Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial.

Background: People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack.

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Geographical variation in the long-arm of childhood.

Scholars have documented the lasting impact of childhood socioeconomic status (SES) on health, but few studies have considered how state contexts in childhood shape health trajectories based on childhood SES across the life course. The current project uses data from the Panel Study of Income Dynamics, 2009-2021 (N = 18,227 person-year observations of adults aged 18-41) to build on these studies by 1) examining state variation in the relationship between childhood SES and adult self-rated health, and 2) assessing the contributions of childhood state-level economic context in moderating this relationship. Logistic regression models first confirmed the expected relationship between childhood SES and adult self-rated health that parallels other literature (OR = 1.

Prolonged length of stay among individuals presenting to the emergency department with psychosis: Associations with sociodemographic and visit-level characteristics.

Introduction: Individuals experiencing psychosis commonly initiate and engage in treatment within an emergency department (ED) setting. Understanding factors contributing to adverse ED experiences is critical for improving psychosis-related treatment. Prolonged ED length of stay (LOS), which can be conversely associated with treatment quality, is not well explored among individuals experiencing psychosis.

Isolated subsegmental pulmonary embolism identification based on international classification of diseases (ICD)-10 codes and imaging reports.

Background: Isolated subsegmental pulmonary embolism (issPE) is a commonly encountered diagnosis. Although the International Classification of Diseases (ICD)-10 codes are used for research, their validity for identifying issPE is unknown. Moreover, issPE diagnosis is challenging, and the findings from radiology reports may conflict with those from expert radiologists.

Cross-Sectional Study Gender Pay Gap in Industry General Payments to U.S. General and Fellowship-Trained Surgeons.

Introduction: Gender disparities exist in nonresearch industry payments to U.S. physicians, but detailed analyses specific to surgeons are limited.

A Comparative Study Between Cold Static Storage and Normothermic Ex-Situ Donor Heart Preservation in a Rat Model of Heterotopic Heart Transplantation.

Introduction: Cold static storage (CSS) and normothermic ex-situ preservation are the most widely used donor heart preservation techniques worldwide. The current study compares both CSS and normothermic ex-situ preservation methods in terms of graft performance, morphologic changes, and acute immune response in an experimental model.

Method And Materials: Twenty rats underwent heterotopic abdominal heart transplantation after 2 h of CSS (group 1; n = 10) or normothermic ex-situ perfusion (group 2; n = 10).

The Anatomy of Gossip: Dissecting Dynamics and Impacts in Surgical Residency.

Background: Gossip, defined by social scientists as "evaluative talk about an absent third party," is anecdotally pervasive yet poorly understood in surgical residency programs. Gossip is known to have both positive and negative impacts. This study sought to deconstruct the role of gossip in surgical residency and evaluate its impact through the lens of surgical residents.

Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade.

Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout.

Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations.

Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo.

Management of renal cell carcinoma with ablation in comparison to nephrectomy: A 5-year analysis of inpatient procedural data to evaluate utilization disparities in the United States.

Purpose: To perform a nationwide analysis of ablation compared to partial and total nephrectomy for the management of renal cell carcinoma (RCC) to evaluate utilization trends and disparities in the USA.

Materials And Methods: The 2016-2020 National Inpatient Sample was analyzed. Using ICD-10, we identified the diagnosis of RCC then analyzed the utilization trends of ablation and nephrectomies (both partial and complete).

Racial and ethnic disparities in post-acute care service utilization after stroke.

Evidence examining disparities in post-acute care (PAC) utilization among various racial and ethnic groups after stroke and the influence of social determinants of health (SDOH) in these decisions is lacking. Thus, we searched the literature from January 2000 to November 2023 regarding PAC among individuals after stroke through: 1) Pubmed, 2) Scopus, 3) Web of Science, 4) Embase, and 5) CINAHL. We found 14 studies.

Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

Infection rate following mandibular distraction with internal and external devices in infants.

Background: Internal and external devices may be utilized in mandibular distraction osteogenesis (MDO) for the correction of symptomatic micrognathia in infants and children.

Purpose: To compare the rate and severity of infection between internal and external MDO devices.

Study Design, Setting, Sample: Retrospective cohort study utilizing an institutional database of patients who underwent MDO.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for assessing and visualizing cell microaggregate formation in whole blood by imaging flow cytometry.

Blood cell aggregates are clinically useful biomarkers in a number of medical disorders. This protocol provides accurate and quantitative analysis of cell aggregates using a small volume of whole blood and imaging flow cytometry. We describe steps for sample collection, staining, and measurement.

Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the Prevention of Recurrent Clostridioides difficile Infection in Participants With Inflammatory Bowel Disease in PUNCH CD3-OLS.

Background: Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD.

Goals as Motives: Implications for Theory, Methods, and Practice.

The concept of human goals is central to the study of psychology (i.e., motivation, behavior, and well-being), sociology (i.

The contribution of cognitive disengagement syndrome symptoms to depressive symptoms among pediatric brain tumor survivors.

Objective: Pediatric brain tumor survivors (PBTS) are at risk for neurocognitive late effects that can resemble symptoms of cognitive disengagement syndrome (CDS). In the current study, we compared the CDS symptoms of PBTS to those of healthy comparison classmates (CC) and examined whether CDS might explain group differences in depressive symptoms. We also explored whether CDS symptoms were associated with engagement-based coping strategies and stress responses, thereby testing one mechanism by which CDS could lead to affective difficulties.

Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.

Background: Sepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1.

Extreme heat risk and the potential implications for the scheduling of football matches at the 2026 FIFA World Cup.

Climate change is making extreme heat events more frequent and intense. This negatively impacts many aspects of society, including organised sport. As the world's most watched sporting event, the FIFA World Cup commands particular attention around the threat of extreme heat.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.