6,243 research outputs found

    What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)

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    In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistancedriving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution

    Modeling of Immunosenescence and Risk of Death from Respiratory Infections: Evaluation of the Role of Antigenic Load and Population Heterogeneity

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    It is well known that efficacy of immune functions declines with age. It results in an increase of severity and duration of respiratory infections and also in dramatic growth of risk of death due to these diseases after age 65. The goal of this work is to describe and investigate the mechanism underlying the age pattern of the mortality rate caused by infectious diseases and to determine the cause-specific hazard rate as a function of immune system characteristics. For these purposes we develop a three-compartment model explaining observed risk-of-death. The model incorporates up-to-date knowledge about cellular mechanisms of aging, disease dynamics, population heterogeneity in resistance to infections, and intrinsic aging rate. The results of modeling show that the age-trajectory of mortality caused by respiratory infections may be explained by the value of antigenic load, frequency of infections and the rate of aging of the stem cell population (i.e. the population of T-lymphocyte progenitor cells). The deceleration of infection-induced mortality at advanced age can be explained by selection of individuals with a slower rate of stem cell aging. Parameter estimates derived from fitting mortality data indicate that infection burden was monotonically decreasing during the twentieth century, and changes in total antigenic load were gender-specific: it experienced periodic fluctuations in males and increased approximately two-fold in females

    Comparison of Theory and Direct Numerical Simulations of Drag Reduction by Rodlike Polymers in Turbulent Channel Flows

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    Numerical simulations of turbulent channel flows, with or without additives, are limited in the extent of the Reynolds number \Re and Deborah number \De. The comparison of such simulations to theories of drag reduction, which are usually derived for asymptotically high \Re and \De, calls for some care. In this paper we present a study of drag reduction by rodlike polymers in a turbulent channel flow using direct numerical simulation and illustrate how these numerical results should be related to the recently developed theory

    Community Participation in Urban Suburbs: The Italian Case of Z.E.N. Slum of Palermo

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    Based on Kurt Lewin’s Action Research theory, the paper focuses on an Action Research project issued in Southern Italy, in the disadvantaged suburb of Palermo (Sicily), called Z.E.N., sadly famous as a dangerous and “criminogenic” urban slum, in order to stimulate social participation and to develop social change. The principal goal was the empowerment of ordinary inhabitants, obtaining their collaboration through participation, giving them acquisition of knowledge for a real social change

    Community Development and Social Participation

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    The paper presents the reslt of the action research project issued in Palermo (Southern Italy), in disadvantaged urban suburbs, methodologically based on Kurt Lewin's field theory - that is a three-step spiral process of planning which involves recoinnaissance; talking actions; and fact-finding about the results of the action - in order to develop the social participation and the social change. The principal aim of the project was the empowerment of participants, obtaining their collaboration through participation, giving them acquisition of knowledge for a real social change
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