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The purpose of this article is to consider the prospects for the integration of blockchain and artificial intelligence (hereinafter referred to as AI) as an innovative approach to modernisation of various economic sectors. The authors analyse the possibilities of using this technological merger to optimise business processes, increase transparency and reduce transaction costs in different sectors, including finance, healthcare, transport, energy, etc. Particular attention is paid to the benefits of synergy between AI and distributed ledger technology, which allows for more efficient and sustainable systems of managing data and assets. The research object in this article is the process of integrating blockchain and AI. The subject of the study is the effectiveness of modernisation of various economic sectors through the combination of these technologies. The research method is an analytical review of scientific publications and successful implemented projects. The results of the current article lie in the analysis of the advantages of integrating blockchain and AI as well as forecasting further prospects for the development of this area. The practical significance of the work consists in the fact that the obtained results can be used to design strategies and plans for the implementation of this technology integration into domestic business.

Background. Non-pharmacological treatments based on collagen as a dietary supplement are emerging as a new area of interest to support preventive or therapeutic effects in patients with osteoarthritis (OA). Aim. In a multicenter, prospective, double-blind, placebo-controlled, randomized study, to evaluate the effectiveness and safety of the use of the Artneo complex containing undenatured chicken collagen type II in patients with OA of the knee joints. Materials and methods. The study enrolled 212 outpatients from 12 centers in the Russian Federation with knee OA, stages II and III according to the Kellgren–Lawrence classification. The participants included 171 women (80.7%) and 41 men (19.3%), with an average age of 60.2±9.0 years (range: 40 to 75 years). The study population was randomly allocated in equal proportions into two groups using an interactive web response system (IWRS). Group 1 (Artneo) consisted of 106 patients who took one capsule of the drug once daily for 180 days. Group 2 (Placebo) also had 106 patients, with the dosage form and regimen identical to Group 1. During the treatment period, the following outcomes were assessed: WOMAC index, KOOS, pain according to VAS, quality of life using the EQ-5D questionnaire, and the need for NSAIDs. All patients underwent a clinical blood test, general urine analysis, biochemical blood test, and ultrasound examination of the affected knee joint. Results. In a prospective, double-blind, placebo-controlled, randomized study, it was demonstrated that the Artneo combination, containing undenatured chicken collagen type II, has a positive effect on all clinical manifestations of OA: it effectively reduces pain, stiffness, and improves the functional state of joints and quality of life. It has a good safety profile and is superior to placebo in all parameters studied. Conclusion. The results of the study confirm the good effectiveness and safety of the Artneo combination in patients with OA of the knee joints.

Aim. To evaluate the relationship of hypercholesterolemia (HCE) with clinical, instrumental, and laboratory parameters in osteoarthritis (OA) in a multicenter, cross-sectional study. Materials and methods. The study included 183 patients aged 40–75 years, with a confirmed diagnosis of stage I–III OA (ACR) of the knee joints, who signed an informed consent. The mean age was 55.6±10.7 years (40 to 75), body mass index was 29.3±6.3 kg/m2, and disease duration was 5 [1; 10] years. For each patient, a case record form was filled out, including anthropometric indicators, medical history, clinical examination data, an assessment of knee joint pain according to VAS, WOMAC, KOOS and comorbidities. All patients underwent standard radiography and ultrasound examination of the knee joints and laboratory tests. Results. HCE was detected in 59% of patients. Depending on its presence or absence, patients were divided into two groups. Patients were comparable in body mass index, waist and hip measurement, and disease duration but differed significantly in age. Individuals with elevated total cholesterol levels had higher VAS pain scores, total WOMAC and its components, an overall assessment of the patient's health, a worse KOOS index, and ultrasound findings (reduced cartilage tissue). HCE patients showed high levels of cholesterol, low-density lipoproteins, triglycerides, STX-II, and COMP (p0.05). However, after stratification by age, many initial intergroup differences became insignificant, and differences in the WOMAC pain score persisted. Conclusion. The results of the study confirmed the high prevalence of HCE in OA patients (59%). Patients with OA and increased total cholesterol have more intense pain in the knee joints.

Bacterial stress adaptive response is formed due to changes in the cell gene expression profile in response to alterations in environmental conditions through the functioning of regulatory networks. The mutual influence of network signaling molecules represented by cells’ natural metabolites, including indole and second messengers (p)ppGpp and cAMP, is hitherto not well understood, being the aim of this study. E. coli parent strain BW25141 ((p)ppGpp+) and deletion knockout BW25141ΔrelAΔspoT which is unable to synthesize (p)ppGpp ((p)ppGpp0) were cultivated in M9 medium supplemented with different glucose concentrations (5.6 and 22.2 mM) in the presence of tryptophan as a substrate for indole synthesis and in its absence. The glucose content was determined with the glucose oxidase method; the indole content, by means of HPLC; and the cAMP concentration, by ELISA. The onset of an increase in initially low intracellular cAMP content coincided with the depletion of glucose in the medium. Maximum cAMP accumulation in the cells was proportional to the concentration of initially added glucose. At the same time, the (p)ppGpp0 mutant showed a decrease in maximum cAMP levels compared to the (p)ppGpp+ parent, which was the most pronounced in the medium with 22.2 mM glucose. So, (p)ppGpp was able to positively regulate cAMP formation. The promoter of the tryptophanase operon responsible for indole biosynthesis is known to be under the positive control of catabolic repression. Therefore, in the cells of the (p)ppGpp+ strain grown in the tryptophan-free medium that were characterized by a low rate of spontaneous indole formation, its synthesis significantly increased in response to the rising cAMP level just after glucose depletion. However, this was not observed in the (p)ppGpp0 mutant cells with reduced cAMP accumulation. When tryptophan was added to the medium, both of these strains demonstrated high indole production, which was accompanied by a decrease in cAMP accumulation compared to the tryptophan-free control. Thus, under glucose depletion, (p)ppGpp can positively regulate the accumulation of both cAMP and indole, while the latter, in its turn, has a negative effect on cAMP formation.

