1,721,020 research outputs found
Una revisión del positivismo en argentina : locura, delito y moral (1880-1930). Relevancia de dos líneas antagónicas del pensamiento argentino
No full textFil: Falcone, Rosa. Universidad de Buenos Aires. Facultad de Psicología. Argentina
Redifferentiation of iodine-refractory metastatic thyroid cancer: from bench to bedside, through a network analysis
Full text linkBACKGROUND: Radioiodine-refractory (RAIR) differentiated thyroid cancers (DTC) lose the ability to efficiently concentrate iodide, rendering RAI (iodine-131; I-131) ineffective. Few studies have shown improved RAI uptake after MEK inhibitors (MEKi) and/or BRAF inhibitors (BRAFi). MicroRNA (miRNA) role in redifferentiation process has been poorly investigated. METHODS: We retrospectively evaluated RAIR DTC patients treated with redifferentiation therapy using kinase inhibitor (KI) therapy with single-agent or combination MEKi and/or BRAFi. Our primary objectives were the percentage of patients with uptake on diagnostic (Dx) and post-treatment (post-Tx) whole body scan (WBS), and the radiologic response to I-131 achieved over that seen with KI. We exploited a bioinformatic approach (SWItchMiner, SWIM) to identify the key genes (switch genes) involved in BRAF-mediated carcinogenesis. MicroRNA Enrichment TURned NETwork (Mienturnet) was used to find the most important miRNAs able to regulate these switch genes. We validated our results by in vitro experiments.
RESULTS: A total of 41 patients with RAIR, advanced DTC (76% BRAF V600E mutant cancer) were included in the study. At post treatment scan, there was uptake, either optimal or suboptimal, in 95% of patients. After I-131, 73% of patients were deemed treatment successes, reaching stable or partial response, that lasted at least one year without treatment on systemic therapy. The median PFS was 29 months from the start of KI and the median TTP was 20 months from RAI administration. The investigation of mutational landscape of BRAF mutated papillaty thiroid cancer (PTC) by SWIM allowed to identify a subset of switch genes (227), 30% of which is regulated by hsa-miR-335-5p. In vitro experiments showed that miRNA-335-5p is lost in primary or continuous BRAF mutated cell lines. Its over-expression in thyroid tumor cell lines harboring BRAF mutation induces the activation of NIS protein and increases intra-cellular iodide uptake.
CONCLUSIONS: Redifferentiation therapy with MEKi and/or BRAFi resensitizes a subset of RAIR DTC patients to RAI and may result in prolonged stable disease off KI. Hsa-miR-335-5p may have a role in redifferentiation of RAIR BRAF-mutated papillary thyroid cancer. MiR-335-5p over-expression may contribute to restoring RAI responsiveness
Variazioni epidemiologiche delle neoplasie tiroidee nel tempo: ruolo della nutrizione iodica
Full text linkLo iodio è cruciale per l’omeostasi tiroidea: oltre ai noti effetti sulla funzione, la deficienza cronica di iodio può favorire lo sviluppo di gozzo o un aumento di prevalenza ed incidenza di noduli tiroidei benigni [1]. La relazione con il carcinoma tiroideo è più controversa e gli studi che hanno indagato questa associazione sono discordi: una revisione della letteratura sull’argomento è stata recentemente pubblicata [2]. Alcuni studi pubblicati negli anni ’90 avevano documentato un rischio incrementato di carcinoma tiroideo nelle popolazioni residenti in aree iodocarenti; in particolare, la distribuzione dei vari istotipi risultava sbilanciata verso una maggiore prevalenza di carcinoma follicolare. Inoltre, alcuni studi longitudinali, effettuati prima e dopo l’introduzione di programmi di iodoprofilassi, hanno documentato un incremento relativo dei carcinomi a rischio più basso (in particolare i carcinomi papilliferi della tiroide). I risultati riportati in letteratura sono comunque discordanti. L’interpretazione di eventi che avvengono durante ampi intervalli temporali, infatti, risulta complicata da molteplici fattori confondenti. Oltre all’implementazione di programmi di profilassi iodica negli anni Ottanta e Novanta, altri fattori possono spiegare la maggior prevalenza (relativa) di carcinomi papilliferi della tiroide. Tali fattori vengono discussi nelle sezioni seguenti e rappresentati in Figura 1 in parallelo all’implementazione dei programmi di profilassi iodica
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
Current achievements and future perspectives of metronomic chemotherapy
No full textIn recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated. We considered current studies dealing with MCT according to the clinical setting of patients. Despite a certain degree of overlap, we were able to identify four main clinical indications for MCT: refractory disease and frailty of patients, advanced stage disease (requiring first and second-line therapy), early stage disease and maintenance therapy after induction chemotherapy. In addition, a section of this review has been addressed to the combination of MCT with immunotherapy following the growing interest in the reinstatement of immune-surveillance. Crucial questions, such as the definition of optimal schedules of continuously delivered, low-dose chemotherapy and the recognition and validation of predictive biomarkers, need to be further addressed. Moreover, comparisons with the best supportive care are especially lacking and thus urgently awaited to establish the key role of MCT in the care of pretreated and frail patients. Maintenance therapy promises to be one of the most worthwhile developments for MCT. Currently, several combination strategies with standard chemotherapy, target agents or immunotherapy are under investigation but further efforts are needed to fill the gaps of knowledge in this field
Tackling pancreatic cancer with metronomic chemotherapy
No full textPancreatic tumours, the majority of which arise from the exocrine pancreas, have recently shown an increasing incidence in western countries. Over the past few years more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to significant improvements. However, despite such advances in therapy, prognosis of pancreatic cancer remains disappointing. Metronomic chemotherapy (MCT), which consists in the administration of continuous, low-dose anticancer drugs, has demonstrated the ability to suppress tumour growth. Thus, it may provide an additional therapeutic opportunity for counteracting the progression of the tumour. Here we discuss evidence arising from preclinical and clinical studies regarding the use of MCT in pancreatic cancer. Good results have generally been achieved in preclinical studies, particularly when MCT was combined with standard dose chemotherapy or antinflammatory, antiangiogenic and immunostimolatory agents. The few available clinical experiences, which mainly refer to retrospective data, have reported good tolerability though mild activity of metronomic schedules. Further studies are therefore awaited to confirm both preclinical findings and the preliminary clinical data
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
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