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The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

Tokamak walls suffer erosion from steady and bursty heat loads. Here, the authors demonstrate that optimizing 3D magnetic field and cooling gas injection can tame destructive plasma bursts while enabling cooler, safer exhaust conditions.

A resource-efficient characterization method to completely characterize multimode second-order nonlinear optical quantum processes is demonstrated, satisfying the required physical condition. Scaling quadratically with the mode number, it enables complete 16-mode analysis.

Here the authors reveal via whole genome sequencing of an East Asian AD cohort a common variant locus (APCDD1), rare noncoding variants in excitatory neurons, and short tandem repeat expansions, suggesting a cumulative effects model for Alzheimer’s risk.

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.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.

TaS₂ can be synthesised in the 4Hb stacking, a natural heterostructure of “H" and “T"-type layers, which exhibits several unusual phenomena in its low temperature superconducting phase. Here, its layer-dependent electronic properties are explored, revealing the T layers are effectively insulating in the bulk, though not at the surface.

Control of liquid-based materials is important for developing materials based on these, but topological flexibility is limited. Here, the authors report a method for digital fabrication of slippery objects with solid-liquid composite interfaces and geometric design freedom.

In patients with hormone receptor positive, human epidermal growth factor receptor 2-negative (HR+/HER-) breast cancer, endocrine therapy is standard of care but resistance often occurs. Here, the authors report a phase I trial investigating the ER degrader, AC699, in patients with locally advanced or metastatic ER+/HER2- breast cancer.

We collect fluorescence photons from a trapped ion into a chip-integrated single waveguide. We introduce a new grating design technique to extend the effective aperture of a large grating.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Clonal hematopoiesis, which increases with age and is implicated in a variety of age-related diseases, is shown here to be associated with a greater risk of acute kidney injury and worse outcome following injury, as demonstrated using multiple patient cohorts, Mendelian randomization analysis and mechanistic studies in mouse disease models.

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.

Lange et al. identify a lipid droplet quality control pathway in which FSP1 safeguards stored neutral lipids from lipid peroxidation, thereby preventing the induction of ferroptosis.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

A previously unsampled deep lineage in central Argentina was discovered that had distinctive genetic drift by 8,500 bp and persisted as the main Native American ancestry component in the region up to the present day.

Cavity phonon-polaritons are a potential platform for controlling phonons. Here, the authors demonstrate multimode ultrastrong coupling between two optical phonon modes embedded in terahertz nanoslot cavities.

A protocol for cryogenic 3D correlative focused ion beam milling using an integrated fluorescence light microscope and montage cryo-ET for nonadherent and adherent mammalian cells, as well as primary Drosophila melanogaster neurons.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

A large-scale livestock prevalence study in Cameroon identified Brucella abortus as the sole endemic species, primarily affecting cattle, and revealed its genetic link to African strains, underscoring the need for regional surveillance and control.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

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

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.

Quantum simulations of the phase diagram of quantum chromodynamics faces hard challenges, such as having to prepare mixed states and enforcing the non-Abelian gauge symmetry constraints. Here, the authors show how to solve the two above problems in a trapped-ion device using motional ancillae and charge-singlet measurements.

The authors identify pathogenic variants in the SMARCA1 gene as the cause of a variable neurodevelopmental disorder. Mouse studies suggest diverse genetic mechanisms related to NURF complex composition mediate the phenotype.

The microbiota may mediate the differential responses to oral cholera vaccine (OCV). Here, the authors reveal that the presence of sphingolipid-producing bacteria is associated with the development of protective immune responses after OCV.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

Chemical modification of mRNA nucleobases alters hydrogen bonding during translation. Here the authors show that the N1-methylpseudouridine (m1ψ), used in therapeutics, does not change translation rate but modestly modulates its fidelity in a codon-position and tRNA dependent manner.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Locksley and colleagues describe a nutrient-sensing circuit in the small intestine. Upon feeding, TSLP production from fibroblasts is increased in a GLP-2-dependent manner, resulting in increased ILC2 activation and tuft cell hyperplasia, thus linking food intake with ILC2 activation.

Here, the authors identify the microbiota-derived corisin as a driver of diabetic kidney fibrosis via cellular aging and show that targeting corisin with a monoclonal antibody alleviates disease in mice, suggesting a potential therapeutic avenue.

Thin FeSe film on SrTiO₃ substrate becomes a superconductor with a transition temperature over 100 K, yet the origin remains controversial. Here, Seo et al. show superconductivity below 20 K on the electron-doped surface of an FeSe crystal, suggesting a decisive role of interfacial effects in the enhancement of superconductivity.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Early high-resolution images of two 2021 novae reveal eruptions unfolding in multiple stages with colliding outflows that produce shocks and gamma rays, reshaping our understanding of stellar explosions.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Polyamines produced by gut bacteria have been proposed to contribute to inflammatory bowel diseases. Here, Nauta et al. show that bacteria can produce a noncanonical polyamine intermediate that functions similarly to deoxyhypusine synthase inhibitors, activates mitochondrial stress responses, and inhibits nematode development and mouse macrophage differentiation.

To function safely and effectively, medical AI models must adapt automatically to differences in users, health systems, geographies, diseases and populations. This Perspective proposes context switching as the defining paradigm of medical AI, outlining early strategies and opportunities for development.

Insights into the mechanism of methylthio-alkane reductase (MAR)—a nitrogenase-like enzyme essential for growth under sulfate-limited conditions—have remained scarce. Now a cryo-EM structure of MAR from Rhodospirillum rubrum, along with spectroscopic investigations, reveals how it uses complex metallocofactors for catalysis.

The cytochrome bc₁ oxidase of Mycobacterium tuberculosis is a potential target in the fight against tuberculosis. Here, the authors evaluate the potential of cytochrome bc₁ inhibitors as partner drugs in tuberculosis treatment regimens.

Lapique, Kim, and colleagues present an open-source approach together with an online probe design platform for in situ RNA and protein analysis. This is an easy-to-use approach that enables vast feature detection, with cycling times under 20 minutes per feature.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.