Sharing sensitive data in life sciences: an overview of centralized and federated approaches.

Biomedical data are generated and collected from various sources, including medical imaging, laboratory tests and genome sequencing. Sharing these data for research can help address unmet health needs, contribute to scientific breakthroughs, accelerate the development of more effective treatments and inform public health policy. Due to the potential sensitivity of such data, however, privacy concerns have led to policies that restrict data sharing. In addition, sharing sensitive data requires a secure and robust infrastructure with appropriate storage solutions. Here, we examine and compare the centralized and federated data sharing models through the prism of five large-scale and real-world use cases of strategic significance within the European data sharing landscape: the French Health Data Hub, the BBMRI-ERIC Colorectal Cancer Cohort, the federated European Genome-phenome Archive, the Observational Medical Outcomes Partnership/OHDSI network and the EBRAINS Medical Informatics Platform. Our analysis indicates that centralized models facilitate data linkage, harmonization and interoperability, while federated models facilitate scaling up and legal compliance, as the data typically reside on the data generator's premises, allowing for better control of how data are shared. This comparative study thus offers guidance on the selection of the most appropriate sharing strategy for sensitive datasets and provides key insights for informed decision-making in data sharing efforts.

Moderate antiangiogenic activity by local, transgenic expression of endostatin in Rip1Tag2 transgenic mice.

Many previous reports have demonstrated that systemic administration of endostatin (ES), a proteolytic cleavage product of collagen type XVIII and an endogenous angiogenesis inhibitor, represses tumor angiogenesis in different preclinical tumor models with varying efficacy. For example, systemic delivery of recombinant ES to rat insulin promoter 1 (Rip1)T-antigen 2 (Tag2)-transgenic mice, a mouse model of pancreatic beta-cell carcinogenesis, has repressed tumor angiogenesis efficiently and with it, tumor growth. Here, we report that the transgenic expression of ES in Rip1ES-transgenic mice only interferes moderately with tumor growth in Rip1Tag2;Rip1ES double-transgenic mice. Tumor incidence is not reduced by the local expression of ES, and tumor outgrowth and progression to tumor malignancy are only retarded slightly. A significant effect of local ES expression on tumor angiogenesis is only apparent during the early stages of tumor development, where less angiogenic hyperplastic lesions are observed. Although efficiently produced and secreted by transgenic beta cells, locally expressed ES appears to be sequestered in the microenvironment, and its systemic levels are not increased. The results indicate that the antiangiogenic functions of ES critically depend on the mode of delivery and the site of expression: although its systemic application represses tumor angiogenesis and tumor growth efficiently, locally expressed ES appears to be less effective, and hence, additional mechanisms of solubilization or activation of latent ES seem to be required. These results have important implications about the modes of delivery used in antiangiogenic, therapeutic strategies, which are based on the antiangiogenic activities of ES.

Cadherins and the tumour progression: is it all in a switch?

Progression to tumour malignancy involves changes in a tumour cell's capabilities to adhere and communicate with neighboring cells and with its extracellular environment. Correlation studies in human cancer specimen and functional experiments with cultured tumour cells and transgenic mouse models have indicated that the loss of the cell adhesion molecule E-cadherin is causally involved in the formation of epithelial cancers (carcinomas). More recently, it has been observed that the function of E-cadherin is replaced or overruled by the expression of mesenchymal cadherins, such as N-cadherin. Although the functional implication of such a 'cadherin switch' remains to be elucidated, recent experimental results demonstrating an interaction of cadherins with tyrosine kinase receptors suggest that changes in cadherin expression may not only modulate tumour cell adhesion but also affect signal transduction and, hence, the malignant phenotype.