Multimodal Associations of FKBP5 Methylation with Emotion-Regulatory Brain Circuits.

BACKGROUND: Understanding the biological processes underlying individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. Yet it remains unclear how FKBP5 DNA methylation (DNAm) in peripheral blood relates to individual differences in measures of neural structure and function, and their relevance to daily-life stress responsivity. METHODS: Here, we characterize multimodal correlates of FKBP5 DNAm by combining epigenetic data with neuroimaging and Ambulatory Assessment in a sample of 395 healthy individuals. RESULTS: First, we show that FKBP5 demethylation as a psychiatric risk factor relates to an anxiety-associated reduction of gray matter volume in the ventromedial prefrontal cortex (vmPFC), a brain area that is involved in emotion regulation and mental health risk and resilience. This effect of epigenetic upregulation of FKBP5 on neuronal structure is more pronounced where FKBP5 is epigenetically downregulated at baseline. Leveraging 208 functional MRI scans during a well-established emotion processing task we find that FKBP5 DNAm in peripheral blood is associated with functional difference of prefrontal-limbic circuits modulating affective responsivity to daily stressors, which we measured using ecological momentary assessment in daily life. CONCLUSIONS: Overall, we demonstrate how FKBP5 contributes to interindividual differences in neural and real-life affect regulation via structural and functional changes in prefrontal-limbic brain circuits.

Exploring HIV-1 transmission features among older individuals in developed eastern China.

The number of newly reported HIV-1 infections among older individuals (aged ≥50 years) has increased rapidly in Hangzhou, a central city in the Yangtze River Delta region of China. To provide a scientific basis for prevention and intervention strategies targeted at older individuals in Hangzhou, an epidemiological survey combined with molecular transmission network analysis was conducted. A total of 2899 individuals with newly confirmed HIV-1 infections, including 635 older individuals and 2264 younger individuals (aged <50 years), were enrolled in this study. Among older individuals, heterosexual contact was the predominant mode of HIV-1 transmission. Additionally, it was observed that older individuals with lower levels of education exhibited a higher susceptibility to HIV-1 infection. The analysis of transmission network which was inferred using HIV-TRACE algorithm revealed that the newly diagnosed HIV-1 infections among older individuals in Hangzhou exhibited a pattern of scattered transmission, with key clusters primarily located in non-main urban areas. The predominant mode of transmission in these areas was non-marital and non-commercial or non-marital and commercial heterosexual transmission. Notably, the study highlighted a significant proportion of older individuals (73.3%, 11/15) within B subtype. Multivariate logistic regression analysis further revealed that the subtype B was a significant factor associated with older individuals having ≥3 node degrees in the network, occurring 5.55 times more frequent than subtype CRF07_BC (95% CI = 1.17-26.22, p = 0.031). Furthermore, the lower CD4 levels observed among older individuals underscored the challenge of late diagnosis in Hangzhou. Taken together, it is imperative to test and intervene for high-risk older individuals. To tackle this issue effectively, it is essential to enhance the detection of the B subtype and implement targeted interventions in key clusters within non-main urban areas. Additionally, proactive measures should be implemented to address the challenge of late diagnosis in Hangzhou by promoting widespread testing among the older individuals, particularly in priority areas.

A primer on the use of machine learning to distil knowledge from data in biological psychiatry.

Applications of machine learning in the biomedical sciences are growing rapidly. This growth has been spurred by diverse cross-institutional and interdisciplinary collaborations, public availability of large datasets, an increase in the accessibility of analytic routines, and the availability of powerful computing resources. With this increased access and exposure to machine learning comes a responsibility for education and a deeper understanding of its bases and bounds, borne equally by data scientists seeking to ply their analytic wares in medical research and by biomedical scientists seeking to harness such methods to glean knowledge from data. This article provides an accessible and critical review of machine learning for a biomedically informed audience, as well as its applications in psychiatry. The review covers definitions and expositions of commonly used machine learning methods, and historical trends of their use in psychiatry. We also provide a set of standards, namely Guidelines for REporting Machine Learning Investigations in Neuropsychiatry (GREMLIN), for designing and reporting studies that use machine learning as a primary data-analysis approach. Lastly, we propose the establishment of the Machine Learning in Psychiatry (MLPsych) Consortium, enumerate its objectives, and identify areas of opportunity for future applications of machine learning in biological psychiatry. This review serves as a cautiously optimistic primer on machine learning for those on the precipice as they prepare to dive into the field, either as methodological practitioners or well-informed consumers.

