Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial.

Importance: There is an unmet need for long-term, safe, effective, and hormone-free treatments for menopausal symptoms, including vasomotor symptoms (VMS) and sleep disturbances.

Objective: To evaluate the 52-week efficacy and safety of elinzanetant, a dual neurokinin-targeted therapy, for treating moderate to severe VMS associated with menopause.

Design, Setting, And Participants: OASIS-3 was a double-blind, placebo-controlled, randomized phase 3 clinical trial that was conducted at 83 sites in North America and Europe from August 27, 2021, to February 12, 2024, and included postmenopausal women aged 40 to 65 years who were seeking treatment for moderate to severe VMS (no requirement for a minimum number of VMS events per week).

A novel information theoretic approach reveals loss of effective biomolecular communication in aging muscle cells.

Maintenance of organismal function requires tightly regulated biomolecular communication. However, with aging, communication deteriorates, thereby disrupting effective information flow. Using information theory applied to skeletal muscle single cell RNA-seq data from young, middle-aged, and aged animals, we quantified the loss of communication efficiency over time.

Accounting for endoscopic screening in colorectal cancer risk models.

Background: Colorectal cancer (CRC) risk models routinely adjust for endoscopic screening because of a) possible confounding with other risk factors and b) possible alteration of natural history of the disease due to adenoma detection and removal.

Methods: In this study, we defined a subject as screen-covered (SC) if a colonoscopy was performed in the past 10 years, and not screen-covered (NSC) otherwise. We created CRC risk models separately for SC and NSC subjects (HRSC, HRNSC) and then obtained a screening-coverage adjusted HR estimate (HRfull) based on a weighted average of ln(HRSC) and ln(HRNSC) with weight equal to the proportion of SC person-time in the NHS population.

A Readily Synthesized All-In-One Nanowire Hydrogel: Toward Inhibiting Tumor Recurrence and Postoperative Infection.

Surgical resection remains the frontline intervention for cancer; however, postoperative tumor recurrence and wound infection remain critical unmet challenge in surgical oncology. Herein, an all-in-one nanowired hydrogel (V-Hydrogel) is developed through a facile one-step assembly employing enzyme-mimetic VO nanowires and bactericidal crosslinker THPS. The V-Hydrogel reserves the glutathione peroxidase-, peroxidase-, catalase-, and oxidase-mimetic enzymatic activities derived from vanadium oxide nanowires, thereby exhibiting efficient tumor-specific catalytic therapy.

Longitudinal Multimodal Magnetic Resonance Imaging Reveals Improvement in Verbal Fluency Over Time in Moderate-to-Severe Traumatic Brain Injury.

Most individuals with moderate-to-severe diffuse axonal injury (DAI) have impaired verbal fluency (VF) capacity. Still, the relationship between brain and VF recovery post-DAI has remained mostly unknown. The aim was to assess brain changes in 13 cortical thickness regions of interest (ROIs), fractional anisotropy (FA), and free water (FW) in three language-related tracts; the VF performance at 6 and 12 months after the DAI; and whether brain changes from 3 to 6 months predict VF performance from 6- to 12-month post-DAI.

Generative artificial intelligence for automated data extraction from unstructured medical text.

Objectives: Unstructured data, such as procedure notes, contain valuable medical information that is frequently underutilized due to the labor-intensive nature of data extraction. This study aims to develop a generative artificial intelligence (GenAI) pipeline using an open-source Large Language Model (LLM) with built-in guardrails and a retry mechanism to extract data from unstructured right heart catheterization (RHC) notes while minimizing errors, including hallucinations.

Materials And Methods: A total of 220 RHC notes were randomly selected for pipeline development and 200 for validation from the Pulmonary Vascular Disease Registry.

Associations of cardiovascular health with arterial health in adults free of cardiovascular disease.

Background: In adults without cardiovascular disease (CVD), there is limited understanding of the association between overall cardiovascular health (CVH) and arterial health.

Methods: In 2330 Framingham Heart Study Offspring participants free of CVD (60±9 years; 57% women) with Life's Essential 8 (LE8) and applanation tonometry data (Exam 7), we calculated CVH scores per American Heart Association's LE8 guidelines. Multivariable-adjusted regression analyses examined the relations of LE8 with aortic stiffness and pressure pulsatility [negative inverse carotid-femoral pulse wave velocity (niCFPWV), central pulse pressure (CPP), respectively], and examined effect modification by age and sex.

Associations of adverse childhood experiences with midlife cardiovascular health in women.

Background: Cardiovascular health (CVH) may be influenced by early life factors, such as adverse childhood experiences (ACEs). Prior work suggests social stressors may particularly influence CVH trajectories across the lifecourse in women; however, this relationship remains poorly understood. We used data from a prospective longitudinal cohort study to evaluate associations of ACEs with CVH and its components among midlife women (mean 51.

Hispanic/Latino ethnic background and genetic ancestry in relation to atherosclerotic cardiovascular disease risk estimation: Findings from the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Hispanics/Latinos are a heterogenous population with no validated atherosclerotic cardiovascular disease (ASCVD) risk estimation tool. We examined performance of the pooled cohort equation (PCE) across Hispanic/Latino background groups and quantiles of African, Amerindian, and European genetic ancestry.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) was used to evaluate the performance of the non-Hispanic Black (NHB) and non-Hispanic White (NHW) PCE defined by predicted to observed (P/O) ratios of 10-year ASCVD events.

Association Between Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor Use and All-Cause Mortality in Patients With Pulmonary Arterial Hypertension.

