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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.

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.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Bennu comprises components of intra- and extra-Solar System origins. The parent bodies of Bennu, Ryugu and CI chondrites likely formed from a shared but heterogeneous reservoir in the outer parts of the solar protoplanetary disk.

SpatialZ generates virtual single-cell spatial transcriptomics slices between experimentally measured sections, enabling accurate and efficient building of 3D cell atlases of different tissues.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Osteocytes are the key cellular components of cortical bone. Here they show that osteocytes transfer mitochondria to the endothelial cells of transcortical vessels (TCVs), which promotes angiogenesis and increases function of the TCV network.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Surfaces are the stage for vital catalytic reactions, but accurately simulating them is computationally expensive. Here, the authors introduce an efficient method using GPUs to model large, complex surfaces with exceptionally high, experiment-matching accuracy

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.

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.

Observations of γ-rays with energies up to 1.4 PeV find that 12 sources in the Galaxy are PeVatrons, one of which is the Crab Nebula.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

This study reveals how pre-mRNA processing factors in Arabidopsis distinctly coordinate cleavage and transcription termination, highlighting complex roles of CPSF, CstF, PAPS1, BORDER proteins, and FPA in efficient mRNA maturation.

Accidental ingestion of Pb-contaminated soils represents a major route of Pb exposure for humans. Here, the authors show an effective and straightforward approach of drinking cola beverages to reduce blood Pb levels following the ingestion of contaminated soils based on animal models data.

The joint analysis of datasets from NOvA and T2K, the two currently operating long-baseline neutrino oscillation experiments, provides new constraints related to neutrino masses and fundamental symmetries.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Understanding transformations of non-equilibrium materials is a key open scientific question. Here the pathway by which different polar supertextures undergo dynamical correlations and collectively transform into a metastable supercrystal state is revealed experimentally and theoretically over seven orders of magnitude timescale.

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.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

Valley dependent spin polarization called spin-valley locking appears in absence of magnetism but it is limited to rare examples of transition metal dichalcogenides. Here, the authors report evidence of spin-valley locking and stacked quantum Hall effect in a bulk Dirac semimetal BaMnSb₂.

A graph-theoretical programmable quantum photonic device composed of about 2,500 components is fabricated on a silicon substrate within a 12 mm × 15 mm footprint. It shows the generation, manipulation and certification of genuine multiphoton multidimensional entanglement, as well as the implementations of scattershot and Gaussian boson sampling.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

While CDK4/6 inhibitors (CDK4/6i) have improved outcomes for breast cancer patients, estrogen receptor (ER + ) breast cancers often develop resistance, and triple negative breast cancer (TNBC) show poor sensitivity. Here, the authors identify a vulnerability of CDK4/6i treated ER+ and TNBC on ferroptosis and identify the combination of CDK4/6i and GPX4 inhibition as synergistic.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

In topological insulators, studies have largely concentrated on the spin part of the wavefunction. But the spin–orbit coupling is strong, so the orbital components of the wavefunction need to be measured as well. Surprisingly, the orbital wavefunction turns out to be asymmetric about the Dirac point.

Many diseases are driven by the insufficient expression of critical genes, but few technologies are capable of rescuing these endogenous protein levels. Here, Cao et al. present an RNA-based technology that boosts protein production from endogenous mRNAs by upregulating their translation.

Investigating the inner structure of baryons is important to further our understanding of the strong interaction. Here, the BESIII Collaboration extracts the absolute value of the ratio of the electric to magnetic form factors and its relative phase for e + e − → J/ψ → ΛΣ decays, enhancing the signal thanks to the vacuum polarisation effect at the J/ψ peak.

Ataxia-telangiectasia mutated protein (ATM) phosphorylates CD98HC to promote neutral amino acid antiporter trafficking. Here the authors show that ATM loss impairs glutamate, cystine, and arginine transport, driving metabolic stress and ataxia telangiectasia–like phenotypes.

Ferroelectric materials possess spontaneous electrical polarization coupled to their underlying lattice structure, which may be utilized technologically. Here, the authors use band-excitation piezoresponse/elastic spectroscopy to study the sub-megahertz dynamics of a structural phase transition in BiFeO₃.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

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.

An extreme Einstein ring ~10,000 times as bright as the Milky Way in the infrared is studied with VLT/ERIS and ALMA, and the authors find that the lensed galaxy is a starburst with a fast-rotating disk, rather than being driven by a major merger.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Experiments realizing the indirect-drive fast ignition scheme for inertial confinement fusion are reported. Enabled by a tightly compressed target, an increase of neutron yield is observed.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Ca₃Ru₂O₇ is a layered ruthenate, which undergoes a spin-reorientation transition where the spins rotate 90 degrees between two anti-ferromagnetic states. Despite extensive study, the driver of this transition has proved elusive. Here, using neutron and resonant x-ray scattering, Dashwood et al. show that this transition is driven by lattice strain.