit mediates cancer cachexia-associated apathy. Cachexia, a severe wasting syndrome associated with inflammatory conditions, often leads to multiorgan failure and death. Patients with cachexia experience extreme fatigue, apathy, and clinical depression, yet the biological mechanisms underlying these behavioral symptoms and their relationship to the disease remain unclear. In a mouse cancer model, cachexia specifically induced increased effort-sensitivity, apathy-like symptoms through a cytokine-sensing brainstem-to-basal ganglia circuit. This neural circuit detects elevated interleukin-6 (IL-6) at cachexia onset and translates inflammatory signals into decreased mesolimbic dopamine, thereby increasing effort sensitivity. We alleviated these apathy-like symptoms by targeting key circuit nodes: administering an anti-IL-6 antibody treatment, ablating cytokine sensing in the brainstem, and optogenetically or pharmacologically boosting mesolimbic dopamine. Our findings uncovered a central neural circuit that senses systemic inflammation and orchestrates behavioral changes, providing mechanistic insights into the connection between chronic inflammation and depressive symptoms.</AbstractText
|
Altered amygdala subregion-related circuits in treatment-naïve post-traumatic stress disorder comorbid with major depressive disorder. Individuals with both post-traumatic stress disorder and major depressive disorder (PTSD+MDD) often show greater social and occupational impairment and poorer treatment response than individuals with PTSD alone. Increasing evidence reveals that the amygdala, a brain region implicated in the pathophysiology of both of these conditions, is a complex of structurally and functionally heterogeneous nuclei. Quantifying the functional connectivity of two key amygdala subregions, the basolateral (BLA) and centromedial (CMA), in PTSD+MDD and PTSD-alone could advance our understanding of the neurocircuitry of these conditions. 18 patients with PTSD+MDD, 28 with PTSD-alone, and 50 trauma exposed healthy controls (TEHC), all from a cohort who survived the same large earthquake in China, underwent resting-state functional magnetic resonance imaging. Bilateral BLA and CMA functional connectivity (FC) maps were created using a seed-based approach for each participant. The analysis of covariance of FC was used to determine between-group differences. A significant interaction between amygdala subregion and diagnostic group suggested that differences in connectivity patterns between the two seeds were mediated by diagnosis. Post-hoc analyses revealed that PTSD+MDD patients showed weaker connectivity between right BLA and (a) left anterior cingulate cortex/supplementary motor area, and (b) bilateral putamen/pallidum, compared with PTSD-alone patients. Higher CMA connectivities left ACC/SMA were also observed in PTSD+MDD compared with PTSD-alone. An inverse relationship between the connectivity of right BLA with right putamen/pallidum and MDD symptoms was found in PTSD+MDD. These findings indicate a relationship between the neural pathophysiology of PTSD+MDD compared with PTSD-alone and TEHC and may inform future clinical interventions.</AbstractText
|
Comparing MEG and EEG measurement set-ups for a brain-computer interface based on selective auditory attention. Auditory attention modulates auditory evoked responses to target vs. non-target sounds in electro- and magnetoencephalographic (EEG/MEG) recordings. Employing whole-scalp MEG recordings and offline classification algorithms has been shown to enable high accuracy in tracking the target of auditory attention. Here, we investigated the decrease in accuracy when moving from the whole-scalp MEG to lower channel count EEG recordings and when training the classifier only from the initial or middle part of the recording instead of extracting training trials throughout the recording. To this end, we recorded simultaneous MEG (306 channels) and EEG (64 channels) in 18 healthy volunteers while presented with concurrent streams of spoken "Yes"/"No" words and instructed to attend to one of them. We then trained support vector machine classifiers to predict the target of attention from unaveraged trials of MEG/EEG. Classifiers were trained on 204 MEG gradiometers or on EEG with 64, 30, nine or three channels with trials extracted randomly across or only from the beginning of the recording. The highest classification accuracy, 73.2% on average across the participants for one-second trials, was obtained with MEG when the training trials were randomly extracted throughout the recording. With EEG, the accuracy was 69%, 69%, 66%, and 61% when using 64, 30, nine, and three channels, respectively. When training the classifiers with the same amount of data but extracted only from the beginning of the recording, the accuracy dropped by 11%-units on average, causing the result from the three-channel EEG to fall below the chance level. The combination of five consecutive trials partially compensated for this drop such that it was one to 5%-units. Although moving from whole-scalp MEG to EEG reduces classification accuracy, usable auditory-attention-based brain-computer interfaces can be implemented with a small set of optimally placed EEG channels.</AbstractText
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25048219
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23991165
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24006024
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The sodium channel isoform transition at developing nodes of Ranvier in the peripheral nervous system: dependence on a Genetic program and myelination-induced cluster formation.
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Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.
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Quantitative lung perfusion evaluation using Fourier decomposition perfusion MRI.
