Uncovering somatic mosaic variants of -related overgrowth disorders - three cases with different clinical presentations.

Introduction: related disorders (PRD, OMIM: *171834) are genetic disorders resulting from pathogenic somatic mosaic variants in the gene, which encodes a protein crucial for regulating cell growth and division. PRD typically manifest during the post-zygotic phase, leading to a broad spectrum of overgrowth and vascular malformations affecting various body regions.

Methods: Conventional diagnostic methods struggle to detect and confirm pathogenic PIK3CA gene variants due to the mosaic nature of these disorders and the limited accessibility of affected tissues.

Applications of Cell-Based Protein Array Technology to Preclinical Safety Assessment of Biological Products.

Off-target evaluation is essential in preclinical safety assessments of novel biotherapeutics, supporting lead molecule selection, endpoint selection in toxicology studies, and regulatory requirements for first-in-human trials. Off-target interaction of a therapeutic antibody and antibody derivatives has been historically assessed via the Tissue Cross-Reactivity (TCR) study, in which the candidate molecule is used as a reagent in immunohistochemistry (IHC) to assess binding of the candidate molecule to a panel of human tissue sections. The TCR approach is limited by the performance of the therapeutic as an IHC reagent, which is often suboptimal to outright infeasible.

Regio-Selective Mechanical Enhancement of Polymer-Grafted Nanoparticle Composites via Light-Mediated Crosslinking.

Polymer-brush-grafted nanoparticles (PGNPs) that can be covalently crosslinked post-processing enable the fabrication of mechanically robust and chemically stable polymer nanocomposites with high inorganic filler content. Modifying PGNP brushes to append UV-activated crosslinkers along the polymer chains would permit a modular crosslinking strategy applicable to a diverse range of nanocomposite compositions. Further, light-activated crosslinking reactions enable spatial control of crosslink density to program intentionally inhomogeneous mechanical responses.

A review of clinical applications of pharmacokinetic simulations for a 2-month long-acting injectable formulation of aripiprazole.

Aripiprazole 2-month ready-to-use (Ari 2MRTU) is a long-acting injectable antipsychotic that was approved for use in Europe in March 2024, for the maintenance treatment of schizophrenia in adult patients stabilized with aripiprazole; it is administered via gluteal intramuscular injection once every two months. This review examines population pharmacokinetic model-based simulations relevant to the use of Ari 2MRTU in Europe, accompanied by expert commentary that contextualizes the simulations and highlights the potential implications of the availability of Ari 2MRTU for patients, caregivers, and clinicians. Various simulations conducted across 8 weeks (representing the first dosing interval), or 32 weeks (representing maintenance dosing) demonstrated an aripiprazole exposure profile for Ari 2MRTU that was similar to aripiprazole once-monthly (AOM), but with an extended dosing interval.

Insights into Chemical and Structural Order at Planar Defects in PbMgWO Using Multislice Electron Ptychography.

Switchable order parameters in ferroic materials are essential for functional electronic devices, yet disruptions of the ordering can take the form of planar boundaries or defects that exhibit distinct properties from the bulk, such as electrical (polar) or magnetic (spin) response. Characterizing the structure of these boundaries is challenging due to their confined size and three-dimensional (3D) nature. Here, a chemical antiphase boundary in the highly ordered double perovskite PbMgWO is investigated using multislice electron ptychography.

Characteristics of TSPO expression in marmoset EAE.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target that is highly expressed in MS brain lesions. It is used as an inflammatory biomarker and has been proposed as a therapeutic target.

FGF21 and APOA1 mRNA-based therapies for the treatment of experimental acute pancreatitis.

Background: Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.

New job, new habits? A multilevel interrupted time series analysis of changes in diet, physical activity and sleep among young adults starting work for the first time.

Background: The workplace is an important determinant of health that people are exposed to for the first-time during adolescence or early adulthood. This study investigates how diet, physical activity, and sleep change as people aged 16-30 years transition into work and whether this varies for different individuals and job types.

Methods: Multilevel linear regression models assessed changes in fruit and vegetable intake, sleep duration, and physical activity among 3,302 UK Household Longitudinal Study (UKHLS) participants aged 16-30 years, who started work for the first time between 2015 and 2023.

