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In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.

A protein biomarker, the NOTCH3 extracellular domain, identifies individuals with idiopathic pulmonary hypertension, correlates with disease progression, improves mortality risk prediction and provides a readily implementable, noninvasive blood test for this disease.

In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo.

A deep learning-based model, developed using the rich, multimodal data available from polysomnography-derived sleep recordings, performs well on common sleep analysis tasks and predicts future disease risk across a range of diseases.

Sexual arousal in women comprises two components: genital arousal and subjective arousal. For some women, genital arousal enhances subjective arousal; for others, the two types of arousal are desynchronous. In this Review, Meston and Stanton describe the mechanisms and the relationship between genital and subjective arousal and consider how they assist in diagnosis and treatment of sexual arousal dysfunction and development of treatments for female sexual arousal dysfunction.

In a multicenter, randomized trial of patients with heart failure with preserved ejection fraction and recent decompensation, treatment with volenrelaxin, a long-acting form of human relaxin, was associated with worsening congestion across multiple endpoints as compared to placebo.

Atherosclerosis promotes clonal hematopoiesis by spurring the proliferation of hematopoietic stem cells, which in turn fuels further atherosclerosis and elevates the risk of heart disease.

To address an evidence gap for the efficacy of hypertension therapy using dual drug combinations in patients of South Asian origin, a randomized clinical trial conducted in India found that three types of dual drug combinations, each administered in a single pill, had similarly large effects on reducing blood pressure.

When tested in a multiethnic cohort of ~2.5 million US veterans, the PREVENT equations, recently developed by the American Heart Association for sex-specific and race-free prediction of cardiovascular disease risk, were shown to accurately estimate this risk with some variability across race and ethnicity groups and to outperform the previously used pooled cohort equation risk score.

A wearable device improves the collection and analysis of sweat for the diagnosis of cystic fibrosis.

An artificial intelligence-enabled drug screen finds small molecules that can correct dysfunctional gene networks in aortic valve disease.

In individuals with long-term cardiac symptoms after an initially mild course of COVID-19 illness, magnetic resonance imaging and measurement of cardiac injury biomarkers commonly detected ongoing cardiac inflammation but not structural heart disease.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

In a cluster-randomized trial conducted across 70 medical centers in six countries, a 16-week structured educational program for healthcare providers improved adherence to guidelines for rhythm control but not for stroke prevention in individuals with atrial fibrillation.

Proteomic analysis of paired cerebrospinal fluid and plasma samples from 2,171 individuals drawn from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium, reveals age-related changes in the ratios of proteins in the cerebrospinal fluid and plasma that are associated with cognitive function, enhancing understanding of blood–brain barrier dynamics in aging.

While fluid restriction is typically recommended for patients with chronic heart failure, this randomized clinical trial showed no difference in health status, as assessed by patient-reported outcomes, between patients recommended to a liberal versus a restrictive fluid regimen over the course of 3 months in an outpatient setting.

In a mechanistic analysis of the SUMMIT trial that tested tirzepatide in patients with heart failure with preserved ejection fraction and obesity, treatment with this dual glucagon-like peptide-1 receptor and gastric inhibitory polypeptide agonist, as compared with placebo, reduced blood pressure and estimated circulatory volume–pressure overload, reduced systemic inflammation and mitigated cardiovascular and kidney injury.

This systematic review and meta-analysis provides an updated assessment of the efficacy and safety of intravenous iron therapy in patients with heart failure and iron deficiency, incorporating the results of the newly conducted FAIF-HF2 trial.

Epigenetic editing of PCSK9 in the liver, designed to induce DNA methylation and silence gene expression, achieved long-lasting reductions in LDL cholesterol levels in both transgenic mice expressing the human PCSK9 gene and cynomolgus monkeys.

In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

In a large-scale analysis of ambulatory electrocardiographic recordings, a deep learning algorithm had a substantially higher sensitivity for the detection of critical arrhythmias as compared to technicians, opening a path toward artificial intelligence-assisted direct-to-physician reporting of ambulatory electrocardiography results.

From an analysis of participants in lipid-lowering trials for primary and secondary prevention of coronary artery disease, a polygenic risk score comprising 35 single nucleotide variants with predicted effects on endothelial cell function identified patients who benefited most from aggressive lipid-lowering therapy.

Islands of inversions are regions of the nuclear chart where deformed configurations are energetically favoured over spherical ones. Now experiments show that ⁶²Cr assumes different shapes with excitation energy, which is a signature of such islands.

Dietary zinc and plant-derived aryl hydrocarbon receptor (AHR) agonists are involved in maintaining intestinal epithelium integrity. The authors show that combined supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders.

In a randomized clinical trial, treatment using a monoclonal antibody targeting interleukin-6 (IL-6) in patients with cardiovascular disease and/or diabetes who were receiving maintenance kidney dialysis reduced levels of inflammatory biomarkers at 12 weeks, including C-reactive protein, paving the way for a phase 3 trial.

For individuals with pacemakers, a care pathway that includes echocardiographic screening to detect signs of heart failure did not improve cardiac outcomes, but patients flagged as having impaired heart function who were managed by a specialized heart failure clinic benefited, as compared to those managed by primary care physicians.

Small-molecule senolytic compounds targeting BCL-xL were beneficial in a mouse model of diabetic edema and well tolerated when tested in a phase 1 trial involving eight patients with diabetic macular edema.

Large language models can be manipulated to generate misinformation by poisoning of a very small percentage of the data on which they are trained, but a harm mitigation strategy using biomedical knowledge graphs can offer a method for addressing this vulnerability.

BMI1 and CHD7 are chromatin remodelling genes with a role in medulloblastoma pathogenesis. Here, the authors demonstrate that the BMI1^High/CHD7^Low signature mediates metabolic adaptation in G4 MB and predicts response to inositol treatment either alone or in combination with chemotherapy.

In a large cohort of patients who underwent non-cardiac surgery, postoperative prescription of oral anticoagulation medication decreased the risk of stroke in patients with postoperative atrial fibrillation (POAF), especially for patients deemed to be at high risk for POAF based on a newly developed risk score.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

In a cohort of 6,785 participants from the All of Us Research Program whose sleep was monitored by a Fitbit over a median of 4.5 years, sleep duration, stages and irregularity were associated with the incidence of obesity and a number of cardiovascular and psychological disorders.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

Based on a systematic analysis of environmental exposures associated with aging and mortality in the UK Biobank, the relative contributions of such exposures and genetic risk for mortality and a range of age-related diseases were compared, highlighting the potential beneficial effects of environment-focused interventions.

Jeremy Green and colleagues determine that the mechanism establishing the pattern of rugae on the embryonic vertebrate palate is an activator-inhibitor reaction-diffusion mechanism rather than an alternative pattern signaling system, such as lateral inhibition.

In an analysis of five large randomized clinical trials testing established therapies for cardiovascular disease, individuals with clonal hematopoiesis had an increased risk for first but not recurrent myocardial infarction as compared to individuals without clonal hematopoiesis, and did not show increased benefit from any of the therapies tested.

A risk score using only three clinical variables—age, body mass index and history of atrial fibrillation—predicts heart failure with preserved ejection fraction, an underdiagnosed condition, without the need for echocardiographic imaging.