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce mortality in heart failure patients with reduced and preserved ejection fraction. Their potential benefits in pulmonary arterial hypertension (PAH) are unknown. This study evaluates the relationship between SGLT2i use and all-cause mortality in patients with PAH.

Artificial Intelligence and Network Medicine: Path to Precision Medicine.

Over the past two decades, network medicine (NM) has evolved to help define disease mechanisms, identify drug targets, and guide increasingly precise therapies. In recent years, the integration of NM with artificial intelligence (AI), particularly deep learning techniques, has evolved with increasing applications. AI techniques help elucidate complex disease mechanisms and define precise therapies.

In Vitro Evaluation of Amide-Linked Coumarin Scaffolds for the Inhibition of α‑Synuclein and Tau Aggregation.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders characterized by continuous loss of functional neurons. The numbers of AD and PD patients will likely double by 2060 and 2040, reaching 13.9 and 1.

The Role of Lifestyle Interventions for the Prevention and Treatment of Type 2 Diabetes: A Narrative Review.

The incidence of type 2 diabetes (T2D) is increasing globally alongside poor diet quality, sedentary lifestyle, and obesity, outpacing the capacity and resources to effectively prevent and manage its impact. The glycemic benefits of lifestyle modification to prevent T2D and its downstream comorbidities and mortality are supported by numerous epidemiologic studies and randomized trials. However, despite lifestyle modification being the standard of care practice both for prevention and treatment of T2D, there has been limited success in curbing this pandemic, possibly due to environmental and socioeconomic barriers to the uptake and long-term adherence to healthy lifestyle programs.

Reduced circulating regulatory T cells in primary Sjögren's syndrome: the contribution of enhanced apoptosis and impaired survival.

Background: Regulatory T cells (Tregs) are found to be critical for maintaining immune tolerance to self-antigens; however, their status in primary Sjögren's syndrome (pSS) remains unclear. We investigated alterations in the abundance of peripheral Tregs in a large pSS cohort and their implications for patients.

Methods: Levels of CD4+CD25+FOXP3+Treg cells in the peripheral blood of 624 patients with pSS, and 93 healthy controls (HCs) were detected using modified flow cytometry (FCM).

Associations between a novel measure of sleep health and cognitive functioning in middle childhood: a crosssectional Environmental Influences on Child Health Outcomes cohort study.

Study Objectives: Research linking children's sleep to cognitive outcomes is inconsistent and has largely focused on one aspect of sleep, such as duration, rather than measuring multiple dimensions of sleep health. We hypothesized that children's sleep health would be positively associated with inhibitory control and cognitive functioning.

Method: We cross-sectionally assessed 1595 participants (ages 7-11) from the Environmental influences on Child Health Outcomes cohort using the NIH Toolbox Cognition Battery, Environmental influences on Child Health Outcomes Sleep Health of Children and Adolescents questionnaire, and Patient Reported Outcome Measurement Information System Sleep Disturbance/Sleep-related Impairment instruments.

Sleep disordered breathing and circulating non-esterified fatty acids: the cardiovascular health study.

Study Objectives: Circulating non-esterified fatty acids (NEFAs) have been associated with impaired glucose metabolism but their modifiable determinants remain uncertain. We sought to determine the association between objectively-measured sleep disordered breathing (SDB), which is also associated with dysglycemia, and NEFA levels among community-dwelling older adults.

Methods: We analyzed 787 older adults who had total fasting and post-load NEFAs measured in 1996-1997 in the Cardiovascular Health Study and underwent polysomnography between 1995 and 1997 in the Sleep Heart Health Study.

Home-based dim light melatonin onset assessment among adults with obesity: feasibility and procedural considerations.

Study Objectives: Dim light melatonin onset (DLMO) is the best-established marker of central circadian phase and may contribute to unraveling the role of the circadian system in obesity. This study evaluated DLMO among individuals with obesity using a home-based assessment and explored its clinical correlates and procedural variations.

Method: Fifty-eight women (mean [SD] age 40.

False equivalence: differences in the activity of ampicillin-sulbactam and amoxicillin-clavulanate in several Enterobacterales species.

Background And Objectives: The β-lactam/β-lactamase inhibitor combinations ampicillin-sulbactam (SAM) and amoxicillin-clavulanate (AMC) are frequently used to treat Enterobacterales infections and are often assumed to be interchangeable, leading some clinical microbiology laboratories to report antimicrobial susceptibility testing (AST) results for only one of these agents. Given differences in β-lactamase inhibition between sulbactam and clavulanate, we hypothesized that the activities of SAM and AMC may differ.

Methods: To understand the prevalence of discordant SAM and AMC susceptibility results in Enterobacterales species, we analysed AST results obtained by broth microdilution (MicroScan WalkAway, Beckman Coulter) for Enterobacterales isolates recovered from clinical specimens between 2018 and 2022 at an academic medical centre in New York City.

Corrigendum to "The Dietary Biomarkers Development Consortium: An Initiative for Discovery and Validation of Dietary Biomarkers for Precision Nutrition. [Current Developments in Nutrition, Volume 9, Issue 5, May 2025, 107435]".

[This corrects the article DOI: 10.1016/j.cdnut.

Window of opportunity evaluation of blood-brain barrier permeability heterogeneity within and across high-grade glioma patients.

Background: Disruption of the blood-brain barrier (BBB) in high-grade brain tumors is characterized by contrast accumulation on diagnostic imaging. This window of opportunity study correlates contrast imaging features with the tumor distribution of BBB-permeable (levetiracetam) and -impermeable (cefazolin) drugs.

Methods: Patients with a clinical diagnosis of a high-grade brain tumor underwent MRI for surgical planning.