1,721,167 research outputs found

    Thymidylate synthase genotypes and tumour regression in stage II/III rectal cancer patients after neoadjuvant fluorouracil-based chemoradiation

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    Purpose: According to the CAO-/ARO-/AIO-94 trial of the German Rectal Cancer Study Group, pre-operative 5-fiuorouracil (5-FU)-based long-term chemoradiotherapy (CT/RT) is recommended for patients with rectal cancer UICC stage II/III. However, despite the local benefit of neoadjuvant treatment, the overall prognostic value remains uncertain in comparison to adjuvant CT/RT. We assessed the impact of standardized pre-operative CT/RT and intratumoural mRNA levels and polymorphisms of the TS gene on histopathological tumour regression. Patients and methods: 40 patients with rectal cancer UICC stage II/III, receiving pre-operative 5-FU-based CT/RT followed by standardized surgery, including total mesorectal excision, were investigated. TS gene expression and TS polymorphisms of surgical specimens were correlated with the grade of histopathological tumour regression (0-4). Patients achieved regression grades 2-4 were determined as responders. Results: TS polymorphisms (5'-28 by repeat + G/C SNP and TS 1494del6) could be determined in 39/40 (97.5%) and in 38/40 (95%) patients, respectively. Quantification of TS mRNA expression was successful in 36/40 (90%) patients. There was a highly significant linkage disequilibrium between 5'- and 3'-TS polymorphisms (p = 0.0013). Interestingly, the majority of patients (82.1%) with 5'-TS genotypes known to be associated with low mRNA expression (2R/2R, 2R/3RC, 3RC/3RC) also possessed the TS1494del6 +6 bp/+6 bp genotype correlating with high TS mRNA expression. TS1494del6 polymorphism was significantly associated with TS mRNA expression. Patients with TS1494del6 -6 bp/-6 bp or -6 bp/+6 bp genotypes showed significantly lower mean TS mRNA expression with 0.55 (range:0.33;0.84) as compared to +6 bp homozygotes with a mean expression of 0.90 (range:0.20;1.91) (p = 0.025). Furthermore, all patients with TS 3'-UTR -6 bp/-6 bp or -6 bp/+6 genotype (11/11) were responders as compared to only 20/26(77%) of patients with TS 3'-UTR +6 bp/+6 bp genotype (p = 0.082). TS 5'-polymorphisms were not associated with neither tumour regression nor gene expression. Conclusion: Our data suggest that the TS1494del6 polymorphism may be an important predictor for histopathological tumour regression in UICC II/III rectal cancer patients receiving neoadjuvant 5-FU-based CT/RT. (c) 2008 Elsevier Ireland Ltd. All rights reserved

    Pharmacogenetic analysis of liver toxicity after busulfan/cyclophosphamide-based allogeneic hematopoietic stem cell transplantation

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    Unlabelled: THE AIM of this study was to evaluate the impact of genomic polymorphisms of methylene-tetrahydrofolate-reductase (MTHFR-C677T, MTHFR-A1298C) and various glutathione S-transferases (GSTP1-Ilel05Val, GSTA1*a/b, GSTM1, GSTT1) on the occurrence of liver toxicity in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Patients and methods: Eighty-four adult patients were enrolled in this retrospective study. All patients were treated with busulfan/cyclophosphamide as a conditioning regimen and received cyclosporine and short-course MTX for GvHD prophylaxis. Genotyping was performed using PCR based restriction-fragment-length-polymorphism (RFLP) techniques. Results: Multivariate analysis identified the MTHFR-A1298C polymorphism as an independent predictor for maximum levels of bilirubin (p=0.0025) and duration of hyperbilirubinaemia (p=0.013). Furthermore, there was an association between this polymorphism and the occurrence of the sinusoidal obstruction syndrome (SOS) (p=0.048). No significant associations between the MTHFR-C677T or the various GST polymorphisms and liver toxicity were observed. Conclusion: The MTHFR-A1298C polymorphism might be associated with liver toxicity in patients receiving allogeneic HSCT

    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

    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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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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
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