Acceptance of influenza vaccination and associated factors among teachers in China: A cross-sectional study based on health belief model.

Teachers played an important role on the transmission of influenza in schools and communities. The study aims to investigate the influenza vaccination coverage and the factors determining flu vaccination acceptance among teachers in Hangzhou, China. A total of 1039 junior high school teachers in Hangzhou were recruited. The self-made questionnaire was used to investigate the influenza vaccine coverage among teachers and the influencing factors of influenza vaccination acceptance. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors. The Influenza vaccine coverage among teachers was 5.9% (62/1039). 52.9% of teachers had the intention to receive influenza vaccine, 25.3% (247/977)/21.8% (213/977) of participants was hesitant/did not have the intention to get influenza vaccine. The top three sources for teachers to gain knowledge about influenza were website (72%), TV/radio (66.1%) and social media (58%). Whether get influenza vaccination before, knowledge about influenza and influenza vaccine, the beliefs for the likelihood of catching flu, the severity of getting flu, the effectiveness of influenza vaccine, the possibility of side effects after vaccination, and the troublesome of vaccination, doctors' recommendation, as well as the situation of vaccination among other teachers were the associated factors of influenza vaccination acceptance. The influenza vaccination coverage was low but the intentions were relatively high among junior high school teachers. Future research should focus on the relationship between vaccination acceptance and behavior to increase influenza vaccination rates.

Associated factors of burnout among Chinese vaccination staff during COVID-19 epidemic: A cross-sectional study.

Objective: During the COVID-19 epidemic, vaccination staff had three main aspects of work: routine vaccination for children and adults, COVID-19 vaccination and COVID-19 prevention and control. All these works significantly increased the workload of vaccination staff. This study aimed to investigate the prevalence and influencing factors of burnout among vaccination staff in Hangzhou, China. Methods: A total of 501 vaccination staff from 201 community/township healthcare centers in Hangzhou were recruited using a cross-sectional survey through WeChat social platform. The Maslach Burnout Inventory-General Scale (MBI-GS) was used to assess the level of burnout. Descriptive statistics were made on the characteristics of participants. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors of burnout. Univariate analysis and multiple linear regression were used to determine the relative predictors of exhaustive emotion, cynicism, and personal accomplishment. Results: During the COVID-19 pandemic, 20.8% of the vaccination staff experienced burnout. Educational level above undergraduate education level, medium professional title, and more working time in COVID-19 vaccination work reported a higher degree of job burnout. The vaccination staff was experiencing a high degree of exhaustive emotion, cynicism, and low personal accomplishment. Professional title, working place, and working time for COVID-19 vaccination were associated with exhaustive emotion and cynicism. Professional title and participation time for COVID-19 prevention and control were associated with personal accomplishment. Conclusions: Our findings suggest that the prevalence rate of burnout is high among vaccination staff during the COVID-19 pandemic, especially with a low level of personal accomplishment. Psychological intervention for vaccination staff is urgently needed.

HIV Detection and Delayed Diagnosis: A Time Series Analysis in China.

BACKGROUND: Insufficient HIV detection and late presentation to antiretroviral therapy (ART) pose significant public health challenges. In China, universal access to HIV testing is available now. Under this background, we aim to analyze the trends of HIV detection and the prevalence of delayed HIV diagnosis (DHD) in order to provide evidence for HIV prevention and treatment in China. METHODS: Data of HIV tests in Hangzhou city between 2007 and 2018 were collected from the Chinese National HIV/AIDS Comprehensive Response Information Management System (CRIMS). Descriptive statistics were used to describe the characteristics of HIV testing and detection and the prevalence of DHD among newly diagnosed HIV cases. Non-parametric tests were employed to examine the prevalence of DHD among newly diagnosed HIV cases. Moreover, logistic regression models were employed to explore the influencing factors of DHD. RESULTS: Testing rates doubled from 14.1% in 2007-2010 to 28.2% in 2016-2018. The total positive rate of HIV tests was 5.3 per 10,000. Preoperative testing was the predominant pathway for HIV tests, accounting for 41.9%, followed by testing for health screening, maternal examination and other patients, accounting for 18.4%, 13.2% and 11.8%, respectively. Meanwhile, the predominant pathway for HIV case detection was also preoperative testing, accounting for 29.1%, followed by testing for other patients, testing at STD clinics and VCT, with the proportions of 18.8%, 15.8% and 13.6%, respectively. MSM (men who have sex with men) contact was the main transmission route, accounting for 55.3%, followed by heterosexual contact, accounting for 41.6%. Overall, DHD occurred in 29.0% of the newly diagnosed cases, and this rate had not improved over the years. A higher prevalence of DHD was found in those diagnosed through a pre-test for receiving blood/products [OR (95%CI): 5.42(2.95-9.97)], detection of other patients [OR (95%CI): 2.08(1.64-2.63)], preoperative testing [OR (95%CI): 1.83(1.44-2.32)] and spouse or sexual partner testing in positive person [OR (95%CI): 1.93(1.34-2.78)] compared with those diagnosed at a VCT clinic. Heterosexuals [OR (95%CI): 1.20(1.06-1.36)] had a higher risk of DHD than MSM. Diagnosis at a CDC [OR (95%CI): 0.68(0.55-0.83)] and community health centers [OR (95%CI): 0.54(0.39-0.75)] had a lower risk of DHD than in hospitals. Older age, males, being single/divorced or widowed and floating population were also associated with DHD. CONCLUSIONS: In China, DHD had not improved in the last 10 years, although HIV testing had been expanded. Therefore, it is important for continued efforts to promote early diagnosis of HIV to prevent transmission, morbidity and early mortality in HIV infection.

