Epigenetic variation in light of population genetic practice.

The evolutionary impact of epigenetic variation depends on its transgenerational stability and source - whether genetically determined, environmentally induced, or due to spontaneous, genotype-independent mutations. Here, we evaluate current approaches for investigating an independent role of epigenetics in evolution, pinpointing methodological challenges. We further identify opportunities arising from integrating epigenetic data with population genetic analyses in natural populations.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Integration of Conventional and Virtual Reality Approaches in Augmented Reality for Theory-Based Psychoeducational Intervention Design for Chronic Low Back Pain: Scoping Review.

Background: Psychoeducation positively influences the psychological components of chronic low back pain (CLBP) in conventional treatments. The digitalization of health care has led to the discussion of virtual reality (VR) interventions. However, CLBP treatments in VR have some limitations due to full immersion.

Lactylation fuels nucleotide biosynthesis and facilitates deuterium metabolic imaging of tumor proliferation in H3K27M-mutant gliomas.

Unlabelled: Oncogenes hyperactive lactate production, but the mechanisms by which lactate facilitates tumor growth are unclear. Here, we demonstrate that lactate is essential for nucleotide biosynthesis in pediatric diffuse midline gliomas (DMGs). The oncogenic histone H3K27M mutation upregulates phosphoglycerate kinase 1 (PGK1) and drives lactate production from [U- C]-glucose in DMGs.

Combined endurance and resistance exercise training in heart failure with preserved ejection fraction: a randomized controlled trial.

Endurance exercise training (ET) is an effective treatment in heart failure with preserved ejection fraction (HFpEF), but the efficacy of resistance training in this patient population has been only scarcely evaluated. In this multicenter, randomized trial, we evaluated the effects of combined endurance and resistance training over 12 months in patients with HFpEF. The primary endpoint was a modified Packer score, including all-cause mortality, hospitalizations classified as potentially related to heart failure or exercise and changes in peak oxygen consumption ( ), diastolic function (E/e'), New York Heart Association (NYHA) class and global self-assessment (GSA).

Long-term persistence of glycemic dysregulation in patients with a history of pheochromocytoma/paraganglioma.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

A foundation model for generalized brain MRI analysis.

Artificial intelligence (AI) applied to brain magnetic resonance imaging (MRI) has the potential to improve disease diagnosis and management but requires algorithms with generalizable knowledge that can perform well in a variety of clinical scenarios. The field has been constrained, thus far, by limited training data and task-specific models that do not generalize well across patient populations and medical tasks. Foundation models, by leveraging self-supervised learning, pretraining, and targeted adaptation, present a promising paradigm to overcome these limitations.

Vasoactive Agents in Burn Patients - Perspectives on Angiotensin-II.

Severe burn injury poses significant clinical challenges, often necessitating the use of vasoactive agents to maintain perfusion. This narrative review explores the current landscape of vasoactive agents in acute burn shock resuscitation and severe burn-injured patients who develop septic shock, with a particular focus on the potential role of the novel vasoactive agent, synthetic angiotensin-II (AT-II), in these settings. While catecholamines and vasopressin remain cornerstone therapies, adverse effects, variable patient response, and a new understanding of burn injury pathophysiology highlight the potentially evolving role of vasoactive agents in these clinical scenarios.

Sexual selection promotes reproductive isolation in barn swallows.

Despite the well-known effects of sexual selection on phenotypes, links between this evolutionary process and reproductive isolation, genomic divergence, and speciation have been difficult to establish. We unravel the genetic basis of sexually selected plumage traits to investigate their effects on reproductive isolation in barn swallows. The genetic architecture of sexual traits is characterized by 12 loci on two autosomes and the Z chromosome.

Reduced fitness of secondary females in a polygynous species: a 32-yr study of Savannah sparrows.

The evolution of mating systems reflects a balance of the often-conflicting interests of males and females. Polygyny, a mating system in which males have multiple mates, presents a fitness benefit to males, but the consequences for females are less clear. Females with polygynous social mates may suffer reduced fitness, especially secondary females who typically receive less male support.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

The perspective during gestural executions alters hemispherical specialization.

Introduction: The left hemisphere may be particularly specialized for gestures from an egocentric movement perspective, i.e., when executing tool-use pantomime (TUP) gestures.

Omnigene-Gut ensures fecal microbiome stability in the pediatric population.

Increasing evidence exists that the gut microbiome influences toxicity as well as outcomes in a variety of cancers. To investigate the role of the gut microbiome in pediatric neuro-oncology, microbiome analysis has been included in multiple prospective pediatric neuro-oncology clinical trials (NCT05009992, NCT04732065, NCT04775485). In these trials, the OMNIgene-GUT preservation tubes are used for the collection of the feces.

Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions.

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors.

Real-world therapy and persistence of patients with neovascular age-related macular degeneration and diabetic retinopathy or diabetic macular edema: a German claims data analysis.

Purpose: Vascular endothelial growth factor (VEGF) inhibition is the current and high-volume standard-of-care for patients with neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) with diabetic macular edema (DME). This study assessed the impact of non-persistence in anti-VEGF treatment using claims data from two German states.

Methods: This study identified adults with nAMD or DR/DME and incident anti-VEGF treatment (= index) in January 2015-June 2019 using the German AOK PLUS claims database (January 2014-June 2021, ~ 3.

Improved tracking of corneal immune cell dynamics using confocal microscopy.

confocal microscopy (IVCM) is a widely used technique for imaging the cornea of the eye with a confocal scanning light ophthalmoscope. Cellular resolution and high contrast are achieved without invasive procedures, suiting the study of living humans. However, acquiring useful image data can be challenging due to the incessant motion of the eye, such that images are typically limited by noise and a restricted field of view.

A Single-Cell Interrogation System from Scratch: Microfluidics and Deep Learning.

Live-cell imaging using fluorescence microscopy enables researchers to study cellular processes in unprecedented detail. These techniques are becoming increasingly popular among microbiologists. The emergence of microfluidics and deep learning has significantly increased the amount of quantitative data that can be extracted from such experiments.

Haplotype-resolved genome and population genomics of the threatened garden dormouse in Europe.

Genomic resources are important for evaluating genetic diversity and supporting conservation efforts. The garden dormouse () is a small rodent that has experienced one of the most severe modern population declines in Europe. We present a high-quality haplotype-resolved reference genome for the garden dormouse, and combine comprehensive short and long-read transcriptomics data sets with homology-based methods to generate a highly complete gene annotation.