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Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav 1.2 are also present at the CNS nodes in early development but gradually diminish later. It has been proposed that myelination is part of a glia-neuron signaling mechanism that produces this change in nodal isoform expression. The present study used isoform-specific antibodies to demonstrate that, in the PNS, four other neuronal sodium channel isoforms were also clustered at nodes in early development but eventually disappeared during maturation. To study possible roles of myelination in such transitions, we investigated the nodal expression of selected isoforms in the sciatic nerve of the transgenic mouse Oct6(ΔSCE/βgeo) , whose PNS myelination is delayed in the first postnatal week but eventually resumes. We found that delayed myelination retarded the formation of nodal channel clusters and altered the expression-elimination patterns of sodium channel isoforms, resulting in significantly reduced expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed myelination did not significantly affect the gene expression, protein synthesis, or axonal trafficking of any isoform studied. Rather, we found evidence for a developmentally programmed increase in neuronal Nav 1.6 expression with constant or decreasing neuronal expression of other isoforms that were unaffected by delayed myelination. Thus our results suggest that, in the developmental isoform switch of the PNS, myelination does not play a signaling role as that proposed for the CNS but rather serves only to form nodal clusters from existing isoform pools.</AbstractText
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Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.</AbstractText Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.</AbstractText These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.</AbstractText
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To quantitatively evaluate lung perfusion using Fourier decomposition perfusion MRI. The Fourier decomposition (FD) method is a noninvasive method for assessing ventilation- and perfusion-related information in the lungs, where the perfusion maps in particular have shown promise for clinical use. However, the perfusion maps are nonquantitative and dimensionless, making follow-ups and direct comparisons between patients difficult. We present an approach to obtain physically meaningful and quantifiable perfusion maps using the FD method.</AbstractText The standard FD perfusion images are quantified by comparing the partially blood-filled pixels in the lung parenchyma with the fully blood-filled pixels in the aorta. The percentage of blood in a pixel is then combined with the temporal information, yielding quantitative blood flow values. The values of 10 healthy volunteers are compared with SEEPAGE measurements which have shown high consistency with dynamic contrast enhanced-MRI.</AbstractText All pulmonary blood flow (PBF) values are within the expected range. The two methods are in good agreement (mean difference = 0.2 mL/min/100 mL, mean absolute difference = 11 mL/min/100 mL, mean PBF-FD = 150 mL/min/100 mL, mean PBF-SEEPAGE = 151 mL/min/100 mL). The Bland-Altman plot shows a good spread of values, indicating no systematic bias between the methods.</AbstractText Quantitative lung perfusion can be obtained using the Fourier Decomposition method combined with a small amount of postprocessing.</AbstractText
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The sodium channel isoform transition at developing nodes of Ranvier in the peripheral nervous system: dependence on a Genetic program and myelination-induced cluster formation. Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav 1.2 are also present at the CNS nodes in early development but gradually diminish later. It has been proposed that myelination is part of a glia-neuron signaling mechanism that produces this change in nodal isoform expression. The present study used isoform-specific antibodies to demonstrate that, in the PNS, four other neuronal sodium channel isoforms were also clustered at nodes in early development but eventually disappeared during maturation. To study possible roles of myelination in such transitions, we investigated the nodal expression of selected isoforms in the sciatic nerve of the transgenic mouse Oct6(ΔSCE/βgeo) , whose PNS myelination is delayed in the first postnatal week but eventually resumes. We found that delayed myelination retarded the formation of nodal channel clusters and altered the expression-elimination patterns of sodium channel isoforms, resulting in significantly reduced expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed myelination did not significantly affect the gene expression, protein synthesis, or axonal trafficking of any isoform studied. Rather, we found evidence for a developmentally programmed increase in neuronal Nav 1.6 expression with constant or decreasing neuronal expression of other isoforms that were unaffected by delayed myelination. Thus our results suggest that, in the developmental isoform switch of the PNS, myelination does not play a signaling role as that proposed for the CNS but rather serves only to form nodal clusters from existing isoform pools.</AbstractText
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Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica. Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.</AbstractText Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.</AbstractText These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.</AbstractText
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Quantitative lung perfusion evaluation using Fourier decomposition perfusion MRI. To quantitatively evaluate lung perfusion using Fourier decomposition perfusion MRI. The Fourier decomposition (FD) method is a noninvasive method for assessing ventilation- and perfusion-related information in the lungs, where the perfusion maps in particular have shown promise for clinical use. However, the perfusion maps are nonquantitative and dimensionless, making follow-ups and direct comparisons between patients difficult. We present an approach to obtain physically meaningful and quantifiable perfusion maps using the FD method.</AbstractText The standard FD perfusion images are quantified by comparing the partially blood-filled pixels in the lung parenchyma with the fully blood-filled pixels in the aorta. The percentage of blood in a pixel is then combined with the temporal information, yielding quantitative blood flow values. The values of 10 healthy volunteers are compared with SEEPAGE measurements which have shown high consistency with dynamic contrast enhanced-MRI.</AbstractText All pulmonary blood flow (PBF) values are within the expected range. The two methods are in good agreement (mean difference = 0.2 mL/min/100 mL, mean absolute difference = 11 mL/min/100 mL, mean PBF-FD = 150 mL/min/100 mL, mean PBF-SEEPAGE = 151 mL/min/100 mL). The Bland-Altman plot shows a good spread of values, indicating no systematic bias between the methods.</AbstractText Quantitative lung perfusion can be obtained using the Fourier Decomposition method combined with a small amount of postprocessing.</AbstractText
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25295758
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14755655
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25912803
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CEST signal at 2ppm (CEST@2ppm) from Z-spectral fitting correlates with creatine distribution in brain tumor.
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Regional variations in normal brain shown by quantitative magnetization transfer imaging.
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The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats.