Gender differences in the prevalence and impact factors of adolescent dissociative symptoms during the coronavirus disease 2019 pandemic.

The purpose of this study was to explore the differences between the prevalence and impact factors of adolescent dissociative symptoms (ADSs) by using sex-stratification during the coronavirus disease 2019 (COVID-19) pandemic. A school-based, two-center cross-sectional study was conducted in Hangzhou City, China, between January 1, 2021 and April 30, 2022. The sample included 1,916 adolescents aged 13-18 years that were randomly selected using a multiphase, stratified, cluster sampling technique. A two-stage assessment procedure was used to find out the ADSs. We used a multivariate logistic regression analysis to assess the impact factors of ADSs during the COVID-19 pandemic. The adolescent dissociative scores (t = 4.88, P < 0.001) and positive ADSs rate (Chi-square = 15.76, P < 0.001) in males were higher than in females. Gender-stratified, stepwise multiple logistic regression analysis revealed that the conflict relationship of teacher-student [adjusted odds ratio (AOR) 1.06, 95% confidence interval (CI) 1.01-1.10], family expressiveness (AOR 0.87, 95% CI 0.78-0.98), family conflict (AOR 1.15, 95% CI 1.05-1.27), family organization (AOR 0.88, 95% CI 0.78-0.99), and family cohesion (AOR 0.87, 95% CI 0.77-0.99) were linked to ADSs only in males, while individual psychological states of somatic complaint (AOR 1.04, 95% CI 1.00-1.08) and paranoid ideation (AOR 1.09, 95% CI 1.01-1.19) were associated with female ADSs only. The ADSs seemed to be prevalent in Hangzhou City, studied during the COVID-19 pandemic. Gender differences in the prevalence and impact factors of dissociative symptoms seem to be significant among adolescents. Thus, gender-specific intervention programs against ADSs should be considered as reducing this risk.

Comparative efficacy and safety of pharmacological interventions for severe COVID-19 patients: An updated network meta-analysis of 48 randomized controlled trials.

BACKGROUND: To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19. METHODS: We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs). RESULTS: We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients. CONCLUSION: This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.

Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits.

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

Efficacy and safety of current treatment interventions for patients with severe COVID-19 infection: A network meta-analysis of randomized controlled trials.

This study aimed to assess the efficacy and safety of different medications available at present for severe coronavirus disease 2019 (COVID-19) infection. We searched databases for randomized controlled trials (RCTs) published up to April 30, 2021, with Chinese or English language restriction, of medications recommended for patients (aged 18 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs). We identified 1855 abstracts and of these included 15 RCTs comprising 3073 participants through database searches and other sources. In terms of efficacy, compared with the standard of care (SOC) group, no significant decrease in ACM was found in α-lipoic acid, convalescent plasma (CP), azithromycin, tocilizumab, methylprednisolone, interferon beta, CP/SOC, high dosage sarilumab, low dosage sarilumab, remdesivir, lopinavir-ritonavir, auxora, and placebo group. Compared with placebo, we found that a significant decrease in ACM was only found in methylprednisolone (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.03-0.75]. With respect to TEAEs, the CP group showed lower TEAEs than placebo (OR: 0.07, 95% CI: 0.01-0.58) or SOC (OR: 0.05, 95% CI: 0.01-0.42) group for the therapy of severe COVID-19 patients. This study only demonstrated that methylprednisolone was superior to placebo in treating patients with severe COVID-19 infection. Meanwhile, this further confirmed that the safety of other treatment interventions might be inferior to CP for the therapy of severe COVID-19 patients.

