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When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Lassa virus is a key pathogen that can cause haemorrhagic fever and further understanding of successful therapeutic strategies are needed. Here the authors explore the use of a Lassa virus glycoprotein-based vaccine and show B cell immunity as a correlate of protection in a mouse model of vaccination and subsequent viral challenge

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.

The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

Here the authors report real-world evidence through a retrospective analysis of a multinational cohort of 1.8 M older adults showing that GLP1RAs and SGLT2 inhibitors carry lower risk for hyperkalemia than sulfonylureas. However, SGLT2 inhibitors increased risk of ketoacidosis. Findings support safety-conscious prescribing for older adults, who are often underrepresented in clinical trials.

Global integration of information is critical for memory and cognition. Here, the authors show that high gamma and ripple frequency oscillations burst coincidentally across sensory and association cortical areas as memories are encoded and recalled.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

JWST phase-curve observations reveal that the two innermost TRAPPIST-1 planets emit thermal radiation consistent with bare rocky surfaces, indicating that both lack thick atmospheres.

Precision oncology requires access to high quality data, as well as the application of current technologies. Here, the authors use federated learning to predict clinical outcomes in anal cancer patients across 16 centres as part of the atomCAT consortium.

Trained and validated on data from 2,344 patients with smoldering multiple myeloma, a new algorithm using longitudinal biomarker dynamics provides accurate prediction of risk of disease progression, outperforming established models.

A population genomic analysis of 1,854 Listeria soil isolates collected across the contiguous United States identifies geographically prevalent phylogroups with increased pangenome openness and recombination, as a result of adaptation to variable environments.

Genome-wide analysis shows European dogs existed by 14,200 years ago, were already genetically distinct, received less Neolithic Southwest Asian admixture than humans did and contributed substantially to later European dogs.

Efficacy of chimeric antigen receptor (CAR)-T in solid tumors are limited by the antigen heterogeneity and tumor microenvironment (TME) induced exhaustion. The authors here manifested that Nr2f6-deficient CAR-T cells have superior anti-tumor effect compared with traditional CAR-T cells, which is associated with enhanced cytotoxic function, followed by durable response due to epitope spreading.

Many genetic loci that are associated with coronary artery disease lack understanding of how they contribute to the disease. Here, the authors combine summary genetic statistics with cell type-specific data of regulatory elements to prioritize candidate disease genes, including non-coding RNA genes.

Ongoing chikungunya virus replication leads to the accumulation of inflammatory macrophages and CD4⁺ T cells in joint-associated tissues. Inhibition of chikungunya virus replication during chronic disease reduced viral RNA and joint inflammation in mice.

Czernilofsky et al. identified factors that reprogram stromal cells into an inflammatory, dysfunctional state, leading to the structural disorganization of lymph nodes in B cell lymphoma at single-cell and spatial resolutions.

Insulin controls adipocyte metabolism through changes in protein localisation. Here, the authors use cell-wide subcellular proteomics to uncover extensive insulin-regulated protein redistribution and identify C3ORF18 as a regulator of adipocyte insulin sensitivity.

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.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Toker et al. present an AI framework that identifies mechanisms of consciousness. The model predicts new drivers of unconsciousness and identifies subthalamic nucleus stimulation as a potential therapy for disorders of consciousness.

Different agricultural management systems, for example, conventional versus organic, can have different benefits and challenges. Authors here examine the biodiversity, crop yield and ecosystem multifunctionality impacts of transitioning from conventional to organic agriculture across 179 global croplands.

An analysis of whole-exome sequencing data linked to longitudinal electronic health records from 44,028 British South Asians finds new gene–phenotype associations and identifies 2,991 genes with rare biallelic predicted loss-of-function genotypes.

In this atlas paper, the authors provide a transcriptomic and spatial taxonomy of myeloid cells in the central nervous system of mice and humans in health and pathology.

In clinical validation of a liquid biopsy assay, the approach enabled fast and accurate molecular diagnosis of EBV⁺ Burkitt’s lymphoma in more than 200 children and young adults in Tanzania and Uganda.

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

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.

This work describes three people living with HIV-1 who maintain long-term immune-mediated control of HIV-1 after pausing antiretroviral therapy. Autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4⁺ and CD8⁺ T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. This serves as a model of ART-free control of HIV-1 and informs new HIV-1 cure strategies.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

HORMAD1 expression is typically restricted to germline cells where it has an important role in meiotic recombination but has been shown to be upregulated in triple negative breast cancer (TNBC). Here, the authors report that aberrant HORMAD1 expression weakens the spindle assembly checkpoint, driving sensitivity to AURORA kinase inhibition.

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).

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

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

The Mouse Cancer Cell line Atlas (MCCA) provides major advances towards a mechanistic understanding of cancer genomes.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

Integrated single-cell and spatial data analysis, combined with bidirectional CRISPR screens, identify the transcription factor GLIS3 as a key driver of chronic inflammation and fibrosis and a potential marker of disease severity in patients with ulcerative colitis.

Exportin-1 (XPO-1) inhibitor selinexor has been reported as a therapeutic option in solid cancer. Here, the authors present a phase 1 clinical trial combining selinexor with chemotherapy by gemcitabine in patients with advanced sarcoma.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Dynamos can generate magnetic fields, which are present across various scales in space plasmas. Here, the authors show evidence for a turbulent dynamo in the terrestrial magnetosheath, indicating that Earth’s magnetosheath may be used as a natural laboratory for testing dynamo theories and simulations.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Reconstructing microbial genomes from 820 reef-building corals collected at 99 reefs across 32 islands throughout the Pacific Ocean highlights the importance of conserving coral reefs as vital reservoirs of molecular diversity.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Forests are essential for both climate change mitigation and biodiversity conservation, yet how to balance these goals in managed forests remains unclear. Here, using a Europe-wide dataset, the authors find that biodiversity increases with carbon stocks, but mostly when deadwood is included.

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.