Pallister-Killian syndrome (PKS) is a rare inherited disease with multiple congenital anomalies, profound intellectual disability, and the presence in the karyotype of sSMC - i(12)(p10). The frequency of PKS may be underestimated due to problems with cytogenetic diagnosis caused by tissue-specific mosaicism and usually a low percentage of peripheral blood cells containing sSMC. Such tissue-specific mosaicism also complicates a detailed analysis of the sSMC, which, along with the assessment of mosaicism in different tissues, is an important part of cytogenetic diagnosis in PKS. Unfortunately, a full-fledged diagnosis in PKS is either practically impossible or complicated. On the one hand, this is due to problems with the biopsy of various tissues (skin biopsy with fibroblast culture is most often used in practice); on the other - a low percentage of dividing peripheral blood cells containing sSMC, which often significantly complicates the analysis of its composition and organization. In the present study, a detailed analysis of sSMC was carried out in a patient with a characteristic clinical picture of PKS. A relatively high percentage of peripheral blood cells with sSMC (50%) made it possible to perform a detailed molecular cytogenetic analysis of de novo sSMC using chromosomal in situ suppression hybridization (CISS-hybridization), multicolor FISH (mFISH), multicolor chromosome banding (MCB), array CGH (aCGH), and quantitative real-time PCR (qPCR), and short tandem repeat (STR) - analysis. As a result, it was found that the sSMC is not a typical PKS derivative of chromosome 12. In contrast to the classical i(12)(p10) for PKS, the patient’s cells contained an acrocentric chromosome consisting of 12p material. Clusters of telomeric repeats were found at the both ends of the sSMC. Furthemore, the results of aCGH and qPCR indicate the presence of interstitial 8.9 Mb duplication at 12p13.1-p12.1 within the sSMC, which leads to different representations of DNA from different segments of 12p within cells containing sSMC. The obtained data raise the question of the instability of the sSMC and, as a consequence, the possible presence of additional rearrangements, which, in traditional cytogenetic analysis of patients with PKS, are usually described as i(12)(p10).

Цель данной работы – показать возможности и перспективы применения интеллектуальных технологий именно в строительстве. В настоящее время для этого наиболее широко используются технология экспертных систем (ЭС), теория нечётких множеств и нечёткой логики и искусственные нейронные сети. Системы искусственного интеллекта дают возможность моделировать накопленные профессиональные знания опытных специалистов, опираясь на современные методы решения практических задач, используя существующее нормативное обеспечение строительной отрасли как готовую системную модель, которую следует адекватно представить в терминах, формализованных в соответствии с определёнными структурными правилами. Компьютер позволяет эксперту автономно использовать это, предлагая возможные варианты на основе логического вывода для решения конкретных задач. Реализована возможность выявлять и контролировать автоматизированным способом причинно-следственную связь между признаками и состоянием конструкций, обеспечивающую поддержу решения инженера-обследователя в вопросе определения категории технического состояния конструкций. Неотъемлемой частью диагностики строительных объектов являются поверочные расчёты несущей способности элементов с учётом их реального состояния. Для расчётов сложных строительных объектов обычно используется численный метод конечных элементов. Учитывая то, что искусственные нейронные сети являются хорошими аппроксиматорами различных нелинейных зависимостей, их сегодня предлагается трактовать как новый универсальный подход к численному решению задач математической физики.

The purpose of the research is to reveal the aspect of the systematic nature of Alfred Rosenberg’s views and the ideological foundations of the Nazi state in their interconnection based on his work Der Mythus des 20. Jahrhunderts: Eine Wertung der seelisch geistigen Gestaltenkдmpfe unserer Zeit. The scientific novelty is caused by the fact that the topic of systematicity in his work Der Mythus ideology has not yet been sufficiently studied by historians. At the same time, since Rosenberg’s work Der Mythus provides a justification of the ideology of National Socialism and racial theory in the context of the “myth of Nordic blood” and its rights to world domination, and examines the ideological principles of building the future German state, historical research on Nazism as a phenomenon that has its own conditions of emergence and specifics of development in all spheres of society, remains a priority area of history studies today. The research methodology is based on general scientific principles and methods of scientific research and the historical and source analysis of Rosenberg’s book Der Mythus des 20. Jahr hunderts. Conclusions. Alfred Rosenberg perceived the ideology of the Der Mythus des 20. Jahrhunderts as a symbiosis of ideas that create a new quality and unity of ideology, which he associated with an intangible and unknowable “integrity factor”. From his point of view, this new ideology would guarantee the construction of a new Germany and, in the future, a new world order, which would lead to the need for a revolution ary revision of the foundations of the German state as a male military alliance. In his worldview, Rosenberg promoted the advantages of Nordic blood, its mystical soul and power, substantiated Germany’s historical rights to dominate the world with an eye to the future war for living space, and the construction of a new Third Reich on a new legal basis. At the same time, Rosenberg recognized five components necessary for the inner world of a person under the new Nazi ideology, namely political religion, morality, art, science, and philosophy, united by the idea of the total nature of National Socialism.

