Компьютерная система для дифференциальной диагностики лизосомных болезней накопления на основе методов искусственного интеллекта

Aim. To improve the efficiency of diagnosis of hereditary lysosomal storage diseases using an intelligent computerbased decision support system.Materials and methods. Descriptions of 35 clinical cases from the literature and depersonalized data of 52 patients from electronic health records were used as material for clinical testing of the computer diagnostic system. Knowledge engineering techniques have been used to extract, structure, and formalize knowledge from texts and experts. Literary sources included online databases and publications (in Russian and English). On this basis, for each clinical form of lysosomal diseases, textological cards were created, the information in which was corrected by experts. Then matrices were formed, including certainty factors (coefficients) for the manifestation, severity, and relevance of signs for each age group (up to 1 year, from 1 to 3 years inclusive, from 4 to 6 years inclusive, 7 years and older). The knowledge base of the expert system was implemented on the ontology network and included a disease model with reference variants of clinical forms. Decision making was carried out using production rules.Results. The expert computer system was developed to support clinical decision-making at the pre-laboratory stage of differential diagnosis of lysosomal storage diseases. The result of its operation was a ranked list of hypotheses, reflecting the degree of their compliance with reference descriptions of clinical disease forms in the knowledge base. Clinical testing was carried out on cases from literary sources and patient data from electronic health records. The criterion for assessing the effectiveness of disease recognition was inclusion of the verified diagnosis in the list of five hypotheses generated by the system. Based on the testing results, the accuracy was 87.4%.Conclusion. The expert system for the diagnosis of hereditary diseases has shown fairly high efficiency at the stage of compiling a differential diagnosis list at the pre-laboratory stage, which allows us to speak about the possibility of its use in clinical practice.Цель – повышение эффективности диагностики наследственных лизосомных болезней накопления с использованием интеллектуальной компьютерной системы поддержки принятий решений.Материалы и методы. В качестве материала для клинической апробации компьютерной диагностической системы использованы описания 35 клинических случаев из литературы и данные 52 пациентов из электронных медицинских карт (в деперсонифицированном виде). Методы инженерии знаний использовались для извлечения, структуризации и формализации знаний из текстов и у экспертов. Литературные источники включали онлайн-базы данных и публикации (русско- и англоязычные). На этой основе для каждой клинической формы лизосомных болезней были сформированы текстологические карты, информация которых корректировалась экспертами. Затем формировались матрицы, включающие факторы уверенности (коэффициенты) для манифестации, выраженности и релевантности признаков по каждой из возрастных групп (до 1 года, от 1 года до 3 лет включительно, от 4 до 6 лет включительно, 7 лет и старше). База знаний экспертной системы реализована на онтологической сети и включает модель заболевания с эталонными вариантами клинических форм. Принятие решений осуществляется с использованием продукционных правил.Результаты. Разработана экспертная компьютерная система поддержки принятия клинических решений на долабораторном этапе дифференциальной диагностики лизосомных болезней накопления. Результатом ее работы является ранжированный перечень диагностических гипотез, отражающий степень их соответствия эталонным описаниям клинических форм болезней в базе знаний. Проведена апробация системы на случаях из литературных источников и на данных пациентов из электронных медицинских карт. Критерием для оценки эффективности распознавания болезни было вхождение верифицированного диагноза в перечень из пяти гипотез, выдаваемых системой. По итогам проведенной апробации точность составила 87,4%.Заключение. Экспертная система для диагностики наследственных болезней показала достаточно высокую эффективность на этапе формирования дифференциально-диагностического ряда на долабораторном этапе, что позволяет говорить о возможности ее использования в клинической практике

Hybrid approach to knowledge extraction: textual analysis and evaluations of experts

The problem of extracting knowledge from medical experts for rare diseases causes difficulties due to the need to involve additional information about the clinical manifestations in this pathology. The report will consider a complex two-stage system of knowledge extraction. First, from literary sources using textological analysis. Then an expert evaluation of the information extracted from the literature with the addition of certainty factors

Motivations and personality characteristics of candidate sperm and oocyte donors according to parenthood status: a national study from the French CECOS network

