429 research outputs found
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 (âFAIRificationâ) 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 ERNsâ registries were collected and categorised into âtrainingâ (31), âcommunityâ (9), âmodellingâ (12), âimplementationâ (26), and âlegalâ (20). After curating and aggregating highly similar challenges, 41 unique FAIRification challenges remained. The two categories with the most challenges were âtrainingâ (15) and âimplementationâ (9), followed by âcommunityâ (7), and then âmodellingâ (5) and âlegalâ (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 âtrainingâ challenges, which ranged from less-technical âcoffee-roundsâ to technical workshops, from informal FAIR Games to formal hackathons. Obtaining implementation support from technical experts was the solution type for tackling the âimplementationâ 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
DIFUSĂO E INOVAĂĂO TECNOLĂGICA: UMA APLICAĂĂO DO MODELO EVOLUCIONĂRIO DE CRESCIMENTO AGRĂCOLA
Especialização e competitividade de Minas Gerais no mercado internacional: um estudo de indicadores de comĂ©rcio exterior no perĂodo de 1992 a 1999
A MIGRAĂĂO INTRAMETROPOLITANA NA REGIĂO METROPOLITANA DE BELO HORIZONTE: UMA COMPARAĂĂO ENTRE OS MUNICĂPIOS DE CONTAGEM E NOVA LIMA, 1991-2000
Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis
Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes
Is there a role for melatonin in fibromyalgia?
Fibromyalgia, characterised by persistent pain, fatigue, sleep disturbance and cognitive dysfunction, is a central sensitivity syndrome that also involves abnormality in peripheral generators and in the hypothalamic pituitary adrenal axis. Heterogeneity of clinical expression of fibromyalgia with a multifactorial aetiology has made the development of effective therapeutic strategies challenging. Physiological properties of the neurohormone melatonin appear related to the symptom profile exhibited by patients with fibromyalgia and thus disturbance of itâs production would be compatible with the pathophysiology. Altered levels of melatonin have been observed in patients with fibromyalgia which are associated with lower secretion during dark hours and higher secretion during daytime. However, inconsistencies of available clinical evidence limit conclusion of a relationship between levels of melatonin and symptom profiles in patients with fibromyalgia. Administration of melatonin to patients with fibromyalgia has demonstrated suppression of many symptoms and an improved quality of life consistent with benefit as a therapy for the management of this condition. Further studies with larger samples, however, are required to explore the potential role of melatonin in the pathophysiology of fibromyalgia and determine the optimal dosing regimen of melatonin for the management of fibromyalgia
Synergistic antimicrobial activity of silver nanoparticles with an emergent class of azoimidazoles
he combination of two or more agents capable of acting in synergy has been reported as a valuable tool to fight against pathogens. Silver nanoparticles (AgNPs) present a strong antimicrobial action, although their cytotoxicity for healthy cells at active concentrations is a major concern. Azoimidazole moieties exhibit interesting bioactivities, including antimicrobial activity. In this work, a class of recently described azoimidazoles with strong antifungal activity was conjugated with citrate or polyvinylpyrrolidone-stabilized AgNPs. Proton nuclear magnetic resonance was used to confirm the purity of the compounds before further tests and atomic absorption spectroscopy to verify the concentration of silver in the prepared dispersions. Other analytical techniques elucidate the morphology and stability of AgNPs and corresponding conjugates, namely ultravioletâvisible spectrophotometry, scanning transmission electron microscopy and dynamic light scattering analysis. The synergistic antimicrobial activity of the conjugates was assessed through a checkerboard assay against yeasts (Candida albicans and Candida krusei) and bacteria (Staphylococcus aureus and Escherichia coli). The conjugates showed improved antimicrobial activity against all microorganisms, in particular towards bacteria, with concentrations below their individual minimal inhibitory concentration (MIC). Furthermore, some combinations were found to be non-cytotoxic towards human HaCaT cells.This work was funded by the European Regional Development Fund through the Oper ational Competitiveness Program and through the National Foundation for Science and Technol ogy of Portugal (FCT) under the projects UID/CTM/00264/2020 of Centre for Textile Science and
Technology (2C2T), UIDB/00686/2020 of the Chemistry Centre of University of Minho (CQUM),
UIBD/04423/2020 and UIDP/04423/2020 of the CIIMAR/CIMAR, Interdisciplinary Centre of Ma rine and Environmental Research and FCT Project MEDCOR PTDC/CTM-TEX/1213/2020. Ana
Isabel Ribeiro acknowledges FCT for the funding of her Ph.D. scholarship SFRH/BD/137668/2018
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