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Primary open-angle glaucoma (POAG) is a leading cause of blindness, yet the biochemical mechanisms underlying disease progression remain poorly understood. This study characterized aqueous humor (AH) across early and advanced stages of POAG using large-scale proteomics. AH samples were collected from patients with mild POAG, advanced POAG, and non-glaucomatous controls in this prospective cross-sectional study. Profiling of 8000 proteins was performed using an antibody array. Hierarchical...

CONCLUSIONS: These findings highlight the modest impact of sex on the cancer proteome, but the very limited power of existing proteomics cohorts for these analyses.

BACKGROUND: Engaging knowledge users, including patient partners and health-system partners, in embedded health services research is increasingly recognized as essential for strengthening the relevance of research and improving the quality and equity of health services and is foundational to the success of team science. Existing engagement frameworks, however, often capture experiences at single time points and do not fully reflect relational dimensions over time such as trust, reciprocity,...

Cellular processes are controlled by interconnected networks of protein-protein interactions that can be dynamically regulated by post-translational modifications such as phosphorylation. Dysregulation of signaling pathways can drive cellular transformation and contribute to cancer treatment resistance. Mass spectrometry (MS)-based approaches have emerged as key technologies to study both protein function and their dynamic regulation at a network level. Modern proteomics allows investigators to...

We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (viral transcriptional regulators [vTRs]) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale profiling of vTR binding, chromatin accessibility alterations, and gene expression impact reveals extensive EBV functional interactions with the human genome,...

Comprehensive exams are a standard component of doctoral-level training programs in epidemiology. In this manuscript, we describe current practices in the administration of comprehensive examinations across doctoral programs in epidemiology and discuss variation in the content, format, and structure of these exams. We present results from a survey about the comprehensive exam process at thirty-three different epidemiology programs. We also discuss a symposium focused on comprehensive exams that...

Amyloid beta (Aβ) oligomers are key mediators of synaptic dysfunction and neural circuit impairment in Alzheimer's disease (AD). While plasma Aβ oligomerization propensity (OAβ) correlates with cerebral amyloid pathology and cognitive decline, the systemic modulators of OAβ remain poorly understood. In this study, we identified the albumin interactome (albumin and its associated proteins) as a critical regulator of OAβ. Selective depletion of the albumin interactome from plasma eliminated the...

CONCLUSIONS: The CANMAT/ICOCS 2025 OCD International Guidelines synthesize the evidence on the efficacy, safety, and tolerability of the range of interventions available for the management of OCD. It is anticipated that these new OCD guidelines will enable psychiatrists and other clinicians to provide systematic, evidence-based care for their patients with OCD across the lifespan.

The biogenesis of multipass membrane proteins challenges the endoplasmic reticulum (ER) quality control, particularly when transmembrane segments contain polar or charged residues required for function. Fks1, the catalytic subunit of yeast β-(1,3)-glucan synthase, exemplifies this challenge because its large multipass transmembrane architecture must support glucan synthesis at the plasma membrane while also undergoing efficient biogenesis in the ER. Here, we investigate the cellular role of PBR1...

Advancements in plant genome sequencing and assembly have enabled the production of increasingly accurate and contiguous genome sequences. Here, we present the chromosome-level assembly of the durum wheat (Triticum turgidum L. ssp. durum, cv. Svevo) reference genome produced using accurate long-reads, optical mapping and Hi-C. The new assembly (Svevo Rel.2.0) comprises 263 hybrid scaffolds with an N50 value of 112.3 Mb, arranged into 14 contiguous pseudomolecules spanning 10.4 Gb. The Svevo...

Critical Dialogues for Action (CDFA) is a structured, equity-centered methodology designed to transform dialogue into systemic change in health professions education and health systems. Developed over five years, it integrates lived expertise, structured facilitation, and implementation science into the dialogue process. CDFA operates through three levels: Foundational Elements, Process and Engagement, and Action and Impact. These levels establish conditions to foster connection, disrupt power...

Administrative workload, the work required to understand systems and complete tasks and associated with navigating complex care for families, is an underrecognized yet powerful driver of inequity in pediatric hospital care. We present the case of Mateo, a 7-year-old child with medical complexity admitted with respiratory distress whose hospitalization and subsequent readmission were shaped not by caregiver disengagement but by the cumulative effects of fragmented systems, language barriers, and...

CONCLUSIONS: This work provides a platform for extending genome engineering in induced pluripotent stem cells to multiplexed assays of variant effects across diverse disease-relevant cellular phenotypes, enhancing our understanding of variant pathogenicity and uncovering novel biological mechanisms that could inform therapeutic strategies.

Evolutionary habitat transitions are known to drive rapid evolution. In fishes, switches between marine and freshwater can promote adaptation in sensory systems; in particular, the disparate visual environments in these aquatic habitats can lead to evolution at all levels of the visual system. We investigate the evolution of dim light-sensitive rhodopsin genes within the sculpin (Cottoidea), a species-rich group of fishes occupying diverse benthic habitats. Two main families include...

Quantum simulation is central to understanding and designing quantum systems across physics and chemistry. However, its practical use is often limited by the exponential growth of Hilbert space and by the increasing complexity of modern quantum-simulation software. Here we introduce{\cinzel El Agente Cuántico}, a multi-agent AI system that automates quantum-simulation workflows by translating natural-language scientific intent into executed and validated computations across heterogeneous...

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated skin disorder of childhood, caused by the exfoliative toxins ETA and ETB released by Staphylococcus aureus. We report on a 4-year-old boy who presented with a 5-day history of painful, progressive blistering of the face, trunk and anogenital region. Clinical examination revealed widespread erythema with coarse lamellar desquamation, flaccid blisters and a positive Nikolsky sign; the mucous membranes were spared, an important...

CONCLUSIONS: Alcohol consumption, including at what may be perceived as "moderate" levels, is associated with increased mortality and morbidity risks. These results support tightening alcohol use guidance in the United States, for both males and females, to no more than 1 drink per day.

Chromosome instability is highly prevalent in cancer and drives large-scale chromosomal imbalances, known as aneuploidies^(1-4). How aneuploidy contributes to tumorigenesis remains difficult to study due to the vast numbers of genes affected. Here we established a CRISPR knockout- and activation-linked assay (CRISPR-KOALA), enabling high-throughput bidirectional genetic screens in immunocompetent mouse models of cancer. We developed a compendium of the ten most frequent human...

Diffuse intrinsic pontine glioma (DIPG) is a dismal pediatric brainstem tumor with a median survival of approximately 12 months and no curative treatments. ONC201, the most clinically characterized small-molecule, selectively activates human caseinolytic protease P (hClpP). Guided by X-ray structure of the hClpP:ONC201 complex, piperazine-based derivatives were designed and identified compound 26 (DA29) as a lead. Structural studies confirmed its binding to the enzyme hydrophobic allosteric...

CONCLUSIONS: This data release advances the global effort to build comprehensive and accessible biodiversity genomic resources for the research community.