The article presents an analysis of the results of experimental studies of the effect of different types of a super absorbent polymer additive on the strength of different types of concrete. The study is aimed at the effectiveness of a new type of super absorbent additive in concrete structures. In the course of full-scale experiments, it was possible to identify the optimum dosage of SAP for fine-grained and heavy concretes. In addition, the results showed that the strength of concrete remains unchanged if the dosage of super absorbent polymer additive (SAP) is 0.5% of the weight of cement or less. The possibility of modern intelligent technologies (artificial neural networks) to predict the properties of concrete mixture and hardened concrete at given values of input parameters (SAP dosage and W/C), influence on concrete characteristics (slump of the cone, bending strength, compressive strength) has also been shown.

Background. Indole and polyamines are involved in the regulation of physiological processes in bacteria associated with adaptation to stress, biofilm formation, antibiotic tolerance, and bacterial persistence. However, the molecular targets and mechanisms of action of these metabolites are still poorly understood. In this work, we studied the effect of polyamines and indole on the expression of such genes as: rpoS, relA, and spoT, encoding regulators of the general stress responses and starvation; hns and stpA, encoding global regulators of gene expression; rmf, yqjD, hpf, raiA, rsfS, sra, ettA, encoding ribosome hibernation factors.The aim. To study the regulatory effects of polyamines and indole on the expression of these genes, which are responsible for the adaptation of Escherichia coli to stress.Materials and methods. We used strains of E. coli in this study. The amount of polyamines was studied by thin layer chromatography. The indole concentration was determined by high performance liquid chromatography. Gene expression was studied using real-time RT-PCR.Results. The addition of polyamines putrescine, cadaverine and spermidine to the medium stimulated the expression of all the studied genes. The maximal stimulation was observed at the stationary phase mostly. Putrescine and spermidine had the most significant effect. At 24 h of cultivation, an equimolar conversion of exogenous tryptophan into indole was showed. At this time, the expression of two genes – rmf and raiA – increased.Conclusions. We have shown that polyamines upregulate the expression of all the studied genes at the transcriptional level. The stimulating effect is specific for the phase of the batch culture and the type of polyamine. Indole has a positive effect on the expression of the rmf and raiA genes.

Signaling molecules such as indole (product of tryptophan catabolism) and (p)ppGpp (stringent response regulator) are involved in regulation of physiological processes in bacterial cells aimed to adapt to antibiotics and stresses. However, question of existence of relationship between the stringent response and indole signaling requires more detailed investigation.The aim. To study effect of stringent response regulator (p)ppGpp on indole production in Escherichia coli depending on glucose content.Materials and methods. In this work, we studied the dynamics of indole accumulation in batch cultures of parent E. coli BW25141 ((p)ppGpp+ strain) and deletion mutant BW25141∆relA∆spoT ((p)ppGpp0 strain) in glucose-mineral tryptophan-free M9 medium, as well as with 2 mM tryptophan addition. In order to study effect of starvation stress on bacterial cell ability to synthesize indole, we used a model of growth limitation by carbon substrate at two glucose concentrations, 0.1 % and 0.4 %.Results. We have shown here that (p)ppGpp absence in E. coli cells reduces their ability to produce indole in the tryptophan-free medium and significantly slows down the rate of its accumulation in the tryptophan-containing one. Low glucose concentration (0.1 %) leads to decrease in indole production by (p)ppGpp+ cells in the tryptophan-free medium. The presence of indole synthesis precursor, tryptophan, in growth medium, on the contrary, increases the production of indole at lower glucose concentration in both (p)ppGpp+ and (p)ppGpp0 strains demonstrating direct dependence of delay time for onset of indole formation on glucose content, which is more pronounced in the culture of deletion mutant unable of synthesizing (p) ppGpp. The data obtained can be interpreted as result of complex regulatory effect of catabolic repression and the stringent response caused by alarmone (p)ppGpp action on expression level of tnaCAB operon responsible for indole biosynthesis.

This review is focused on the issue of terminology in patients with multiple coexisting diseases in modern clinical practice. We articulate that multimorbidity is one of the leading problems in the field of public healthcare and that the treatment of these patients demands an integral approach derived from the combined nature of the pathology . It was shown that multiple coexisting diseases have a negative effect both on the course of osteoarthritis (OA) and its concomitant ailments, including higher risk of polypharmacy and death. Extra attention is paid to slow-acting symptomatic drugs, which often have positive pleiotropic effects towards both the OA and the concomitant diseases. In particular, there is more and more research showing evidence of the beneficial effects of chondroitin sulfate both on the OA treatment effectiveness as well as on the terms of cardiometabolic prognosis, mitigation of glucose metabolism deficiency and mortality.

