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Prostate cancer is characterized by profound clinical and molecular heterogeneity. While its genomic heterogeneity is well-characterized, its epigenomic heterogeneity remains less understood. We therefore created a compendium of 3,001 multi-ancestry prostate methylomes spanning normal tissue through localized disease of all grades to poly-metastatic disease. A subset of 884 samples had multi-omic DNA and/or RNA characterization. We identify four epigenomic subtypes that risk-stratify patients...

CONCLUSIONS AND RELEVANCE: The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

CONCLUSION: The consensus highlights the potential of auditory-perceptual assessment and acoustic metrics to inform screening for swallowing dysfunction in older adults and offers expert insights for clinical investigators who aim to analyze voice, speech, and/or cough sounds as clinically meaningful indicators of laryngeal function to improve early detection and intervention, thereby enhancing patient outcomes.

Plants respond to environmental cues, such as light and temperature, which regulate their growth and development. In the model plant Arabidopsis (Arabidopsis thaliana), PHYTOCHROME-INTERACTING FACTORS (PIFs) are central regulators of both shade-avoidance and thermomorphogenesis. However, their functional roles in crop species are less well known. Here, we generated a tomato (Solanum lycopersicum) mutant lacking all eight known PIF genes (slpifo), to investigate their roles under controlled and...

PTCHD1 is an X-linked three-exon gene associated with autism spectrum disorder (ASD) and/or intellectual disability (ID). Mice lacking Ptchd1 exon 2 (Ptchd1^(Δexon2)) exhibit hyperactivity and learning impairments, but do not recapitulate ASD-like traits. Through mapping of clinically reported loss-of-function mutations in human patients, we determined that PTCHD1 exon 3 is a high-risk locus. We therefore generated an alternative Ptchd1 knockout mouse model by targeting Ptchd1 exon 3...

While COVID-19 mortality was relatively low in many Sub-Saharan African countries during the first wave of the pandemic, SARS-CoV-2 transmission was extensive. We hypothesized that female sex workers (FSWs) would be at enhanced risk of acquisition of this novel respiratory viral infection, due to intimate contact with multiple sexual partners and solicitation of clients in crowded venues. Here we describe the seroincidence, socio-behavioural associations and clinical outcomes of SARS-CoV-2...

BACKGROUNDLiquid biopsy has emerged as a minimally invasive method for tumor diagnosis, monitoring, and therapeutic guidance. For CNS tumors, cerebrospinal fluid (CSF) provides a reliable and accessible source of tumor-derived cell-free DNA (ctDNA).METHODSThis study evaluates the clinical utility of CSF liquid biopsy in a real-world prospective setting. A total of 148 CSF samples from 120 patients underwent molecular analysis using droplet digital PCR (ddPCR) and/or next-generation sequencing to...

CONCLUSIONS: Machine learning models demonstrated moderate predictive performance for in-hospital mortality in post-cardiotomy cardiogenic shock patients on extracorporeal life support. The random forest model demonstrated moderate discriminative performance, highlighting the relevance of readily available clinical variables. External validation and calibration analysis are required before clinical implementation. The model is best interpreted as a tool for dynamic risk assessment during ECMO...

CONCLUSIONS: ECP demonstrated clinical outcomes comparable to IS in sr/sd-irAEs, with significantly lower cumulative corticosteroid exposure and improved QoL. Furthermore, ECP was associated with a favorable safety profile and showed no evidence of compromised antitumor activity. A multicenter trial is planned for further investigation.

CONCLUSIONS: In this registry cohort, higher-volume centers did not have greater fetal aortic valvuloplasty technical success or fewer complications but did have fewer periprocedural fetal deaths. Fetal gestational age and number of cardiac punctures influenced outcomes, suggesting that unmeasured fetal selection criteria, such as different referral patterns, and technical expertise, indicative of overall center/team experience, may influence fetal survival.

CONCLUSION: Opportunistic GS demonstrated that many individuals harbor GS findings impacting their health, illustrating the potential of GS to inform personalized and proactive health care for Canadians.

The R2TP chaperone complex comprises two AAA+ proteins, RUVBL1 and RUVBL2, along with RPAP3 and PIH1D1. R2TP functions in concert with other chaperones, such as HSP90 and HSP70, to facilitate the assembly of macromolecular complexes integral to the regulation of cell growth and proliferation. Moreover, several adaptors interact with R2TP to impart substrate specificity. Nevertheless, the precise mechanism underlying R2TP-mediated complex assembly remains unknown. This review summarizes the...

Chemical pollution is a global threat to human health, yet the toxicity mechanisms of most contaminants remains unknown. Here, we applied an ultrahigh-throughput affinity selection-mass spectrometry (AS-MS) platform to systematically identify protein targets of prioritized chemical contaminants. After benchmarking the platform, we screened 50 human proteins against 481 prioritized chemicals, including 446 ToxCast chemicals and 35 per- and polyfluoroalkyl substances (PFAS). Among 24,050...

Microplastics are complex contaminants, potentially posing both a physical and chemical risk to aquatic organisms. To better understand the physical and chemical impacts of microplastics, we conducted a large in situ pelagic mesocosm experiment in a freshwater boreal lake at the International Institute for Sustainable Development-Experimental Lakes Area. An equal mixture of polyethylene, polystyrene, and polyethylene terephthalate fragments with and without chemical additives were added to...

Alcoholic hepatitis (AH) is an acute form of alcohol-associated liver disease with very few treatment options. Recent studies highlighted liver metabolic reprogramming in AH as an indicator of severity. We aim at identifying new intervention points to reverse liver metabolic dysregulation across varying degrees of AH. We develop 89 personalized genome-scale metabolic models by integrating a generic human cellular metabolic model with liver transcriptomics data from AH patients with varying...

BACKGROUND: Antibiotic misuse is a key driver of antimicrobial resistance globally, with high rates of inappropriate use observed in rural China. We evaluated the effectiveness of a comprehensive package based on quantified point-of-care testing (POCT) for C-reactive protein and serum amyloid A (CRP&SAA) in reducing inappropriate antibiotic use for acute respiratory infections (ARIs) in village clinics in rural China.

Diagnosing lymphoma traditionally relies on invasive tissue biopsies, which can yield insufficient material for histopathological evaluation and carry a risk of complications. Minimally invasive assessment of cell-free DNA (cfDNA) in plasma offers a promising alternative for lymphoma detection that could aid the rapid evaluation of malignant vs. benign lymphadenopathy. Here, we examine the methylome of plasma samples from 165 lymphoma patients and 47 controls using cell-free methylated DNA...

Fungal pathogens pose an increasing threat to human health. The limited diversity of antifungal drug classes and the rapid emergence of resistance highlight the urgent need for the identification and development of agents with novel mechanisms of action. Here, we identified NPD2560, a coumarin-derived compound, as an antifungal agent that exhibits fungicidal activity against Candida krusei, a clinically challenging non-albicans Candida species often associated with treatment failure....

CONCLUSIONS: These findings enhance our understanding of how early life factors, particularly LTRAU, and genetic factors synergistically affect AR risk, offering valuable insights for prevention and treatment strategies.

CONCLUSION: This study provides the first longitudinal mapping of clinical and neural trajectories in an RCT of EEG-NFB for PTSD, demonstrating early stabilization of response and identifying neural mechanisms associated with symptom improvement. These findings may inform the optimization of EEG-NFB protocols and support its role as an adjunctive, symptom-stabilizing scaffold for psychotherapy.