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Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Vertebra lengths differ from the neck to the tail tip and differ between species, evidenced by extreme differences in mouse and jerboa tails. Here, Weber and colleagues identify cellular mechanisms and candidate genes that shape vertebral proportion.

STM investigations and first principles calculations provide an understanding of the microscopic mechanism behind the mobility of N-heterocyclic carbenes (NHCs) on gold surfaces. Now, it is shown that a ballbot-type motion allows the formation of self-assembled monolayers due to the NHC extracting a gold atom from the surface, leading to a ligated gold adatom.

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.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

High-affinity IL-2Rα expressed by T_regs mitigates the potential of IL-2 use in cancer therapy. Here, the authors fuse IL-2 with an NKDG2 binding domain, and show that it induces IL-2 signalling selectively in NKG2D⁺cells, delaying tumour growth in mice without the side effects of conventional IL-2 therapy.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Monolithically integrated superconducting single-photon detectors and Josephson junctions can be used to create superconducting optoelectronic synapses with analogue weighting and temporal leaky integration of single-photon presynaptic signals

Comparisons of a chimeric recombinant version of SARS-CoV-2, the ancestral SARS-CoV-2 strain and an Omicron isolate show that the attenuated virulence of Omicron is caused by mutations in both the spike protein and nsp6.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

An exome wide association study of UK Biobank data revealed 158 variants and 105 genes significantly associated with kidney function traits and disease. The findings are supported by functional evidence for a previously unreported mutation in CLDN10.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Azobenzene is perhaps the archetypal light-activated molecule, widely used for photoswitching applications, but the mechanism of isomerisation remains in doubt. Here, the authors provide high-resolution excitation spectra of trans-azobenzene, identifying the structural changes accompanying photoisomerisation.

A neoadjuvant treatment regimen of anti-PD-L1 monotherapy followed by anti-PD-L1 plus chemotherapy was well tolerated and led to a major pathologic response rate of 70% in patients with resectable gastric or gastroesophageal junction adenocarcinoma.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Grant Stewart, Andrew Jackson, Christopher Mathew, Fowzan Alkuraya and colleagues identify a novel replication fork protein, DONSON, which is important for maintaining genome stability. Mutations in DONSON cause microcephalic dwarfism and lead to stalled replication forks and DNA damage.

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

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.

A multi-omic atlas of breast cancers, integrating single-cell RNA sequencing, spatial transcriptomics and immunophenotyping, identifies nine ecotypes associated with cellular heterogeneity and prognosis.

A genome-wide-association meta-analysis of 18,381 austim spectrum disorder (ASD) cases and 27,969 controls identifies five risk loci. The authors find quantitative and qualitative polygenic heterogeneity across ASD subtypes.

Phenotypic and genetic intra-tumor heterogeneity have an important role in cancer progression and therapeutic resistance. Here, the authors show that phenotypically variable tumor subpopulations exhibit higher metastatic potential and display enhanced intra-clonal transcriptomic variability, likely promoted by deregulated spliceosome activity.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Using a rigid tip removes artefacts associated with imaging the strongly varying tip–sample potential of intermolecular sites by atomic force microscopy.

The antiferromagnetic spin 1/2 Kitaev model is known to have an intermediate phase under a magnetic field before transitioning to a fully polarized state. However, the nature of this phase for higher spins remained unclear. This paper explores the quantum phase diagram of the antiferromagnetic Kitaev honeycomb model in a magnetic field using tensor-network methods and high-order linked cluster expansions, uncovering an intermediate phase with distinct local magnetization patterns across different spin values.