A guide to writing systematic reviews of rare disease treatments to generate FAIR-compliant datasets: Building a Treatabolome

Background: Rare diseases are individually rare but globally affect around 6% of the population, and in over 70% of cases are genetically determined. Their rarity translates into a delayed diagnosis, with 25% of patients waiting 5 to 30 years for one. It is essential to raise awareness of patients and clinicians of existing gene and variant-specific therapeutics at the time of diagnosis to avoid that treatment delays add up to the diagnostic odyssey of rare diseases' patients and their families. Aims: This paper aims to provide guidance and give detailed instructions on how to write homogeneous systematic reviews of rare diseases' treatments in a manner that allows the capture of the results in a computer-accessible form. The published results need to comply with the FAIR guiding principles for scientific data management and stewardship to facilitate the extraction of datasets that are easily transposable into machine-actionable information. The ultimate purpose is the creation of a database of rare disease treatments ("Treatabolome") at gene and variant levels as part of the H2020 research project Solve-RD. Results: Each systematic review follows a written protocol to address one or more rare diseases in which the authors are experts. The bibliographic search strategy requires detailed documentation to allow its replication. Data capture forms should be built to facilitate the filling of a data capture spreadsheet and to record the application of the inclusion and exclusion criteria to each search result. A PRISMA flowchart is required to provide an overview of the processes of search and selection of papers. A separate table condenses the data collected during the Systematic Review, appraised according to their level of evidence. Conclusions: This paper provides a template that includes the instructions for writing FAIR-compliant systematic reviews of rare diseases' treatments that enables the assembly of a Treatabolome database that complement existing diagnostic and management support tools with treatment awareness data

Hippocampal Volume Reduction in Congenital Central Hypoventilation Syndrome

Children with congenital central hypoventilation syndrome (CCHS), a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI) scans, with impaired responses in specific hippocampal regions, suggesting localized injury

Distribution and behavior of manganese in the Alto do Paranapanema Basin

This paper reports manganese (Mn) fractionation in samples collected from the water column and sediments in an environmental protection area in the Alto do Paranapanema Basin (Sao Paulo State, Brazil). The three locations studied showed equivalent Mn levels, with moderate seasonal differences (p < 0.05). The sediment samples contained five Mn species (p < 0.05): iron and manganese (hydr)oxides > Mn bound to carbonates approximate to exchangeable Mn approximate to Mn bound to silicates > Mn bound to organic matter (p < 0.05). The water samples contained three species (p < 0.05): particulate Mn > labile Mn approximate to non-labile Mn. The data suggest that Mn has a natural origin (Enrichment Factor EF < 2; Geoaccumulation Index I(geo) < 0) and moderate environmental risk (Risk Assessment Code RAC similar to 30%). At the same time, under certain conditions some manganese species could be present in a state of equilibrium between the water column and sediment. These results could provide a basis for Mn management in the Alto do Paranapanema Basin.FAPESP (Fundacao de Amparoa Pesquisa do Estado de Sao Paulo)CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico

Sporothrix schenckii complex biology: environment and fungal pathogenicity

Sporothrix schenckii is a complex of various species of fungus found in soils, plants, decaying vegetables and other outdoor environments. It is the aetiological agent of sporotrichosis in humans and several animals. Humans and animals can acquire the disease through traumatic inoculation of the fungus into subcutaneous tissue. Despite the importance of sporotrichosis, it being currently regarded as an emergent disease in several countries, the factors driving its increasing medical importance are still largely unknown. There have only been a few studies addressing the influence of the environment on the virulence of these pathogens. However, recent studies have demonstrated that adverse conditions in its natural habitats can trigger the expression of different virulence factors that confer survival advantages both in animal hosts and in the environment. in this review, we provide updates on the important advances in the understanding of the biology of Spor. schenckii and the modification of its virulence linked to demonstrated or putative environmental factors.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Bioscience and Biotechnology Applied to Pharmacy Pos-graduate Program from Pharmaceutical Sciences Faculty, UNESP, Araraquara, SP, BrazilOriente Univ, Fac Chem Engn, Santiago de Cuba, CubaUniv Estadual Paulista, Fac Pharmaceut Sci, UNESP, BR-14801902 Araraquara, SP, BrazilMed Sci Univ, Toxicol & Biomed Ctr TOXIMED, Immunotoxicol Lab, Santiago de Cuba 90400, CubaUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilCAPES: 07610130Web of Scienc

Sporothrix schenckii complex biology: environment and fungal pathogenicity

Sporothrix schenckii is a complex of various species of fungus found in soils, plants, decaying vegetables and other outdoor environments. It is the aetiological agent of sporotrichosis in humans and several animals. Humans and animals can acquire the disease through traumatic inoculation of the fungus into subcutaneous tissue. Despite the importance of sporotrichosis, it being currently regarded as an emergent disease in several countries, the factors driving its increasing medical importance are still largely unknown. There have only been a few studies addressing the influence of the environment on the virulence of these pathogens. However, recent studies have demonstrated that adverse conditions in its natural habitats can trigger the expression of different virulence factors that confer survival advantages both in animal hosts and in the environment. In this review, we provide updates on the important advances in the understanding of the biology of Spor. schenckii and the modification of its virulence linked to demonstrated or putative environmental factors.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

P192 The open-access treatabolome platform enhances the visibility of treatable and actionable genes in RD-connect's GPAP and other clinical diagnosis support tools

Rare diseases are individually rare but globally affect 3.5 to 5.9% of the population, i.e. 263-446 million people worldwide, according to the latest calculations. Recent estimates point to over 10000 rare diseases, of which 6172 disorders are listed in Orphanet, about 70% of which being genetic and around 70% having paediatric onset. Disease rarity translates into a delayed diagnosis, with 25% of patients having to wait for 5 to 30 years to have one. It is essential, at the time of diagnosis, to be able to relay information about potential gene and variant-specific therapies to patients. The Treatabolome (www.treatabolome.org) was conceived to enhance the visibility of existing treatments for non-specialists and avoid delays to treatment initiation. Currently, the Treatabolome contains datasets related to 77 genes, most of which associated to on a wide spectrum of neuromuscular disorders. Interactions with other Projects are ongoing, such as MAxO (https://github.com/monarch-initiative/MAxO) for improving the Medical Action Ontology and the French FILNEMUS network which reported the list of 63 actionable genes in myopathies following ClinGen criteria. The idea is to have the therapeutic information for each gene and variant-specific treatment in an online freely available database and make it interoperable with clinical decision and diagnosis support tools (e.g., RD-Connect´s GPAP https://rd-connect.eu/what-we-do/omics/gpap/), allowing that information to be provided simultaneously with the diagnosis

The Treatabolome flags treatable genes and variants: an emerging concept

International audienc

The Treatabolome flags treatable genes and variants: an emerging concept

International audienc

The Treatabolome flags treatable genes and variants: an emerging concept

International audienc