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INTRODUCTION: Inflammation is a common pathological condition. On the one hand, inflammation plays a protective role, without it dangerous local processes would remain unrecognized. On the other hand, a cytokine storm can develop under conditions of systemic inflammation, which, in turn, can lead to multiple organ failure. Therefore, it is important to understand the mechanisms involved in the regulation of cytokine production in the early stages of inflammation. OBJECTIVE: The aim of this study was to evaluate the immunomodulatory properties of human defensin (HNP-1) and porcine protegrin (PG-1) antimicrobial peptides in vivo under conditions of inflammatory process initiation. METHODS: Lipopolysaccharide was administered intraperitoneally to laboratory rats to initiate an inflammatory response. Following the onset of inflammation, antimicrobial peptides were also administered intraperitoneally. The immunomodulatory effect of the peptides was evaluated by measuring the changes in gene expression of toll-like receptor 4 (TLR4) and cytokines IL1β and IL10 in the blood leukocytes of the animals using real-time PCR. RESULTS: The lipopolysaccharide-induced expression of Il1b and Il10 in leukocytes, as well as the lipopolysaccharide-induced Tlr4 expression in whole blood leukocytes and isolated mononuclear cells, was reduced to varying degrees by the introduction of HNP-1 and PG-1. CONCLUSION: It can be assumed that at the early stage of the inflammatory process, defensins can act as moderate pro-inflammatory factors, suppressing the gene expression of the anti-inflammatory cytokine IL10, but at the same time slightly reducing the gene expression of the pro-inflammatory cytokine IL1β.

The article presents the results of a clinical investigation on the administration of the Grippol Quadrivalent vaccine (influenza tetravalent inactivated subunit adjuvant vaccine) in children from 6 months to 5 years old. The vaccine has demonstrated no less effectiveness in comparison with the Grippol plus vaccine (influenza trivalent inactivated polymer-subunit vaccine).comparable results were obtained for all evaluated indicators of immunological efficacy against matching strains of the influenza virus, while for additional strain B (Yamagata line) there was a statistically significant difference in the increase in the immune response in the Grippol Quadrivalent group. The results of the assessment of the reactogenicity and frequency of systemic adverse events indicated a favorable and comparable safety profile of the vaccines Grippol Quadrivalent and Grippol plus in children from 6 months to 5 years old. The data obtained allowed us to conclude that the immunological efficacy of the Grippol Quadrivalent vaccine is no less when compared to the Grippol plus vaccine, as well as a comparable safety and reactogenicity profile. According to the results of the clinical investigation, on 08/04/2023, the Ministry of Health of the Russian Federation amended the “Instructions for the medical use of the drug”: Grippol Quadrivalent is indicated for children from the age of 6 months.

The aim of the work was to study the epidemiological situation on West Nile fever (WNF) in the Republic of Tatarstan in 2023.Materials and methods. An operational epidemiological analysis of WNF cases registered in the Republic of Tatarstan in 2023 was performed. In order to establish sources and risk factors for infection of the population, 987 samples of zoo-entomological material were examined for the presence of West Nile virus (WNV) markers. A set of laboratory diagnostic methods was used: ELISA, RT-PCR, sequencing.Results and discussion. It has been established that all cases of WNF were registered in the region in the summer-autumn period of 2023, mainly in August, among residents of the city of Kazan who had not traveled outside the Russian Federation and the Republic of Tatarstan over the past six months. The incidence rate of WNF in the Republic of Tatarstan was 0.20 per 100 thousand population, the mortality rate reached 12.5 %. Signs of damage to the central nervous system were present in 6 out of 8 (75 %) patients. The majority of people with severe clinical symptoms belonged to older age groups and had concomitant diseases. Cases of the infection were reported in all age groups, with the exception of children and adolescents. The spatial characteristics of morbidity have been investigated, indicating the diffuse nature of the distribution of cases. The integrated use of methods, consisting in the concurrent use of polymerase chain reaction and enzyme-linked immunosorbent assay, made it possible to laboratory confirm cases of WNF in patients at different stages of the disease. The circulation of a subvariant of the WNV of the second genotype in the Republic of Tatarstan, currently dominant in the southern and central regions of Russia, has been established. A set of measures has been proposed to optimize epidemiological surveillance and control of WNF in the Republic of Tatarstan.

