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Subject. The mechanisms of occlusion disturbance are associated with various pathogenic factors. Determining the relationship between the characteristics of the patient's dental status is a mandatory stage of diagnosis. There are a large number of mathematical models of tooth movements within the dentition, but the disadvantage of such models, mainly, is the lack of consideration of local conditions that affect the movement of individual teeth. In addition, there are currently no data on the influence of local factors and age on the total duration of orthodontic treatment. The aim is to determine the factors that significantly affect the timing of orthodontic treatment. Methodology. The base of the study was the department of pediatric dentistry and orthodontics of the research institute of dentistry, St. Petersburg State Medical University. The object of the research were 146 medical records of orthodontic patients No. 043-1 / y. A database was created based on a retrospective analysis of medical records and further statistical processing to identify regression correlation. Results. It was revealed that such parameters of a dental patient as the presence of gum recession, the presence of mobility and the presence of a concomitant dentoalveolar anomaly affect the duration of treatment. Parameters that are not correlated with the timing: the type of vestibule, the presence of bleeding, and the patient's age. Conclusions. In the future, such data can be used to predict the timing of orthodontic treatment, create a mathematical model and a personalized criterion for the movement of teeth, which in turn will expand the possibilities of planning orthodontic treatment and increase compliance with the upcoming correction of dentoalveolar anomalies.

Introduction: There is growing evidence of a connection between tumor clonal profile and its clinical impact. However, there is a lack of a feasible and reliable method for clonal profiling in actual clinical practice. Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder characterized by morphological dysplasia, cytopenia and a high risk of evolution to acute myeloid leukemia. The clinical outcome of myelodysplastic syndrome is greatly heterogeneous; therefore, specific examination of clonal profiles is needed to resolve the prognosis of patients with such complex disorders. Purpose: Development of a pipeline specifically for determining the clonal profiles in patients with myelodysplastic syndrome on the basis of target next-generation sequencing data. Results: The pipeline was developed and evaluated on a set of 35 patients with high-risk myelodysplastic syndrome. It is possible to use the target sequencing data in order to assess the heterogeneity of clonal profiles and characterize their genetic features. This approach allows you to identify the consistency between a specific individual profile and the disease prognosis, which can be critical for the treatment decision. Herein, the characterization and analysis of clonal profiles are presented. Practical relevance: The information about relation patterns between clonal profile characteristics (number of subclones, mutations-per-clone rate) and clinical outcome can be used by doctors in current practice for a more accurate therapy selection depending on the identified individual specificity of the disease.

Purpose: To determine the features of circulatory disorders in the lungs in patients with ordinary interstitial pneumonia (OIP) at different stages of the pathological process and with the development of comorbid conditions. Material and methods: The analysis of the results of radiation research methods: computer tomography, computed angiography and single photon emission computed tomography in 64 patients with common interstitial pneumonia. The selection criteria were the presence of respiratory failure and pulmonary hypertension. Results: The combination of interstitial and alveolar changes, their distribution in the lower parts of both lungs with subpleural localization are mainly pathognomonic for IPI. In 85 % of patients with OIP and the formation of a “cellular lung”, local perfusion disorders of various forms, of small size, subsegmental level, located symmetrically in the diaphragm regions were determined. The main distinctive CT signs of adherence to vascular pathology: pulmonary pattern mosaic; subpleural infiltration sites of the lung tissue of heterogeneous structure; defects in filling the pulmonary artery with a contrast agent during CT angiography; triangular subpleurally located areas of perfusion disturbance on SPECT (when SPECT/CT is combined), localized in the area of lung infarction, or in the zone of no changes on CT. Conclusion: The development of pulmonary hypertension and chronic respiratory failure in OIP is determined by several factors that have an active or passive effect on pulmonary hemodynamics. Worsening of the patient’s condition and an increase in the degree of respiratory failure and pulmonary hypertension, contributes to complication of the pulmonary vascular system – pulmonary thromboembolism and (or) thrombosis in situ, as well as persistent infectious inflammatory processes. In the presence of irreversible morphological changes in the lung parenchyma therapeutic measures do not affect the state of microcirculation in the lungs.

