1,720,953 research outputs found
Molecular characterization of thyroid tumors of dogs and cats – a multicentric Portuguese series
No full textThyroid carcinoma (TC) is the most common endocrine malignancy in humans, dogs, and cats. In human TC, mutations in BRAF, NRAS, HRAS, and KRAS genes (key players in the MAPK pathway) are key predictors of diagnosis, prognosis, and treatment of thyroid neoplasms. However, in veterinary medicine, molecular studies on thyroid tumors are scarce, and treatment options are limited, particularly for animals with unresectable thyroid tumors, which underscores the importance of investigating the molecular patterns of canine and feline thyroid tumors. Therefore, our aim was to clarify if the same molecular players of human TC are present in canine and feline thyroid tumors and if those mechanisms could result in the same biological consequences. Our study population was composed of 83 animals: 67 dogs (5 adenomas (7%) and 62 carcinomas (93%)), and 16 cats (12 adenomas (75%) and 4 carcinomas (25%)). To assess the mutational landscape, we performed DNA extraction, PCR amplification, and Sanger sequencing, targeting human homologous hotspots of MAPK-related genes (BRAF, NRAS, HRAS, and KRAS) in formalin-fixed paraffin-embedded (FFPE) tissue samples. Immunohistochemistry was employed to evaluate the activation status of MAPK and mTOR signaling pathways, targeting their downstream phosphorylated effectors, pERK (Thr202/Ty204 to assess MAPK activation), pS6 (Ser235/236 to assess mTORC1 activation), and pAKT (Ser473 to assess mTORC2 activation). The mutational analysis of MAPK-related genes revealed a low mutational burden in both canine and feline thyroid tumors. In canine well-differentiated TCs (WDTCs), KRAS missense mutations (p.Gly12Arg and Gly60Ser) were identified in two cases (4%), with one HRAS missense mutation (p.Gly77Ser) in another case (2%). In feline thyroid tumors, a single KRAS missense mutation (p.Gln232His) was detected in one adenoma (9%) and one carcinoma (33%), both of follicular pattern. Regardless of the mutational status of the tumors, pERK was expressed in 39% of canine WDTC, pS6 in 67%, and pAKT in 89%, while in feline adenomas pERK was expressed in 92%, pS6 in 100%, and pAKT in 67% of the cases. Our findings suggest that BRAF and RAS mutations are rare driving events in canine thyroid tumorigenesis. Dogs are not likely to mirror the molecular mechanisms described in human TC, as pERK, pS6, and pAKT were found to be associated with less aggressive clinicalpathological features. Nevertheless, similarly to human TC, mTORC2 is most likely to have a higher involvement than mTORC1 or MAPK in canine TC. In feline adenomas, the expression profiles of pERK, pS6, and pAKT, along with their associations with clinical-pathological features, appear to resemble the dynamics of human thyroid tumorigenesis more closely. Notably, pAKT expression was associated with multifocal tumors in feline adenomas. In conclusion, dogs may not serve as ideal animal models for human TC, but further exploration is needed to understand their relevance for the most advanced histotypes of human TC. Our findings, however, underscore the potential of cats as animal models for human TC, with further research required to confirm this potential.O carcinoma de tiroide (TC) é a malignidade endócrina mais comum em humanos, cães e gatos. No TC humano, deteção de mutações nos genes BRAF, NRAS, HRAS e KRAS (efetores na via das MAPKs) são importantes no prognóstico, diagnóstico e tratamento de neoplasias tiroidianas. No entanto, na medicina veterinária, estudos moleculares em tumores da tiroide são escassos, e as opções de tratamento são limitadas, principalmente para animais com tumores não admissíveis a cirurgia, evidenciando a importância de investigar os padrões moleculares destes tumores em cães e gatos. Posto isto, o nosso objetivo foi explorar se os mesmos padrões moleculares do TC humano estão presentes em tumores da tiroide de cães e gatos e se esses mecanismos podem resultar nas mesmas consequências biológicas. A população em estudo era composta por 83 animais: 67 cães (5 adenomas (9%) e 62 carcinomas (93%)) e 16 gatos (12 adenomas (75%) e 4 carcinomas (25%)). Foi realizada extração de DNA, amplificação PCR e sequenciação de Sanger visando os hotspots do TC humano dos genes envolvidos na via das MAPK (BRAF, NRAS, HRAS e KRAS), em amostras de tecido embebidas em parafina e formalina (FFPE). Realizamos imunohistoquímica para avaliar o estado de ativação das vias MAPK e mTOR, marcando as formas fosforiladas dos seus efetores: pERK (Thr202/Tyr204 preditor da ativação das MAPK), pS6 (Ser235/236 preditor da ativação de mTORC1) e pAKT (Ser473 preditor da ativação de mTORC2). Detetámos uma baixa incidência de mutações nos genes investigados. Nos TCs bem diferenciados (WDTCs) caninos, identificamos duas mutações missense em KRAS (p.Gly12Arg e Gly60Ser) (4%) e uma mutação missense em HRAS (p.Gly77Ser) (2%). Nos gatos, detetamos uma mutação missense em KRAS (p.Gln232His) em um adenoma (9%) e um carcinoma (33%), ambos de padrão folicular. Independentemente do padrão mutacional dos tumores, observamos a marcação positiva de pERK em 39% dos WDTCs caninos, pS6 em 67% e pAKT em 89%, enquanto em adenomas da tiroide felina, a marcação positiva de pERK foi detetada em 92%, pS6 em 100% e pAKT em 67% dos casos. Estes resultados sugerem que as mutações em BRAF e RAS raramente estão envolvidas no TC canino. Os cães não parecem refletir os mecanismos moleculares descritos no TC humano, uma vez que pERK, pS6, e pAKT associaram-se a características clínicopatológicas mais favoráveis. No entanto, semelhante ao TC humano, mTORC2 provavelmente tem maior envolvimento do que mTORC1 ou MAPK no TC canino. Em adenomas da tiroide felina, a expressão de pERK, pS6 e pAKT, juntamente com as suas associações com características clínico-patológicas, parecem assemelhar-se mais à dinâmica da tumorigénese tiroidiana humana. A expressão de pAKT associou-se com características clínico-patológicas menos favoráveis em adenomas. Concluindo, os cães podem não servir como modelos animais para o TC humano, mas seria importante explorar a sua relevância para os histotipos de maior agressividade. Em gatos, os nossos resultados destacam o potencial destes animais como modelos para o TC humano, embora seja necessária investigação adicional para confirmar esse potencial
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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