It is proved and illustrated that by taking the main frame of the surface, consisting of three plane curves placed in three coordinate planes, three different algebraic surfaces with the same rigid frame can be designed. For the first time, one three of new ruled surfaces in a family of five threes of ruled surfaces, formed on the basis of some shapes of hulls of river and see ships, which, in turn, are projected in the form of algebraic surfaces with a main frame of three superellipses or of three other plane curves, is under consideration in detail with a standpoint of differential geometry. The geometrical properties of the ruled surfaces taken as the middle surfaces of thin shells for industrial and civil engineering are presented. Analytical formulas for determination of force resultants with using the approximate momentless theory of shells of zero Gaussian curvature given by non-orthogonal conjugate curvilinear coordinates are offered for the first time. The results derived using these formulae will help to correct the results obtained by numerical methods.

Background. Vascular endothelial growth factor A (VEGFA) is one of the most important factors for regulation of hematopoietic stem cells differentiation. It is involved in leukemogenesis and central nervous system (CNS) damage in acute leukemia. According to the literature, the VEGFA production by blast cells is increased, but the values of serum concentration and the associations with CNS involvement are contradictory.Aim. evaluate the VEGFA, VEGFR1, VEGFR2 concentration in serum and cerebrospinal fluid of patient with different types of acute leukemia in disease onset and during treatment.Materials and methods. The concentration of VEGFA in serum and cerebrospinal fluid was studied in 74 primary patients with acute leukemia. The comparison group consisted of 67 healthy donors. VEGFR1, VEGFR2 were studied in serum and cerebrospinal fluid in 34 patients at the onset of the disease. The comparison group consisted of 10 healthy donors. For the analysis, an enzyme immunoassay was used on a semi-automatic Personal Lab analyzer (Adaltis) and Affymetrix eBioscience human VEGF-A Platinum ELISA reagents.Results. Serum VEGFA concentration was statistically significantly lower in acute leukemia patients than that of donors (median 149.78 and 432.19 pg/ml respectively; p

Background. Current chemotherapy protocols for T-cell acute lymphoblastic leukemia (T-ALL) allow achieving a 5-year overall survival of 60–90 %, but relapsed and refractory forms remain incurable situations.Aim. To determine the significance of immunophenotypic, cytogenetic and molecular markers in adult T-ALL patients receiving therapy according to the ALL-2016 protocol.Materials and methods. From December 2016 to June 2022, 113 patients with primary T-ALL were included in the study. Cytogenetic study was performed in 104 (92 %) patients; anomalies in the IKZF1 and NOTCH1 genes were investigated in 43 (38 %) patients.Results. The worst prognosis was in patients with ETP and near-ETP variants of T-ALL (3-year disease-free survival was 54 % in ETP group, 33 % in near-ETP group vs TI/II – 79 %, TIII – 89 %, TIV – 75 %). In early T-ALL variants, abnormal karyotype was most common (ETP – 80.7 %, near-ETP – 60 %). Aberrations in NOTCH1 gene were found in 53 % of cases (in 23 out of 43 patients), and no mutations were found in IKZF1 gene in our study. In the group with no NOTCH1 abnormalities, the overall survival was significantly worse than in the group with abnormalities (NOTCH1– – 52 % vs NOTCH1+ –81 %; p = 0.05).

Background: An increasing number of drugs are used each year in the treatment of small pets (cats and dogs), including medicines (cephalosporins and fluoroquinolones) used in human therapy. Aim: The purpose of this study was to isolate and explore the antibiotic resistance of opportunistic Enterobacteriaceae (E. coli, Klebsiella, Proteus, Citrobacter, Enterobacter) from cats and dogs, and to isolate resistance genes in the microorganisms. Methods: During 2021, 808 samples of biological material from small domestic animals were collected in veterinary clinics in Kostanay. From these, 210 microorganisms were isolated and identified. Results: A large majority of the strains sampled belonged to E. coli – 149 (70.9%), Enterobacter – 11 (5.2%), Klebsiella – 28 (13.3%), Proteus – 12 (5.7%) and 10 Citrobacter isolates (4.8%). In all isolates identified, antibiotic resistance/sensitivity was determined by disc-diffusion method to ampicillin, cefoxitin, gentamicin, levomycetin, tetracycline, ciprofloxacin, norfloxacin, ofloxacin, cefoperazone, cefpodoxime, streptomycin, kanamycin, doxycycline, gemifloxacin, nalidixic acid, furazolidone, furadonine, amoxicillin and enrofloxacin. Conclusion: Study has demonstrated that the greatest number of Enterobacteriaceae were sensitive to the action of meropenem, which belongs to the group of beta-lactam antibiotics; resistance was demonstrated against tetracycline, doxycycline, ampicillin, amoxicillin, ofloxacin and cefpodoxime. The most common genes encoding antimicrobial resistance were as follows: BlaTEM and OXA in 41 and 28 isolates, respectively, encoding resistance to beta-lactams; StrA and StrB in 45 and 48 isolates encoding aminoglycosides; and tetA and tetB in 43 and 28 isolates encoding tetracyclines. Obtained data demonstrate that uncontrolled and frequent use of beta-lactam and tetracycline antibacterials, in cats and dogs, results in the spread of genotypic resistance among micro-organisms of the family Enterobacteriaceae. [Open Vet J 2024; 14(2.000): 604-616]

