Increased Mortality Rate and Not Impaired Ribosomal Biogenesis is Responsible for Proliferative Defect in Dyskeratosis Congenita Cell Lines

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The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells

The expression of the asialoglycoprotein receptor (ASGP-R) on human hepatocellular carcinoma (HCC) cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis inhibitors by their conjugation with galactosyl-terminating peptides. In the present study we first assessed the frequency of ASGP-R expression in 60 HCCs. Secondly, we investigated whether the receptor was maintained on the plasma membranes of DNA synthesizing cancer cells. Needle biopsies of HCC were evaluated. Diagnosis and grading of HCC were performed on routine haematoxylin and eosin-stained sections according to Edmondson and Steiner (1953). Thirty-five tumours were grade I and II and were classified as well differentiated, while 25 tumours were grade III and IV and were classified as poorly differentiated. Sections from formalin-fixed, paraffin-embedded samples were incubated, after antigen retrieval, with an anti-ASGP-R monoclonal antibody revealed by secondary biotinylated antibody and streptavidin–biotin–peroxidase–diaminobenzidine reaction. A clear immunolabelling of plasma membranes of HCC cells was observed in 28 out of 35 (80%) well differentiated (grade I and II) and in five out of 25 (20%) poorly differentiated (grade III and IV) HCCs. The presence of the ASGP-R on the surface of DNA synthesizing cancer cells was also investigated after in vitro bromodeoxyuridine (BrdU) labelling of HCC samples by immunohistochemical visualization of both the ASGP-R and incorporated BrdU on the same section. The results obtained clearly demonstrated that DNA synthesizing cancer cells expressed the ASGP-R on their surface. The presence of ASGP-R on cell plasma membrane in the majority of differentiated HCCs and its maintenance on proliferating cells encourages studies in order to restrict the action of the inhibitors of DNA synthesis of HCC cells by their conjugation with galactosyl-terminating carriers internalized through this receptor. © 1999 Cancer Research Campaig

MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary

Metastasis is responsible for the majority of cancer‐related deaths. Particularly, challenging is the management of metastatic cancer of unknown primary site (CUP), whose tissue of origin (TOO) remains undetermined even after extensive investigations and whose therapy is rather unspecific and poorly effective. Molecular approaches to identify the most probable TOO of CUPs can overcome some of these issues. In this study, we applied a predetermined set of 89 microRNAs (miRNAs) to infer the TOO of 53 metastatic cancers of unknown or uncertain origin. The miRNA expression was assessed with droplet digital PCR in 159 samples, including primary tumors from 17 tumor classes (reference set) and metastases of known and unknown origin (test set). We combined two different statistical models for class prediction to obtain the most probable TOOs: the nearest shrunken centroids approach of Prediction Analysis of Microarrays (PAMR) and the least absolute shrinkage and selection operator (LASSO) models. The molecular test was successful for all formalin‐fixed paraffin‐embedded samples and provided a TOO identification within 1 week from the biopsy procedure. The most frequently predicted origins were gastrointestinal, pancreas, breast, lung, and bile duct. The assay was applied also to multiple metastases from the same CUP, collected from different metastatic sites: The predictions showed a strong agreement, intrinsically validating our assay. The final CUPs' TOO prediction was compared with the clinicopathological hypothesis of primary site. Moreover, a panel of 13 miRNAs proved to have prognostic value and be associated with overall survival in CUP patients. Our study demonstrated that miRNA expression profiling in CUP samples could be employed as diagnostic and prognostic test. Our molecular analysis can be performed on request, concomitantly with standard diagnostic workup and in association with genetic profiling, to offer valuable indications about the possible primary site, thereby supporting treatment decisions

SARS-CoV-2/COVID-19 Testing: The Tower of Babel

Background and aim: Testing represents one of the main pillars of public health response to SARS-CoV-2/COVID-19 pandemic. This paper shows how accuracy and utility of testing programs depend not just on the type of tests, but on the context as well. Methods: We describe the testing methods that have been developed and the possible testing strategies; then, we focus on two possible methods of population-wide testing, i.e., pooled testing and testing with rapid antigen tests. We show the accuracy of split-pooling method and how, in different pre-test probability scenarios, the positive and negative predictive values vary using rapid antigen tests. Results: Split-pooling, followed by retesting of negative results, shows a higher sensitivity than individual testing and requires fewer tests. In case of low pre-test probability, a negative result with antigen test could allow to rule out the infection, while, in case of a positive result, a confirmatory molecular test would be necessary. Conclusions: Test performance alone is not enough to properly choose which test to use; goals and context of the testing program are essential. We advocate the use of pooled strategies when planning population-wide screening, and the weekly use of rapid tests for close periodic monitoring in low-prevalence populations

Il semaforo di Pollara in Malfa (Salina-Isole Eolie). Il progetto di miglioramento sismico

La tesi si occupa del restauro architettonico e miglioramento sismico del semaforo di Pollara, nel comune di Malfa a Salina nelle isole Eolie

L’efficienza operativa delle banche italiane. Un'analisi empirica di alcune relazioni.

Il lavoro analizza il tema dell’efficienza operativa delle banche italiane attraverso un'analisi specifica di diverse relazioni:1. analisi dell’efficienza tecnico-operativa attraverso l'adozione di una diversa suddivisione del processo produttivo bancario; 2. verifica di specifiche caratterizzazioni qualitative delle banche in grado di spiegare alcune diversità nei livelli di efficienza rilevati, con particolare attenzione all’utilizzo e alla gestione del fattore lavoro.Il lavoro è organizzato nel seguente modo. Il paragrafo 1 rappresenta l’introduzione al lavoro. Il paragrafo 2 illustra sinteticamente il campione di banche analizzato e le scelte compiute in termini di variabili input-output e di relativi pesi prescelti e i risultati ottenuti in termini di valori dell’efficienza, ponendo l’accento sulle principali caratterizzazioni qualitative del campione bancario analizzato. Il paragrafo 3 analizza la coerenza tra la misura di efficienza stimata ed una serie di tradizionali indicatori di bilancio, avendo riguardo alle specificità che emergono per spiegare i diversi livelli in termini di struttura dei costi e dei ricavi del campione di banche analizzato. Come anticipato, grazie ad una serie di dati aggiuntivi richiesti alle banche, è stato possibile inserire un breve approfondimento sulle principali determinanti della relazione esistente tra l’efficienza operativa e l’organizzazione e la gestione del fattore lavoro. Il paragrafo 4 esamina tale interazione approfondendo, in particolare, il caso di una banca che ha vissuto negli ultimi anni intensi fenomeni di concentrazione con conseguenti problemi di riordino e di riorganizzazione dei costi aziendali e delle risorse umane. Il paragrafo 5 offre alcuni spunti di riflessione finali al lavoro. Le due appendici al capitolo riportano rispettivamente il quadro teorico metodologico relativo al tema dell’efficienza e la metodologia DEA utilizzata, oltre ad una scomposizione delle spese amministrative diverse dal costi del lavoro rapportate al margine di intermediazione