scFseCluster: a feature selection-enhanced clustering for single-cell RNA-seq data.

Single-cell RNA sequencing (scRNA-seq) enables researchers to reveal previously unknown cell heterogeneity and functional diversity, which is impossible with bulk RNA sequencing. Clustering approaches are widely used for analyzing scRNA-seq data and identifying cell types and states. In the past few years, various advanced computational strategies emerged. However, the low generalization and high computational cost are the main bottlenecks of existing methods. In this study, we established a novel computational framework, scFseCluster, for scRNA-seq clustering analysis. scFseCluster incorporates a metaheuristic algorithm (Feature Selection based on Quantum Squirrel Search Algorithm) to extract the optimal gene set, which largely guarantees the performance of cell clustering. We conducted simulation experiments in several aspects to verify the performance of the proposed approach. scFseCluster performed very well on eight benchmark scRNA-seq datasets because of the optimal gene sets obtained using the Feature Selection based on Quantum Squirrel Search Algorithm. The comparative study demonstrated the significant advantages of scFseCluster over seven State-of-the-Art algorithms. In addition, our analysis shows that feature selection on high-variable genes can significantly improve clustering performance. In conclusion, our study demonstrates that scFseCluster is a highly versatile tool for enhancing scRNA-seq data clustering analysis.

Caspase-1 affects chronic restraint stress-induced depression-like behaviors by modifying GABAergic dysfunction in the hippocampus.

Major depression disorder (MDD) is one of the most common psychiatric disorders and one of the leading causes of disability in worldwide. Both inflammation and GABAergic dysfunction have been implicated in the pathophysiology of MDD. Caspase-1, a classic inflammatory caspase, regulates AMPARs-mediated glutamatergic neurotransmission. However, the role of caspase-1 in chronic stress-induced GABAergic dysfunction remains largely unknown. In this study, we found that serum and hippocampal caspase-1-IL-1ß levels increased significantly in chronic restraint stress (CRS) mice, and a significant negative correlation occurred between levels of caspase-1 and depression-like behaviors. Furthermore, CRS significantly decreased GAD67 mRNA levels and GABAergic neurotransmission accompanied by the reduction of GABA concentration, reduced the amplitude and frequency of mIPSCs inhibitory postsynaptic currents (mIPSCs) and the decreased surface expression of GABAARs γ2 subunit in the hippocampus. Genetic deficiency of caspase-1 not only blocked CRS-induced depression-like behaviors, but also alleviated CRS-induced impairments in GABAergic neurotransmission. Finally, reexpression of caspase-1 in the hippocampus of Caspase-1-/- mice increased susceptibility to stress-induced anxiety- and depression-like behaviors through inhibiting GAD67 expression and GABAARs-mediated synaptic transmission. Our study suggests that CRS dysregulates GABAergic neurotransmission via increasing the levels of caspase-1-mediated neuroinflammation in the hippocampus, ultimately leading to depression-like behaviors. This work illustrates that targeting caspase-1 may provide potential therapeutic benefits to stress-related GABAergic dysfunction in the pathogenesis of MDD.

Can neurological soft signs and neurocognitive deficits serve as a combined endophenotype for Han Chinese with bipolar disorder?

BACKGROUND: Bipolar disorder's (BD) potential endophenotypes include neurological soft signs (NSS) and neurocognitive disorders (ND). Few research, meanwhile, has coupled NSS and ND as combined endophenotypes of BD. OBJECT: This study intends to investigate NSS and ND and compare their differences in euthymic patients with bipolar disorder (EBP), their unaffected first-degree relatives (FDR), and healthy controls (HC). Additionally, search for potential endophenotypic subprojects of NSS and ND and construct and verify a composite endophenotypic. METHODS: The subjects were all Han Chinese and consisted of 86 EBP, 81 FDR, and 81HC. Cambridge Neurological Inventory and MATRICSTM Consensus Cognitive Battery tested NSS and ND independently. RESULTS: All three groups displayed a trapezoidal distribution of NSS levels and cognitive abnormalities, with EBP having the most severe NSS levels and cognitive deficits, followed by FDR and HC. Among them, motor coordination in NSS and Information processing speed (IPS), Verbal learning (VL), and Working memory (WM) in neurocognitive function are consistent with the traits of the endophenotype of BD. The accuracy in differentiating EBP and HC or FDRs and HC was higher when these items were combined as predictor factors than in differentiating EBP and FDR. CONCLUSION: These results provide more evidence that motor coordination, IPS, VL, and WM may be internal characteristics of bipolar disease. When these characteristics are combined into a complex endophenotype, it may be possible to distinguish BD patients and high-risk groups from normal populations.

Cocultivation of Chinese prescription and intestine microbiota: SJZD alleviated the major symptoms of IBS-D subjects by tuning neurotransmitter metabolism.

Objective: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a recurrent and common disease featuring dysbiotic intestinal microbiota, with limited treatments. Si-Jun-Zi Decoction (SJZD), a classic Chinese prescription, has been extensively used for IBS-D. This work aimed to explore the ex vivo interactions of SJZD and IBS-D's intestinal microbiota. Methods: Five samples of intestinal microbiota collected from IBS-D volunteers and five age-matched healthy controls were recruited from the Affiliated Hospital, Chengdu University of Traditional Chinese Medicine (TCM). A representative mixture of intestinal microbiota was composed of an equal proportion of these fecal samples. To simulate the clinical interaction, this microbiota was cocultivated with SJZD at clinical dosage in an anaerobic incubator at 37°C for 35 h. Microbiota and metabolic alterations were assessed by 16S rRNA gene sequencing in the V3/V4 regions and a nontargeted metabolome platform, respectively. Results: After being cocultivated with SJZD, the dysbiotic intestine microbiota from IBS-D subjects was largely restored to those of the healthy controls. A total of 624 differentially expressed metabolites were detected by nontargeted metabolomics, of which 16 biomarkers were identified. These metabolites were then enriched into 11 pathways by KEGG, particularly those involved in neurotransmitter metabolism responses for the major symptom of IBS-D. Correlation analysis of bacterial metabolites demonstrated a synergistic pattern of neurotransmitter metabolism between Streptococcus and E. Shigella. Conclusion: SJZD rescued the dysbiotic intestinal microbiota and ameliorated the dysfunctional neurotransmitter metabolism involved in IBS-D's major symptoms.

Prevalence of prolonged grief disorder and its symptoms in Chinese parents who lost their only child: A systematic review and meta-analysis.

Background: Parents who lost their only child and cannot have a second child ("Shidu") have been a large population in China. Prolonged grief disorder (PGD) in Shidu parents is of clinical and public health concern but the reported PGD prevalence varies widely. To facilitate the planning of grief counseling services, this meta-analysis estimated prevalence of PGD and its symptoms and identified subgroups at elevated risk for PGD. Methods: We searched English and Chinese literature databases to identify cross-sectional surveys reporting prevalence of PGD or PGD symptoms in Chinese Shidu parents. The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data ("JBI") was used to assess risk of bias of included studies. Results: Seven studies with a total of 2,794 Shidu parents were included and their JBI scores ranged from five to eight. The pooled prevalence of PGD and PGD symptoms was 20.9% and 75.0%, respectively. Greater risk of PGD was observed in mothers [vs. fathers, OR (odds ratio) = 1.89, P = 0.001] and in parents with religious beliefs (vs. without religious beliefs, OR = 1.65, P = 0.040). More severe PGD symptoms were presented in parents whose only child died from accidents [vs. illness, MD (mean difference) = 3.99, P < 0.001]. Deceased children of PGD parents were older than those of non-PGD parents (MD = 1.64, P = 0.035) and PGD parents had a shorter duration since the loss than non-PGD parents (MD = -3.26, P = 0.013). Conclusions: PGD is prevalent among Shidu parents. Grief counseling services for Shidu parents would be more effective if they target those who are mothers and have religious beliefs and those whose children died from accidents, lost children are older, and loss occurs more recently.

Prevalence and correlates of suspected dementia in older adults receiving primary healthcare in Wuhan, China: A multicenter cross-sectional survey.