International audienceAbstract STUDY QUESTION In a non-commercial national gamete donation programme, do the motivations and personality characteristics of candidate sperm and oocyte donors differ according to their parenthood status? SUMMARY ANSWER Moderate differences exist between non-parent and parent candidate donors in motivations for gamete donation and representations as well as in personality characteristics. WHAT IS KNOWN ALREADY Several studies have analysed the motivations and experiences of oocyte or sperm donors, but mainly in countries where gamete donation is a commercial transaction, and very few studies have reported results of personality traits using personality inventory tests. No study has specifically investigated the motivations and personality characteristics of candidate gamete donors according to parenthood status. STUDY DESIGN, SIZE, DURATION A prospective study was carried out including 1021 candidate donors from 21 centres (in university hospitals) of the national sperm and egg banking network in France between November 2016 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1021 candidate gamete donors were included in the study. During their first visit, male (n = 488) and female candidate donors (n = 533) completed a questionnaire on sociodemographic characteristics, their motivations for donation and their representations of donation, infertility and family. Secondly, a NEO Personality Inventory (NEO-PI-R) exploring the Big Five personality traits was completed online. Results were compared between parent and non-parent candidate donors. MAIN RESULTS AND THE ROLE OF CHANCE Altruistic values were the principal motive for donation irrespective of parenthood status. Reassurance about their fertility or preservation of sperm for future use was more often reported in non-parent than in parent candidate donors. With regard to representation of gamete donation or of the family, independently of their parenthood status, candidate donors more frequently selected social rather than biological representations. Mean personality characteristics were in the normal range. Non-parent candidate donors had higher scores on openness and depression than parents, while parent candidate donors appeared more social than non-parents. LIMITATIONS, REASONS FOR CAUTION The personality characteristics inventory was not completed by all candidate donors included in the study. However, family status did not differ between the two groups (NEO-PI-R completed (n = 525) or not), while the group who completed the NEO-PI-R had a higher educational level. This national study was performed in a country where gamete donation is subject to strict legislation. WIDER IMPLICATIONS OF THE FINDINGS In a global context where reproductive medicine is commercialized and gamete donor resources are limited, this study found that altruism and social representations of gamete donation and family are the main motivations for gamete donation in a country which prohibits financial incentive. These findings are relevant for health policy and for gamete donation information campaigns. STUDY FUNDING/COMPETING INTEREST(S) Grant from the Agence de la Biomédecine, France. The authors have nothing to disclose related to this study. TRIAL REGISTRATION NUMBER N/A

Natal origins and timing of migration of two passerine species through the southern Alps: Inferences from multiple stable isotopes (δ2H, δ13C, δ15N, δ34S) and ringing data

Understanding spatial linkages between areas used by migratory animals during the annual cycle is fundamental to their conservation. Stable isotope measurements of animal tissues can be a valuable tool in understanding spatial connectivity and migration phenology of migratory wildlife. We inferred natal origins of two migratory passerines, European Pied Flycatcher Ficedula hypoleuca and European Robin Erithacus rubecula, captured during autumn migration in the Italian Alps by combining feather δ2H (δ2Hf) and ring recovery data. We used a spatially -explicit likelihood -based method to assign individuals to a precipitation δ2H surface calibrated to represent feather δ2H, together with the directional probability of origin from ring recoveries. The highest probabilities of origin for most individuals of both species were in central and north -eastern Europe. Seasonal trends in δ2Hf, which described the species’ migratory phenology through the Italian Alps , were correlated with feather δ13C, δ15N and δ34S values, indicating strong spatial discrimination related to continental patterns for these isotopes. We demonstrate how this combined information can define catchment areas and migratory connectivity of birds intercepted in the Alps. We highlight the importance of ringing data in defining directional priors to define Bayesian -based probability surfaces using continental δ2Hf isoscapes, and how such information can be used to inform estimates of migratory connectivit

Transcriptional Profiles of Cytokine/Chemokine Factors of Immune Cell-Homing to the Parasitic Lesions: A Comprehensive One-Year Course Study in the Liver of E. multilocularis-Infected Mice

Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only parasitostatic effect of benzimidazoles in AE