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To deliver services to users, central and local Public Administrations (PA) make extensive use of data. Various qualitative estimates suggest that databases contain 10-20 This work has two objectives: to summarize the experiences carried out over the past four years by the National Interuniversity Consortium for Informatics (CINI) in the Datalake project funded by the CRUI in collaboration with the Directorate General of Automated Information Systems (DGSIA) of the Ministry of Justice, in synergy with other related projects of the Ministry; and to demonstrate how the experiences, Proof of Concepts, and functional specifications produced can serve as a repository of functionalities for a “semantic document management system for PA,” which aims to evolve the information systems of PAs into platforms where unstructured data can be exploited and integrated with structured data to enhance and add value to the digital services provided by the PA, and where governance processes can be conducted using all knowledge expressed in documents and other forms of unstructured data. The judicial organization, proceedings, processes, user needs, functional structure of the Datalake, and implementation architecture are described, aiming towards a design and production pathway directed at all PAs.

Background: The objective of this study is to present the psychometric and cultural adaptation of the I COPPE scale to the Italian context. The original 21-item I COPPE was developed by Isaac Prilleltensky and colleagues to integrate a multidimensional and temporal perspective into the quantitative assessment of people’s subjective well-being. The scale comprises seven domains (Overall, Interpersonal, Community, Occupation, Psychological, Physical, and Economic well-being), which tap into past, present, and future self-appraisals of well-being. Methods: The Italian adapted version of the I COPPE scale underwent translation and backtranslation procedure. After a pilot study was conducted on a local sample of 683 university students, a national sample of 2432 Italian citizens responded to the final translated version of the I COPPE scale, 772 of whom re-completed the same survey after a period of four months. Respondents from both waves of the national sample were recruited partly through on-line social networks (i.e. Facebook, Twitter, and SurveyMonkey) and partly by university students who had been trained in Computer-Assisted Survey Information Collection. Results: Data were first screened for non-valid cases and tested for multivariate normality and missing data. The correlation matrix revealed highly significant correlation values, ranging from medium to high for nearly all congeneric variables of the I COPPE scale. Results from a series of nested and non-nested model comparisons supported the 7-factor correlated-traits model originally hypothesised, with factor loadings and inter-item reliability ranging from medium to high. In addition, they revealed that the I COPPE scale has strong internal reliability, with composite reliability always higher than .7, satisfactory construct validity, with average variance extracted nearly always higher than .5, and and full strict invariance across time. Conclusions: The Italian adaptation of the I COPPE scale presents appro

Background: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be the best efficacious approach for the majority of patients. However, a consistent fraction (30%) of cases progress after surgery with curative intent. It is currently largely debated the use of adjuvant therapy for high-risk patients and the clinical and molecular parameters for stratifying beneficiary categories. In addition, the treatment of advanced forms lacks reliable driver biomarkers for the appropriated therapeutic choice. Thus, renal cancer patient management urges predictive molecular indicators and models for therapy-decision making. Methods: Here, we developed and optimized new models and tools for ameliorating renal cancer patient management. We isolated from fresh tumor specimens heterogeneous multi-clonal populations showing epithelial and mesenchymal characteristics coupled to stem cell phenotype. These cells retained long lasting-tumor-propagating capacity provided a therapy monitoring approach in vitro and in vivo while being able to form parental tumors when orthotopically injected and serially transplanted in immunocompromised murine hosts. Results: In line with recent evidence of multiclonal cancer composition, we optimized in vitro cultures enriched of multiple tumor-propagating populations. Orthotopic xenograft masses recapitulated morphology, grading and malignancy of parental cancers. High-grade but not the low-grade neoplasias, resulted in efficient serial transplantation in mice. Engraftment capacity paralleled grading and recurrence frequency advocating for a prognostic value of our developed model system. Therefore, in search of novel molecular indicators for therapy decision-making, we used Reverse-Phase Protein Arrays (RPPA) to analyze a panel of total and phosphorylated proteins in the isolated populations. Tumor-propagating cells showed several deregulated kinase cascades associated with grading, including angiog

Adaptive resistance to therapy is a hallmark of cancer progression. To date, it is not entirely clear how microenvironmental stimuli would mediate emergence of therapy-resistant cell subpopulations, although a rearrangement of the cancer cell secretome following therapy-induced stress can be pivotal for such a process. Here, by using the highly chemoresistant malignant pleural mesothelioma (MPM) as an experimental model, we unveiled a key contribution of the chaperone HSP90 at assisting a chemotherapy-instigated Senescence-Associated-Secretory-Phenotype (SASP). Thus, administration of a clinical trial grade, HSP90, inhibitor blunted the release of several cytokines by the chemotherapy-treated MPM cells, including interleukin (IL)-8. Reduction of IL-8 levels hampered the FAK-AKT signaling and inhibited 3D growth and migration. This correlated with downregulation of key EMT and chemoresistance genes and affected the survival of chemoresistant ALDHbright cell subpopulations. Altogether, inhibition of HSP90 provoked a switch from a pro-tumorigenic SASP to a pro-apoptotic senescence status, thus resulting in chemosensitizing effects. In mouse xenografts treated with first- line agents, inhibiting HSP90 blunted FAK activation and reduced the expression of ALDH1A3 and the levels of circulating human IL-8, these latter strongly correlating with the effect on tumor growth. We validated the above findings in primary mesothelioma cultures, a more clinically relevant model. We unveiled here a key contribution of the chaperone HSP90 at assisting the secretory stress in chemotherapy-treated cells, which may warrant further investigation in combinatorial therapeutic settings.