1,721,581 research outputs found

    Non-invasive minimal residual disease (MRD) analysis in diffuse large B-cell lymphoma (DLBCL)

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    Introduction: diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with genetic diversity and variable outcomes. It arises from a mature clonal B cell population that exhibits clonal immunoglobulin (IG) gene rearrangements. The current standard for monitoring DLBCL response to therapy relies on the estimation of tumor reduction by CT or PET/CT scan. Clonality analysis using a next-generation sequencing (NGS)-based approach is a powerful tool not only to detect clonal B cells in lymph node tissue but also to track minimal residual disease (MRD). In this context, one major obstacle is the absence of circulating cells. cell-free DNA (cfDNA) might be the best analyte for MRD assessment, as it is easily accessible from peripheral blood (PB). MRD analysis is of great interest since it could help to identify patients at high risk of recurrence and to guide treatment decisions. Aims: to test IG heavy (IGH) and light (IGK) chain rearrangements as target of clonality using NGS on formalin-fixed paraffin embedded (FFPE) lymph node biopsies and on cfDNA extracted from PB, in newly diagnosed DLBCL patients; to explore if tracking IG clones by NGS on cfDNA samples during/after treatment can be a valid non-invasive way to study MRD; to study the correlation with radiologic assessment of early and final response and with clinical variables. Results and methods: NGS-based clonality testing was performed using the LymphoTrack assay (Invivoscribe Inc, San Diego, CA) in 53 patients provided with DNA from the tumor biopsies and with cfDNA extracted from PB samples. Tumor-specific clonotypes were detected in 88.5% of 52 evaluable FFPE samples and 80.5% of 46 cfDNA samples. Clonality identification rate on cfDNA at diagnosis correlated with disease stage and a trend for association with extra-nodal disease was observed. MRD was performed by tracing the disease-specific clonotypes in plasma samples collected at interim, at the end of treatment (EOT), and at follow-up. MRD at interim was positive in 8 of the 26 evaluated cases and 67% of them subsequently relapsed; it was negative in 18 patients and 12% of them relapsed (p<0.0001). MRD at interim allowed to better categorize the 15 cases with partial response assessed by CT scans: 8 patients were MRD negative and two relapsed, 7 were MRD positive and 5 relapsed (p=0.08). MRD at EOT proved promising for the identification of patients at high risk of relapse, as the best PFS was observed in patients who achieved MRD negativity at this time point (p=0.001). Indeed, MRD was positive in 7 cases and all relapsed; of these 7 patients, only one had a positive PET/CT at EOT. Nine patients were MRD negative and never experienced relapse; 2/9 showed a PET/CT false-positive result. Finally, we showed that cfDNA was detectable in the plasma before clinical progression in most cases. Conclusions: NGS-based assays are suitable for IG-based biomarker identification and MRD analysis in plasma samples of DLBCL patients, since this analysis identifies patients with a high risk of relapse. MRD evaluation both at interim and at EOT allows to better stratify DLBCL patients’ outcome. The role of cfDNA for MRD detection and its impact on prognosis has to be further explored in larger series of DLBCL patients, in order to validate these results and to explore the possibilities of MRD-adapted therapy regimens that can ultimately improve patients’ care

    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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    Inibitori dell’aromatasi nel trattamento dell’endometriosi profonda

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    Recent case reports and pilot studies suggested that aromatase inhibitors might be effective in treating pain symptoms related to the presence of endometriosis. We present the case of a 32-year-old woman who suffered dysmenorrhea, dyspareunia, chronic pelvic pain, and dyschezia caused by rectovaginal endometriosis. Pain symptoms recurred after treatment with the oral contraceptive pill; the patient refused surgery.Therefore a double-drug regimen including letrozole (2.5 mg/day) and norethisterone acetate (2.5 mg/day) was offered to the patient. The scheduled length of treatment was six months. This double-drug regimen determined a quick and significant improvement in all pain symptoms. During treatment, the patient complained mild arthralgia. After the interruption of treatment, pain symptoms quickly recurred and at 6-month follow-up their intensity was similar to baseline values. Operative laparoscopy was performed, the presence of rectovaginal endometriosis was confirmed and all visible endometriotic lesions were excised. Aromatase inhibitors might be offered when pain symptoms caused by endometriosis persist during the administration of other hormonal therapies and the patient refuses surgery. However, women must be informed that these drugs determine only a temporary relief of pain symptoms and might cause adverse effects (such as arthralgia)

    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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