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    L'enzima Nicotinamide N-metiltrasferasi: un nuovo marker diagnostico e target terapeutico nel carcinoma uroteliale della vescica

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    L’enzima nicotinamide N-metiltrasferasi: un nuovo marker diagnostico e target terapeutico del carcinoma uroteliale della vescica Il carcinoma uroteliale della vescica è uno dei tumori urologici di più frequente riscontro e rappresenta un’impostante causa di morte per cancro. Sebbene la cistoscopia e l’analisi citologica del sedimento urinario costituiscano il "gold standard" per la diagnosi e il monitoraggio di tale tumore, entrambe le procedure presentano dei limiti. Pertanto, risulta di fondamentale importanza l’identificazione di biomarcatori che possano impiegati per la diagnosi precoce e non invasiva del carcinoma uroteliale della vescica. Oggetto del presente lavoro di ricerca è l’enzima nicotinamide N-metiltrasferasi (NNMT). E’ stato dapprima analizzato il profilo di espressione genica del tessuto sano e canceroso di un paziente affetto da carcinoma della vescica. I risultati hanno mostrato l’overespressione del gene per NNMT nel tessuto patologico rispetto a quello sano. L’analisi dei livelli di espressione dell’enzima è stata pertanto estesa a 28 pazienti affetti da carcinoma vescicale. Le indagini svolte hanno evidenziato un’overespressione dell’NNMT (mRNA e proteina) nel carcinoma rispetto al tessuto sano adiacente. I livelli di espressione dell’NNMT sono stati inoltre valutati nelle cellule di sfaldamento dell’urotelio vescicale reperite in campioni urinari ottenuti da 55 pazienti affetti da carcinoma della vescica e 107 soggetti sani, mediante Real-Time PCR. I risultati hanno mostrato un significativo aumento dell'espressione dell'NNMT nelle urine dei soggetti affetti da neoplasia rispetto ai controlli. L’analisi della curva ROC ha consentito di determinare un’eccellente accuratezza diagnostica relativa al test basato sulla valutazione dei livelli urinari dell'NNMT e di individuare il valore di cut-off che meglio discrimina i soggetti malati da quelli sani. I risultati riportati nel presente studio indicano l'NNMT quale potenziale marcatore molecolare del carcinoma uroteliale della vescica e suggeriscono un suo impiego nella diagnosi precoce e non invasiva di tale neoplasia.Nicotinamide N-methyltransferase: a novel diagnostic marker and therapeutic target for bladder urothelial carcinoma. Bladder urothelial carcinoma represents one of the most common urologic malignancies and is a major cause of cancer-related death. Although cystoscopy and urine cytology represent the “gold standard” methods for detection and monitoring of this neoplasm, both procedures have limitations. Therefore, the identification of reliable biomarkers for early and non-invasive detection of bladder cancer are urgently required. The present study is focused on the enzyme nicotinamide N-methyltransferase (NNMT). We first analyzed gene expression profiles of tumor and normal tissue samples obtained from the same patient affected with bladder cancer. The enzyme NNMT was identified as a highly expressed gene in tumor compared with control. Therefore, we evaluated NNMT expression in 28 patients with bladder cancer. NNMT mRNA and protein levels were significantly higher in bladder cancer compared to adjacent normal tissue. In addition, NNMT expression levels were evaluated in urinary exfoliated cells obtained from 55 patients with bladder cancer and 107 healthy donors, using Real-Time PCR. Results showed that urinary NNMT expression was significantly higher in bladder cancer patients compared with controls. Receiver operating characteristic (ROC) analyses revealed the excellent diagnostic accuracy of a urine-based NNMT test and the best cut-off value to discriminate bladder cancer patients from healthy subjects. Data reported in the current study suggest that NNMT could represent a molecular biomarker of bladder cancer and could be used for the development of a urine-based test for the early and non-invasive detection of this tumor

    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
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