Myelodysplastic syndrome (MDS) refers to a heterogeneous group of closely related clonal hematopoietic disorders, which are characterized by accumulation of somatic mutations. The acquired mutation burden is suggested to define the pathway and consequent phenotype of the pathology. Recent studies have called attention to the role of miRNA biogenesis genes in MDS progression; in particular, the mutational pressure of the DROSHA gene was determined. Therefore, this highlights the importance of studying the impact of all collected missense mutations found within the DROSHA gene in oncohematology that might affect the functionality of the protein. In this study, the selected mutations were extensively examined by computational screening, and the most deleterious were subjected to a further molecular dynamic simulation in order to uncover the molecular mechanism of the structural damage to the protein altering its biological function. The most significant effect was found for variants I625K, L1047S, and H1170D, presumably affecting the endonuclease activity of DROSHA. Such alterations arisen during MDS progression should be taken into consideration as evoking certain clinical traits in the malignifying clonal evolution.

Aim. To assess the prognostic value of the mutation of DNA methylation genes, SF3B1, and TP53 in patients with myelodysplastic syndrome (MDS). Materials & Methods. Out of 35 MDS patients included into the trial 2 had multilineage dysplasia, 13 with excess blasts-I, 19 with excess blasts-II, and 1 had 5q-syndrome (criteria WHO 2016). In 30 patients primary MDS was identified, in 5 patients it was detected after prior chemo- or radiotherapy. 25 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to IPSS-R there were 1 low-risk, 5 intermediate risk, 17 high-risk, and 12 very highrisk patients. Hypomethylating agents were administered to 28 patients. Median age of patients was 49 years (range 18-80 years). Next-generation sequencing was applied for identifying somatic mutations in DNA methylation genes (TET2, IDH1/2, ASXL1, and DNMT3A) as well as in SF3B1, TP53, and RUNX1. Time to progression (TTP) was defined as the time from the initial diagnosis to the date of acute leukemia diagnosis. Allo-HSCT- or antitumor therapy-associated death was considered as competing risk. Results. Methylation gene analysis showed no mutation in 37 % of patients, in 40 % mutation was detected only in one of the genes, in 23 % mutation was identified in > 2 genes. SF3B1 mutations were reported in 23 % and TP53 in 11 % of patients. Median follow-up was 25 months (range 5-116 months). Univariate analysis showed no considerable differences in overall survival depending on mutation status. Median TTP in the group with allo-HSCT was not achieved, in the group without allo-HSCT it was 6 months (p = 0.0001). In patients with no SF3B1 mutation median TTP was 35 months, in patients with this mutation it was not achieved (p = 0.043). With ≥ 2 mutations in methylation genes median TTP was 12 months, in other cases it was not achieved (p = 0.024). In cases of TP53 mutation median TTP was 6 months, in cases without this mutation it was 43 months (p = 0.023). Multivariate analysis confirmed unfavorable prognostic value of TP53 mutation or ≥ 2 mutations in methylation genes in terms of TTP regardless of the drug treatment or allo-HSCT performed (hazard ratio 7.1; 95% confidence interval 2.6-19.6; p = 0.0001). Conclusion. The analysis of molecular markers yields additional data concerning the MDS prognosis. Further research is required to determine the prognostic value of molecular markers in clinical practice which will enable to individualize approaches to MDS treatment.

The research is devoted to the analysis and classification of young people’s communicative behavior in social network. We define this behavior as information provided within the user’s profiles in the social network. To classify young people’s communicative behavior we use the scales of Ego-structure test (by G. Ammon). The neural networks are used for classification. The paper describes the feature extraction process for neural network training. The features are based on the information provided within the user’s profiles. The experimental results for different classifiers are given. The analysis of the used classification is conducted and directions of future work are described.

The study objective is to develop a new algorithm for diagnosing lung function disorder types. A retrospective analysis of lung function tests results (spirometry, body plethysmography and lung elasticity measurement with the esophageal balloon) was performed in 575 patients with diffuse parenchymal lung diseases. The algorithm, recommended by the expert commission of American Thoracic Society and European Respiratory Society in 2005, showed low sensitivity: disturbances of respiratory mechanics were determined only in 43% of cases. The proposed algorithm, based on the analysis of vital capacity, total lung capacity, residual volume, the ratio of RV/TLC and FEV1/VC, was more sensitive, basically due to better diagnosis of restrictive syndrome of ventilation disorders. The accuracy of the proposed algorithm depends on the method of normal limits definition. When normal limits were defined as percentage of predicted values, ventilation disorders were detected in 72% of cases. Utilizing equations for upper and lower limits of norm, the algorithm recognized ventilation disorders in 62% of cases.