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In general, multiple components such as water direct saturation, magnetization transfer (MT), chemical exchange saturation transfer (CEST) and aliphatic nuclear Overhauser effect (NOE) contribute to the Z-spectrum. The conventional CEST quantification method based on asymmetrical analysis may lead to quantification errors due to the semi-solid MT asymmetry and the aliphatic NOE located on a single side of the Z-spectrum. Fitting individual contributors to the Z-spectrum may improve the quantification of each component. In this study, we aim to characterize the multiple exchangeable components from an intracranial tumor model using a simplified Z-spectral fitting method. In this method, the Z-spectrum acquired at low saturation RF amplitude (50 Hz) was modeled as the summation of five Lorentzian functions that correspond to NOE, MT effect, bulk water, amide proton transfer (APT) effect and a CEST peak located at +2 ppm, called CEST@2ppm. With the pixel-wise fitting, the regional variations of these five components in the brain tumor and the normal brain tissue were quantified and summarized. Increased APT effect, decreased NOE and reduced CEST@2ppm were observed in the brain tumor compared with the normal brain tissue. Additionally, CEST@2ppm decreased with tumor progression. CEST@2ppm was found to correlate with the creatine concentration quantified with proton MRS. Based on the correlation curve, the creatine contribution to CEST@2ppm was quantified. The CEST@2ppm signal could be a novel imaging surrogate for in vivo creatine, the important bioenergetics marker. Given its noninvasive nature, this CEST MRI method may have broad applications in cancer bioenergetics.</AbstractText
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A quantitative magnetization transfer imaging (qMTI) study, based on a two-pool model of magnetization transfer, was performed on seven normal subjects to determine, on a regional basis, normal values for the pool sizes, exchange, and relaxation parameters that characterize the MT phenomenon. Regions were identified on high-resolution anatomical scans using a combination of manual and automatic methods. Only voxels identified as pure tissue at the resolution of the quantitative scans were considered for analysis. While no left/right differences were observed, significant differences were found among white-matter regions and gray-matter regions. These regional differences were compared with existing cytoarchitectural data. In addition, the pattern and magnitude of the regional differences observed in white matter was found to be different from that reported previously for an alternative putative MRI measure of myelination, the 10-50-ms T2 component described as myelin water.</AbstractText
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Muscle wound healing process is a typical inflammation-evoked event. The monoacylglycerol lipase (MAGL) inhibitor (4-nitrophenyl)4-[bis(1,3-benzodioxol -5-yl)-hydroxymethyl]piperidine-1-carboxylate (JZL184) has been previously reported to reduce inflammation in colitis and acute lung injury in mice, which provide a new strategy for primary care of skeletal muscle injury. We investigated the effect of JZL184 on inflammation in rat muscle contusion model, and found decreased neutrophil and macrophage infiltration and pro-inflammatory cytokine expression. With extension of post-traumatic interval, myofiber regeneration was significantly hindered with increased collagen types I and ІІІ mRNAfibroblast infiltration as well as promoted fibrosis. Furthermore, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide (AM281, a selective cannabinoid CB1 receptor antagonist) and [6-iodo-2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone (AM630, a selective cannabinoid CB2 receptor antagonist) treatment alleviated the anti-inflammatory effect of JZL184. Our findings demonstrate that JZL184 is able to inhibit the inflammatory response and interfere with contused muscle healing, in which the anti-inflammatory action may be mediated through cannabinoid CB1 and CB2 receptors.</AbstractText
|
CEST signal at 2ppm (CEST@2ppm) from Z-spectral fitting correlates with creatine distribution in brain tumor. In general, multiple components such as water direct saturation, magnetization transfer (MT), chemical exchange saturation transfer (CEST) and aliphatic nuclear Overhauser effect (NOE) contribute to the Z-spectrum. The conventional CEST quantification method based on asymmetrical analysis may lead to quantification errors due to the semi-solid MT asymmetry and the aliphatic NOE located on a single side of the Z-spectrum. Fitting individual contributors to the Z-spectrum may improve the quantification of each component. In this study, we aim to characterize the multiple exchangeable components from an intracranial tumor model using a simplified Z-spectral fitting method. In this method, the Z-spectrum acquired at low saturation RF amplitude (50 Hz) was modeled as the summation of five Lorentzian functions that correspond to NOE, MT effect, bulk water, amide proton transfer (APT) effect and a CEST peak located at +2 ppm, called CEST@2ppm. With the pixel-wise fitting, the regional variations of these five components in the brain tumor and the normal brain tissue were quantified and summarized. Increased APT effect, decreased NOE and reduced CEST@2ppm were observed in the brain tumor compared with the normal brain tissue. Additionally, CEST@2ppm decreased with tumor progression. CEST@2ppm was found to correlate with the creatine concentration quantified with proton MRS. Based on the correlation curve, the creatine contribution to CEST@2ppm was quantified. The CEST@2ppm signal could be a novel imaging surrogate for in vivo creatine, the important bioenergetics marker. Given its noninvasive nature, this CEST MRI method may have broad applications in cancer bioenergetics.</AbstractText
|
Regional variations in normal brain shown by quantitative magnetization transfer imaging. A quantitative magnetization transfer imaging (qMTI) study, based on a two-pool model of magnetization transfer, was performed on seven normal subjects to determine, on a regional basis, normal values for the pool sizes, exchange, and relaxation parameters that characterize the MT phenomenon. Regions were identified on high-resolution anatomical scans using a combination of manual and automatic methods. Only voxels identified as pure tissue at the resolution of the quantitative scans were considered for analysis. While no left/right differences were observed, significant differences were found among white-matter regions and gray-matter regions. These regional differences were compared with existing cytoarchitectural data. In addition, the pattern and magnitude of the regional differences observed in white matter was found to be different from that reported previously for an alternative putative MRI measure of myelination, the 10-50-ms T2 component described as myelin water.</AbstractText
|
The monoacylglycerol lipase inhibitor JZL184 decreases inflammatory response in skeletal muscle contusion in rats. Muscle wound healing process is a typical inflammation-evoked event. The monoacylglycerol lipase (MAGL) inhibitor (4-nitrophenyl)4-[bis(1,3-benzodioxol -5-yl)-hydroxymethyl]piperidine-1-carboxylate (JZL184) has been previously reported to reduce inflammation in colitis and acute lung injury in mice, which provide a new strategy for primary care of skeletal muscle injury. We investigated the effect of JZL184 on inflammation in rat muscle contusion model, and found decreased neutrophil and macrophage infiltration and pro-inflammatory cytokine expression. With extension of post-traumatic interval, myofiber regeneration was significantly hindered with increased collagen types I and ІІІ mRNAfibroblast infiltration as well as promoted fibrosis. Furthermore, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-morpholin-4-ylpyrazole-3-carboxamide (AM281, a selective cannabinoid CB1 receptor antagonist) and [6-iodo-2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone (AM630, a selective cannabinoid CB2 receptor antagonist) treatment alleviated the anti-inflammatory effect of JZL184. Our findings demonstrate that JZL184 is able to inhibit the inflammatory response and interfere with contused muscle healing, in which the anti-inflammatory action may be mediated through cannabinoid CB1 and CB2 receptors.</AbstractText
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37322742
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28655433
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37716349
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Magnetic Resonance Imaging Brain Findings in Chikungunya Virus (CHIKV) Infection with Neurological Complication during Epidemic Outbreak.
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Role of chemical shift and Dixon based techniques in musculoskeletal MR imaging.
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Orbitofrontal cortex conveys stimulus and task information to the auditory cortex.