The review systematizes modern data indicating effective pain control and a significant improvement in the functional activity of patients suffering from osteoarthritis (OA) using pharmaceutical substances of chondroitin sulfate (CS) and glucosamine (GA). The effect of a combination of CS and GA on subclinical inflammation (low-grade inflammation) in the joints, slowing down the progression of OA, reducing cardiovascular risk, metabolic disorders, etc. are discussed. There are promising reports of a possible decrease in overall mortality and mortality from cardiovascular diseases during long-term therapy with symptomatic delayed-acting drugs (SYSADOA). A wide range of pleiotropic effects of CS and HA allows us to classify these drugs as geroprotectors and recommend their use not only in OA, but also in various comorbid conditions.

This paper presents a review of the current status and development trends of the non-fungible tokens’ technology (NFT), which are digital rights to unique objects recorded in the blockchain. The object of the study is the non-interchangeable token technology. The subject of the study is the fields of practical application of NFT. The method is an analytical review of scientific publications. The current state and socio-cultural sources of the NFT market related to works of art and media objects are analysed. The technological and legal problems preventing the wide spread of NFT in the business environment are identified. The prospects for the use of non-fungible tokens in the field of protection and commercialization of patent law objects are considered.

Introduction The deductive method: from karyotyping to aCGH and WES is an important aspect in the diagnosis and search for the causes of intellectual disability due to congenital brain anomalies. There is recommendation to exclude the presence of CNV or monogenic variants for patients with a normal karyotype, but with a clinical picture of syndromic disease. Objectives Improvement of diagnosis of intellectual disability. Methods aCGH with 60K Agilent microarrays, WES with SureSelect Human All Exon V8 Results Pathogenic or potentially pathogenic CNVs were excluded previously by aCGH for 10 families (total 32 people, 2 families had 2 children) with intellectual disability and congenital brain anomalies (for example, polymicrogyria, pachygyria, lissencephaly). The WES identified candidate variants for all families that can lead to impaired neurodevelopment, including 3 pathogenic variants in 3 families, 3 likely pathogenic in three other families, and 10 variants with uncertain clinical significance for 4 families. Almost all of these variants were identified de novo, except for one family, where the proband has been a compound heterozygous for two variants in the RELN gene. The first case of pathogenic mutation de novo was detected in a girl with agenesis of the corpus callosum. It was a missense mutation DYNC1H1 (NM_001376.5): c.4868G>A (p.Arg1623Gln), which leads to impaired intellectual development in autosomal dominant type 13 (OMIM 614563). The second variant was detected in a boy with corpus callosum agenesis, pontine hypogenesis, pachygyria in the frontal lobes. It was a missense variant MACF1 (ENST00000567887.5): c.21989A>G(p.Asp7330Gly), which leads to lissencephaly 9 with complex brainstem malformation (OMIM 614563). The third variant was found in a girl with epilepsy and impaired myelination of the white matter of the parietal-occipital areas of the cerebral hemispheres. It was a missense variant CDKL5 (NM_001323289.2):c.404-1G>A that leads to developmental and epileptic encephalopathy 2 (OMIM 300672). Conclusions Sixteen candidate variants potentially responsible for mental health were reported in this study. Most of these variants were missense changes in genes. All except one anomalies arisen de novo. Trio-based WES has been shown to be an important step in making a genetic diagnosis if other chromosomal and subchromosomal abnormalities had been excluded. The clinical description of the patient is the most important step for the correct interpretation of WES results, which allows to establish the exact genetic cause of the disease if several variants with unclear clinical significance were previously identified. This study was supported by the Russian Science Foundation, grant 21-65-00017, https://rscf.ru/project/21-65-00017/ Disclosure of Interest None Declared

