Volume 28 Issue 5, May 2022

Drones are increasingly used to deliver essential health supplies in remote, underserved and Indigenous communities, but drone suppliers are keen to expand into the lucrative prescription drug market in the US.

The pandemic is far from over in Africa, but there is also a funding gap in preparing for endemic COVID-19, which will require long-term investment in healthcare infrastructure.

Genetic ancestry affects human health, but this is distinct from the impact of race, a social construct that has its foundations in systemic racism. These terms need to be better defined and understood in medical research to achieve health equity.

Many governments are rolling back restrictions, but the pandemic will end only with a renewed focus on equitable distribution of vaccines and therapeutics, responsive public health plans, and policies to protect the vulnerable.

Open datasets, curated around unsolved medical problems, are vital to the development of computational research in medicine, but remain in short supply. Nightingale Open Science, a non-profit computing platform, was founded to catalyse research in this nascent field.

Electronic cigarettes might be superior to nicotine replacement therapy as a quitting aid for pregnant women — but enthusiasm is hampered by low rates of smoking cessation and unknown long-term harm.

The DAWN and SEED trials demonstrate the potential of glucokinase activators for the treatment of type 2 diabetes, but how they fit in the overall treatment algorithm remains to be determined.

As the pandemic evolves, questions remain but field studies are increasingly difficult; if carefully designed, human challenge models could offer a practical and timely solution.

Two new studies provide robust epidemiological evidence and a mechanistic link, with potential implications for strategies that target Epstein–Barr virus.

PIK3CA gain-of-function mutations are among the most common alterations in human solid cancers. Through the use of stimulation-induced functional T cell receptor (TCR) sequencing (SIFT-seq), a panel of TCRs that bind a mutant PI3Kα shared neoantigen was identified, including a potential clinical candidate that engages cancer cells via a distinctive CDR3β loop.

Phenotypic heterogeneity in type 2 diabetes (T2D) was visualized by non-linear dimensionality reduction in a cohort of over 23,000 people. Variation in the T2D phenotype mapped to variation in drug response, risk of disease complications and underlying genetic architecture.

Certain acute infections (including SARS-CoV-2) are associated with an unexplained chronic disability in a minority of patients; this Review summarizes what is known about these understudied and complex illnesses.

The DECIDE-AI checklist, resulting from a multi-stakeholder group of experts in a Delphi process and following the EQUATOR Network’s recommendations, includes key items that should be reported in early-stage clinical studies of AI-based decision support systems, to ensure a responsible and transparent deployment of AI systems in healthcare.

A multi-scale model using population-level transmission and individual-level vaccination data suggests that vaccine dose fractionation could be a cost-effective strategy for mitigating the COVID-19 pandemic in India.

The randomized B-F1RST trial evaluating the clinical utility of blood tumor mutational burden as a predictor of benefit from atezolizumab in patients with advanced lung cancer did not meet its pre-specified primary objective, underscoring the need to further investigate the significance of bTMB as a relevant biomarker for patient selection.

A new high-throughput platform to find rare T cells that can recognize shared cancer neoantigens identifies T cell receptors specific for a conserved, immunogenic and therapeutically actionable epitope in mutant PI3Kα, one of the most common driver oncogenes

A randomized controlled trial comparing the efficacy of electronic cigarettes and nicotine patches for smoking cessation in pregnant women found no differences between the interventions. However, electronic cigarettes were found to have some benefit when only the data from women who adhered strictly to the trial protocol were analyzed.

The SEED study is a phase 3 clinical trial demonstrating a beneficial effect on glycemic control of dorzagliatin, a glucokinase activator, in drug-naive patients with newly diagnosed type 2 diabetes.

The DAWN study is a phase 3 clinical trial that demonstrates effective glycemic control of dorzagliatin as an add-on therapy to metfomin in patients with type 2 diabetes.

A new analysis of patients newly diagnosed with diabetes uses a data dimenionality reduction approach to understand how phenotypic variation drives diseaese onset, clinical outcomes and responses to glycemic-lowering medications.

Analysis of a multicenter cohort of kidney transplants shows that mismatches in the MICA locus and the presence of anti-MICA donor-specific antibodies are associated with reduced graft survival and increased rejection.

The analysis of large transplant cohorts reveals that in the context of liver transplant, but not kidney transplant, both the donor and the recipient type 2 diabetes polygenic risk scores influence the risk of developing post-transplant diabetes.

The first report from the prospective GenoVA Study provides preliminary insights into the development of a polygenic risk score assay in a clinical setting and discusses the challenges of generating, interpreting and reporting results.

Intravitreal administration of the antisense oligonucleotide sepofarsen in patients with Leber congenital amaurosis type 10 showed a manageable safety profile, ocular adverse events being dose dependent, and achieved meaningful improvements of visual function.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

In the first SARS-CoV-2 challenge study in humans, 36 young, healthy adult participants were intranasally inoculated with virus and monitored for productive infection, symptoms, virus kinetics, antibody response and safety in a controlled setting.

A third dose of the COVID-19 vaccine mRNA-1273 is safe and boosts SARS-CoV-2 neutralizing antibody titers almost two-fold higher than the peak levels observed after completion of a two-dose series, highlighting the potential clinical benefit of a booster dose.

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.

A test-negative case–control analysis using data from a diverse population in California, USA, demonstrates that vaccine efficacy of a three-dose regimen of the mRNA-1273 COVID-19 vaccine is reduced against infection with the Omicron SARS-CoV-2 variant in comparison to Delta, but that efficacy against hospitalization remained high for both variants.

A large study in the United Kingdom shows that virus-specific antibody levels associated with at least 67% protection against SARS-CoV-2 Delta variant infection last longer after two doses of BNT162b2 vaccine than after two doses of ChAdOx1 vaccine in previously uninfected individuals.

A microfluidic CRISPR-based platform enables multiplexed and high-throughput identification of a wide range of respiratory viruses, including the ability to identify specific SARS-CoV-2 variants such as Delta and Omicron.