Developing a clinical prediction model to modify empirical antibiotics for non-typhoidal Salmonella bloodstream infection in children under-five in the Democratic Republic of Congo.

Background: Non-typhoidal Salmonella (NTS) frequently cause bloodstream infection in children under-five in sub-Saharan Africa, particularly in malaria-endemic areas. Due to increasing drug resistance, NTS are often not covered by standard-of-care empirical antibiotics for severe febrile illness. We developed a clinical prediction model to orient the choice of empirical antibiotics (standard-of-care versus alternative antibiotics) for children admitted to hospital in settings with high proportions of drug-resistant NTS.

Activated Cardiac Fibroblasts are a Primary Source High Molecular Weight Hyaluronan Production.

During acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored.

The biodiversity of ice-free Antarctica database.

Antarctica is one of Earth's most untouched, inhospitable, and poorly known regions. Although knowledge of its biodiversity has increased over recent decades, a diverse, wide-ranging, and spatially explicit compilation of the biodiversity that inhabits Antarctica's permanently ice-free areas is unavailable. This absence hinders both Antarctic biodiversity research and the integration of Antarctica in global biodiversity-related studies.

Design and Validation of a High-Fidelity Left Atrial Cardiac Simulator for the Study and Advancement of Left Atrial Appendage Occlusion.

Purpose: Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia that increases the risk of stroke, primarily due to thrombus formation in the left atrial appendage (LAA). Left atrial appendage occlusion (LAAO) devices offer an alternative to oral anticoagulation for stroke prevention. However, the complex and variable anatomy of the LAA presents significant challenges to device design and deployment.

Determinants of frailty among hospitalized older adults across various wards in a tertiary care hospital in Nepal.

Introduction: Frailty, characterized by decreased resilience due to physiological decline, affects approximately 65% of community-dwelling elderly in Nepal. This study assessed frailty and its factors among hospitalized older adults in a tertiary hospital in Nepal.

Methods: This cross-sectional study included 124 participants aged 60 and above, admitted to a tertiary hospital in Nepal.

Machine learning meta-analysis identifies individual characteristics moderating cognitive intervention efficacy for anxiety and depression symptoms.

Cognitive training is a promising intervention for psychological distress; however, its effectiveness has yielded inconsistent outcomes across studies. This research is a pre-registered individual-level meta-analysis to identify factors contributing to cognitive training efficacy for anxiety and depression symptoms. Machine learning methods, alongside traditional statistical approaches, were employed to analyze 22 datasets with 1544 participants who underwent working memory training, attention bias modification, interpretation bias modification, or inhibitory control training.

A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Optimized design and experimental analysis of the vertical mixing plow for enhancing planosol improvement machine.

Improved soil fertility to sustain crop productivity is important to enhance agroecosystem services. To address the low nutrient content, subsoil compaction, and poor root penetration in Planosol, a new machine was designed to improve these conditions. This machine integrates subsoil mixing and fertilizer application.

Developing anti-TDE vaccine for sensitizing cancer cells to treatment and metastasis control.

Tumor-derived exosomes (TDEs) mediate oncogenic communication, which modifies target cells to reinforce a tumor-promoting microenvironment. TDEs support cancer progression by suppressing anti-tumor immune responses, promoting metastasis, and conferring drug resistance. Thus, targeting TDEs could improve the efficacy of anti-cancer treatments and control metastasis.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

Who is American? A comprehensive analysis of the American = White/Foreign = Asian stereotype (2007-2023).

Against the backdrop of increasing ethnic diversity in the U.S., we replicate, extend, and challenge previous examinations of the American = White/Foreign = Asian stereotype in the largest sample to date (N = 666,623 respondents) over 17 years (2007-2023).

Genetic coupling of enhancer activity and connectivity in gene expression control.

Gene enhancers often form long-range contacts with promoters, but it remains unclear if the activity of enhancers and their chromosomal contacts are mediated by the same DNA sequences and recruited factors. Here, we study the effects of expression quantitative trait loci (eQTLs) on enhancer activity and promoter contacts in primary monocytes isolated from 34 male individuals. Using eQTL-Capture Hi-C and a Bayesian approach considering both intra- and inter-individual variation, we initially detect 19 eQTLs associated with enhancer-eGene promoter contacts, most of which also associate with enhancer accessibility and activity.

Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.