Mitochondrial DNA mutations transmitted maternally within the oocyte cytoplasm often cause life-threatening disorders. Here we explore the use of nuclear genome transfer between unfertilized oocytes of two donors to prevent the transmission of mitochondrial mutations. Nuclear genome transfer did not reduce developmental efficiency to the blastocyst stage, and genome integrity was maintained provided that spontaneous oocyte activation was avoided through the transfer of incompletely assembled spindle-chromosome complexes. Mitochondrial DNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or β-cells, and after cellular reprogramming. Stem cells and differentiated cells had mitochondrial respiratory chain enzyme activities and oxygen consumption rates indistinguishable from controls. These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans.

Objective This research aims to evaluate the impact of eligibility criteria on recruitment and observable clinical outcomes of COVID-19 clinical trials using electronic health record (EHR) data. Materials and Methods On June 18, 2020, we identified frequently used eligibility criteria from all the interventional COVID-19 trials in ClinicalTrials.gov (n = 288), including age, pregnancy, oxygen saturation, alanine/aspartate aminotransferase, platelets, and estimated glomerular filtration rate. We applied the frequently used criteria to the EHR data of COVID-19 patients in Columbia University Irving Medical Center (CUIMC) (March 2020–June 2020) and evaluated their impact on patient accrual and the occurrence of a composite endpoint of mechanical ventilation, tracheostomy, and in-hospital death. Results There were 3251 patients diagnosed with COVID-19 from the CUIMC EHR included in the analysis. The median follow-up period was 10 days (interquartile range 4–28 days). The composite events occurred in 18.1% (n = 587) of the COVID-19 cohort during the follow-up. In a hypothetical trial with common eligibility criteria, 33.6% (690/2051) were eligible among patients with evaluable data and 22.2% (153/690) had the composite event. Discussion By adjusting the thresholds of common eligibility criteria based on the characteristics of COVID-19 patients, we could observe more composite events from fewer patients. Conclusions This research demonstrated the potential of using the EHR data of COVID-19 patients to inform the selection of eligibility criteria and their thresholds, supporting data-driven optimization of participant selection towards improved statistical power of COVID-19 trials.

Derived from follicular epithelial cells, differentiated thyroid cancer (DTC) accounts for the majority of thyroid malignancies. The threefold increase in DTC incidence over the last three decades has been largely attributed to advancements in detection of papillary thyroid microcarcinomas. Efforts to address the issue of overtreatment have notably included the reclassification of encapsulated follicular variant papillary thyroid cancers (EFVPTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In the last 5 years, the overall management approach for this relatively indolent cancer has become less aggressive. Although surgery and radioiodine ablation remain the mainstay of DTC therapy, the role of active surveillance is being explored. Furthermore, the most recent American Thyroid Association (ATA) guidelines offer flexibility between lobectomy and total thyroidectomy for thyroid nodules between 1 cm and 4 cm in the absence of extrathyroidal extension or nodal disease. As our understanding of the natural history and molecular underpinnings of DTC evolves, so might our approach to managing low-risk patients, obviating the need for invasive intervention. Simultaneously, advances in interventional and systemic therapies have greatly expanded treatment options for high-risk surgical candidates and patients with widespread disease, and continue to be areas of active investigation. Continued research efforts are essential to improve our ability to offer effective individualized therapy to patients at all disease stages and to reduce the incidence of recurrent and progressive disease.

Background The principles of global surgery should be taught as a part of the core curriculum in medical schools. The need for medical students to be familiar with the topic is increasing in acceptance. There is, however, a paucity of data on how medical students are exposed to global surgery. This study aims to evaluate exposure of medical students to global surgery, awareness of the key messages of the Lancet Commission on Global Surgery, global surgery career aspirations and barriers to said aspirations. Methods ISOMERS was a multi-centre, online, cross-sectional survey of final year medical students globally. The questionnaire utilised a combination of Likert-scale, multiple-choice, and free text questions. Results In this study, 1593 final year medical students from 144 medical schools in 20 countries participated. The majority (n = 869/1496, 58.1%) believed global surgery to be relevant, despite 17.7% (n = 271/1535) having any exposure to global surgery. Most participants (n = 1187/1476, 80.4%) wanted additional resources on global surgery. Difficulty in providing appropriate care for patients living abroad (n = 854/1242, 68.8%) was the most common perceived barrier to a career in global surgery. Conclusions Participants believed global surgery was a relevant topic for medical students and wanted additional resources that they could access on global surgery. It is critical for medical students to become aware that global surgery is a field that aims to address inequity in surgical care not just internationally, but nationally and locally as well.

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