A number of sequencing studies identified the prognostic impact of somatic mutations in myelodysplastic syndrome (MDS). However the majority of them focused on methylation regulation, apoptosis and proliferation genes. Despite the number of experimental studies published on the role of micro-RNA processing and checkpoint genes in the development of MDS, the clinical data about mutational landscape in these genes is limited. We performed a pilot study which evaluated mutational burden in these genes and their association with common MDS mutations. High prevalence of mutations was observed in the genes studied: 54% had mutations in DICER1, 46% had mutations in LAG3, 20% in CTLA4, 23% in B7-H3, 17% in DROSHA, 14% in PD-1 and 3% in PD-1L. Cluster analysis that included these mutations along with mutations in ASXL1, DNMT3A, EZH2, IDH1, RUNX1, SF3B1, SRSF2, TET2 and TP53 effectively predicted overall survival in the study group (HR 4.2, 95%CI 1.3–13.6, p = 0.016). The study results create the rational for incorporating micro-RNA processing and checkpoint genes in the sequencing panels for MDS and evaluate their role in the multicenter studies.

Osteopetrosis is a group of rare inheritable disorders of the skeleton characterized by increased bone density. The disease is remarkably heterogeneous in clinical presentation and often misdiagnosed. Therefore, genetic testing and molecular pathogenicity analysis are essential for precise diagnosis and new targets for preventive pharmacotherapy. Mutations in the CLCN7 gene give rise to the complete spectrum of osteopetrosis phenotypes and are responsible for about 75% of cases of autosomal dominant osteopetrosis. In this study, we report the identification of a novel variant in the CLCN7 gene in a patient diagnosed with osteopetrosis and provide evidence for its significance (likely deleterious) based on extensive comparative genomics, protein sequence and structure analysis. A set of automated bioinformatics tools used to predict consequences of this variant identified it as deleterious or pathogenic. Structure analysis revealed that the variant is located at the same “hot spot” as the most common CLCN7 mutations causing osteopetrosis. Deep phylogenetic reconstruction showed that not only Leu614Arg, but any non-aliphatic substitutions in this position are evolutionarily intolerant, further supporting the deleterious nature of the variant. The present study provides further evidence that reconstructing a precise evolutionary history of a gene helps predicting phenotypical consequences of variants of uncertain significance.

Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ∼5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ∼4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets—by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human., Phenome-wide association is a novel method that links sequence variants to a spectrum of phenotypes and diseases. Here the authors generate detailed mouse genetic and phenome data which links their phenome-wide association study (PheWAS) of mouse to corresponding PheWAS in human.

Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIII-containing genomes also contain pilT , a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design. IMPORTANCE Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.

Aim: To study the accuracy of the ATS/ERS decision tree (2005) in the interpretation of lung function tests in patients with interstitial lung diseases (ILDs). Methods: The dicision tree was applied to spirometry, body plethysmography and lung diffusion capacity test results in 575 ILDs patients: 202 male (age M 42.5 SD 15.3 yr) and 373 female (age M 48.8 SD 13.2 yr). Results: According to spirometry and body plethysmography results, 56% ILDs patients had no ventilatory disorders, 21% had obstuctive abnormalities, 20% restictive and 3% mixed ones. Diffusion capacity analysis classified 40% cases to “Pulmonary vascular disorders” group. Three groups were represented similarly: “ILD, pneumonitis” (19%), “Emphysema” (18%) and “Normal” (16%). Finally, “Chest wall and neuromuscular disorders” (4%) and “Asthma, chronic bronchitis” (3%) were the smallest groups. We noted that all diseases had representatives in each group of decision tree classification. For example, only 42% patients with idiopathic interstitial pneumonias were identified as having restrictive abnormalities and therefore assigned to the “ILD, pneumonitis” group. Conclusions: The ATS/ERS decision tree (2005) had unsatisfactory accuracy in ILDs patients. In most patients with diagnosed disseminated lung processes, the tree did not recognize ventilatory disorders and significant number of cases were classified as absence of disease.