Ventral Striatal-Hippocampus Coupling During Reward Processing as a Stratification Biomarker for Psychotic Disorders.

BACKGROUND: Altered ventral striatal (vST) activation to reward expectancy is a well-established intermediate phenotype for psychiatric disorders, specifically schizophrenia (SZ). Preclinical research suggests that striatal alterations are related to a reduced inhibition by the hippocampal formation, but its role in human transdiagnostic reward-network dysfunctions is not well understood. METHODS: We performed functional magnetic resonance imaging during reward processing in 728 individuals including healthy control subjects (n = 396), patients (SZ: n = 46; bipolar disorder: n = 45; major depressive disorder: n = 60), and unaffected first-degree relatives (SZ: n = 46; bipolar disorder: n = 50; major depressive disorder: n = 85). We assessed disorder-specific differences in functional vST-hippocampus coupling and transdiagnostic associations with dimensional measures of positive, negative, and cognitive symptoms. We also probed the genetic underpinning using polygenic risk scores for SZ in a subset of healthy participants (n = 295). RESULTS: Functional vST-hippocampus coupling was 1) reduced in patients with SZ and bipolar disorder (pFWE < .05, small-volume corrected [SVC]); 2) associated transdiagnostically to dimensional measures of positive (pFWE = .01, SVC) and cognitive (pFWE = .02, SVC), but not negative, (pFWE > .05, SVC) symptoms; and 3) reduced in first-degree relatives of patients with SZ (pFWE = .017, SVC) and linked to the genetic risk for SZ in healthy participants (p = .035). CONCLUSIONS: We provide evidence that reduced vST-hippocampus coupling during reward processing is an endophenotype for SZ linked to positive and cognitive symptoms, supporting current preclinical models of the emergence of psychosis. Moreover, our data indicate that vST-hippocampus coupling is familial and linked to polygenic scores for SZ, supporting the use of this measure as an intermediate phenotype for psychotic disorders.

Quality of life and its influencing factors among people living with HIV/AIDS in Hangzhou City / 预防医学

Objective @#To investigate the quality of life among people living with HIV/AIDS in Hangzhou City and analyze the influencing factors, so as to provide insights into the control of AIDS.@*Methods @#From 1 January 2014 to 30 June 2018, the demographic characteristics, medical expenditures and disease status were collected from HIV/AIDS patients living in Hangzhou City, and the quality of life was assessed using the simplified Chinese version of Medical Outcomes Study-HIV Health Survey ( MOS-HIV ). Factors affecting the quality of life were identified among HIV/AIDS patients using multivariable linear regression analysis. @*Results @#A total of 2 808 HIV/AIDS patients were surveyed, including 1 684 cases with HIV infections and 1 124 cases with AIDS. The participants included 2 510 men ( 89.39% ) and 298 women ( 10.61% ), and were predominantly at ages of 25 to 39 years ( 1 531 cases, 54.52% ). The physical and mental health scores were 53.87±6.96 and 46.03±9.09, respectively. Multivariable linear regression analysis identified age, average monthly income, self-paid medical expenses during the past year, and the latest CD4+T cell count as factors affecting physical and mental health ( P<0.05 ).@*Conclusions @#The quality of life is low among people living with HIV/AIDS in Hangzhou City, and is associated with age, income, medical expenditures and CD4+T cell count.

Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody.

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs.

Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients: an updated network meta-analysis of randomized placebo-controlled trials.

BACKGROUND: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs). METHODS: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates. RESULTS: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients. CONCLUSION: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.

Differential resting-state patterns across networks are spatially associated with Comt and Trmt2a gene expression patterns in a mouse model of 22q11.2 deletion.

