Репозиторий Университета

Background: It remains unclear whether alcohol use disorders (AUDs) can be characterized by specific levels of average daily alcohol consumption. The aim of the current study was to model the distributions of average daily alcohol consumption among those who consume alcohol and those with alcohol dependence, the most severe AUD, using various clustering techniques. Methods: Data from Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used in the current analyses. Clustering algorithms were applied in order to group a set of data points that represent the average daily amount of alcohol consumed. Gaussian Mixture Models (GMMs) were then used to estimate the likelihood of a data point belonging to one of the mixture distributions. Individuals were assigned to the clusters which had the highest posterior probabilities from the GMMs, and their treatment utilization rate was examined for each of the clusters. Results: Modeling alcohol consumption via clustering techniques was feasible. The clusters identified did not point to alcohol dependence as a separate cluster characterized by a higher level of alcohol consumption. Among both females and males with alcohol dependence, daily alcohol consumption was relatively low. Conclusions: Overall, we found little evidence for clusters of people with the same drinking distribution, which could be characterized as clinically relevant for people with alcohol use disorders as currently defined.

© 2020 The Author(s). Published by IOP Publishing Ltd Printed in the UK Graphene-based nano-porous materials (GNM) are potentially useful for all those applications needing a large specific surface area (SSA), typical of the bidimensional graphene, yet realized in the bulk dimensionality. Such applications include for instance gas storage and sorting, catalysis and electrochemical energy storage. While a reasonable control of the structure is achieved in micro-porous materials by using nano-micro particles as templates, the controlled production or even characterization of GNMs with porosity strictly at the nano-scale still raises issues. These are usually produced using dispersion of nano-flakes as precursors resulting in little control on the final structure, which in turn reflects in problems in the structural model building for computer simulations. In this work, we describe a strategy to build models for these materials with predetermined structural properties (SSA, density, porosity), which exploits molecular dynamics simulations, Monte Carlo methods and machine learning algorithms. Our strategy is inspired by the real synthesis process: starting from randomly distributed flakes, we include defects, perforation, structure deformation and edge saturation on the fly, and, after structural refinement, we obtain realistic models, with given structural features. We find relationships between the structural characteristics and size distributions of the starting flake suspension and the final structure, which can give indications for more efficient synthesis routes. We subsequently give a full characterization of the models versus H2 adsorption, from which we extract quantitative relationship between the structural parameters and the gravimetric density. Our results quantitatively clarify the role of surfaces and edges relative amount in determining the H2 adsorption, and suggest strategies to overcome the inherent physical limitations of these materials as adsorbers. We implemented the model building and analysis procedures in software tools, freely available upon request.

© 2020 Elsevier Ltd Background: A beneficial impact of robotic proctectomy on circumferential resection margin (CRM) is expected due to the robot's articulating instruments in the pelvis. There are however concerns about a negative impact on the quality of total mesorectal excision (TME) due to the lack of tactile feedback. The aim of this study was to assess whether surgeons' learning curve impacted CRM and TME quality. Methods: In a multicenter study, individual patient data of robotic proctectomy for resectable rectal cancer were pooled. Patients were stratified into two phases of surgeons’ learning curve. Cumulative sum (CUSUM) analysis was used to determine the transition from learning phase (LP) to plateau phase (PP), which were compared. CRM was microscopically measured in mm by pathologists. TME quality was classified by pathologists as complete, nearly complete or incomplete. T-test and Chi-squared tests were used to compare continuous and categorical variables, respectively. Results: 235 patients underwent robotic proctectomy by five surgeons. 83 LP patients were comparable to 152 PP patients for age (p = 0.20), gender (67.5% vs. 65.1% males; p = 0.72), BMI (p = 0.82), cancer stage (p = 0.36), neoadjuvant chemoradiation (p = 0.13), distance of tumor from anal verge (5.8 ± 4.4 vs. 5.5 ± 3.3; p = 0.56). CRM did not differ (7.7 ± 11.4 mm vs. 8.4 ± 10.3 mm; p = 0.62). The rate of complete TME quality was significantly improved in PP patients as compared to LP patients (73.5% vs. 92.1%; p < 0.001). Conclusion: While learning had no impact on circumferential resection margins, the quality of TME significantly improved during surgeons’ plateau phase as compared to their learning phase.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2019 Elsevier B.V. A massive-scale production of engineered nanoparticles (ENPs) becomes one of the most important environmental issues. The mechanisms of ENPs' (eco)toxic action are not fully understood, and the estimation of those mechanisms is a complicated task because even slight changes in particle characteristics could dramatically change their toxicity. As a result of continuous manufacturing of ENPs with specific functionality and different physicochemical properties, conventional methods of in vivo and in vitro testing would not be able to fill the existing knowledge gap in nanotoxicology. The objectives of this review are to overlook the current achievements based on the new approaches of ENPs' risk assessment, such as bioinformatics approaches and machine learning tools. These methods confirmed their ability to reliable prediction and evaluation of ENPs' behavior and their toxic endpoints. Databases and projects based on these methods and approaches would be highly useful in addressing the problem of ENPs’ regulation.