Introduction aCGH determines pathogenic copy number variations (CNVs) in about 10% of patients with intellectual disability (ID). In another 20% of patients, probably pathogenic CNVs or variants with uncertain clinical significance are detected. It may be variants that do not fully explain the patient’s symptoms, aberrations with reduced penetrance or inherited from healthy parents. The use of a sequencing method for such cases is advisable. Objectives Improvement of diagnosis of intellectual disability. Methods aCGH with 60K Agilent microarrays, qPCR, targeted sequencing, whole exome sequencing (WES). Results Six patients with ID and inherited deletions/duplications detected by aCGH and their parents if available were further examined by sequencing. Four patients had maternal CNVs: (1) del1q41 (SPATA17, LINC00210, RRP15), (2) del7q35 (TCAF2, exon 8), (3) dup8p22p21.3 (PSD3, exons 1-11), and (4) del12p11.1 (SYT10, exons 1-2). Two patients had paternal CNVs: (5) dup1q44 (SMYD3, exons 2-5) and (6) del15q11.2 (TUBGCP5, CYFIP1, NIPA1, NIPA2, LOC283683). The severe phenotype of patient (5) with dup1q44 could not be explained by the paternally inherited disruption of the single SMYD3 gene. WES determined probably pathogenic SNV in the MID1 gene associated with Opitz GBBB syndrome (OMIM 300000), which corresponds better to the patient’s phenotype and is likely to be the cause of the disease. Although del1q41 is included in the region of chromosome 1q41-q42 deletion syndrome (OMIM 612530) the phenotype of the patient (1) is much milder; WES in the patient detected two pathogenic (MPO, MAN2C1) and one probably pathogenic (ARID1B) SNVs. In patient (6) with del15q11.2 pat WES detected additional pathogenic SNV in exon 7 of the ARSE gene. In patient (3) with dup8p22p21.3 WES determined two SNVs with uncertain significance in the KIDINS220, FOXG1 genes. No SNVs were detected by WES in patient (2) with del7q35. For patient (4) with del12p11.1 targeted SYT10 sequencing revealed no pathogenic SNVs as well. Conclusions Sometimes aCGH-analysis is sufficient to identify the causes of ID, however, in the case of detection of CNVs with uncertain clinical significance and/or inherited from healthy parents, it may be necessary to further examine the patient using sequencing methods. So, the accurate diagnosis was made by WES for one patient of eight. For another two patients the combination of CNVs and SNPs should be considered. For the last three patients the described aberrations could not explain the phenotype and whole genome sequencing may be the solution.This study was supported by the Russian Science Foundation, grant 21-65-00017, https://rscf.ru/project/21-65-00017/ Disclosure of Interest None Declared

The purpose of the publication is to analyze the documents of the NSDAP Office of Foreign Affairs (German: AuЯenpolitisches Amt der NSDAP, hereinafter - APA) (1933-1942) as sources of the ideology of Nazi foreign policy, to find out the directions of activity of the APA in the spread of National Socialist ideology and its contribution to the formation of militaristic attitudes in the Third Reich and the strategy of the future war. The research methodology is based on general scientific principles and methods of scientific research, in particular, on the principles of historicism and objectivity, methods of structural-functional and comparative analysis and synthesis, problem-thematic, chronological methods, as well as methods of source studies and document studies. The novelty of the research is in determining the entire documentary composition of the APA archive, clarifying the directions of its activities, highlighting its contribution to the formation of the Nazi foreign policy of the Third Reich, which, among other things, contained the prospects of developing a new “living space”. Conclusions. Creation of a positive image of National Socialism, the organization of the pro-Nazi movement, the search for allies on the international arena, among other things with the aim of creating an “anti-Bolshevik block” of European states, the development of trade relations with various countries for the food and military equipment, others should be mentioned among the tasks of the APA in European countries in 1933-1939. Collection of information about the internal situation in various countries was an important part, and personal contacts, support of pro-Nazi leaders, publishing houses, ideological training of German diplomats, distribution of NSDAP publications, organization of cultural events, support of the emigrant movement were used. At the end of the 1930 s, the formation of the strategy of Germany’s foreign policy and economic activity, and the development of the concept of the “new European order”, became of great importance. The activities of the APA actually ceased at the beginning of 1943. Most of its documents are kept in the Federal Archives of Germany, in the fond NS 43 (“AuЯenpolitisches Amt der NSDAP”), which includes 480 archival files, among which analytical and informational materials occupy a leading place. APA documents are also among the materials of the NS 8 fond (“Kanzlei Rosenberg”). Correspondence is another important part of the documents of the APA archive.

The purpose of the research is to characterize the composition and content of the documents of the Commissioner of the Fuehrer for the Supervision of the Entire Intellectual and Ideological Schooling and Training of the NSDAP (here in after - the Rosenberg Office) to determine the place of these documents in the source base of the study of the history of the Third Reich, to analyze their information potential as sources on the history of national socialist ideology and occupation policy. The research methodologyis based on scientific principles of historicism, objectivity, and systematicity, represented by historical-comparative and historical-archival methods, as well as methods of source analysis. The scientific novelty. The documents of the Rosenberg Office as a complete documentary complex have not yet been the subject of scientific research, although some historians have used these documents as sources for the history of National Socialism, A. Rosenberg’s biographical portrait, but they were not considered as sources for the ideological component of the Nazi occupation policy. Conclusions. A brief analysis of the documents of the Rosenberg Office allows us to conclude that these documents are valuable sources for studying the history of the development of the National Socialism ideology and itsinfluence through the NSDAP system. Among them, there are plans, orders, instructions, reflecting objectives and structure of the Rosenberg Office, functionsof its departments, ideological materialson anti-Semitism, Bolshevism, religion, as well as reference materialson National Socialist figures in the field of culture. A special place amongthe documents of the Service is held by materials covering its participation in the ideological training of Wehrmacht officers, as well as biographical sources documents on the activities of the staff of the Rosenberg Office. These documents also reveal its ties with a wide range of ot her Nazi agencies that participated in the process of creating Nazi propaganda.