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The Chikungunya virus is an alphavirus RNA of the family Togaviridae transmitted by the Aedes mosquito. We aim to report magnetic resonance imaging (MRI) brain findings for neurological complications at our institute during epidemic outbreak.</AbstractText A total of 43 seropositive cases of Chikungunya infection underwent MRI brain.</AbstractText Out of 43 patients, 27 (63%) had discrete and confluent supra-tentorial T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) hyper-intense white matter foci. A total of 14 patients (33%) showed multiple foci/areas of diffusion restriction, and four of these patients had infra-tentorial T2 & FLAIR hyper-intense foci with restricted diffusion. In three pediatric age group patients including two neonates, the pattern of involvement was diffuse white matter changes with restricted diffusion. In 30% cases, MRI was normal.</AbstractText Detection of focal or confluent white matter hyper-intense foci with restricted diffusion on MRI in patients presenting with fever and neurological symptoms has potential to conclude the diagnosis of Chikungunya encephalitis, especially in epidemic settings.</AbstractText
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Fat suppression technique is a valuable resource in musculoskeletal magnetic resonance (MR) imaging that is helpful in the diagnosis and differentiation of various pathologies. Multiple different techniques are available for fat suppression, including frequency selective pulse sequence, inversion recovery, hybrid technique, chemical shift imaging (CSI) and the related Dixon based approach. The utility of CSI and Dixon approach is not well recognized in the domain of musculoskeletal MR imaging. The aim of this article is to review the various options for fat suppression and present focused discussion of the role of CSI and Dixon techniques for musculoskeletal MR imaging.</AbstractText
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Auditory cortical neurons modify their response profiles in response to numerous external factors. During task performance, changes in primary auditory cortex (A1) responses are thought to be driven by top-down inputs from the orbitofrontal cortex (OFC), which may lead to response modification on a trial-by-trial basis. While OFC neurons respond to auditory stimuli and project to A1, the function of OFC projections to A1 during auditory tasks is unknown. Here, we observed the activity of putative OFC terminals in A1 in mice by using in vivo two-photon calcium imaging of OFC terminals under passive conditions and during a tone detection task. We found that behavioral activity modulates but is not necessary to evoke OFC terminal responses in A1. OFC terminals in A1 form distinct populations that exclusively respond to either the tone, reward, or error. Using tones against a background of white noise, we found that OFC terminal activity was modulated by the signal-to-noise ratio (SNR) in both the passive and active conditions and that OFC terminal activity varied with SNR, and thus task difficulty in the active condition. Therefore, OFC projections in A1 are heterogeneous in their modulation of auditory encoding and likely contribute to auditory processing under various auditory conditions.</AbstractText
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Magnetic Resonance Imaging Brain Findings in Chikungunya Virus (CHIKV) Infection with Neurological Complication during Epidemic Outbreak. The Chikungunya virus is an alphavirus RNA of the family Togaviridae transmitted by the Aedes mosquito. We aim to report magnetic resonance imaging (MRI) brain findings for neurological complications at our institute during epidemic outbreak.</AbstractText A total of 43 seropositive cases of Chikungunya infection underwent MRI brain.</AbstractText Out of 43 patients, 27 (63%) had discrete and confluent supra-tentorial T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) hyper-intense white matter foci. A total of 14 patients (33%) showed multiple foci/areas of diffusion restriction, and four of these patients had infra-tentorial T2 & FLAIR hyper-intense foci with restricted diffusion. In three pediatric age group patients including two neonates, the pattern of involvement was diffuse white matter changes with restricted diffusion. In 30% cases, MRI was normal.</AbstractText Detection of focal or confluent white matter hyper-intense foci with restricted diffusion on MRI in patients presenting with fever and neurological symptoms has potential to conclude the diagnosis of Chikungunya encephalitis, especially in epidemic settings.</AbstractText
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Role of chemical shift and Dixon based techniques in musculoskeletal MR imaging. Fat suppression technique is a valuable resource in musculoskeletal magnetic resonance (MR) imaging that is helpful in the diagnosis and differentiation of various pathologies. Multiple different techniques are available for fat suppression, including frequency selective pulse sequence, inversion recovery, hybrid technique, chemical shift imaging (CSI) and the related Dixon based approach. The utility of CSI and Dixon approach is not well recognized in the domain of musculoskeletal MR imaging. The aim of this article is to review the various options for fat suppression and present focused discussion of the role of CSI and Dixon techniques for musculoskeletal MR imaging.</AbstractText
|
Orbitofrontal cortex conveys stimulus and task information to the auditory cortex. Auditory cortical neurons modify their response profiles in response to numerous external factors. During task performance, changes in primary auditory cortex (A1) responses are thought to be driven by top-down inputs from the orbitofrontal cortex (OFC), which may lead to response modification on a trial-by-trial basis. While OFC neurons respond to auditory stimuli and project to A1, the function of OFC projections to A1 during auditory tasks is unknown. Here, we observed the activity of putative OFC terminals in A1 in mice by using in vivo two-photon calcium imaging of OFC terminals under passive conditions and during a tone detection task. We found that behavioral activity modulates but is not necessary to evoke OFC terminal responses in A1. OFC terminals in A1 form distinct populations that exclusively respond to either the tone, reward, or error. Using tones against a background of white noise, we found that OFC terminal activity was modulated by the signal-to-noise ratio (SNR) in both the passive and active conditions and that OFC terminal activity varied with SNR, and thus task difficulty in the active condition. Therefore, OFC projections in A1 are heterogeneous in their modulation of auditory encoding and likely contribute to auditory processing under various auditory conditions.</AbstractText
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38152865
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37532963
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40166314
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The effect of acute and chronic formaldehyde exposure on learning and memory in male and female rats.
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Exposure Therapy and Its Mechanisms.
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Neural Synchrony Links Sensorimotor Cortices in a Network for Facial Motor Control.
