Baicalein relieves lung graft ischemia-reperfusion injury by reducing advanced glycation endproducts: From screens to mechanisms.

Background: The lack of effective drugs for treating ischemia-reperfusion injury (IRI) in lung transplants (LTx) remains an issue. Traditional Chinese medicine (TCM) ingredients are promising but poorly studied in LTx. This study aimed to identify potential ingredients and elucidate their mechanisms.

Effectiveness of abdominal electroacupuncture therapy for poststroke constipation: a meta-analysis.

Background: Electroacupuncture (EA) has been employed to address the symptoms of constipation in individuals who have experienced a stroke. However, supporting evidence for its efficacy is lacking. This meta-analysis aims to investigate whether EA was effective in treating poststroke constipation.

Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis.

Background: We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.

Beyond guilty by association at scale: searching for causal variants on the basis of genome-wide summary statistics.

Understanding the causal genetic architecture of complex phenotypes will fuel future research into disease mechanisms and potential therapies. Here, we illustrate the power of a novel framework: it detects, starting from summary statistics, and across the entire genome, sets of variants that carry non-redundant information on the phenotypes and are therefore more likely to be causal in a biological sense. The approach, implemented in open-source software, is also computationally efficient, requiring less than 15 minutes on a single CPU to perform genome-wide analysis.

Results of Immediate Postpartum Long Acting Reversible Contraception Provision After Expanded Reimbursement Policy Implementation at an Academic Medical Institution.

Introduction: Immediate postpartum (IPP) Long Acting Reversible Contraception (LARC) is effective in reducing short birth spacing, which is highest among minoritized and younger women with lower socioeconomic status. The structural barrier of cost for pregnant people who desire IPP LARC insertion was alleviated in 2016 when New York State provided statewide reimbursement for Medicaid recipients.

Methods: Analyses of existing electronic medical records (EMR) were conducted on women who received IPP LARC between 3/2/17 and 9/2/19 at two hospitals after a term delivery, defined as gestational age 37 0/7 weeks or greater.

CARMA is a new Bayesian model for fine-mapping in genome-wide association meta-analyses.

Fine-mapping is commonly used to identify putative causal variants at genome-wide significant loci. Here we propose a Bayesian model for fine-mapping that has several advantages over existing methods, including flexible specification of the prior distribution of effect sizes, joint modeling of summary statistics and functional annotations and accounting for discrepancies between summary statistics and external linkage disequilibrium in meta-analyses. Using simulations, we compare performance with commonly used fine-mapping methods and show that the proposed model has higher power and lower false discovery rate (FDR) when including functional annotations, and higher power, lower FDR and higher coverage for credible sets in meta-analyses.

BIGKnock: fine-mapping gene-based associations via knockoff analysis of biobank-scale data.

We propose BIGKnock (BIobank-scale Gene-based association test via Knockoffs), a computationally efficient gene-based testing approach for biobank-scale data, that leverages long-range chromatin interaction data, and performs conditional genome-wide testing via knockoffs. BIGKnock can prioritize causal genes over proxy associations at a locus. We apply BIGKnock to the UK Biobank data with 405,296 participants for multiple binary and quantitative traits, and show that relative to conventional gene-based tests, BIGKnock produces smaller sets of significant genes that contain the causal gene(s) with high probability.

GhostKnockoff inference empowers identification of putative causal variants in genome-wide association studies.

Recent advances in genome sequencing and imputation technologies provide an exciting opportunity to comprehensively study the contribution of genetic variants to complex phenotypes. However, our ability to translate genetic discoveries into mechanistic insights remains limited at this point. In this paper, we propose an efficient knockoff-based method, GhostKnockoff, for genome-wide association studies (GWAS) that leads to improved power and ability to prioritize putative causal variants relative to conventional GWAS approaches.

KnockoffTrio: A knockoff framework for the identification of putative causal variants in genome-wide association studies with trio design.

Family-based designs can eliminate confounding due to population substructure and can distinguish direct from indirect genetic effects, but these designs are underpowered due to limited sample sizes. Here, we propose KnockoffTrio, a statistical method to identify putative causal genetic variants for father-mother-child trio design built upon a recently developed knockoff framework in statistics. KnockoffTrio controls the false discovery rate (FDR) in the presence of arbitrary correlations among tests and is less conservative and thus more powerful than the conventional methods that control the family-wise error rate via Bonferroni correction.

Comprehensive analysis of lncRNA-mRNAs co-expression network identifies potential lncRNA biomarkers in cutaneous squamous cell carcinoma.

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer, the prognosis for patients with metastatic cSCC remains relatively poor. Thus, there is an urgent need to identify new diagnostic, prognostic, and therapeutic targets and pathways in cSCC.

Results: It detected a total of 37,507 lncRNA probes and 32,825 mRNA probes and found 3593 differentially expressed lncRNAs and 3236 differentially expressed mRNAs.

Powerful gene-based testing by integrating long-range chromatin interactions and knockoff genotypes.

