Expected outcomes. The generation of an innovative multidisciplinary biobank will improve our knowledge about craniosynostosis with a particular emphasis on surgical levels. Indeed, one of the expected outcomes will be the increasing weight and importance of functional advanced MR imaging in the pre-operative evaluation and post-operative outcome definition. Angio MRV, Cerebral perfusion, tractography, and connectomics will be exploited to study the pre-operative conditions and the cerebral functional response to the surgical treatment that has been historically too often evaluated only with geometric bone landmarks and volumetric criteria. Of note, our group has been the first to observe and describe dramatic changes in the venous drainage pattern following posterior distraction surgery in syndromic craniosynostosis (doi 10.3171/2022.6.PEDS22171). Similar changes are expected in other functional and anatomical parameters (arterial blood flow, tractography, connectomics) that require advanced functional MRI technology, sequences, and post-processing know- how. For each clinical case, the obtained 3D models, as well as the radiomic markers, will be released through the biobank infrastructure in order to provide researchers with a suitable anatomical phenotype of the pathology for clinical, research and educational purposes. Possible risks related to the generation of biobanks could be at economic, infrastructural, institutional, research community, and participant levels. The budget required in the present project is sufficient to reach the goal of generating an innovative biobank with state-of-the-art technologies. Moreover, considering the rarity of the disease and the values of the collected samples, we planned to have a backup biobank settled in unit-2 and a master biobank in unit-1. In both cases, dedicated spaces and instruments will be made available. The generation of a comprehensive dataset will be appealing to external researchers since for each biosample a detailed genetic and imaging characterization will be made available. No risks are foreseen in the case of the young patients since all samples will be embedded during the clinical practice procedures. Finally, both institutions aim to create a pediatric collection with a long-term viewpoint to allow the research community to exploit our biobank as long as possible.
Expected outcomes. Establish human liver slice cultures as preclinical platform to explore pathological fibrosis processes and screen for new biomarkers and/or therapeutic approaches - Identify novel putative liver fibrosis gene signatures and biomarkers - Identify HIPK2 functions in liver fibrosis - Validate HIPK2 as perspective target for prevention/treatment of liver fibrosis Human organotypic slice cultures have been successfully obtained and applied from different human cancers.
Expected outcomes. Improved mental and physical well-being in the targeted group of people treated with SGA. - Development of a biobank of biological materials related to the study of MetS in people treated with SGA. - Creation of a strong evidence base for programmes aimed at improving the physical health of people treated with SGA. - Development of preventative strategies which may have a real effect of reducing comorbidities associated with SGA utilization. We forecast 4 main problems: 1.LOWER NUMBER OF PATIENTS RECRUITED. A contingency action, already accounted for in the clinical study design, is to recruit more patients than what is required by the calculations of sample size. Another contingency action will be to recruit patients intensively in the early stages of the project, to safeguard the pre-set enrolment target in the expectation of later refusals to participate. Other contingency actions, that will be activated only in case of need, include the extension of the enrolment period by 6 months and the involvement of additional clinical sites to increase recruitment. Partners, thanks to their networks, will identify other services, settings and scientists who might be invited to join the study.
Expected outcomes. Our project is expected to provide a breakthrough in the management of melanoma patients maximizing patients' life expectancy and quality of life through a combinatorial approach. To reach our goal we will make us of oncosuppressor miRNAs encapsulated in LNPs, that represent a promising approach for therapy relying on their ability to i) target multiple oncogenic pathways relevant for melanoma progression and/or adopted by melanoma cells to survive upon treatment with target therapy, ii) circumvent the main drawbacks of delivering naked RNAs, i.e. poor cellular uptake, off-target activity and nuclease degradation. We expect that this project could have a relevant impact for the NHS, in terms of increased chance of cure and overcoming of drug resistance. Patients who, for various reasons, cannot benefit from currently available therapies or who develop resistance after initial treatment could benefit from new therapeutic strategies identified through this project. As most of the techniques required to reach the proposed aims are performed on a regular basis, the team does not foresee substantial issues in carrying out the planned experiments. If necessary the team has the ability to carry out additional approaches as outlined below:
Expected outcomes. Aim1: TO CREATE A NETWORK OF CENTERS WITH EXPERTISE IN RCVD throughout ITALY. Through the ALIGNED project, we would like to make the effort to strengthen cooperation not only in research, but also at health care level to improve the diagnostic and therapeutic pathways. The project will promote the creation of a network, connecting experts and researchers from nationally dispersed hospitals, promptly ensuring the highest available quality of care also to rural areas. It is expected to decrease patients' travels to secondary or tertiary centers, then reducing their difficulties and expenditures but also the waiting lists and costs for the National Health System. Through the ALIGNED project, peripheral hospitals would easily interact with the most experienced Italian centers. This will represent an advantage not only for healthcare professionals but, above all, for patients, who will no longer have the need to physically move to third-level healthcare facilities to obtain a diagnosis.
Expected outcomes. The following are the expected outcomes from this phase.
Expected outcomes. PLASTi@Risk will provide science, tools and a high level strategic framework for capacity building.