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Theorization of the foundations of project activities in the structure of teaching technical disciplines at a university is a system, process and product of managing the quality of personality development in the structure of lifelong education. The integrity of the ideas of scientific research and scientific theorization, construction, clarification and implementation of ideas of project activities in the structure of teaching technical disciplines at the university is of interest from the standpoint of ensuring the quality of the student’s inclusion in the process of productive self-expression and cooperation, self-organization of orientation and technological effectiveness of the implementation of ideas of humanistic and creative activity potential personality development in the system of continuous education. The components of theorization of the fundamentals of project activities in the structure of teaching technical disciplines at a university can be specified in a broad, narrow and local sense (classical pedagogy), personified, unified, multifunctional and other senses (innovative pedagogy). The definition and use of ideas and technologies of classical and innovative modeling in theorization and technologization of project activities in the structure of teaching technical disciplines at a university determine the prospects for ensuring the quality of personality development in the system of continuous engineering and construction education and a high potential for self-organization of the quality of the formed values of productivity, creativity, flexibility, competitiveness.

The aim of present study was to investigate the hBD-3 gene expression in the surface epithelium of mucosa in ORL organs. We have studied a total of 210 mucosal samples, obtained at the most frequent surgical intervantions from 5 different anatomical functional areas: nose and paranasal sinuses, middle ear, nasopharynx, oropharynx, larynx. The inferior turbinate mucosa (1) and the normal middle nasal passage mucosa (2) served as controls. Estimation of hBD-3 and β-actin gene expression was performed by reverse transcription and realtime PCR. In the nasal and sino-nasal mucosa, only negligible expression levels were detected in 14.29-33.33% of samples, most often in the specimens from the middle nasal passage and ethmoid labyrinth polyps (53.84%), being absent in hypertrophic inferior turbinate. In the middle ear cavity, the frequency detection of the hBD-3 gene expression varied from 7.69% in the stapes superstructures mucosa to 53.85% of the mucosal samples in the presence of cholesteatoma. hBD-3 gene expression was detected in most tissue samples with high microbial contamination: palatine tonsils (100%); adenoid hypertrophy (84.62%); adenoids in hypertrophic states of adenoids and palatine tonsils (87.5%); laryngeal fibrous-vascular polyps (87.5%); other laryngeal pathology (77.78% of the samples). The highest levels of hBD-3 gene expression were found in laryngeal fibrous-vascular polyps. The findings presumed two functionally different types of immune response in mucosa of the ORL organs. In the anatomical-functional areas lined with ciliated epithelium (middle and inferior nasal passages, maxillary and ethmoid sinuses, middle ear), significantly lower frequencies (Fisher's exact test, p < 0.05 to p < 0.001) and levels (Mann-Whitney test, p < 0.05 to p < 0.001) of hBD-3 gene expression were detected, except of polyps of the middle nasal passage and ethmoid labyrinth, and mucosa of the tympanic cavity in cholesteatoma, which may be related to the nature of the pathological process. In the areas lined with squamous epithelium or a combination of squamous and ciliated epithelium, hBD-3 gene expression was detected almost everywhere and at significantly higher levels. In the context of chronic inflammation and infection-related diseases of the ORL organs, in addition to the direct microbicidal activity of hBD-3 as the first line of immune response, one may suggest peptide dysregulation and, even, pathogenetic effects of hBD-3, e.g., increased sensitivity to infections, pathological changes in the composition of the commensal bacteria, fibrous remodeling.

An adaptive-constructive approach to the implementation of the ideas of facilitation and support of students in a technical university is determined by one of the promising methodological approaches and conditions for ensuring the proper quality of solutions to the problems of personality development in the scientific and technical vocational educational environment of the university. In the structure of theorizing the foundations and prospects for solving problems and tasks of facilitating and supporting students in a technical university, an adaptive-constructive approach is a condition for a qualitative clarification of all components of the scientific and pedagogical activity of scientific and pedagogical workers, in the selected direction ideas of facilitation and support of students in a technical university are determined as a value – semantic ways of theorizing conditions and technologies for solving problems of personality development, trends in facilitation and support of students in a technical university as natural phenomena and products of holistic comprehension and clarification of the correctness of personality development and ensuring the functionality of the scientific and technical vocational educational environment of the university, the position of facilitation and support of students in technical university as products of theorization of the process and prospects of quality management of development and technologization of the integral development of the individual in the created and updated scientific and technical vocational and educational environment of the university.