Gene-based tests are valuable techniques for identifying genetic factors in complex traits. Here, we propose a gene-based testing framework that incorporates data on long-range chromatin interactions, several recent technical advances for region-based tests, and leverages the knockoff framework for synthetic genotype generation for improved gene discovery. Through simulations and applications to genome-wide association studies (GWAS) and whole-genome sequencing data for multiple diseases and traits, we show that the proposed test increases the power over state-of-the-art gene-based tests in the literature, identifies genes that replicate in larger studies, and can provide a more narrow focus on the possible causal genes at a locus by reducing the confounding effect of linkage disequilibrium.

Genome-wide analysis of common and rare variants via multiple knockoffs at biobank scale, with an application to Alzheimer disease genetics.

Knockoff-based methods have become increasingly popular due to their enhanced power for locus discovery and their ability to prioritize putative causal variants in a genome-wide analysis. However, because of the substantial computational cost for generating knockoffs, existing knockoff approaches cannot analyze millions of rare genetic variants in biobank-scale whole-genome sequencing and whole-genome imputed datasets. We propose a scalable knockoff-based method for the analysis of common and rare variants across the genome, KnockoffScreen-AL, that is applicable to biobank-scale studies with hundreds of thousands of samples and millions of genetic variants.

Identification of putative causal loci in whole-genome sequencing data via knockoff statistics.

The analysis of whole-genome sequencing studies is challenging due to the large number of rare variants in noncoding regions and the lack of natural units for testing. We propose a statistical method to detect and localize rare and common risk variants in whole-genome sequencing studies based on a recently developed knockoff framework. It can (1) prioritize causal variants over associations due to linkage disequilibrium thereby improving interpretability; (2) help distinguish the signal due to rare variants from shadow effects of significant common variants nearby; (3) integrate multiple knockoffs for improved power, stability, and reproducibility; and (4) flexibly incorporate state-of-the-art and future association tests to achieve the benefits proposed here.

Acute myocardial infarction associated with unconventional natural gas development: A natural experiment.

Background: Whereas it is plausible that unconventional natural gas development (UNGD) may adversely affect cardiovascular health, little is currently known. We investigate whether UNGD is associated with acute myocardial infarction (AMI).

Methods: In this observational study leveraging the natural experiment generated by New York's ban on hydraulic fracturing, we analyzed the relationship between age- and sex-specific county-level AMI hospitalization and mortality rates and three UNGD drilling measures.

Predicting Risk for Incident Heart Failure With Omega-3 Fatty Acids: From MESA.

Objectives: The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial.

Background: Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear.

The Impact of Timing of Concurrent Chemoradiation in Patients With High-Grade Glioma in the Era of the Stupp Protocol.

The purpose of this study is to provide a critical review of current evidence for the impact of time to initiation of chemoradiation on overall survival in patients with newly diagnosed high-grade gliomas treated with radiation and concurrent temozolomide chemotherapy. A literature search was conducted using PubMed/MEDLINE and EMBASE databases. Studies were included if they provided separate analysis for patients treated with current standard of care: radiation and concurrent temozolomide.

A semi-supervised approach for predicting cell-type specific functional consequences of non-coding variation using MPRAs.

Predicting the functional consequences of genetic variants in non-coding regions is a challenging problem. We propose here a semi-supervised approach, GenoNet, to jointly utilize experimentally confirmed regulatory variants (labeled variants), millions of unlabeled variants genome-wide, and more than a thousand cell/tissue type specific epigenetic annotations to predict functional consequences of non-coding variants. Through the application to several experimental datasets, we demonstrate that the proposed method significantly improves prediction accuracy compared to existing functional prediction methods at the tissue/cell type level, but especially so at the organism level.

Convergence rates of a partition based Bayesian multivariate density estimation method.

We study a class of non-parametric density estimators under Bayesian settings. The estimators are obtained by adaptively partitioning the sample space. Under a suitable prior, we analyze the concentration rate of the posterior distribution, and demonstrate that the rate does not directly depend on the dimension of the problem in several special cases.

Daidzein impairs Leydig cell testosterone production and Sertoli cell function in neonatal mouse testes: An in vitro study.

Isoflavone is a type of phytoestrogen that exists in soy‑based products. Previous studies have reported that certain foods containing isoflavones, particularly infant formula, may have potential adverse effects on male reproductive function. However, few studies have focused on the effects of isoflavones on testosterone biosynthesis and Sertoli cell function during the neonatal period.

[Potential detrimental effect of soy isoflavones on testis sertoli cells].

Objective: To determine the effect of soy isoflavones on cell proliferation and the transcription levels of follicle-stimulating hormone receptor (FSHR), inhibin α (INHα), INHβB, androgen binding protein (ABP), transferrin (Tf) and vimentin in testis sertoli cells in SD rats.

Methods: Sertoli cells were cultured in vitro, exposed to daidzein at 0.03, 0.