Aim: to classify diffusion disturbances in patients with ILDs in four patterns, using body plethysmography and single-breath carbon monoxide diffusing capacity (DLCO): the pattern of alveolar-capillary membrane damage (AMD), the pattern of air trapping (AT), the pattern of gas-exchanging surface reduction (GSR) and the pattern of mixed gas exchange abnormalities (MA). Results: the parameters of DLCO and body plethysmography were analyzed in 336 patients with ILDs: 110 male (age M 45.3 SD 15.3 yr) and 226 female (age M 51.3 SD 12.3 yr). The alveolar volume (VA) is informative for the characteristic of gas-exchanging surface. Non-communicating gas volume (ΔTLC=TLCpleth–TLCHe) is informative for air trapping assessment. The AMD pattern (n=96) is defined as decreased DLCO, normal VA and ΔTLC. In this case membrane is damaged, but surface is still not reduced. Patients with AT pattern (n=75) have decreased DLCO, normal VA and increased ΔTLC. The GSR pattern (n=119) is defined as decreased DLCO, decreased VA and normal ΔTLC. Patients with MA pattern (n=46) have decreased DLCO, decreased VA and increased ΔTLC. Ventilation disorders and diffusion disturbance patterns correlate, but not determine each other. In patients with restrictive disorder GSR pattern was prevailed (67%). Almost half of the cases with obstructive disorder had AT pattern (49%). However, in normal, obstructive, restrictive and mixed ventilation disorder groups, all patterns of diffusion disturbance were detected. Conclusions: Recognition of four patterns of diffusion disturbance in ILDs patients provides significant details to ventilatory disorder study and helps to determine the individual characteristics of the disease course.

Aims and objectives: To study morphological changes in different types of ventilation disorders in patients with PLCH. Methods: The pulmonary function tests, conventional histological techniques, immunohistochemistry tests with CD1a, CD68 and protein S-100 were performed for 51 PLCH patients. Mean follow-up was 4.2±3.8 yrs. Initial distribution of disorders was the following: 23(45%) obstruction, 13(25%) normal, 12(24%) restriction and 3(6%) mixed. Obstruction was caused by infiltration of histiocytes, pigmented macrophages, eosinophils and lymphocytes, which were located around the respiratory bronchioles and small bronchi and/or cysts. Restriction was caused by the prevalence of fibrosis: interstitial and focal. The combination of fibrotic changes with near fibrous emphysema and cysts was typical for mixed disorders. Expression of CD1a and protein S-100 was revealed in all cases. At the end of the observation period, the number of patients with obstruction was increased (30, 59%), the number of mixed (6, 12%), restrictive (7, 14%) and normal (8, 15%) patterns was decreased. The obstructive (most stable) pattern preserved in 93% of patients, restrictive — in 58%. The "normal" group was most unstable: 54% got obstruction and 15% — mixed. The mixed pattern was always a final result of either obstruction or restriction. Obstructive to restrictive to mixed transformation was never observed. Conclusions: Obstructive disorders are typical for PLCH. Restrictive pattern is probably a particular course of the disease, when proliferative processes predominate over destructive. Mixed pattern is a final pattern of initially obstructive or initially restrictive disorders.

To build a powerful and flexible security policy verification tool, it is very important to use the approach which allows covering all possible inconsistencies, has open (extendable) architecture and efficient verification implementation. We suggest using a family of different verification modules each of which can work with acceptable computational complexity for the particular types of conflicts, the system scale and the policy complication. The poster describes a common approach to security policy verification and presents a novel hybrid multi-module security checker (SEC) software tool that can serve as a security policy debugger for various categories of security policy, including authentication, authorization, filtering, channel protection and operational rules.

Policy-based management systems are now the object of steadfast attention in network security theory and applications. Due to a complex structure of subject role hierarchies, target grouping, and action mutual dependence the security policy conflicts are complicated to detect and resolve. Moreover, an initially consistent policy ruleset may lead to inconsistent or unenforceable rules during the system lifecycle. The paper presents the architecture of Security Checker module (intended for disclosure and resolution of policy conflicts) and illustrates conflict detection based on event calculus.