High KIR diversity in Uganda and Botswana children living with HIV.

Killer-cell immunoglobulin-like receptors (s) are essential components of the innate immune system found on the surfaces of natural killer (NK) cells. The s encoding genes are located on chromosome 19q13.4 and are genetically diverse across populations.

The impact of retirement on loneliness in Europe.

This article investigates the short- and long-term impacts of retirement on loneliness using panel data from the Survey of Health, Aging, and Retirement in Europe. To identify causal effects, we exploit differences in retirement rules across and within countries and use retirement thresholds in an instrumental variable setting. On average, we find that entering retirement leads to a reduction in loneliness in the long run and no clear effect in the short run.

Antigen specificity of clonally-enriched CD8+ T cells in multiple sclerosis.

CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naïve MS patients and control participants.

Real-time tracking of structural evolution in 2D MXenes using theory-enhanced machine learning.

In situ Electron Energy Loss Spectroscopy (EELS) combined with Transmission Electron Microscopy (TEM) has traditionally been pivotal for understanding how material processing choices affect local structure and composition. However, the ability to monitor and respond to ultrafast transient changes, now achievable with EELS and TEM, necessitates innovative analytical frameworks. Here, we introduce a machine learning (ML) framework tailored for the real-time assessment and characterization of in operando EELS Spectrum Images (EELS-SI).

MHConstructor: A high-throughput, haplotype-informed solution to the MHC assembly challenge.

The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit the usefulness of reference-based alignment methods for sequence assembly. We incorporate a short read assembly algorithm into a workflow for novel application to the MHC. MHConstructor is a containerized pipeline designed for high-throughput, haplotype-informed, reproducible assembly of both whole genome sequencing and target-capture short read data in large, population cohorts.

Prenatal stress and hair cortisol in a sample of Latina women.

Background: Stress during pregnancy adversely impacts maternal and infant health. Dysregulation of the hypothalamic pituitary axis is a mediator of the relationship between stress and health. Evidence supporting an association between prenatal chronic stress and cortisol is limited, and the majority of research published has been conducted amongst White participants, who experience less chronic stress than people of color.

The association of hospital profitability and digital maturity - An explorative study using data from the German DigitalRadar project.

Introduction: German hospitals largely rely on public investments for digitization. As these have been insufficient, hospitals had to use own profits to foster digital transformation. Thus, we assess if profitability affects digital maturity, and what other factors might be influential.

High-resolution DNA methylation screening of the major histocompatibility complex in multiple sclerosis.

Background: The gene in the major histocompatibility complex (MHC) region in chromosome 6p21 is the strongest genetic factor identified as influencing multiple sclerosis (MS) susceptibility. DNA methylation changes associated with MS have been consistently detected at the MHC region. However, understanding the full scope of epigenetic regulations of the MHC remains incomplete, due in part to the limited coverage of this region by standard whole genome bisulfite sequencing or array-based methods.

β-Hydroxybutyrate Effects on Bovine Caruncular Epithelial Cells: A Model for Investigating the Peri-Implantation Period Disruption in Ketotic Dairy Cows.

Ketosis is a metabolic disorder arising from a negative energy balance (NEB). It is characterized by high β-Hydroxybutyrate (BHBA) blood levels and associated with reduced fertility in dairy cows. To investigate the impact of BHBA on bovine caruncular epithelial cells (BCEC) in vitro, these cells were stimulated with different concentrations of BHBA.

β-Hydroxybutyrate affects cell physiological parameters, inflammatory markers and hormone receptor expression in bovine endometrial gland cells in vitro.

Introduction: After calving, dairy cows are commonly affected by negative energy balance (NEB), indicated by high β-Hydroxybutyrate (BHBA) blood levels. These are associated with subfertility frequently related to uterine inflammation. Since this could compromise functionality of endometrial glands that are essential for proper embryo implantation in sheep, we investigated effects of BHBA on bovine endometrial gland cells (BEGC) in vitro.

Exceptional diversity of KIR and HLA class I in Egypt.

Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen resistance and reproductive health, combined with demographic structure and dispersal. Despite significant importance to multiple health conditions of differential effect across populations, the nature and extent of immunogenetic diversity is under-studied for many geographic regions.

A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection.

Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes.

Genotype List String 1.1: Extending the Genotype List String grammar for describing HLA and Killer-cell Immunoglobulin-like Receptor genotypes.

The Genotype List (GL) String grammar for reporting HLA and Killer-cell Immunoglobulin-like Receptor (KIR) genotypes in a text string was described in 2013. Since this initial description, GL Strings have been used to describe HLA and KIR genotypes for more than 40 million subjects, allowing these data to be recorded, stored and transmitted in an easily parsed, text-based format. After a decade of working with HLA and KIR data in GL String format, with advances in HLA and KIR genotyping technologies that have fostered the generation of full-gene sequence data, the need for an extension of the GL String system has become clear.

A Predictive Autoantibody Signature in Multiple Sclerosis.

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. Here, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster of PwMS that share an autoantibody signature against a common motif that has similarity with many human pathogens.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland in April 2022 and has now been identified in 35 countries. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility.

Implementation of standardized asthma management programs in outpatient settings.

Purpose Of Review: This article reviews new approaches, facilitators, barriers, and opportunities to increasing adoption of standardized asthma management programs in the outpatient care setting.

Recent Findings: Primary care clinicians providing asthma care in the outpatient setting are challenged by the complexity of guidelines and want standardization of tools that are easy to use and that can be integrated within their practice's workflow. Programs that integrate clinical decision support tools within a practice's electronic health record and provide support from specialists may enhance uptake of asthma management programs in the outpatient setting and reduce asthma morbidity.

Software update: Interpreting killer-cell immunoglobulin-like receptors from whole genome sequence data with PING.

Here, we demonstrate improvements to our bioinformatic pipeline, PING, which provides high-resolution genotyping of killer-cell immunoglobulin-like receptor (KIR) sequencing data, that expand the method to provide KIR interpretation from whole genome sequencing (WGS) data. We evaluated performance using synthetic sequence datasets and real-world data from the 1000 Genomes Project (1KGP). PING demonstrated high exonic genotyping performance on the synthetic sequence dataset meant to approximate real-world data at 95% accuracy (N = 1366).