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Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. To elucidate the role of EMT in the development of aberrant basaloid cells from the bronchial epithelium, we mapped EMT-induced transcriptional changes at the population and single-cell levels. Human bronchial epithelial cells grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Comparison of submerged and ALI cultures revealed differential expression of 8,247 protein coding (PC) and 1,621 long noncoding RNA (lncRNA) genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,020 PC and 907 lncRNA genes. Although there was no evidence for fibroblast/myofibroblast conversion following EMT induction, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. The substantial transcriptional differences between submerged and ALI cultures highlight that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and an interactive browser ( https://bronc-epi-in-vitro.cells.ucsc.edu/ ) of single-cell RNA-Seq data for further exploration of potential roles in the lung epithelium in health and lung disease. 

Lipid vesicles play a key role in fundamental biological processes. Despite recent progress, we lack a complete understanding of the non-equilibrium dynamics of vesicles due to challenges associated with long-time observation of shape fluctuations in strong flows. In this work, we present a flow-phase diagram for vesicle shape and conformational transitions in planar extensional flow using a Stokes trap, which enables control over the center-of-mass position of single or multiple vesicles in precisely defined flows [A. Shenoy, C. V. Rao and C. M. Schroeder, Proc. Natl. Acad. Sci. U. S. A. , 2016, 113 (15), 3976–3981]. In this way, we directly observe the non-equilibrium conformations of lipid vesicles as a function of reduced volume ν , capillary number Ca, and viscosity contrast λ . Our results show that vesicle dynamics in extensional flow are characterized by the emergence of three distinct shape transitions, including a tubular to symmetric dumbbell transition, a spheroid to asymmetric dumbbell transition, and quasi-spherical to ellipsoid transition. The experimental phase diagram is in good agreement with recent predictions from simulations [V. Narsimhan, A. P. Spann and E. S. Shaqfeh, J. Fluid Mech. , 2014, 750 , 144]. We further show that the phase boundary of vesicle shape transitions is independent of the viscosity contrast. Taken together, our results demonstrate the utility of the Stokes trap for the precise quantification of vesicle stretching dynamics in precisely defined flows. 

Abstract Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic 1,2 . Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches 1 , while maintaining proven prevention measures using a vaccines-plus approach 2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities 3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.