Leveraging Large Language Models in Extracting Drug Safety Information from Prescription Drug Labels.

Introduction: Adverse drug reactions (ADRs), including those resulting from drug interactions, remain a leading cause of morbidity and mortality. Structured product labels (SPLs) serve as a primary source for drug safety information. Having machine-readable product labels, including adverse reactions (ARs) and drug interactions, readily available would allow researchers to streamline medication safety studies.

Protocol optimization improves the performance of multiplexed RNA imaging.

Spatial transcriptomics has emerged as a powerful tool to define the cellular structure of diverse tissues. One such method is multiplexed error robust fluorescence in situ hybridization (MERFISH). MERFISH identifies RNAs with error tolerant optical barcodes generated through sequential rounds of single-molecule fluorescence in situ hybridization (smFISH).

Clonal Hematopoiesis and Risk of New-Onset Myocarditis and Pericarditis.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related clonal expansion of hematopoietic stem cells with leukemia-associated mutations. Certain CHIP mutations promote atherosclerosis and heart failure through immune-related pathways.

Objective: To test whether CHIP is associated with the development of myocarditis and pericarditis.

Sialyl-T Antigen: A Novel Red Blood Cell Determinant for Plasmodium falciparum Invasion.

Malaria continues to pose significant health challenges globally despite advances in control measures. Plasmodium falciparum, the parasite responsible for most severe malaria cases, uses multiple redundant invasion pathways to enter the red blood cell (RBC) during the blood stage of infection. Through a combination of RNA interference screening in erythroid cells and validation by CRISPR/Cas9-mediated knockout in primary human hematopoietic stem cells, we identified the glycosyltransferase Core 1 Synthase Glycoprotein-N-Acetylgalactosamine 3-Beta-Galactosyltransferase 1 (C1GALT1) as a novel host determinant for P.

Faithful inheritance: Parental histone recycling and epigenetic memory in fission yeast.

Accurate transmission of chromatin states during DNA replication is central to epigenetic inheritance. Recent advances have illuminated mechanisms by which parental histones, which carry key post-translational modifications, are recycled and redistributed to daughter strands. This review synthesizes emerging insights into the molecular machinery that mediates histone recycling during replication.

IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk.

Human genetics supports a causal involvement of IL-6 signaling in atherosclerotic cardiovascular disease, prompting the clinical development of anti-IL-6 therapies. Genetic evidence has historically focused on IL6R missense variants, but emerging cardiovascular treatments target IL-6, not its receptor, questioning the translatability of genetic findings. Here we develop a genetic instrument for IL-6 signaling downregulation comprising IL6 locus variants that mimic the effects of the anti-IL-6 antibody ziltivekimab and use it to predict the effects of IL-6 inhibition on cardiometabolic and safety endpoints.

Quantifying the impact of immortal time bias: empirical evidence from meta-analyses.

ObjectivesImmortal time bias (ITB) occurs when a period during which, by design, participants cannot experience the outcome (like death) is incorrectly included in the treatment group's follow-up, artificially making the treatment look better than it truly is. We aimed to identify a systematic sample of cases of ITB in the literature of studies using survival analysis and assess the impact of ITB on the results.DesignMeta-epidemiological study (PROSPERO[CRD42022356073]).

Targeting cancer metabolism: Therapeutic potential of the fatty acid synthase (FASN) inhibitors.

Metabolic rewiring is a hallmark of cancer, enabling tumor cells to proliferate rapidly and survive under adverse conditions. Fatty acid synthase (FASN), a key enzyme in de novo lipogenesis, is significantly upregulated in various cancers and is associated with poor prognosis and increased tumor aggressiveness. This review examines the crucial role of FASN in cancer metabolism and evaluates the therapeutic potential of FASN inhibitors.

Phenome-wide association study of male and female sex chromosome trisomies in 1.5 million participants of MVP, FinnGen, and UK Biobank.

Sex chromosome trisomies (SCTs) are the most common whole-chromosome aneuploidy in humans. Yet, our understanding of the prevalence and associated health outcomes is largely driven by observational studies of clinically diagnosed individuals, resulting in a disproportionate focus on 47,XXY and associated hypogonadism. We analyzed microarray intensity data of sex chromosomes for 1.

Computer vision detects covert voluntary facial movements in unresponsive brain injury patients.

Background: Many brain injury patients who appear unresponsive retain subtle, purposeful motor behaviors, signaling capacity for recovery. We hypothesized that low-amplitude movements precede larger-amplitude voluntary movements detectable by clinicians after acute brain injury. To test this hypothesis, we developed a novel, as far as we are aware, computer vision-based tool (SeeMe) that detects and quantifies low-amplitude facial movements in response to auditory commands.

MutationAssessor in cBioPortal.

MutationAssessor (MA) helps researchers evaluate the likely functional impact of somatic and germline mutations in cancer. It provides an evolution-based functional impact score (FIS) to classify mutations based on their likely effect on protein function. FIS scores are based on analysis of patterns of conservation in protein families (conserved residues) and subfamilies (specificity residues).

Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.

Background: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

Methods: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

Results: We replicated the well-known association at the locus (lead single-nucleotide polymorphism [SNP]: rs147144681,  = 1.

Association of the HDL lipidome with HDL traits before and after exercise training: HERITAGE family study.

