High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH.

Gonioscopy-Assisted Transluminal Trabeculotomy Outcomes Under Different Levels of Glaucoma Severity: A Multicenter, Comparative Study.

Purpose: To evaluate the outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) under different levels of glaucoma severity.

Design: Retrospective, multicenter, before-and-after study.

Methods: One eye from all primary open-angle glaucoma patients who underwent GATT combined with cataract surgery (Phaco-GATT) or GATT stand-alone with 12 months of follow-up were included and divided according to glaucoma severity (mild = GI, moderate = GII, and advanced = GIII) and the outcomes compared.

Large language models to identify social determinants of health in electronic health records.

Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information.

Design of New Dispersants Using Machine Learning and Visual Analytics.

Artificial intelligence (AI) is an emerging technology that is revolutionizing the discovery of new materials. One key application of AI is virtual screening of chemical libraries, which enables the accelerated discovery of materials with desired properties. In this study, we developed computational models to predict the dispersancy efficiency of oil and lubricant additives, a critical property in their design that can be estimated through a quantity named blotter spot.

Regulation of Expression of Cannabinoid CB and Serotonin 5HT Receptor Complexes by Cannabinoids in Animal Models of Hypoxia and in Oxygen/Glucose-Deprived Neurons.

Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB and serotonin 5HT receptors included. These two receptors may interact to form heteromers (CB-5HT-Hets) that are also a target of CBD.

Apixaban and Dalteparin for the Treatment of Venous Thromboembolism in Patients with Different Sites of Cancer.

Efficacy and safety of anticoagulant treatment for venous thromboembolism (VTE) may vary in patients with different cancer sites. We evaluated the rates of VTE recurrence and major bleeding and the relative efficacy and safety of 6-month treatment with oral apixaban or subcutaneous dalteparin in patients with different cancer sites randomized in the Caravaggio study. Primary cancer was located at gastrointestinal sites in 375 patients (32.

International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer.

Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data.

Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens.

Energy Dissipation in Resynchronization Therapy: Impact of Atrioventricular Delay.

Background: Optimal atrioventricular delay (AVD) achieves maximum cardiac output in patients undergoing cardiac resynchronization therapy (CRT). Nonoptimal AVD decreases left ventricular (LV) end-diastolic volume and causes loss of flow momentum prior to LV ejection.

Objective: We investigated the potential role of energy dissipation (ED) in these changes in cardiac output through the study of intraventricular flow.

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals.

Mitral-Aortic Flow Reversal in Cardiac Resynchronization Therapy: Coupling With Ejection and Impact of Variations in Atrioventricular Delay.

Background: Flow entering the left ventricle is reversed toward the outflow tract through rotating reversal flow around the mitral valve. This was thought to facilitate early ejection, but had not been proved to date. We hypothesized that perfect coupling between reversal and ejection flow would occur at optimal atrioventricular delay (AVD), contributing to its hemodynamic superiority, and evaluated its applicability for AVD optimization.

KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.

A Cysteine-Rich Protein Kinase Associates with a Membrane Immune Complex and the Cysteine Residues Are Required for Cell Death.

Membrane-localized proteins perceive and respond to biotic and abiotic stresses. We performed quantitative proteomics on plasma membrane-enriched samples from Arabidopsis (Arabidopsis thaliana) treated with bacterial flagellin. We identified multiple receptor-like protein kinases changing in abundance, including cysteine (Cys)-rich receptor-like kinases (CRKs) that are up-regulated upon the perception of flagellin.

Cardiovascular Risk in Women With Premature Ovarian Insufficiency Compared to Premenopausal Women at Middle Age.

Context: A young age at menopause has been associated with increased cardiovascular disease (CVD) risk.

Objective: To compare the cardiovascular risk profile between women with premature ovarian insufficiency (POI) and premenopausal controls of comparable age.

Design: Cross-sectional case control study.

Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features.

Study Question: Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities?

Summary Answer: Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition.

What Is Known Already: Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women.

A role for site-specific phosphorylation of mouse progesterone receptor at serine 191 in vivo.

Progesterone receptors (PRs) are phosphorylated on multiple sites, and a variety of roles for phosphorylation have been suggested by cell-based studies. Previous studies using PR-null mice have shown that PR plays an important role in female fertility, regulation of uterine growth, the uterine decidualization response, and proliferation as well as ductal side-branching and alveologenesis in the mammary gland. To study the role of PR phosphorylation in vivo, a mouse was engineered with homozygous replacement of PR with a PR serine-to-alanine mutation at amino acid 191.

Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies.