Best practices and QA protocols for code development

The OperaHPC project aims to improve the numerical capabilities of 3D fuel performance modelling as part of its strategic objectives. To achieve this goal, an open-source approach has been chosen for the tools developed in the framework of the project, namely MMM and OFFBEAT, the latter coupled to the SCIANTIX code. As the open-source approach is relatively new in the domain of nuclear safety studies, this document presents a framework for achieving quality assurance targets for the open-source scientific computing tools within the OperaHPC project. First, the document provides a brief review of the most common QA programs and standards employed in the field, with a particular focus to the aspects that are more relevant to OperaHPC. Then, it discusses modern software development practices to improve code quality, highlighting the importance of revision control systems, testing methodologies, and documentation. Finally, it describes the concept of governance model for regulating interactions between contributors, users, and decision-makers. The framework presented in this document provides a backbone for the verification and validation actions that will be carried out within the project and contributes to the qualification of the MMM, OFFBEAT and SCIANTIX tools for nuclear safety studies

Cholera with severe renal failure in an Italian tourist returning from Cuba, July 2013

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Distribution of Salmonella enterica isolates from human cases in Italy, 1980 to 2011

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Il video 360 in educazione: una panoramica della letteratura

For years now, the need for renewal of higher education has been discussed at a national and international level, with a focus on both new teaching methods and technological innovations. The integration and use of ICTs can, in fact, represent a catalyst for wider processes of improvement of the teaching-learning process, with implications not only at organizational and communication level, but also in terms of increasing students’ protagonism and collaboration. Among the latest generation of tech-nologies, a particularly interesting area is that of immersive environments, ranging from augmented to virtual reality. According to recent literature, they may have a positive impact both in terms of involvement and transfer of knowledge into real contexts. In this article, the focus is on 360-degree video technology: through the systematic analysis of the literature here presented, their educational uses will be highlighted, especially with respect to the university. Ormai da anni si discute a livello nazionale e internazionale della necessità di rinnovamento dell’istruzione superiore, con una particolare attenzione sia verso le nuove metodologie didattiche sia verso le innovazioni tecnologiche. L'integrazione e l'uso delle TIC possono infatti rappresentare un catalizzatore per processi più ampi di miglioramento del processo di insegnamento-apprendimento, con ricadute non solo sul piano dell’organizzazione e della comunicazione, ma anche su quello del livello di protagonismo e collaborazione da parte degli studenti. Tra le tecnologie di ultima generazione, un ambito particolarmente interessante è quello degli ambienti immersivi, dalla realtà aumentata a quella virtuale, che potrebbero garantire un impatto positivo sia a livello di coinvolgimento che di trasferimento delle conoscenze in contesti reali. Nel presente articolo, il focus è posto sulla tecnologia del video a 360 gradi: una analisi sistematica della letteratura permette di avere un quadro degli attuali utilizzi nei diversi contesti educativi, ed in particolare nel settore universitario

Potential roads for reaching the summit: an overview on target therapies for high-grade gliomas

Background: The tailored targeting of specific oncogenes represents a new frontier in the treatment of high-grade glioma in the pursuit of innovative and personalized approaches. The present study consists in a wide-ranging overview of the target therapies and related translational challenges in neuro-oncology. Methods: A review of the literature on PubMed/MEDLINE on recent advances concerning the target therapies for treatment of central nervous system malignancies was carried out. In the Medical Subject Headings, the terms “Target Therapy”, “Target drug” and “Tailored Therapy” were combined with the terms “High-grade gliomas”, “Malignant brain tumor” and “Glioblastoma”. Articles published in the last five years were further sorted, based on the best match and relevance. The ClinicalTrials.gov website was used as a source of the main trials, where the search terms were “Central Nervous System Tumor”, “Malignant Brain Tumor”, “Brain Cancer”, “Brain Neoplasms” and “High-grade gliomas”. Results: A total of 137 relevant articles and 79 trials were selected. Target therapies entailed inhibitors of tyrosine kinases, PI3K/AKT/mTOR pathway, farnesyl transferase enzymes, p53 and pRB proteins, isocitrate dehydrogenases, histone deacetylases, integrins and proteasome complexes. The clinical trials mostly involved combined approaches. They were phase I, II, I/II and III in 33%, 42%, 16%, and 9% of the cases, respectively. Conclusion: Tyrosine kinase and angiogenesis inhibitors, in combination with standard of care, have shown most evidence of the effectiveness in glioblas-toma. Resistance remains an issue. A deeper understanding of the molecular pathways involved in gliomagen-esis is the key aspect on which the translational research is focusing, in order to optimize the target therapies of newly diagnosed and recurrent brain gliomas. (www.actabiomedica.it)

The impact of stem cells in neuro-oncology: applications, evidence, limitations and challenges

Background: Stem cells (SCs) represent a recent and attractive therapeutic option for neuro-oncology, as well as for treating degenerative, ischemic and traumatic pathologies of the central nervous system. This is mainly because of their homing capacity, which makes them capable of reaching the inaccessible SC niches of the tumor, therefore, acting as living drugs. The target of the study is a comprehensive overview of the SC-based therapies in neuro-oncology, also highlighting the current translational challenges of this type of approach. Methods: An online search of the literature was carried out on the PubMed/MEDLINE and ClinicalTrials.gov websites, restricting it to the most pertinent keywords regarding the systematization of the SCs and their therapeutic use for malignant brain tumors. A large part of the search was dedicated to clinical trials. Only preclinical and clinical data belonging to the last 5 years were shortlisted. A further sorting was implemented based on the best match and relevance. Results: The results consisted in 96 relevant articles and 31 trials. Systematization involves a distinction between human embryonic, fetal and adult, but also totipo-tent, pluripotent or multipotent SCs. Mesenchymal and neuronal SCs were the most studied for neuro-oncological illnesses. 30% and 50% of the trials were phase I and II, respectively. Conclusion: Mesenchymal and neuronal SCs are ideal candidates for SCs-based therapy of malignant brain tumors. The spectrum of their possible applications is vast and is mainly based on the homing capacity toward the tumor microenvironment. Availability, delivery route, oncogenicity and ethical issues are the main translational challenges concerning the use of SCs in neuro-oncology. (www.actabiomedica.it)

