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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.

Three-dimensional imaging is crucial for biomedical research, yet microscopy faces axial resolution limitations. Here, authors introduce SSAI-3D that adapts training datasets and sparsely finetunes a network to achieve robust results across various biological samples and microscopy systems.

A synthetic hydrogel has been developed to mimic the physicochemical properties of pancreatic tissue and is shown to support the culture of pancreatic cancer organoids, revealing the role of laminin–integrin interactions in their growth.

Mitochondrial complex II is normally composed of four subunits. Here the authors show that bioenergetic stress conditions give rise to a partially assembled variant of complex II, which shifts the anabolic pathways to less energy demanding processes.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

An analysis based on data from the Global Dietary Database shows mean animal-sourced food intakes among children and adolescents increased modestly from 1990 to two portions per day in 2018, but remain low in sub-Saharan Africa, India and Bangladesh.

Cell adhesion proteins have been described at sites away from the cell surface, including in the nucleus. Here, the authors report the scale of nuclear localisation of adhesion proteins, establishing a nucleo-adhesome and showing that nuclear adhesion proteins can cooperate to control transcription.

There has been limited success in generating tissues from human induced pluripotent stem cells (hiPSCs). Here, the authors genetically engineer expression of the transcription factor Gata6 in a single isogenic hiPSC population resulting in complex tissue structures that exhibit liver bud-like properties.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Tissue engineering has opened up the possibility of studying physiological and pathophysiological processesin vitro. The foundation of this technology is a set of design principles for building three-dimensional tissues that are based on the quantitative analyses of cell and tissue behaviour.

The authors find that the insulin receptor forms dynamic clusters during insulin signaling and that these clusters become dysfunctional in insulin resistance. This dysfunction is partially rescued by metformin, a drug used to treat type 2 diabetes.

Stable carbon isotope analysis of modern and archaeological pandanus nutshell from Australia’s oldest known archaeological site of Madjedbebe reveals precipitation fluctuations over the last 65,000 years.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

The resource-poor countries of Africa have traditionally relied on Western nations for their drug supply, but a new drug development center with a promising antimalarial agent could pave the way for a homegrown pharmaceutical pipeline. Linda Nordling investigates how this one facility at the southern tip of the continent promises to embolden an entire African drug industry.

Modelled estimates of the environmental impact of dietary choices often fail to reflect true dietary practice. This study links a dietary dataset from 55,000 UK consumers with food-level data on GHG emissions, land use, water use, eutrophication and biodiversity to compare the environmental burden of different levels of meat consumption.

Osteocrin is a non-neuronal secreted protein in mice that has been evolutionarily repurposed to act as a neuronal development factor in primates.

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.

Acquired resistance limits the efficacy of PARP inhibitors (PARPi) in high grade serous ovarian cancer (HGSOC). Here, the authors show that inhibition of RNA polymerase I transcription using CX-5461 increases the therapeutic efficacy of PARPi and overcomes PARPi resistance in PDX models of HGSOC.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

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.

Conservation actions focused on flagship species are effective at raising funds and awareness. Here, McGowan et al. show that prioritizing areas for conservation based on the presence of flagship species results in the selection of areas with ~ 79-89% of the total species that would be selected by maximizing biodiversity representation only.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

A platform for genetic circuit design in a human gut commensal bacterium brings microbiome therapies that respond to gastrointestinal signals a step closer.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Rett syndrome is caused by mutations in MeCP2, and this study identifies a site on MeCP2, T308, whose phosphorylation is regulated by neuronal activity: phosphorylation of T308 blocks the interaction of MeCP2 with the NCoR co-repressor complex, suppressing MeCP2's ability to repress transcription, and mice carrying mutations of MeCP2 T308 show Rett-syndrome-related symptoms.

As multiple UN fora develop parallel rules for sharing benefits from digital sequence information, we urge better coordination. International policymakers should focus on harmonizing new benefit-sharing rules to ensure open access to data, database interoperability, and better benefit sharing outcomes.

The protocol describes coculture of a primary human colon monolayer derived from cells growing in colon organoids with aerotolerant bacteria, such as strains of B. thetaiotaomicron genetically engineered to respond to different stimuli in colonic microenviroments.