Inactivation of GSK3β by Ser phosphorylation prevents thymocyte necroptosis and impacts Tcr repertoire diversity.

The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.

Adjusting for principal components can induce collider bias in genome-wide association studies.

Principal component analysis (PCA) is widely used to control for population structure in genome-wide association studies (GWAS). Top principal components (PCs) typically reflect population structure, but challenges arise in deciding how many PCs are needed and ensuring that PCs do not capture other artifacts such as regions with atypical linkage disequilibrium (LD). In response to the latter, many groups suggest performing LD pruning or excluding known high LD regions prior to PCA.

Joint testing of rare variant burden scores using non-negative least squares.

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins.

Post-pandemic seasonal dynamics of hospitalised COPD exacerbations and aetiologies in the COPD population.

https://bit.ly/3wN71h0.

Yield of genetic association signals from genomes, exomes and imputation in the UK Biobank.

Whole-genome sequencing (WGS), whole-exome sequencing (WES) and array genotyping with imputation (IMP) are common strategies for assessing genetic variation and its association with medically relevant phenotypes. To date, there has been no systematic empirical assessment of the yield of these approaches when applied to hundreds of thousands of samples to enable the discovery of complex trait genetic signals. Using data for 100 complex traits from 149,195 individuals in the UK Biobank, we systematically compare the relative yield of these strategies in genetic association studies.

Admixture Mapping of Chronic Kidney Disease and Risk Factors in Hispanic/Latino Individuals From Central America Country of Origin.

Background: Chronic kidney disease (CKD) is highly prevalent in Central America, and genetic factors may contribute to CKD risk. To understand the influences of genetic admixture on CKD susceptibility, we conducted an admixture mapping screening of CKD traits and risk factors in US Hispanic and Latino individuals from Central America country of origin.

Methods: We analyzed 1023 participants of HCHS/SOL (Hispanic Community Health Study/Study of Latinos) who reported 4 grandparents originating from the same Central America country.

Predictive Factors for Intraoperative Determination for the Need of Femoral Osteochondroplasty After Periacetabular Osteotomy for Acetabular Dysplasia.

Background: Determination of need for osteochondroplasty (OCP) during periacetabular osteotomy (PAO) commonly relies on intraoperative assessment of internal rotation at 90° flexion (IRF). Performing an OCP helps decrease the risk of iatrogenic femoroacetabular impingement from PAO reduction. Avoiding impingement helps decrease risks of accelerated secondary osteoarthritis.

Adjusting for principal components can induce spurious associations in genome-wide association studies in admixed populations.

Principal component analysis (PCA) is widely used to control for population structure in genome-wide association studies (GWAS). Top principal components (PCs) typically reflect population structure, but challenges arise in deciding how many PCs are needed and ensuring that PCs do not capture other artifacts such as regions with atypical linkage disequilibrium (LD). In response to the latter, many groups suggest performing LD pruning or excluding known high LD regions prior to PCA.

Utility of MR Neurography for the Evaluation of Peripheral Trigeminal Neuropathies in the Postoperative Period.

Peripheral trigeminal neuropathies are assessed by MR neurography for presurgical mapping. In this clinical report, we aimed to understand the utility of MR neurography following nerve-repair procedures. We hypothesized that postoperative MR neurography assists in determining nerve integrity, and worsening MR neurography findings will corroborate poor patient outcomes.

Efficacy of MR Neurography of Peripheral Trigeminal Nerves: Correlation of Sunderland Grade versus Neurosensory Testing.

Background And Purpose: The current reference standard of diagnosis for peripheral trigeminal neuropathies (PTN) is clinical neurosensory testing (NST). MR neurography (MRN) is useful for PTN injury diagnosis, but it has only been studied in small case series. The aim of this study was to evaluate the agreement of Sunderland grades of nerve injury on MRN and NST by using surgical findings and final diagnoses as reference standards.

Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI.

Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes.

Evaluating broiler welfare and behavior as affected by growth rate and stocking density.

This study evaluated the welfare and behaviors of Cobb 700 broilers as affected by growth rate (GR) and stocking density (SD). Slower-growth (weight gain < 50 g/d) and medium-growth (weight gain = 50-60 g/d) broilers were produced by providing 57.1% and 78.

Pain catastrophizing and risk of progression to widespread pain among patients with chronic low back pain: A retrospective cohort study.

Background: Chronic low back pain often progresses to widespread pain. Although many factors are associated with progression, their roles in contributing to chronic widespread pain (CWP) are often unclear.

Objective: To determine if pain catastrophizing is an independent risk factor for CWP.

The impact of lipopolysaccharide on cerebrovascular function and cognition resulting from obesity-induced gut dysbiosis.

Obesity is a worldwide epidemic coinciding with a concomitant increase in the incidence of neurodegenerative diseases, particularly dementia. Obesity is characterised by increased adiposity, chronic low-grade systemic inflammation, and oxidative stress, which promote endothelial dysfunction. Endothelial dysfunction reduces cerebrovascular function leading to reduced cerebral blood flow and, eventually, cognitive decline, thus predisposing to a neurodegenerative disease.

Is Retention of the Acetabular Component at Revision Surgery a Long-Term Solution?

Background: Acetabular retention in revision total hip arthroplasty (THA) may be advantageous, yet long-term survival data is limited. Thus, we investigated long-term survivorship of retained acetabular components in revision THA with analysis of rerevision rate, instability risk, and clinical outcomes.

Methods: We reviewed 98 hips with polyethylene wear and/or osteolysis that were revised with retained acetabular components.

Mechanisms underlying the prolonged activation of the genioglossus following arousal from sleep.

Study Objectives: Transient arousal from sleep has been shown to elicit a prolonged increase in genioglossus muscle activity that persists following the return to sleep and which may protect against subsequent airway collapse. We hypothesized that this increased genioglossal activity following return to sleep after an arousal is due to persistent firing of inspiratory-modulated motor units (MUs) that are recruited during the arousal.

Methods: Thirty-four healthy participants were studied overnight while wearing a nasal mask with pneumotachograph to measure ventilation and with 4 intramuscular genioglossus EMG electrodes.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

Background: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear.

Objective: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort.

Exposure Levels of Airborne Fungi, Bacteria, and Antibiotic Resistance Genes in Cotton Farms during Cotton Harvesting and Evaluations of N95 Respirators against These Bioaerosols.

The USA is the third-leading cotton-producing country worldwide and cotton farming is common in the state of Georgia. Cotton harvest can be a significant contributor to airborne microbial exposures to farmers and nearby rural communities. The use of respirators or masks is one of the viable options for reducing organic dust and bioaerosol exposures among farmers.

Admixture mapping implicates 13q33.3 as ancestry-of-origin locus for Alzheimer disease in Hispanic and Latino populations.

Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown.

A deep catalog of protein-coding variation in 985,830 individuals.

Coding variants that have significant impact on function can provide insights into the biology of a gene but are typically rare in the population. Identifying and ascertaining the frequency of such rare variants requires very large sample sizes. Here, we present the largest catalog of human protein-coding variation to date, derived from exome sequencing of 985,830 individuals of diverse ancestry to serve as a rich resource for studying rare coding variants.