1,720,961 research outputs found
The role of natural killer cell killer immunoglobulin-like receptors in the development and treatment of hepatocellular carcinoma
No full textHepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide, and incidence is increasing related to increasing prevalence of chronic liver disease. Survival is poor, and systemic treatments are limited. Immunotherapies are increasingly important in the treatment of many cancer types. NK cells are innate lymphocytes with an important role in tumour surveillance and are an attractive target for immunotherapy. Their function is regulated the balance of activating and inhibitory receptors, an important component of which is the killer immunoglobulin-like receptor (KIR) family. KIR genotype has been associated with the outcome of various diseases. The activating KIR2DS2 receptor recognises flavivirus peptides in the context of HLA-C. This is a potential therapeutic target. Exosomes are extracellular vesicles with a role in cellular communication, which are a potential vehicle for cancer immunotherapies. I aimed to investigate the relationship between KIR genotype and hepatocellular carcinoma development in patients with hepatitis C. I then aimed to produce exosomes expressing HLA-C and the Dengue virus peptide DP1, and examine their potential to activate NK cells, and enhance killing cancer cell lines. In a cohort of 169 patients with hepatitis C, no patients with the KIR2DS3 gene developed HCC (p=0.04). Increasing age was significantly associated with the development of cirrhosis (p=0.007) and HCC(p=0.02). Exosomes were successfully purified from a 721:221 cell line expressing HLA-C + DP1. This was confirmed with electron microscopy, nanoparticle tracking analysis and Western blotting. In-vitro co-culture of exosomes with peripheral blood mononuclear cells (PBMCs) from KIR2DS2 positive donors did not produce KIR2DS2 positive NK cell expansion, increased degranulation, or produce enhanced killing of HCC cell lines. Injection of DP1 exosomes into a KIR transgenic mouse model produced significantly increased total NK frequency (p=0.014), and increased frequency of mature CD27-/CD11b+ NK cells compared to controls. This effect was not peptide specific. KIR2DS2 positive NK cells exhibited significantly greater frequency of the liver residence and memory marker CXCR6 and activation marker CD69 than KIR2DS2 negative NK cells in C01 control and DP1 exosome injected mice. A heterotopic syngeneic murine cancer model using the RMA-S murine lymphoma cell line did not find any difference in survival, tumour volume, or NK cell tumour infiltration in DP1 exosome injected mice versus controls. In this cohort of patients with hepatitis C from the UK, KIR2DS3 positivity was significantly associated with reduced incidence of HCC. In-vitro, DP1 exosomes did not impact NK cell proliferation or function. In a mouse model DP1 exosomes were significantly associated with increased NK cell frequency and maturity, which were not peptide specific. A tumour model did not demonstrate any reduction in tumour growth in exosome injected mice
Hepatitis C bio-behavioural surveys in people who inject drugs-a systematic review of sensitivity to the theoretical assumptions of respondent driven sampling
No full textBackgroundNew, more effective and better-tolerated therapies for hepatitis C (HCV) have made the elimination of HCV a feasible objective. However, for this to be achieved, it is necessary to have a detailed understanding of HCV epidemiology in people who inject drugs (PWID).Respondent-driven sampling (RDS) can provide prevalence estimates in hidden populations such as PWID. The aims of this systematic review are to identify published studies that use RDS in PWID to measure the prevalence of HCV, and compare each study against the STROBE-RDS checklist to assess their sensitivity to the theoretical assumptions underlying RDS.MethodSearches were undertaken in accordance with PRISMA systematic review guidelines. Included studies were English language publications in peer-reviewed journals, which reported the use of RDS to recruit PWID to an HCV bio-behavioural survey. Data was extracted under three headings: (1) survey overview, (2) survey outcomes, and (3) reporting against selected STROBE-RDS criteria.ResultsThirty-one studies met the inclusion criteria. They varied in scale (range 1–15 survey sites) and the sample sizes achieved (range 81–1000 per survey site) but were consistent in describing the use of standard RDS methods including: seeds, coupons and recruitment incentives.Twenty-seven studies (87%) either calculated or reported the intention to calculate population prevalence estimates for HCV and two used RDS data to calculate the total population size of PWID. Detailed operational and analytical procedures and reporting against selected criteria from the STROBE-RDS checklist varied between studies. There were widespread indications that sampling did not meet the assumptions underlying RDS, which led to two studies being unable to report an estimated HCV population prevalence in at least one survey location.ConclusionRDS can be used to estimate a population prevalence of HCV in PWID and estimate the PWID population size. Accordingly, as a single instrument, it is a useful tool for guiding HCV elimination. However, future studies should report the operational conduct of each survey in accordance with the STROBE-RDS checklist to indicate sensitivity to the theoretical assumptions underlying the method.Systematic review registrationPROSPERO CRD4201501924
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
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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