© Springer Science+Business Media, LLC, part of Springer Nature 2020. Intracellular molecular pathways (IMPs) control all major events in the living cell. IMPs are considered hotspots in biomedical sciences and thousands of IMPs have been discovered for humans and model organisms. Knowledge of IMPs activation is essential for understanding biological functions and differences between the biological objects at the molecular level. Here we describe the Oncobox system for accurate quantitative scoring activities of up to several thousand molecular pathways based on high throughput molecular data. Although initially designed for gene expression and mainly RNA sequencing data, Oncobox is now also applicable for quantitative proteomics, microRNA and transcription factor binding sites mapping data. The Oncobox system includes modules of gene expression data harmonization, aggregation and comparison and a recursive algorithm for automatic annotation of molecular pathways. The universal rationale of Oncobox enables scoring of signaling, metabolic, cytoskeleton, immunity, DNA repair, and other pathways in a multitude of biological objects. The Oncobox system can be helpful to all those working in the fields of genetics, biochemistry, interactomics, and big data analytics in molecular biomedicine.

© 2017 John Wiley  &  Sons Ltd and International Behavioural and Neural Genetics Society  Anxiety disorders result from a complex interplay of genetic and environmental factors such as stress. On the level of cellular signaling, regulator of G protein signaling 2 (Rgs2) has been implicated in human and rodent anxiety. However, there is limited knowledge about the role of Rgs2 in fear learning and reactivity to stress. In this study, Rgs2 −/− mice showed increased fear learning, male mice displayed increased contextual and cued fear learning, while females showed selectively enhanced cued fear learning. Male Rgs2 −/− mice displayed increased long-term-contextual fear memory, but increased cued fear extinction. Learning in spatial non-aversive paradigms was also increased in Rgs2 −/− mice. Female, but not male mice show increased spatial learning in the Barnes maze, while male mice showed enhanced place preference in the IntelliCage, rendering enhanced cognitive function non-specific for aversive stimuli. Consistent with the previous results, Rgs2 deletion resulted in increased innate anxiety, including neophobic behavior expressed as hypolocomotion, in three different tests based on the approach-avoidance conflict. Acute electric foot shock stress provoked hypolocomotion in several exploration-based tests, suggesting fear generalization in both genotypes. Rgs2 deletion was associated with reduced monoaminergic neurotransmitter levels in the hippocampus and prefrontal cortex and disturbed corresponding GPCR expression of the adrenergic, serotonergic, dopaminergic and neuropeptide Y system. Taken together, Rgs2 deletion promotes improved cognitive function as well as increased anxiety-like behavior, but has no effect on acute stress reactivity. These effects may be related to the observed disruption of the monoaminergic systems.

