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This study shows that ice loss and human water use models explain global and regional satellite-observed ocean mass changes since 2003 and thereby pinpoint the main cause of sea level rise, with a negligible role coming from natural variability.

While antivirals like nirmatrelvir/ritonavir and molnupiravir are known to reduce severe COVID-19, their impact on cardiovascular outcomes is unclear. Here, the authors use a target trial emulation design to show that nirmatrelvir/ritonavir significantly lowers long-term cardiovascular risks among hospitalized patients, highlighting its potentials over molnupiravir for mitigating post-COVID-19 cardiovascular complications.

In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo.

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

Water consumption in line with natural water supply ensures sustainable and equitable access to freshwater resources worldwide. This study assesses whether renewable surface water is enough to meet people’s basic needs and, where it is not, estimates how much groundwater would be required.

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.

The T-cell receptor (TCR) activation mechanism has remained uncertain. Here, the authors present molecular structures for the apo and ligand-bound human TCR–CD3 complex in lipid nanodiscs, revealing large conformational changes during activation.

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.

An intercomparison exercise reassesses mass loss from glaciers worldwide based on the main in situ and satellite methods from 2000 to 2023; the results are consistent with previous assessments and provide a refined and comprehensive observational baseline for future impact and modelling studies.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Confidence is key to decision-making, but the dynamics of confidence formation remain elusive. We show that neural populations in parietal cortex reflect the parallel processes of forming a decision and confidence in the decision.

In this Expert Recommendation, a working group integrating diverse perspectives presents a comprehensive overview of the clinical relevance and applicability of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the rationale for its use as an outcome measure in clinical trials, addressing a long-standing roadblock in the development of new drugs for CLE.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

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).

Grace Nambatya Kyeyune uses modern technology and clinical trials to help validate the efficacy and safety of products based on traditional medicine.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

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 blooming alga Emiliania huxleyi and its viruses are a model for density-dependent virulent dynamics. However, Knowles et al. show that this host–virus system exhibits temperate dynamics at natural host densities, in a manner dependent on host physiology.

The acceleration of sea-level rise continues, but this has not been clear in the short altimeter record. This study closes the sea-level rise budget for 1993–2014 and illustrates the increased contribution from the Greenland ice sheet.

Fresh basaltic glass preserved in a sample of volcanic breccia record a single eruptive event at the Alpha Ridge around 90 Ma, suggesting that parts of the ridge were emergent during the final stages of magmatism in the High Arctic Large Igneous Province, according to geochemical and geochronological analysis of the sample.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

There has been recent interest in understanding why the biodiversity-productivity relationship varies among studies and across scales. Here Fei et al. show that climatic variation drives forest biodiversity-productivity relationships at large spatial scales, whilst biotic and abiotic factors are important in given climate units.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

There are a number of competing explanations for the late Pleistocene extinction of many North American megafauna species. Here, the authors apply a Bayesian regression approach that finds greater concordance between megafaunal declines and climate change than with human population growth.

The RNA methyltransferase activity of SPOUT1/CENP-32 is crucial for accurate mitotic spindle organization. Here, the authors describe a neurodevelopmental disorder caused by bi-allelic pathogenic SPOUT1 variants with reduced activity and compromised function in spindle organization.

Alaskan mountain glaciers are losing ice and contribute to sea level rise, but contributions from specific ice-loss mechanisms are not known. Here, calving losses in Central Alaska are found to equal 36% of the net regional mass change each year and regional flux is dictated largely by snow accumulation rates.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.