Copy number variations (CNV) involving multiple genes are ideal models to study polygenic neuropsychiatric disorders. Since 22q11.2 deletion is regarded as the most important single genetic risk factor for developing schizophrenia, characterizing the effects of this CNV on neural networks offers a unique avenue towards delineating polygenic interactions conferring risk for the disorder. We used a Df(h22q11)/+ mouse model of human 22q11.2 deletion to dissect gene expression patterns that would spatially overlap with differential resting-state functional connectivity (FC) patterns in this model (N = 12 Df(h22q11)/+ mice, N = 10 littermate controls). To confirm the translational relevance of our findings, we analyzed tissue samples from schizophrenia patients and healthy controls using machine learning to explore whether identified genes were co-expressed in humans. Additionally, we employed the STRING protein-protein interaction database to identify potential interactions between genes spatially associated with hypo- or hyper-FC. We found significant associations between differential resting-state connectivity and spatial gene expression patterns for both hypo- and hyper-FC. Two genes, Comt and Trmt2a, were consistently over-expressed across all networks. An analysis of human datasets pointed to a disrupted co-expression of these two genes in the brain in schizophrenia patients, but not in healthy controls. Our findings suggest that COMT and TRMT2A form a core genetic component implicated in differential resting-state connectivity patterns in the 22q11.2 deletion. A disruption of their co-expression in schizophrenia patients points out a prospective cause for the aberrance of brain networks communication in 22q11.2 deletion syndrome on a molecular level.

Limited polymorphism in k13 gene of Plasmodium falciparum and k12 of Plasmodium vivax isolates imported from African and Asian countries between 2014 and 2019 in Hangzhou city, China.

BACKGROUND: Malaria causes major public health problems globally and drug resistance hinders its control and elimination. Molecular markers associated with drug resistance are considered as a beneficial tool to monitor the disease trends, evolution and distribution so as to help improve drug policy. METHODS: We collected 148 Plasmodium falciparum and 20 Plasmodium vivax isolates imported into Hangzhou city, China between 2014 and 2019. k13 gene of P. falciparum and k12 of P. vivax were sequenced. Polymorphisms and prevalence of k13 and k12 were analyzed. RESULTS: Most (98.65%, 146/148) P. falciparum infections were imported from Africa, and half P. vivax cases came from Africa and the other half from Asia. Nucleotide mutation prevalence was 2.03% (3/148) and the proportion of amino acid mutations was 0.68% (1/148). The amino acid mutation, A676S, was observed in an isolate from Nigeria. No mutation of k12 was observed from the parasites from African and Asian countries. CONCLUSIONS: Limited polymorphism in k13 gene of P. falciparum isolates imported from African countries, but no evidence for the polymorphism of k12 in P. vivax samples from African and Asian countries was found. These results provide information for drug policy update in study region.

Brain network dynamics during working memory are modulated by dopamine and diminished in schizophrenia.

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory performance entails brain-wide switching between activity states using a combination of functional magnetic resonance imaging in healthy controls and individuals with schizophrenia, pharmacological fMRI, genetic analyses and network control theory. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Individuals with schizophrenia show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations. Our results demonstrate the relevance of dopamine signaling for the steering of whole-brain network dynamics during working memory and link these processes to schizophrenia pathophysiology.

Efficacy and Safety of Anticoagulation Treatment in COVID-19 Patient Subgroups Identified by Clinical-Based Stratification and Unsupervised Machine Learning: A Matched Cohort Study.

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning. Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC. Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 µg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC. Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.

Vaccination pattern of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in Hangzhou, China: a coverage and adverse events following immunization of different age groups.

Background: 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been used to prevent pneumococcal disease, and PPSV23 became available in 2003 in Hangzhou, China as a private-sector, vaccinee-chosen vaccine. No national guidelines for PPSV23 have been developed. We analyzed PPSV23 coverage and utilization in Hangzhou to determine patterns of PPSV23 use and the occurrence of adverse events following immunization (AEFI) in Hangzhou. Materials and Methods: Individuals over 2 years of age in Hangzhou were included. Vaccination data during 2006-2017 was retrieved from Hangzhou's Immunization Information System (HZIIS). We used descriptive epidemiological methods to determine PPSV23 usage patterns and AEFI occurrence. Results: In 2017, there were 9,027,973 persons above 2 years of age with the coverage of PPSV23 of 2.98%. The coverage of PPSV23 among elders ranged from 0.17% to 0.69%, and the overall coverage was higher in urban areas (3.70%) than in rural (3.34%) and suburban areas (2.16%). 93.45% of 268957 recipients were vaccinated with PPSV23 at 2-4 years of age. 394 AEFI of PPSV23 cases were reported to the Chinese national adverse event following immunization information system (CNAEFIS) during 2008-2017, with the reporting rate of 140.39 per 100,000 doses. Conclusion: Persons in Hangzhou had overall low PPSV23 vaccination coverage especially for adults. Most of PPSV23 were used in children, while the proportion of the old population over 60 years slightly increased over year. PPSV23 was safe with a low reported AEFI rate, which was a little higher for children than for the elderly (over 60 years).