In patients with acute leukemia (AL), malignant cells and therapy modify the properties of multipotent mesenchymal stromal cells (MSCs) and their descendants, reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the alterations in MSCs at the onset and after therapy in patients with AL. The study included MSCs obtained from the bone marrow of 78 AL patients (42 AML and 36 ALL) and healthy donors. MSC growth characteristics, gene expression pattern, proteome and secretome were studied using appropriate methods. The concentration of MSCs in the bone marrow, proliferative potential, the expression of several genes, proteomes and secretomes were altered in AL-MSCs. Stromal progenitors had been affected differently in ALL and AML patients. In remission, MSC functions remain impaired despite the absence of tumor cells and the maintenance of benign hematopoietic cells. AL causes crucial and, to a large extent, irreversible changes in bone marrow MSCs. [ABSTRACT FROM AUTHOR]

This article addresses the issues of scalability and security in blockchain networks, with a focus on sharding algorithms and decentralized data storage. Key challenges include the low throughput and high transaction latency in public networks such as Bitcoin and Ethereum. Sharding is examined as a method to enhance performance through data distribution, but it raises concerns regarding node management and reliability. Sharding schemes, such as Elastico, OmniLedger, Pyramid, RepChain, and SSchain, are analyzed, each presenting its own advantages and drawbacks. Alternative architectures like Directed Acyclic Graphs (DAGs) demonstrate potential for improved scalability but require further refinement to ensure decentralization and security. Protocols such as Brokerchain, Meepo, AHL, Benzene, and CycLedger offer unique approaches to addressing performance and transaction consistency issues. This article emphasizes the need for a comprehensive approach, including dynamic sharding, multi-level consensus, and inter-shard coordination. Additionally, a conceptual model is proposed that incorporates the sharding of transactions, states, and networks, which enables greater scalability and efficiency. [ABSTRACT FROM AUTHOR]

The article provides data on biological diversity of plants, animals, and fungi inhabiting Salt Lake Natural Monument and its surroundings (Tyumen Oblast, Russia). The authors used route and sample plot census methods. The natural monument area is situated within the forest steppe ecotone of the West Siberian Plain. Thus species typical for the adjoining boreal and steppe zones are also registered in the biological communities under study. Aquatic ecosystems of the area include two instances opposed from the species diversity and abundance point of view: the poor one of mineralized Salt Lake and the rich one of fresh water Dolgoye Lake. The total of 166 vascular plant species, 110 vertebrate and 95 invertebrate species, as well as 60 fungi species were registered on the territory. Among these, two plant and eight animal species are listed in different Red Data Books. Recreational use of the territory makes the composition and structure of flora and fauna complexes unique, as the species intolerant to anthropogenic load are depressed, and synanthropes are implanted in the assemblages. Biological diversity transformation accelerates due to an increase of the investigated territory aridity.

The fundamentals of modeling and implementation of technologies for facilitation and support of junior students in a technical university are determined in the process of scientific understanding of the quality of solving development problems and ensuring the proper level of productivity by the priority of choice, the mechanism and perspective of managing the quality of the functionality of modern lifelong education. By defining the components of the process of modeling and implementation of technologies for facilitating and supporting undergraduate students in a technical university in line with the values of humanism and self-organization of the level of success, it is possible to reveal the most expedient solutions to the problems of building and innovatively updating the structure and content of modern professional activities of scientific and pedagogical workers – teachers of a technical university. The paper defines the basic concepts and pedagogical conditions for ensuring the quality of modeling and implementation of facilitation technologies and support for junior students in a technical university. The prospects of innovative construction and correction of processes and ideas of modeling and implementation of technologies of facilitation and support of junior students in a technical university are theorized.

The article highlights the problems of theorization and quality management of the formation of the professional and technical culture of a civil engineer. The concepts of «quality management principles for the formation of a professional and technical culture of a civil engineer», «quality managementfunctions for the formation of a professional and technical culture of a civil engineer», «quality management models for the formation of a professional and technical culture of a civil engineer», «quality management technology the formation of the professional and technical culture of the civil engineer», «pedagogical conditions for effective quality management of the formation of the professional and technical culture of the civil engineer». The prospects for theorization and quality management of the formation of the professional and technical culture of a civil engineer in the context of modern continuous education are determined.