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Formaldehyde is a chemical that lies behind the various systemical failures in organism. Many products that people use contain formaldehyde. Owing to its tissue fixative properties, scientists who work in life sciences are exposed to this substance more than others. Several studies have shown that formaldehyde affects the CA1 and CA3 regions of the hippocampus, which play crucial roles in memory consolidation. In this study, we aimed to investigate anxiety levels and indicate the short and long term effects of formaldehyde and sex-related differences by exposing formaldehyde to male and female rats.</AbstractText Formaldehyde (10 mg/kg) was administered intraperitoneally for 7 days for acute exposure and 30 days for chronic exposure. Cognitive assessment was performed using fear conditioning, elevated plus maze, and Morris water maze tests. TUNEL staining was used to identify apoptosis in the brains obtained after decapitation.</AbstractText Exposure to intraperitoneal formaldehyde does not impair learning and memory in acute and chronic periods and has no effect on depression or anxiety. After acute exposure, apoptosis was observed in the hippocampal CA1 and CA3 regions in males. When the cognitive test results were examined, no differences were found between the experimental and control groups. There was also no significant difference between males and females.</AbstractText
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Exposure therapy is the gold-standard treatment approach for pathological anxiety. This therapeutic approach builds on principles of extinction training from traditional fear conditioning and extinction protocols. In this chapter, we discuss principles of exposure therapy in the clinic and the laboratory experimental results that guide our decisions in the therapy. We discuss emotional processing theory and inhibitory learning principles, with a focus on expectation violation. We conclude with future research directions needed to improve exposure therapy outcomes among patients with anxiety-related disorders.</AbstractText
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Primate societies rely on the production and interpretation of social signals, in particular those displayed by the face. Facial movements are controlled, according to the dominant neuropsychological schema, by two separate circuits, one originating in medial frontal cortex controlling emotional expressions, and a second one originating in lateral motor and premotor areas controlling voluntary facial movements. Despite this functional dichotomy, cortical anatomy suggests that medial and lateral areas are directly connected and may thus operate as a single network. Here we test these contrasting hypotheses through structural and functional magnetic resonance imaging (fMRI) guided electrical stimulation and simultaneous multi-channel recordings from key face motor areas in the macaque monkey brain. These areas include medial face motor area M3 (located in the anterior cingulate cortex); two lateral face-related motor areas: M1 (primary motor) and PMv (ventrolateral premotor); and S1 (primary somatosensory cortex). Cortical responses evoked by intracortical stimulation revealed that medial and lateral areas can exert significant functional impact on each other. Simultaneous recordings of local field potentials in all face motor areas further confirm that during facial expressions, medial and lateral face motor areas significantly interact, primarily in the alpha and beta frequency ranges. These functional interactions varied across different types of facial movements. Thus, contrary to the dominant neuropsychological dogma, control of facial movements is not mediated through independent (medial/lateral) functional streams, but results from an extensive interacting sensorimotor network.</AbstractText
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The effect of acute and chronic formaldehyde exposure on learning and memory in male and female rats. Formaldehyde is a chemical that lies behind the various systemical failures in organism. Many products that people use contain formaldehyde. Owing to its tissue fixative properties, scientists who work in life sciences are exposed to this substance more than others. Several studies have shown that formaldehyde affects the CA1 and CA3 regions of the hippocampus, which play crucial roles in memory consolidation. In this study, we aimed to investigate anxiety levels and indicate the short and long term effects of formaldehyde and sex-related differences by exposing formaldehyde to male and female rats.</AbstractText Formaldehyde (10 mg/kg) was administered intraperitoneally for 7 days for acute exposure and 30 days for chronic exposure. Cognitive assessment was performed using fear conditioning, elevated plus maze, and Morris water maze tests. TUNEL staining was used to identify apoptosis in the brains obtained after decapitation.</AbstractText Exposure to intraperitoneal formaldehyde does not impair learning and memory in acute and chronic periods and has no effect on depression or anxiety. After acute exposure, apoptosis was observed in the hippocampal CA1 and CA3 regions in males. When the cognitive test results were examined, no differences were found between the experimental and control groups. There was also no significant difference between males and females.</AbstractText
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Exposure Therapy and Its Mechanisms. Exposure therapy is the gold-standard treatment approach for pathological anxiety. This therapeutic approach builds on principles of extinction training from traditional fear conditioning and extinction protocols. In this chapter, we discuss principles of exposure therapy in the clinic and the laboratory experimental results that guide our decisions in the therapy. We discuss emotional processing theory and inhibitory learning principles, with a focus on expectation violation. We conclude with future research directions needed to improve exposure therapy outcomes among patients with anxiety-related disorders.</AbstractText
|
Neural Synchrony Links Sensorimotor Cortices in a Network for Facial Motor Control. Primate societies rely on the production and interpretation of social signals, in particular those displayed by the face. Facial movements are controlled, according to the dominant neuropsychological schema, by two separate circuits, one originating in medial frontal cortex controlling emotional expressions, and a second one originating in lateral motor and premotor areas controlling voluntary facial movements. Despite this functional dichotomy, cortical anatomy suggests that medial and lateral areas are directly connected and may thus operate as a single network. Here we test these contrasting hypotheses through structural and functional magnetic resonance imaging (fMRI) guided electrical stimulation and simultaneous multi-channel recordings from key face motor areas in the macaque monkey brain. These areas include medial face motor area M3 (located in the anterior cingulate cortex); two lateral face-related motor areas: M1 (primary motor) and PMv (ventrolateral premotor); and S1 (primary somatosensory cortex). Cortical responses evoked by intracortical stimulation revealed that medial and lateral areas can exert significant functional impact on each other. Simultaneous recordings of local field potentials in all face motor areas further confirm that during facial expressions, medial and lateral face motor areas significantly interact, primarily in the alpha and beta frequency ranges. These functional interactions varied across different types of facial movements. Thus, contrary to the dominant neuropsychological dogma, control of facial movements is not mediated through independent (medial/lateral) functional streams, but results from an extensive interacting sensorimotor network.</AbstractText
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26487807
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21942230
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26172545
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A systematic review of the neural bases of psychotherapy for anxiety and related disorders.
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Determination of emotional endophenotypes: a validation of the Affective Neuroscience Personality Scales and further perspectives.
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Does Traumatic Brain Injury Lead to Criminality? A Whole-Population Retrospective Cohort Study Using Linked Data.
