1,721,192 research outputs found

    Immunologic Correlates in the Course of Treatment With Immunomodulating Antibodies

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    Monoclonal antibodies (Ab) targeting immune checkpoints like CTLA-4 or PD-1 have come of age in the treatment of metastatic melanoma and further approvals are expected for other malignancies like lung and renal cell cancer as well. However, the majority of patients still do not experience clinical benefit upon these therapies. Moreover, immune-related side effects and the costs of these therapies prompt the search for their precise mode of action and for biomarker discovery. Here, we describe different classes of immunologic correlates such as pharmacodynamic changes observed in all treated patients, correlates with response during treatment (surrogate markers) or at the time-point of tumor assessment, as well as predictive markers for response and for immune-related adverse events. This review gives an overview of available data about correlates analyzed in the serum, all in immune cell subsets in the peripheral blood or in tumor-infiltrating lymphocytes. We will discuss how to prospectively validate and integrate these parameters for routine assessment of patients in daily clinical practice and give an outlook on promising future directions of biomarker research

    Immunogenic chemotherapy: discovery of a critical protein through proteomic analyses of tumor cells.

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    The aim of chemotherapy and radiotherapy is to eliminate tumor cells. While the outcomes of these cytotoxic treatments have previously been assigned to their direct effects on tumor cells, recent findings have shown that the host's immune system also contributes to the success of chemotherapeutic and radiotherapeutic regimens. The finding that some cytotoxic antitumor coumpounds such as anthracyclines were capable of triggering a potent T-cell-dependent antitumor response has prompted the search for molecular determinants responsible for the immunogenicity of anthracyclines. Proteomic analyses of anthracycline-treated tumor cells have recently revealed the critical involvement of calreticulin in mediating the immunogenicity of dying tumor cells. Here, we focused on the molecular study of immunogenic chemotherapy which led to the characterization of calreticulin as a critical protein in immunogenic cancer cell death

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Viral strategies for the evasion of immunogenic cell death

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    Driven by co-evolutionary forces, viruses have refined a wide arsenal of strategies to interfere with the host defences. On one hand, viruses can block/retard programmed cell death in infected cells, thereby suppressing one of the most ancient mechanisms against viral dissemination. On the other hand, multiple viral factors can efficiently trigger the death of infected cells and uninfected cells from the immune system, which favours viral spreading and prevents/limits an active antiviral response, respectively. Moreover, several viruses are able to inhibit the molecular machinery that drives the translocation of calreticulin to the surface of dying cells. Thereby, viruses block the exposure of an engulfment signal that is required for the efficient uptake of dying cells by dendritic cells and for the induction of the immune response. In this review, we discuss a variety of mechanisms by which viruses interfere with the cell death machinery and, in particular, by which they subvert immunogenic cell death

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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