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Multimodal machine learning reveals that tumour microenvironments can be decomposed into spatially organized multicellular ecosystems, termed spatial ecotypes, that can be accessed non-invasively via liquid biopsy and used to profile individual cancers and target treatments.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Over three decades, rapid expansion of the transposable element ISL3 has reshaped Enterococcus faecium, which helps to explain this pathogen’s growing clinical threat.

A collection of antigen-stabilizable fluorescent nanobodies becomes fluorescent upon binding to their intracellular targets and enables background-free multicolor imaging and biosensing in living systems, revealing protein dynamics, metabolites and signaling across cellular and in vivo models, including the zebrafish embryo and mouse brain.

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.

An in vitro toolkit for studying VSG diversification defines key molecular requirements underlying the formation of mosaic VSGs, providing an experimental framework for the exploration of antigen diversification in Trypanosoma brucei and in other pathogenic microorganisms.

Starburst galaxies are seen to host galaxy-scale winds, which are super-fast and could be powered entirely by the thermal pressure of gas heated by supernovae.

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.

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

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

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).

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

Yücel et al. examine how skin and hair characteristics impact functional near-infrared spectroscopy (fNIRS) signal quality and provide recommendations for inclusive use of fNIRS.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

XRISM spectroscopy of the nucleus of the Circinus galaxy indicates elemental abundances suggestive of a dominant enrichment from core-collapse supernovae with progenitors below 20 solar masses; more massive stars may directly collapse into black holes.

Baum et al. present a synthesis of field data, remote-sensed data, media reports and process-based modelling analyses examining the effects of the 2021 heatwave in western North America for 32 terrestrial and marine taxa as well as gross primary productivity, streamflow and wildfire activity.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

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 identify key enzymes, including four cytochrome P450s, a dehydrogenase and a sulfotransferase, that together build the core chemical scaffold of withanolides, medicinal compounds from ashwagandha with neurological and anti-cancer activities.

In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.

An online experiment compared 12 brief online interventions for depression. Most improved mental health immediately, but these gains decreased over time, with only two interventions significantly reducing depression 4 weeks later.

Hominin fossils from the Ledi-Geraru Research Project area, Ethiopia, suggest that early Homo and Australopithecus species co-existed in the region more than 2.5 million years ago.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Using nitrogen isotopes from ancient and modern fish otoliths and corals, the study shows Caribbean reef food webs are now 60–70% shorter and functionally less diverse, indicating human-driven trophic simplification and increased risk of collapse.

This study reports on excavations of hearths and stone artefacts from 20,000-year-old deposits at Dargan Shelter, which at an elevation of 1,073 m is believed to be the oldest occupied high-altitude site in Australia.

In this paper, the authors describe the energy state-dependent regulation of the PVN^GLP-1R to DVC circuit, resulting in altered food intake and metabolic health, mediated by GLP-1 receptor signalling.

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.

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.

Cavity-stimulated Raman spin-flip emission is demonstrated by coupling a negatively charged InAs/GaAs quantum dot to a photonic crystal defect cavity. The emission is spectrally narrow and tunable over a range of about 125 GHz. The process can be made spin selective by tuning the scattered photons to be in resonance with the cavity.

The development of new classes of isosteres and building blocks is crucial to the advancement of medicinal chemistry programs. Here, the authors report the synthesis and development of ladderanes to act as replacements for meta-substituted aromatic rings and cyclohexanes.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

In this Tools of the Trade article, Erin Brown describes the development of CytoSPACE, a computational tool that aligns single-cell transcriptomes and spatial transcriptomic data, and highlights its use in identifying spatially resolved cell states in the tumour microenvironment.

Here the authors functionally characterize hepatocellular carcinoma associated tertiary lymphoid structures (TLS) in patients treated with neoadjuvant immunotherapy and present further evidence for using these TLS as a biomarker of response to therapy.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

HER2-targeted therapy improves patient’s outcome in early breast cancer. Here, the authors present the efficacy and biomarker analysis of two HER2-targeted combinations (ado-trastuzumab emtansine plus pertuzumab and paclitaxel, trastuzumab and pertuzumab) in the context of the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence.

High near-surface nitrogen-fixation rates that promoted the recent growth of the Great Atlantic Sargassum Belt were tied to greater upwelling of phosphorus from the equatorial Atlantic, according to coral-bound nitrogen isotope records from the Caribbean.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Mouse models of NF1-associated optic pathway glioma show that tumour initiation and growth are driven by aberrantly high levels of NLGN3 shedding in the optic nerve in response to retinal neuron activity.