Towards FAIRification of sensitive and fragmented rare disease patient data: challenges and solutions in European reference network registries

Introduction: Rare disease patient data are typically sensitive, present in multiple registries controlled by different custodians, and non-interoperable. Making these data Findable, Accessible, Interoperable, and Reusable (FAIR) for humans and machines at source enables federated discovery and analysis across data custodians. This facilitates accurate diagnosis, optimal clinical management, and personalised treatments. In Europe, twenty-four European Reference Networks (ERNs) work on rare disease registries in different clinical domains. The process and the implementation choices for making data FAIR (‘FAIRification’) differ among ERN registries. For example, registries use different software systems and are subject to different legal regulations. To support the ERNs in making informed decisions and to harmonise FAIRification, the FAIRification steward team was established to work as liaisons between ERNs and researchers from the European Joint Programme on Rare Diseases. Results: The FAIRification steward team inventoried the FAIRification challenges of the ERN registries and proposed solutions collectively with involved stakeholders to address them. Ninety-eight FAIRification challenges from 24 ERNs’ registries were collected and categorised into “training” (31), “community” (9), “modelling” (12), “implementation” (26), and “legal” (20). After curating and aggregating highly similar challenges, 41 unique FAIRification challenges remained. The two categories with the most challenges were “training” (15) and “implementation” (9), followed by “community” (7), and then “modelling” (5) and “legal” (5). To address all challenges, eleven types of solutions were proposed. Among them, the provision of guidelines and the organisation of training activities resolved the “training” challenges, which ranged from less-technical “coffee-rounds” to technical workshops, from informal FAIR Games to formal hackathons. Obtaining implementation support from technical experts was the solution type for tackling the “implementation” challenges. Conclusion: This work shows that a dedicated team of FAIR data stewards is an asset for harmonising the various processes of making data FAIR in a large organisation with multiple stakeholders. Additionally, multi-levelled training activities are required to accommodate the diverse needs of the ERNs. Finally, the lessons learned from the experience of the FAIRification steward team described in this paper may help to increase FAIR awareness and provide insights into FAIRification challenges and solutions of rare disease registries

Peat properties, dominant vegetation type and microbial community structure in a tropical peatland

Tropical peatlands are an important carbon store and source of greenhouse gases, but the microbial component, particularly community structure, remains poorly understood. While microbial communities vary between tropical peatland land uses, and with biogeochemical gradients, it is unclear if their structure varies at smaller spatial scales as has been established for a variety of peat properties. We assessed the abundances of PLFAs and GDGTs, two membrane spanning lipid biomarkers in bacteria and fungi, and bacteria and archaea, respectively, to characterise peat microbial communities under two dominant and contrasting plant species, Campnosperma panamensis (a broadleaved evergreen tree), and Raphia taedigera (a canopy palm), in a Panamanian tropical peatland. The plant communities supported similar microbial communities dominated by Gram negative bacteria (38.9–39.8%), with smaller but significant fungal and archaeal communities. The abundance of specific microbial groups, as well as the ratio of caldarchaeol:crenarchaeol, isoGDGT: brGDGTs and fungi:bacteria were linearly related to gravimetric moisture content, redox potential, pH and organic matter content indicating their role in regulating microbial community structure. These results suggest that tropical peatlands can exhibit significant variability in microbial community abundance even at small spatial scales, driven by both peat botanical origin and localised differences in specific peat properties

Development of peach flower buds under low winter chilling conditions

Here, we reviewed both endogenous and exogenous factors involved in the processes of flower bud formation and flower development in peach, analyzing how they can be affected by climatic change in temperate zones, explored the expansion of peach to tropical or subtropical zones. The process of flower bud formation in peach differs between low winter chilling and temperate conditions. Although the main steps of flower development are maintained, the timing in which each one occurs is different, and some processes can be altered under low winter chilling conditions, with a great impact on fruit production and crop management. Further studies on flower bud induction and differentiation under warmer conditions are fundamental for addressing the alterations in flower bud development that negatively impact on next season’s harvest. In the future, horticulturalists and scientists will face several challenges, mainly how high temperatures affect the expression of the main genes regulating flower formation and how to improve crop management in these conditions

Charge-density waves in the Hubbard chain: evidence for 4k_F instability

Charge density waves in the Hubbard chain are studied by means of finite-temperature Quantum Monte Carlo simulations and Lanczos diagonalizations for the ground state. We present results both for the charge susceptibilities and for the charge structure factor at densities \rho=1/6 and 1/3; for \rho=1/2 (quarter filled) we only present results for the charge structure factor. The data are consistent with a 4k_F instability dominating over the 2k_F one, at least for sufficiently large values of the Coulomb repulsion, U. This can only be reconciled with the Luttinger liquid analyses if the amplitude of the 2k_F contribution vanishes above some U^*(\rho).Comment: RevTeX, 4 two-column pages with 7 colour figures embedded in tex

Photoionization of ultracold and Bose-Einstein condensed Rb atoms

Photoionization of a cold atomic sample offers intriguing possibilities to observe collective effects at extremely low temperatures. Irradiation of a rubidium condensate and of cold rubidium atoms within a magneto-optical trap with laser pulses ionizing through 1-photon and 2-photon absorption processes has been performed. Losses and modifications in the density profile of the remaining trapped cold cloud or the remaining condensate sample have been examined as function of the ionizing laser parameters. Ionization cross-sections were measured for atoms in a MOT, while in magnetic traps losses larger than those expected for ionization process were measured.Comment: 9 pages, 7 figure

Kinin b(1) receptor in adipocytes regulates glucose tolerance and predisposition to obesity

BACKGROUND: Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B(1) receptor knockout mice (B(1) (-/-)) are leaner and exhibit improved insulin sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that kinin B(1) receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B(1) receptors. In these cells, treatment with the B(1) receptor agonist des-Arg(9)-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B(1) (-/-) mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B(1) receptor was limited to cells of the adipose tissue (aP2-B(1)/B(1) (-/-)). Similarly to B(1) (-/-) mice, aP2-B(1)/B(1) (-/-) mice were leaner than wild type controls. However, exclusive expression of the kinin B(1) receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B(1) (-/-) mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B(1) receptor in adipose tissue. In agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B(1)/B(1) (-/-) when compared to B(1) (-/-) mice. When subjected to high fat diet, aP2-B(1)/B(1) (-/-) mice gained more weight than B(1) (-/-) littermates, becoming as obese as the wild types. CONCLUSIONS/SIGNIFICANCE: Thus, kinin B(1) receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity