Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

BACKGROUND: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear. METHODS: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in idiopathic pulmonary fibrosis patient tissues in situ as well as in cell differentiation and invasion assays using patient lung fibroblasts. Cell differentiation and invasion assays established a function of SFRP1 in regulating human lung fibroblast invasion in response to transforming growth factor (TGF)ß1. MEASUREMENTS AND MAIN RESULTS: We discovered a transitional fibroblast state characterised by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1 + cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage-specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1 + transitional fibroblasts and Cthrc1 + myofibroblasts. TGFß1 downregulated SFRP1 in noninvasive transitional cells and induced their switch to an invasive CTHRC1+ myofibroblast identity. Finally, using loss-of-function studies we showed that SFRP1 modulates TGFß1-induced fibroblast invasion and RHOA pathway activity. CONCLUSIONS: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFß1-driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.

Prognostic impact of liver resection side in peri-hilar cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a highly lethal hepatobiliary cancer. Radical resection offers the best chance for extended survival, but the efficacy of left-sided hepatectomy (LH) versus right-sided hepatectomy (RH) remains controversial. METHODS: A systematic review and meta-analysis of non-randomized cohort studies comparing LH and RH in patients with resectable pCCA was conducted. Subanalyses were performed based on year of publication, region, number of cases and Bismuth classification (BC) ≥ III. RESULTS: Nineteen studies involving 3838 patients were included, with 1779 (46 %) undergoing LH and 2059 (54 %) undergoing RH. LH was associated with increased overall survival (OS) in subgroup analysis of studies reporting hazard ratios (HR) (logHR 0.59; p = 0.04). LH showed higher rates of arterial resection (14 % vs. 1 %), transfusion (51 % vs. 41 %), operation time (MD 31.44 min), and bile leakage (21 % vs. 18 %), but lower rates of post-hepatectomy liver failure (9 % vs. 21 %) and 90-day mortality (8 % vs 16 %). Three-year disease-free survival rates increased in Western centers but decreased in Eastern centers. CONCLUSION: LH is linked to higher OS in this analysis but is a more demanding technique. Resection side decision should consider several factors, including future liver remnant, tumor location, vascular involvement, and surgical expertise.

Construcción de subjetividad trans a partir de la ocupación entendida como hacer, ser y llegar a ser / Construção da subjetividade trans a partir da ocupação compreendida como fazer, ser e chegar a ser / Construction of trans subjectivity from the occupation understood as doing, being and becoming

Resumen Introducción Esta investigación indaga la influencia del sistema binario de género en la construcción del sujeto trans desde la perspectiva del Hacer y las potencialidades de Llegar a Ser, en el contexto sociocultural y político chileno, centrándose en las experiencias de los participantes mediante el rescate de la historia ocupacional. Objetivos Analizar la construcción del sujeto trans a través del hacer, ser y llegar a ser en base a sus narrativas y en relación a la estructura social chilena en la cual se desenvuelven, visualizando la influencia en sus estados de salud. Metodo Desde una perspectiva cualitativa con enfoque de conocimientos situados, se utiliza la metodología de producciones narrativas y técnicas discontinuas a múltiples voces. La información fue recolectada mediante entrevistas individuales y un grupo focal. Resultados El proceso de tránsito se presenta como un continuo ocupacional, identificando la performatividad del género mediante la ocupación, así como las transformaciones corporales en la construcción de subjetividad. Además se identifica un contexto sociocultural y político que vulnera derechos, lo cual impacta en la salud y el involucramiento en ocupaciones colectivas. Conclusiones La ocupación se presenta como un elemento reproductor del sistema binario de sexo-género, no obstante, también puede ser entendida como una herramienta de emancipación en la medida que permite transgredirla. En este sentido, se interpela a la Terapia Ocupacional a promover ocupaciones colectivas que potencien la capacidad de agencia de sujetos abyectos, determinando estados de salud favorables.

