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Mucosal immunity is an important component of the anti-SARS-CoV-2 response and may contribute to the relatively better protection provided by infection compared to vaccination of children against serious disease. Here, the authors analyse the antigen-specific B cell response in the tonsils, adenoids, and blood of children following infection with SARS-CoV-2 or vaccination with SARS-CoV-2 mRNA vaccines to find evidence that tissue-specific B cell memory is formed with both, albeit with characteristic differences between the two groups.

CheckMate 650 was a multicohort phase 2 trial designed to study the safety and clinical activity of nivolumab plus ipilimumab combination therapy in patients with metastatic castration-resistant prostate cancer. Here the authors report the results of the randomized portion of the trial, including three different immunotherapy treatment cohorts and a current standard-of-care chemotherapy cohort (cabazitaxel).

Researchers designed two-component proteins forming quasisymmetric cages via geometric frustration, enabling tunable virus-like assemblies for cargo delivery, cellular uptake and studying intracellular diffusion and protein localization.

Androgens have distinct roles in the brain, acting as immune-based tumour suppressors through neuroinflammation and neuroendocrine mechanisms.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

International trade shifts part of the health burden of air pollution across countries. This study shows that about 14–18% of global deaths from fine particulate pollution—800,000 annually—are linked to trade, where consumption in higher-income economies drives exposure in lower-income ones.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

Beta-adrenergic signalling modulates histone variant H2A.Z deposition, chromatin accessibility and chromatin loop reorganization to regulate thermogenesis in mouse and human adipocytes.

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.

This study profiles gene expression of individual cell types that are present during the formation of human and mouse faces. The authors identify specific cell types that play roles in facial shape differences and contribute to risk for craniofacial diseases like cleft lip and palate.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

This study uses two large fundus cohorts to show that retinal foundation models generalize well across populations but exhibit age-related fairness gaps. It highlights how pre-training data composition shapes model generalisability and fairness.

Stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads using a two-vector system of enveloped delivery vehicles and adeno-associated viruses.

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.

Epigenetic programming of myeloid and CD4⁺ T cells promotes decay of the SIV reservoir in rhesus macaques and a similar molecular pathway is found in HIV elite controllers.

Wu et al. identify circulating proteins associated with cardiovascular and neurological imaging traits and diseases, and validate GDF15 as a shared determinant of heart and brain pathologies in mice.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

A wearable that continuously measures the concentration of a drug is demonstrated in humans.

In this attempt at xenotransplantation of a lung from a genetically modified pig into a brain-dead recipient, although the grafted lung initially maintained viability and functionality, antibody-mediated rejection rapidly occurred, contributing to xenograft damage.

Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage colony-stimulating factor signaling and resulted macropinocytosis with the downstream, potentially IRF8-mediated genetic program to bias progenitor differentiation to neutrophil instead of TRM.

Yang et al. apply high-throughput structure probing approaches to characterize the secondary structure throughout the SARS-CoV-2 WT and VOC genomes, uncovering an ultra-long-range RNA-RNA interaction that directly binds ADAR1 to promote viral fitness.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Detection of hot intracluster gas in SPT2349−56 with the Atacama Large Millimeter/submillimeter Array provides new insights into early cluster formation.

Olfactory neuroblastoma (ONB) is a rare malignant tumor whose genetic basis is poorly understood. Here the authors identify recurrent deletions involving dystrophin in the majority of ONB patient tumors examined.

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

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.

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.

A clinical trial using continuous glucose monitoring found that a Dietary Approaches to Stop Hypertension (DASH)-style diet tailored for diabetes reduced hyperglycemia and improved glucose control compared to a typical American diet in patients with type 2 diabetes.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

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.

Expressing the Pseudomonas ethylene-forming enzyme (Efe) in Synechocystis 6803 causes it to produce ethylene. Tracer experiments and metabolic modelling show that this is achieved by plasticity of fluxes through the tricarboxylic acid cycle.

The origin of the nematic state in the kagome metal CsTi₃Bi₅ remains unclear. Here, using polarization-dependent angle-resolved photoelectron spectroscopy and ab initio based field theoretical methods, the authors propose a d-wave nematic order driven by electronic correlations via an orbital-selective mechanism.

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.

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.

In an ongoing phase 1 trial, the combination of two new immunotherapies targeting CTLA-4 and PD-1 was overall well tolerated and elicited encouraging clinical responses in patients with relapsed/refractory microsatellite stable colorectal cancer, a tumor type typically unresponsive to immune checkpoint blockade.

Drosophila Microproteins Simba1/2 act in neural stem cells and blood-brain-barrier glia to promote reactivation of neural stem cells via activating WNT/Wingless signaling, while human ortholog ZNF706 is found to have a conserved role in activating WNT pathway.

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.

The link between neuroinflammation and the progression of multiple sclerosis (MS) is unclear. Here, the authors show that in MS lesions, neuronal somatic mutations accumulate 2.5 times faster than in controls, equivalent to 1,291 excess mutations by age 70, suggesting that neuroinflammation can be mutagenic.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.