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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.

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.

This work challenges the view of nucleation governing halide perovskite grain morphology, showing that most additives act post-nucleation by boosting ion mobility across grain boundaries, triggering grain coarsening, similar to post-processing effects.

Caroline Fox and colleagues report results of a large genome-wide association meta-analysis and replication study for indices of renal function. Their work identifies 13 new loci associated with renal function and 7 loci associated with creatinine production and secretion.

Bubble formation is a signal of false vacuum decay, in which a system transitions from a local energy minimum to a true vacuum. Now, simulations on a quantum annealer show how interactions between bubbles drive the long-time dynamics of this process.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

Tilgner et al. demonstrated the formation of the quantum spin Hall insulator bismuthene on SiC, intercalated underneath a protective graphene layer. A hydrogen-induced orbital filtering effect is the driving force behind this reversible phase transition.

In mammals, the enzyme TGDS produces UDP-4-keto-6-deoxyglucose, which binds to the catalytic pocket of UDP-xylose synthase, thereby regenerating the essential NAD⁺ cofactor of UDP-xylose synthase in conditions of low NAD⁺.

Nona Sotoodehnia and colleagues report a meta-analysis of 14 genome-wide association studies for QRS interval, an electrocardiogram measurement of cardiac ventricular conduction. They identify 22 loci associated with QRS duration.

MERS-CoV is enzootic in dromedary camels, can spread to humans but undergoes limited onward transmission. Here, Schroeder et al. compare clinical isolates of MERS-CoV in vitro and show that the predominantly circulating recombinant lineage 5 possess a fitness advantage over parental lineage 3 and 4 due to reduced activation of innate immune signaling.

In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.

Rainfall induces nanoparticle bursts within the Amazon rainforest canopy by scavenging large particles and bringing down ozone-rich air, according to aerosol, trace gas and meteorology data from the Amazon Tall Tower Observatory.

Autoimmune Addison’s disease is a rare complex disease, which has not yet been characterized by non-biased genetic studies. Here, the authors perform the first GWAS for the disease, identifying nine loci including two coding variants in the gene Autoimmune Regulator (AIRE).

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Single molecules on metal surfaces are paradigmatic systems for the study of many-body phenomena. Here, the authors show that several spectroscopic experiments on iron phthalocyanine on Au(111) surface can be described in a unified way in terms of a strongly interacting topologically non-trivial (non-Landau) Fermi liquid.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Heterotopic ossification is a disorder characterized by the transformation of soft tissue to bone. In this study the authors report heterotopic ossification in a child caused by enhancer hijacking at the ARHGAP36 gene, the ectopic activation by an enhancer that it not its own.

Challenges in obtaining empirical trait data hinder the development of trait-based frameworks for soil microbes. Here, the authors analyse traits of saprobic fungal isolates from a grassland site to propose a fungal economics spectrum, suggesting a general trait framework for soil fungi.

Genome-wide association analyses identify new susceptibility loci for Brugada syndrome. Functional studies implicate microtubule-related trafficking effects on sodium channel expression as an underlying molecular mechanism.

Optical microcavities have been fabricated in single-crystal diamond and tuned into resonance with the zero phonon line of an ensemble of silicon-vacancy colour centres, which results in an enhancement of spontaneous emission.

Cancer cells frequently harbour genetic aberrations that protect them from programmed cell death. Here, the authors show in non-small cell lung cancer that the anti-apoptotic gene MCL-1 is subject to copy number gains and that deletion of MCL-1 reduces tumour formation.

A reduction in mechanical loading of the skeleton resulting from aging or a sedentary lifestyle can confer an increased risk of fracture through reductions in bone quantity and quality. Not only are mechanical signals crucial in defining and maintaining bone mass, but they also have the potential—in a high-frequency, low-intensity form—to be used in the treatment of osteoporosis.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

Biomass combustion smoke transported from Africa accounts for about 60% of black carbon concentrations in the central Amazon during the rainy season, according to long-term measurements of refractory black carbon in 2019 and 2020

Phage capsids modified with spatially defined patterns of host cell ligands can act as multivalent binders for the influenza A virus to prevent viral infection.

Analysis of 179 new Ebola virus sequences from patient samples collected in Guinea between March 2014 and January 2015 shows how different lineages evolved and spread in West Africa.

Fatal Ebola virus disease is characterized by a high proportion of CD4⁺ and CD8⁺ T cells expressing the inhibitory molecules CTLA-4 and PD-1, correlating with high virus load; individuals who survive the infection exhibit lower expression of these inhibitory molecules and generate Ebola-specific CD8⁺ T cells, suggesting that dysregulation of the T cell response is a key component of Ebola virus disease pathophysiology.

Volumetric 3D printing is an emerging set of technologies enabling layerless, fast fabrication of complex, multicomponent objects. This Review explores challenges in materials design and process engineering, highlighting future directions for the widespread adoption and novel applications of these technologies.