Operational description of rare diseases: a reference to improve the recognition and visibility of rare diseases.

Improving health and social equity for persons living with a rare disease (PLWRD) is increasingly recognized as a global policy priority. However, there is currently no international alignment on how to define and describe rare diseases. A global reference is needed to establish a mutual understanding to inform a wide range of stakeholders for actions.

Perspectives, Expectations, and Concerns of European Patient Advocates on Advanced Therapy Medicinal Products.

This paper presents the results of a qualitative study based on semi-structured interviews of 10 expert patient advocates on several different issues around Advanced Therapy Medicinal Products (ATMPs). The interviews were conducted between February and May 2020 based on a guideline with a list of 8 topics that covered concerns about safety and ethics, access problems and limitations, pricing of ATMPs and educational needs for patient communities. Overall, the interviewees expressed a high degree of convergence of opinions on most of the topics and especially on the identification of the reasons for concern.

Governance of Access in Biobanking: The Case of Telethon Network of Genetic Biobanks.

The discussion concerning the measure of the quality of a biobank should focus not only on the number of stored samples and their quality but also on the assessment of their access arrangements and governance. This article aims at contributing to the ongoing debate on samples and data access governance in biobanking by presenting the case of the Telethon Network of Genetic Biobanks (TNGB). We attempt to contribute to the need for clear and available access criteria and harmonization in access arrangements to maximize the influence of biobanks in the progress of biomedical research.

"Integrating China in the International Consortium for Personalized Medicine": The Coordination and Support Action to Foster Collaboration in Personalized Medicine Development between Europe and China.

"Integrating China in the International Consortium for Personalized Medicine" (IC2PerMed) is a coordination and support action funded within the Horizon 2020 work program. Following the guidance of the International Consortium for Personalized Medicine (ICPerMed), the project's overarching aim is to align the European Union and China's research agendas in the field of personalized medicine (PM) to enable a swift development of PM approaches in the EU with strong leverage upon EU-Chinese collaboration. Living in the CO-VID-19 era, we are witnessing how the challenges imposed by the pandemic all around the globe have been acting as a catalyst for collaborations and knowledge sharing among national health systems worldwide.

The RD-Connect Registry & Biobank Finder: a tool for sharing aggregated data and metadata among rare disease researchers.

In rare disease (RD) research, there is a huge need to systematically collect biomaterials, phenotypic, and genomic data in a standardized way and to make them findable, accessible, interoperable and reusable (FAIR). RD-Connect is a 6 years global infrastructure project initiated in November 2012 that links genomic data with patient registries, biobanks, and clinical bioinformatics tools to create a central research resource for RDs. Here, we present RD-Connect Registry & Biobank Finder, a tool that helps RD researchers to find RD biobanks and registries and provide information on the availability and accessibility of content in each database.

The alliance between genetic biobanks and patient organisations: the experience of the telethon network of genetic biobanks.

Background: Rare diseases (RDs) are often neglected because they affect a small percentage of the population (6-8 %), which makes research and development of new therapies challenging processes. Easy access to high-quality samples and associated clinical data is therefore a key prerequisite for biomedical research. In this context, Genetic Biobanks are critical to developing basic, translational and clinical research on RDs.

Adenosine triphosphate acts as a paracrine signaling molecule to reduce the motility of T cells.

Organization of immune responses requires exchange of information between cells. This is achieved through either direct cell-cell contacts and establishment of temporary synapses or the release of soluble factors, such as cytokines and chemokines. Here we show a novel form of cell-to-cell communication based on adenosine triphosphate (ATP).

The challenge for a European network of biobanks for rare diseases taken up by RD-Connect.

Access to biological materials is a key prerequisite for scientific research in any medical field and in particular for research into rare diseases (RDs), for which obtaining high-quality samples and the related clinical data remains a major hurdle. RD biobanks play a pivotal role in making such materials and data available to the scientific community. In order to increase the effectiveness of RD biobanks, three major challenges need to be met: maximise access to rare biological samples stored in RD biobanks spread globally by the international scientific community, promote networking among such biobanks to share quality standards and procedures and allow collaboration with RD registries and databases, and finally adopt an efficient management model compliant with legal and ethical issues and ensuring biobank sustainability.

Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells.

T cell-intrinsic transforming growth factor β (TGFβ) receptor signaling plays an essential role in controlling immune responses. The RING-type E3 ligase Cbl-b has been shown to mediate the sensitivity of T cells to TGFβ; however, the mechanism underlying this process is unknown. This study shows that SMAD7, an established negative regulator of TGFβ receptor (TGFβR) signaling, is a key downstream effector target of Cbl-b.

Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases.

Background: Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available.

Principal Findings: In wound edge biopsies from human venous leg ulcers we found a striking upregulation of dermal N-cadherin, Zonula Occludens-1 and the gap junction protein Connexin43 (Cx43) compared to intact skin, and in stark contrast to the down-regulation of Cx43 expression seen in acute, healing wounds. We targeted the expression of these proteins in 3T3 fibroblasts to evaluate their role in venous leg ulcers healing.

667C>T and 1298A>C polymorphisms of MTHFR do not predict response to methotrexate in patients with gestational trophoblastic neoplasia.

Objective: Approximately one third of patients treated with methotrexate for gestational trophoblastic neoplasia (GTN) following a molar pregnancy are reported to develop resistance to methotrexate and need to change to different chemotherapeutic agents. Previous studies, in other clinical settings, have suggested that polymorphisms in key folate metabolising enzymes such as 5,10-methylenetetrahydrofolate reductase (MTHFR) influence both toxicity and efficacy of methotrexate. Our objective was to investigate the impact of two common functional MTHFR polymorphisms, 677C>T and 1298A>C, on the efficacy of methotrexate in women treated for GTN following a molar pregnancy.

Abnormal connexin expression underlies delayed wound healing in diabetic skin.

Objective: Dynamically regulated expression of the gap junction protein connexin (Cx)43 plays pivotal roles in wound healing. Cx43 is normally downregulated and Cx26 upregulated in keratinocytes at the edge of the wound as they adopt a migratory phenotype. We have examined the dynamics of Cx expression during wound healing in diabetic rats, which is known to be slow.

Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration.

Experimental downregulation of connexin43 (Cx43) expression at skin wound sites appears to markedly improve the rate and quality of healing, but the underlying mechanisms are currently unknown. Here, we have compared physiological and cell biological aspects of the repair process with and without Cx43 antisense oligodeoxynucleotide treatment. Treated wounds exhibited accelerated skin healing with significantly increased keratinocyte and fibroblast proliferation and migration.