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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.

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.

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.

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.

Consensus exists on the urgent need for food systems to be more sustainable, but defining their environmentally safe operating space is challenging. This study proposes food system boundaries as a share of planetary boundaries, defining budgets across nine boundaries and revealing where boundary transgression is most critical.

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.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Indicators proposed for nutrient and pesticide pollution in the current text of the Convention on Biological Diversity’s post-2020 Global Biodiversity Framework (GBF) are inadequate for tracking progress and informing policy. We highlight a set of more relevant pollution indicators that would strengthen the monitoring framework of the GBF and discuss conditions for their successful implementation.

Evaluating soil metal(loid) mobility at large scales is nearly intractable by laboratory experiments. This study uses theory-guided machine learning methods to map the global distribution of soil metal(loid) mobility and analyzes its primary drivers.

Pesticide pollution is a risk for two-thirds of agriculture land. A third of high-risk areas are in high-biodiversity regions and a fifth are in low- and lower-middle-income areas, according to environmental modelling combined with pesticide application data.

A comprehensive model framework is used to estimate the global net direct radiative forcing of anthropogenic reactive nitrogen as being about −0.34 W m⁻², which has a cooling effect on the climate.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Antimicrobial resistance has evolved over decades due to widespread antimicrobial use, with resistance genes now circulating across humans, animals and the environment, creating complex cross-sector connectivity challenges. This Perspective advocates for genomics-based studies of AMR connectivity to enable coordinated global action and investment under the One Health framework.

Secretory autophagy (SA) plays a crucial role in neuroinflammation-driven neurodegeneration, through SKA2 and FKBP5. SKA2 regulation of SA can inhibit IL-1β release. Its dysfunction leads to neurodegeneration, and is linked to Alzheimer’s disease.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Maternal immunological dysregulation might affect the immunological development of the fetus. Here the authors show that decreased maternal acetate is associated with preeclampsia, impaired fetal thymic output and regulatory T cell development.

Incidence of food allergy in westernized populations is associated with low abundance of Prevotella. Here, the authors analyse the microbiome of a mother-infant prebirth cohort and find that maternal carriage, but not infant carriage, of P. copri during pregnancy predicts the absence of food allergy in the offspring.

Pesticide use in agriculture helps protect crop yields and support global food security, but environmental contamination and residues on food products pose risks to ecosystems and human health. This Review explores transboundary pesticide impacts of internationally traded foods, finding that fruit and vegetables have the highest embodied impacts.

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.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Prenatal bisphenol A exposure is associated with an increased risk of ASD in boys through a mechanism involving aromatase suppression. These resulting ASD-related behaviors and brain abnormalities may be reversed through postnatal intervention with 10HDA in mice.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

Dong, Hao, Zhang, Zhu, Cheng et al. use single-cell RNA sequencing to characterize 28 haematopoietic cell populations and subsequently follow the fate and kinetics of HSCs upon transplantation in the mouse.

China, Germany and UK were the largest net importers of pesticide hazard loads embodied in commodities in 2015, while the USA, Brazil and Spain were the largest net exporters, according to a top-down multi-region input-output analysis of footprints for 82 countries and territories.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

By means of a model of calcite single crystals containing high and tunable amounts of occluded amino acids, the hardness of the crystals can be quantitatively correlated with their composition.

Introducing organic guests to a crystal is a convenient way to tailor its properties. Here, the authors occlude fluorescent dyes within calcite to reveal that additives can occupy distinct zones of a crystal, and strategically embed green, blue, and red dyes to create white fluorescent calcite.

The term mesocrystal describes three-dimensional crystals formed by oriented assembly and that exhibit nanoparticle substructures. Here, the authors perform detailed structural analyses on synthetic calcium carbonate/polymer crystals, and show that common signatures used to assign mesocrystals may be unreliable.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

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.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Calcium carbonate biomineralisation has long been linked to acidic macromolecules. Here, the authors challenge this view and show that a huge number of gold nanoparticles coated with hydroxyl-rich proteins can be incorporated into a calcium carbonate crystal while maintaining single crystal character.

The authors implement a collection of patient-derived xenograft tumors to test cancer drug responses.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

Georgia Chenevix-Trench and colleagues report meta-analyses of genome-wide association studies identifying six loci newly associated with epithelial ovarian cancer (EOC). They also test variants at the 12 known and 6 new EOC susceptibility loci for association in BRCA1 and BRCA2 mutation carriers.

The FarmGTEx Project aims to understand genetic control of gene activity under diverse biological and environmental contexts in domestic animals, providing a foundation for improving animal precision breeding, adaptation and human health.

Cardelino leverages variant information from single-cell RNA-seq data for inferring clonal tree configuration and mapping cells to their clone of origin.