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Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Here, the authors show that IFNγ blockade does not impair resistance to Mycobacterium tuberculosis infection in macaques, opposed to what has been observed in mice, due to a species-specific induction of iNOS by IFNγ.

An open-label, randomized controlled phase 2 trial comparing favipiravir with ribavirin for the treatment of mild-to-moderate Lassa fever in Nigeria found that favipiravir was safe and well tolerated and supports its further optimization as a treatment alternative.

PTCHD1-AS, which encodes a long non-coding RNA, is associated with the aetiology of autism spectrum disorder in humans through striatal molecular and circuit-level dysregulation.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

Owen et al. used single-cell RNA sequencing and spatial transcriptomics to analyze graft cells in heart transplants with cardiac allograft vasculopathy, showing that vascular smooth muscle cells and macrophages drive interferon-mediated inflammation and that JAK signaling blockade prolongs allograft survival.

The authors performed computational and experimental analyses to reveal how Smoothened directly inhibits PKA through an intrinsically disordered region, defining a central step in Hedgehog signaling and a mechanism of G-protein-coupled receptor–kinase regulation.

A single-cell spatial atlas identifies a B cell-predominant microenvironment within the profibrotic tubular niche that marks a subset of patients with diabetic kidney disease with rapid progression.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Mapping DNA variants that modulate mortality using a starting population of 6,438 young mice defined 29 distinct loci that influence lifespan and mortality with divergent age- and sex-specific effects, as well as 30 loci that specifically couple body mass with longevity.

Authors investigate ancient DNA from animal remains and identify multiple signatures of ancient zoonotic pathogens. They find ancient pathogen genomics from archaeological animal remains may inform zoonotic disease emergence.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Phylogeographic analysis and ecological niche modelling identify environmental factors associated with dispersal events, range expansion and local circulation risk of Oropouche virus in people in Brazil.

In a randomized trial enrolling 354 patients with heterozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy, treatment with the cholesteryl ester transfer protein inhibitor obicetrapib was well tolerated and significantly lowered low-density lipoprotein cholesterol by 36.3% as compared to placebo.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Tydeman et al. analyze pregnancy outcomes before the COVID-19 pandemic, during lockdowns, and after restrictions were lifted in >30,000 pregnancies from ethnically and socio-economically diverse individuals in the UK. Most pregnancy outcomes follow pre-pandemic temporal trends, either stable, increasing, or decreasing.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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.

Adherens junctions mediate force transmission and connect the cytoskeleton of adjacent cells. This study demonstrates that force transmission can be achieved through direct and functional β-catenin/vinculin interaction in the absence of α-catenin.

Synovial sarcoma (SyS) is a cancer driven by a fusion oncoprotein, SS18::SSX, but the mechanism underlying the oncoprotein-mediated tumorigenesis remains unclear. Here, the authors employ transgenic mouse models and multi-omics to show how SS18:SSX modifies the activity and recruitment of BAF-family chromatin remodeling complexes to drive SyS tumorigenesis.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Persistent marine heatwave events in the Northeast Pacific preferentially begin in winter, with El Niño-Southern Oscillation and re-emergence influencing duration, according to empirical dynamical modelling of the Northeast Pacific.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

Despite exhibiting ferroelectric features, SrTiO₃ fails to display long-range polar order at low temperatures due to quantum fluctuations. An ultrafast X-ray diffraction experiment now probes polar dynamics of this material at the nanometre scale.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.