Rationale and Design of the Comparative Effectiveness of ICD Versus Non-ICD Therapy in Contemporary Heart Failure Patients at a Low Risk for Arrhythmic Death (CONTEMP-ICD) trial.

Background: Current recommendations for a prophylactic (primary prevention) implantable cardioverter defibrillator (ICD) in patients with both ischemic and non-ischemic heart failure with reduced ejection fraction (HFrEF) originate from clinical trials conducted in selected patients over 20 years ago that showed an overall statistically significant survival benefit associated with a primary prevention ICD in the range of 23%-34%. The recent introduction of angiotensin receptor-neprilysin inhibitors [ARNI] and sodium glucose co-transporter 2 inhibitors [SGLT2i]) was shown to further reduce the risk of sudden cardiac death (SCD) in patients with HFrEF. Thus, there is an unmet need appropriately designed comparative effectiveness clinical trials aimed to reassess the survival benefit of a primary prevention ICD in contemporary patients with HFrEF.

Quantifying Choriocapillaris Flow Deficits in Diabetic Retinopathy Using Projection-Resolved OCT Angiography.

Purpose: To quantify choriocapillaris (CC) flow deficits using projection-resolved optical coherence tomographic angiography (PR-OCTA) and to evaluate whether they are correlated with diabetic retinopathy (DR).

Methods: In this retrospective study, OCTA scans covering a range of DR severities were acquired. Shadowing artifacts caused by hard exudates, large inner retinal vessels, and vitreous floaters were detected, along with the retinal fluid area.

Chronic endometritis and its association with implantation history, BCL6, and ERA in infertility patients.

Purpose: To compare the prevalence of chronic endometritis (CE) in patients with and without a history of implantation failure and to assess whether CE is associated with BCL6 overexpression or a nonreceptive endometrial receptivity analysis (ERA).

Methods: Retrospective cohort study of infertility patients at the University of California, San Francisco (01/2019-12/2024) who underwent evaluation for CE. Endometrial biopsies were performed in the luteal phase.

Individualized Estimation of Baseline Retinal Nerve Fiber Layer Thickness Using Conditional Variational Autoencoder.

Purpose: Use generative deep learning (DL) models to estimate baseline reference nerve fiber layer thickness (NFLT) profiles, taking into account individual ocular characteristics.

Design: A cross-sectional study.

Participants: Six hundred eighty-six individuals from the Hong Kong FAMILY cohort and 75 individuals from the Casey Eye Institute (CEI) cohort.

Single-Cell Profiling Reveals Altered Endometrial Cellular Features Across the Menstrual Cycle in Endometriosis Patients.

Endometriosis is a chronic, estrogen-dependent condition affecting over 190 million women globally, characterized by the ectopic presence of endometrial-like tissue that leads to inflammation, pain, and infertility. Despite its prevalence, the pathogenesis of endometriosis remains poorly understood. Here, we present a comprehensive single-cell transcriptomic atlas comprising 228,000 cells derived from 43 eutopic endometrial biopsies from patients with endometriosis, fibroid controls and healthy controls, sampled across the menstrual cycle.

Nanog overexpression enhances the therapeutic efficacy of ADMSCs in AMI rats via the upregulation of JAK/STAT3 signaling and cyclin-mitochondrial expression.

This study investigated whether Nanog-overexpressing adipose-derived mesenchymal stem cells (Nanog-ADMSCs) are superior to unmodified ADMSCs in improving the left ventricular ejection fraction (LEVF) in acute myocardial infarction (AMI) patients. We utilized silencing and overexpression of Nanog gene in ADMSCs and performed a wound healing assay/transwell migration assay/MTT cell viability assay/left coronary artery ligation for AMI induction. Additionally, we categorized the cells into three classes [i.

Reappraisal of adverse obstetric outcomes independently associated with contemporary fertility treatment practices: a US prospective cohort study.

Background: Obstetric complications linked to assisted reproductive technology could be confounded by underlying parental factors and were often derived from databases not designed to study these complications. With evolving assisted reproductive technology practices, it is unclear to what extent contemporary assisted reproductive technology independently contributes to obstetric risks.

Objective: We aimed to prospectively evaluate obstetric risks associated with contemporary fertility practices, adjusting for parental and assisted reproductive technology parameters.