The article highlights and correctly describes the models and definitions associated with the process of theorizing the prospects for the development of higher technical education in the system of training civil engineers. The problems, ideas, functions, principles, methods, technologies of implementation and stimulation of the development of higher technical education in the system of training civil engineers are comprehensively reflected. The pedagogical conditions for ensuring the quality of the development of higher technical education in the system of training civil engineers are indicated in a uniied form, the clarification of the components of which can be carried out at the macro-, meso-, micro-levels of scientific research and scientific theorization. Software and methodological support for theorizing the prospects for the development of higher technical education in the system of training civil engineers are determined in the system of continuing education as a future solution to the problems of increasing the efficiency of management of professional training of scientific and pedagogical workers in the system of continuous engineering and construction education.

The relevance of the study is dictated by the need for constant environmental monitoring of environmental objects in the Sverdlovsk region, in particular, soils due to the high level of anthropogenic load on the territory. The purpose of the work is to assess the degree of contamination of residential landscapes and agricultural lands in the Sverdlovsk region with heavy metals by determining the concentration of gross forms of heavy metals and calculating quantitative criteria for contamination with heavy metals. Objects: soil samples from several points of the Sverdlovsk region, representing urbanized territories and agricultural land. Methods: mechanical and chemical sample preparation of soils; potentiometric method for determining the nature of the soil environment; inversion voltammetry method for determining the concentration of gross forms of heavy metals. Results. The correspondence of sampling points to soil provinces is established, a brief description of the granulometric and geochemical composition of the studied soils is given. It was found that the analyzed soils are contaminated with nickel, zinc, lead and copper; there is a multiple excess of the approximate permissible concentrations of nickel in the soils of Ekaterinburg and Pervouralsk. The main sources of technogenic soil pollution of the Sverdlovsk region with heavy metals are listed. Natural factors contributing to the accumulation of metals are considered; possible mechanisms of fixing heavy metals in the soils of the region are described. The ranking of metal pollutants by their content in the studied soils was carried out. Quantitative criteria for the degree of soil pollution are calculated: the total pollution index and the geoaccumulation index. Based on the obtained values of the specified parameters, it is shown that the soils of residential landscapes are characterized by a moderately dangerous level of pollution, agricultural soils – an acceptable level of pollution. It was found that the greatest contribution to the total pollution index is made by cadmium.

Nowadays there are various calculation methods for solving a wide range of problems in construction, hydrodynamics, thermal conductivity, aerospace research and many other areas of industry. Analytical methods that make up one class for solving problems, and numerical calculation methods that make up another class, including those implemented in computing complexes, are used for the design and construction of various thin-walled structures such as shells. Due to the fact that thin-walled spatial structures in the form of various shells are widely used in many areas of human activity it is useful to understand and know the capabilities of different calculation methods. Research works on the study of the stress-strain state of the torse shell of equal slope with an ellipse at the base are not widely available at the moment. For the first time the derivation of the differential equations of equilibrium of momentless theory of shells to determine the normal force Nu from the action of uniformly distributed load tangentially directed along rectilinear generatrixes to the middle surface of the torse of equal slope with a directrix ellipse is presented in this article. The parameters of the stress state of the studied torse are also obtained by the finite element method and the variational-difference method. The SCAD software based on the finite element method and the program SHELLVRM written on the basis of the variational-difference method are used. The numerical results of the parameters of the stress state of the studied torse are analyzed, and the advantages and disadvantages of the analytical method and two numerical calculation methods are determined.

The article is devoted to an overview of studies on the discursive embodiment of historical memory, particularly, in the media. The research is aimed at the overview and systematization of, predominantly, international and Russian concepts of historical memory in academic literature. The scientific significance of research results is determined by the possibility of clarifying the definitions of historical memory in the process of systematizing the existing overseas and domestic studies. With that, the “starting point” of historical memory in this research are global political conflicts, particularly, World War I and World War II. The focus of research interest is the memory of the world wars which is discursively expressed in modern media space with various pragmatic tasks. Analysis of media materials allows for revealing the mechanisms of using historical memory as a tool for creating assessment and images while covering World War I and World War II. The research makes it possible to obtain a general discursive picture of the mass consciousness and, what is especially, important, to get specific data on the linguistic “content” of historical memory reflected in online media. The article is addressed to researchers in various fields of the Humanities, journalists and a wide circle of readers who are interested in the problem.

Background. An evidence-based diagnostic tactics for follicular thyroid gland neoplasia is lacking to date. First-line priority are radiography diagnostic techniques, which vary in capacities and therefore must be regulated in use.Objectives. An efficacy evaluation of multiparametric ultrasound (US), sonoelastography (SEG) and radionuclide scintigraphy (RS) in diagnosis of follicular thyroid neoplasms (FTN).Methods. Preoperative examination was interpreted in 222 FTN patients (86 with follicular thyroid adenoma, FTA, and 136 with follicular thyroid cancer, FTC) with subsequent surgery. A retrospective statistical data analysis was performed for B-mode US, colour Doppler imaging (CDI), power Doppler imaging (PDI), sonoelastography and Tc-99m pertechnetate scintigraphy.Results. Novel FTN descriptive evidence has been obtained. Particularly, an FTA vs. FTC trait comparison showed no reliable US marker of a node assignment to FTA or FTC. Trials of the national-manufactured TI-RADS system showed its good diagnostic potential: FTN sensitivity 89.55, specificity 77.58 and accuracy 83.52%. A SEG picture of FTN was typically motley-colour and mosaic. Young’s modulus in FTA was 27.5 ± 7.1 kPa, a higher stiffness (62.1 ± 12.1 kPa) in FTC indicated a higher likelihood of malignancy. Scintigraphy exhibited a modest capacity for FTN diagnosis (sensitivity 86.67, specificity 48.08 and accuracy 56.72%). AUC values (0.617) indicate its limited use for differential FTN diagnosis, mainly in hyperfunctioning nodules. Our experience elaborated an original algorithm for radiographic techniques application in FTN diagnosis.Conclusion. Several radiographic methods are warranted in suspected FTN. First-line is multiparametric US B-mode imaging to detect FTN priority markers and US symptom complexes. Sonoelastography is second-line in ambiguous cases to further clarify structure (stiffness) of the thyroid nodule examined. Unlike SEG, scintigraphy assesses the functional traits of thyroid nodule and so has limited indications, an important factor to consider in FTN.

Introduction. The study of schoolchildren’s nutrition features in different regions of the Russian Federation is one of the important tasks to health promotion of children by developing regional practices for optimization the nutrition of schoolchildren.Objective. To study schoolchildren’s nutrition features in industrial cities of the Siberian federal district (Siberian FD).Materials and methods. Specialized questionnaire was developed in order to study the nutrition organization of schoolchildren in various regions of the Russian Federation. 323 parents (legal representatives) of children aged 7-18 years living in the biggest industrial cities of south-eastern Siberia (the cities of Angarsk and Irkutsk) took part in the survey, based on the questionnaire. The obtained data was compared to the result of studies conducted in the Central federal district (Central FD), that included 162 observations. The frequency method was used to analyze the food consumption.Results. The study established that consumption of milk, meat, cereals, potatoes, nuts, vegetables and fruits by children in the Siberian federal district was, all in all, significantly higher than in the Central federal district and in the Russian Federation in general. The nutrition of schoolchildren in the SFD is defined by a higher consumption of confectionery products, including chocolate, and such products as mayonnaise and margarine. It is noted that 75% of children in Angarsk and about 60% of children in Irkutsk regularly include chips and crackers in their diet and about 60% of children regularly consume fast food. At the same time, children living in Angarsk consume more food products with a high content of carbohydrates (cereals, potatoes, as well as added sugar in cookies, chocolates, sweet carbonated drinks), salt (in salted and dried fish), mayonnaise, and significantly less fermented dairy products and fresh fish compared to children in Irkutsk. Frozen products are more commonly consumed in the city of Angarsk than in Irkutsk. Physical development of children and its correlation with the variety of their diet was also assessed in the study. The assessment showed that children living in Angarsk have a significantly higher prevalence of obesity, which is a reflection of the irrational food diversity in their diets.Conclusions. The obtained data reflect the need of the introduction of educational programs on healthy nutrition among schoolchildren and their parents, taking into account the regional specifics of nutrition.

