Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

Gestational gigantomastia with pseudoangiomatous stromal hyperplasia - a case report of rare entities.

Gestational gigantomastia (GG) is a rare and severe clinical complication of pregnancy. It is characterized by dramatic and uncontrolled growth of the breasts, often leading to physical discomfort, psychological distress and significant surgical complications. Its pathophysiology is poorly understood; management options include conservative pharmacological and surgical interventions.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

INCREASED CITRULLINATED HISTONE H3 LEVELS AND ACCELERATED THROMBIN KINETICS IN TRAUMA PATIENTS WHO DEVELOP VENOUS THROMBOEMBOLISM.

Background: Neutrophil extracellular traps (NETs), and its formation and release, known as NETosis, may play a role in the initiation of thrombin generation (TG) in trauma. The objective of this study was to assess whether trauma patients, who develop symptomatic venous thromboembolism (VTE), have increased levels of plasma citrullinated histone H3 (CitH3) and accelerated TG kinetics.

Methods: Patients presenting to a Level I Trauma Center as trauma activations had samples collected within 12 hours of time of injury (TOI), alongside healthy volunteers (HV).

Recent methane surges reveal heightened emissions from tropical inundated areas.

Record breaking atmospheric methane growth rates were observed in 2020 and 2021 (15.2±0.5 and 17.

New tools to monitor infection and biofilms in .

Introduction: Antimicrobial resistance is a growing health problem. Pseudomonas aeruginosa is a pathogen of major concern because of its multidrug resistance and global threat, especially in health-care settings. The pathogenesis and drug resistance of depends on its ability to form biofilms, making infections chronic and untreatable as the biofilm protects against antibiotics and host immunity.

Longitudinal associations between air pollution and incident dementia as mediated by MRI-measured brain volumes in the UK Biobank.

Background: Although there is increasing evidence that environmental exposures are associated with the risk of neurodegenerative conditions, there is still limited mechanistic evidence evaluating potential mediators in human populations.

Methods: UK Biobank is a large long-term study of 500,000 adults enrolled from 2006 to 2010 age 40-69 years. ICD-10 classified reports of dementia cases up to 2022 (Alzheimer's disease, vascular dementia, dementia in other classified diseases, and unspecified dementia) were identified from health record linkage.

Correction: Determining cost and placement decisions for moderate complexity NAATs for tuberculosis drug susceptibility testing.

[This corrects the article DOI: 10.1371/journal.pone.

Sentinel lymph node biopsy for early stage vulvar squamous cell carcinoma.

Background: Patients with regional lymph node involvement from squamous cell carcinoma (SCC) of the vulva have a 48% 5-year relative survival. Recently, sentinel lymph node (SLN) biopsy has become a viable alternative to inguinofemoral lymphadenectomy. We sought to identify risk factors for predicting a positive SLN in patients with vulvar SCC.

Non-ionotropic NMDAR signalling activates Panx1 to induce P2X4R-dependent long-term depression in the hippocampus.

In recent years, evidence supporting non-ionotropic signalling by the NMDA receptor (niNMDAR) has emerged, including roles in long-term depression (LTD). Here, we investigated whether niNMDAR-pannexin-1 (Panx1) contributes to LTD at the CA3-CA1 hippocampal synapse. Using whole-cell, patch clamp electrophysiology in rat hippocampal slices, we show that a low-frequency stimulation (3 Hz) of the Schaffer collaterals produces LTD that is blocked by continuous but not transient application of the NMDAR competitive antagonist, MK-801.

Morbidity associated with schistosomiasis in adult population of Chókwè district, Mozambique.

Background: Mozambique is one of the countries with the highest prevalence of schistosomiasis, although there is little data on the prevalence of disease and associated morbidity in the adult population. This study aimed to describe and characterize the morbidity associated with schistosomiasis in the adult population of Chókwè district and to explore the use of anamnestic questionnaires and urine dipsticks, as well as point-of-care ultrasound for urinary related findings, to better characterize disease prevalence and morbidity.

Methodology: Between April and October 2018, we conducted a cross-sectional study embedded within the Chókwè Health Research and Training Centre.

The impact of natural climate variability on the global distribution of Aedes aegypti: a mathematical modelling study.

Background: Aedes aegypti spread pathogens affecting humans, including dengue, Zika, and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution of Ae aegypti and therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (eg, atmosphere-land and atmosphere-ocean interactions), determines climate outcomes.

NRF2 activation in the heart induces glucose metabolic reprogramming and reduces cardiac dysfunction via upregulation of the pentose phosphate pathway.

Aims: The transcription factor NRF2 is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances resistance of mouse hearts to chronic hemodynamic overload at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear.

Taking theory of mind research into much needed new terrain - a commentary on Kochanska et al. (2025).

Contemporary research on developing theory of mind emphasizes its cognitive and neurobiological foundations, but studies of its relational origins have potential for opening new terrain in this expansive literature. The study by Kochanska and colleagues shows this in several ways. First, it offers a model for constructing theoretically guided causal models built on longitudinal research enlisting multiple predictors of developing theory of mind that can be examined in concert.

Individualized Coordination and Empowerment for Care Partners of Persons with Dementia (ICECaP): Feasibility and acceptability.

Background: Informal care partners (CPs) of persons with dementia (PWDs), who are at risk of negative health outcomes, benefit from psychosocial interventions. Individualized Coordination and Empowerment for CPs of PWDs (ICECaP) is a year-long, multi-component intervention comprised of in-person and telehealth psychoeducation and emotional support from dementia care coordinators (DCCs). ICECaP feasibility and acceptability were examined during a pilot randomized controlled trial.

Intraoperative Tranexamic Acid in Radical Cystectomy: Impact on Bleeding, Thromboembolism, and Survival Outcomes.

Purpose: Perioperative blood transfusion has been reported in > 50% of patients undergoing radical cystectomy (RC). Unfortunately, perioperative blood transfusion (PBT) in patients undergoing RC has been associated with poor oncological outcomes. Tranexamic acid (TXA) use has been proposed to decrease the need for PBT.

Glucose measurements in sheep using a long-term continuous glucose monitor designed for humans.

This study evaluated the feasibility of utilizing a continuous glucose monitors (CGM) designed for use in humans to measure glucose levels in sheep. Four Suffolk x Dorset sheep were fitted with jugular catheters and FreeStyle Libre 2 (Abbott®) glucose monitors. Glucose concentration from the CGM were compared with those from a glucometer and traditional assays during a hyperglycemic clamp, aiming to explore a broader range of physiological glucose concentrations in a controlled manner.