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.

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.

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.

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.

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).

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.

Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study.

Introduction: The prognostic value of PAM50 intrinsic subtypes (IS), cell cycle, and immune-related gene expression in HR+ /HER2- advanced breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) in a first-line metastatic setting is unclear. This study evaluates these biomarkers in metastatic biopsies from patients diagnosed with HR+ /HER2- advanced BC.

Methods: CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals.

Benefit and Harms of Radical Nephroureterectomy as Part of a Multimodal Treatment Strategy for Upper Tract Urothelial Carcinoma Patients Presenting with Clinical Evidence of Regional Lymph Node Metastasis: A Systematic Review and Meta-analysis by the European Association of Urology Guidelines.

Background And Objective: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate.

Dry eye disease and morphological changes in the anterior chamber in people with cystic fibrosis.

Background: Cystic fibrosis (CF) is caused by variants in a gene that encodes a protein essential for water and ion transport in the epithelial cells of exocrine organs. Given the possible relationship of this protein and conjunctival and corneal epithelium, the aim of this study was to evaluate ophthalmologic alterations in people with CF.

Methods: Forty-five people with CF underwent pulmonary evaluation including inflammatory score (IS).

Monitoring of the Local Extracellular Environment Using Chiral Gold Nanoparticles.

In three-dimensional (3D)-printed tissue models, sensitive, noninvasive techniques are required to detect changes in hydrogel structure caused by cellular remodeling. We demonstrate herein that circular dichroism (CD) spectroscopy provides a reliable method for detecting hydrogel structural variations. We probe directly the plasmonic optical activity of chiral gold nanorods (c-AuNRs) embedded within the hydrogel matrix, in response to variations in the local environment.

Assessing the influence of recurrent urinary tract infections on sexual function: a case-control study.

Background: Urinary tract infections (UTIs) significantly impact quality of life and can also lead to changes in sexual function.

Aim: This study aims to assess the symptoms associated with recurrent urinary tract infections (rUTIs) and their influence on both quality of life and sexual activity.

Methods: A case-control study was conducted, involving 383 patients with rUTIs and 161 healthy controls.

Harmonization of alcohol use data and mortality across a multi-national HIV cohort collaboration.

Background: Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi-cohort collaborations, such as studies of people with HIV (PWH).

Methods: Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration.

Bioavailability study of OTA, ZEN, and AFB1 along with bioactive compounds from tiger nut beverage and its by-products.

Mycotoxins pose significant health risks due to their prevalence in food products and severe health implications, including carcinogenicity. This study investigates the bioavailability of mycotoxins aflatoxin B1 (AFB1), ochratoxin A (OTA), and zearalenone (ZEN) individually and combined, in the presence of identified polyphenols from tiger nut beverage (TNB) and tiger nut by-product (TNBP) using the in vitro model Caco-2 cells, which simulates the human intestinal barrier. The objective is to understand how bioactive compounds from TNBP can mitigate the effects of AFB1, OTA and ZEN (and their combination) by bioavailability interference, contributing to safer food products and innovative food safety strategies.

Bench scale Layer-by-Layer microencapasulation of Lactiplantibacillus plantarum WCFS1.

Layer-by-Layer (LbL) self-assembly encapsulation is a promising technology for the protection and delivery of lactic acid bacteria. However, laboratory-scale encapsulation is often time-consuming, involves intensive protocols tailored for small-scale operations, requires substantial amounts of energy and water, and results in a low yield of encapsulated biomass. Scaling-up this process to a bench-bioreactor scale is not simply a matter of increasing culture volume as different key parameters (not particularly relevant at lab scale) become critical, including biomass production, the number of polymer layers, and the biomass-to-polymer mass ratio.