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Achieving optimal glycemic control remains challenging for most adults with type 1 diabetes using multiple daily injections. Here, the authors show that a decision support system for insulin dose optimisation improves HbA1c in this population.

Massively parallel reporter assay in primary human CD4⁺ T cells and bulk and single-cell CRISPR-interference screens identify candidate causal variants linked to autoimmune disease risk that modulate T cell gene expression and proliferation.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Infant KMT2A-rearranged acute lymphoblastic leukemia is associated with poor overall survival rates. Here, the authors use WGS and WES of 36 relapsed KMT2A-rearranged ALL and AML patients and find alterations in drug response genes in ALL, which may correspond with relapse time. Longitudinal analyses of >250 samples could track residual leukemia cells, clonal drug responses, and the upcoming relapse.

Aortopathy poses a high risk of aortic dissection, particularly during pregnancy and the postpartum period. Here the authors report a retrospective case series of seven women with aortopathy who underwent PEARS, a surgical strategy to prevent aortic root dilatation, and a subsequent pregnancy.

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.

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.

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.

Sydnor et al. developed a new tractography atlas of thalamocortical structural connections and applied it to three youth samples. They uncovered coordinated development between thalamic connectivity and hierarchical cortical plasticity in humans.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Boccella, Yu and colleagues reveal that the transmembrane protein ANTXR1 regulates post-infarction fibrotic remodeling, and its inhibition blocks collagen turnover and improves heart function.

Perception can occur in the absence of report. Here, the authors use intracranial recordings to show that sequential sampling of sensory evidence in the ventral visual cortex supports perception beyond report.

The diversity of ponerine ants varies widely across the globe. This study finds that the origin and early colonization in Gondwana’s tropical regions mainly shaped this distribution, while differences in diversification and dispersal have balanced regional diversity over time.

State leaders given league table of environmental performance.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

This paper introduces a method, termed the 'rank clock', to visualize the dynamical behaviour of city size distributions over long periods of time. The clocks show that cities and civilizations rise and fall in size at many times and on many scales, ruling out universal rank-size scaling at the micro-level and associated models of growth by proportionate effect.

In a mouse model of Erbb2-driven mammary tumours, this study finds a role for RANKL in the formation of lung metastases. RANKL is produced by regulatory T cells infiltrating the primary tumours and acts via its receptor RANK expressed on the cancer cells. Targeting RANKL may therefore prove useful in reducing breast cancer metastases.

Heller et al. showed dense longitudinal imaging in four females, including one with endometriosis and one using oral contraceptives, and the finding that different hormonal milieus influence widespread brain volume changes linked to progesterone or estradiol.

Profiling assays measure thousands of features to uncover biological insights but lack reliable methods for quality evaluation. Here, the authors develop a versatile information retrieval framework to robustly quantify sample activity and similarity in large-scale profiling data.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Accurate segmentation of ischemic stroke lesions from brain MRI is crucial for timely diagnosis and treatment planning. Here, the authors present DeepISLES, an AI ensemble for stroke MRI analysis that outperforms previous methods and matches expert radiologist performance in identifying stroke lesions.

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.

Here, the authors provide molecular insight into the remarkable ability of Tardigrades to withstand high levels of radiation by demonstrating that their Dsup protein interacts with multiple surfaces of the nucleosome to protect the genome from oxidative DNA damage.

Analyses of ancient human DNA show that cultural and political transformations in Central Europe during the second half of the first millennium ce were associated with movements of Slavic populations into Germany, Poland and Croatia.

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.

Indonesian cattle are unique due to their history of admixture involving both zebu and banteng. Here, Wang et al. identify ~3.5 million novel introgressed SNP variants and provide a genomic map of banteng introgression within and across many cattle breeds, each with unique introgression histories.

Bodogai et al. identify a unique subset of CD8⁺ T cells expressing CD39 and CD73 that accumulate during aging and are recruited to and actively promote tumor progression by suppressing antitumor CD4⁺ T cells. Targeting their function or recruitment attenuates tumor growth in aged mice.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Analysis of multiple cohorts of patients with melanoma demonstrates a positive association between cytomegalovirus serostatus and overall survival in patients treated with monotherapy but not combination immune checkpoint blockade, as well as delayed onset of immune-related adverse events across both treatment types, as well as delayed development of metastatic disease in seropositive patients.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

The computational mechanism by which the mediodorsal (MD) thalamus enhances prefrontal activity to enable cognitive flexibility in context-dependent decision making is not fully understood. Here authors build a computational model incorporating genetically identified thalamocortical connectivity and interneuron cell types. Together with experimental testing, authors show that addition of a feedforward MD thalamus to the recurrent prefrontal cortex circuit increases robustness to low cueing signal-to-noise ratio, enhances working memory, and enables rapid context switching.

Analysis of human Robertsonian chromosomes originating from 13, 14 and 21 reveal that they result from breaks at the SST1 macrosatellite DNA array and recombination between homologous sequences surrounding SST1.

Integrated single-cell transcriptomic and genetic characterization of 121 adult glioblastomas identifies heterogeneity at cell type, cell state and baseline expression program levels associated with specific mutations that form three stereotypical ecosystems.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

The dorsal peduncular area of the mouse brain functions as a network hub that integrates diverse cortical and thalamic inputs to regulate neuroendocrine and autonomic responses.

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

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.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

The neuronal architecture that develops after spinal cord injury and causes autonomic dysreflexia is uncovered.

Chapman, Klaourakis and colleagues reveal that a lymphatic vasculature with poor clearance capacity in perinatal, regeneration-competent mouse hearts is required to retain pro-reparative macrophages and allow cardiac regeneration.

The authors report a meta-analysis of methylome-wide association studies, identifying 15 significant CpG sites linked to major depression, revealing associations with inflammatory markers and suggesting potential causal relationships through Mendelian randomization analysis.

Basidiomycete fungi typically have two mating-type loci located on different chromosomes. Here, Lucotte et al. report the convergent loss-of-function of mating-type genes across several species of phytopathogenic fungi of the genus Microbotryum.

Sperm–egg adhesion is crucial for mammalian reproduction. Here, authors report the human Izumo1:Juno complex, a key regulator of sperm-egg adhesion, forms an unusually strong bond through a secondary binding site, which is impaired in an infertility-associated Juno mutant.

Using historical aerial photographs and new bed topography data, accelerating changes on Kennicott and Root Glaciers, Alaska since 1938 are documented. These observations inform projections showing 38–63% mass loss by 2100, depending on future climate.

Polyneuropathy causes are difficult to pinpoint. Here, authors used single-nucleus and spatial transcriptomics of 37 human peripheral nerves to identify focal perineurial hyperplasia and endoneurial lipid-associated macrophages in polyneuropathies.