1,720,956 research outputs found
Leucemie linfoblastiche acute T pediatriche: Analisi di mutazione attraverso il sequenziamento di ampliconi o dell'intero esoma
Full text linkBackground. Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disease in children and it is generally characterized by favorable outcome, with the long-term cure rate approaching 90%. The stratification of patients into risk groups allows a more specific risk-adapted treatment, saving patients with a low risk of relapse from excessive toxicity, while improving outcome in patients with a high risk of relapse by intensive treatment. Risk stratification has been based on clinical features and response to treatment. NOTCH1 activation and PTEN inactivation are common events implied in leukemogenesis, and appear attractive candidates as drivers for risk stratification. NOTCH1 is involved in transcriptional upregulation of IL7R, a gene known to be mutated in 10% of T-ALL cases. In addition, the NOTCH1 signaling is also involved in the regulation of cyclin D3. This protein is involved in cell proliferation and it is necessary for T-ALL development. Given the fact, in recent studies new genetic alterations are associated with prognosis and could be used for patient's stratification, as well as for targeted therapy. All these highlight the import of the identification of new mutations that could play a pivotal role in the leukemogenesis.
Aim of the study. The purpose of this study was to evaluate the prognostic significance NOTCH1 and PTEN alterations in childhood T-ALL. To this purpose, a large pediatric T-ALL patient cohort treated according to the AIEOP ALL2000/R2006 and AIEOP ALL2009 protocols was comprehensively characterized with respect to NOTCH1 and PTEN; the NOTCH1/PTEN mutational status were then correlated with the cumulative incidence of relapse and event free survival. Using the somatic mutations as specific genetic markers for tumor cell we applied next-generation ultra-deep sequencing technologies to detect the presence of residual cells in the bone marrow samples during therapy is the second aim of this study. Therefore, the mutational status of IL7R at diagnosis and +33 day therapy was characterized and it was then correlated with MRD RQ-PCR. Finally, it was analyzed the CCND3 mutation recurrence to identify new genes involved in leukemogenesis.
Materials and methods. Bone marrow samples from 272 children with T-ALL obtained at the time of first diagnosis were analyzed with Sanger sequencing for PTEN mutations. Activating NOTCH1 mutations were detected by Sanger sequencing of the exons coding for the heterodimerisation (HD), PEST and TAD domains. Activating IL7R mutations were analyzed by Sanger sequencing and deep-amplicon sequencing of 227 T-ALL patients. The exome from 8 children with T-ALL diagnosis high-risk and related control was analyzed by Ion Torrent Technology. Finally, CCND3 mutations were analyzed in 80 T-ALL patients at diagnosis by Sanger sequencing.
Results. The frequency of PTEN and NOTCH1 alterations was 12% and 65% respectively. The survival analysis on the total cohort on T-ALL patients shows a higher incidence of relapse and a lower survival in patients with inactivating PTEN mutations. Kaplan-Meyer estimate of event free survival (EFS) show a positive prognostic significance of NOTCH1 mutations in AIEOP T-ALL total cohort, but this result is not confirmed in the last therapeutic protocol analyzed AIEOP ALL2009. Because the only detectable difference between this cohort and those described in the literature is the treatment that has been applied, we hypothesize that the effect of NOTCH1 and PTEN mutational status on the risk of relapse depends on the treatment applied. By deep-sequencing the IL7R clonal mutations have been identify with great sensitivity, even if the frequency of the mutation was less than 10%. Finally, the Ion Proton System technology identified a missense mutation in CCND3 gene, this mutation have shown a recurrence 6% within a larger cohort of T-ALL by Sanger sequencing.
Conclusions. In the patient cohort that has been analyzed, the PTEN mutation were correlated with outcome and were generally important for patients stratification in high risk groups; in contrast, the NOTCH1 mutation correlation on outcome depends on the type of therapeutic treatment adopted and is not generally useful for risk stratification. Future models of risk stratification will need to include more genetic markers. Preliminary results of IL7R show that ultra deep-sequencing have allow detecting mutations at subcloanl level and it was possible follow the leukemic clone with the IL7R mutation during therapy. Finally, the identification of somatic mutations and the expression of the CCND3 gene in onset blasts suggests that these genetic alterations could help the disease progression. The future functional studies will need to evaluate the possible gain-of-function of the mutated protein in leukemic blasts and to provide a new therapeutic target
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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