The purpose of the publication is to analyze the research methodology of a complex of documentary sources on the ideology of Nazism, created as a result of the activities of a number of structures in the system of state and party management in the Third Reich, which operated under the leadership of Alfred Rosenberg in 1934-1945 within the structure of the NSDAP and known as Rosenberg’s office. The research methodologyis based on the theoretical and practical principles of applying the methodology of historical research in the field of source studies, archival studies, document studies, and also relies on general scientific principles and methods of research. The novelty of the research is in defining a complex of general scientific methods regarding the subject of research, which the author used in her studies of documentary complexes of sources on Nazi ideology produced by Rosenberg’s office in 1934-1945. Conclusions. As a result of the activities of Rosenberg’s office, primarily during Rosenberg’ sterm as the Commissioner of the Fьhrer for the Supervision of the Entire Intellectual and Ideological Schooling and Training of the NSDAP, a set of documents was formed, which is a source for studying the role of these services in the formation of the ideology of National Socialism and their influence on the politics of the Third Reich. During the study of the formation of the documentary system of these services and its functioning as a source base, it was established that the use of general scientific methods, principles and approaches is based not only on the principles of historicism and objectivity, butalso on a systemic approach, based on the method of structural-functional analysis.The structure of this documentary system was studied on the basis of the analysis of the documents of Rosenberg’s office as its elements, their typological classification. Their functional purpose and connections were also examined and it was determined that problem and thematic, comparative, logical, chronological methods and the method of periodization should be applied to perform the study.

Abstract The presence of an extra chromosome in the embryo karyotype often dramatically affects the fate of pregnancy. Trisomy 16 is the most common aneuploidy in first-trimester miscarriages. The present study identified changes in DNA methylation in chorionic villi of miscarriages with trisomy 16. Ninety-seven differentially methylated sites in 91 genes were identified (false discovery rate (FDR) 0.15) using DNA methylation arrays. Most of the differentially methylated genes encoded secreted proteins, signaling peptides, and receptors with disulfide bonds. Subsequent analysis using targeted bisulfite massive parallel sequencing showed hypermethylation of the promoters of specific genes in miscarriages with trisomy 16 but not miscarriages with other aneuploidies. Some of the genes were responsible for the development of the placenta and embryo (GATA3-AS1, TRPV6, SCL13A4, and CALCB) and the formation of the mitotic spindle (ANKRD53). Hypermethylation of GATA3-AS1 was associated with reduced expression of GATA3 protein in chorionic villi of miscarriages with trisomy 16. Aberrant hypermethylation of genes may lead to a decrease in expression, impaired trophoblast differentiation and invasion, mitotic disorders, chromosomal mosaicism and karyotype self-correction via trisomy rescue mechanisms.

Создание и развитие правил и классификаций для информационных моделей определяют процесс создания моделей для диагностики строительных объектов. В статье описан опыт построения информационных моделей истори­ческих зданий с применением классификаторов строительной информации. Сформулированы задачи, которые могут быть применимы к информационным моделям архитектурного на­следия. Отмечено, что множество элементов, которые исполь­зуются при моделировании исторических зданий, не имеют общепринятого кодирования. Стандартизация параметров, классификаторов, и библиотек элементов - путь информати­зации и оптимизации процесса построения модели. Создание каталогов элементов и общепринятых классификаций может ускорить процессы оптимизации информационного модели­рования существующих зданий.

Modern therapy of osteoarthritis (OA) consists of four sequential stages and includes non-pharmacological, pharmacological and surgical methods of treatment, and also assumes the possibility of collaborative management of the patient by doctors of different specialties, which allows to optimize the processes of diagnosis and treatment. The article presents simple and convenient algorithms, including diagnostic criteria, options for providing medical care, as well as situations (so-called red flags) that require referral of a patient to a specialist, primarily a rheumatologist. It has been demonstrated that the early use of the well-proven SYSADOA in any localization of OA, in particular the combined drugs of chondroitin sulfate and glucosamine, can increase the effectiveness of treatment, reduce possible functional disorders, and minimize the adverse effects of analgesic therapy.

The electronic document management system is one of the most popular products for implementation at various enterprises in various industries, ranging from heavy industry to state organizations and federal authorities. Document flow in many companies is carried out on paper, and this, in turn, causes great difficulties in processing, storing and executing documents. Paper archives occupy hundreds of square meters of storage space, and if necessary, it is very difficult to find the right document among a large amount of waste paper. In this regard, many companies begin to review their activities and move away from paper document management to electronic

Currently chondroitin sulfate (CS) is the most studied drug from the group of «chondroprotectors». The article shows the role of CS in the treatment of osteoarthritis (OA): mechanism of action, clinical efficacy and safety in patients with OA with comorbidity. Evidence for the effectiveness and safety of the use of CS has been analyzed. The place of this drug in Russian and international clinical guidelines for the management of patients with OA is discussed.In domestic practice, the parenteral form of CS is often used in patients with OA. The parenteral form of CS for intramuscular and intra-articular administration (Chondroguard®) has a number of advantages, including the rapid onset of the effect. This enables reducing the dose in a short time or completely abandon the use of non-steroidal anti-inflammatory drugs (NSAIDs), which is extremely important for patients with OA with comorbidity. Chondroguard® can be recommended for initial use in exacerbations of chronic joint and back pain in OA, including in patients with relative and absolute contraindications for NSAID therapy.

