1,720,969 research outputs found

    Ottimizzazione preclinica di vettori oncolitici basati sul virus herpes simplex di tipo 1

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    I virus oncolitici (OV) sono agenti terapeutici emergenti che si replicano selettivamente nelle cellule tumorali, o naturalmente o in seguito a modificazioni genetiche. Gli OV provocano anche una risposta immunitaria antitumorale e pertanto hanno anche un effetto immunoterapeutico. Inoltre, i virus oncolitici possono anche essere modificati per esprimere geni terapeutici. Un OV basato sul virus herpes simplex di tipo 1 (HSV1), il talimogene laherparepvec (T-VEC), è stato approvato negli Stati Uniti nel 2015 e nell’Unione Europea nel 2016 per il trattamento del melanoma in stadio avanzato. T-VEC ha una delezione del gene della neurovirulenza γ34.5 e del gene Us12 (Δγ34.5/ΔUs12), inoltre è armato col gene dello human granulocyte-monocyte colony stimulating factor (hGM-CSF). Il nostro gruppo di ricerca ha sviluppato diversi HSV-1 oncolitici (oHSV1) basati su un backbone Δγ34.5/ΔUs12, armati con diversi geni immunoterapeutici diversi da GM-CSF. Durante questo progetto di dottorato, il focus è stato spostato sullo sviluppo di un sistema di somministrazione sistemico basato su cellule carrier al fine di raggiungere un’ottimizzazione preclinica di oHSV1. I monociti sono stati scelti perchè 1)hanno un tropismo intrinseco per i tumori, essendo i precursori dei macrofagi associati a tumore (TAMs), 2)sono in grado di migrare nella maggior parte dei distretti corporei, incluso il sistema nervoso centrale, 3)i monociti autologhi possono essere recuperati in grande quantità con un semplice prelievo di sangue periferico. Usando la linea cellulare monocitaria umana THP-1, abbiamo dimostrato che i monociti possono migrare verso cellule di carcinoma mammario umano e trasmettere l’infezione da oHSV1. Queste osservazioni sono state confermate usando monociti umani primari. Le cellule THP-1 infettate sono state in grado anche di trasmettere l’infezione a cellule umane di carcinoma squamoso testa-collo (UM-SC-11B) che crescono sulla membrana corioallantoica di uova embrionate di pollo, in seguito a iniezione intravascolare. Infine, abbiamo sviluppato un nuovo sistema di neuroattenuazione basato su miRNA per oHSV1 per aumentare ulteriormente la sicurezza in seguito a somministrazione sistemica.Oncolytic viruses (OVs) are emerging therapeutics that selectively replicate in cancer cells, either naturally or following genetic engineering. OVs also elicit an immune response against cancer and are therefore an immunotherapeutic tool. Furthermore, OVs can be modified to express therapeutic genes. An OV based on an attenuated herpes simplex virus type 1 (HSV-1), talimogene laherparepvec (T-VEC), has been approved in the US in 2015 and in the EU in 2016 for the treatment of advanced-stage malignant melanoma. T-VEC has deletions in the neurovirulence γ34.5 gene and Us12 gene (Δγ34.5/ΔUs12) and is further armed with human granulocyte-monocyte colony stimulating factor (hGM-CSF) gene. Our research group developed several oncolytic HSV-1 (oHSV1s) with a Δγ34.5/ΔUs12 backbone, armed with an array of immunotherapeutic genes other than GM-CSF. During this PhD project, we focused on developing a systemic delivery system by means of carrier cells, to achieve a pre-clinical optimization of oncolytic HSV-1. Monocytes were chosen because 1)they have an inherent tropism for tumors, being the precursors of tumor associated macrophages (TAMs), 2)they are capable of migrating into most compartments of the body, including the central nervous system, 3)autologous monocytes can be easily recovered in large amount from peripheral blood. Using the human monocytic cell line THP-1, we demonstrated that monocytic cells can migrate towards human breast cancer cells and transmit oHSV1 infection. These findings were confirmed with primary human monocytes. THP-1 cells also delivered oHSV1 to human head-and-neck UM-SC-11B cancer cells growing on the chorioallantoic membrane (CAM) of embryonated chicken eggs, following intravascular injection. Finally, we developed a new miRNA-based neuroattenuation system for oHSV1 to enhance safety following intravenous injection

    Mandible dentigerous cyst: etiology, surgical management and special considerations. Clinical case report

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    Fil: Reale, Alberto Maria. Universidad Nacional de CórdobaEl quiste dentígero deriva del epitelio reducido del esmalte que rodea a la corona de un diente no erupcionado, es una entidad patológica la cual se presenta en maxilar o mandíbula, siempre relacionado a la corona de un diente incluido. El quiste dentígero es el segundo quiste odontogénico más común. Generalmente está asociado con la corona de un diente normal impactado. Presentamos un caso clínico de quiste dentígero en la mandíbula relacionado con un canino inferior derecho, el cual se presenta como un hallazgo radiográfico. El manejo fue de manera oportuna con biopsia excisional y extracción del diente incluido. Describimos etiología, características clínicas e imagenológicas, técnica quirúrgica, análisis histopatológico y consideraciones especiales.Dentigerous cyst derives from the reduced epithelium of enamel that surrounds the crown of an unerupted tooth, is a pathological entity that occurs in maxilla and jaw. Always related to the crown of the included tooth. The dentigerous cyst is the second most common odontogenic cyst. It is generally associated with the crown of an impacted normal tooth. We present a clinical case of dentigerous cyst in the mandible related to a lower canine right, which is presented as a radiographic finding. Was handled in a timely manner with excisional biopsy and extraction of the included tooth. We describe its etiology, clinical and imaging characteristics, surgical technique, histopathology and special considerations.Fil: Reale, Alberto Maria. Universidad Nacional de Córdob

    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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    The silent enemy: Celiac disease goes viral

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    Celiac disease is a multifactorial autoimmune chronic inflammatory disorder affecting approximately one percent of the worldwide population. In such patients, ingestion of gluten proteins from cereals like wheat, barley, and rye causes damage of the small intestine mucosa, with potentially severe consequences. Onset of the disease in predisposed individuals is believed to require a still not clearly identified external trigger, such as viral infections. A very recent study has begun to shed light on a possible mechanistic basis for this hypothesis, and surprisingly linked intestinal infections caused by common reoviruses to the onset of celiac diseas

    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
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