Search

In the CheckMate 142 study, nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) was shown to induce durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Here, the authors perform exploratory biomarker analysis of the CheckMate 142 study.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

2023 CX1 is the only L-chondrite-like asteroid analysed from space to ground. It catastrophically fragmented in the atmosphere, depositing 98% of its energy in one burst—an unusual, high-risk fragmentation mode with implications for planetary defence.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

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).

Andrew Robinson reviews five of the best science picks.

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.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

EchoNext, a deep learning model for electrocardiograms trained and validated in diverse health systems, successfully detects many forms of structural heart disease, supporting the potential of artificial intelligence to expand access to heart disease screening at scale.

In an ongoing adaptive-design trial exploring different combinations of neoadjuvant immunotherapies including the anti-PD-1 agent pembrolizumab, the anti-TIGIT agent vibostolimab and the oncolytic virus gebasaxturev, neoadjuvant pembrolizumab-based regimens elicited encouraging clinical responses in patients with resectable melanoma.

The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the authors report that BRCA1/2 and ADAR1 are synthetic lethal, showing that ADAR1 depletion in BRCA1-mutant cells causes autocrine interferon poisoning

Effective solutions for food systems transformation must be designed in a participatory way. This study illustrates the application of an integrated assessment framework to explore stakeholder-driven scenarios towards climate-smart nutrition security in Malawi, South Africa, Tanzania and Zambia.

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.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

Four decades after a test mining experiment that removed nodules, the biological impacts in many groups of organisms persist, although populations of several organisms have begun to re-establish despite persistent physical changes at the seafloor.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Results from the PRADO extension cohort of the OpACIN-neo trial show that pathologic response rate to neoadjuvant ipilimumab and nivolumab can be used as a criterion for personalization of further treatment in stage III nodal melanoma, with the potential to reduce treatment morbidity and increase patient quality of life.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

Hosseinzadeh et al. demonstrate use of a publicly accessible automated machine learning platform to differentiate between a common benign tumor and malignant transformation of it within the paranasal sinuses. This AI algorithm beat prior human prediction, and showed that physicians with no coding background can effectively utilize this tool.

NIPBL perturbation activates long terminal repeat (LTR)-derived alternative promoters due to reorganization of chromatin’s hierarchical structure, leading to LTR co-option and oncogene activation in melanoma cell lines.

Protection afforded by inorganic minerals is assumed to make mineral-associated organic carbon less susceptible to loss under climate change than particulate organic carbon. However, a global study of soil organic carbon from drylands suggests that this is not the case.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Hepatitis E virus exists in two forms in patients: naked and quasi-enveloped. Using a new imaging method, the authors found that these forms enter cells through different pathways, directed by interaction of the capsid protein with integrin beta 1.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

Live birth and an annual life cycle potentially enable access to new ecological niches and subsequent species diversification. Here, Helmstetter et al.build the phylogeny for fish in the order Cyprinodontiformes and find that, though live birth and annualism have each evolved multiple times, only live birth is associated with increased diversification.

In global drylands, soils tend to be more fertile beneath tree, shrub and grass islands. Soil fertility was greater beneath taller and wider plants but was unaffected by either grazing pressure or the type of herbivore.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

uMAIA is an analytical framework designed to enable the construction of metabolic atlases at high resolution using mass spectrometry imaging data.

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.

There are limited in vitro and in vivo models to study human fetal exposure to environmental noise. Here, the authors develop a computational model to quantify fetal exposure to acoustic fields, obtaining acoustic transfer characteristics across the human audio range.

Widespread grassland degradation poses major societal and environmental challenges. Here, the authors propose multiple targeted interventions as a crucial strategy for simultaneously enhancing grassland ecosystem services and improving their equitability.

Hexacoordinate silicon is seen often in molecular compounds, but very rarely in crystalline silicate materials. Now, reversible Si–O chemistry has been used to assemble octahedral dianionic SiO₆ building units and anthracene derivatives into crystalline microporous silicate organic frameworks that share characteristics of both covalent organic frameworks and inorganic zeolites.

Small cell lung cancer presents high and multi-site metastatic potential. Here, the authors discover that FOXA2, regulated by ASCL1, promotes multi-site metastasis in small cell lung cancer by inducing a fetal neuroendocrine gene expression program.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.