1,721,026 research outputs found
Novel approaches towards precision medicine in acute and chronic heart failure
Full text linkL'infart de miocardi (IM) és causat per una aturada sobtada del flux de sang que provoca isquèmia local al cor i desencadena un remodelat patològic, que es pot desenvolupar en insuficiència cardíaca (IC). Tot i que pot presentar-se com un esdeveniment estàtic, aquest és un procés complex i dinàmic. En aquesta tesi, es va valorar la IC considerant tot l'espectre de la malaltia. A més, estudis recents donen suport a la idea que processos biològics específics probablement estiguin influïts pel context biològic (p. ex: un teixit específic o una determinada malaltia). Aquesta aproximació constantment genera grans quantitats de dades, de manera que el recull, l'anàlisi i la interpretació d'aquesta informació constitueixen una tasca aclaparadora. En conseqüència, vam utilitzar tècniques d'intel·ligència artificial per combinar dades moleculars amb respostes clíniques observades en pacients, generant així un model matemàtic capaç de discernir els MoAs ocults en milers d'interaccions moleculars, altrament inaccessibles. Primer, vam voler analitzar els dos fàrmacs que estan revolucionant la gestió de la IC: Sacubitril/Valsartan, que ha demostrat una reducció del nombre de morts i ingressos en un 22% en assajos clínics recents, i Empagliflozina (un inhibidor de SGLT2 indicat per a pacients amb diabetis mellitus tipus 2) que va sorprendre amb una disminució del 32% en el desenvolupament de nous casos de IC a l'assaig EMPAREG. El nostre primer estudi va revelar que Sacubitril/Valsartan actua de manera sinèrgica bloquejant tant la mort cel·lular com el remodelat patològic de la matriu extracel·lular dels cardiomiòcits. El que és més important, vam descobrir un nucli de 8 proteïnes que es posicionen com a actors clau en aquest procés. En segon lloc, el MoA d'Empagliflozina suggeria una millora de la mort cardiomiocítica mitjançant la restauració de l'activitat de dos gens suprimits durant la IC, XIAP i BIRC5. Aquests resultats es van confirmar en un model de rata in vivo i van demostrar ser independents de la presència de diabetis, indicant que Empagliflozina podria establir-se com a nou tractament en el maneig de la IC. Tot i que ambdós fàrmacs presenten indicacions i mecanismes moleculars molt diferents, els seus beneficis en la reducció de la progressió de la IC eren notablement similars, evidenciant un paper clau del remodelat ventricular. Així doncs, a continuació vam voler explorar aquest remodelat per delinear una imatge estructurada i clara del procés complet post-IM. Aquí, vam identificar aquelles proteïnes alterades més relacionades amb la remodelació cardíaca tant en IM com en IC, i les vam utilitzar per buscar processos amb un enriquiment sostingut al llarg de la progressió de l'infart. Un cop establerts quins processos es veuen afectats en diferents etapes i la seva evolució durant l'IM, finalment vam identificar les proteïnes clau que impulsen aquestes cascades de senyalització. La IC crònica és la principal causa de mortalitat interhospitalària a tot el món, i es constitueix com a autèntica pandèmia. Tot i això, molts d'aquests pacients o bé desenvolupen IC derivat d'un esdeveniment agut o experimenten un deteriorament dràstic de la condició durant les hospitalitzacions recurrents. De fet, l'IC aguda és la principal causa de mortalitat intrahospitalària en països més desenvolupats, i el xoc cardiogènic (CS) representa la seva forma més agressiva. No obstant això, la IC aguda rep poca atenció en comparació amb la forma crònica de la malaltia Mitjançant tècniques de proteòmica i transcriptòmica avançades, primer vam investigar nous biomarcadors per ajudar a la gestió del CS. Avaluant els microRNAs i les proteïnes expressades diferencialment en pacients afectats, hem descrit l'estat actual de la investigació sobre biomarcadors en CS, així com desenvolupat un nou test molecular, el CS4P, per predir de forma fiable els resultats pronòstics d'aquests pacients.Myocardial infarction (MI) is caused by a sudden stop of blood flow that can lead to local ischemia in the heart and cause a pathologic remodeling, which ultimately give rise to heart failure (HF). Although it might present as a static event, this is a complex and dynamic process. In this thesis, we aimed to assess HF considering the whole spectrum of the disease. From the acute phase, in which a patient suddenly falls victim to a drastic illness, to investigate the molecular transition towards its chronification and elucidate the mechanisms of action (MoA) of the most novel pharmaceutical therapies in chronic HF. Moreover, growing evidence supports the idea that specific biological processes are likely influenced by their biological context-for example, a specific tissue or a certain disease. This approach constantly generates vast amounts of data, such that putting together, analyzing, and interpreting this information constitutes an overwhelming task. Consequently, we harnessed artificial intelligence techniques to combine molecular data with clinical responses observed in patients, thus generating a mathematical model capable of both reproducing existing knowledge and discern MoAs hidden under thousands of molecular interactions, otherwise inaccessible. First, we analyzed the two drugs that are revolutionizing HF management: Entresto® (Sacubitril/Valsartan), which showed a reduction in the number of deaths and admissions by 22% in recent clinical trials, and Empagliflozin (a SGLT2 inhibitor indicated for type2 diabetes mellitus patients) that showed an unexpected 32% slash in development of new HF cases in the EMPAREG trial. Our first study revealed that Sacubitril/Valsartan acts synergistically by blocking both cell death and the pathological makeover of the extracellular matrix of cardiac cells. Most importantly, we discovered a core of 8 proteins that emerge as key players in this process. Secondly, the MoA of Empagliflozin was deciphered using deep learning analyses, which achieved 94.7% accuracy and showed an amelioration of cardiomyocyte cell death by restoring the activity of two genes suppressed during HF, XIAP and BIRC5. These results were confirmed in an in vivo rat model, and proved independent of the presence of diabetes, suggesting that Empagliflozin may emerge as a new standalone treatment in HF. Although both drugs have very distinct indications and intrinsic MoAs, their benefits in slowing HF progression were remarkably similar, evidencing a key role for ventricular remodeling. Thus, next we aimed to explore cardiac remodeling to delineate a structured and clear picture of the complete post-MI remodeling process towards HF. Here, we identified those altered proteins most related to cardiac remodeling in both MI and HF, and used them to look for processes with sustained enrichment throughout MI progression. Once we established which processes are affected at different stages and their evolution during MI, we finally sought to identify the key proteins driving these signaling cascades. Chronic HF is the leading cause of inter-hospital mortality worldwide, which constitutes an authentic pandemic. However, many of these patients either develop HF derived from an acute event or experience a drastic worsening of the condition during the recurrent hospitalizations. Indeed, acute HF is the leading cause of intra-hospital mortality in more-developed countries, in which cardiogenic shock (CS) represents its most aggressive form. Yet, acute HF receives little attention compared to the chronic form of the disease By using transcriptomic and advanced proteomics techniques, we first investigated new potential biomarkers to aid CS management, which remains the leading intra-hospital cardiovascular cause of death worldwide. Assessing microRNA and proteins differentially expressed in afflicted patients, we describe the current status of biomarker research in CS, as well as a new molecular score, the CS4P, to reliably predict the prognostic outcomes of these patients
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
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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