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Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions.</AbstractText Los estudios de imaginología cerebral desde hace más de dos décadas ban delineado los circuitos neurales de la ansiedad y los trastornos relacionados, particularmente las regiones involucradas en el procesamiento del miedo y en los síntomas obsesivo compulsivos. El circuito neural del procesamiento del miedo incluye la amígdala y las cortezas cingulada anterior e insular, mientras que el circuito tálamo-estriado-cortical juega un papel clave en el trastorno obsesivo-compulsivo. Más recientemente, los estudios de neuroimágenes han examinado cómo la psicoterapia para la ansiedad y los trastornos relacionados impacta en estos circuitos neurales. En este artículo se realiza una revision sistemática de los hallazgos de estos trabajos, los que comprenden 19 estudios de resonancia magnética functional que examinan las bases neurales de la terapia cognitivo-conductual (TCC) en 509 patientes con ansiedad y trastornos relacionados. Se concluye que aunque la ansiedad y cada uno de los trastornos relationados está mediado por circuitos neurales algo diferentes, la TCC puede actuar de manera similar para aumentar el control prefrontal de las estructuras subcorticales. Estos hallazgos son consistentes con el énfasis de la neurociencia cognitivo-afectiva en el potential valor terapéutico del aumento de la regulación emocional en varias condiciones psiquiátricas.</AbstractText Ces 20 dernières années, des études d'imagerie cérébrale ont défini les circuits neuronaux de l'anxiété et des troubles apparentés, en particulier les régions impliquées dans les processus de peur et les symptômes obsessionnels-compulsifs. L'amygdale, le cortex insulaire et le cortex cingulaire antérieur sont impliqués dans les circuits neuronaux des processus de peur, tandis que le circuit cortico-striato-thalamique joue un rôle dans les troubles obsessionnels-compulsifs. Plus récemment, des études de neuro-imagerie ont analysé comment la psychothérapie pour l'anxiété et les troubles apparentés influent sur ces circuits neuronaux. Nous menons ici une étude méthodique sur les résultats de ces travaux, qui a permis d'aboutir à 19 études d'imagerie fonctionnelle par résonance magnétique analysant les bases neuronales d'une thérapie cognitivo-comportementale (TCC) chez 509 patients atteints d'anxiété et de troubles apparentés. Bien que l'anxiété et les troubles apparentés soient induits par différents circuits neuronaux, nous concluons que la TCC peut agir de la même façon pour accroître le contrôle préfrontal des structures sous-corticales. Ces résultats sont cohérents avec l'accent mis dans les neurostiences cognitivo-affectives, sur la valeur thérapeutique potentielle de l'amélioration de la régulation émotionnelle dans diverses pathologies psychiatriques.</AbstractText
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The study of endophenotypes, notably with configured self-reports, represents a promising research pathway to overcome the limits of a syndromal approach of psychiatric diseases. The Affective Neuroscience Personality Scales (ANPS) is a self-report questionnaire, based on neuroethological considerations, that could help to assess emotional endophenotypes related to the activity in 6 core cerebral emotional systems (FEAR, ANGER, SADNESS, CARING, PLAYFULNESS, SEEKING). We further investigated its psychometric properties among 830 young adults and showed that they were satisfactory. As participants also completed several other self-reports that shared potential traits with the ANPS, we offer new validity evidence based on relations to other variables. We also provide additional evidence to consider that the ANPS scores can be validly interpreted for the characterization of emotional endophenotypes involved in a variety of psychiatric disorders. On the grounds of present results, of previous clinical studies, as well as some preliminary neuroimaging findings, we discuss new steps in the ANPS validation.</AbstractText
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Traumatic brain injury (TBI) may be a risk factor for criminal behaviour however multiple factors potentially confound the association.</AbstractText Record linkage and Cox proportional hazards regression analyses were used to examine the association between hospital-recorded TBI (n = 7,694) and subsequent first criminal conviction in a retrospective cohort matched 1:3 with 22,905 unaffected community controls and full-sibling controls (n = 2,397). Aboriginality, substance abuse, social disadvantage, and mental illness were included in analyses as potential confounders.</AbstractText In multivariable models, relative to general population controls, TBI was associated with any conviction (males: Hazard Ratio (HR) = 1.58 (95% CI 1.46 to 1.72); females: HR = 1.52 (95% CI 1.28 to 1.81)); and similar Hazard Ratios were obtained for the sibling analyses in males (HR = 1.68 (95% CI 1.31-2.18)) and females (HR 1.27 (95% CI 0.71-2.29)). TBI was also associated with violent convictions relative to the general population, (males: HR = 1.65 (95% CI 1.42 to 1.92); females HR = 1.73 (95% CI 1.21 to 2.47)), and in analyses with sibling controls in men (HR = 1.89 (95% CI 1.20-3.00)), but not in women (HR 0.73, 95% CI 0.29-1.81)).</AbstractText The results support a modest causal link between TBI and criminality after comprehensive adjustment for confounding. Reducing the rate of TBI, a major public health imperative, might have benefits in terms of crime reduction.</AbstractText
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A systematic review of the neural bases of psychotherapy for anxiety and related disorders. Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions.</AbstractText Los estudios de imaginología cerebral desde hace más de dos décadas ban delineado los circuitos neurales de la ansiedad y los trastornos relacionados, particularmente las regiones involucradas en el procesamiento del miedo y en los síntomas obsesivo compulsivos. El circuito neural del procesamiento del miedo incluye la amígdala y las cortezas cingulada anterior e insular, mientras que el circuito tálamo-estriado-cortical juega un papel clave en el trastorno obsesivo-compulsivo. Más recientemente, los estudios de neuroimágenes han examinado cómo la psicoterapia para la ansiedad y los trastornos relacionados impacta en estos circuitos neurales. En este artículo se realiza una revision sistemática de los hallazgos de estos trabajos, los que comprenden 19 estudios de resonancia magnética functional que examinan las bases neurales de la terapia cognitivo-conductual (TCC) en 509 patientes con ansiedad y trastornos relacionados. Se concluye que aunque la ansiedad y cada uno de los trastornos relationados está mediado por circuitos neurales algo diferentes, la TCC puede actuar de manera similar para aumentar el control prefrontal de las estructuras subcorticales. Estos hallazgos son consistentes con el énfasis de la neurociencia cognitivo-afectiva en el potential valor terapéutico del aumento de la regulación emocional en varias condiciones psiquiátricas.</AbstractText Ces 20 dernières années, des études d'imagerie cérébrale ont défini les circuits neuronaux de l'anxiété et des troubles apparentés, en particulier les régions impliquées dans les processus de peur et les symptômes obsessionnels-compulsifs. L'amygdale, le cortex insulaire et le cortex cingulaire antérieur sont impliqués dans les circuits neuronaux des processus de peur, tandis que le circuit cortico-striato-thalamique joue un rôle dans les troubles obsessionnels-compulsifs. Plus récemment, des études de neuro-imagerie ont analysé comment la psychothérapie pour l'anxiété et les troubles apparentés influent sur ces circuits neuronaux. Nous menons ici une étude méthodique sur les résultats de ces travaux, qui a permis d'aboutir à 19 études d'imagerie fonctionnelle par résonance magnétique analysant les bases neuronales d'une thérapie cognitivo-comportementale (TCC) chez 509 patients atteints d'anxiété et de troubles apparentés. Bien que l'anxiété et les troubles apparentés soient induits par différents circuits neuronaux, nous concluons que la TCC peut agir de la même façon pour accroître le contrôle préfrontal des structures sous-corticales. Ces résultats sont cohérents avec l'accent mis dans les neurostiences cognitivo-affectives, sur la valeur thérapeutique potentielle de l'amélioration de la régulation émotionnelle dans diverses pathologies psychiatriques.</AbstractText
