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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.

The functional impact of most missense variants remains unknown. Here the authors perform deep mutational scanning of the tumor suppressor SMARCB1 and find missense mutations that retain detectable protein expression but disrupt function similar to protein-null mutations

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.

Maize cultivar evolution boosts maize yield, yet the response pattern of maize to extreme climates is unclear. This study clarifies the synergy and trade-off mechanisms underlying the increase of yield per unit area and adaptation to extreme climates.

Phosphorus locked in carbonate rocks from seven global sites shows simultaneous marine phosphorus spikes during major mass extinctions. Modelling ties high marine phosphorus to eutrophication, CO2 drawdown, and global cooling.

Gene correction in the lung is achieved with inhalable mRNA lipid nanoparticles containing an amino acid-derived ionizable lipid identified from screening and structure–function optimization studies.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

mRNA–lipid-nanoparticle vaccines do not require type 1 conventional dendritic (cDC1) cells or the WDFY4-dependent cross-presentation pathway for CD8⁺ T cell priming but, instead, engage both cDC1 and cDC2 cells redundantly.

Appel et al. found that deceptive networks reached over 37 million Facebook and 3 million Instagram users during the 2020 US elections, with the majority of this exposure driven by 3 networks and amplified by ordinary users resharing the content.

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.

A monolithically integrated photonic ski-jump enables scalable, diffraction-limited 2D beam scanning from photonic chips, achieving ultrahigh spot rates, compact footprints and applications spanning displays, sensing and quantum photonics.

Bacteria are able to covalently incorporate n:3 polyfluoroalkyl carboxylates into phosphatidylethanolamine and phosphatidylglycerol, two major components of bacterial lipid bilayers.

A platinum(II) azido complex (complex 1) that releases platinonitrene upon X-ray exposure induces DNA damage and enhances immune checkpoint blockade outcomes via the abscopal effect.

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.

A pan-haematologic cancer approach, involving analysis of data from 256 patients across 5 cancer types and 13 clinical trials, revealed predictive biomarkers for understanding the response or non-response of patients to CAR-T therapy.

Sticky-ended cohesion has historically been the driving force for DNA self-assembly and was employed for self-assembled crystals to avoid unpredictable packing; however, this limits the diversity of resulting architectures. Here, the authors employ composable DNA tiles to form complex 3D architectures using blunt-ended motifs with single duplex interfaces, leveraging the geometry of the tile and the terminal nucleobase identity to control self-assembly outcomes.

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.

This study presents an organ-wide spatial transcriptomic analysis of human skin from different anatomical sites using a combination of MERFISH technology and existing datasets from healthy and diseased skin.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

The rapid evolution of SARS-CoV-2 challenges antibody therapeutics, but glycan-masked antigens enable isolation of class 3 monoclonal antibodies that potently neutralize diverse Omicron variants and reveal cross-reactive epitopes.

In the nonpivotal stage 1 of the randomized phase 3 PRESERVE-003 trial, patients with immunochemotherapy-resistant metastatic squamous non-small cell lung cancer without actionable genomic alterations treated with the next-generation, pH-sensitive anti-CTLA-4 agent gotistobart had encouraging overall survival outcomes compared to docetaxel.

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).

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.

Plasmas can unlock unconventional reactivity for established catalytic systems, but understanding the resulting mechanistic changes is a complex endeavour. Here in situ characterization techniques allow us to rationalize the promotional role of non-thermal plasma on the catalytic hydrogenation of CO₂ to methanol on Cu–Zn systems.

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.

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.

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.

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.

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.

Repurposing existing drugs to target new disease-associated genes is a promising strategy, but identifying these targets can be challenging. Here, the authors develop GenT, an approach that uses GWAS data to identify disease-associated druggable genes.

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.

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.

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.

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.

Allcott et al. conducted an experiment in 2020, removing political ads from the feeds of randomly selected Facebook and Instagram users. There were no statistically significant effects on political outcomes such as knowledge, polarization and turnout.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Mendelian randomization (MR) identifies causal relationships from observational data but has increased error rates when the genetic variants used as instruments come from a single region, a typical scenario when assessing molecular traits like protein or metabolite levels as risk factors. Here the authors introduce a single-region pleiotropy-robust MR method, validating the method on three ground truth sources, showing its capability to identify disease-causing molecular traits.

Photoinduced ligand-to-metal charge transfer is used to enable abiotic cross-couplings in metalloenzymes. Engineering a 2-histidine metal site and substituting iron with nickel activates PsEFE for nickel-catalysed C(sp²)–S coupling reactions between thiols and aryl bromides. Directed evolution yielded metalloenzyme variants that can produce a range of thioethers with high efficiency.

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.

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

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

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.

A battery-free smart mask enables multiday exhaled breath condensate monitoring by integrating a regenerable hydrogel, an electrochemical lactate sensor and a perovskite solar cell, allowing autonomous tracking of metabolic lactate in humans.

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.

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.

Safe lithium-ion batteries require stable electrolytes with high chemical resistance and high thermal tolerance. Chen et al. find a solid lithium-salt electrolyte that is able to give rise to a prolonged battery life and a delayed decomposition of battery cathodes.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

All-van der Waals multiferroic tunnel junctions exhibit four non-volatile resistance states with full layer tailorability, enabling up to 10⁶% tunnelling electroresistance, 10⁴ A cm⁻² ON-state current density and room temperature operation.