Innate-like T cells in liver disease.

Mammalian innate-like T cells (ILTCs), including mucosal-associated invariant T (MAIT), natural killer T (NKT), and γδ T cells, are abundant tissue-resident lymphocytes that have recently emerged as orchestrators of hepatic inflammation, tissue repair, and immune homeostasis. This review explores the involvement of different ILTC subsets in liver diseases. We explore the mechanisms underlying the pro- and anti-inflammatory effector functions of ILTCs in a context-dependent manner. We highlight latest findings regarding the dynamic interplay between ILTC functional subsets and other immune and parenchymal cells which may inform candidate immunomodulatory strategies to achieve improved clinical outcomes in liver diseases. We present new insights into how distinct gene expression programs in hepatic ILTCs are induced, maintained, and reprogrammed in a context- and disease stage-dependent manner.

Exploring timescale-specific functional brain networks and their associations with aging and cognitive performance in a healthy cohort without dementia.

INTRODUCTION: Functional brain networks (FBNs) coordinate brain functions and are studied in fMRI using blood-oxygen-level-dependent (BOLD) signal correlations. Previous research links FBN changes to aging and cognitive decline, but various physiological factors influnce BOLD signals. Few studies have investigated the intrinsic components of the BOLD signal in different timescales using signal decomposition. This study aimed to explore differences between intrinsic FBNs and traditional BOLD-FBN, examining their associations with age and cognitive performance in a healthy cohort without dementia. MATERIALS AND METHODS: A total of 396 healthy participants without dementia (men = 157; women = 239; age range = 20-85 years) were enrolled in this study. The BOLD signal was decomposed into several intrinsic signals with different timescales using ensemble empirical mode decomposition, and FBNs were constructed based on both the BOLD and intrinsic signals. Subsequently, network features-global efficiency and local efficiency values-were estimated to determine their relationship with age and cognitive performance. RESULTS: The findings revealed that the global efficiency of traditional BOLD-FBN correlated significantly with age, with specific intrinsic FBNs contributing to these correlations. Moreover, local efficiency analysis demonstrated that intrinsic FBNs were more meaningful than traditional BOLD-FBN in identifying brain regions related to age and cognitive performance. CONCLUSIONS: These results underscore the importance of exploring timescales of BOLD signals when constructing FBN and highlight the relevance of specific intrinsic FBNs to aging and cognitive performance. Consequently, this decomposition-based FBN-building approach may offer valuable insights for future fMRI studies.

Psychiatrist density and risk of suicide: a multilevel case-control study based on a national sample in Taiwan.

AIM: No previous studies, to our knowledge, have investigated the association between psychiatrist density and suicide, accounting for individual- and area-level characteristics. METHODS: We investigated all suicide cases in 2007-2017 identified from the national cause-of-death data files, with each suicide case matched to 10 controls by age and sex and each suicide case/control assigned to one of the 355 townships across Taiwan. Our primary outcome was the odds ratio (OR) of suicide and its 95% confidence interval (CI) estimated via multilevel models, which included both individual- and area-level characteristics. Townships with no psychiatrists were compared with the quartiles of townships with psychiatrists (density per 100,000 population): quartile 1 (Q1) (0.01-3.02); quartile 2 (Q2) (3.02-7.20); quartile 3 (Q3) (7.20-13.82); and quartile 4 (Q4) (>13.82). RESULTS: A total of 40,930 suicide cases and 409,300 age- and sex-matched controls were included. We found that increased psychiatrist density was associated with decreased suicide risk (Q1: adjusted OR [aOR], 0.95 [95% CI, 0.90-1.01]; Q2: aOR, 0.90 [95% CI, 0.85-0.96]; Q3: aOR, 0.89 [95% CI, 0.83-0.94]; Q4: aOR, 0.89 [95% CI, 0.83-0.95]) after adjusting for individual-level characteristics (employment state, monthly income, physical comorbidities, and the diagnosis of psychiatric disorders) and area socioeconomic characteristics. CONCLUSIONS: The psychiatrist density-suicide association suggests an effect of increased availability of psychiatric services on preventing suicide. Suicide prevention strategies could usefully focus on enhancing local access to psychiatric services.