Resumo Introdução Esta pesquisa investiga a influência do sistema binário de gênero na construção do sujeito trans desde a perspectiva do fazer e as potencialidades do tornar-se a ser, no contexto sociocultural e político chileno, enfocando as experiências dos participantes através do resgate de História Ocupacional. Objetivos Analisar a construção do sujeito trans através do fazer, ser e tornar-se, com base em suas narrativas e em relação à estrutura social chilena em que atuam, visualizando a influência em seus estados de saúde. Método Em uma perspectiva qualitativa, com foco no conhecimento situado, foi utilizada a metodologia de produção de narrativa e técnicas descontínuas com múltiplas vozes. As informações foram coletadas por meio de entrevistas individuais e um grupo focal. Resultados O processo de trânsito é apresentado como um continuum ocupacional, identificando a performatividade de gênero através da ocupação, bem como transformações corporais na construção da subjetividade. Além disso, é identificado um contexto sociocultural e político que viola os direitos, com impacto na saúde e no envolvimento em ocupações coletivas. Conclusões A ocupação é apresentada como um elemento reprodutor do sistema binário sexo-gênero, no entanto, também pode ser entendida como uma ferramenta de emancipação, na medida em que permite transgredi-la. Nesse sentido, interpela-se a Terapia Ocupacional a promover ocupações coletivas que aumentem a capacidade de agência de sujeitos abjetos, determinando estados de saúde favoráveis.

Abstract Introduction This research inquires the influence of the binary gender system on the construction of the trans subject from the perspective of Doing and the potential of becoming, in the Chilean socio-cultural and political context, focusing on the experiences of the participants through the rescue of history occupational. Objectives Analyze the construction of the trans subject through doing, being and becoming based on their narratives, the Chilean social structure in which they develop, visualizing the influence on their health states. Method From a qualitative perspective with focus on situated knowledge, the methodology of narrative productions and discontinuous techniques is used to multiple voices. The information was collected through individual interviews and a focus group. Results The transit process is presented as an occupational continuum, identifying the performativization of gender through occupation, such as bodily transformations, in the construction of subjectivity. In addition, a sociocultural and political context that violates rights is identified, which impacts on health and participation in collective occupations. Conclusions Occupation is presented as a reproductive element of the binary sex-gender system, however, it can also be understood as a tool of emancipation insofar as it transgresses it. In this sense, Occupational Therapy is called upon to promote collective occupations that enhance the capacity of agency of abject subjects, determining favorable health states.

Instrucción entre pares como metodología a utilizar en enfermería / Peer instruction as a methodology to be used in nursing

Este trabajo presenta resultados de una revisión de la literatura acerca de la implementación de la metodología interactiva de enseñanza Peer Instruction (PI). Se pretende con esta búsqueda responder a las siguientes preguntas: ¿En qué contextos de enseñanza se ha investigado el Peer Instruction (PI)? ¿Qué impactos ha producido el PI en el aprendizaje de los estudiantes? ¿Cuáles son los resultados de la implementación del PI en relación a las actitudes de los estudiantes y profesores frente al uso de la metodología? Se realizó la búsqueda en las bases de datos Pubmed, Web of Science, EBSCO y Google Scholar. Los resultados de la literatura apuntan que gran parte de las publicaciones fueron conducidas en universidades norteamericanas, mayoritariamente enfocadas a la disciplina de Física11,16-18 , pero también las ciencias médicas3-6,10 y matemáticas7-9 . La adopción del PI presenta impactos positivos en el aprendizaje conceptual de los estudiantes, en la capacidad de resolución de problemas y en el desempeño académico. Desarrolla sentimientos positivos relacionados con el aprendizaje de los contenidos y la metodología. Los profesores realizan modificaciones al implementar el PI integrándolo con otras metodologías, demostrando su flexibilidad. En enfermería se ha utilizado escasamente el PI, siendo mezclado con otras metodologías en donde el estudiante es centro del aprendizaje; peer teaching and peer learning, por ejemplo; con buenos resultados en el logro de los resultados de aprendizajes de los estudiantes, dando un puntapié inicial a seguir aplicando e investigando el impacto de esta metodología en los estudiantes de enfermería.

This paper presents the results of a review of the literature about the implementation of the Peer Instruction interactive teaching methodology (PI). The aim of this search is to answer the following questions: In what teaching contexts has Peer Instruction (PI) been investigated? What impacts has IP produced on student learning? What are the results of the implementation of the IP in relation to the attitudes of the students and professors in front of the use of the methodology? The search was performed in Pubmed, Web of Science, EBSCO and Google Scholar databases. The results of the literature indicate that a large part of the publications were conducted in North American universities, mostly focused on the discipline of Physics, but also the medical sciences,and mathematics. The adoption of the PI has positive impacts on students' conceptual learning, problem-solving ability and academic performance. Develop positive feelings related to the learning of content and methodology. The professors make modifications when implementing the PI integrating it with other methodologies, demonstrating their flexibility. In nursing, the PI has been used sparingly, being mixed with other methodologies where the student is the center of learning; peer teaching and peer learning, for example; with good results in the achievement of student learning outcomes, giving an initial kick to continue applying and investigating the impact of this methodology on nursing students.