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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.

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.

Femtosecond photoexcitation drives a coherent twist–untwist motion of the moiré superlattice in 2° and 57° twisted WSe₂/MoSe₂ heterobilayers.

Identification of cancer genes altered by non-genetic mechanisms in B-cell lymphoma is challenging. Here, the authors report the development of transposon tools to perform genome-wide recessive screens in vivo and validate identified putative tumor suppressor genes using a CRISPR/Cas9 validation platform.

Mixed-cation perovskites promise improved solar cell stability. Here, the authors reveal a morphotropic phase boundary in MA_1−xFA_xPbI₃ that links structural dynamics to electronic behavior, offering new design routes for high-performance devices.

Many animals can do simple quantity discrimination, but they often perform poorly when food is used. Here, the authors show that monkeys are good at food quantity discrimination when they are not allowed to eat it, suggesting that the mental representation of the stimuli is more important than the physical quality.

In this Review, Grapsa and colleagues provide an overview of the imaging modalities used in the diagnosis and management of tricuspid regurgitation, describe the valve repair and replacement strategies undergoing clinical testing, and highlight the technological innovations that aim to optimize diagnosis, patient selection and the device development process.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

Accessing synthetic two-dimensional polymers that are analogous to graphene is synthetically and analytically challenging. Now, single crystals of a simple-to-make monomer have been grown and then photopolymerized to form layered single crystals of covalently bonded two-dimensional polymer. Much like natural graphite, these crystals can be exfoliated to form thin sheets and single layers of the polymer.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

When a water drop bounces back from a hydrophobic surface, its initial, spherical shape is usually restored. Now, experiments with a specially engineered superhydrophobic surface made from micrometre-sized tapered pillars covered with copper oxide ‘nanoflowers’ show that droplets can bounce back with a flat, pancake-like shape.

Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

Designing superhydrophobic surfaces that water does not wet is crucial for many applications ranging from water harvesting to self-cleaning. Here, Liu et al.show how to minimize the contact of liquid drops impacting on solid surfaces with convex and concave macrotextures comparable to the size of drops.

A neural epigenetic signature detectable via plasma analyses is prognostic in patients with glioblastoma, resembling an oligodendrocyte-progenitor- and neuronal-progenitor-cell-like state and showing increased neuro-to-glioma synapse formation.

SUMOylation is a post-translational modification that has been shown to be altered in cancer. Here, the authors show that loss of the SUMO isopeptidase SENP6 leads to unrestricted SUMOylation and genomic instability promoting lymphomagenesis and generating vulnerability to PARP inhibition.

A phase I open-label trial evaluating the immunogencity, reactogenicity and safety of a peptide-based SARS-CoV-2 vaccine candidate to induce SARS-CoV-2-specific T cell responses.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

High atmospheric concentrations of isoprene have been observed in the Southern Ocean. The authors investigate their potential marine sources and show how these emissions impact the modelling of atmospheric processes and composition in remote environments.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Complex tissue flows in epithelia arise from the coordination of mechanical forces, where cell shape anisotropy and nematic order play a significant role. By introducing internal viscous dissipation in an active nematic vertex model, this study explains the emergence of organised, long-range flows in epithelial sheets, linking cellular dynamics to continuum active nematic and collective cell migration.

Graham and colleagues analyzed locally advanced esophageal adenocarcinoma clinical trial patient samples and identified major changes in gene expression profiles and immune microenvironment composition independent of changes in clonal composition.

Neoantigens determine anti-cancer immunoreactivity and are important functional targets for immunotherapy. Here, the authors use deep mass spectrometry to characterize neoepitopes from human melanoma tissue and show the presence of tumour-reactive T cells with specificity for selected neoantigens.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

Using cryo-electron microscopy and integrative modeling, the authors defined the structure of vimentin intermediate filaments, revealing a helical tube built of five protofibrils that enclose a fiber of low-complexity N-terminal domains.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Juan Cadiñanos and colleagues perform an insertional mutagenesis screen with a single-copy inactivating Sleeping Beauty transposon to look for Pten-cooperating tumor suppressor genes in mice. They find novel candidate cancer genes, verify their clinical relevance in patient cohorts and functionally demonstrate their synergistic relationship to Pten in tumor suppression.

Corals may vary in their ability to regulate reactive oxygen species (ROS) that can influence coral health. Diaz and colleagues conductin vivomeasurements of the ROS superoxide at the surface of corals and find substantial species-level variation in superoxide regulation that is independent of bleaching status.

Two-dimensional photocurrent spectroscopy can identify coherent electronic dynamics and offers promise for studies of numerous material systems. Karki et al. now show that the method can be used to study ultrafast carrier processes in lead sulphide quantum dots, such as multiple exciton generation.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

Looking at genes that are differentially responsive to pathogens depending on the genetic background may help in the identification of therapeutic targets in personalized medicine. Here, using challenge of monocytes with three pathogens the authors identified eQTL that are shared between pathogens and loci that are pathogen specific.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Lifespan can be affected by both physiological ageing and specific sets of pathologies associated with old age. Here the authors report a resource of large-scale cross-sectional phenotyping of aging male mice at different time points to analyse a large set of phenotypes and molecular markers, including during genetic and diet interventions affecting lifespan.

Manchado and colleagues combine CRISPR screening and transcriptomics to identify INPP5A as a dependency and therapeutic target in uveal melanoma driven by mutations in GNAQ/GNA11 and show that IP4 levels correlate with sensitivity to INPP5A loss.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

The authors investigate the broad-scale climatological and soil properties that co-vary with major axes of plant functional traits. They find that variation in plant size is attributed to latitudinal gradients in water or energy limitation, while variation in leaf economics traits is attributed to both climate and soil fertility including their interaction.