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Determination of emotional endophenotypes: a validation of the Affective Neuroscience Personality Scales and further perspectives. The study of endophenotypes, notably with configured self-reports, represents a promising research pathway to overcome the limits of a syndromal approach of psychiatric diseases. The Affective Neuroscience Personality Scales (ANPS) is a self-report questionnaire, based on neuroethological considerations, that could help to assess emotional endophenotypes related to the activity in 6 core cerebral emotional systems (FEAR, ANGER, SADNESS, CARING, PLAYFULNESS, SEEKING). We further investigated its psychometric properties among 830 young adults and showed that they were satisfactory. As participants also completed several other self-reports that shared potential traits with the ANPS, we offer new validity evidence based on relations to other variables. We also provide additional evidence to consider that the ANPS scores can be validly interpreted for the characterization of emotional endophenotypes involved in a variety of psychiatric disorders. On the grounds of present results, of previous clinical studies, as well as some preliminary neuroimaging findings, we discuss new steps in the ANPS validation.</AbstractText
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Does Traumatic Brain Injury Lead to Criminality? A Whole-Population Retrospective Cohort Study Using Linked Data. Traumatic brain injury (TBI) may be a risk factor for criminal behaviour however multiple factors potentially confound the association.</AbstractText Record linkage and Cox proportional hazards regression analyses were used to examine the association between hospital-recorded TBI (n = 7,694) and subsequent first criminal conviction in a retrospective cohort matched 1:3 with 22,905 unaffected community controls and full-sibling controls (n = 2,397). Aboriginality, substance abuse, social disadvantage, and mental illness were included in analyses as potential confounders.</AbstractText In multivariable models, relative to general population controls, TBI was associated with any conviction (males: Hazard Ratio (HR) = 1.58 (95% CI 1.46 to 1.72); females: HR = 1.52 (95% CI 1.28 to 1.81)); and similar Hazard Ratios were obtained for the sibling analyses in males (HR = 1.68 (95% CI 1.31-2.18)) and females (HR 1.27 (95% CI 0.71-2.29)). TBI was also associated with violent convictions relative to the general population, (males: HR = 1.65 (95% CI 1.42 to 1.92); females HR = 1.73 (95% CI 1.21 to 2.47)), and in analyses with sibling controls in men (HR = 1.89 (95% CI 1.20-3.00)), but not in women (HR 0.73, 95% CI 0.29-1.81)).</AbstractText The results support a modest causal link between TBI and criminality after comprehensive adjustment for confounding. Reducing the rate of TBI, a major public health imperative, might have benefits in terms of crime reduction.</AbstractText
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33970388
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29876265
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34210374
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What Executive Function Network is that? An Image-Based Meta-Analysis of Network Labels.
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Dynamic network dysfunction in cocaine dependence: Graph theoretical metrics and stop signal reaction time.
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Development and validation of the Maudsley Modified Patient Health Questionnaire (MM-PHQ-9).
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The current state of label conventions used to describe brain networks related to executive functions is highly inconsistent, leading to confusion among researchers regarding network labels. Visually similar networks are referred to by different labels, yet these same labels are used to distinguish networks within studies. We performed a literature review of fMRI studies and identified nine frequently-used labels that are used to describe topographically or functionally similar neural networks: central executive network (CEN), cognitive control network (CCN), dorsal attention network (DAN), executive control network (ECN), executive network (EN), frontoparietal network (FPN), working memory network (WMN), task positive network (TPN), and ventral attention network (VAN). Our aim was to meta-analytically determine consistency of network topography within and across these labels. We hypothesized finding considerable overlap in the spatial topography among the neural networks associated with these labels. An image-based meta-analysis was performed on 158 group-level statistical maps (SPMs) received from authors of 69 papers listed on PubMed. Our results indicated that there was very little consistency in the SPMs labeled with a given network name. We identified four clusters of SPMs representing four spatially distinct executive function networks. We provide recommendations regarding label nomenclature and propose that authors looking to assign labels to executive function networks adopt this template set for labeling networks.</AbstractText
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Graphic theoretical metrics have become increasingly popular in characterizing functional connectivity of neural networks and how network connectivity is compromised in neuropsychiatric illnesses. Here, we add to this literature by describing dynamic network connectivities of 78 cocaine dependent (CD) and 85 non-drug using healthy control (HC) participants who underwent fMRI during performance of a stop signal task (SST). Compared to HC, CD showed prolonged stop signal reaction time (SSRT), consistent with deficits in response inhibition. In graph theoretical analysis of dynamic functional connectivity, we examined temporal flexibility and spatiotemporal diversity of 14 networks covering the whole brain. Temporal flexibility quantifies how frequently a brain region interacts with regions of other communities across time, with high temporal flexibility indicating that a region interacts predominantly with regions outside its own community. Spatiotemporal diversity quantifies how uniformly a brain region interacts with regions in other communities over time, with high spatiotemporal diversity indicating that the interactions are more evenly distributed across communities. Compared to HC, CD exhibited decreased temporal flexibility and increased spatiotemporal diversity in the great majority of neural networks. The graph metric measures of the default mode network negatively correlated with SSRT in CD but not HC. The findings are consistent with diminished temporal flexibility and a compensatory increase in spatiotemporal diversity, in association with impairment of a critical executive function, in cocaine addiction. More broadly, the findings suggest that graph theoretical metrics provide new insights for connectivity analyses to elucidate network dysfunction that may elude conventional measures.</AbstractText