Most Major Hospitals Fail to Comply With Federal Price Transparency Regulations.

PURPOSE: To present hospital compliance with federal price transparency regulations for sports medicine procedures. METHODS: Online price estimator and machine-readable files were recovered for U.S. News and World Report's top 100 orthopaedic hospitals. From June to November 2023, compliance and monetary values were recorded for each of Centers for Medicare and Medicaid Services price transparency regulations. Price estimator data were assessed on the basis of hospital placement in the bottom and top 50 of the 100 institutions under review, as well as by region (Northeast, South, Midwest, West). Statistical analyses included 2-sample t tests and Kruskal-Wallis tests. RESULTS: In total, 95% of hospitals had a price estimator tool for both subacromial decompression (Current Procedural Terminology [CPT] code 29826) and meniscectomy (CPT code 29881). Only 38% were compliant with all regulations for subacromial decompression and 39% for meniscectomy; the remaining did not list minimum or maximum procedure charges. Higher-ranked hospitals were significantly more likely to charge a greater cash price for subacromial decompression and meniscectomy (P = .040 and P = .009, respectively). Compliance with machine-readable file reporting was poor, with less than 20% meeting requirements for each CPT code. Reported prices varied greatly by hospital. CONCLUSIONS: This study demonstrates that U.S. News and World Report's top 100 orthopaedic hospitals exhibit poor overall compliance with federal price transparency regulations for sports medicine procedures. Most often they lack full compliance by not reporting minimum or maximum charges as part of their price estimator tool or do not report procedure prices in their machine-readable files. Hospitals also exhibit wide variation in prices reported for specific procedures. CLINICAL RELEVANCE: Consumer price transparency continues to be an important goal in health care, as it allows patients to make informed decisions when selecting appropriate treatment options and providers. To realize the full benefits of price transparency, hospitals should address areas of improvement.

Prediction of early postoperative pain using sleep quality and heart rate variability.

PURPOSE: Accurate predictions of postoperative pain intensity are necessary for customizing analgesia plans. Insomnia is a risk factor for severe postoperative pain. Moreover, heart rate variability (HRV) can provide information on the sympathetic-parasympathetic balance in response to noxious stimuli. We developed a prediction model that uses the insomnia severity index (ISI), HRV, and other demographic factors to predict the odds of higher postoperative pain. METHODS: We recruited gynecological surgery patients classified as American Society of Anesthesiologists class 1-3. An ISI questionnaire was completed 1 day before surgery. HRV was calculated offline using intraoperative electrocardiogram data. Pain severity at the postanesthesia care unit (PACU) was assessed with the 0-10 numerical rating scale (NRS). The primary outcome was the model's predictive ability for moderate-to-severe postoperative pain. The secondary outcome was the relationship between individual risk factors and opioid consumption in the PACU. RESULTS: Our study enrolled 169 women. Higher ISI scores (p = 0.001), higher parasympathetic activity (rMSSD, pNN50, HF; p < 0.001, p < 0.001, p < 0.001), loss of fractal dynamics (SD2, alpha 1; p = 0.012, p = 0.039) in HRV analysis before the end of surgery were associated with higher NRS scores, while laparoscopic surgery (p = 0.031) was associated with lower NRS scores. We constructed a multiple logistic model (area under the curve = 0.852) to predict higher NRS scores at PACU arrival. The five selected predictors were age (OR: 0.94; p = 0.020), ISI score (OR: 1.14; p = 0.002), surgery type (laparoscopic or open; OR: 0.12; p < 0.001), total power (OR: 2.02; p < 0.001), and alpha 1 (OR: 0.03; p < 0.001). CONCLUSION: We employed a multiple logistic regression model to determine the likelihood of moderate-to-severe postoperative pain upon arrival at the PACU. Physicians could personalize analgesic regimens based on a deeper comprehension of the factors that contribute to postoperative pain.