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.

Background. Professional burnout (PB) among medical staff, namely hematologists, is of major importance, especially given the current shortage of personnel. It is of extreme value during the COVID-19 pandemic.Aim. To determine the degree of PB development among hematologists and nursing staff of hematological departments of federal and regional medical institutions in the context of the COVID-19 pandemic and to identify the associated factors.Materials and methods. The study was conducted in the period from July 2022 to September 2022 in the form of a onetime online survey of hematologists and nursing staff of hematology departments of federal and regional medical institutions in different cities of the Russian Federation. To interview specialists, a special checklist based on an Internet resource (Google forms) was used. It included burnout questionnaire Maslach Burnout Inventory (MBI) and questions related to factors that may be associated with the formation of PB. Statistical analysis included pairwise and multiple comparisons, as well as χ2 test, correlation and logistic regression analysis.Results. A total of 162 specialists took part in the online survey. More than half of the specialists (52 %) had high degree of emotional exhaustion, high level of depersonalization was detected in 39.5 % of specialists, and low level of personal accomplishment – in one third of specialists (32.1 %). It was shown that physicians, compared with nurses, had significantly higher indicators of PB. The level of problems for all PB components was significantly lower among specialists working in federal health facilities than among specialists working in regional clinics. The specialists who worked in the “red zone” showed a greater degree of emotional exhaustion and depersonalization than the specialists who did not work in the “red zone” during the pandemic. The formed PB syndrome was observed in 16 % of specialists, and its signs – in 42 %. The risk of PB was significantly greater in hematologists than in nurses, as well as among specialists with increased levels of depression and anxiety and dissatisfaction with the level of personal protective measures.Conclusion. The high importance of PB and the need for preventive measures among specialists of hematological centers and hematology departments in the Russian Federation is shown.

Existing research in the field of political communication and rhetoric often focuses on general principles and strategies of the speech, leaving aside cultural-specific considerations. This study is aimed at analyzing the discursive characteristics of British public political rhetoric, which will fill this gap and expand knowledge about the relationship between language, culture, and politics. The work aims to identify the discursive features of the British public political speech from the perspective of its cultural specificity. The results of the study show that, despite the universal nature of the public political rhetoric, British public political speeches differ in certain specifics. The speeches of British politicians are marked by features characteristic of each type in the structure of the text, the use of vivid rhetorical techniques, strict adherence to the protocol, emphasis on the sense of national pride, as well as some unique attributes. This study provides a deeper understanding of the role of language and cultural factors in political communication, and it is also able to expand the theoretical foundations in the field of linguistics and political science. The article is intended for researchers and specialists in the field of linguistics, rhetoric, and political communication. It can also serve as a useful resource for students, postgraduates, and teachers interested in a detailed analysis of the discursive characteristics of British political rhetoric.

On July 3, 2023, an interdisciplinary Council of Experts The burden of COVID-19 in a heterogeneous population of immunocompromised patients post-pandemic realities was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.

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.

