Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.

Background: TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.

Triglyceride-independent associations between circulating levels of apolipoprotein C-III and biomarkers of inflammation.

Backgrounds And Aims: Preclinical studies suggest that a triglyceride (TG)-independent proinflammatory action of apolipoprotein C-III (apoCIII) exists. We aimed to investigate the relationship between circulating apoCIII levels and subclinical inflammation markers across different cohorts with distinctive inflammatory patterns: patients with metabolic disorders (MDs), patients with rheumatoid arthritis (RA), and controls. Specifically, we assessed the associations of apoCIII with acute inflammation biomarkers (e.

A systematic realist synthesis of digital interventions for enhancing mental health at work: contexts, mechanisms, and outcomes.

Background: Digital interventions (DIs) have emerged as promising tools for promoting mental health in the workplace. However, evidence on if, how, and under what circumstances they affect positive outcomes requires elucidation. This systematic realist review aimed to synthesize current knowledge on contexts, mechanisms, and outcomes of workplace DIs to enhance mental health at work.

Insights into Treponema pallidum genomics from modern and ancient genomes using a novel mapping strategy.

Background: Treponemal diseases are a significant global health risk, presenting challenges to public health and severe consequences to individuals if left untreated. Despite numerous genomic studies on Treponema pallidum and the known possible biases introduced by the choice of the reference genome used for mapping, few investigations have addressed how these biases affect phylogenetic and evolutionary analysis of these bacteria. In this study, we ascertain the importance of selecting an appropriate genomic reference on phylogenetic and evolutionary analyses of T.

Hybrid natural language processing tool for semantic annotation of medical texts in Spanish.

Background: Natural language processing (NLP) enables the extraction of information embedded within unstructured texts, such as clinical case reports and trial eligibility criteria. By identifying relevant medical concepts, NLP facilitates the generation of structured and actionable data, supporting complex tasks like cohort identification and the analysis of clinical records. To accomplish those tasks, we introduce a deep learning-based and lexicon-based named entity recognition (NER) tool for texts in Spanish.

Profiling the epigenome using long-read sequencing.

The advent of single-molecule, long-read sequencing (LRS) technologies by Oxford Nanopore Technologies and Pacific Biosciences has revolutionized genomics, transcriptomics and, more recently, epigenomics research. These technologies offer distinct advantages, including the direct detection of methylated DNA and simultaneous assessment of DNA sequences spanning multiple kilobases along with their modifications at the single-molecule level. This has enabled the development of new assays for analyzing chromatin states and made it possible to integrate data for DNA methylation, chromatin accessibility, transcription factor binding and histone modifications, thereby facilitating comprehensive epigenomic profiling.

Decreased impulsiveness and MEG normalization after AI-digital therapy in ADHD children: a RCT.

Attention-deficit/hyperactivity disorder (ADHD) presents with symptoms like impulsiveness, inattention, and hyperactivity, often affecting children's academic and social functioning. Non-pharmacological interventions, such as digital cognitive therapy, are emerging as complementary treatments for ADHD. The randomized controlled trial explored the impact of an AI-driven digital cognitive program on impulsiveness, inattentiveness, and neurophysiological markers in 41 children aged 8-12 with ADHD.

Control optimization of air traffic emissions in a two-variable dynamic model.

Since 1999, every report released by the International Panel on Climate Change has advocated a decrease in the greenhouse gas emissions associated with aviation in order to preserve the current climate. This study used a two variable differential equations model with a non-linear control term to address several aspects of the emissions stabilization issue. By optimizing the control term parameter, several management alternatives can be obtained based on the properties of the phase plane of the model solutions, as identified by a stability analysis.

One-quarter of freshwater fauna threatened with extinction.

Freshwater ecosystems are highly biodiverse and important for livelihoods and economic development, but are under substantial stress. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods are used to guide environmental policy and conservation prioritization, whereas recent proposals for target setting in freshwaters use abiotic factors.

Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Site-saturation mutagenesis of 500 human protein domains.

Missense variants that change the amino acid sequences of proteins cause one-third of human genetic diseases. Tens of millions of missense variants exist in the current human population, and the vast majority of these have unknown functional consequences. Here we present a large-scale experimental analysis of human missense variants across many different proteins.

Molecular and cellular dynamics of the developing human neocortex.

The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence.

Experimental data on aerosols exhaled into the environment from different wind musical instruments.

Brass bands that include wind instruments are heavily affected by rules established during the pandemic. The aim of this experimental work was to assess the aerosols emitted through different wind instruments. The Aerodynamic Particle Sizer (APS) was used to measure the aerosols emitted and transmit those characteristics to a database.

