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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.

CONCLUSION: By identifying these gaps, this review offers a foundation for developing frameworks that support systematic DEI integration across the GenAI lifecycle, from innovation development and implementation through to evaluation, and informs future research directions by calling for multi-perspective collaboration and institutional accountability in how GenAI is monitored and evaluated. This scoping review represents an important first step upon which future efforts can build to advance the...

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Joint models for longitudinal and event-time data can be used to understand the co-development of multiple correlated non-fatal outcomes, such as those encountered when studying diabetic microvascular complications. However, such models were not developed for event-times characterized by a multistate process where the entry time into certain states is interval-censored, which is an important feature of interval cohort study designs. Our aim was to develop a joint model for this setting....

Researchers are increasingly interested in identifying different parts of the genome which work together to influence a phenotypic trait. A major objective in bioinformatics involves finding groups of variables determined from omics technologies such as DNA methylation sites, transcriptome profiling, etc. Given one set of variables, one could determine how variables within work together to influence an outcome. These groups of variables are called functional modules and previous work has...

Many patients with chronic myeloid leukemia (CML) treated with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) experience persistent adverse events (AEs) that negatively impact daily living and the ability to remain on treatment. Asciminib, an allosteric inhibitor of BCR::ABL1, was designed to enhance efficacy and reduce off-target effects vs ATPcompetitive TKIs. The phase 3 randomized ASC4FIRST trial established the overall favorable safety profile of asciminib in...

Osmotic stressors impair tissue expansion and slow crop development, which can ultimately reduce yield. The mechanisms through which dividing and differentiating cells perceive, integrate, and respond to stress are not well understood. To explore this knowledge gap, we assessed Asian rice (Oryza sativa) seedling responses to drought and salinity stress by performing single-nucleus transcriptome analyses on developing leaves and by assaying ion distribution using ICP-MS and CoroNa Green staining....

Relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) remains a leading cause of cancer-related death in children and young adults. While CD19-directed chimeric antigen receptor T cell (CAR-T) therapy offers promise, high rates of long-term failure underscore the need to understand resistance mechanisms. Our studies found p53 inactivation promotes CAR-T resistance in human pre-B-ALL cell lines. Through genome-wide CRISPR/Cas9 screening of CAR-sensitive TP53-wildtype and CAR-resistant...

Accurate representation of plant photosynthesis in terrestrial biosphere models (TBMs) is critical for reliable carbon-cycle simulations. Most TBMs employ the Farquhar-von Caemmerer-Berry (FvCB) model, which uses an empirical representation of electron transport that limits the simulation of gross primary productivity (GPP) and solar-induced chlorophyll fluorescence (SIF) under variable conditions. Here, we present BEPS-CB6F, an improved model that incorporates the mechanistic cytochrome b(6)f...

To advance the computational simulation of cellular life, we propose a virtual yeast, an artificial intelligence (AI)-driven agent that models eukaryotic cellular behaviours by integrating multimodal biological data, mechanistic reasoning and active experimentation using Saccharomyces cerevisiae as a genetically tractable and data-rich model system. Cellular complexity is decomposed into eight function-centred modules, spanning genetic, metabolic and structural systems, each realized as a...

CONCLUSIONS: The framework facilitates benchmarking and expert assessment of AI-driven auto-segmentation tools, addressing the need for transparency and reproducibility in this domain. Through its emphasis on clinical acceptability, our framework fosters the integration of AI models into clinical environments, specifically within radiation therapy.

Undifferentiated pleomorphic sarcoma (UPS) is one of the most common adult soft tissue sarcomas (STS), yet therapeutic progress remains limited due to the absence of recurrent oncogenic driver mutations. To identify tumor suppressors contributing to UPS pathogenesis, we performed a customized in vivo CRISPR/Cas9 screen in mice. This approach identified BRCA1-associated protein 1 (BAP1) as a potent tumor suppressor in STS. Integrative analyses using RNA sequencing, multiplex immunohistochemistry,...

Family physicians are well-positioned to support both persons living with dementia (PLWD) and their caregivers. However, current electronic medical record (EMR) systems do not capture the relational and interdependent nature of dementia care. Dyadic data, linking the records of persons living with dementia (PLWD) and their caregivers, could support more integrated, proactive, and personalized care. While there is growing interest in leveraging EMRs for this purpose, few systems enable routine...