Structure Modeling Protocols for Protein Multimer and RNA in CASP16 With Enhanced MSAs, Model Ranking, and Deep Learning.

We present the methods and results of our protein complex and RNA structure predictions at CASP16. Our approach integrated multiple state-of-the-art deep learning models with a consensus-based scoring method. To enhance the depth of multiple sequence alignments (MSAs), we employed a large metagenomic sequence database.

What are community perspectives and experiences around GLP-1 receptor agonist medications for weight loss? A cross-sectional survey study in the UK.

Introduction: Obesity is a critical public health challenge globally. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated significant efficacy in weight loss; however, their adoption is influenced by various individual and societal factors. This study sought to examine awareness, motivations and barriers to adoption of GLP-1RAs in the UK, with a focus on demographic differences.

Retinal neurovascular coupling evaluation with circular-scan OCTA.

Neurovascular coupling (NVC) is the mechanism by which neuronal activity regulates blood flow. Detection of abnormalities in NVC may be clinically useful as they could signal early retinal dysfunction before structural damage becomes apparent. While optical coherence tomography angiography (OCTA) enables high-contrast, non-invasive functional imaging of the retina, its conventional form cannot detect light-evoked hemodynamic responses, which are the key indicators of NVC.

Trends in blood-based metabolic and cardiovascular risk profiles in men during treatment for testosterone deficiency: a longitudinal, retrospective cohort study.

Background: Cross-sectional analyses demonstrate associations between lower endogenous testosterone, poorer metabolic health, and cardiovascular risk. However, the longitudinal associations between treating testosterone deficiency (TD) and key markers are unclear.

Aim: To examine 12-month trends in total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), haemoglobin A1c (HbA1c), triglycerides, and triglyceride:HDL ratios during treatment for TD.

Dosimetric evaluation of a novel automated noncoplanar volumetric modulated arc therapy technique for treating optic nerve sheath meningiomas.

Purpose: This study aimed to evaluate the dosimetric outcomes for the target and organs at risk (OARs) in patients with optic nerve sheath meningiomas (ONSMs), comparing HyperArc (HA), a novel automated noncoplanar volumetric modulated arc therapy (VMAT) technique, with two other advanced VMAT techniques.

Methods: Nine patients with ONSMs were re-planned using three radiotherapy techniques: HA employing four preconfigured noncoplanar partial arcs on the Varian TrueBeam, a two-arc coplanar VMAT on the Varian TrueBeam (TB-VMAT), and a two-arc coplanar VMAT on the Varian Halcyon (HAL-VMAT). All treatment plans aimed to deliver 50.

Awareness and prevalence of the symptoms of testosterone deficiency: a cross-sectional survey of community-dwelling men in the UK.

Objectives: Non-specific symptoms of testosterone deficiency (TD) and lack of awareness impact diagnosis and appropriate treatment. This study aimed to characterise the awareness of key symptoms of TD in community-dwelling men and contextualise this against the reported prevalence of these symptoms.

Design: Cross-sectional survey comprising 54 questions (including assessment of symptoms as per the qADAM questionnaire and where relevant, men's experiences while on TD treatment).

Measuring Progress Toward Target Attainment and the Elimination of Health Disparities in Healthy People 2030.

Introduction: The Healthy People initiative provides science-based, 10-year public health objectives and targets for the U.S. population.

A cross-sectional survey of experiences and outcomes of using testosterone replacement therapy in UK men.

Background: Prevalence of late-onset testosterone deficiency (TD) ranges between 6-30% depending on diagnostic criteria. Recent data highlights various benefits of testosterone replacement therapy (TRT), including increased libido, mood, bone mineral density, and lean body mass. This study investigated the personal experiences of men with TD around low testosterone and TRT, including barriers to accessing TRT.

Widefield OCT angiography.

Optical coherence tomography angiography (OCTA) is a volumetric, non-invasive, high-resolution vascular imaging modality capable of acquiring highly detailed visualizations of retinal microvasculature. It has become an important tool for diagnosis and prognosis in prevalent diseases and pathologies such as diabetic retinopathy, retinopathy of prematurity, and vein occlusions, as well as more rare conditions, including inherited retinal dystrophies. It is also useful for measuring treatment response and assessing which patients would benefit from treatment.