Background: Integrating the management of dementia into primary healthcare is a cost-effective way to reduce the burden of dementia but the clinical epidemiology of dementia in primary healthcare settings remains unclear. This study investigated the prevalence and correlates of suspected dementia in Chinese older adults receiving primary healthcare. Methods: In this multicenter cross-sectional survey, a total of 773 older adults (≥65 years) were consecutively recruited from seven urban and six rural primary care clinics in Wuhan, China, and interviewed with the validated Chinese version of the Brief Community Screening Instrument for Dementia (BCSI-D). Participants with suspected dementia were those who were screened positive on the BCSI-D. Results: The prevalence of suspected dementia in older primary healthcare adults was 26.8%. Factors significantly associated with suspected dementia were female sex (OR = 1.95, P < 0.001), age-group of 75+ (OR = 1.68, P = 0.004), poor financial status (OR = 4.79, P < 0.001), rural residence (OR = 1.47, P = 0.032), no regular physical exercise (OR = 1.74, P = 0.002), and stroke and other cerebrovascular diseases (OR = 1.97, P = 0.015). Conclusions: Chinese older adults receiving primary healthcare are at high risk of suspected dementia. Screening and intervention efforts for dementia in primary healthcare settings may be more useful to target older adults who are women, are 75 years and above, have poor economic status, are rural residents, have no exercise habit, and suffer from cerebrovascular diseases.

Prevalence and correlates of suicidal ideation among older adults attending primary care clinics in Wuhan, China: A multicenter cross-sectional study.

Background: Primary care represents an ideal setting for screening for and managing suicidal older adults but the clinical epidemiology of suicidal ideation in Chinese older primary care patients remains unclear. This study investigated the prevalence and correlates of suicidal ideation in older Chinese adults receiving primary care. Methods: This multicenter cross-sectional survey included a total of 769 older adults (≥65 years) from seven urban and six rural primary care clinics in Wuhan, China. The presence of depressive symptoms and suicidal ideation was assessed with the Geriatric Depression Scale and a single-item question "In the past 12 months, did you think about ending your life?," respectively. Results: The 12-month prevalence of suicidal ideation in older primary care patients was 16.6%. Significant correlates of suicidal ideation were poor economic status (vs. good, OR = 2.80, P = 0.008), heart disease (OR = 2.48, P = 0.005), chronic gastric ulcer (OR = 3.55, P = 0.012), arthritis (OR = 2.10, P = 0.042), and depressive symptoms (OR = 11.29, P < 0.001). Conclusions: Suicidal ideation is common among older adults attending Chinese primary care clinics. It is necessary to integrate psychological crisis intervention into primary care to prevent late-life suicide.

Meta-Analysis of the Efficacy and Safety of Olanzapine versus Clozapine when Treating Senile Dementia.

Objective: To systematically assess the safety and efficacy of olanzapine versus clozapine when treating senile dementia and to provide evidence-based medicine basis for its promotion and use. Methods: PubMed, Embase, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database were searched for randomized controlled trials (RCT) of olanzapine and clozapine when treating senile dementia. The retrieval time limit is from the establishment of the database to the present. The data were extracted independently by two researchers, and the bias risk of each contained literature was analyzed in accordance with the standard of Cochrane Handbook 5.3. RevMan 5.4 statistical software was used to analyze the collected data by meta-analysis. Results: Finally, 6 randomized controlled trial articles were included, with a total of 490 samples. Meta-analysis of clinical efficacy showed that the clinical efficacy was similar and there was no significant difference (P > 0.05). Two articles used Alzheimer's disease pathological behavior rating scale (BEHAVE-AD) to compare the pathological behavior of different stages after treatment. Statistical analysis showed that there was no significant difference between the total score of BEHAVE-AD and the scores of each factor in each week after treatment. The non-treatment adverse reaction scale (TESS) of the study group and the control group was analyzed by meta-analysis. The TESS score of the study group after treatment was significantly lower than that of the control group. The BPRS scores of different stages after treatment were analyzed by meta-analysis, and there was no significant difference in the total score and factor scores of BPRS in each week after treatment. Two clinical trials reported the incidence of neurological symptoms after treatment. Olanzapine and clozapine treatment can effectively reduce the risk of aging. There was no significant difference in the incidence of neurological symptoms in patients with dementia (P > 0.05). According to the analysis of meat products, the incidence of adverse reactions in the study group was significantly lower than that in the control group (P < 0.05). Conclusion: Olanzapine and clozapine have similar efficacy when treating mental and behavioral disorders in patients with senile dementia, in which olanzapine is more effective in improving the symptoms of patients with Alzheimer's disease (AD), with less adverse reactions and high safety, which is worth popularizing in clinical practice. However, more studies and follow-up with higher methodological quality and longer intervention time are needed to further verify.

Torsional Low-Strain Test for Nondestructive Integrity Examination of Existing High-Pile Foundation.

