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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.

Negative refraction—light bending opposite to conventional refraction—and a hyperlens effect is observed in an excitonic system in the two-dimensional magnet CrSBr. The effect is mediated by the magnetic order of the material.

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.

Little is known about the environmental benefits of housing reallocation. This study fills the gap, presenting an information-enabled housing exchange framework that, in the case of Beijing, Munich and Singapore, could substantially reduce the carbon emissions from commuting.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Absorption in one-port passive systems is known to be bound by causality constraints. Here, authors study reflection and transmission of a two-port system to introduce a generalized causality constraint based on duality symmetry. Experimentally, the broadened bandwidth of their meta-absorbers shows the untapped absorption potential of broadband acoustic metamaterials.

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, but platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, the authors design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone, which exhibit the activity of both parent anticancer compounds and can overcome drug efflux effectively due to covalent binding to intracellular biomolecules.

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.

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.

The authors present a soft metalens (SML) with tungsten-gel composite for ultra-broadband transcranial focus, significantly enhancing intracranial sound pressure and spatial resolution. This breakthrough advances underwater sonar, medical ultrasound imaging, and non-invasive detection for energy transmission.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Plasmons excited in gratings create strong resonant absorptions that depend on the nanostructure period. By patterning a gold grating on a silicon substrate, Sobhani et al. exploit plasmon-induced hot electron photocurrent generation to create a narrowband infrared photodetector with greatly enhanced absorption efficiency.

While BH3-mimetics can be effective for treatment of haematological malignancies, their efficacy in solid tumours is limited. Here, using a range of patient-derived prostate cancer models, the authors demonstrate that increased replication stress induced by RB1 loss confers sensitivity to BH3 mimetics targeting BCL-XL.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Photoelectrochemical etching relies on light-driven carrier migration to catalyze reactions on semiconductor surfaces. Here, the authors show that lateral photon gradients induce anomalous etching of undoped semiconductor materials.

Li-Fraumeni syndrome is a cancer predisposition disorder caused by TP53 variants, but the way different TP53 variants contribute remains unclear. Here, the authors analyse TP53 mutagenesis datasets and identify five TP53 variant clusters that show associations with specific cancer patterns as well as potential clinical strategies.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

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.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Florez Ariza and Lue et al. use cryo-electron microscopy to investigate how the RECQL5 helicase regulates transcription. Their structural findings suggest that RECQL5 can modulate RNA polymerase II’s translocation state, potentially restarting stalled transcription.

The few options available for the measurement of in-plane and cross-plane thermal conductivity of covalent organic frameworks films limit their application for lightweight thermal management. Here, the authors measure both, the in-plane and cross-plane thermal conductivity of two dimensional covalent organic frameworks with different pore sizes using laser-based pump-probe techniques.

Shark antibodies (Variable New Antigen Receptors, VNARs) are the smallest naturally occurring antibody fragments. Here, the authors screen a VNAR phage display library against the SARS-CoV2 receptor binding domain (RBD) and identify VNARs that neutralize the SARSCoV-2 virus and discuss their mechanisms of viral neutralization.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Romer’s Gap describes the period with few known fossils when early tetrapods were becoming increasingly terrestrial. Here, five new species, three stem tetrapods and two stem amphibians, are described from a location in Scotland shedding light on the phylogeny and environment of this period.

Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

Water scarcity is a global issue that demands urgent resolution, but current approaches are inadequate. Now a metre-scale atmospheric water harvester, featuring a hygroscopic origami hydrogel panel and a window-like glass chamber, demonstrates exceptional efficiency in extracting water from air, even in extremely arid conditions.

Multi-ancestry genome-wide association meta-analysis of major depression identifies new risk loci, assesses the transferability of risk loci across ancestry groups, and improves fine-mapping resolution and prioritization of candidate effector genes.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Adeno-associated vectors (AAVs) are frequently used for the delivery of genetic cargo but their small packaging capacity is not suitable for delivery of large constructs, including most CRISPR/dCas9-effector systems. Here the authors report a compact dCas9-based repressor system packaged within a single, optimized AAV vector.

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.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

An analysis of the localization and intensity of intracortical microstimulation in three participants with cervical spinal cord injury shows that overlapping projected fields from multiple electrodes produce sensations that are more easily localizable.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

A large-area fabrication approach to achieve three-dimensional architectured metamaterials, with structural features spanning seven orders of magnitude, results in advanced mechanical properties, including high elasticity.

Mass spectrometry facilitates large-scale glycosylation profiling but in-depth analysis of intact glycopeptides is still challenging. Here, the authors show that activated ion electron transfer dissociation is suitable for glycopeptide fragmentation and improves glycoproteome coverage.

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.

The two dimensional magnetoplasmon edge state has been observed for a long time, but its nature is yet to be uncovered. Here, Jin et al. report that such a state is actually topological protected, analogous to the chiral Majorana edge state in a p-wave topological superconductor.

Melanocytic nevus count is associated with melanoma risk. In this study, a meta-analysis of 11 nevus GWAS studies identifies novel SNPs in KITLG and 9q32, and bivariate analysis with melanoma GWAS meta-analysis reveals that most nevus genes affect melanoma risk, while melanoma risk loci do not alter the nevus count.