Anatomy of the Macular Ganglion Cell Layer Plexus on Projection-Resolved Optical Coherence Tomographic Angiography.

Purpose: The purpose of this study was to characterize the central macular ganglion cell layer plexus (GCLP) boundaries using projection-resolved optical coherence tomographic angiography (PR-OCTA) in healthy eyes.

Methods: Participants were scanned using a commercial OCTA system (Avanti; Optovue/Visionix Inc., Fremont, CA, USA) in a 6 × 6-mm area centered on foveal fixation.

Best practices for clinical trials data harmonization and sharing on NHLBI bioData catalyst (BDC) learned from CONNECTS network COVID-19 studies.

The need for collaborative and transparent sharing of COVID-19 clinical trial and large-scale observational study data to accelerate scientific discovery and inform clinical practice is critical. Responsible data-sharing requires addressing challenges associated with data privacy and confidentiality, data linkage, data quality, variable harmonization, data formats, and comprehensive metadata documentation to produce a high-quality, contextually rich, findable, accessible, interoperable, and reusable (FAIR) dataset. This communication explores the experiences and lessons learned from sharing National Heart Lung and Blood Institute (NHLBI) COVID-19 clinical trial (including adaptive platform trials) and cohort study datasets through the NHLBI BioData Catalyst® (BDC) ecosystem, focusing on the challenges and successes of harmonizing these datasets for broader research use.

Tocilizumab, sarilumab and anakinra in critically ill patients with COVID-19: a randomised, controlled, open-label, adaptive platform trial.

Introduction: Tocilizumab improves outcomes in critically ill patients with COVID-19. Whether other immune-modulator strategies are equally effective or better is unknown.

Methods: We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients.

ZMYND8 Reads H3K36me2 to Activate CEBPE Transcription and Suppress Multiple Myeloma Progression through the Inhibition of Adaptive UPR Pathways.

Multiple myeloma (MM) pathogenesis is closely associated with aberrant epigenetic regulation and resulting modifications, such as dimethylation of lysine 36 in histone H3 (H3K36me2). However, the recognition signature of H3K36me2 and its functional role in MM remain largely unknown. Here, the zinc-finger MYND-type-containing 8 (ZMYND8) is identified as a potential reader of the H3K36me2 mark that suppresses MM progression.

Risk factors and outcomes associated with failed implantable cardioverter-defibrillator shocks.

Background: Implantable cardioverter-defibrillators (ICDs) deliver shocks to terminate ventricular tachycardia/ventricular fibrillation (VT/VF) to reduce the risk of sudden cardiac death. Failure of ICD shocks to terminate VT/VF, even if not resulting in death immediately, may signal patients at high risk of adverse outcomes.

Objective: We sought to identify predictors and outcomes associated with failed appropriate ICD shocks in patients with reduced left ventricular ejection fraction with a primary prevention ICD.

Determinants of post-stroke cognitive impairment in patients with periodontal disease.

Introduction: Periodontal disease (PD) is a risk factor for stroke and cardiovascular disease. The effect of PD on post-stroke cognitive impairment (PSCI) remains underexplored.

Methods: A cross-sectional analysis of the Periodontal tReatment to Eliminate Minority InEquality and Rural disparities in Stroke (PREMIERS) study participants was conducted.

Re-appraising assays on permeabilized blood cancer cells testing venetoclax or other BH3 mimetic agents selectively targeting pro-survival BCL2 proteins.

BH3 mimetic drugs that selectively target the pro-survival BCL2 proteins are highly promising for cancer treatment, most notably for treating blood cancers. Venetoclax, which inhibits BCL2, is now approved for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Preferably, robust and validated assays would identify patients most likely to benefit from therapy with venetoclax itself or with inhibitors of other pro-survival proteins.

Characterization of Directional Reflectance in Corneal Tissue: A Comprehensive Optical Coherence Tomography Analysis.

Purpose: To characterize the directional reflectance properties of the cornea using optical coherence tomography (OCT) imaging and develop a mathematical model describing corneal reflectance as a function of depth and incidence angle across different corneal layers.

Methods: A retrospective analysis was conducted on OCT scans from normal subjects using the Visionix Avanti OCT system (840 nm). Reflectance values for the epithelium, Bowman's layer, stroma, and endothelium/Descemet's membrane were extracted and analyzed as functions of incidence angle and corneal depth.