Introduction. Combined drugs have the greatest efficacy and safety in arterial hypertension treatment. The combination of candesartan and hydrochlorothiazide (AT1-receptor antagonist and a thiazide diuretic, respectively) provides high efficiency of antihypertensive combination therapy, therefore it is widely used in medical practice. Developing a method for simultaneous determination of candesartan and hydrochlorithiazide in human blood plasma is necessary for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs.Aim. The aim of this study is to develop a method for quantitative determination of candesartan and hydrochlorothiazide in human plasma by high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) for further bioequivalence studies.Materials and methods. Determination of candesartan and hydrochlorothiazide in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: mixed solution of valsartan and indapamide. Mobile phase: 0.1 % formic acid solution in water (eluent A), 0.1 % formic acid in acetonitrile (eluent B). Column: Phenomenex Luna Phenyl-Hexyl, 50x4.6 mm, 5 μm. Analytical range: 2.00–300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. Ionization source: electrospray ionization. Detection conditions: 441.10 → 192.00 m/z, 441.10 → 263.15 m/z (candesartan), 295.85 → 269.00 m/z (hydrochlorothiazide), 436.00 → 207.05 m/z (valsartan), 363.85 → 132.10, 363.85 → 189.00 m/z (indapamide).Results and discussion. This method was validated by selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. The developed method meets the requirements for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union.Conclusion. The analytical range was 2.00–300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. The method was applied in BE study of the combination of candesartan and hydrochlorothiazide.

Introduction. Lappaconitine is an alkaloid, contained into Aconitum leucostomum Vorosh. roots and herbs. The alkaloid is indicated to arrhythmia. The lappaconitine drugs are metabolized into eight pharmacologically active substances, but N-desacetyllappaconitine is the most effective. Drugs based on a lappaconitine has narrow therapeutic range and many kinds of side effects. Pharmacokinetics of lappaconitine should be more studied for safety medical use of lappaconitine drugs.Aim. The aim of this study is to develop method for the quantitative determination of lappaconitine and its active metabolite N-desacetyllappaconitine in human plasma and blood by high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS).Materials and methods. Determination of lappaconitine and N-desacetyllappaconitine in plasma and blood was carried out by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation.Results and discussion. This method was validated by next parameters: selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, lower limit of quantification, carry-over effect and stability.Conclusion. The method of the quantitative determination of lappaconitine and N-desacetyllappaconitine in human plasma and blood was developed and validated by HPLC-MS/MS. The analytical range of the was 0.50-50.00 ng/ml for lappaconitine and 0.50-100.00 ng/ml for N-desacetyllappaconitine in biological matrix. Method could be applied to determination of lappaconitine and N-desacetyllappaconitine for PK studies.

In the article the avatar-based learning and teaching (A-BL&T) as a concept of control and managing knowledge in modern socio-economic conditions is proposed to use for assessment a university's economic efficiency. It is shown that all elements, methods and techniques (tools) do not operate in isolation, but rather are interrelated, complementing each other. All of them are used in the process of management and, in a combination, are powerful tools for increasing efficiency of management. Based on the example of avatar-based learning and teaching in Russian universities as modern educational environments, a conceptual model, methodology, and methods have been obtained for the automation of planning and calculation of the academic load in the university.

The relevance of the article lies in formulation of the problem of analyzing the role of children in the design of a child-oriented urban environment in which they develop and grow. The purpose of the article is to study the methods of inclusion of children in the decision-making process on issues of urban design (as full-fledged participants), during which an active urban development environment is formed. The object of the research is the urban environment as a set of conditions for the life of children. As a subject area, the possibility of applying the concept and methodology of participatory design in the formation of this kind of child-friendly urban environment was chosen. The conclusions reached by the authors relate to the situation surrounding the creation of child-friendly cities, as well as the various consequences associated with the emphasis on the importance of integration, institutionalization and innovation. Integration implies the involvement of children in the development of projects focused on them; institutionalization – the need to create appropriate structures and institutions that meet the needs of children in practice; innovation involves new ways of including children in urban development scenarios as full participants in civil proceedings. In other words, there must be the integration of ideas, actions and knowledge, the institutionalization of positive social experience, the innovation of effective ways to meet the child's needs. The authors also came to the conclusion that the main problem of the environment of modern cities is its unfriendliness in relation to the needs of child development, its low educational and upbringing potential since the environment significantly limits the possibilities of dynamic activity of children.

