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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.

Quantum lock-in detection (QLID) is crucial for extracting oscillating signals from noise, while quantum entanglement is vital to surpass the standard of quantum limit in precision measurement. Here, the authors experimentally realise entanglement-enhanced QLID using two trapped ions, achieving frequency measurement precision at the Heisenberg limit and demonstrating an improved inverse-quadratic temporal scaling.

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.

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

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.

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

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

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.

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.

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.

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.

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.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

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.

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

It remains to be seen if high-T_c superconductors rely on similar Fermi-surface instabilities as their BCS counterparts. Miao et al. study the high-T_c compound LiFe_1−xCo_xAs with high-resolution ARPES and find a robust gap with Co doping that suggests the order parameter is not tied to such instabilities.

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 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.

The origin of superconductivity enhancement in FeSe monolayer grown on SrTiO₃ compared to bulk FeSe is still a debated issue. Here, Shi et al. report a further 15 K jump of T_c accompanying a second Lifshitz transition triggered by electron doping in FeSe/SrTiO₃monolayer films.

Magnetic reconnection is a fundamental energy release process taking place in various astrophysical environments, but it is difficult to observe it directly. Here, the authors provide evidence of three-dimensional magnetic reconnection in a solar eruption using combined perspectives of two spacecraft.

A stable tokamak plasma has been demonstrated with a high plasma density and a high energy confinement quality, both of which are simultaneously important for fusion reactors.

The role Tibetan Plateau uplift played in Asian inland aridification remains unclear due to a paucity of accurately dated records. Here, the authors present a continuous aeolian sequence for the period >51–39 Ma, analysis of which indicates that aridification was driven by global climatic forcing rather than uplift.

Weyl semimetals exhibit exotic properties owing to the presence of Weyl fermions. Here, Xu et al. show that tantalum phosphide is an ideal platform for studying the transport properties of these particles because its low-energy properties are dominated by a single type of Weyl fermion.

Iron pnictide compounds have recently been shown to have superconducting properties. Xuet al. show that the superconducting gap of underdoped pnictides scales linearly with the transition temperature, and that a pseudogap develops with underdoping.

Factors that determine the cellular tropism of SARS-CoV-2 beyond the host cell receptor, ACE2, are poorly defined. Here, the authors show that tonic activation of the cGAS-STING sensing pathway potently blocks SARS-CoV-2 replication in a subset of ACE2-expressing airway-derived cells.

Interface effects in complex oxides could have interesting technological applications. Ariandoet al. demonstrate electronic phase separation and rich physics at a complex oxide interface between the two non-magnetic insulators LaAlO₃ and SrTiO₃.

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.

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.

It was recently proposed that the coupling between phonons and fractional excitations of a Kitaev quantum spin liquid can be detected in its phonon dynamics. Here, the authors report signatures of this coupling, manifested in low-energy phonon anomalies measured by inelastic X-ray scattering with meV resolution.

The growth of wafer-scale single-crystalline 2D semiconductors on sapphire is important for their electronic applications, but the underlying mechanisms are not yet fully understood. Here, the authors study the influence of air-induced sapphire surface hydrolysis on the growth process of 2D WS₂ and propose an ultraviolet light healing method to repair the degraded substrates.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Investigations of quantum thermal machines and Liouvillian exceptional points have rarely crossed each other. Here, the authors realize experimentally a quantum Otto engine using a single trapped ion, and show that crossing a Liouvillian exceptional point during the cycle increases the engine performance.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

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.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

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.

Analysis of antigen-specific B cells in lymph nodes of individuals vaccinated with BNT162b2 reveals lasting germinal centre responses, explaining the robust humoral immunity induced by SARS-CoV-2 mRNA-based vaccines.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

Plasma fusion devices like tokamaks are important for energy generation but there are many challenges for their steady state operation. Here, the authors show that full divertor detachment is compatible with high-confinement high-poloidal-beta core plasmas and this prevents the damage to the divertor target plates and the first wall.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

A new type of fermion, corresponding to a three-fold degeneracy in the electronic band structure of crystalline molybdenum phosphide, is observed, which lies conceptually between Dirac and Weyl fermions.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.