Two studies expand the applications of mRNA-based therapeutics. August et al. show that mRNA-based therapeutics can drive expression of a functional antibody in humans at levels capable of neutralizing Chikungunya virus ex vivo. In a separate study, Lusso et al. show that an mRNA vaccine platform to prevent HIV-1 infection generated broadly neutralizing antibodies in nonhuman primates and protected some animals from infection, raising hope that optimization of this approach might lead to an effective HIV vaccine.

See Lusso et al.

In this issue, Nature Medicine is launching a Series on Diversity, Equity and Inclusion in medical research. The first installment brings a perspective on the role of funders in addressing the continued lack of diversity in science and medicine in the United States, and an overview of how governmental, societal and philanthropic stakeholders are approaching lack of diversity and inequalities in their research programs.

See Series on Diversity, Equity and Inclusion [https://www.nature.com/collections/hbifidcdbe]

Germline predisposition plays a major part in myelodysplastic syndromes in children. Sahoo et al. report that germline mutations in the genes SAMD9 and SAMD9L account for 8% of pediatric myelodysplastic syndromes. These genes produce overlapping phenotype patterns and comparable clinical outcomes. The causative mutations suppress cell growth and are associated with genetic rescue, which results in heterogeneous patterns of clonal hematopoiesis in 61% of patients. This high rate of somatic mosaicism is unprecedented in human disease. The cover depicts the concept of mosaicism and the exceptional plasticity of hematopoiesis in children.

See Sahoo et al.

Rui-Hua Xu and colleagues at Sun Yat-sen University Cancer Center, in Guangzhou (China), report interim results of the phase 3 randomized JUPITER-02 trial evaluating the frontline anti-PD-1 antibody toripalimab in combination with standard chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma. The watercolor displays a mountainous landscape at sunrise that transforms into the silhouette of a face, illustrating the combination of art and medicine. A bright red sun rising over the nose-like peak symbolizes the hope brought forth by a new treatment for patients with advanced nasopharyngeal carcinoma, who have limited therapeutic options available.

See Rui-Hua Xu and colleagues

Spiegel et. al report a phase 1 trial of a bispecific CD19–CD22 chimeric antigen receptor (CAR) that met safety and efficacy endpoints. Antigen expression in relapsed patients demonstrated absent or low CD19 with preservation of CD22, and single-cell assays revealed greater cytokine production by the CAR T cells in response to CD19 than in response to CD22. The cover shows the bispecific CAR recognizing both antigens but eliciting a stronger response to CD19 than to CD22, which illustrates the challenge of ensuring equipotent targeting of antigens by multi-specific CAR T cells.

SeeSpiegel et al.

Rachel McKendry, Valérian Turbé and colleagues at University College London and the Africa Health Research Institute use deep-learning algorithms to classify images of rapid human immunodeficiency virus lateral-flow tests acquired in rural South Africa. The pilot study demonstrated high levels of sensitivity and specificity relative to that of traditional visual interpretation. The cover, by Da Huang, a postdoctoral fellow in the University College London i-sense team, is influenced by African designs and illustrates the use of a mobile tablet to collect and analyze test results. This research highlights the potential of deep learning–enabled diagnostics in low-resource settings.

SeeMcKendry and colleagues

McIntosh et al. describe an artificial intelligence (AI) model that generates radiation treatment plans for patients with prostate cancer. Following a stepwise framework, AI was successfully deployed in a standard-of-care clinical setting, providing gains in efficiency, improved treatment quality, and an understanding of physicians’ decision-making and perceptions of AI use when patient care is at stake. The cover by Adam Badzynski illustrates the AI embedded within the therapeutic clinical realm, with the patient at the center and the AI working collaboratively with the healthcare team to achieve an optimal personalized radiation treatment.

See McIntosh et al.

Carraro and colleagues report results from a study by a multi-institute consortium in which single-cell transcriptomics was applied to compare the airway cell subtypes of patients with cystic fibrosis (CF) with those of previously healthy patients. The cover by Matthew Gangl, a scientist at the Cystic Fibrosis Foundation, illustrates how single-cell transcriptomics shines a light on the tapestry of cellular subtypes in the airway and how CF lung disease alters the landscape. Collectively, this work aims to provide a framework for the development of therapies for CF.

See Carraro and colleagues

Although brain perivascular fibroblast cells were not previously considered to be involved in the etiology of amyotrophic lateral sclerosis (ALS), their activity shows a promising early indication of disease symptoms. Månberg and colleagues show that perivascular fibroblast cells become activated in patients with sporadic ALS and in mouse models at an early stage that precedes neuronal loss. The cover artwork by Mattias Karlen shows the location of perivascular fibroblast cells in the neurovascular unit and the formation of an enlarged perivascular space.

See Månberg et al.

The cover image was painted by Ali Al-Nasser, a medical laboratory technologist from Zahra (Kuwait), and portrays him working at the bench while preparing SARS-CoV-2 nasopharyngeal swabs for DNA extraction. The COVID-19 pandemic disrupted the course of normal life; like Ali Al-Nasser, many scientists turned to art to provide them with an escape from the stress of everyday life in lockdown.

See Focus

Grover and colleagues report that non-invasive modulation of high-frequency brain rhythms improves obsessive–compulsive behaviors. Using personalized high-definition transcranial alternating-current stimulation (HD-tACS), the team modulated brain rhythms in the reward-processing circuitry to reduce obsessive–compulsive symptoms. The cover depicts the neuromodulation electrodes placed on the scalp of the study participants, and represents the consequent improvements in mental health. The cover exemplifies the dawn of non-invasive neuromodulation in experimental psychiatric medicine.

See Grover and colleagues

The study by Simon Hay and colleagues at the IHME COVID-19 Forecasting Team employs statistical and mathematical modeling to build projections of future courses of the COVID-19 pandemic in the USA under various scenarios of social-distancing measures and universal mask use, as represented in the cover image.

See Hay and colleagues