1,720,962 research outputs found
Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade
Full text linkImmune checkpoint inhibitors are becoming standard treatments in several cancer types, profoundly changing the prognosis of a fraction of patients. Currently, many efforts are being made to predict responders and to understand how to overcome resistance in non-responders. Given the crucial role of myeloid cells as modulators of T effector cell function in tumors, it is essential to understand their impact on the clinical outcome of immune checkpoint blockade and on the mechanisms of immune evasion. In this review we focus on the existing clinical evidence of the relation between the presence of myeloid cell subsets and the response to anti-PD(L)1 and anti-CTLA-4 treatment. We highlight how circulating and tumor-infiltrating myeloid populations can be used as predictive biomarkers for immune checkpoint inhibitors in different human cancers, both at baseline and on treatment. Moreover, we propose to follow the dynamics of myeloid cells during immunotherapy as pharmacodynamic biomarkers. Finally, we provide an overview of the current strategies tested in the clinic that use myeloid cell targeting together with immune checkpoint blockade with the aim of uncovering the most promising approaches for effective combinations
Role of Microenvironment on the Fate of Disseminating Cancer Stem Cells.
Full text linkDisseminating Cancer Stem Cells (CSCs) initiate growth in specific niches of the host tissues, the cellular and molecular components of which sustain signaling pathways that support their survival, self-renewal dormancy and reactivation. In the metastatic niche, tumor cells may enter in a dormant state to survive and, consequently, the metastasis can remain latent for years. Despite the clinical importance of metastatic latency, little is known about what induces CSCs to enter a dormant state and what allows them to remain viable for years in this state. CSCs exhibit genetic, epigenetic and cellular adaptations that confer resistance to classical therapeutic approaches. The identification of potential CSC targets is complicated by the fact that CSCs may arise as a consequence of their relationship with the local microenvironment into the metastatic niches. Indeed, microenvironment modulates the capability of CSCs to evade the innate immune response and survive. Some new therapeutic options that include drugs targeting microenvironment components are achieving encouraging results in reducing the number of CSCs in tumors and/or overcoming their resistance in preclinical studies. This review will focus on specific CSC features with an emphasis on the role of tumor microenvironment in supporting metastatic dissemination of CSCs. In addition, it sheds light on potential microenvironment-targeted therapies aimed to counteract seeding and survival of CSCs in the metastatic niche
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Treatment with a Urokinase Receptor-derived Cyclized Peptide Improves Experimental Colitis by Preventing Monocyte Recruitment and Macrophage Polarization
No full textBackground:Leukocyte migration across the blood barrier and into tissues represents a key process in the pathogenesis of inflammatory bowel diseases. The urokinase receptor (urokinase-type plasminogen activator receptor) is a master regulator of leukocyte recruitment. We recently found that cyclization of the urokinase-type plasminogen activator receptor-derived peptide Ser-Arg-Ser-Arg-Tyr [SRSRY] inhibits transendothelial migration of monocytes. Now, we have explored the effects of [SRSRY] administration during experimental colitis.Methods:The effects of [SRSRY] on cytokine profile, cytoskeletal organization, and cell migration were investigated using phorbol-12-myristate acetate-differentiated THP-1 cells exposed to polarizing stimuli. In vivo, [SRSRY] was intraperitoneally administered during dextran sodium sulfate- or 2,4,6-trinitrobenzene sulfonic acid-induced colitis in wild-type or urokinase-type plasminogen activator receptor knockout mice. Levels of pro-inflammatory cytokines and inflammatory monocytes in mucosal infiltrates were assessed by enzyme-linked immunosorbent assay and flow cytometry, respectively.Results:[SRSRY] prevents M0 to M1 transition and migration of M1 polarized macrophages. In vivo, [SRSRY] reduces intestinal inflammation diminishing body weight loss and disease activity index. These beneficial effects are accompanied by a reduction of interleukin 1, interleukin 6, and tumor necrosis factor , an increase of interleukin 10, and an abridged recruitment of inflammatory monocytes to the inflamed tissue.Conclusions:Altogether, these findings indicate that [SRSRY] may be considered as a new drug useful for the pharmacological treatment of chronic inflammatory diseases, such as inflammatory bowel diseases.BACKGROUND: Leukocyte migration across the blood barrier and into tissues represents a key process in the pathogenesis of inflammatory bowel diseases. The urokinase receptor (urokinase-type plasminogen activator receptor) is a master regulator of leukocyte recruitment. We recently found that cyclization of the urokinase-type plasminogen activator receptor-derived peptide Ser-Arg-Ser-Arg-Tyr [SRSRY] inhibits transendothelial migration of monocytes. Now, we have explored the effects of [SRSRY] administration during experimental colitis.METHODS: The effects of [SRSRY] on cytokine profile, cytoskeletal organization, and cell migration were investigated using phorbol-12-myristate acetate-differentiated THP-1 cells exposed to polarizing stimuli. In vivo, [SRSRY] was intraperitoneally administered during dextran sodium sulfate- or 2,4,6-trinitrobenzene sulfonic acid-induced colitis in wild-type or urokinase-type plasminogen activator receptor knockout mice. Levels of pro-inflammatory cytokines and inflammatory monocytes in mucosal infiltrates were assessed by enzyme-linked immunosorbent assay and flow cytometry, respectively.RESULTS: [SRSRY] prevents M0 to M1 transition and migration of M1 polarized macrophages. In vivo, [SRSRY] reduces intestinal inflammation diminishing body weight loss and disease activity index. These beneficial effects are accompanied by a reduction of interleukin 1β, interleukin 6, and tumor necrosis factor α, an increase of interleukin 10, and an abridged recruitment of inflammatory monocytes to the inflamed tissue.CONCLUSIONS: Altogether, these findings indicate that [SRSRY] may be considered as a new drug useful for the pharmacological treatment of chronic inflammatory diseases, such as inflammatory bowel diseases
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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