Introduction. Tranexamic acid is one of the most common drugs used to stop bleeding after trauma, in surgery and gynecology. The most common analytical method for the determination of this compound is reversed-phase high-performance liquid chromatography (HPLC). However, this compound belongs to the group of so-called poorly retained compounds due to its chemical structure. It is necessary to develop an analytical method that will allow the determination of tranexamic acid in human blood plasma with the least time, resource costs and without the use of specialized columns.Aim. The aim of this study is to develop a method for tranexamic acid in human plasma by high performance liquid chromatography with tandem mass-spectrometry (HPLC-MS/MS) for pharmacokinetic studies.Materials and methods. Determination of tranexamic acid in plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation.Results and discussion. This method was validated by next parameters: selectivity, matrix effect, calibration curve, accuracy, precision, recovery, lower limit of quantification, carry-over effect and stability.Conclusion. The method of the determination of tranexamic acid in human plasma was developed and validated by HPLC-MS/MS. The linearity in plasma sample was achieved in the concentration range of 100.00–15000.00 ng/ml. Method could be applied to tranexamic acid determination in plasma for pharmacokinetics and bioequivalence studies.

Orthoflaviviruses are arthropod-borne viruses that are transmitted by mosquitoes or ticks and cause a range of significant human diseases. Among the most important tick-borne orthoflaviviruses (TBFVs) is tick-borne encephalitis virus (TBEV), which is endemic in Eurasia, and Powassan virus, which is endemic in Asia and North America. There is a significant controversy regarding species assignment in the tick-borne encephalitis virus complex due to the complex phylogenetic, serological, ecological, and pathogenetic properties of viruses. Comparing the rate of non-synonymous to synonymous substitutions (dN/dS) over the course of tick-borne orthoflavivirus diversification suggests that there is a very strong stabilizing selection (Nei-Gojobori dN/dS < 0.1) among tick-borne orthoflaviviruses that differ by less than 13.5% amino acid/21.4% nucleotide sequences, and discretely more rapid accumulation of non-synonymous substitutions (dN/dS > 0.13) among more divergent viruses that belong to distinct species. This pattern was similarly observed in genome regions encoding structural (E) and non-structural (NS3) proteins. Below this distance threshold, viruses appear fit and strongly tied to their ecological niche, whereas above the threshold, a greater degree of adaptation appears necessary. This species criterion suggests that all subtypes of TBEV, all related ovine/caprine encephalomyelitis viruses, and Omsk hemorrhagic fever virus (OHFV) together correspond to a single species. Within this species, viruses make up 11 subtypes that are reliably segregated by a 10% nucleotide distance cut-off suggested earlier for TBEV. The same 10% subtype cut-off suggests that Powassan virus includes two subtypes, Powassan and Deer Tick virus. [ABSTRACT FROM AUTHOR]

Tumor cells of acute lymphoblastic leukemia (ALL) may have various genetic abnormalities. Some of them lead to a complete loss of certain genes. Our aim was to reveal biallelic deletions of genes in Ph–negative T-ALL. Chromosomal microarray analysis (CMA) was performed for 47 patients with de novo Ph–negative T-ALL, who received treatment according to RALL-2016m clinical protocol at the National Medical Research Center for Hematology (Moscow, Russia) from 2017 to 2023. Out of forty-seven patients, only three had normal molecular karyotype. The other 44 patients had multiple gains, losses, and copy neutral losses of heterozygosity. Biallelic losses were found in 14 patients (30%). In ten patients (21%), a biallelic deletion of 9p21.3 involved a different number of genes, however CDKN2A gene loss was noted in all ten cases. For seven patients (15%), a biallelic deletion of 7q34 was found, including two genes—PRSS1, PRSS2 located within the T-cell receptor beta (TRB) locus. A clonal rearrangement of the TRB gene was revealed in 6 out of 7 cases with 7q34 biallelic loss. Both biallelic deletions can be considered favorable prognostic factors, with an association with 9p21 being statistically significant (p = 0.01) and a trend for 7q34 (p = 0.12) being observed. [ABSTRACT FROM AUTHOR]

