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Two nationwide randomized controlled trials in England with over 4 million participants found that text messages highlighting that people had reached the ‘top of the queue’ increased COVID-19 vaccination rates.

A meta-analysis using the Burden of Proof framework, drawing on 16 systematic reviews and 843 observational studies, finds that alcohol consumption increases risk for most health outcomes, with high intake uniformly harmful for all tested outcomes and only limited, outcome-specific U-shaped associations at low-to-moderate levels for some cardiometabolic and neurological conditions.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

Strain rates across higher-elevation supraglacial lake basins are unperturbed while multiple hydro-fracture events occur at lower elevations, demonstrating the short inland distance over which inter-lake, hydro-fracture event triggering acts.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Interactions between the tumor microenvironment and antibody drugs are imaged with spatial proteomics.

Global soil mineral data from orbital spectroscopy reduce uncertainty in dust’s solar radiative impact and improve estimates of Earth’s energy imbalance, according to analyses integrating high-resolution soil composition into Earth system models.

Severe SARS-CoV-2 infection and COVID-19 can associate with autoantibodies neutralizing inflammatory cytokines. The authors here investigate the presence of autoantibodies targeting specific anti-inflammatory mediators. They identify severe COVID-19 to associate with autoantibodies depleting IL-1Ra and PGRN, which coincide with hyperphosphorylated antigen isoforms induced by inflammatory stress.

Massively parallel reporter assays promise rapid in vivo characterization of enhancer AAVs. Here, through systematic testing, authors uncover pervasive technical and biological noise, including chimeric AAV species, that exposes fundamental limitations in pooled enhancer screening.

The mechanical stability of proteins affects their import into the nucleus. Now it is shown that protein transport in and out of the nucleus depends on the local mechanostability of the protein cargo.

Torres et al. present ApexGO, a generative approach capable of redesigning peptide antibiotics to better kill drug-resistant bacteria. They validated candidates in laboratory tests and mouse infections and matching or outperforming standard antibiotics.

Long COVID is associated with challenges in energy management, with limited interventions available. In this study, a just-in-time app-based energy management intervention for long COVID did not reduce postexertional malaise compared to usual care, though both groups improved over time, showing the approach was safe but not effective.

This study shows that atmospheric desert dust keeps about twice as much infrared heat from escaping to space as climate models predict, highlighting that improving dust in models could sharpen weather forecasts and climate projections.

While anti-retroviral therapy (ART) helps contain HIV, whether adoptive T cell therapy further improve the prognosis is unclear. Here the authors conduct an open-label, single-arm phase 1 study to assess the safety (primary outcome) and characteristic (secondary outcome) of autologous, HIV-specific T cell therapy to find it safe to warrant further efficacy assessment.

The Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

GLP-1–GIP–lanifibranor, a single-molecule agonist of GLP-1R, GIPR, PPARα, PPARγ and PPARδ, shows promising therapeutic efficacy against obesity-linked metabolic dysfunction in vitro and in mouse models via synergistic incretin and PPAR activity.

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.

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.

Gut microbiota-targeted therapeutics for lupus are lacking. Here, the authors show that a human isolate of Faecalibacterium prausnitzii ameliorates gut microbial dysbiosis and alleviates autoimmune activation, autoantibody production and kidney damage in a lupus-prone mouse model.

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.

A new optical imaging study demonstrates that norepinephrine and the state of arousal influence hemodynamic correlations across cerebral cortex, calling for a conceptual shift in interpreting functional magnetic resonance imaging data.

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.

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.

Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

In targeted protein degradation, a degrader molecule brings a neosubstrate protein proximal to a hijacked E3 ligase for its ubiquitination. Here, pseudo-natural products derived from (−)-myrtanol—iDegs—are identified to inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs prime apo-IDO1 ubiquitination and subsequent degradation using its native proteolytic pathway.

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.

Using single-cell tissue imaging and spatial proteomics to study mitochondria–lipid droplet coupling in hepatocytes, PLIN5 phosphorylation is identified as a mediator of lipid flux and nutrient stress responses.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

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.

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.

Age-related microbiome changes increase medium-chain fatty acid-producing bacteria, driving GPR84-mediated myeloid inflammation, impaired vagal signalling and hippocampal dysfunction; targeting this gut–brain pathway restores memory in aged mice.

Regulatory approval of blood-based biomarkers for Alzheimer’s disease could change diagnosis, trial design and therapeutic development. As these tests move into the clinic, physicians must assess how best to deploy them in real-world care.

C-COMPASS is an open-source software designed to predict the spatial cellular distribution of proteins and lipids from cellular organelle profiling using a neural network-based regression model.

Here the authors report that lipidomics analysis of over 13,000 Australians from two cohorts identifies distinct blood lipid signatures linked to habitual dietary exposures. Lipid markers of healthier diets were associated with lower cardiovascular risk and reduced all-cause mortality.

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.

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.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Insulin signaling plays a crucial role in coordinating skeletal development with whole‑body energy metabolism. Here, the authors use phosphoproteomics to show insulin-signaling rewiring in aged, insulin-resistant bone and identify defective phosphorylation of AFF4 as a key mechanism for regulating gene-specific transcriptional activation.

Treatment with 4′-fluorouridine (also known as EIDD-2749) in an African green monkey (Chlorocebus aethiops) model of Lassa disease resulted in complete clearance of infectious virus in a high proportion of cases and prolonged survival to the pre-determined study end-point in all cases.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

The transformations for aragonite precursors in coral are not fully understood but have implications in bio, biogenic and geological mineralization. Here, the authors use high-resolution mapping and observe exponential decay from the edge of four precursors to coral aragonite skeleton in Stylophora pistillata.

Robust protein synthesis by the ribosome is required for rapid cancer growth. Here authors present interdictors, small molecule inhibitors of protein synthesis with context-dependent activity that inhibit MYC-driven cancer cell growth in a mouse model.

Surgical sterilization alone cannot control global stray and feral domestic cat populations. Here, Godin et al. show that a single-dose injectable female sterilant administered before puberty safely and completely prevents pregnancy after maturity.

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.

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.

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.