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    Next generation sequence-based targeted somatic mutation analysis in low and intermediade-1 risk group patients with myelodysplastic syndrome

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    Amaç: Miyelodisplastik sendromda klinik spektrum oldukça değişken olduğu için hastaların prognoz tahmini oldukça önemlidir. Prognoz tahmini ile yüksek riskli hastaları daha erken belirleyebilmek mümkündür. Bunun için kemik iliği blast yüzdesi, sitopeni varlığı ve sitogenetik bulgular kullanılarak çeşitli prognostik skorlama sistemleri geliştirilmiştir. Fakat bu skorlama sistemlerinde düşük riskli olarak belirlenen hastaların bile mortalite ve morbidite oranlarının yüksek olduğu görülmektedir. Bu nedenle son yıllarda moleküler parametreler mevcut prognostik skorlama sistemlerine ek olarak kullanılmaya başlanmıştır ve prognoz tahmininde oldukça etkili olduğu görülmüştür. Çalışmamızda düşük ve orta derece-1 (intermediate-1) MDS hastalarında sitogenetik testlere ek olarak somatik mutasyon analizi yapılarak; moleküler testlerin klinik pratikte düşük-yüksek risk ayrımına etkisinin araştırılması hedeflenmiştir. Gereç ve Yöntem: Çalışmamıza 21 adet kemik iliği aspirasyon örneği dahil edildi. Örnekler daha önce yapılan karyotip ve FISH sonuçları normal, düşük ve orta derece-1 MDS tanısı almış ve ölen hastalara aitti. Örneklerin somatik mutasyon analizinde, 58 geni kapsayan yeni nesil dizileme paneli kullanıldı. Elde edilen moleküler veriler ve hastaların klinik verileri IPSS-M risk skorlama programına girildi ve hastaların yeni risk grupları belirlendi. Bulgular: Analiz sonucunda 21 hastadan 20 hastada (%95), 26 farklı gende toplam 222 Tier 1 veya Tier 2 mutasyon saptandı. Çalışmaya dahil edilen hastalardan IPSS'e göre 7 tanesi düşük risk ve 14 tanesi orta derece-1 (intermediate-1) risk grubundaydı. Moleküler analiz sonrasında elde edilen mutasyonlar IPSS-M risk skorlama programına girilerek yeni risk grupları oluşturuldu. Hastalar içerisinden toplamda 16 hasta (%76) daha yüksek risk gruplarına geçiş gösterdi. AML dönüşümü gösteren sadece iki hasta vardı ve hastaların bir tanesinde IDH2 R140Q mutasyonu (AF: %43) saptanırken, diğerinde allel fraksiyonu %20'nin üstünde 4 farklı gende (RUNX1, ETV6, U2AF1 ve DNMT3A) Tier 1 mutasyon saptandı. Sonuç: Tüm hastaların kemik iliği aspirasyon örneklerinden elde edilen DNA konsantrasyonları çalışma için yeterli olmuştur. Moleküler analizler sonucunda düşük riskli hasta grubumuzun risk grupları %76 (16 hasta) oranında yükselmiştir. Çalışma düşük riskli MDS hastalarında moleküler testlerin rutin pratikte kullanılması gerekliliğinin önemini vurgulamaktadır. Ayrıca çalışmamızın ülkemizde sonraki çalışmaların önünü açması hedeflenmiştir.Objective: Prognostic assessment is of significant importance in myelodysplastic syndrome (MDS) due to the high variability in its clinical spectrum. Accurate prognostic estimation allows for the early identification of high-risk patients. Various prognostic scoring systems have been developed using parameters such as bone marrow blast percentage, the presence of cytopenia, and cytogenetic findings. However, it has been observed that even patients categorized as low-risk in these scoring systems exhibit high mortality and morbidity rates. Consequently, in recent years, molecular parameters have been used in addition to existing prognostic scoring systems and have been seen to be highly effective in prognostic prediction. This study aims to investigate the impact of molecular testing on the discrimination of low and intermediate-1 MDS patients, in addition to cytogenetic tests, in clinical practice. Materials and Methods: We included 21 bone marrow aspiration samples in our study. These samples belonged to patients whose low and intermediate-1 risk group with died patients with MDS. Also, these patients' karyotype and FISH analysis results were normal. Next generation sequencing panel covering 58 genes was used in the somatic mutation analysis of the samples. The molecular data obtained, along with the patients' clinical data, were input into the IPSS-M risk scoring program, and the patients' new risk groups were determined. Results: The analysis detected a total of 222 mutations, which are Tier 1 or Tier 2, in 26 different genes in 20 out of 21 patients (95%). According to IPSS, seven of the included patients were classified as low risk, and 14 were categorized as intermediate-1 risk. Following molecular analysis, the detected mutations were input IPSS-M risk scoring program and new risk group was created. Amongst the examined patients, 16 patients (76%) have been reclassified to higher-risk groups. Only two patients exhibited transformation to acute myeloid leukemia (AML), with one patient being detected with the IDH2 R140Q mutation (AF: 43%) and the other having mutations in four different genes (RUNX1, ETV6, U2AF1 and DNMT3A) with allele fractions above 20%. Conclusion: The DNA concentrations extracted from bone marrow aspiration samples of all patients were sufficient for the study. As a result of molecular analyzes, 76% (16 patients) of the patients, which are low-risk MDS, in our study were reclassified as a higher risk group. This study underscores the necessity of incorporating molecular tests into routine clinical practice for low-risk MDS patients. Furthermore, our study aims to pave the way for future studies in our country

    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

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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