The article considers the concept, specificity and importance of design in the integrated development of secondary education institutions. The author does this from the standpoint of sociological theory, in the discourse of the sociology of management. The concept of project and design is revealed as a formalized activity to determine the problems and plan a number of activities aimed at solving problems within the specified time frame and within certain resources. The typology of projects is briefly described, the forms of projects (service, event), as well as the nature of projects (innovative, supportive) are highlighted. The current trends of the sociological analysis of design are outlined. It is substantiated that participatory design can be aimed at creating active educational environment in a secondary educational institution. Such environment determines the growth in the quality of provision of educational services and their results during a special kind of configured events, with the participation of not only schoolchildren, but also all interested participants in school relations – the administration, parents, NPO, etc. The principle of participatory is cultivated and revealed in the design process. Actors themselves are involved in the design and implementation of the project, in which they are really interested. As a result, the effectiveness of such project increases significantly. And the project itself becomes a catalyst for the formation of team relationships within and between different communities (management, teachers, students, parents, others). It is concluded that participatory design has the potential to form a special type of developmental environment within the framework of a secondary education institution.

Aim: To assess the specificity of COVID-19- associated pneumonia detection by radiologists using a chest CT scan.Materials and methods: From mid-February to early March 2020, 65 patients have been retrospectively selected from the Moscow City Clinical Hospital database; all of them had been treated in an inpatient facility with a verified diagnosis of COVID-19. In addition, 75 patients from the Unified Radiological Information Service have been randomly selected. In December 2019, these outpatients had been sent by an attending physician for a chest CT scan with suspected pneumonia. The imaging studies showed non-specific inflammation signs in the lungs. All 140 scans were analyzed by seven radiologists from different Russian cities, who independently categorized each study as “COVID-19” or “Other pneumonia”.Results: Chest computed tomography had a 92% specificity in the differential diagnosis of COVID-19-associated pneumonia, and its specificity in the general population is expected to be at least 80% with a high probability. The inter-rater variability was low (coefficient of variation for specificity 12.6%). The sensitivity in our study was 76.2%, and the coefficient of variation for sensitivity 23.5%. These findings are generally consistent with other studies. The primary study limitation is the absence of a sample with confirmed pneumonia caused by other viruses.Conclusion: Chest CT is highly specific for the detection of COVID-19-associated pneumonia.

Background: Since 2017, a pilot project for lung cancer screening by chest low dose computed tomography (LDCT) has been implemented in Moscow. Patients to be included into the screening have risk factors for ischemic heart disease (IHD). The association between epicardial adipose tissue (EAT) volume and coronary artery atherosclerosis, IHD, and atrial fibrillation has been demonstrated previously.Aim: To demonstrate the feasibility of LDCTbased EAT volumetry using a dynamic (contracting) heart phantom.Materials and methods: The study was performed with the designed dynamic heart phantom and chest phantom in two stages. At stage I, two adipose tissue pieces were scanned inside and outside the chest phantom using CT and LDCT. At stage II, the dynamic heart phantom was scanned outside and inside the chest phantom. In addition, we scanned the heart phantom with a coronary calcium phantom. The contracting heart phantom was developed within three months. All scans of the phantom were performed within one day. We determined the adipose tissue thresholds in LDCT and the EAT volumetric error with both chest CT and LDCT. Measurements of the adipose tissue volumes were performed by the radiologist twice with semi-automatic software.Results: The results of stage I helped to identify optimal density thresholds for LDCT-based adipose tissue volumetry in lung cancer screening, ranging from -250 HU to -30 HU. The stage II results showed that for all heart phantom scanning variants, the average EAT volumetry error did not exceed 5%, except for the case of contracting heart phantom with added coronary calcium in a chest phantom with body mass index (BMI) 29 (-5.92%). Adding the coronary calcium phantom to the heart phantom in LDCT increased the error by an average of 4% in BMI 23 and BMI 29 chest phantoms.Conclusion: LDCT-based EAT volumetry with fat density threshold from -250 HU to -30 HU is feasible in lung cancer screening, including patients with coronary calcium. However, considering the phantom design, further patient studies, and correlation of EAT volumes between LDCT for lung cancer screening and сoronary CT angiography are required.

