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The coronavirus disease 2019 (COVID-19) pandemic altered education, exams, and residency applications for United States medical students.To determine the specific impact of the pandemic on US medical students and its correlation to their anxiety levels.An 81-question survey was distributed397 medical students from 29 states were analyzed. Approximately half of respondents reported feeling depressed since the pandemic onset. 62% of participants rated 7 or higher out of 10 when asked about anxiety levels. Stressors correlated with higher anxiety scores included "concern about being unable to complete exams or rotations if contracting COVID-19" (RR 1.34; 95%CI: 1.05-1.72,COVID-19 significantly impacted medical students in numerous ways. Medical student education and clinical readiness were reduced, and anxiety levels increased. It is vital that medical students receive support as they become physicians. Further research should be conducted on training medical students in telemedicine to better prepare students in the future for pandemic planning and virtual healthcare.

Mesodermal progenitors in the second heart field (SHF) express Delta-like-ligand 4 (Dll4) that regulates Notch-mediated proliferation. As cells of SHF lineage mature to assume endocardial and myocardial cell fates, we have shown that Dll4 expression is lost, and the subsequent expression of another Notch ligand Jagged1 regulates Notch-mediated maturation events in the developing heart. A subset of SHF progenitors also matures to form the pharyngeal arch artery (PAA) endothelium. Dll4 was originally identified as an arterial endothelial-specific Notch ligand that plays an important role in blood vessel maturation, but its role in aortic arch maturation has not been studied to date secondary to the early lethality observed in Dll4 knockout mice. We show that, unlike in SHF-derived endocardium and myocardium, Dll4 expression persists in SHF-derived arterial endothelial cells. Using SHF-specific conditional deletion of Dll4, we demonstrate that as SHF cells transition from their progenitor state to an endothelial fate, Dll4-mediated Notch signalling switches from providing proliferative to maturation cues. Dll4 expression maintains arterial identity in the PAAs and plays a critical role in the maturation and re-organization of the 4th pharyngeal arch artery, in particular. Haploinsufficiency of Dll4 in SHF leads to highly penetrant aortic arch artery abnormalities, similar to those observed in the clinic, primarily resulting from aberrant reorganization of bilateral 4th pharyngeal arch arteries. Hence, we show that cells of SHF lineage that assume an arterial endothelial fate continue to express Dll4 and the resulting Dll4-mediated Notch signalling transitions from an early proliferative to a later maturation role during aortic arch development.