Introduction Disease-causing deletions/amplifications may include a single gene, several exons or single/part of exon, contributing to detection of novel pathogenic genes. The localization of single-gene deletion/amplification within the gene can affect its clinical manifestation. Objectives Improvement of diagnosis of intellectual disability. Methods aCGH with 60K Agilent microarrays, qPCR. Results Among 1099 patients with intellectual disability potentially pathogenic single-gene deletions/amplifications were detected in 51 individuals (5%). qPCR was used to verify aberrations in 21 patients (41%). Ten mutations were of maternal origin, four - paternal, two - de novo, another two were confirmed without analysis of parents, and three could not be confirmed. Single-gene aberrations involving the AGBL4 (exon 2), ASMT (exon 9), CYP2C18 (whole gene), DDX10 (promoter, exons 1-13), GYPA (whole gene), LIG4 (exon 1), LSAMP (intron 1), PSD3 (promoter, exons 1-11), SNTB1 (intron 1), SPOCK3 (exons 6-12), STAG2 (exons 7-34), SYT10 (promoter, exons 1-2), TCAF2 (exon 8), TMPRSS15 (promoter, exons 1-12), and ZDHHC7 (promoter, exons 1-4) genes were described by us for the first time. Deletion or amplification of several exons within a gene can affect transcription as point mutation does, while the copy number change of a whole gene can lead to an abnormal amount of the protein. Conclusions Fifteen novel genes potentially responsible for mental health were identified. In most of them aberrations were partial deletions/duplications. Most of abnormalities were inherited from healthy parents indicating the possible presence of a point mutation on the second allele or some modifying factors. This study was supported by the Russian Science Foundation, grant 21-65-00017. Disclosure No significant relationships.

Introduction About 66% of chromosomal microdeletions and microduplications associated with pathological conditions are inherited [Smajlagić D. et al., 2021]. The mechanisms of incomplete penetrance and variable expressivity of CNV are not fully understood. The presence of concomitant CNVs in the genome of healthy parents may have a modifying effect. Objectives Identification of additional CNVs in healthy carriers with 7q31.1 microdeletions. Methods CNVs were revealed by Agilent Technologies 60K microarray and confirmed by qPCR. Results We examined 3 families with inherited 7q31.1 microdeletions affecting only the IMMP2L gene, which is associated with intellectual disability, developmental delay and autism spectrum disorders. Family 1: Proband has intellectual disability, developmental delay, sensorimotor alalia. Microdeletion was inherited from the father, and a healthy sibling is also a carrier of rearrangement. In sibs, additional CNVs were identified: arr[hg19]: 4q31.21(144722583_144939143)×3; 9p12p11.2(43588066_43836428)×3; 16p11.2(32066967_33773163)×1; and 17q21.31(44199517_44577208)×3. Family 2: Proband suffers from development delay, speech disorder and autism. Microdeletion was of paternal origin. The father additionally demonstrated microduplication 16p11.2p11.1(33967926-35204414)×3. Family 3: Proband was diagnosed with development delay and cerebral palsy. The mother is a carrier of a similar 7q31.1 microdeletion; two concomitant CNVs were identified in her karyotype: 9p13.1(39176840_40614884)×3; and 16p11.2p11.1(32833891_35204414)×3. Thus, healthy parents in 3 families have CNV in a common region 16p11.2, which contains the TP53TG3 gene. It is important that TP53TG3 expression is associated with epistatic CNV-CNV interactions [Sun, Kardia 2010]. Conclusions Multiple CNVs in apparently healthy carriers of IMMP2L microdeltions may suppress disease phenotype due to the epistatic CNV-CNV interaction. This study was supported by Russian Science Foundation, grant no. 21-75-00112. Disclosure No significant relationships.

Experimental studies of the resistance of cement stone and concrete to the influence of mold fungi have been carried out. The effectiveness of the use of nanomodified calcium carbonate and the PHMG biocide as bactericidal additives for concrete has been investigated. The influence of Glenium and C-3 plasticizers on the effectiveness of the action of bactericidal additives has been investigated. Both investigated biocidal additives showed a fungicidal effect on concrete specimens. The use of nanomodified calcium carbonate as a bactericidal additive for concrete is effective as the use of PHMG biocide. The introduction of this bactericidal additives does not reduce the strength of the hardened concrete.

Внедрение интеллектуальных технологий в экспертную деятельность инженера-строителя мотивировано необходи­мостью передачи знаний опытных экспертов специалистам разной квалификации для расширения и укрепления их профессиональных возможностей. Экспертные системы (ЭС), имитирующие логику рассуждений опытного человека-эксперта, включающие знания, накопленные и описанные в на­учной, методической литературе и нормативных документах, расширяют профессиональные возможности специалистов и позволяют принимать эффективные решения о категории технического состояния строительных объектов. В данной статье представлены пользовательский интерфейс разра­ботанной ЭС для практической диагностики строительных конструкций и пример практической реализации на реальном промышленном предприятии. Реализована возможность выявлять и контролировать автоматизированным способом причинно-следственную связь между признаками и техни­ческим состоянием конструкций, обеспечивающая поддержу решения инженера-обследователя в вопросе определения категории технического состояния конструкций.