Genome-wide association study in the Taiwan Biobank identifies four novel genes for human height: NABP2, RASA2, RNF41 and SLC39A5.

Numerous genome-wide association studies (GWASs) have been conducted for the identification of genetic variants involved with human height. The vast majority of these studies, however, have been conducted in populations of European ancestry. Here, we report the first GWAS of adult height in the Taiwan Biobank using a discovery sample of 14 571 individuals and an independent replication sample of 20 506 individuals. From our analysis, we generalize to the Taiwanese population genome-wide significant associations with height and 18 previously identified genes in European and non-Taiwanese East Asian populations. We also identify and replicate, at the genome-wide significance level, associated variants for height in four novel genes at two loci that have not previously been reported: RASA2 on chromosome 3 and NABP2, RNF41 and SLC39A5 at 12q13.3 on chromosome 12. RASA2 and RNF41 are strong candidates for having a role in height with copy number and loss of function variants in RASA2 previously found to be associated with short stature disorders, and decreased expression of the RNF41 gene resulting in insulin resistance in skeletal muscle. The results from our analysis of the Taiwan Biobank underscore the potential for the identification of novel genetic discoveries in underrepresented worldwide populations, even for traits, such as height, that have been extensively investigated in large-scale studies of European ancestry populations.

Investigating genetic variants for treatment response to selective serotonin reuptake inhibitors in syndromal factors and side effects among patients with depression in Taiwanese Han population.

Major depressive disorder (MDD) is associated with high heterogeneity in clinical presentation. In addition, response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably among patients. Therefore, identifying genetic variants that may contribute to SSRI treatment responses in MDD is essential. In this study, we analyzed the syndromal factor structures of the Hamilton Depression Rating Scale in 479 patients with MDD by using exploratory factor analysis. All patients were followed up biweekly for 8 weeks. Treatment response was defined for all syndromal factors and total scores. In addition, a genome-wide association study was performed to investigate the treatment outcomes at week 4 and repeatedly assess all visits during follow-up by using mixed models adjusted for age, gender, and population substructure. Moreover, the role of genetic variants in suicidal and sexual side effects was explored, and five syndromal factors for depression were derived: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. Subsequently, several known genes were mapped to suggestive signals for treatment outcomes, including single-nucleotide polymorphisms (SNPs) in PRF1, UTP20, MGAM, and ENSG00000286536 for psychomotor-insight and in C4orf51 for anorexia. In total, 33 independent SNPs for treatment responses were tested in a mixed model, 12 of which demonstrated a p value <0.05. The most significant SNP was rs2182717 in the ENSR00000803469 gene located on chromosome 6 for the core syndromal factor (ß = -0.638, p = 1.8 × 10-4) in terms of symptom improvement over time. Patients with a GG or GA genotype with the rs2182717 SNP also exhibited a treatment response (ß = 0.089, p = 2.0 × 10-6) at week 4. Moreover, rs1836075352 was associated with sexual side effects (p = 3.2 × 10-8). Pathway and network analyses using the identified SNPs revealed potential biological functions involved in treatment response, such as neurodevelopment-related functions and immune processes. In conclusion, we identified loci that may affect the clinical response to treatment with antidepressants in the context of empirically defined depressive syndromal factors and side effects among the Taiwanese Han population, thus providing novel biological targets for further investigation.

Population-attributable risk of psychiatric disorders for suicide among adolescents and young adults in Taiwan.