Low-strain tests are widely utilized as a nondestructive approach to assess the integrity of newly piled foundations. So far, the examination of existing pile foundations is becoming an indispensable protocol for pile recycling or post-disaster safety assessment. However, the present low-strain test is not capable of testing existing pile foundations. In this paper, the torsional low-strain test (TLST) is proposed to overcome this drawback. Both the upward and downward waves are considered in the TLST wave propagation model established in this paper so that a firm theoretical basis is grounded for the test signal interpretations. A concise semi-analytical solution is derived and its rationality is verified by comparisons with the existing solutions for newly piled foundations and the finite element results. The main conclusions of this study can be drawn as follows: (1). by placing the sensors where the incident wave is applied, the number of reflected signals can be minimized; (2). the defects can be more evidently identified if the incident wave/sensors are input/installed close to the superstructure/pile head.

Social Support and Coping Style of Medical Residents in China: The Mediating Role of Psychological Resilience.

Objectives: Recent surveys have paid insufficient attention to the psychological status of medical residents, but medical residents, as a special group of medical workers, need to be focused on. This study aimed to investigate medical residents' levels of social support, psychological resilience, and coping style, and explore the mediating role of psychological resilience, which can ultimately provide a new theoretical basis for improving medical residents' psychological status and quality of work and life. Methods: A total of 577 medical residents from China were investigated by an online questionnaire, using convenience sampling. Associations between social support, psychological resilience, and coping styles were assessed using Pearson correlation analysis. The mediating effect of psychological resilience was tested using SPSS Process. Results: Positive correlations between social support, psychological resilience and coping style were found (r = 0.474, P < 0.001; r = 0.473, P < 0.001; r = 0.353, P < 0.001). The mediating effect of psychological resilience in the relationship between social support and coping style was significant (95% CI: 0.168, 0.384), and accounted for 25.84%. Conclusion: Attention should be paid to the psychological status of medical residents, and social support and psychological flexibility can be used to increase the enthusiasm for their coping style and promote their mental health.

A Novel Computational Framework for Precision Diagnosis and Subtype Discovery of Plant With Lesion.

Plants are often attacked by various pathogens during their growth, which may cause environmental pollution, food shortages, or economic losses in a certain area. Integration of high throughput phenomics data and computer vision (CV) provides a great opportunity to realize plant disease diagnosis in the early stage and uncover the subtype or stage patterns in the disease progression. In this study, we proposed a novel computational framework for plant disease identification and subtype discovery through a deep-embedding image-clustering strategy, Weighted Distance Metric and the t-stochastic neighbor embedding algorithm (WDM-tSNE). To verify the effectiveness, we applied our method on four public datasets of images. The results demonstrated that the newly developed tool is capable of identifying the plant disease and further uncover the underlying subtypes associated with pathogenic resistance. In summary, the current framework provides great clustering performance for the root or leave images of diseased plants with pronounced disease spots or symptoms.

Neurological soft signs and neurocognitive deficits in remitted patients with schizophrenia, their first-degree unaffected relatives, and healthy controls.

Neurological soft signs (NSS) and neurocognitive deficits (ND) are highly prevalent in schizophrenia, and have been separately proposed as candidate endophenotypes of schizophrenia. However, few relevant studies focus on remitted patients with schizophrenia (RP) and integrate NSS and ND as a composite endophenotype. This study aimed to explore the NSS and ND and examine the comparative relationship between them in RP, their first-degree unaffected relatives (FDR), and healthy controls, furthermore, to seek potential endophenotypes subitems of NSS and ND and create a composite endophenotype. 86 RP, 86 FDR, and 86 healthy controls were included. NSS and ND were independently assessed with Cambridge Neurological Inventory and MATRICSTM Consensus Cognitive Battery. RP had more NSS and ND than FDR in all subitems except disinhibition, information processing speed, working memory, and visual memory. Similarly, FDR presented poorer performance than controls in all subscales except disinhibition, sensory integration, working memory, and visual memory. Six subitems of NSS and ND met the criteria of endophenotype and the three groups were most accurately classified (71.2%) with these subitems working as a composite endophenotype. Moreover, information processing speed, attention, and social cognition were associated with sensory integration in RP and FDR. These findings add evidences that certain subitems of NSS and ND might be the endophenotypes of schizophrenia and integrating these endophenotypes may prove useful in identifying schizophrenia and high-risk individuals. Furthermore, sensory integration and specific cognitive domains covary, hence suggesting an overlap of compromised underlying neural systems.