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The authors use a physiological approach, finding recent extreme heat events had deadly heat stress conditions, particularly for fully exposed older people. Conditions were well below wet-bulb temperatures of 35˚C, a common heat stress indicator.

Structural studies demonstrate that myosin generates forces that cause structural changes in actin, modulating cooperative binding by α-catenin and thus signal transduction and intercellular communication via adhesion complexes.

Using a machine learning framework to predict antidepressant response in major depressive disorder by analyzing structural and functional connectivity, this study reveals distinct predictive patterns and highlights specific brain regions associated with treatment efficacy, advancing personalized therapeutic approaches.

In the C-TRACT trial involving patients with post-thrombotic syndrome, the addition of endovascular treatment to standard care reduced the severity of symptoms and improved quality of life, but increased the risk of bleeding, compared with standard care alone.

The authors used a machine learning model to distinguish patients with cocaine use disorder and polysubstance use history from healthy controls, using resting-state functional magnetic resonance imaging functional connectivity data.

Here, the authors sample air and surfaces in hospital rooms of COVID-19 patients, detect SARS-CoV-2 RNA in air samples of two of three tested airborne infection isolation rooms, and find surface contamination in 66.7% of tested rooms during the first week of illness and 20% beyond the first week of illness.

Pacific salmon transport of nutrients and contaminants to freshwaters increased by 30% and 20%, respectively, between 1976 and 2015, an increase dominated by pink salmon, which had the highest nutrient-to-contaminant ratios.

With rich, multi-layered baseline data and long-term follow-up through linkage, the HELIOS Study provides a resource to investigate the behavioural, environmental, genomic, and molecular factors impacting health in Asian populations.

Superconductivity is the result of many-body interactions between excitations in a solid. Zhang et al.use time- and angle-resolved photoemission to compare photo-induced changes in the electron self-energy of a unconventional superconductor to those in a related material in the metallic state.

In the HI-PEITHO trial, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation improved outcomes compared with anticoagulation alone in patients with acute, intermediate-risk pulmonary embolism.

In the CHIP-BCIS3 trial, elective left ventricular unloading with a microaxial flow pump did not reduce the risk of major adverse clinical outcomes in patients with severely impaired left ventricular function undergoing complex percutaneous coronary intervention.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Oxygen levels regulate the stability of the transcription factor HIF-1 through the action of prolyl hydroxylases and the VHL ubiquitin ligase. Sharp and colleagues now identify a protein complex in which the Ajuba LIM-domain protein LIMD1 brings together prolyl hydroxylases and VHL to ensure efficient degradation of HIF-1.

A heart–brain loop, which involves vagal sensory neurons in the heart, the paraventricular nucleus in the brain and sympathetic signalling via the superior cervical ganglia, mediates adverse cardiac remodelling after myocardial infarction in mice.

Examining human brain organoids and ex vivo neonatal murine cortical slices demonstrates that structured neuronal sequences emerge independently of sensory input, highlighting the potential of brain organoids as a model for neuronal circuit assembly.

The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts.

3D higher-order topological insulators (HOTIs) exhibit 1D hinge states depending on extrinsic sample details, while intrinsic features of HOTIs remain unknown. Here, K.S. Lin et al. introduce the framework of spin-resolved topology to show that helical HOTIs can realize a doubled axion insulator phase with nontrivial partial axion angles.

A comparison of fetal hemoglobin gene editing strategies using human sickle cell disease donor cells and in vivo transplantation finds that adenine base editing of the –175A>G site in the γ-globin gene promoters results in durable and potent expression.

In a new study, treatment with self-amplifying RNA contained in lipid nanoparticles to increase the production of atrial natriuretic peptide preserved ventricular function and reduced cardiac fibrosis in mouse and pig models of myocardial infarction.

S-acylation of adipose triacylglyceride lipase, the rate-limiting enzyme of lipolysis, is shown to be required for lipolysis and lipid droplet homoeostasis in mice.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

In the VESALIUS-CV trial, the PCSK9 inhibitor evolocumab reduced the risk of a first cardiovascular event in patients with atherosclerosis or diabetes mellitus but without a previous myocardial infarction or stroke.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The size of an ion affects everything from the structure of water to life itself. Here, a sub-nanometer diameter pore sputtered through a thin silicon nitride membrane is used to systematically test ion permeability by measuring the electrolytic current and current noise and show that the ions move with a grossly distorted hydration shell in a correlated way.

Elaborate traits like birdsong are thought to be sexually selected in males but are poorly understood in females. This study shows that year-round territoriality and biparental care are selected for female birdsong, whereas migration, seasonal territoriality, and loss of male care led to losses of female song.

In the DIGIT-HF trial, treatment with digitoxin in addition to guideline-directed medical therapy reduced the risk of hospitalization for worsening heart failure or all-cause death compared with placebo in patients with heart failure with reduced ejection fraction.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Previously, OLIG2-expressing stems cells have been identified as having a role in medulloblastoma recurrence. Here, the authors investigate the effects of targeting this OLIG2+ stem cell population in Sonic Hedgehog (SHH) medulloblastoma using CT-179, an OLIG2 inhibitor.

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

Dividing a metabolic pathway between yeast and Escherichia coli enables synthesis of a small molecule.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Rational strategies to prioritize candidate biomarkers should save resources and accelerate progress in diagnostics development. Addona et al. integrate proteomics into a pipeline for biomarker validation and use it to identify markers of cardiovascular injury in a scenario where patients serve as their own biological controls.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Mutations in two previously unreported Plasmodium falciparum genes, acetyl-CoA transporter (pfact) and UDP-galactose transporter (pfugt), convey resistance to two imidazolopiperazine antimalarial compounds.

A screening approach finds VH-domain antibodies that bind the SARS-CoV-2 Spike protein receptor-binding domain at its interface with host ACE2. Bi-paratopic and multivalent binders have high affinity and potency.