Comparative genetic architectures of schizophrenia in East Asian and European populations

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations

Understanding young people’s we-intention to contribute in Danmaku websites: Motivational, social, and subculture influence

Various social media have promoted the emergence and development of diverse subcultures among the young generation. ACG (Animation, Comic, and Game) is such an adolescent subculture which is fascinating to a group of young people, named Otaku. Danmaku video sharing website is an important social media for them to communicate, and reflects an obvious hedonic characteristic of usage. In this study, we propose a research model in the context of Danmaku websites. First, we include an important social driver, sense of virtual community (SOVC), to predict we-intention of participants. Second, we employ social presence theory and uses and gratifications theory to understand the formation of SOVC. In addition, we argue that when considering young people’s usage of innovative IT product, the degree of their identity within the subcultural involved in the product should also be included. Finally, a longitudinal field study is designed to test the research model and hypotheses

A PDMS–Agar Hybrid Microfluidic Device for the Investigation of Chemical–Mechanical Associative Learning Behavior of <i>C. elegans</i>

Associative learning is a critical survival trait that promotes behavioral plasticity in response to changing environments. Chemosensation and mechanosensation are important sensory modalities that enable animals to gather information about their internal state and external environment. However, there is a limited amount of research on these two modalities. In this paper, a novel PDMS–agar hybrid microfluidic device is proposed for training and analyzing chemical–mechanical associative learning behavior in the nematode Caenorhabditis elegans. The microfluidic device consisted of a bottom agar gel layer and an upper PDMS layer. A chemical concentration gradient was generated on the agar gel layer, and the PDMS layer served to mimic mechanical stimuli. Based on this platform, C. elegans can perform chemical–mechanical associative learning behavior after training. Our findings indicated that the aversive component of training is the primary driver of the observed associative learning behavior. In addition, the results indicated that the neurotransmitter octopamine is involved in regulating this associative learning behavior via the SER-6 receptor. Thus, the microfluidic device provides a highly efficient platform for studying the associative learning behavior of C. elegans, and it may be applied in mutant screening and drug testing

Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis

Objective: It is not well determined whether liver metastasis is a prognostic factor for survival of metastatic non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitors (ICIs). We compared the efficacy of ICIs in patients with NSCLC with or without liver metastases, aiming to evaluate the impact of liver metastasis on survival of NSCLC. Methods: We systematically searched Pubmed, Embase, and the Cochrane library databases for randomized controlled trials (RCTs) on the efficacy of ICIs in the treatment of NSCLC patients with or without liver metastases. The duration of this search was from January 1, 2000 to June 1, 2022. The reviewers screened the literature, extracted data and conducted quality assessment, and used RevMan 5.4 software and Stata 14 to perform analyses. Results: A total of 17 RCTs were included, published from 2019 to 2022. For NSCLC patients with liver metastases, the risk of disease progression decreased by 36% (HR = 0.64; 95% CI: 0.55-0.75; P  < .01) when treated with ICIs, and the death risk (HR = 0.82; 95% CI: 0.72-0.94; P  < .01) was also reduced after ICIs treatment. For those without liver metastases, they had significantly improved PFS (HR = 0.56; 95% CI: 0.52-0.60; P  < .01) and OS (HR = 0.73; 95% CI: 0.67-0.80; P  < .01), compared to those of the control group. Subgroup analysis of OS in liver metastases patients suggested that OS benefit was associated with treatment strategy (for anti-PD-L1 plus chemotherapy versus chemotherapy, HR=1.04; 95% CI: 0.81-1.34; P = .75). Conclusion: For NSCLC patients with or without liver metastases, ICIs administration could improve both PFS and OS, especially for those without liver metastases. More RCTs are essential to verify these findings

Baseline Albumin-Bilirubin grade as a predictor of response and outcome of regorafenib therapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis

Abstract Background The use of regorafenib in the treatment of hepatocellular carcinoma (HCC) is widespread. Albumin-Bilirubin (ALBI) has been shown to be a potential prognostic marker for regorafenib treatment, but its prognostic value remains controversial. Therefore, we conducted a meta-analysis to investigate the value of the baseline ALBI grade in predicting the efficacy and survival outcomes of HCC patients after regorafenib treatment. Methods PubMed, Embase, Cochrane library, Web of Science, CNKI, Wan Fang Data, and Vip Database were searched from January 2010 to October 2022. Studies treating HCC patients with regorafenib and with ALBI as a categorical variable, overall survival (OS) and progression-free survival (PFS) as outcome indicators were included. After applying Newcastle–Ottawa Scale (NOS) to evaluate the quality of the included studies, Review Manager 5.4 was used to statistically analyze. Chi-square Q test and I2 statistics were used to detect heterogeneity. Funnel plot asymmetry, Egger’s and Begg’s test were used to evaluate publication bias. Results A total of 12 studies, comprising 1,918 patients, were included in the meta-analysis. The included studies were all evaluated as high quality. Compared to the high-grade baseline ALBI group, patients in the low-grade group had a longer survival time after receiving regorafenib and also more suitable for regorafenib treatment [odds ratio (OR) = 6.50, 95% confidence interval (CI): 2.22–18.96, P < 0.01]. The low-grade baseline ALBI group before sorafenib treatment was significantly correlated with better OS [hazard ratio (HR) = 2.36, 95% CI: 1.68–3.31, P < 0.00001] and PFS (HR = 1.56, 95% CI: 1.16–2.08, P = 0.003). Likewise, the low-grade baseline ALBI group before regorafenib was also significantly correlated with better OS (HR = 1.56, 95% CI: 1.15–2.13, P = 0.005) and PFS (HR = 2.06, 95% CI: 1.37–3.11, P = 0.0005). In addition, the ALBI grade was significantly correlated with disease control rate (DCR) (OR = 2.90, 95% CI: 1.45–5.79, P = 0.003), but not the objective response rate (OR = 1.98, 95% CI: 0.71–5.46, P = 0.19). Conclusions The baseline ALBI grade could be a valuable prognostic indicator for predicting response and outcomes in HCC patients treated with regorafenib