In this issue, Tadesse and colleagues investigated transmission after a dry-season malaria outbreak in Dire Dawa, Ethiopia. Spatial clustering of Plasmodium falciparum infections around patients with malaria was associated with the presence of Anopheles stephensi carrying Plasmodium sporozoites with molecular signatures of drug and diagnostic resistance. On the cover, using a mouth aspiratory, a researcher captures a mosquito in a goat shelter at the study site.

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In this issue, the NCD Risk Factor Collaboration quantify the prevalence of diagnosed diabetes identified by elevated levels of fasting plasma glucose (FPG), HbA1c or both, demonstrating regional variation in screen-detected diabetes and suggesting that FPG alone might underestimate accurate diabetes prevalence. The icebergs on the cover represent different world regions with varying extents of undiagnosed diabetes submerged below the surface; the colors of the ice illustrate detection with FPG or HbA1c.

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In this issue, Harrold et al. show that immune checkpoint blockade therapy can decrease the risk of the development of specific cancer types in patients with Lynch syndrome. Lynch-syndrome-associated cancers, represented on the cover by a wave of crabs, are blocked by a wall of immunotherapy, with only some cancers occurring in these patients.

See Harrold et al.

In this issue, Zou and colleagues present a multimodal artificial intelligence model that extracts images and their associated descriptions from pathology-related tweets, and show its potential for clinically relevant tasks such as tissue classification. The cover shows a uniform manifold approximation and projection visualization of the pathology images shared on Twitter. These image data were curated and then used to develop the visual-language model.

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In this issue, Hassan et al. show that engineered HLA-independent T cells specific for mesothelin, an antigen that is overexpressed in many cancers, exhibit toxicities as well as anti-tumor activity in patients with treatment-refractory mesothelioma or ovarian cancer. The school of omnivorous koi fish on the cover represents the T cells, which are shown attacking a solid tumor.

See Raffit Hassan et al.

There has been tremendous improvement in human health over the past century, but new threats and growing inequalities have emerged. This Focus issue presents a variety of news, opinions, reviews and original research studies on critical areas and challenges that must be addressed in order to build healthy communities, with special consideration given to the unique needs of younger and older people. The cover depicts planet Earth as a puzzle in progress, with the pieces representing diverse global populations.

In a phase 1/2 clinical trial with patients with glioblastoma, Zadeh and colleagues showed that a single dose of the oncolytic virus DNX-2401, followed by treatment with pembrolizumab, was safe, but no differences were observed in object response rates. A warm tumor microenvironment induced by the oncolytic virus is depicted on the cover. Infiltration of immune cells into typically immunologically cold glioblastomas augments the anti-tumor activity of antibodies to the immunoinhibitory receptor PD-1.

See Farshad Nassiri et al.

Jia et al. leverage neuroimaging, genetic and behavioral data from a cohort of adolescents followed into early adulthood to define a reproducible and general neural basis underlying symptoms of multiple mental health disorders. On the cover, the brain on the floor represents a neurological map, with the highlighted pathways from different psychiatric and mental health disorders converging at a common locale on the map indicating a shared origin for these conditions.

See Xie et al.

Two papers in this issue, by Jamal-Hanjani and colleagues and Al-Sawaf et al., leverage data from the TRACERx lung cancer study to explore the relationships between tissue morphology and the underlying genetic landscape of lung adenocarcinomas and between cancer-associated cachexia and body composition in patients with non–small-cell lung cancer, respectively. The abstract watercolor image on the cover shows a pair of lungs with two tumors, highlighting their spread through air spaces, as well as the effects of cachexia on the diaphragm and adipose tissues.

See Karasaki et al. and Swanton et al.

In this issue, Hazen and colleagues show that erythritol, an artificial sweetener commonly found in low-sugar and sugar-free foods, is associated with incident risk for major adverse cardiovascular events, including heart attack and stroke. The spoon on the cover contains a broken heart drawn with erythritol granules, which represents the health effects of this food additive.

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In this issue, Lazarus et al. find that although acceptance of COVID-19 vaccines has increased in 23 surveyed countries in 2022 relative to 2021, vaccine hesitancy has also increased in some places. The shadow of a dinosaur behind the gloved hand on the cover represents the fears some people have about COVID-19 vaccines due to the spread of misinformation.

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In this issue, Oki et al. show an association between circulating tumor DNA after surgery and recurrence risk in patients with colorectal cancer. The test tube on the cover contains a mixture of red blood cells, immune cells and circulating tumor DNA, reflecting the ability of personalized sequencing technology to identify residual disease at the molecular level, which can in turn help optimize patient management.

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