BACKGROUND: Youth suicide rates have increased markedly in some countries. This study aimed to estimate the population-attributable risk of psychiatric disorders associated with suicide among Taiwanese youth aged 10-24 years. METHODS: Data were obtained from the National Death Registry and National Health Insurance (NHI) claims database between 2007 and 2019. Youth who died by suicide were included, and comparisons, 1:10 matched by age and sex, were randomly selected from the Registry for NHI beneficiaries. We used multivariable logistic regression to estimate suicide odds ratios for psychiatric disorders. The population-attributable fractions (PAF) were calculated for each psychiatric disorder. RESULTS: A total of 2345 youth suicide and 23 450 comparisons were included. Overall, 44.8% of suicides had a psychiatric disorder, while only 7.9% of the comparisons had a psychiatric disorder. The combined PAF for all psychiatric disorders was 55.9%. The top three psychiatric conditions of the largest PAFs were major depressive disorder, dysthymia, and sleep disorder. In the analysis stratified by sex, the combined PAF was 45.5% for males and 69.2% for females. The PAF among young adults aged 20-24 years (57.0%) was higher than among adolescents aged 10-19 years (48.0%). CONCLUSIONS: Our findings of high PAF from major depressive disorder, dysthymia, and sleep disorder to youth suicides suggest that youth suicide prevention that focuses on detecting and treating mental illness may usefully target these disorders.

Sex-specific autosomal genetic effects across 26 human complex traits.

Previous studies have shown that men and women have different genetic architectures across many traits. However, except waist-to-hip ratio (WHR) and waist circumference (WC), it remains unknown whether the genetic effects of a certain trait are weaker or stronger on men/women. With ~18 000 Taiwan Biobank subjects, we comprehensively investigate sexual heterogeneity in autosomal genetic effects, for traits regarding cardiovascular health, diabetes, kidney, liver, anthropometric profiles, blood, etc. 'Gene-by-sex interactions' (G $\times$ S) were detected in 18 out of 26 traits, each with an interaction P-value (${{P}}_{{INT}}$) less than $0.05/104={0.00048}$, where 104 is the number of tests conducted in this study. The most significant evidence of G $\times$ S was found in WHR (${{P}}_{{INT}}$ = 3.2 $\times{{10}}^{-{55}}$) and WC (${{P}}_{{INT}}$ = 2.3$\times{{10}}^{-{41}}$). As a novel G$\times$S investigation for other traits, we here find that the autosomal genetic effects are weaker on women than on men, for low-density lipoprotein cholesterol (LDL-C), uric acid (UA) and diabetes-related traits such as fasting glucose and glycated hemoglobin. For LDL-C and UA, the evidence of G$\times$S is especially notable in subjects aged less than 50 years, where estrogen can play a role in attenuating the autosomal genetic effects of these two traits. Men and women have systematically distinct environmental contexts caused by hormonal milieu and their specific society roles, which may trigger diverse gene expressions despite the same DNA materials. As many environmental exposures are difficult to collect and quantify, sex can serve as a good surrogate for these factors.

Associations of Reduced Sympathetic Neural Activity and Elevated Baroreflex Sensitivity With Non-Rapid Eye Movement Sleep: Evidence From Electroencephalogram- and Electrocardiogram-Based Sleep Staging.

OBJECTIVE: Autonomic neural controls in sleep regulation have been previously demonstrated; however, whether these alternations can be observed by different sleep staging approaches remains unclear. Two established methods for sleep staging-the standardized visual scoring and the cardiopulmonary coupling (CPC) analysis based on electrocardiogram-were used to explore the cardiovascular profiles of sleep. METHODS: Overnight polysomnography was recorded together with continuous beat-to-beat blood pressure. Cortical activity, heart rate variability, blood pressure variability, and baroreflex sensitivity during sleep stages from 24 nights of sleep were obtained from 15 normotensive participants and analyzed. RESULTS: Non-rapid eye movement sleep (NREM) from visual scoring and restful sleep (RS) of CPC both showed the highest delta power of electroencephalogram (EEG) and lowest beta activity of EEG in comparison with other sleep stages (p < .001); likewise, the lowest total power of heart rate variability and suppressed vascular-sympathetic activity, reflected by low-frequency power of blood pressure variability, as well as a trend in elevated baroreflex sensitivity, were observed in the NREM or RS. This suppressed vascular-sympathetic activity during stable sleep further exhibited a significant correlation with increased slow-wave activity (NREM: r = -0.292 ± 0.34, p = .002; RS: r = -0.209 ± 0.30, p = .010). CONCLUSIONS: Autonomic nervous system is evidently associated with stable sleep, as indicated by the similar findings obtained from sleep stages categorized by standardized visual scoring or CPC analysis. Such association between cardiovascular neural activity and sleep EEGs can be observed regardless of the sleep staging approach followed.

