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RAS-driven cancers depend on SHOC2–PP1C. Here, the authors reveal that KRAS forms a low-affinity SHOC2–PP1C complex with fewer contacts than MRAS and show that dual inhibition of KRAS- and MRAS-dependent assemblies strengthens SHOC2 suppression and may overcome resistance.

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.

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.

Elevated ceramides have been implicated in endothelial dysfunction, preceding cardiometabolic diseases. Yet, direct in vivo evidence is lacking. Here we show that suppression of ceramides and S1P are causally linked to endothelial dysfunction contributing to cardiometabolic disease in obese mice

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

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.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

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.

This work examines future coastal risks in Europe’s Outermost Regions and Overseas Countries and Territories. By 2150, 3,000 km² could flood yearly, with €5.9 bn in annual damages and 0.5 million people exposed. Mitigation cuts impacts nearly in half, but long-term resilience strategies are needed.

Authors show that single-molecule mapping of sugar–receptor interactions on immune cells uncovers strong subcellular variation linked to receptor function.

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.

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.

In a trial involving 45 clinics and 15,596 visits, the use of an AI-based screening tool applied to ECG for opportunistic detection of advanced chronic liver disease led to a significant increase in new diagnoses compared to the standard workflow.

Reliably probing rejuvenation and memory effects in spin glasses by means of simulations is difficult. Now, a state-of-the-art numerical study shows that at least three different length scales play a crucial role in aging dynamics of spin glasses.

GATA2 deficiency is one of the major causes of hereditary pediatric myelodysplastic neoplasms (MDS). Using iPSC-based models, this work recapitulates stepwise mutational trajectories in GATA2-related MDS and reveals their impact on myeloid differentiation.

The rapid expansion of agricultural irrigation raises concerns about exacerbating water scarcity, but land–atmosphere interactions are often overlooked. This study isolates irrigation impacts from other drivers using a multi-model framework to reveal that historical irrigation expansion substantially reduces net atmospheric water influx, intensifying drying trends and accelerating terrestrial water storage depletion, urging immediate mitigation strategies.

For the development and application of quantum technologies, devices capable of implementing more than two-photon processes are vital. Towards this aim, Spagnolo et al.build a three-port beam splitter and demonstrate mutual interference between the three photons.

It takes extreme sensitivity to measure the elementary excitations in liquid helium-4. An optomechanical cavity with a thin film of superfluid inside can be used to both observe and control phonons in real time.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

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.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

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

The primitive hominins from Dmanisi in the Republic of Georgia are often thought to be akin to Homo erectus and are arguably the earliest known members of the human family outside Africa. This conclusion has come, so far, from the presentation of postcranial material: now a partial skeleton of an adolescent individual associated with a skull, and remains from three adult individuals, suggest that the Dmanisi hominids are even more primitive than that, akin to Homo habilis.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

The long-standing problem of determining the classical communication capacities of Gaussian bosonic channels is addressed by determining upper and lower bounds for the classical capacities of important active and passive bosonic channels. The results apply to any bosonic thermal-noise channel, including electromagnetic signaling at any frequency.

Recent experiments reported the Kondo effect in 1H/1T dichalcogenide hetero-bilayers. Crippa et al. re-examine this interpretation using ab initio calculations and dynamical mean-field theory demonstrating strong charge transfer sensitive to the interlayer separation, indicative of a doped Mott insulator regime.

Closely related plant species can have drastically different abundances of transposable elements. Now it is shown that the genome of Arabis alpina has experienced a striking expansion of retrotransposons, probably shaped by reduced DNA methylation.

Exploiting the full structuration of light fields for storing multiple degrees of freedom holds great promise for applications in classical and quantum optics. Here, the authors demonstrate the storage of spatio-polarization-patterned beams into an optical memory, and its retrieval at the single-photon level.

Molecular shuttles are bi-stable and stimuli-responsive systems that are considered potential elements for molecular machinery. Here, the authors use optical tweezers to measure the force dependent real-time kinetics of individual molecular shuttles under aqueous conditions.

In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

The first steps of charge transfer in molecules after their interaction with light occur on an ultrafast timescale. Now, by combining attosecond pump/few-femtosecond probe spectroscopy with quantum chemistry calculations, it has been shown that a concerted nuclear and electronic motion drives electron transfer in donor–π–acceptor molecules on a sub-10-fs timescale.

The catalytic performance of dilute Pd-in-Au alloys depends on the Pd ensemble size on the bimetallic nanoparticle surface. Here the authors reveal how Pd ensemble formation on Au nanoparticles depends on the deposition sequence and nanoparticle–support wetting interactions, consequently affecting reactivity.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

The global atlas of unburnable oil shows that the most socio-environmentally sensitive areas, such as protected areas or biodiversity hotspots, need to be kept entirely off-limits to oil extraction in order to keep global warming under 1.5 °C.

Observing quantum effects in a mechanical oscillator requires it to be close to a pure quantum state, rather than a thermal mixture. Here a librational mode of a levitated nanoparticle is cooled close to its ground state without using cryogenics.

Under field conditions, acquisitive tree species generally grow slowly, whereas conservative species show generally higher realized growth, owing to their ability to tolerate unfavourable environmental conditions.

Using mathematical models calibrated to clinical trial results on vaccine efficacy, this study projects the potential impact of the vaccine at population level, showing the conditions for it to be effective in reducing cases and hospitalizations and helping to design vaccination campaigns.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.