Women living with HIV-1 are at high risk of infection with human papillomavirus of high carcinogenic risk (HR HPVs). M. tuberculosis (TB) promotes HPV infection and increases the risk to develop HPV-associated cancer. Our knowledge of persisting HR HPVs genotypes, and of the factors promoting HR HPV infection in people living with HIV-1 with clinical TB manifestations is sparse. Here, we analyzed 58 women living with HIV-1 with clinical TB manifestations (WLWH with TB) followed up in specialized centers in Russia, a middle income country endemic for HIV-1 and TB, for the presence in cervical smears of DNA of twelve HR HPV genotypes. DNA encoding HPV16 E5, E6/E7 was sequenced. Sociodemographic data of patients was collected by questionnaire. All women were at C2-C3 stages of HIV-infection (by CDC). The majority were over 30 years old, had secondary education, were unemployed, had sexual partners, experienced 2-3 pregnancies and at least one abortion, and were smokers. The most prevalent was HPV16 detected in the cervical smears of 38% of study participants. Altogether 34.5% of study participants were positive for HR HPV types other than HPV16; however, but none of these types was seen in more than 7% of tested samples. Altogether, 20.7% of study participants were positive for several HR HPV types. Infections with HPVs other than HPV16 were common among WLWH with generalized TB receiving combined ART/TB-therapy, and associated with their ability to work, indirectly reflecting both their health and lifestyle. The overall prevalence of HR HPVs was associated with sexual activity of women reflected by the number of pregnancies, and of HPV 16, with young age; none was associated to CD4+-counts, route of HIV-infection, duration of life with HIV, forms of TB-infection, or duration of ART, characterizing the immune status. Thus, WLWH with TB-especially young-were predisposed to infection with HPV16, advancing it as a basis for a therapeutic HPV vaccine. Phylogenetic analysis of HPV16 E5, E6/E7 DNA revealed no common ancestry; sequences were similar to those of the European and American HPV16 strains, indicating that HPV vaccine for WLWH could be the same as HPV16 vaccines developed for the general population. Sociodemographic and health correlates of HR HPV prevalence in WLWH deserve further analysis to develop criteria/recommendations for prophylactic catch-up and therapeutic HPV vaccination of this highly susceptible and vulnerable population group.

Lactoferrin is a multifunctional glycoprotein of the transferrin family with a molecular mass of about 80 kDa. We studied the effect of human lactoferrin on stress- and lipopolysaccharide-induced changes in blood corticosterone levels, as well as on the gene expression of the cytokine IL4 and the pattern-recognition receptor TLR4 in rat splenocytes. Stress in rats was modeled by swimming in cold water (1-4°C) for 2 min. Lactoferrin and lipopolysaccharide (LPS) were administered intraperitoneally before the stress exposure. Corticosterone level in the plasma was determined by enzyme immunoassay, and changes in gene expression were assessed by real-time polymerase chain reaction (PCR) with reverse transcription. We showed that preventive intraperitoneal administration of lactoferrin reduced the stress and LPS-induced increase in the gene expression of both IL4 and TLR4 in rat splenocytes but did not change the concentration of corticosterone in the blood.

SARS-CoV-2 infection is the etiopathogenetic factor of the new coronavirus infection. Susceptibility to the virus and, accordingly, the incidence differs in children and adults. On the one hand, this reflects the age-related features of the immune response. On the other hand, it is realized through the production of a number of cytokines, including IL-2, and reflects the genetically determined features of cytokine production. The aim of the study was to analyze the frequency of occurrence of T-330G polymorphic variants of the IL2 gene in patients with a new coronavirus infection. A total of 145 patients were examined, including 31.0% of children (n = 45) and 69.0% of adults (n = 100). The diagnosis of a new coronavirus infection was verified by RT-PCR confirming the presence of the SARS-CoV-2 virus and identifying clinical symptoms of an upper respiratory tract infection. The control group consisted of 50 healthy volunteer donors. Allele-specific PCR with electrophoretic detection in 3% agarose gel (Litech, Russia) was used to analyze the T-330G polymorphism of the IL2 gene. To compare the frequencies of allele combinations, the χ2 test and the odds ratio OR and (95% CI) were used.The dominant genotype in patients with COVID-19 was the heterozygous GT genotype of the T-330G polymorphism of the IL2 gene. In the group of children at risk of developing a new coronavirus infection, the GG genotype of the T-330G polymorphism of the IL2 gene was associated (31.1% in children and 18.0% in the control group, p < 0.05, OR = 2.047). While the homozygous TT genotype of the T-330G polymorphism of the IL2 gene was a protective genotype (its occurrence rate was 26.7% in patients, 54.0% in the control group, p < 0.05, OR = 0.315). In adults, the heterozygous GT genotype of the T-330G polymorphism of the IL2 gene was associated with the risk of developing a new coronavirus infection (in the group of patients – 44.0% versus control – 28.0%, p = 0.028, OR = 2.020). A low risk of developing the disease was associated with the homozygous TT variant of the T-330G polymorphism of the IL2 gene (in the group of patients 37.0% versus control – 54.0%, p = 0.024, OR = 0.500).The T-330G polymorphism of the promoter zone of the IL2 gene differently affects its production. The direction of the immune response and its effectiveness depend on the level of IL-2. Understanding the individual factors that determine the features of the immune response can help in understanding the mechanisms of development of COVID-19-associated diseases and the selection of approaches to personalized methods of their treatment.

