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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.

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.

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.

Strong interaction is blind to quark flavor, so collisions of nuclei with the same number of protons and neutrons should generate the same number of charged and neutral kaons. Here, instead, the authors show a significant excess of charged over neutral kaon production in Ar+Sc nuclei collisions, compatibly with earlier measurements which however suffered from larger uncertainties, and show that known effects cannot explain the result.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

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.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Metallofullerenes typically have polar single bonds between metals and non-metals. Here, through arc-discharge experiments, the authors observe the formation of an endohedral fullerene with an encapsulated tri-coordinate μ₃-carbon centre and a stable titanium-carbon double bond.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

Combined analysis of proton-proton collision data from the Large Hadron Collider at CERN by the CMS and LHCb collaborations leads to the observation of the extremely rare decay of the strange B meson into muons; the result is compatible with the standard model of particle physics, and does not show any signs of new physics, such as supersymmetry.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.

Hyperactivation of Akt promotes tumorigenesis. Here, the authors show that SAV1, a member of Hippo signalling, interacts with Akt to suppress Akt activity and MERTK-mediated Akt phosphorylation relieves this suppression to facilitate Akt oncogenic activity in clear cell renal carcinomas.

This Expert Recommendation describes how high conversion efficiency in high-order harmonic generation can be achieved over a large range of pressures and medium lengths, following a hyperbolic equation, and provides design guidance for future high-flux extreme ultraviolet sources.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

The Large Hadron Collider beauty collaboration reports a test of lepton flavour universality in decays of bottom mesons into strange mesons and a charged lepton pair, finding evidence of a violation of this principle postulated in the standard model.

Edge-localized plasma modes in a tokamak can damage its innermost wall. Simulations now show that fast ions can modify the spatio-temporal structure of these modes. These effects need to be considered in the optimization of control techniques.

The LHCb collaboration reports an improved measurement of the oscillation frequency of mesons consisting of a bottom quark and strange quark, which is then combined with previous results.

Gaining insight on the structural transformations from atomic clusters to bulk materials is challenging. Here the authors synthesize a continuous cluster of germanium Ge₂₄⁴⁻, which can be viewed as two terminal Ge₉ units bridged via a Ge₆ central fragment, and characterize it by several techniques including X-ray diffraction; theoretical analysis indicates the presence of three aligned independent aromatic fragments.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Genomic and functional analysis of intratumor heterogeneity in pediatric glioma uncovers early clonal divergence and stable spontaneous cooperation between subclonal populations throughout tumor evolution.

In 2001 superconductivity with a high critical temperature of 39 K was discovered in MgB₂, but efforts since then to identify other diboride-family superconductors have been mostly unsuccessful. Here, the authors report the discovery of superconductivity in pressurized WB₂, originating from the formation of metastable stacking faults and twin boundaries that exhibit a local structure resembling MgB₂.

The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.

Rhodopsin genes have been identified in some large double-stranded DNA viruses, but the structure and functions of viral rhodopsins remain unknown. Here authors present crystal structure and characterization of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII) which forms a pentamer and is a weak proton pump.

Nucleocytoplasmic Large DNA Viruses (NCLDV) that infect algae encode two distinct families of microbial rhodopsins. Here, the authors characterise two proteins form the viral rhodopsin group 1 OLPVR1 and VirChR1, present the 1.4 Å crystal structure of OLPVR1 and show that viral rhodopsins 1 are light-gated cation channels.

Kwong et al. use nanoparticles coated with protease substrates to generate mass-encoded synthetic biomarkers for sensitive detection of fibrosis and cancer in mice.

Structural Variant Search, a combination of a chimera-free library preparation and a non-consensus-based SV-calling algorithm, enables the quantitative detection of rare somatic variants.

Progressive fibrosis is a driver of morbidity and mortality in many chronic liver diseases, but the underlying mechanisms are incompletely understood. Here, the authors show that mitochondria-derived damage-associated molecular patterns are released from injured hepatocytes and can trigger fibrogenic activation of hepatic stellate cells.

An adeno-associated virus (AAV) receptor protein essential for AAV2 entry into cells is identified; AAV receptor binds directly to the virus, and its ablation renders a diverse range of mammalian cell types and mice resistant to infection by AAV of multiple serotypes.

The accurate determination of quark mixing parameters is essential for the understanding of the Standard Model. The LHCb collaboration now reports the coupling strength of the b quark to the u quark through the measurement of a baryonic decay mode.

CP violation has deep implications for particle physics and cosmology. Previously observed only in meson decays, signs of CP violation have now been spotted in baryon decays by analysing the proton–proton collision data from the LHCb detector.

The T2K experiment constrains CP symmetry in neutrino oscillations, excluding 46% of possible values of the CP violating parameter at a significance of three standard deviations; this is an important milestone to test CP symmetry conservation in leptons and whether the Universe’s matter–antimatter imbalance originates from leptons.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

Honeycomb lattices of divalent, high-spin Co ions are predicted to host dominant Kitaev exchange interactions expanding opportunities to realize the elusive Kitaev Quantum Spin Liquid (KQSL) state. Hydrostatic pressure studies on leading candidate material Na₃Co₂SbO₆ revealed a transition into a low-spin Co state, quenching the orbital degrees of freedom necessary to realize a KQSL state, but leading to possible emergence of quantum paramagnetism in the compressed honeycomb lattice of S=1/2 divalent Co ions.

The LHCb Collaboration reports the observation of an exotic, narrow, tetraquark state that contains two charm quarks, an up antiquark and a down antiquark.

New vaccine approaches that safely elicit immunity are needed to protect against infectious disease. Erasmus et al. report their development of an insect-virus-based platform that they use to engineer a protective vaccine against chikungunya fever.

The National Cancer Institute (NCI) Genomic Data Commons (GDC) contains more than 2.9 petabytes of genomic and associated clinical data from more than 60 NCI-funded and other contributed cancer genomics research projects. The GDC consists of five applications over a common data model and a common application programming interface.