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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.

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to alleviate pain by reducing inflammation. To the contrary, here, the authors show that selective inhibition of the prostaglandin E2 receptor (EP2) in Schwann cells eliminates pain without disrupting the protective and healing functions of inflammation.

This work presents GōMartini 3, an improved coarse-grained protein model combining physics- and structure-based approaches. It boosts computational efficiency and accuracy for structured soluble and membrane as well as disordered peptides/proteins.

The functional morphology of the fluid-filled semicircular ducts of the inner ear is adapted to body temperature and behavioural activity and can be used to investigate the evolution of endothermy.

Moreno-Loaiza et al. found that interleukin-1β, acting upon cardiac resident macrophages, promotes atrial fibrillation in mice, and this mechanism may represent a common pathway connecting various risk factors to this arrhythmia.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Experimental demonstrations of genuine high-dimensional multipartite quantum nonlocality have been lacking so far. Here, the authors fill this gap using entangled photons, surpassing qubit-based limits and paving the way for device-independent quantum information processing in more complex systems.

The authors analyse tree responses to an extreme heat and drought event across South America to understand long-term climate resistance. While no more sensitive to this than previous lesser events, forests in drier climates showed the greatest impacts and thus vulnerability to climate extremes.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

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).

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

This Brain Somatic Mosaicism Network analysis of 283 cases of malformations of cortical development identifies 69 candidate and known genes in 76 patients. Single-nucleus RNA sequencing and mouse modeling implicate radial glia and daughter excitatory neurons.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Most Amazon tree species are rare but a small proportion are common across the region. The authors show that different species are hyperdominant in different size classes and that hyperdominance is more phylogenetically restricted for larger canopy trees than for smaller understory ones.

African Americans have an elevated risk of developing chronic kidney disease, yet only a fraction of those with high-risk genotypes develop the disease. Here, the authors show that a missense variant in APOL1 has a strong protective effect when co-inherited with the high-risk G2 allele of APOL1, with important implications for clinical practice and translational research.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

The importance of optimizing the contact between catalyst particles, hydrogen and plastic melt in polyolefin chemical recycling has been overlooked, leading to suboptimal performance. The authors develop a criterion based on the dimensionless power number to optimize catalyst effectiveness. Stirring conditions can now be selected to treat commercial-grade polyethylene and polypropylene.

Analysis of 20 chemical and morphological plant traits at diverse sites across 6 continents shows that the transition from semi-arid to arid zones is associated with an unexpected 88% increase in trait diversity.

Whole genome sequencing (WGS) data on non-European and admixed individuals remains scarce. Here, the authors analyse WGS data from 1,171 admixed elderly Brazilians from a census cohort, characterising population-specific genetic variation and exploring the clinical utility of this expanded dataset.

Ecosystem services provided by dung beetles are an underappreciated component of terrestrial ecosystems. Here, the authors report a standardized distributed experiment which shows that dung removal rate, a key ecosystem process in pastures, is greater under high beetle functional diversity regardless of grazing intensity.

Using 13 functional traits we characterize the Amazonian trees and the communities they form. Amazonian tree communities are distributed along a fast-slow-spectrum. This results in clear differences in traits among these forests, as well as their biomass and biomass productivity.

Using a global interaction dataset, the authors quantify the distribution of trophic interactions among marine fish, finding a high degree of geographic connectivity but low spatial modularity.

Here, the authors investigate the effectiveness of the Oxford-AstraZeneca (ChAdOx1) vaccine during extensive Gamma variant SARS-CoV-2 circulation in São Paulo state, Brazil, and find that a two-dose regime is more effective than one dose against mild to severe Covid-19 outcomes in older adults.

Previous gene editing in haematopoietic stem cells (HSCs) has focussed on a heterogeneous CD34⁺ population. Here, the authors demonstrate high efficiency CRISPR/Cas9-based editing of purified long-term HSCs using non-homologous end joining and homology-directed repair, by directing isoform-specific expression of GATA1.

Characterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease.

The final step in an ECF transporters transport cycle involves the expulsion of the membrane embedded substrate binding protein (the S-component) from the motor (the ECF module). Here the authors show how the motor uses ATP binding to load a molecular spring, and adjusts the shape of the membrane, to achieve this step.

Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.

This study found that millennial periods of higher rainfall combined with rising sea level enhanced sediment accumulation in Amazonian rivers valleys. This fuelled synchronous expansion of vegetation adapted to seasonally flooded substrates and its specialized bird populations, showing how global climate changes can affect specific Amazonian species.

It has been conjectured that not only states but also quantum operations can be placed in a superposition of causal order. Here, the authors use a qubit superpose the order in which two photonic gates are applied, which is shown to enable a more efficient detection of their commutation relations.

AgRP neurons in the hypothalamus elicit feeding behavior. Here the authors show that interfering with AgRP neuron function, either by selective knockout of Sirt1 or by early postnatal ablation, leads to increased exploratory behavior and enhanced response to cocaine, which is associated with increased forebrain dopamine levels.

A violation of Bell’s inequality would prove that a classical deterministic view of the universe is incorrect; however, despite long-standing efforts, irrefutable experimental proof of such a violation has yet to be produced. Teo et al. propose a realistic scenario that may finally overcome this challenge.

The significance of biofluorescence across taxonomic groups is understudied. Here the authors document biofluorescence in South American tropical amphibians, suggesting that biofluorescence corresponds with wavelengths of light at twilight and may be used in communication.

The degree to which species tolerate human disturbance contributes to shape human-wildlife coexistence. Here, the authors identify key predictors of avian tolerance of humans across 842 bird species from open tropical ecosystems.

Cerebral malaria is an often fatal complication ofPlasmodium infection involving accumulation of inflammatory leukocytes in the central nervous system. Here the authors map the development and trafficking of CCR5⁺ monocyte-derived dendritic cells from the spleen to the brains of Plasmodium bergheiANKA infected mice.

Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.

Using a data set consisting of 400,000 records covering 3,000 Pyrenean species, it is shown that sampling and scale effects alone can give rise to many conflicting species-richness patterns. Rather than a monotonic decreasing pattern of richness with altitude, a hump-shaped pattern corresponding to a mid-altitudinal richness peak is identified. Apart from sampling issues, it is argued that global reduction in natural lowland habitats also hampers our ability to detect universal patterns in biodiversity.

The Iberian lynx has suffered severe population declines in the twentieth century. An ecological modelling study that accounts for the effects of climate change, prey availability and management intervention now shows that lynx are likely to become extinct in the wild in the next 50 years. However, a carefully planned reintroduction program could avert extinction this century.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.