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Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

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.

Koina is an open-source, online platform that simplifies access to machine learning models in proteomics, enabling easier integration into analysis tools and helping researchers adopt and reuse ML models more efficiently.

Environmental justice and drinking water in the US: Higher proportions of Hispanic/Latino, American Indian/Alaskan Native, and non-Hispanic Black residents were associated with higher public water arsenic and uranium at the county-level, findings differed by region.

Mathematical modelling and experimental tests reveal principles that govern displacement of a resident strain by an invader in microbial communities.

Here, the authors show that pre-infection gastrointestinal microbial composition predicts parasite levels in rhesus macaques infected with P. fragile and humans infected with P. falciparum in a controlled human malaria infection (CHMI) study.

The endoplasmic-reticulum (ER) transmembrane protein IRE1 mitigates ER stress through kinase-ribonuclease and scaffolding activities. However, a significant nonenzymatic IRE1 dependency has been shown in cancer. Here, the authors design a proteolysis-targeting chimera (PROTAC) to fully disrupt cellular IRE1 protein, selectively blocking growth of IRE1-dependent cancer cells.

The benefits and risks of nature to human health have been studied, however, robust empirical research on forest biodiversity and health outcomes is still lacking. Here the authors use a unique dataset from 164 European forest stands to explore the associations between forest types and well-being.

Efficient theoretical methods for the structural analysis of nanoparticles are very much needed. Here the authors demonstrate the use of machine-learning force fields and of a data-driven approach to study the thermodynamical stability and elucidate the melting process of gold nanoparticles.

Bacteria employ a range of competition systems that deliver toxins to inhibit competing strains. This study shows that these systems are particularly important for the ecology of virulent and antibiotic resistant bacteria.

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).

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.

A quantitative analysis of mite symbionts of a brood parasitic passerine bird indicates that conspecific horizontal transmission plays a key role in host colonization and it can also promote codiversification at the macroevolutionary scale.

Artificial Intelligence has achieved success in a variety of single-player or competitive two-player games with no communication between players. Here, the authors propose an approach where Artificial Intelligence agents have ability to negotiate and form agreements, playing the board game Diplomacy.

Single-cell DNA methylation and transcriptomic glioma analyses link local DNA methylation disorder and cellular plasticity. Increases in disorder are associated with stress and disease progression, suggesting a role in shaping the therapeutic response.

Wireless large-scale recordings of neural activity in freely flying fruit bats reveal that hippocampal ensemble properties are associated with sensorimotor rhythms, and that previous models of replay and sequential dynamics, based on experiments in rodents, might not be applicable to other species.

Understanding the factors that control island orientation in the growth of two-dimensional materials is likely to improve their quality. Here, using low-energy electron microscopy, the authors show that post-nucleation annealing of 2D materials can improve rotational order.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Human iPSC-CMs are invaluable for cardiac disease modeling and regeneration. Here, authors developed an optimized suspension culture protocol to efficiently and reproducibly differentiate hiPSCs into cardiomyocytes and cardiac organoids.

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

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

The basic five-digit limb of tetrapods has been altered many times during evolution, usually by the progressive loss of digits — this study tracks the molecular underpinnings of this change, showing that in comparison to mouse, the polarized gene expression in the bovine limb bud is progressively lost due to evolutionary alteration of the cis-regulatory sequences that control Ptch1 expression in response to SHH signalling in the digit-forming handplate.

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.

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.

Treadmilling of cytoskeletal filaments is crucial for their functional self-organization. Now the mechanism underpinning this collective organization is shown to be the dissolution of misaligned filaments.

Ecosystems must be able to bounce back from perturbations to persist without species extinctions. This study uses theoretical modelling to show the importance of reactivity—how species respond in the short term to perturbations—for assessing the health of complex ecosystems, revealing that it can be a better predictor of extinction risk than stability.

Lipo-chitooligosaccharides (LCOs) are signaling molecules produced by certain bacteria and fungi that establish symbiotic relationships with plants. Here, the authors show that LCOs are produced also by many other, non-symbiotic fungi, and regulate fungal growth and development.

Hild et al. find that a wild-derived microbiome protects against weight gain through early postnatal metabolic programming and brown adipose tissue activation.

Game theory has contributed much to the understanding of social evolution. In an elegant combination of experimental tests and modelling, this study suggests that when bacteria face intense competition, repeated retaliation outcompetes a single tit-for-tat response to attack.

Sleep and wakefulness is stabilized by a population of orexin-expressing neurons. In this study, the authors demonstrate how these neurons drive arousal by silencing sleep-promoting neurons in the ventrolateral preoptic nucleus.

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.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Existing methods for non-invasively monitoring water flow in plants have limited spatial/temporal resolution. Here, the authors report that Raman microspectroscopy, complemented by hydrodynamic modelling, can monitor hydrodynamics within living root tissues at cell- and sub-second-scale resolutions.

Bacterial biofilms rely on shared extracellular polymeric substances (EPS) and are often highly tolerant to antibiotics. Here, the authors show in in vitro experiments that Salmonella does not evolve resistance to EPS inhibition because such strains are outcompeted by a susceptible strain under inhibitor treatment.

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.

This study showed that vagal sensory neurons in the nodose ganglia selectively encode specific cytokines, enabling real-time body-brain communication of immune signals. This neural encoding of cytokines is disrupted during inflammation associated with a colitis model.

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.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Interplay of western diet and gut microbiota has been reported to be involved in the development of nonalcoholic steatohepatitis (NASH). Here the authors report that Blautia producta and 2-oleoylglycerol are bacterial and metabolic mediators that promote liver inflammation and hepatic fibrosis in male mice.

Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects.

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.