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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.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Multielectron quantum dots offer a promising platform for high-performance spin qubits; however, previous demonstrations have been limited to single-qubit operation. Here, the authors report a universal gate set and two-qubit Bell state tomography in a high-occupancy double quantum dot in silicon.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

For solid-state qubits, the material environment hosts sources of errors that vary in time and space. This systematic analysis of errors affecting high-fidelity two-qubit gates in silicon can inform the design of large-scale quantum computers.

Initialization and operation of spin qubits in silicon above 1 K reach fidelities sufficient for fault-tolerant operations at these temperatures.

Understanding the microscopic variability of CMOS spin qubits is crucial for developing scalable quantum processors. Here the authors report a combined experimental and numerical study of the effect of interface roughness on variability of quantum dot spin qubits formed at the Si/SiO₂ interface.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

High-performance all-electrical control is a prerequisite for scalable silicon quantum computing. The switchable interaction between spins and orbital motion of electrons in silicon quantum dots now enables the electrical control of a spin qubit with high fidelity and speed, without the need for integrating a micromagnet.

Using large-scale data describing five decades of wheat breeding progress in western Europe, a study shows that breeding for high performance enhances wheat productivity under not only optimal conditions but also conditions with reduced agrochemical inputs.

With a changing climate and a growing population, the world increasingly needs more-productive and resilient crops. But improving them requires a knowledge of what actually works in the field.

Substantial water savings can be achieved by coating toilet bowl surfaces to repel liquids, bacteria and viscoelastic solids such as human faeces. In this Article, the authors develop a sprayable, non-fouling coating that can reduce cleaning water consumption by ~90% compared with untreated surfaces.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Predictions suggest that a high proportion of plant species will be threatened with extinction in the near future. A global assessment of the threat status of cacti suggests that these iconic plants are amongst the most threatened taxonomic groups, with 31% of the 1,478 evaluated species at risk of extinction.

Including participants from 45 countries, Bago et al. find that the situational factors that affect moral reasoning are shared across countries, with diminished observed cultural variation.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

The nucleotide diversity present in maize exceeds that in humans by an order of magnitude, and it has been challenging to characterize the high levels of diversity in this important crop. Doreen Ware and colleagues have identified 55 million SNPs in 103 domesticated and pre-domestication Zea mays varieties, as well as in a representative from the sister genus Tripsacum.

Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. In this Review, Prendergast and colleagues discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden.

Full-length spliced RNA isoforms are identified in thousands of single cerebellar cells.