1,720,958 research outputs found
CXCL5-mediated accumulation of SiglecFhigh neutrophils in lung tumor tissues impairs CD8 T cell responses and limits the efficacy of PD-L1 checkpoint blockade
Neutrophils are recruited in different type of cancer, including lung cancer, where they emerged as the most significant negative prognostic factor. Most experimental reports converge toward a rotumorigenic role of neutrophils via direct induction of cancer cell proliferation, promotion of metastasis, stimulation of angiogenesis and modulation of T cell responses. Nevertheless, in some
cancer type and tumor stages, neutrophils exert anti-tumoral properties through direct killing of cancer cells and activation of T cell-dependent anti-tumor immunity. Thus, neutrophils in cancer
display an enormous plasticity and heterogeneity which may be strongly influenced by the tissue and the constellation of immune modulating factors. Evaluate the complexity of neutrophils in
tissue specific tumor microenvironment to unequivocal distinguish immunosuppressive neutrophils from other neutrophil subsets represent an important challenge in the field. In addition,
understanding how these cells accumulate in tissues and how polarize to a pro- or anti-tumorigenic phenotype is crucial to develop successful cancer therapies. A critical subset of neutrophils expressing high levels of the sialic-acid-binding protein SiglecF (neuSiglecFhigh) was identified in KrasG12D/+; Trp53-/-(KP) mouse lung adenocarcinoma that correspond to a transcriptionally related human counterpart associated to negative outcomes. Neu-SiglecFhigh are mature, long-lived, cells that display tumor promoting functions associated to angiogenesis, matrix remodeling and production of ROS. However, the mechanism of recruitment of neu-SiglecFhigh in lung cancer and their impact on endogenous anti-tumor T cell responses are still unknown.Here, we used a transplantable KP line to investigate the role of the C-X-C motif chemokine 5 (CXCL5) in recruitment and accumulation of neu-SiglecFhigh in the microenvironment of lung tumors. By genome editing we abrogated the expression of CXCL5 in immunogenic KP cells (KP OVA KOCXCL5) and we characterized neutrophils frequencies and T cell activation within lung tumor tissues. We observed a drastic decrease of Cxcl5 transcripts followed by a strong reduction of neu-SiglecFhigh in KOCXCL5 tumors proving that the chemokine is a key player for their accumulation. Moreover, phenotypic and functional analysis of endogenous anti-cancer responses revealed a significant expansion of highly activated and cytotoxic tumor specific CD8+ T cells in tumor lacking neuSiglecFhigh. Immunofluorescence analysis of lung tissues shown tight CD8 T cell-neutrophils interactions, suggesting a contact-mediated mechanism of inhibition. Moreover, administration of antibodies to PD-L1 during challenge proved that neu-SiglecFhigh, due to a high expression of PD-L1, hamper the full activity of checkpoint blockade. Thus, we infer that targeting the CXCL5-axis could be a viable improvement to existing immunotherapy
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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