Introduction: HDL particle functionality is influenced by its structure, including lipid composition. However, the effects of exercise training on the HDL lipidome and its relationship with HDL-related traits are largely unknown.

Objective: To investigate the HDL lipidome of 154 adults before and after 20 weeks of endurance exercise training in the HERITAGE Family Study.

Revisiting an old therapy for new, promising combinations: biology and perspectives of lomustine in glioma treatment.

The alkylating agents temozolomide (TMZ) and lomustine (CCNU) are the most effective systemic agents for malignant gliomas. However, resistance - whether intrinsic or acquired - inevitably develops in all patients, and these tumors remain incurable. Although CCNU has demonstrated clinical benefit, its clinical use has been relatively limited due to a less favorable safety profile compared to TMZ.

The Continuum of Prevention and Heart Failure in Cardiovascular Medicine: A Joint Scientific Statement from the Heart Failure Society of America and The American Society for Preventive Cardiology.

Heart disease is the leading cause of death worldwide, with heart failure (HF) recognized as its most severe and debilitating manifestation. Though remarkable advancements have led to the establishment of life-saving and quality-of-life-enhancing medical and device-based therapies for HF, HF-related mortality trends have increased over the past decade. To combat this worldwide epidemic, care must evolve so that preventative recommendations are not siloed from HF management.

Ageing, immune fitness and cancer.

The immune system undergoes substantial changes throughout life, with ageing broadly impacting immune cell composition, function and regenerative capacity. Emerging evidence suggests that age-associated changes in immune fitness - the ability to respond to and eliminate infection, pathogens and malignancy while maintaining self-tolerance - reshape antitumour immunity and influence the efficacy of immunotherapies. Technological advances in high-dimensional immunoprofiling have begun to reveal the complex interplay between ageing, immune fitness and cancer biology, uncovering new therapeutic vulnerabilities and challenges.

Engraftment and persistence of base-edited hematopoietic stem cells in nonhuman primates.

Sickle cell disease (SCD) is caused by a single nucleotide change in the β-globin gene that adenine base editors can convert to the nonpathogenic Makassar β-globin variant. Here, we evaluated the long-term efficiency and off-target editing potential of autologous Makassar base editing in three rhesus macaques as a step toward human translation. Base editing of CD34CD90 hematopoietic stem cells (HSCs) at the Makassar locus reached greater than 60% efficiency using a bystander nucleotide as a proxy for the sickle cell target in cells from healthy macaques.

Plasma Metabolome, Long-term Body Weight Change, and Type 2 Diabetes in U.S. Individuals.

Objective: Body weight influences the blood metabolome, but whether specific plasma metabolomic profiles predict long-term weight change remains unclear. We aimed to investigate associations among plasma metabolites, current weight, weight change trajectories, and incident type 2 diabetes (T2D) in adults.

Research Design And Methods: We profiled 260 plasma metabolites in 7,499 U.

Molecular organization of the New World arenavirus spike glycoprotein complex.

Of the multiple arenaviruses that cause haemorrhagic fevers in the Americas, all lack reliable therapeutic options, and only one has a vaccine. The arenavirus glycoprotein complex (GPC) binds cellular receptors and mediates pH-dependent fusion of viral and host cell membranes during entry. GPC comprises GP1, GP2 and stable signal peptide (SSP) subunits.

Implementing a context-augmented large language model to guide precision cancer medicine.

The rapid expansion of molecularly informed therapies in oncology, coupled with evolving regulatory FDA approvals, poses a challenge for oncologists seeking to integrate precision cancer medicine into patient care. Large Language Models (LLMs) have demonstrated potential for clinical applications, but their reliance on general knowledge limits their ability to provide up-to-date and niche treatment recommendations. To address this challenge, we developed a RAG-LLM workflow augmented with Molecular Oncology Almanac (MOAlmanac), a curated precision oncology knowledge resource, and evaluated this approach relative to alternative frameworks (i.

Deep-learning triage of 3D pathology datasets for comprehensive and efficient pathologist assessments.

Standard-of-care slide-based 2D histopathology severely undersamples spatially heterogeneous tissue specimens, with each thin 2D section representing <1% of the entire tissue volume (in the case of a biopsy). Recent advances in non-destructive 3D pathology, such as open-top light-sheet microscopy (OTLS), enable comprehensive high-resolution imaging of large clinical specimens. While fully automated computational analyses of such 3D pathology datasets are being explored, a potential low-risk route for accelerated clinical adoption would be to continue to rely upon pathologists to provide final diagnoses.

Adrenergic signaling coordinates distant and local responses to amputation in axolotl.

Many species regenerate lost body parts following amputation. Most limb regeneration research has focused on the immediate injury site. Meanwhile, body-wide injury responses remain largely unexplored but may be critical for regeneration.

An image-based transcriptomics atlas reveals the regional and microbiota-dependent molecular, cellular, and spatial structure of the murine gut.

The gastrointestinal environment is home to a massive diversity of diet-, host-, and microbiota-derived small molecules, collectively sensed by a remarkable variety of cells. To explore the cellular and spatial organization of sensation, we used MERFISH to profile receptor expression across 2.1 million cells in multiple regions of the murine gut under specific-pathogen-free (SPF) and germ-free (GF) conditions.