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Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

Genomic analyses of DNA from modern individuals show that, about 800 years ago, pre-European contact occurred between Polynesian individuals and Native American individuals from near present-day Colombia, while remote Pacific islands were still being settled.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

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.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Analyzing data of the Mexican Biobank project, a new study finds regional differences in clinically relevant genetic frequencies and presents MexVar, a publicly accessible resource designed to support ancestry-informed genetic testing.

Solid tumors often resist immunotherapy due to an immunosuppressive tumor microenvironment. Here, the authors develop CancerPAM, a multiomics CRISPR pipeline that enables tumor-specific cytokine expression to boost immune infiltration and CAR T cell efficacy in neuroblastoma.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Culos, Manas et al. construct machine learning surrogate frailty metrics from activity data collected in a nominally intrusive manner. They show that a limited amount of activity data is necessary to model frailty metrics allowing for an increased proliferation of their application along with a robust source of data for other age-related outcomes.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Ionizing radiation can cause simultaneous charge noise in multi-qubit superconducting devices. Here, the authors measure space- and time-correlated charge jumps in a four-qubit system in a low-radiation underground facility, achieving operation with minimal correlated events over 22 h at qubit separations beyond 3 mm.

DNA replication follows a precise temporal schedule that varies across cell types. Here, the authors show that, in embryonic stem cells, the pluripotency factor OCT4 promotes early activation of normally late-firing replication origins by increasing local chromatin accessibility.

APOBEC deaminases restrict retroviruses but can also mutate human DNA. Here, the authors show that cancerassociated APOBEC3s with low RNA binding, known to enter the nucleus, are selectively recognized by E3 ligases and degraded, eliminating harmful nuclear enzymes, and limiting genome mutation.

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.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

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.

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).

Covalent KRAS inhibitors show initial responses but resistance limits durability. Here drug-induced hapten peptides are identified and characterized, enabling production of high affinity, cross-HLA T cell engagers that stabilize low density hapten peptide MHCs to drive tumor-specific killing.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

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.

The combination of JWST and ALMA data here unravel the history of the gas content of a quiescent galaxy, which became quenched through an act of self-sabotage. Black-hole accretion feedback heated the galaxy’s surrounding material, preventing its accretion.

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.

Extrachromosomal circular DNAs (ecDNAs) are prevalent in human cancers and are thought to drive tumor evolution and drug resistance by amplifying oncogenes. Here, authors develop ec3D to reconstruct three-dimensional ecDNA structures, revealing how their spatial organization rewires regulatory circuits.

The impact of tumour heterogeneity on metastatic potential in prostate cancer remains poorly understood. Here, the analysis of single nuclei RNA sequencing and whole-genome sequencing from samples from five patients suggests an interplay between clonal evolution and cellular plasticity driving metastatic seeding.

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A_2A adenosine receptor ligands and solve their crystal structures to close the Artificial Intelligence Structure-Based Drug Design loop.

Kidney organoids derived from human pluripotent stem cells are infused in a normothermic machine perfusion system to condition explanted porcine kidneys, and the feasibility and viability of their in vivo engraftment are demonstrated.

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.

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.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Sex differences are well established in the prevalence and symptoms of depression. Here, the authors identify a novel X chromosome variant, greater genetic risk, and stronger links to metabolic traits in females, highlighting the importance of sex-aware approaches.

Combination immunotherapy approaches might be effective in inducing sustained control of HIV by slowing rebound and improving CD8⁺ T cell responses.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

In this study, Kennedy et al. combine crystallography, biophysical measurements and biochemical assays to define a structural cycle for Werner syndrome helicase (WRN) and reveal how nucleotide binding and ssDNA engagement lead to conformational transitions.

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.

Xie and colleagues show that MRI-based brain function maps can identify patient-specific abnormalities in temporal lobe epilepsy, track how they spread along brain networks, and help diagnose, lateralize seizure focus, and predict surgical outcomes.

High atmospheric concentrations of isoprene have been observed in the Southern Ocean. The authors investigate their potential marine sources and show how these emissions impact the modelling of atmospheric processes and composition in remote environments.