945 research outputs found

    Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium.

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    Lung epithelial lineages have been difficult to maintain in pure form in vitro, and lineage-specific reporters have proven invaluable for monitoring their emergence from cultured pluripotent stem cells (PSCs). However, reporter constructs for tracking proximal airway lineages generated from PSCs have not been previously available, limiting the characterization of these cells. Here, we engineer mouse and human PSC lines carrying airway secretory lineage reporters that facilitate the tracking, purification, and profiling of this lung subtype. Through bulk and single-cell-based global transcriptomic profiling, we find PSC-derived airway secretory cells are susceptible to phenotypic plasticity exemplified by the tendency to co-express both a proximal airway secretory program as well as an alveolar type 2 cell program, which can be minimized by inhibiting endogenous Wnt signaling. Our results provide global profiles of engineered lung cell fates, a guide for improving their directed differentiation, and a human model of the developing airway

    ABC messages for HIV prevention in Kenya: Clarity and confusion, barriers and facilitators

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    The Horizons Program and FHI/IMPACT developed a collaborative research study to explore how adults and youth in Kenya define and perceive the ABC (abstinence/being faithful/consistent condom use) terms and behaviors. Additional objectives of the study were to identify attitudes and norms around the ABC behaviors that influence perceptions of them, and the role of important actors in transmitting messages about them. Findings highlight potential challenges in promoting each of the ABC behaviors, as well as some positive elements that can be built upon when developing programs. HIV prevention programs that incorporate ABC messages—both in Kenya and elsewhere—should consider a number of lessons highlighted in this study

    ABCs for HIV prevention in Kenya: Messages, beliefs, and barriers

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    A great deal of attention has been focused recently on promoting the “ABCs” of HIV prevention— abstinence or delaying sex, being faithful to one sexual partner or reducing the number of sexual partners, and consistently using condoms during sex. Yet even as programs that focus on the ABCs to prevent sexual HIV transmission are rolled out, questions remain about how well different groups in varied cultural contexts understand the terms, as well as how best to address challenges to adopting the ABC behaviors. The Horizons Program and FHI/IMPACT developed a collaborative research study in 2004 to explore how adults and youth in Kenya define and perceive the ABC terms and behaviors. Additional study objectives, noted in this research summary, were to identify attitudes and norms around the ABC behaviors that influence perceptions of them, and the role of important actors in transmitting messages about them. Findings highlight potential challenges in promoting each of the ABC behaviors, as well as some positive elements that can be built upon when developing programs

    Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study

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    Assessing the association of the newborn metabolic state with severity of subsequent respiratory tract infection may provide important insights on infection pathogenesis. In this multi-site birth cohort study, we identified newborn metabolites associated with lower respiratory tract infection (LRTI) in the first year of life in a discovery cohort and assessed for replication in two independent cohorts. Increased citrulline concentration was associated with decreased odds of LRTI (discovery cohort: aOR 0.83 [95% CI 0.70-0.99], p = 0.04; replication cohorts: aOR 0.58 [95% CI 0.28-1.22], p = 0.15). While our findings require further replication and investigation of mechanisms of action, they identify a novel target for LRTI prevention and treatment
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