Human induced pluripotent stem cell (iPSC) line, ICGi040-A, was obtained from skin fibroblasts derived from a male patient with mosaic ring small supernumerary marker chromosome 4 (sSMS(4)) and infertility. ICGi040-A cells have karyotype 47,XY,+r(4) in 97% of cells and express a set of pluripotent markers, as well as are able to differentiate in vitro into derivatives of all three embryonic germ layers.

Abstract Human ring chromosomes are often unstable during mitosis, and daughter cells can be partially or completely aneuploid. We studied the mitotic stability of four ring chromosomes, 8, 13, 18, and 22, in long-term cultures of skin fibroblasts and induced pluripotent stem cells (iPSCs) by GTG karyotyping and aCGH. Ring chromosome loss and secondary aberrations were observed in all fibroblast cultures except for r(18). We found monosomy, fragmentation, and translocation of indexed chromosomes. In iPSCs, aCGH revealed striking differences in mitotic stability both between iPSC lines with different rings and, in some cases, between cell lines with the same ring chromosome. We registered the spontaneous rescue of karyotype 46,XY,r(8) to 46,XY in all six iPSC lines through ring chromosome loss and intact homologue duplication with isoUPD(8)pat occurrence, as proven by SNP genotype distribution analysis. In iPSCs with other ring chromosomes, karyotype correction was not observed. Our results suggest that spontaneous correction of the karyotype with ring chromosomes in iPSCs is not universal and that pluripotency is compatible with a wide range of derivative karyotypes. We conclude that marked variability in the frequency of secondary rearrangements exists in both fibroblast and iPSC cultures, expanding the clinical significance of the constitutional ring chromosome.

Objective: to evaluate the efficacy and safety of glycosaminoglycan-peptide complex (GPC, Rumalon) used in patients with knee osteoarthritis (OA) and comorbidities (hypertension and/or type 2 diabetes mellitus (T2DM).Patients and methods: A 10-month multicenter (13 centers from 10 subjects of the Russian Federation) prospective study included 179 patients with Stages II–III primary tibiofemoral knee OA and comorbidity, a walking pain intensity of ≥40 mm on a visual analogue scale (VAS), and a need for nonsteroidal anti-inflammatory drugs (for at least 30 days in the previous 3 months). The efficiency of treatment was evaluated from the changes in VAS scores for knee pain intensity during walking, the overall WOMAC score and scores of its individual indicators, laboratory parameters, and ultrasound data. All the patients received 2 cycles of GPC treatment with 25 injections, by following the manufacturer's instructions.Results and discussion. Even at 2 months after starting the treatment, there was a statistically significant reduction in pain during walking from 60 (50–69) to 40 (27–53.5) mm on the VAS (p< 0.05), which persisted during the follow-up period. A similar pattern was found when assessing the WOMAC index and its components. The drug demonstrated an anti-inflammatory effect: a decrease in the number of patients with synovitis from 55.7 to 39.2% (p=0.02), the level of high-sensitivity C-reactive protein (hsCRP) from 3.2 (1.3–6.2) to 2.6 (1.2–5.7) mg/l (p< 0.05). GPC was ascertained to have a safety profile.Conclusion. The data of this study confirm the good therapeutic effect and safety of GPC Rumalon in knee OA patients with hypertension and/or T2DM. The drug is shown to have a rapid analgesic and anti-inflammatory effect, as well as a positive influence on all clinical manifestations of OA.

Purpose. The main purpose of this documentary publication is to introduce to a scientific community a previously unknown World War II document with the topic of the library policy in the occupied territory of the Union Of Soviet Socialist Republics (USSR) and to analyze it as a historical source that can supplement already known information and add new knowledge on the role of libraries in a Nazi cultural policy in Ukraine during the Second World War, Nazi plans for book collections, personnel policy, and the importance of libraries for Nazi propaganda. Methodology. The methodology of research is comprised of the historical-archival and historical-comparative research methods, as well as methods of source analysis. Document’s authorship, time, purpose, circumstances of its creation, its informational potential, and its place in an archival complex of similar documents of German occupation services involved in the determination of the fate of libraries, and its place in the documentary collections created by Nazi structures in the occupied territory of the USSR, as well as the potential of using this document in further historical research makes it possible to consider the document a historical resource. Scientific novelty of the research. The object of this study is the document "On the importance of libraries" created by the employee of the Sonderstab Bibliothekswesen (Special Staff “Library Science”) by the Einsatzstab Reichsleiter Rosenberg (the Reichsleiter Rosenberg Taskforce or ERR) Fritz-Joachim Starke in occupied Ukraine in May 1942, which hadn’t been introduced to historians yet. But unlike other documents, this document covered not the state of libraries and the fate of their collections, but the Nazi vision of local libraries as part of the occupation policy. Conclusion. The analysis of this document in an archival complex of similar documents for the topic of the Nazi library policy in the occupied territory of the USSR shows us that German employees perceived local libraries not only as a place of the concentration of printed materials needed for public administration, or as a place of storage of valuable collections, but as institutions that would support the German authorities. At the same time, the document reflects the perception of libraries by the occupiers as an additional resource, especially in the development of the economic and scientific potential of the occupied territories, for example, in the organization of local production and training of local employees.