Aim. To study the effectiveness of the use of Neovir (sodium oxodihydroacridinyl acetates) as immunomodulatory and antiviral drug in the comprehensive treatment of various grade cervical intraepithelial neoplasia (CIN). Study design: prospective comparative study. Materials and methods. The study included 60 patients (mean age 34.78.2 years) with morphologically verified various grade CIN, who were received comprehensive treatment, including the use of Neovir (sodium oxodihydroacridinyl acetate) as the drug with immunomodulatory and antiviral activity, 250 mg/2 ml intramuscularly every 48 hours, 10 injections before (group 1) or after (group 2) multi-stage radiosurgical diagnostic and treatment procedure or only a similar surgical intervention (group 3). All patients underwent complete clinical, morphological and laboratory examination with monitoring for the presence of high-risk human papillomavirus (HPV) in the cervical scraping and the dynamics of peripheral blood lymphocyte subpopulations. Results. Dynamic follow-up showed that in a month after surgery, patients who were treated with radiosurgical resection as monotherapy (group 3) had the lowest rate of complete epithelialization of the cervical stump 30.0% vs 55.0 and 65,0% in the group 1 and group 2 respectively. In this group, the proportion of patients with persistent viral infection was 1.52 times higher than in the groups where an antiviral drug was used in combination with radiosurgical intervention 35.7% vs 17.6 and 22.2% in the group 1 and group2, respectively. In 6 months, elimination of high-risk HPV in groups with comprehensive treatment reached 94.5 in the group 1 and 94.1% in the group 2 (p0.05) vs 78.6% in the group 3. The lowest number of TNK- and NK-cells was found in the group of patients who received radiosurgical treatment as monotherapy, which correlated with the highest incidence of high-risk HPV persistence after treatment in this group. Conclusions. In patients with various grade CIN, the use of an immunomodulatory drug with antiviral activity in combination with radiosurgical intervention promotes early epithelialization of the cervix and elimination of high-risk HPV, which is confirmed by significant changes in the lymphocyte subpopulations which provide antiviral immunity.

Introduction. Cancer is one of the most serious and common diseases with a high level of mortality. Due to this reason the searching of new directions and methods of cancer treatment is becoming more and more important with each passing year. Significant advances in cancer immunotherapy have been reached over the past few decades. Moreover, an inhibition of the interaction between the programmed cell death receptor (PD-1) and its ligand (PD-L1), is sure to be perspective direction of the immuno-oncological therapy development.Text. PD-1/PD-L1 interaction plays a pivotal role in negative regulation of immune system, that protects host’s cells and tissues from the excessive immune response. However, it is also used by tumor cells to avoid the host's immune system. The discovery of this mechanism led to the development of inhibiting PD-1 or PD-L1 agents that enhance anti-tumor immunity. Meanwhile, anti-PD-L1 agents provide less toxicity in comparison with anti-PD-1 agents. FDA currently approved Atesolizumab, Durvalumab, and Avelumab PD-L1 inhibitors for cancer treatment. These agents demonstrated effective response during the clinical trials, however, they are used for a limited number of oncological diseases. In addition, BMS-936559 is a promising agent that had passed the first stage of the clinical trials. Nevertheless, immunotherapy involving PD-L1 inhibitors is closely related to a vast number of severe side effects including immune-mediated effects caused by the inhibition of PD-L1 ligands located on healthy cells. In these terms, the development of new agents deprived of these disadvantages is the reason for further studies.Conclusion. Immunotherapy in cancer uncovers new perspectives in treatment of refractory to standard therapies forms of cancer. And the development of new and improvement of existing PD-L1 blocking agents are of great importance in fighting against tumoral diseases.

Introduction. Currently, physicochemical methods of quantification are actively used to determine the content of drugs in biological fluids. High-performance liquid chromatography with various detection methods is particularly widespread. One of the most difficult practical tasks is the chromatographic separation of so-called poorly retained compounds – drug substances poorly retained on the chromatographic column. Valganciclovir and Ganciclovir are among such substances.Aim. The aim of this study is to develop a method for valganciclovir and ganciclovir in human plasma by high performance liquid chromatography with tandem mass-spectrometry (HPLC-MS/MS) for pharmacokinetic studies.Materials and methods. Determination of valganciclovir and ganciclovir in plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation.Results and discussion. This method was validated by next parameters: selectivity, matrix effect, calibration curve, accuracy, precision, recovery, lower limit of quantification, carry-over and stability.Conclusion. The method of the determination of valganciclovir and ganciclovir in human plasma was developed and validated by HPLC-MS/MS. The linearity in plasma sample was achieved in the concentration range of 5.00–1000.00 ng/ml for valganciclovir and 50.00–10000.00 ng/ml for ganciclovir. Method could be applied to valganciclovir and ganciclovir determination in plasma for PK and BE studies.