Brain white matter hyperintensities-predicted age reflects neurovascular health in middle-to-old aged subjects.

BACKGROUND: age-related neurovascular structural and functional impairment is a major aetiology of dementia and stroke in older people. There is no single marker representative of neurovascular biological age yet. OBJECTIVE: this study aims to develop and validate a white matter hyperintensities (WMH)-based model for characterising individuals' neurovascular biological age. METHODS: in this prospective single-site study, the WMH-based age-prediction model was constructed based on WMH volumes of 491 healthy participants (21-89 years). In the training dataset, the constructed linear-regression model with log-transformed WMH volumes showed well-balanced complexity and accuracy (root mean squared error, RMSE = 10.20 and mean absolute error, MAE = 7.76 years). This model of neurovascular age estimation was then applied to a middle-to-old aged testing dataset (n = 726, 50-92 years) as the testing dataset for external validation. RESULTS: the established age estimator also had comparable generalizability with the testing dataset (RMSE = 7.76 and MAE = 6.38 years). In the testing dataset, the WMH-predicted age difference was negatively associated with visual executive function. Individuals with older predicted-age for their chronological age had greater cardiovascular burden and cardiovascular disease risks than individuals with normal or delayed predicted age. These associations were independent of chronological age. CONCLUSIONS: our model is easy to use in clinical practice that helps to evaluate WMH severity objective to chronological age. Current findings support our WMH-based age measurement to reflect neurovascular health and have potential diagnostic and prognostic value for clinical or research purposes in age-related neurovascular disorders.

Hip, vertebral, and wrist fracture risks and schizophrenia: a nationwide longitudinal study.

BACKGROUND: Fractures are a great health issue associated with morbidity, quality of life, life span, and health care expenditure. Fractures are correlated with cardiovascular disease, type 2 diabetes mellitus, cerebrovascular disease, and some psychiatric disorders. However, representative national data are few, and longitudinal cohort studies on the association between schizophrenia and the subsequent fracture risk are scant. We designed a nationwide population-based cohort study to investigate the association of schizophrenia with hip, vertebral, and wrist fractures over a 10-year follow-up. METHODS: Data of patients with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification code 295) and matched over January 2000-December 2009) were extracted from Taiwan National Health Insurance Research Database. A Cox proportional-hazards regression model was constructed to calculate hazard ratios (HRs) for fractures between the schizophrenia and control cohorts. RESULTS: Of 2028 people with schizophrenia (mean age: 36.3 years, 49.4% female), 89 (4.4%) reported newly diagnosed fractures-significantly higher than the proportion in the control population (257, 3.2%; P = 0.007). The incidences of hip (1.2%, P = 0.009) and vertebral (2.6%, P = 0.011) fractures were significantly higher in the schizophrenia cohort than in the control cohort. In Cox regression analysis, hip (adjusted HR: 1.78, 95% confidence interval [CI]: 1.08-2.93) and vertebral (adjusted HR: 1.40, 95% CI: 1.01-1.95) fracture risks were significantly higher in patients with schizophrenia. Furthermore, a sex-based subgroup analysis revealed that the risk of hip fracture remained significantly higher in female patients with schizophrenia (HR: 2.68, 95% CI: 1.32-5.44) than in female controls. On the other hand, there was no significant interaction between effects of sex and schizophrenia on the risk of fractures. CONCLUSIONS: Over a 10-year follow-up, hip and vertebral fracture risks were higher in the people with schizophrenia than in the controls. The risk of fractures in patients with schizophrenia does not differ between female and male.