BACKGROUND: The DutchBelgian Randomized Lung Cancer Screening Trial (NELSON) used a volume-based protocol and significantly reduced the prevalence of false-positive results (2.1%). AIM: To compare the performance of manual linear diameter and semi-automated volumetric nodule measurement in the pilot project Moscow Lung Cancer Screening ultra-low-dose computed tomography pilot study. MATERIALS AND METHODS: The study included individuals with a lung nodule of at least 4 mm on baseline-computed tomography of the Moscow lung cancer screening between February 2017 and February 2018, without verified lung cancer diagnosis until 2020. The radiation dose was selected individually and did not exceed 1 mSv. All scans were assessed by three blinded readers to measure the maximum and minimum transversal nodule diameter and extrapolated volume. As a reference value of size and volume, the average value from the results of expert measurements was obtained. A false-positive nodule was defined as a nodule 6 mm/100 mm3 and a false-negative nodule as a nodule 6 mm/100 mm3. RESULTS: Overall, 293 patients were included (166 men; mean age, 64.6 5.3years); 199 lung nodules were 6 mm/100 mm3 and 94 were 6 mm/100 mm3. Regarding volumetric measurements, 32 [10.9%; 4 false-positive, 28 false-negative], 29 [9.9%; 17 false-positive, 12 false-negative], and 30 [10.2%; 6 false-positive, 24 false-negative] nodule discrepancies were reported by readers 1, 2, and 3 respectively. For linear diameter measurement, 92 [65.5%; 107 false-positive, 85 false-negative], 146 [49.8%; 58 false-positive, 88 false-negative], and 102 [34.8%; 23 false-positive, 79 false-negative] nodule discrepancies were reported by readers 1, 2, and 3 respectively. CONCLUSIONS: The use of lung nodule volumetry strongly reduces the number of false-positive and false-negative nodules compared with nodule diameter measurements, in an ultra-low-dose computed tomography lung cancer screening program.

In the article "Volumetry versus linear diameter lung nodule measurement: an ultra-low-dose computed tomography lung cancer screening study" published in Digital Diagnostics journal Volume 4 Issue 1 in 2023 (doi: 10.17816/DD117481) contained an error in the paragraph with data of funding sources for the study. At the request of the authors team, the error was eliminated, the original version of the published article and the information on the journals site was replaced with the corrected one. Correct text of the changed: This paper was prepared by a group of authors as part of the research work (USIS No. 123031400009-1) in accordance with the Order issued by the Moscow Health Care Department No. 1196 dated December 21, 2022. The authors and the publisher apologize to readers for the published error and express their confidence that this mistake could not significantly affect the perception and interpretation of the results of the study described in the text of the article.

Currently, a common phenomenon in the economy is a global increase in various fluctuations, which are both cyclical and non-cyclical – shock – in nature. The subject of modern discussions is often the discussion of the short-term impact of shocks and the adequacy of the market mechanism to the challenges created by shocks. Overcoming the consequences of the impact of various shocks on the economy, as well as the formation of its shock resistance, is associated by most authors with increased market flexibility, increased government spending and large-scale money emissions – traditional countercyclical tools. At the same time, today exogenous shocks (technological breakthroughs and restrictions, pandemic, sanctions and embargoes) are the most destructive force, which, being outsiders in relation to the economic system, are not sufficiently sensitive to economic countermeasures. Purpose: supplementing the existing methodology for studying economic shocks with new principles and typology, reflecting their connection with structural changes – the key to shock-resistance of the economy. Methods: analysis of the works of Russian and foreign authors in the field of research, generalization of scientific approaches and critical analysis of theoretical positions. The results represent a typology of economic shocks, structured in terms of a number of principles for their study and specification criteria, which form the author's contribution to the development of the methodology for studying non-cyclical phenomena in the economy. Constructive criticism of the existing approaches made it possible to develop a theoretical proposition about the relationship between economic shocks and the structure of the economy, positive changes in which should form the basis of anti-shock regulation. Conclusions. The existing approaches to the analysis of economic shocks adequately describe their impact on economic cycles and are based on the main achievement of the modern market economy – the flexibility of markets and their regulation. At the same time, the strongest exogenous shocks observed today, the impact of which on the transformational Russian economy can become destructive, actualize the search for structural principles to counteract them, which cannot be implemented both without an appropriate theory and methodology, an important part of which is a structurally determined typology of shocks.