Adoptive immunotherapies in neuro-oncology: classification, recent advances, and translational challenges

BACKGROUND: Adoptive immunotherapies are among the pillars of ongoing biological breakthroughs in neuro-oncology, as their potential applications are tremendously wide. The present literature review comprehensively classified adoptive immunotherapies in neuro-oncology, provides an update, and overviews the main translational challenges of this approach. METHODS: The PubMed/MEDLINE platform, Medical Subject Heading (MeSH) database, and ClinicalTrials.gov website were the sources. The MeSH terms "Immunotherapy, Adoptive," "Cell- and Tissue-Based Therapy," "Tissue Engineering," and "Cell Engineering" were combined with "Central Nervous System," and "Brain." "Brain tumors" and "adoptive immunotherapy" were used for a further unrestricted search. Only articles published in the last 5 years were selected and further sorted based on the best match and relevance. The search terms "Central Nervous System Tumor," "Malignant Brain Tumor," "Brain Cancer," "Brain Neoplasms," and "Brain Tumor" were used on the ClinicalTrials.gov website. RESULTS: A total of 79 relevant articles and 16 trials were selected. T therapies include chimeric antigen receptor T (CAR T) cell therapy and T cell receptor (TCR) transgenic therapy. Natural killer (NK) cell-based therapies are another approach; combinations are also possible. Trials in phase 1 and 2 comprised 69% and 31% of the studies, respectively, 8 of which were concluded. CAR T cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) was demonstrated to reduce the recurrence rate of glioblastoma after standard-of-care treatment. CONCLUSION: Adoptive immunotherapies can be classified as T, NK, and NKT cell-based. CAR T cell therapy redirected against EGFRvIII has been shown to be the most promising treatment for glioblastoma. Overcoming immune tolerance and immune escape are the main translational challenges in the near future of neuro-oncology

Innovative therapies for malignant brain tumors: the road to a tailored cure

Background: Immune tolerance, immune escape, neoangiogenesis, phenotypic changes, and glioma stem cells are all responsible for the resistance of malignant brain tumors to current therapies and persistent recurrence. The present study provides a panoramic view of innovative therapies for malignant brain tumors, especially glioblastoma, aimed at achieving a tailored approach. Methods: PubMed/Medline and ClinicalTri-als.gov were the main sources of an extensive literature review in which “Regenerative Medicine,” “Cell-Based Therapy,” “Chemotherapy,” “Vaccine,” “Cell Engineering,” “Immunotherapy, Active,” “Immunotherapy, Adoptive,” “Stem Cells,” “Gene Therapy,” “Target Therapy,” “Brain Cancer,” “Glioblastoma,” and “Malignant Brain Tumor” were the search terms. Only articles in English published in the last 5 years were included. A further selection was made according to the quality of the studies and level of evidence. Results: Cell-based and targeted therapies represent the newest frontiers of brain cancer treatment. Active and adoptive im-munotherapies, stem cell therapies, and gene therapies represent a tremendous evolution in recent years due to many preclinical and clinical studies. Clinical trials have validated the effectiveness of antibody-based immunotherapies, including an in-depth study of bevacizumab, in combination with standard of care. Pre-clinical data highlights the role of vaccines, stem cells, and gene therapies to prevent recurrence. Conclusion: Monoclonal antibodies strengthen the first-line therapy for high grade gliomas. Vaccines, engineered cells, stem cells, and gene and targeted therapies are good candidates for second-line treatment of both newly diagnosed and recurrent gliomas. Further data are necessary to validate this tailored approach at the bedside. (www.actabiomedica.it)

Targeting the medulloblastoma: A molecular-based approach

Background: The lack of success of standard therapies for medulloblastoma has highlighted the need to plan a new therapeutic approach. The purpose of this article is to provide an overview of the novel treatment strategies based on the molecular characterization and risk categories of the medulloblastoma, also focusing on up-to-date relevant clinical trials and the challenges in translating tailored approaches into clinical practice. Methods: An online search of the literature was carried out on the PubMed/MEDLINE and ClinicalTrials.gov websites about molecular classification of medulloblastomas, ongoing clinical trials and new treatment strategies. Only articles in the English language and published in the last five years were selected. The research was refined based on the best match and relevance. Results: A total 58 articles and 51 clinical trials were analyzed. Trials were of phase I, II, and I/II in 55%, 33% and 12% of the cases, respectively. Target and adoptive immunotherapies were the treatment strategies for newly diagnosed and recurrent me-dulloblastoma in 71% and 29% of the cases, respectively. Conclusion: Efforts are focused on the fine-tuning of target therapies and immunotherapies, including agents directed to specific pathways, engineered T-cells and oncoviruses. The blood-brain barrier, chemoresistance, the tumor microenvironment and cancer stem cells are the main translational challenges to be overcome in order to optimize medulloblastoma treatment, reduce the long-term morbidity and increase the overall survival. (www.actabiomedica.it)