Performing different kinds of physical exercise differentially attenuates the genetic effects on obesity measures: Evidence from 18,424 Taiwan Biobank participants.

Obesity is a worldwide health problem that is closely linked to many metabolic disorders. Regular physical exercise has been found to attenuate the genetic predisposition to obesity. However, it remains unknown what kinds of exercise can modify the genetic risk of obesity. This study included 18,424 unrelated Han Chinese adults aged 30-70 years who participated in the Taiwan Biobank (TWB). A total of 5 obesity measures were investigated here, including body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Because there have been no large genome-wide association studies on obesity for Han Chinese, we used the TWB internal weights to construct genetic risk scores (GRSs) for each obesity measure, and then test the significance of GRS-by-exercise interactions. The significance level throughout this work was set at 0.05/550 = 9.1x10-5 because a total of 550 tests were performed. Performing regular exercise was found to attenuate the genetic effects on 4 obesity measures, including BMI, BFP, WC, and HC. Among the 18 kinds of self-reported regular exercise, 6 mitigated the genetic effects on at least one obesity measure. Regular jogging blunted the genetic effects on BMI, BFP, and HC. Mountain climbing, walking, exercise walking, international standard dancing, and a longer practice of yoga also attenuated the genetic effects on BMI. Exercises such as cycling, stretching exercise, swimming, dance dance revolution, and qigong were not found to modify the genetic effects on any obesity measure. Across all 5 obesity measures, regular jogging consistently presented the most significant interactions with GRSs. Our findings show that the genetic effects on obesity measures can be decreased to various extents by performing different kinds of exercise. The benefits of regular physical exercise are more impactful in subjects who are more predisposed to obesity.

Ten-year trends in depression care in Taiwan.

BACKGROUND/PURPOSE: The number of psychiatrists working in community clinics in Taiwan has increased dramatically in the recent decade. This study aimed to investigate the trend of prevalence and incidence of depressive disorders and assess the quality of depression care between 2007 and 2016 in Taiwan. METHODS: We used the claims database derived from Taiwan's National Health Insurance (NHI) program, in which approximately 23.0 million individuals were enrolled, translating to a coverage rate of 99%. Patients with depressive disorders were identified based on International Classification of Diseases codes. The process indicators of depression care quality included visit, duration, and dose adequacy. The outcome indicators included the rate of psychiatric hospitalisation, emergency visit, self-harm hospitalisation, and suicide. RESULTS: The prevalence of treated depressive disorders increased from 1.61% in 2007 to 1.92% in 2016, i.e., a 25% increase, whereas the incidence of first-ever or recurrent depressive disorder did not change significantly. The number of patients treated by psychiatrists and in community clinics also increased. The quality of depression care improved, the proportion of patients receiving minimum psychiatric clinic follow-up and adequate medication increased, and the rate of emergency visits, psychiatric hospitalisation, and self-harm hospitalisation declined. CONCLUSION: The community-based psychiatric services increased and the quality indicators of depression care in Taiwan improved during 2007-2016. The causality warrants further investigations.

The Polar Flagellar Transcriptional Regulatory Network in Vibrio campbellii Deviates from Canonical Vibrio Species.

