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This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.

To evaluate the effectiveness of current national policies in achieving global temperature targets is important but a systematic multi-model evaluation is still lacking. Here the authors identified a reduction of 3.5 GtCO₂ eq of current national policies relative to a baseline scenario without climate policies by 2030 due to the increasing low carbon share of final energy and the improving final energy intensity.

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.

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.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

Plasmacytoid dendritic cells produce type I interferons in response to viral sensing. Here the authors show that amines inhibit these plasmacytoid dendritic cell responses through CXCR4 engagement.

Predicting gene expression from H&E slides is a cost-effective alternative to Spatial Transcriptomics for clinical use. Here the authors introduce a Multiple Instance Learning approach to infer single-cell expression, unlike prior methods which operate at coarser patch level.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

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.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

This study estimates construction-related emissions and carbon budgets for over 1,000 cities worldwide. Through quantitative analysis and an accessible open dashboard, this study empowers city stakeholders to craft science-based strategies for aligning future construction growth with climate goals.

Researchers applied high resolution inversions of satellite methane observations to estimate methane emissions from 161 countries, finding that global anthropogenic emissions are 15% larger than Paris Agreement reporting.

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 scale and nature of energy investments under diverging technology and policy futures is of great importance to decision makers. Here, a multi-model study projects investment needs under countries’ nationally determined contributions and in pathways consistent with achieving the 2 °C and 1.5 °C targets as well as certain SDGs.

The viscosity of tumour cells is shown to govern their ability to disseminate through the bloodstream and extravasate, establishing a key biomechanical factor of metastasis.

An observationally calibrated ice sheet–shelf model suggests that global warming of 3 °C will trigger rapid Antarctic ice loss, contributing about 0.5 cm per year of sea-level rise by 2100.

Fundamental value judgments about acceptable maximum levels of climate change and future reliance on controversial technologies can be made explicitly in climate scenarios, thereby addressing the intergenerational bias present in the scenario literature.

Even when neocortical neurons form in abnormal locations, they retain their identity and function, revealing that brain circuit formation can be guided by intrinsic developmental programs rather than physical position.

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.

The explosion of Vesuvius in 79 AD carbonized a library of papyrus scrolls, namely Herculaneum papyri, the contents of which are thus still largely unknown. Here, Mocella et al.show the capability of X-ray phase-contrast tomography to read letters in these scrolls without the need to unroll them first.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

This multicenter study demonstrates use of dried and capillary blood as a minimally invasive, scalable approach for Alzheimer’s biomarker testing in research, with potential as a widely scalable population-based research approach, especially in resource-limited settings.

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.

Metabolic and proteomic profiles derived from fossilized skeletal remains of animals enable inferences regarding physiological health and disease as well as diet to provide reconstructions of ancient soil, vegetation and palaeoclimate characteristics.

The extreme hot and dry conditions of 2023 reduced soil respiration and enhanced net forest carbon sequestration in Canada, offsetting wildfire emissions, according to satellite-based and in situ observations of CO₂ fluxes.

In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo.

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.

Liver neuroendocrine neoplasms (NEN) without clinically known primary tumor are often classified as primary hepatic NEN. Here, the authors build a classifier accurately predicting the origin sites for NEN based on DNA methylation patterns and show that hepatic NEN with unknown primary tumor are predicted to display a non-hepatic origin.

Trends in global H₂ sources and sinks are analysed from 1990 to 2020, and a comprehensive budget for the decade 2010–2020 is presented.

The Type 3 Secretion System (T3SS) of Pseudomonas aeruginosa injects effectors into host cells to promote infection. Here, the authors reveal a new regulatory role for the T3SS effector ExoY in modulating ExoT-induced cytotoxicity via cGMP signalling.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

Specificity in interactions with otherwise common glycan structures is likely achieved through glycan context. Here, the authors show that such glycan context is generated through tunable glycan arrangements that are translated into function by galectins.

Understanding the dual role of neuraminidase and hemagglutinin antibodies in influenza transmission is crucial for enhancing vaccine efficacy. Here, the authors use household transmission studies and mathematical models and find that neuraminidase immunity reduces infectivity, suggesting vaccines targeting both glycoproteins could lower community transmission and offer broader protection.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

In key European cities, stabilizing climate warming at 1.5 °C would decrease extreme heat-related mortality by 15–22% per summer compared with stabilization at 2 °C.

In this study, the authors use a combination of experimental and modeling approaches to show that a human gut bacterial community can exist in different states under the same conditions. The mechanism behind these alternative states is likely based on metabolic change in response to nutrient depletion.

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.

A decision-support system that automates the Banff classification system for diagnosis of kidney allograft rejection leads to reclassification and correction of pathologists’ diagnoses and improves risk stratification of allograft outcomes.

Elhan et al. show that ATG2A acts with DGAT2, the enzyme producing triacylglycerol (TAG), in lipid droplet growth. By delivering diacylglycerol to lipid droplets, ATG2A not only fuels TAG production but also promotes the recruitment of DGAT2 to droplet surfaces.

Enhanced weathering of basalt (EW) removes CO2 chemically, and biotically by enhancing ecosystem growth through phosphorus release. This study shows that leveraging the biotic process can triple the contribution of EW to climate change mitigation.