Cross-sectional Survey of Medical student Attitudes to Research and Training pathways (SMART) in the UK: study protocol.

BACKGROUND: An understanding and appreciation of scientific research is a key quality of the modern clinician. Yet the Medical Schools Council has previously reported a reduction in the number of clinicians performing research. To explore the reasons for this difficulty, this multicentre, cross-sectional study aims to determine the medical student involvement and perceptions of research and research-orientated careers. It will additionally identify perceived barriers and incentives to participating in research as a student. METHODS AND ANALYSIS: This cross-sectional study of medical students at UK medical schools recognised by the General Medical Council will be administered using an online questionnaire. This will be disseminated nationally over a 2-month period through collaborative university medical school and student networks. The primary outcome is to determine the extent to which medical students are currently involved in research. Secondary outcomes include identifying the personal and demographic factors involved in incentivising and deterring medical students from becoming involved in research during medical school. This will be achieved using a selection of Likert scale, multiple-choice and free text questions. Ordinal logistic regression analysis will be performed to understand the association between specific factors and student involvement in research. This study will also characterise the proportion of medical students who are currently interested in conducting research in the future. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Sciences Interdivisional Research Ethics Committee, Oxford, England. The results will be disseminated via publication in a peer-reviewed medical journal and may be presented at local, regional, national and international conferences by medical student collaborators.

What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 1 million deaths in the first 6 months of the pandemic and huge economic and social upheaval internationally. An efficacious vaccine is essential to prevent further morbidity and mortality. Although some countries might deploy COVID-19 vaccines on the strength of safety and immunogenicity data alone, the goal of vaccine development is to gain direct evidence of vaccine efficacy in protecting humans against SARS-CoV-2 infection and COVID-19 so that manufacture of efficacious vaccines can be selectively upscaled. A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. In this Review, we explore the challenges in assessing the efficacy of candidate SARS-CoV-2 vaccines, discuss the caveats needed to interpret reported efficacy endpoints, and provide insight into answering the seemingly simple question, "Does this COVID-19 vaccine work?"

Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells.

Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.

The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells.

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.