Swimming motility is a critical virulence factor in pathogenesis for numerous Vibrio species. Vibrio campbellii DS40M4 is a wild-type isolate that has been recently established as a highly tractable model strain for bacterial genetics studies. We sought to exploit the tractability and relevance of this strain for characterization of flagellar gene regulation in V. campbellii. Using comparative genomics, we identified homologs of V. campbellii flagellar and chemotaxis genes conserved in other members of the Vibrionaceae and determined the transcriptional profile of these loci using differential RNA-seq. We systematically deleted all 63 predicted flagellar and chemotaxis genes in V. campbellii and examined their effects on motility and flagellum production. We specifically focused on the core regulators of the flagellar hierarchy established in other vibrios: RpoN (σ54), FlrA, FlrC, and FliA. Our results show that V. campbellii transcription of flagellar and chemotaxis genes is governed by a multitiered regulatory hierarchy similar to other motile Vibrio species. However, there are several critical differences in V. campbellii: (i) the σ54-dependent regulator FlrA is dispensable for motility; (ii) the flgA, fliEFGHIJ, flrA, and flrBC operons do not require σ54 for expression; and (iii) FlrA and FlrC coregulate class II genes. Our model proposes that the V. campbellii flagellar transcriptional hierarchy has three classes of genes, in contrast to the four-class hierarchy in Vibrio cholerae. Our genetic and phenotypic dissection of the V. campbellii flagellar regulatory network highlights the differences that have evolved in flagellar regulation across the Vibrionaceae. IMPORTANCE Vibrio campbellii is a Gram-negative bacterium that is free-living and ubiquitous in marine environments and is an important global pathogen of fish and shellfish. Disruption of the flagellar motor significantly decreases host mortality of V. campbellii, suggesting that motility is a key factor in pathogenesis. Using this model organism, we identified >60 genes that encode proteins with predicted structural, mechanical, or regulatory roles in function of the single polar flagellum in V. campbellii. We systematically tested strains containing single deletions of each gene to determine the impact on motility and flagellum production. Our studies have uncovered differences in the regulatory network and function of several genes in V. campbellii compared to established systems in Vibrio cholerae and Vibrio parahaemolyticus.

Beyond the disconnectivity hypothesis of schizophrenia.

To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model. Effective connectivity (EC) was measured in 180 participants with schizophrenia and 208 controls. For the significantly different effective connectivities in schizophrenia, on average the forward (stronger) effective connectivities were smaller, whereas the backward connectivities tended to be larger. Further, higher EC in schizophrenia was found from the precuneus and posterior cingulate cortex (PCC) to areas such as the parahippocampal, hippocampal, temporal, fusiform, and occipital cortices. These are backward effective connectivities and were positively correlated with the positive symptoms of schizophrenia. Lower effective connectivities were found from temporal and other regions and were negatively correlated with the symptoms, especially the negative and general symptoms. Further, a signal variance parameter was increased for areas that included the parahippocampal gyrus and hippocampus, consistent with the hypothesis that hippocampal overactivity is involved in schizophrenia. This investigation goes beyond the disconnectivity hypothesis by drawing attention to differences in schizophrenia between backprojections and forward connections, with the backward connections from the precuneus and PCC implicated in memory stronger in schizophrenia.

Large-Scale Structural Covariance Networks Predict Age in Middle-to-Late Adulthood: A Novel Brain Aging Biomarker.

The aging process is accompanied by changes in the brain's cortex at many levels. There is growing interest in summarizing these complex brain-aging profiles into a single, quantitative index that could serve as a biomarker both for characterizing individual brain health and for identifying neurodegenerative and neuropsychiatric diseases. Using a large-scale structural covariance network (SCN)-based framework with machine learning algorithms, we demonstrate this framework's ability to predict individual brain age in a large sample of middle-to-late age adults, and highlight its clinical specificity for several disease populations from a network perspective. A proposed estimator with 40 SCNs could predict individual brain age, balancing between model complexity and prediction accuracy. Notably, we found that the most significant SCN for predicting brain age included the caudate nucleus, putamen, hippocampus, amygdala, and cerebellar regions. Furthermore, our data indicate a larger brain age disparity in patients with schizophrenia and Alzheimer's disease than in healthy controls, while this metric did not differ significantly in patients with major depressive disorder. These findings provide empirical evidence supporting the estimation of brain age from a brain network perspective, and demonstrate the clinical feasibility of evaluating neurological diseases hypothesized to be associated with accelerated brain aging.

Predicting Norovirus in the United States Using Google Trends: Infodemiology Study.