© 2018 Media Sphera Publishing Group. All rights reserved. Russia joined the Bologna process in 2003 and since that time has become integrated into the unified European educational space. The key element of the new form of the higher education process is the self-guided unsupervised work of the students. Motivation is needed to promote the involvement of the students in the educational process which implies the necessity of the goal-oriented initiative for the acquisition of professional knowledge and practical experience in the field of forensic medicine. To achieve this goal, the Department of Forensic Medicine of I.M. Sechenov First Moscow State Medical University places special emphasis on the experience with carrying out student competitions. Each such competition consists of several contests focused on the solution of a specific problem, e.g. the inspection of the place of occurrence under investigation with a gunshot or punctured-and-incised wound, forensic medical autopsy, problem studies, and intelligence tests. All the contests and problem studies are held in the form of an interactive game. The experience gained in the course of the student competitions gives practical evidence that the interdepartmental intelligence contests contribute to raising the interest of students in forensic medicine. The open competition provides a highly efficient tool for the popularization of scientific knowledge and the promotion of interest in the participation in the forensic medical research activities. Moreover, the student competitions facilitate formation of the earlier professional skills indispensable for team working and the development of abilities for making decisions under the extreme conditions. In addition, the contests teach the participants the art of public appearance. They improve the quality of vocational training in forensic medicine and help to establish the first professional contacts at the interinstitutional (including international) level.

© 2011–2018 NSPU Bulletin All rights reserved  Introduction. The authors investigate the problem of effective use of distance technologies in the educational process. The purpose of the article is to identify the potential of the Moodle electronic distance learning platform as a source for improving the quality of technical education. Materials and Methods. The authors used a set of research methods, including: 1) analysis of scientific literature on the topic of the article; 2) proposition of a hypothesis about the possibility of expanding the didactic functions of the Moodle distance learning platform by integrating interactive content into it; 3) constructing a methodological model which includes innovative educational content, characterized by an interactive format; 4) experimental approbation of teaching methods with elements of statistical analysis of the results of the control and experimental groups of students using the Pearson criteria – χ 2 . Results. As a result of the research, the following statements were identified: 1) determining factors for the realization of the capabilities of the Moodle platform in the educational process for the disciplines of physical, mathematical and technical fields; 2) the authors developed an algorithm for evaluating students’ work and showed the possibilities of placing models in a distance learning system to perform laboratory work necessary for the qualitative studying these disciplines; 3) the statistical analysis showed a positive result in terms of improving the quality of mastering basic knowledge elements. Conclusions. The authors summarize the characteristic features of the potential of the Moodle e-learning platform as a source for improving the quality of technical education.

© 2018, ABV-Press Publishing House. Attention deficit hyperactivity disorder (ADHD) is the most common cause of behavioral disorders and learning difficulties in preschool and school-age children. Patients with ADHD are often diagnosed with concomitant diseases, which creates additional diagnostic and therapeutic challenges and leads to a more significant reduction in the quality of life. ADHD is often associated with epilepsy: ADHD manifestations are more common in individuals with epilepsy, and vice versa, patients with ADHD are more likely to have epilepsy. The estimated prevalence of ADHD in children is 7-9 %, whereas in children with epilepsy, it reaches 20-50 %. Epilepsy is also one of the most common diseases in children (affecting approximately 1 % of the pediatric population), which is often aggravated by concomitant diseases, including cognitive, behavioral and emotional disorders. Various factors, such as characteristics of epileptic process and lesions in particular portions of the brain, can underlie the development of ADHD in epilepsy. Epileptiform activity and adverse effects of antiepileptic drugs can also play an important etiological role. Some antiepileptic drugs (such as barbiturates) may cause symptoms similar to those in ADHD (in this case, inattentiveness and hyperactivity shall be considered as adverse events that can be reduced or eliminated after cessation of the drug) or exacerbate ADHD symptoms in patients with these disorders. Therefore, the drugs with no negative impact on concomitant diseases or with a positive therapeutic effect for both diseases are preferable in these cases. High prevalence of the ADHD/epilepsy combination leads to a greater reduction in the quality of life, suggesting high relevance of this problem and requiring a revision of therapeutic approaches.