Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Efficacy, safety, and quality of life of dabrafenib plus trametinib treatment in Chinese patients with mutation-positive metastatic non-small cell lung cancer.

Background: Dabrafenib plus trametinib (Dab + Tram) is an approved targeted therapy in patients with mutated metastatic non-small cell lung cancer (NSCLC). Here, we report the efficacy, safety, and quality of life (QoL) results of Dab + Tram treatment in Chinese patients with mutation-positive metastatic NSCLC.

Methods: This is a single-arm, open-label, multicentre, phase II study (NCT04452877).

Extended Rhythm Monitoring to Assess for Ventricular Arrhythmias After Transcatheter Pulmonary Valve Replacement With the Harmony Valve.

Background: Varying rates of nonsustained ventricular tachycardia (NSVT) have been reported early after transcatheter pulmonary valve replacement (TPVR) with the Harmony valve, but data regarding rhythm outcomes beyond hospital discharge are limited. This study aims to characterize ventricular arrhythmias after Harmony TPVR from implant through mid-term follow-up.

Methods: Ventricular arrhythmia data from postimplant telemetry and follow-up extended rhythm monitoring (ERM) were analyzed after Harmony TPVR.

Systematic review and meta-analysis of the impact of the refreezing and rebiopsy embryos on reproductive outcomes in patients undergoing freeze-thaw embryo transfer.

Objective: To explore whether refreezing and rebiopsy affect reproductive outcomes.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Prognostic Value of Coronary CT Angiography-Derived Quantitative Flow Ratio in Suspected Coronary Artery Disease.

Background The prognostic value of coronary CT angiography (CTA)-derived quantitative flow ratio (CT-QFR) remains unknown. Purpose To determine the prognostic value of CT-QFR in predicting the long-term outcomes of patients with suspected coronary artery disease (CAD) in comparison with invasive coronary angiography (ICA)/SPECT and to determine the influence of prior percutaneous coronary intervention (PCI) on the prognostic value of CT-QFR. Materials and Methods In this secondary analysis of the prospective international CORE320 study, 379 participants who underwent coronary CTA and SPECT within 60 days before ICA between November 2009 and July 2011 were included for follow-up.

Blood Pressure Predicted From Artificial Intelligence Analysis of Retinal Images Correlates With Future Cardiovascular Events.

Background: High systolic blood pressure (SBP) is one of the leading modifiable risk factors for premature cardiovascular death. The retinal vasculature exhibits well-documented adaptations to high SBP and these vascular changes are known to correlate with atherosclerotic cardiovascular disease (ASCVD) events.

Objectives: The purpose of this study was to determine whether using artificial intelligence (AI) to predict an individual's SBP from retinal images would more accurately correlate with future ASCVD events compared to measured SBP.

Feasibility and safety of endomyocardial biopsy by lumenless pacing lead sheath-directed method during cardiac implantable electronic device implantation.

Background: Patients with an indication for a cardiovascular implantable electronic device (CIED) are complicated with special cardiomyopathy or other unspecified cardiac abnormalities and may need endomyocardial biopsy (EMB). However, EMB by a bioptome is usually avoided to reduce the risk of lead displacement in the CIED periprocedural period.

Objective: We aimed to assess the safety and feasibility of a novel approach for transvenous right ventricular (RV) EMB using the lead sheath method (L-S-M) during CIED implantation and compared it with the traditional bioptome method (T-B-M).

Immunogenicity and cross-protective efficacy induced by delayed attenuated with regulated length of lipopolysaccharide in mice.

Non-typhoidal (NTS) is a major global foodborne pathogen that poses a major public health concern worldwide, and no vaccines are available for protecting against infection of multiple serotypes, therefore, the development of vaccines to provide broad protection is valuable. In this work, we aimed to regulate lipopolysaccharide (LPS) synthesis of live for exposing conserved protein antigens on the outer membrane while maintaining smooth LPS patterns to keep their original ability to invade host cells for inducing cross-protection against infection of multiple serotypes. We generated a series of mutants defective in genes to affect the length of LPS.

Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets.

Macrophage LRRK2 hyperactivity impairs autophagy and induces Paneth cell dysfunction.

polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson's disease and Crohn's disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinson's disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction is a precursor to gut inflammation in CD.

Salt-Responsive Gut Microbiota Induces Sex-Specific Blood Pressure Changes.

Background: Tryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota.

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Risk of Stroke or Systemic Embolism According to Baseline Frequency and Duration of Subclinical Atrial Fibrillation: Insights From the ARTESiA Trial.

Background: In the ARTESiA trial (Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation), apixaban, compared with aspirin, reduced stroke or systemic embolism in patients with device-detected subclinical atrial fibrillation (SCAF). Clinical guidelines recommend considering SCAF episode duration when deciding whether to prescribe oral anticoagulation for this population.

Methods: We performed a retrospective cohort study in ARTESiA.

Does participation in sports competitions enhance interprofessional teamwork among medical students? Evidence from a medical school curriculum experiment.

Background: Effective interprofessional teamwork is essential for the efficiency, safety and quality of healthcare system services and requires interprofessional education for medical students. Physical education is a simple and easy way to teach teamwork, which translates into team performance in the work environment. This study was conducted to examine the effectiveness of the physical education competition model, instead of the exams model, for improving teamwork skills among medical students.

Multi-omics characterization of type 2 diabetes associated genetic variation.

Discerning the mechanisms driving type 2 diabetes (T2D) pathophysiology from genome-wide association studies (GWAS) remains a challenge. To this end, we integrated omics information from 16 multi-tissue and multi-ancestry expression, protein, and metabolite quantitative trait loci (QTL) studies and 46 multi-ancestry GWAS for T2D-related traits with the largest, most ancestrally diverse T2D GWAS to date. Of the 1,289 T2D GWAS index variants, 716 (56%) demonstrated strong evidence of colocalization with a molecular or T2D-related trait, implicating 657 -effector genes, 1,691 distal-effector genes, 731 metabolites, and 43 T2D-related traits.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

A foundation model for clinical-grade computational pathology and rare cancers detection.

The analysis of histopathology images with artificial intelligence aims to enable clinical decision support systems and precision medicine. The success of such applications depends on the ability to model the diverse patterns observed in pathology images. To this end, we present Virchow, the largest foundation model for computational pathology to date.

Lead Tolerance and Remediation Potential of Four Species in Lead-Contaminated Soil.

plants are low-growing shrubby bamboos with growth advantages, such as high biomass and strong resistance, and they are rich in germplasm resources in southern China. This study conducted soil lead (Pb) stress experiments on (Keng) McClure (LA), B.M.

Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions.

Impact of Topical 0.05% Cyclosporine A Eye Drops on Post-Femtosecond-Assisted Laser In Situ Keratomileusis Ocular Surface Recovery: A Randomized Clinical Trial.

Objectives: To investigate the effect of topical 0.05% cyclosporine A (CsA) eye drops as an adjunct to conventional therapy in maintaining post-femtosecond-assisted laser in situ keratomileusis (FS-LASIK) ocular surface stability.

Methods: Sixty-six patients (eyes) undergoing FS-LASIK were randomized into 2 groups: 33 patients (eyes) in group I (conventional treatment group) and 33 patients (eyes) in group II (CsA group).