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The Patient Health Questionnaire-9 (PHQ-9) is a widely used measure of depression in primary care. It was, however, originally designed as a diagnostic screening tool, and not for measuring change in response to antidepressant treatment. Although the Quick Inventory of Depressive Symptomology (QIDS-SR-16) has been extensively validated for outcome measurement, it is poorly adopted in UK primary care, and, although free for clinicians, has licensing restrictions for healthcare organisation use.</AbstractText We aimed to develop a modified version of the PHQ-9, the Maudsley Modified PHQ-9 (MM-PHQ-9), for tracking symptom changes in primary care. We tested the measure's validity, reliability and factor structure.</AbstractText A sample of 121 participants was recruited across three studies, and comprised 78 participants with major depressive disorder and 43 controls. MM-PHQ-9 scores were compared with the QIDS-SR-16 and Clinical Global Impressions improvement scale, for concurrent validity. Internal consistency of the scale was assessed, and principal component analysis was conducted to determine the items' factor structure.</AbstractText The MM-PHQ-9 demonstrated good concurrent validity with the QIDS-SR-16, and excellent internal consistency. Sensitivity to change over a 14-week period was d = 0.41 compared with d = 0.61 on the QIDS-SR-16. Concurrent validity between the paper and mobile app versions of the MM-PHQ-9 was r = 0.67.</AbstractText These results indicate that the MM-PHQ-9 is a valid and reliable measure of depressive symptoms in paper and mobile app format, although further validation is required. The measure was sensitive to change, demonstrating suitability for use in routine outcome assessment.</AbstractText
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What Executive Function Network is that? An Image-Based Meta-Analysis of Network Labels. The current state of label conventions used to describe brain networks related to executive functions is highly inconsistent, leading to confusion among researchers regarding network labels. Visually similar networks are referred to by different labels, yet these same labels are used to distinguish networks within studies. We performed a literature review of fMRI studies and identified nine frequently-used labels that are used to describe topographically or functionally similar neural networks: central executive network (CEN), cognitive control network (CCN), dorsal attention network (DAN), executive control network (ECN), executive network (EN), frontoparietal network (FPN), working memory network (WMN), task positive network (TPN), and ventral attention network (VAN). Our aim was to meta-analytically determine consistency of network topography within and across these labels. We hypothesized finding considerable overlap in the spatial topography among the neural networks associated with these labels. An image-based meta-analysis was performed on 158 group-level statistical maps (SPMs) received from authors of 69 papers listed on PubMed. Our results indicated that there was very little consistency in the SPMs labeled with a given network name. We identified four clusters of SPMs representing four spatially distinct executive function networks. We provide recommendations regarding label nomenclature and propose that authors looking to assign labels to executive function networks adopt this template set for labeling networks.</AbstractText
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Dynamic network dysfunction in cocaine dependence: Graph theoretical metrics and stop signal reaction time. Graphic theoretical metrics have become increasingly popular in characterizing functional connectivity of neural networks and how network connectivity is compromised in neuropsychiatric illnesses. Here, we add to this literature by describing dynamic network connectivities of 78 cocaine dependent (CD) and 85 non-drug using healthy control (HC) participants who underwent fMRI during performance of a stop signal task (SST). Compared to HC, CD showed prolonged stop signal reaction time (SSRT), consistent with deficits in response inhibition. In graph theoretical analysis of dynamic functional connectivity, we examined temporal flexibility and spatiotemporal diversity of 14 networks covering the whole brain. Temporal flexibility quantifies how frequently a brain region interacts with regions of other communities across time, with high temporal flexibility indicating that a region interacts predominantly with regions outside its own community. Spatiotemporal diversity quantifies how uniformly a brain region interacts with regions in other communities over time, with high spatiotemporal diversity indicating that the interactions are more evenly distributed across communities. Compared to HC, CD exhibited decreased temporal flexibility and increased spatiotemporal diversity in the great majority of neural networks. The graph metric measures of the default mode network negatively correlated with SSRT in CD but not HC. The findings are consistent with diminished temporal flexibility and a compensatory increase in spatiotemporal diversity, in association with impairment of a critical executive function, in cocaine addiction. More broadly, the findings suggest that graph theoretical metrics provide new insights for connectivity analyses to elucidate network dysfunction that may elude conventional measures.</AbstractText
|
Development and validation of the Maudsley Modified Patient Health Questionnaire (MM-PHQ-9). The Patient Health Questionnaire-9 (PHQ-9) is a widely used measure of depression in primary care. It was, however, originally designed as a diagnostic screening tool, and not for measuring change in response to antidepressant treatment. Although the Quick Inventory of Depressive Symptomology (QIDS-SR-16) has been extensively validated for outcome measurement, it is poorly adopted in UK primary care, and, although free for clinicians, has licensing restrictions for healthcare organisation use.</AbstractText We aimed to develop a modified version of the PHQ-9, the Maudsley Modified PHQ-9 (MM-PHQ-9), for tracking symptom changes in primary care. We tested the measure's validity, reliability and factor structure.</AbstractText A sample of 121 participants was recruited across three studies, and comprised 78 participants with major depressive disorder and 43 controls. MM-PHQ-9 scores were compared with the QIDS-SR-16 and Clinical Global Impressions improvement scale, for concurrent validity. Internal consistency of the scale was assessed, and principal component analysis was conducted to determine the items' factor structure.</AbstractText The MM-PHQ-9 demonstrated good concurrent validity with the QIDS-SR-16, and excellent internal consistency. Sensitivity to change over a 14-week period was d = 0.41 compared with d = 0.61 on the QIDS-SR-16. Concurrent validity between the paper and mobile app versions of the MM-PHQ-9 was r = 0.67.</AbstractText These results indicate that the MM-PHQ-9 is a valid and reliable measure of depressive symptoms in paper and mobile app format, although further validation is required. The measure was sensitive to change, demonstrating suitability for use in routine outcome assessment.</AbstractText
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