431 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

    Expression profiles of hydrophobic surfactant proteins in children with diffuse chronic lung disease

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    BACKGROUND: Abnormalities of the intracellular metabolism of the hydrophobic surfactant proteins SP-B and SP-C and their precursors may be causally linked to chronic childhood diffuse lung diseases. The profile of these proteins in the alveolar space is unknown in such subjects. METHODS: We analyzed bronchoalveolar lavage fluid by Western blotting for SP-B, SP-C and their proforms in children with pulmonary alveolar proteinosis (PAP, n = 15), children with no SP-B (n = 6), children with chronic respiratory distress of unknown cause (cRD, n = 7), in comparison to children without lung disease (n = 15) or chronic obstructive bronchitis (n = 19). RESULTS: Pro-SP-B of 25–26 kD was commonly abundant in all groups of subjects, suggesting that their presence is not of diagnostic value for processing defects. In contrast, pro-SP-B peptides cleaved off during intracellular processing of SP-B and smaller than 19–21 kD, were exclusively found in PAP and cRD. In 4 of 6 children with no SP-B, mutations of SFTPB or SPTPC genes were found. Pro-SP-C forms were identified at very low frequency. Their presence was clearly, but not exclusively associated with mutations of the SFTPB and SPTPC genes, impeding their usage as candidates for diagnostic screening. CONCLUSION: Immuno-analysis of the hydrophobic surfactant proteins and their precursor forms in bronchoalveolar lavage is minimally invasive and can give valuable clues for the involvement of processing abnormalities in pediatric pulmonary disorders

    Braving difficult choices alone: children's and adolescents' medical decision making.

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    OBJECTIVE: What role should minors play in making medical decisions? The authors examined children's and adolescents' desire to be involved in serious medical decisions and the emotional consequences associated with them. METHODS: Sixty-three children and 76 adolescents were presented with a cover story about a difficult medical choice. Participants were tested in one of four conditions: (1) own informed choice; (2) informed parents' choice to amputate; (3) informed parents' choice to continue a treatment; and (4) uninformed parents' choice to amputate. In a questionnaire, participants were asked about their choices, preference for autonomy, confidence, and emotional reactions when faced with a difficult hypothetical medical choice. RESULTS: Children and adolescents made different choices and participants, especially adolescents, preferred to make the difficult choice themselves, rather than having a parent make it. Children expressed fewer negative emotions than adolescents. Providing information about the alternatives did not affect participants' responses. CONCLUSIONS: Minors, especially adolescents, want to be responsible for their own medical decisions, even when the choice is a difficult one. For the adolescents, results suggest that the decision to be made, instead of the agent making the decision, is the main element influencing their emotional responses and decision confidence. For children, results suggest that they might be less able than adolescents to project how they would feel. The results, overall, draw attention to the need to further investigate how we can better involve minors in the medical decision-making process

    Guessing imagined and live chance events: adults behave like children with live events

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    An established finding is that adults prefer to guess before rather than after a chance event has happened. This is interpreted in terms of aversion to guessing when relatively incompetent: After throwing, the fall could be known. Adults (N=71, mean age 18;11, N=28, mean age 48;0) showed this preference with imagined die-throwing as in the published studies. With live die-throwing, children (N=64, aged 6 and 8 years; N=50, aged 5 and 6 years) and 15-year-olds (N=93, 46) showed the opposite preference, as did 17 adults. Seventeen-year-olds (N=82) were more likely to prefer to guess after throwing with live rather than imagined die-throwing. Reliance on imagined situations in the literature on decision-making under uncertainty ignores the possibility that adults imagine inaccurately how they would really feel: After a real die has been thrown, adults, like children, may feel there is less ambiguity about the outcome

    Sources of pro-cyclicality in east Asian financial systems

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    Procyclicality is a normal feature of economic systems, but financial sector weaknesses can exacerbate it sufficiently to pose a threat to macroeconomic and financial stability. These include shortcomings in bank risk management and governance, in supervision and in terms of dependence on volatile sources of funds. The paper tests econometrically for the importance of such features leading to pro-cyclicality in the financial systems of 11 East Asian countries. This analysis makes it possible to identify specific policy measures for East Asian countries that could limit the extent to which financial systems exacerbate pro-cyclicality

    A virtual reality and retailing literature review: Current focus, underlying themes and future directions

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    This literature review reveals the current research focus, underlying themes and prominent research gaps in the Virtual Reality (VR) literature. 89 journal articles from the 22 years are thematically analysed in order to non-obvious reveal interconnections and themes, including research focus over time and underlying themes by research discipline. Over half of all papers focus on the need to understand the VR shopping consumer, yet no consensus exists as to what the optimal experience is or how to design effective v-Commerce stores. The most prominent research gaps are related to the unique HCI aspects in v-Commerce that influence shopping behaviours. The impact of this review is establishing the current challenges and future directions for academia in order to make v-Commerce a viable reality. Specifically, future research should focus on develop human factor theory in VR shop design (i.e. social dimension, eye-tracking etc.)

    Hostile and Benevolent Sexism: The Differential Roles of Human Supremacy Beliefs, Women’s Connection to Nature, and the Dehumanization of Women

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    Scholars have long argued that sexism is partly rooted in dominance motives over animals and nature, with women being perceived as more animal-like and more closely connected to nature than men. Yet systematic research investigating these associations is currently lacking. Five studies (total N=2,409) consistently show that stronger beliefs in human supremacy over animals and nature were related to heightened hostile and benevolent sexism. Furthermore, perceiving women as more closely connected to nature than men was particularly associated with higher benevolent sexism, whereas subtle dehumanization of women was uniquely associated with higher hostile sexism. Blatant dehumanization predicted both types of sexism. Studies 3 and 4 highlight the roles of social dominance orientation and benevolent beliefs about nature underpinning these associations, while Study 5 demonstrates the implications for individuals’ acceptance of rape myths and policies restricting pregnant women’s freedom. Taken together, our findings reveal the psychological connections between gender relations and human-animal relations
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