Impact of obesity on iron metabolism and the effect of intravenous iron supplementation in obese patients with absolute iron deficiency.

Obesity and iron deficiency (ID) are widespread health issues, with subclinical inflammation in obesity potentially contributing to ID through unclear mechanisms. The aim of the present work was to elucidate how obesity-associated inflammation disturb iron metabolism and to investigate the effect of intravenous (IV) iron supplementation on absolute iron deficient pre-obese (BMI 25.0-29.

Uncertainty maps for model-based global climate classification systems.

Climate classification systems (CCSs) are emerging as essential tools in climate change science for mitigation and adaptation. However, their limitations are often misunderstood by non-specialists. This situation is especially acute when the CCSs are derived from Global Climate Model outputs (GCMs).

Pan-inhibition of super-enhancer-driven oncogenic transcription by next-generation synthetic ecteinascidins yields potent anti-cancer activity.

The plasticity of cancer cells facilitates their ability to adopt heterogeneous differentiation states, posing a significant challenge to therapeutic interventions. Specific gene expression programs, driven in part by super-enhancers (SEs), underlie cancer cell states. Here we successfully inhibit SE-driven transcription in phenotypically distinct metastatic melanoma cells using next-generation synthetic ecteinascidins.

High-Throughput Effect-Directed Analysis of Androgenic Compounds in Hospital Wastewater: Identifying Effect Drivers through Non-Target Screening Supported by Toxicity Prediction.

The increasing number of contaminants released into the environment necessitates innovative strategies for their detection and identification, particularly in complex environmental matrices like hospital wastewater. Hospital effluents contain both natural and synthetic hormones that might significantly contribute to endocrine disruption in aquatic ecosystems. In this study, HT-EDA has been implemented to identify the main effect-drivers (testosterone, androsterone and norgestrel) from hospital effluent using microplate fractionation, the AR-CALUX bioassay and an efficient data processing workflow.

Small variant benchmark from a complete assembly of X and Y chromosomes.

The sex chromosomes contain complex, important genes impacting medical phenotypes, but differ from the autosomes in their ploidy and large repetitive regions. To enable technology developers along with research and clinical laboratories to evaluate variant detection on male sex chromosomes X and Y, we create a small variant benchmark set with 111,725 variants for the Genome in a Bottle HG002 reference material. We develop an active evaluation approach to demonstrate the benchmark set reliably identifies errors in challenging genomic regions and across short and long read callsets.

Systematic review of computational techniques, dataset utilization, and feature extraction in electrocardiographic imaging.

This study aimed to analyze computational techniques in ECG imaging (ECGI) reconstruction, focusing on dataset identification, problem-solving, and feature extraction. We employed a PRISMA approach to review studies from Scopus and Web of Science, applying Cochrane principles to assess risk of bias. The selection was limited to English peer-reviewed papers published from 2010 to 2023, excluding studies that lacked computational technique descriptions.

Diagnosing Helicobacter pylori using autoencoders and limited annotations through anomalous staining patterns in IHC whole slide images.

Purpose: This work addresses the detection of Helicobacter pylori (H. pylori) in histological images with immunohistochemical staining. This analysis is a time-demanding task, currently done by an expert pathologist that visually inspects the samples.

The effects of nickel tungstate nanoparticles (NiWO NPs) on freshwater microalga Raphidocelis subcapitata (Chlorophyceae).

Among the vast array of functional nanoparticles (NPs) under development, nickel tungstate (NiWO) has gained prominence due to its potential applications as a catalyst, sensor, and in the development of supercapacitors. Consequently, new studies on the environmental impact of this material must be conducted to establish a regulatory framework for its management. This work aims to assess the effects of NiWO (NPs) on multiple endpoints (e.

Germ cell tumors in children.

Pediatric germ cell tumors represent a rare but biologically diverse group of neoplasms arising from pluripotent primordial germ cells. The 2022 edition of the WHO Classification of Pediatric Tumors introduced the first organ independent classification of germ cell tumors, reflecting advances in molecular biology, histopathology, and clinical practice. This review highlights the key changes, including the refined distinctions between the different subtypes.

Early life factors and later metabolic syndrome in European children and adolescents.

Background And Aims: Early life factors have been suggested to be associated with later cardiometabolic risk in children, adolescents and adults. Our study aimed to investigate the associations between early life factors and metabolic syndrome (MetS) in children and adolescents.

Methods And Results: Our analysis sample comprised of 8852 children aged 2-9 years at baseline that participated in up to three examination waves of the pan-European IDEFICS/I.