Cerezo-Wallis and colleagues report that melanoma-secreted midkine (MDK) educates macrophages to support immunoevasion and immunotherapy resistance in melanoma. The cover, which was hand-painted by a Venezuelan artist (mother of the first author), depicts what she envisioned when the duality of the immune system in cancer was explained to her. Specifically, the artist represented in the cover the ability of macrophages to switch their phenotypic and functional features to either kill melanoma cells (upper part) or favor their metastatic potential (bottom), in the absence or presence of MDK, respectively.

See Cerezo-Wallis and colleagues

Conventional mesenchymal stromal cell (MSC)-based manufacturing approaches are hampered by challenges with scalability and inter-donor variability, which leads to inconsistent results from diverse clinical trials. Novel induced pluripotent stem cell (iPSC)-based techniques have the potential to overcome these challenges by facilitating the clinical-grade production of very large quantities of consistently differentiated cells. This illustration by Patton'd Studios represents an iPSC-derived mesenchymoangioblast colony, which is a crucial intermediate step in an optimized good manufacturing practice–compliant process for MSC production.

See Rasko and colleagues

The path to productive collaboration between researchers and patients is not always easy, with language differences, knowledge gaps and power dynamics setting considerable barriers along the way. In this issue, we explore how patient- and community-led research is achievable if both sides make it a priority. The cover, designed by illustrator Sarah Lippett, a person living with a rare disease who explores her diagnostic odyssey in her work, shows how effective and equitable patient–researcher collaboration can be transformative to research.

See Collection

The image on the cover illustrates the potential of artificial intelligence (AI) to enhance healthcare delivery. In this issue, new extensions of SPIRIT and CONSORT guidelines dedicated to randomized clinical trials involving AI delineate the reporting standards for these interventions, and Nimri and colleagues report the results of a randomized clinical trial evaluating the performance of an AI for optimizing insulin dosing in patients with type 1 diabetes.

See Revital Nimri et al.

The COVID-19 pandemic has necessitated the acceleration of the development of digital technologies to monitor the spread of the outbreak. Emergency powers are being used to track not just individuals’ health data, but other personal information. The image shows the data that are being monitored on people’s cell phones, and the effects on healthcare are discussed in this focus issue on COVID-19 and digital privacy.

See Focus

The cover illustration represents the artist’s impression of a tumor microenvironment releasing fragments of cell-free DNA (cfDNA) into the bloodstream. Nassiri, Chakravarthy, Feng et al. report that DNA-methylation profiling of these cfDNA fragments allows non-invasive detection and classification of common primary intracranial tumors. Similarly, Nuzzo, Berchuck et al. report that methylation profiling of cfDNA from plasma and urine allows accurate classification of patients with renal-cell carcinoma.

See Nassiri et al. and Nuzzo et al.

The cover illustration showcases the concept and functionality of the machine-learning model developed by Liu et al. to identify and assist in the diagnosis of skin conditions in routine clinical practice through everyday technology such as cellphones and laptops. By leveraging these devices, this research potentially expands universal access to high-quality information about skin conditions and may accelerate the deployment of digital solutions into clinical practice.

See Liu et al.

Locoregional delivery of CAR T cells to the central nervous system (CNS) shows promise for the treatment of atypical teratoid/rhabdoid tumors in infants. Theruvath and colleagues identify overexpression of B7-H3 in these tumors that can be targeted with B7-H3-CAR T cells. The cover shows that CNS-delivered CAR T cells are more potent and traffic more rapidly to the tumor, and induce less systemic inflammation with equivalent persistence, compared with systemically delivered CAR T cells.

See Theruvath et al.

Pediatric patients have been shown to be less likely than adult patients to develop severe symptoms after infection by the novel SARS-CoV-2 virus. Zhang and colleagues report the epidemiological and clinical features of ten children who tested positive for viral infection, and provide evidence for viral excretion through the gastrointestinal and respiratory tracts. The cover image illustrates viral particles in the intestine, representing persistent viral shedding in rectal swabs in otherwise asymptomatic children.

See Xu et al.

Monitoring of infants and children in intensive care units (ICUs) typically involves hard-wired devices and catheters that can complicate care and impede close contact between parent and child. Rogers and colleagues describe a platform for comprehensive monitoring in neonatal and pediatric ICUs using wireless, soft biosensor patches. The cover image shows that these patches, placed on the back and ankle, allow close contact between mother and child.

See Rogers and colleagues

Research into rare cancers is challenging due to their low incidence and the high geographical dispersion of patients. In this issue, Painter et al. describe a patient-partnered research framework that uses social media to engage and partner with patients across the USA and Canada who have been diagnosed with angiosarcoma. The cover art illustrates how this initiative enables patients to participate and accelerate research in this rare disease.

See Painter et al.

Temperatures that deviate from long-term local norms affect human health and are projected to become more frequent as the global climate changes. In this issue, Parks et al. report an association between anomalously warm temperatures and deaths from intentional and unintentional injuries, with increases in deaths from drownings, transport, assault and suicide. The cover art is an illustrated portrayal of the association between rising temperatures and increased injury mortality, and how big data has made such insights possible.

See Parks et al.