Instrumental Variable Model Average With Applications in Nonlinear Causal Inference.

The instrumental variable method is widely used in causal inference research to improve the accuracy of estimating causal effects. However, the weak correlation between instruments and exposure, as well as the direct impact of instruments on the outcome, can lead to biased estimates. To mitigate the bias introduced by such instruments in nonlinear causal inference, we propose a two-stage nonlinear causal effect estimation based on model averaging.

A weighted Bayesian integration method for predicting drug combination using heterogeneous data.

Background: In the management of complex diseases, the strategic adoption of combination therapy has gained considerable prominence. Combination therapy not only holds the potential to enhance treatment efficacy but also to alleviate the side effects caused by excessive use of a single drug. Presently, the exploration of combination therapy encounters significant challenges due to the vast spectrum of potential drug combinations, necessitating the development of efficient screening strategies.

A Quantitative Computational Framework for Allopolyploid Single-Cell Data Integration and Core Gene Ranking in Development.

Polyploidization drives regulatory and phenotypic innovation. How the merger of different genomes contributes to polyploid development is a fundamental issue in evolutionary developmental biology and breeding research. Clarifying this issue is challenging because of genome complexity and the difficulty in tracking stochastic subgenome divergence during development.

Exploring Causal Relationships Between Gut Microbiota and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study.

Background: Many observational studies have investigated the link between the gut microbiota and Alzheimer's disease (AD), but the causality remains uncertain.

Objective: This study aimed to evaluate the causal impact of gut microbiota on AD.

Methods: A two-sample Mendelian randomization (MR) study was conducted employing summary data.

The change of intimate relationship between people with Alzheimer's disease and their adult child caregivers: An interpretative phenomenological analysis.

This study aims to explore the change of intimate relationship between people with Alzheimer's disease and their adult child caregivers as the disease progresses. Twelve adult child caregivers were recruited through purposive sampling. Explanatory phenomenological analysis was conducted to analyse data collected by semi-structured in-depth interviews.

Identification of a coagulation-related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation-related genes (CRGs) for prognosis in LUAD has yet to be determined.

Bi-directional causal effect between vitamin B12 and non-alcoholic fatty liver disease: Inferring from large population data.

Objectives: Many observational studies evaluate the association between vitamin B12 and non-alcoholic fatty liver disease (NAFLD). However, the causality of this association remains uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to explore the association between vitamin B12 and NAFLD.

MR-BOIL: Causal inference in one-sample Mendelian randomization for binary outcome with integrated likelihood method.

Mendelian randomization is a statistical method for inferring the causal relationship between exposures and outcomes using an economics-derived instrumental variable approach. The research results are relatively complete when both exposures and outcomes are continuous variables. However, due to the noncollapsing nature of the logistic model, the existing methods inherited from the linear model for exploring binary outcome cannot take the effect of confounding factors into account, which leads to biased estimate of the causal effect.

Inferring causal effects of homocysteine and B-vitamin concentrations on bone mineral density and fractures: Mendelian randomization analyses.

Objectives: In the progress of bone metabolism, homocysteine (Hcy) and B vitamins play substantial roles. However, the causal associations of homocysteine, B-vitamin concentrations with bone mineral density (BMD), and fractures remain unclear. Therefore, we employed a two-sample Mendelian randomization (MR) design to infer the causal effects of Hcy and B vitamins on BMD and fractures.

Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study.

Objectives: Although homocysteine (Hcy) increases the risk of cardiovascular diseases, its effects on obesity and musculoskeletal diseases remain unclear. We performed a Mendelian randomization study to estimate the associations between Hcy and B vitamin concentrations and their effects on obesity and musculoskeletal-relevant diseases in the general population.

Methods: We selected independent single nucleotide polymorphisms of Hcy ( = 44,147), vitamin B12 ( = 45,576), vitamin B6 ( = 1864), and folate ( = 37,465) at the genome-wide significance level as instruments and applied them to the studies of summary-level data for fat and musculoskeletal phenotypes from the UK Biobank study ( = 331,117), the FinnGen consortium ( = 218,792), and other consortia.

Efficacy and safety of simultaneous rTMS-tDCS over bilateral angular gyrus on neuropsychiatric symptoms in patients with moderate Alzheimer's disease: A prospective, randomized, sham-controlled pilot study.

Background: Treating neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) remains highly challenging. Noninvasive brain stimulation using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) is of considerable interest in this context.

Objective: To investigate the efficacy and safety of a novel technique involving simultaneous application of rTMS and tDCS (rTMS-tDCS) over bilateral angular gyrus (AG, P5/P6 electrode site) for AD-related NPS.

Association between homocysteine and nonalcoholic fatty liver disease: Mendelian randomisation study.

Background: Many observational studies explore the relationship between homocysteine (Hcy) and nonalcoholic fatty liver disease (NAFLD), whereas the causality of this association remains uncertain, especially in European populations. We performed a bidirectional Mendelian randomisation study to elucidate the causal association between Hcy and NAFLD. Furthermore, we explored the relationship of Hcy with liver enzymes, including alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Causal Association of Thyroid Signaling with C-Reactive Protein: A Bidirectional Mendelian Randomization.

Methods: Based on the latest genome-wide association study summary data, bidirectional two-sample Mendelian randomization (MR) was employed to detect the causal relationship and effect direction between TSH, fT4, and CRP. Furthermore, in view of obesity being an important risk factor of CVD, obesity trait waist-hip ratio (WHR) and body mass index (BMI) were treated as the research objects in MR analyses for exploring the causal effects of TSH and fT4 on them, respectively.

Results: Genetically increased CRP was associated with increased TSH ( = -0.

A Novel Hierarchical Clustering Approach for Joint Analysis of Multiple Phenotypes Uncovers Obesity Variants Based on ARIC.

Genome-wide association studies (GWASs) have successfully discovered numerous variants underlying various diseases. Generally, one-phenotype one-variant association study in GWASs is not efficient in identifying variants with weak effects, indicating that more signals have not been identified yet. Nowadays, jointly analyzing multiple phenotypes has been recognized as an important approach to elevate the statistical power for identifying weak genetic variants on complex diseases, shedding new light on potential biological mechanisms.

Development of Models to Predict Postoperative Complications for Hepatitis B Virus-Related Hepatocellular Carcinoma.

Background: Surgical treatment remains the best option for patients with hepatocellular carcinoma (HCC) caused by chronic hepatitis B virus (HBV) infection. However, there is no optimal tool based on readily accessible clinical parameters to predict postoperative complications. Herein, our study aimed to develop models that permitted risk of severe complications to be assessed before and after liver resection based on conventional variables.

A tacrine-tetrahydroquinoline heterodimer potently inhibits acetylcholinesterase activity and enhances neurotransmission in mice.

Cholinergic neurons are ubiquitous and involved in various higher brain functions including learning and memory. Patients with Alzheimer's disease exhibit significant dysfunction and loss of cholinergic neurons. Meanwhile, such cholinergic deficits can be potentially relieved pharmacologically by increasing acetylcholine.

Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq data.

Intronic polyadenylation (IpA) usually leads to changes in the coding region of an mRNA, and its implication in diseases has been recognized, although at its very beginning status. Conveniently and accurately identifying IpA is of great importance for further evaluating its biological significance. Here, we developed IPAFinder, a bioinformatic method for the de novo identification of intronic poly(A) sites and their dynamic changes from standard RNA-seq data.

A Novel Method for Mendelian Randomization Analyses With Pleiotropy and Linkage Disequilibrium in Genetic Variants From Individual Data.

Mendelian randomization makes use of genetic variants as instrumental variables to eliminate the influence induced by unknown confounders on causal estimation in epidemiology studies. However, with the soaring genetic variants identified in genome-wide association studies, the pleiotropy, and linkage disequilibrium in genetic variants are unavoidable and may produce severe bias in causal inference. In this study, by modeling the pleiotropic effect as a normally distributed random effect, we propose a novel mixed-effects regression model-based method PLDMR, pleiotropy and linkage disequilibrium adaptive Mendelian randomization, which takes linkage disequilibrium into account and also corrects for the pleiotropic effect in causal effect estimation and statistical inference.

A Novel Approach Integrating Hierarchical Clustering and Weighted Combination for Association Study of Multiple Phenotypes and a Genetic Variant.

As a pivotal research tool, genome-wide association study has successfully identified numerous genetic variants underlying distinct diseases. However, these identified genetic variants only explain a small proportion of the phenotypic variation for certain diseases, suggesting that there are still more genetic signals to be detected. One of the reasons may be that one-phenotype one-variant association study is not so efficient in detecting variants of weak effects.

Influencing Factors of Psychological Well-Being of the Non-designated Hospital Staff in China During the COVID-19 Pandemic.

Recent studies report that hospital staff at the forefront of caring for COVID-19 patients experience increased psychological distress. To effectively manage the outbreak of COVID-19, China established COVID-19 designated and non-designated hospitals. To date, few studies have examined the impacts of COVID-19 on psychological health of staff working at non-designated hospitals.

A novel similarity score based on gene ranks to reveal genetic relationships among diseases.

Knowledge of similarities among diseases can contribute to uncovering common genetic mechanisms. Based on ranked gene lists, a couple of similarity measures were proposed in the literature. Notice that they may suffer from the determination of cutoff or heavy computational load, we propose a novel similarity score among diseases based on gene ranks.

A Pentacyclic Triterpene from Targets γ-Secretase.

Amyloid-beta peptides generated by β-secretase- and γ-secretase-mediated successive cleavage of amyloid precursor protein are believed to play a causative role in Alzheimer's disease. Thus, reducing amyloid-beta generation by modulating γ-secretase remains a promising approach for Alzheimer's disease therapeutic development. Here, we screened fruit extracts of Ait.

Novel gene signatures for prognosis prediction in ovarian cancer.

Ovarian cancer (OV) is one of the leading causes of cancer deaths in women worldwide. Late diagnosis and heterogeneous treatment result to poor survival outcomes for patients with OV. Therefore, we aimed to develop novel biomarkers for prognosis prediction from the potential molecular mechanism of tumorigenesis.