BACKGROUND: Norovirus is a contagious disease. The transmission of norovirus spreads quickly and easily in various ways. Because effective methods to prevent or treat norovirus have not been discovered, it is important to rapidly recognize and report norovirus outbreaks in the early phase. Internet search has been a useful method for people to access information immediately. With the precise record of internet search trends, internet search has been a useful tool to manifest infectious disease outbreaks. OBJECTIVE: In this study, we tried to discover the correlation between internet search terms and norovirus infection. METHODS: The internet search trend data of norovirus were obtained from Google Trends. We used cross-correlation analysis to discover the temporal correlation between norovirus and other terms. We also used multiple linear regression with the stepwise method to recognize the most important predictors of internet search trends and norovirus. In addition, we evaluated the temporal correlation between actual norovirus cases and internet search terms in New York, California, and the United States as a whole. RESULTS: Some Google search terms such as gastroenteritis, watery diarrhea, and stomach bug coincided with norovirus Google Trends. Some Google search terms such as contagious, travel, and party presented earlier than norovirus Google Trends. Some Google search terms such as dehydration, bar, and coronavirus presented several months later than norovirus Google Trends. We found that fever, gastroenteritis, poison, cruise, wedding, and watery diarrhea were important factors correlated with norovirus Google Trends. In actual norovirus cases from New York, California, and the United States as a whole, some Google search terms presented with, earlier, or later than actual norovirus cases. CONCLUSIONS: Our study provides novel strategy-based internet search evidence regarding the epidemiology of norovirus.

Production of electricity and reduction of high-fat diet-induced IL-6 by glucose fermentation of Leuconostoc mesenteroides.

Electrogenic bacteria can mediate electron transfer to conserve energy and promote growth. To examine bacterial electrogenicity, an L. mesenteroides EH-1 strain was cultured in rich media in the presence and absence of 2% glucose. After 12 h incubation, glucose triggered fermentation of L. mesenteroides EH-1 to produce >10 mmol/l acetate and elicit electricity measured by voltage changes. The electricity production was mediated by glucose fermentation since pre-treatment of L. mesenteroides EH-1 with furfural, a fermentation inhibitor, completely diminished the voltage increases. The deficiency of furfural pre-treated L. mesenteroides EH-1 in electricity production can be restored by the external addition of acetate into the bacterial culture, suggesting the function of acetate as an electron donor. Oral administration of HFD-fed mice with L. mesenteroides EH-1 in the presence or absence of glucose significantly attenuated the high level of pro-inflammatory IL-6 cytokine in blood. Bacterial electricity can be elicited by fermentation. Supplementation of fermenting and electrogenic L. mesenteroides EH-1 may provide a novel approach for the reduction of pro-inflammatory IL-6 cytokine that increased in chronic inflammation, autoimmune diseases, cancers, and infections.

Risk of Parkinson's disease following gout: a population-based retrospective cohort study in Taiwan.

BACKGROUND: The progressive neurodegenerative disorder Parkinson disease (PD) is well-established as the second most common neurodegenerative disease. Associations between the sequential risk of PD and gout have been addressed in other studies, but findings have been inconclusive. Accordingly, we executed the present study with the purpose of assessing PD risk in patients with gout. METHODS: From Taiwan's National Health Insurance Research Database, we identified the data of patients newly diagnosed as having gout between January 1, 2000 and December 1, 2000. A cohort of patients without gout, matched for sex and age, was constructed for comparison. Hazard ratios (HRs) and the incidence rate of subsequent PD were calculated for both cohorts and separately for male and female groups. The gout and comparison cohorts consisted of 7900 patients each. RESULTS: The HR for PD was not significantly higher in the gout cohort compared with the control cohort (HR 1.01, 95% confidence interval [CI], 0.93-1.31, P = .268), even after adjustment for age, urbanization, monthly income, sex, and comorbidities. We did not observe gender differences in the gout-PD association (male: HR 1.01, 95% CI, 0.88-1.36, P = .400; female: HR 1.11, 95% CI, 0.84-1.46, P = .466). CONCLUSIONS: Our study identified that there was no protective effect of gout for the risk of PD in the Taiwanese population.