Epigenomics regulates gene expression and is as important as genomics in precision personal health, as it is heavily influenced by environment and lifestyle. In this issue of Nature Medicine, Michael Snyder and colleagues report that changes in different types of ‘omics’ data associate with different physiological aspects of a human volunteer studied over a period of 36 months: DNA methylation with chronic conditions and transcriptome with acute events.

See Snyder and colleagues

Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment. In this issue of Nature Medicine, two independent groups report the results of clinical trials testing the feasibility of neoadjuvant immune check point blockade in patients with high-risk melanoma. The cover art represents the concept of finding the right timing for combination of immunotherapy and conventional therapies to improve the outcome of patients with cancer.

See Wargo and colleagues, Blank et al. and Perspective by Robert

Clinical studies have demonstrated that the composition of the gut microbiome often links to patient health. However, recent work has also revealed extensive variation in the composition of the gut microbiome, even among seemingly healthy patients. In this issue of Nature Medicine, two large-scale clinical microbiome studies provide transformative insight into two factors contributing to this variation: ethnicity and geography. The cover art is a conceptual representation of the work by Hong-wei Zhou and colleagues identifying host location as having the strongest association with microbiota variation in a cohort of 7,009 individuals from 14 districts within a single province in China.

See Zhou and colleagues, Deschasaux et al. and News & Views by Sharpton and Gaulke

Artificial intelligence (AI) approaches can be employed to classify medical imaging data, with the hope that these systems might aid in clinical diagnoses. In this issue, Eric Oermann and colleagues apply deep learning to triage and prioritize radiological workflows to accelerate time to diagnosis for urgent neurological events. In a separate study, Olaf Ronneberger and colleagues report on a deep-learning framework that can recommend how patients should be referred for treatment for over 50 eye diseases with the same accuracy as expert ophthalmologists. Conor Liston discusses the implications of these studies in an accompanying News & Views. The cover depicts abstract 'layers' through the human eye, making the connection between layers of the retina and layers within a neural network and demonstrating the transparency of the approach developed by Ronneberger and colleagues.

See Oermann and colleagues, Ronneberger and colleagues and News & Views by Liston

In this issue, Iannis Aifantis and colleagues report that the oncogenic NOTCH1 controls activation of the heat-shock response in T cell acute lymphoblastic leukemia, and they uncover potential biomarkers of response to HSP90 inhibition. The cover art is a reproduction of ‘The Heat Factor’ (Despina Stokou, 2018; oil, markers, charcoal and collage on canvas). Text from the manuscript was incorporated in the artwork.

See Aifantis and colleagues

Studying a cohort of women who were healthy at study baseline but eventually developed acute myeloid leukemia (AML) during follow-up, Pinkal Desai and colleagues(p1015) find that specific somatic mutations impacting the risk of developing disease can be detected years before the clinical diagnosis. Benjamin Ebert discusses the implications of this study and a related manuscript in Nature by Liran Shlush and colleagues in a News & Views(p904). The cover depicts a conceptual representation of the passage of time and transformation of normal cells into leukemia.

See Desai et al. and News & Views by Ebert

Cytokine release syndrome (CRS) and neurotoxicity limit the application of CAR T cell therapies in the clinic. In this issue, Bondanza and colleagues (p. 739) recapitulate key features of CRS in a mouse model and identify a causative role of monocyte-derived IL-1 in these adverse events, both of which can be blocked by IL-1 inhibition. In a related study, Sadelain and colleagues (p. 731) show that macrophages mediate CRS and develop a strategy to prevent CRS by expressing IL-1 inhibitor in CAR T cells. Cliona Rooney discusses both studies in a News & Views (p. 705). The cover depicts an activated monocyte producing IL-1 and IL-6.

See Bondanza et al., Sadelain et al. and News & Views by Rooney

Diffuse midline gliomas (DMGs) with the histone H3 K27M mutation are fatal pediatric tumors. In this issue, Michelle Monje and colleagues report that CAR T cells targeting the disialoganglioside GD2 are capable of killing DMG cells in preclinical models, offering hope for clinical translation of this immunotherapy. The cover depicts a tiger attacking hyenas, which do not naturally coexist in the same geographic region, to represent an exogenously introduced CAR T cell attacking glioma cells.

See Monje et al.

Badders, Korf et al. (p 427) report that a selective androgen receptor modulator rescues degeneration in a preclinical trial using a mouse model of Spinobulbar muscular atrophy. The cover shows a wide-field image depicting the degeneration within hindlimb muscle of SBMA mice. Nuclei are labeled blue, acetylcholine receptors are labeled green and synaptophysin is labeled red. Image Credit: Jamshid Temirov, James Messing, and Ane Kroff, St. Jude Children's Research Hospital.

The ability of macrophages to integrate metabolic and immune signaling is a key determinant of atherogenesis. Sallam et al. (p 304) report the identification of a non-coding RNAs, MeXis, that coordinates cellular responses to cholesterol overload in macrophages and lesion development. The cover image is a scanning electron micrograph depicting a dying cholesterol-loaded macrophage with cholesterol crystals piercing the cell and extending from the cell surface. Image Credit: Thomas Weston, Cuiwen He and Stephen G Young, UCLA.

In this issue, C. Krieg and colleagues (p 144) characterize hundreds of myeloid and lymphoid cell subsets in the blood of patients with melanoma, and report that classical monocyte frequency is one of the strongest predictors of response to PD-1 blockade therapy among these cell populations. The image features a colored scanning electron micrograph of different types of human leucocytes and red blood cells. Credit: Dennis Kunkel Microscopy/Science Source

In this issue, X.-J. Zhang et al. (p 73) and P. Zhang et al. (p 84) report on the identification and testing of a potential therapeutic pathway for ischemia-reperfusion liver injury and for nonalcoholic fatty liver disease, respectively, in mice and in large animal models. The cover image features a colored scanning electron micrograph of the intracellular space of a hepatocyte. Image credit: Pietro M. Motta and Tomonori Naguro/Science Source.