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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).

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.

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.

Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.

Integrating Australian Aboriginal art and narratives with soil excavation data suggests that the regularly spaced bare circles in Australian arid grasslands (sometimes known as ‘fairy circles’) are in fact linyji or mingkirri, termite pavement nests used by Aboriginal people for domestic and sacred purposes over generations.

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.

Preclinical models are essential to study disease pathogenesis and test novel treatments. Here, a broad overview of metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models is provided, detailing main features, advances and limitations of in vitro and in vivo models, and how they translate to human disease.

Even if net-zero emissions are reached well before 2100, West Antarctic ice-sheet retreat could still drive multi-meter sea-level rise by 2300. Emission reductions in the coming years are critical to limit long-term ice loss from Antarctica.

As presented at the ESMO Congress 2025: Results of the phase 2/3 AGITG DYNAMIC-III trial show that de-escalated chemotherapy based on ctDNA-negative status in patients with stage III colon cancer did not meet non-inferiority for 3-year recurrence-free survival when compared to standard of care, although it enables better informed treatment decisions.

The literature assumes that intergroup contact is naturally occurring, positive and consistently associated with positive outcomes, but these premises are inconsistent with everyday intergroup contact experiences. In this Perspective, Paolini et al. propose that variations in contact valence and environmental affordances for self-selection influence segregation dynamics, leading to stable trajectories of contact and intergroup bias.

An updated analysis of the DYNAMIC biomarker-driven trial, including mature survival data at 5 years, supports a ctDNA-guided approach to adjuvant chemotherapy for stage II colon cancer.

Peng and colleagues present SpatialTopic, a scalable computational method that decodes spatial tissue structure from large-scale multiplexed images, thereby enabling rapid, integrative analysis of millions of cells across multiple tissue slides.

T helper 17 (T_H17) cells can have both pro-tumour and antitumour effects. Understanding how they are regulated by environmental and regulatory cues according to context will inform strategies to harness their activity for the development of next-generation cancer immunotherapies.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

The control of translation during mitosis has an important role in cancer cell biology. Here the authors report that in mitotically arrested cancer cells, redistribution of ribosomes towards upstream open reading frames results in enhanced presentation of immunogenic peptides on cancer cell surface.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Combining functional genomic data from mouse and chicken with a synteny-based strategy identifies positionally conserved cis-regulatory elements in the absence of direct sequence conservation.

The authors report shotgun sequences from airborne environmental DNA samples, identifying local biodiversity and enabling deeper analysis of specific species and genomic regions of interest.

A combined modelling and tumour analysis approach is used to study the temporal and spatial patterns of subclone evolution in the TRACERx renal study. Studying the tumour shape and spatial features of clonal diversity in early-stage tumours may allow the prediction of tumour progression and patterns of subclone diversification over time.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

Columnar joints in lavas form during cooling, but the temperature this occurs at is unclear. Here, the authors perform thermo-mechanical experiments on basaltic rocks to examine the temperature of columnar joints in lavas and find that failure occurs at 890–840 °C, which is below the solidus temperature of 980 °C.

Camera-trap images of 55 mammal species in 14 logging concessions in western equatorial Africa reveal greater animal encounter rates in FSC-certified than in non-certified forests, especially for large mammals and species of high conservation priority.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Biological nitrogen fixation may impose stronger constraints on the carbon sink in natural terrestrial biomes and represent a larger source of agricultural nitrogen than is generally considered in analyses of the global nitrogen cycle.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Halbrook et al. report two metabolic subgroups of pancreatic ductal adenocarcinoma cells defined by differential integrated stress response and asparagine production that permit symbiosis and phenformin resistance.

Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

A global assessment of the mobility of 92 agricultural pesticides from points of application in major agricultural catchments downstream to rivers and oceans identifies flow pathways and pollution hotspots in which monitoring could improve risk mitigation.

Modelling oral squamous cell carcinoma (OSCC) is a complex endeavour. Here, the authors provide a comprehensive analysis of an OSCC mouse model and show its mutational signatures mirror human OSCC, providing insights into OSCC clonal dynamics, the microenvironment and evolution.

An online tailored coaching intervention, delivered over 3 years, improved global cognition, dementia risk, physical activity, nutrition and depression in older dementia-free community-dwelling individuals.

Here the authors describe a fluorescent lipid droplet reporter mouse, which allows the staining-free detection of these important lipid-storing organelles. Using this model, they show that LDs are highly abundant in the developing and adult brain.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

van Eijs et al. explore correlates of steroid non-response in blood and tissue of cancer patients with immune-related adverse events in this multi-omics study. An enhanced type 1/17 response in blood and tissue is associated with steroid non-response, while rapid steroid effects occur in circulating and tissue immune cells in steroid responders.

The DANIO-CODE consortium leverages a large-scale multiomic dataset to improve zebrafish genome annotation. They identify ~140,000 cis-regulatory elements throughout development and perform a comparison with the mouse regulatory landscape.

Australian archaeological finds of 12,000-year-old fireplaces and artefacts match nineteenth-century GunaiKurnai ritual practices. They represent approximately 500 generations of cultural transmission of this ritual.

Genome-wide analyses of vaccine antibody responses in 2,499 infants from Uganda, South Africa and Burkina Faso identify associations between specific HLA genes and response to eight vaccines, providing insights that could be considered for population-adjusted vaccine design strategies.

HIV-1 immune evasin Nef reduces activation-induced cell death and promotes survival of chimeric antigen receptor (CAR) T cells; thus, virus-like immune escape enhances therapeutic efficacy of allogeneic CAR T cells.

Roy-Chowdhury et al. report structures of the human leak channel K_2P13.1 that identify a hydrophilic pore restriction and a polyunsaturated-fatty-acid-binding site corresponding to a small-molecule agonist site in the K_2P family.

Tightness-looseness theory predicts that social norms strengthen following threat. Here the authors test this and find that, after the emergence of the COVID-19 pandemic, hand washing norms increased, but no evidence was observed for a robust change in most other norms.

msTrawler improves quantitative analysis of multiplexed mass spectrometry proteomics data when combining isobaric data across multiple batches.

This study assessed COVID-19 social science preprints’ replicability using structured groups. Both beginners and more-experienced participants used a elicitation protocol to make better-than-chance predictions about the reliability of research claims under high uncertainty.

Deep sequencing technologies allow for the investigation of clonal evolution in human cancers. Here the authors, combining sequencing data from human skin with mathematical modelling and simulations, suggest that the spatial context of a mutation with respect to other mutant clones may lead to differential clonal evolution.

Wildlife hunting can support diets and socio-economic well-being in communities around the world, but overexploitation can have cascading ecosystem effects. This study examines socio-cultural, economic and landscape factors associated with wildlife hunting in tropical forests in Africa.

Mucin glycoproteins are biologically relevant but are challenging to study. Here, the authors characterized the SmE enzyme and used it to glycoproteomic ally map immune checkpoint proteins. This information then drove MD simulations and binding assays to understand how glycosylation controls structure and function.