1,721,173 research outputs found
EZH2 gene mutations and copy number variation as prognostic markers in advanced follicular lymphoma
Full text linkIntroduction. Among the most common genetic alterations in follicular lymphoma (FL) there are the gain-of-function mutations in the Enhancer of Zeste Homolog 2 (EZH2) gene, encoding for a
histone methyltransferase, which can also be over-expressed by copy number variations (CNV).
The clinical impact of EZH2 aberrations in FL is debated, with some studies suggesting a
favourable outcome, especially when patients received R-CHOP/CVP. Aims. In the “FOLL-EZ”
study we aimed to explore the role of EZH2 aberrations in modifying the treatment effect of R-
CHOP vs bendamustine-rituximab (BR) in the prospective trial “FOLL12” of the Fondazione
Italiana Linfomi (FIL, EudraCT 2012-003170-60), enrolling advanced FL patients treated with
frontline R-CHOP or BR, according to physician’s choice. Methods. Leftover DNA samples from
unsorted bone marrow (BM) aspirates at baseline, centralized at the FIL MRD Network labs, were
tested by a multiplex droplet digital PCR (ddPCR) for the detection of the recurrent EZH2
mutations and by a ddPCR CNV assay for the EZH2 region (chr 7q36.1). Results. Overall, 409 BM
samples were tested for mutations and 359 for CNV (337 for both). An EZH2 mutation was found
in 137 cases (33%), concordantly with literature, being more frequent in patients with a documented
histological infiltration at the BM biopsy (BM+ n=124/309, 40%) than in BM- (n=13/100, 13%). In
detail 68 cases were mutated in Y646 (50%), 41 in A682G (30%) and 73 in A692V (53%). 102
cases (74%) showed one single mutation: 52 in Y646, 13 in A682G, 37 in A692V. 6 cases showed
all 3 mutations, 21 cases showed mutation in both 682 and 692 and 9 samples in 646 and 682 or
692. The most common mutation in Y646 was the Y646N 38/68 (56%) with a variant allele
frequency (VAF) of 0.25% (0.03-32%), the less frequent the Y646S 8/68 (12%), VAF 0.59% (0.03-
21%). Notably 8/68 Y646 cases (12%) carried 2 distinct mutations and only one sample showed 3
distinct mutations. Interestingly, the 137 EZH2 mutated patients showed less favourable clinical
features than the WT, in terms of higher B2M (>ULN 72% vs 53%, p<0.001), lower Hb values
(Hb<12, 26% vs 15%, p=0.015), more frequent BM+ (91% vs 68%, p<0.001) and higher FLIPI-2
(61% HR vs 40%, p<0.001); also baseline PET parameters were more unfavorable among EZH2
mutated cases, namely metabolic tumor volume (MTV) >200 ml (71% vs 57%, p=0.011) and
maximum tumor dissemination (Dmax) >400 mm (34% vs 21%, p=0.013): nonetheless, this did not
translate into a statistically significant worse outcome (5-year PFS 59% vs 64%, p=0.324). Overall,
no difference in PFS was observed between R-CHOP (n=239) and BR-treated (n=170) patients (5-y
PFS 60% vs 67%, p=0.652): EZH2 mutations had no statistically significant impact in modifying
the treatment effect of either therapeutic schedule (HR R-CHOP vs BR: 1.77 (95CI 0.96-3.29)
p=0.067 for mutated and 0.89 (95CI 0.60-1.32), p=0.564 for WT patients, Figure 1A). In a
subgroup analysis, the 30 EZH2 mutated patients who received R-CHOP not followed by R
maintenance experienced the worst outcome (5-y PFS 24%, p=0.007). Regarding EZH2 CNV, a
CN gain was found in 50 cases (14%) and a CN loss in 9 (3%): among the 337 patients analysed for
both mutations and CNV, 13 carried both EZH2 mutation and gain (4%), 106 had mutations only
(31%) and 31 had CN gain only (9%). The 50 patients with CN gain had overall less BM
involvement (62% vs 79%, p=0.018) but no significant differences in other baseline clinical
features nor in outcome; interestingly, among the 199 patients treated with R-CHOP those with CN
gain only (n=20) showed a more favorable outcome than the others (5-y PFS: 75% vs 59%,
p=0.053, Figure 1B). Conclusions. EZH2 mutations and CNV were tested by ddPCR in 409 BM
samples from the largest, prospective series of FL: they had no clear impact in modifying the
treatment effect (R-CHOP/BR), so a modulation of the first line treatment choice in FL based on
EZH2 does not seem appropriate, so far. To better address this issue, mutational and CNV testing ofdiagnostic lymph node samples is currently ongoing
Asciminib in chronic myeloid leukemia
No full text: Despite the fact that, in the last years, life expectancy of chronic myeloid leukemia (CML) patients has reached that of the normal population, a significant proportion of CML patients is likely to fail treatment with first- or second-generation tyrosine kinase inhibitors (TKIs). Failure to first-line treatment is commonly due to molecular resistance or unbearable toxicity. New specific compounds are tested in this setting to fulfill this unmet clinical need in CML; of these, asciminib has shown efficacy based on allosteric inhibition which allows to overcome resistance and off-target toxicity. This review aims to cover how asciminib will change the therapeutic scenario of CML, highlighting its mechanism of action, pharmacokinetics, efficacy and toxicity. Asciminib will be a possible option as third-line therapy for patients carrying resistant mutations, such as T315I, and/or not eligible for treatment with other TKIs
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
- …
