Objetivos:Com o incremento da disponibilidade de documentos eletrônicos em bases bibliográficas e de documentação clínica, a recuperação dessas informações requer a adoção de técnicas e interfaces amigáveis ao usuário. Métodos:Apresenta-se neste artigo uma estratégia específica para a recuperação de documentos, no domínio da indexação semântica de textos. A estratégia é baseada em um thesaurus de subwords e no mapeamento de textos, em diferentes linguagens, para uma representação única, interlingual, permitindo a busca entre diferentes coleções de documentos. Resultados:Três casos são apresentados empregando a metodologia desenvolvida: uma base de dados bibliográfica, um sistema departamental de prontuário eletrônico de pacientes e um portal Web. Conclusões:A utilização da metodologia de indexação e recuperação semântica revelou-se útil em diferentes protótipos e rotinas de trabalho, tendo sido bem aceita por diferentes grupos de usuários. Por fim, ressalta-se que a avaliação da performance da indexação já fora realizada, empiricamente, em estudos anteriores.

Objectives: The increasing amount of electronically available documents in bibliographic databases and the clinical documentation requires user-friendly techniques for content retrieval. Methods: A domain-specific approach on semantic text indexing for document retrieval is presented. It is based on a subword thesaurus and maps the content of texts in different European languages to a common interlingual representation, which supports the search across multilingual document collections. Results: Three use cases are presented where the semantic retrieval method has been implemented: a bibliographic database, a department EHR system, and a consumer-oriented Web portal. Conclusions: It could be shown that a semantic indexing and retrieval approach, the performance of which had already been empirically assessed in prior studies, proved useful in different prototypical and routine scenarios and was well accepted by several user groups.

• Klíčová slova
• MorphoSaurus,
• MeSH
• chorobopisy - počítačové systémy MeSH
• databáze bibliografické MeSH
• financování organizované MeSH
• lékařská informatika MeSH
• lingvistika metody   normy   MeSH
• mnohojazyčnost MeSH
• překládání MeSH
• řízený slovník MeSH
• sémantika MeSH
• ukládání a vyhledávání informací metody   MeSH
• zpracování přirozeného jazyka MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. METHODS: For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. FINDINGS: We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. INTERPRETATION: In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. FUNDING: Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

• MeSH
• dítě MeSH
• dystonie diagnóza   epidemiologie   genetika   MeSH
• exom genetika   MeSH
• genetická variace genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvenování exomu metody   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

• MeSH
• autofagie * fyziologie   MeSH
• autofagozomy MeSH
• biologické markery MeSH
• biotest normy   MeSH
• lidé MeSH
• lyzozomy MeSH
• proteiny spojené s autofagií metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• směrnice MeSH

• MeSH
• biomedicínské inženýrství MeSH
• biomedicínské technologie MeSH
• telemedicína MeSH
• výpočetní biologie MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH
• zprávy MeSH

• Konspekt
• Biotechnologie. Genetické inženýrství
• NLK Obory
• biomedicínské inženýrství
• lékařská informatika