The author presents the results of a study of the geometry and stress-strain state of a surface with a frame of three flat curves in coordinate planes, which have found application today mainly in the shipbuilding industry. The purpose of the work is to identify from the point of view of the stress-strain state from the action of a constant uniformly distributed load the most optimal shell of a diagonal transfer of a velaroidal type with the same main frame of three superellipses. The static calculation was performed using the SCAD program based on the finite element method, designed to perform strength calculations of various types and purposes of structures. The influence of parametric equations for defining a surface depending on the generative family of the same type of cross sections on the distribution pattern of normal stresses and bending moments is shown. The results obtained can help architects and designers with choosing the shape of shells for new projects.

Background. The effectiveness of therapy for acute T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) has significantly improved over the past decades, including through the implementation of hematopoietic stem cell transplantation (HSCT). The Russian multicenter ALL-2009 study (ClinicalTrials.gov NCT01193933) showed that performing autologous HSCT (auto-HSCT) in patients with T-ALL/LBL improves long-term results. However, the study was non-randomized and the need for auto-HSCT in clinical practice requires careful study.Aim. To assess the significance of auto-HSCT in patients with T-ALL/LBL in the framework of ALL-2016 multicenter, prospective, randomized study (ClinicalTrials.gov NCT03462095).Materials and methods. The study included 109 adult patients with T-ALL/LBL (m:f 82:27). Median age was 31 (18– 52) years. T-ALL was diagnosed in 88 (81 %) patients, T-LBL in 21 (19 %) patients. All patients are treated according to the ALL-2016 protocol. Using the web platform, upon completion of induction therapy (+70 days), all T-ALL/LBL patients who achieved clinical and hematological remission were randomized to the auto-HSCT arm or chemotherapy alone (CT). Centralized monitoring of minimal residual disease (MRD) in bone marrow samples was performed by multicolor flow cytometry at the control points according to the ALL-2016 protocol. Statistical analysis was performed using SAS 9.4.Results. 87 patients with T-ALL/LBL were randomized: 44 to the auto-HSCT arm and 43 to the CT arm. Further analysis included 25 patients who underwent auto-HSCT and 36 patients receiving only CT. Three-year relapse-free survival in T-ALL is estimated at 62 % (auto-HSCT) vs. 81 % (CT) (p = 0.3422), and in T-LBL – 67 % (auto-HSCT) vs. 79 % (CT) (p = 0.59). MRD persistence on the +70th day of therapy according to the ALL-2016 protocol was determined in 40 % of patients (autoHSCT) and in 67 % (CT) (p = 0.057). In a multivariate analysis, it was determined that T-ALL from early T-cell precursor (ETP-variant) and MRD persistence after the end of II phase induction are the main risk factors for relapse in the treatment according to the ALL-2016 protocol.Conclusion. Performing auto-HSCT both in patients with T-ALL and T-LBL, and with MRD persistence on day +70 according to the ALL-2016 protocol did not improve long-term results. The development of new programs for the treatment of patients with MRD persistence, as well as the ETP variant of T-ALL, is of current interest.

Aim. To identify the relationship between the presence of a "missed" root canal and the periapical status.Materials and methods. 500 CBCT images of patients of both sexes were studied: 2915 teeth after endodontic treatment, of which 1549 were multicanal. Profile diagnostic criteria were used to identify the "missed" canal.Results. 518 "missed" root canals were revealed, which accounted for 33.4% of the number of multi-canal teeth. In 228 cases, changes in periapical tissues were noted, including 1 case of widening of periodontal ligament space, which accounted for 44% of the total number of "missed" canals. It was noted that the risk of developing apical periodontitis is higher for cases with "missed" canals (p < 0.001). The relationship between the untreated canal and the periapical status is statistically assessed as medium or relatively strong, which confirms the relevance of accurate diagnosis of the anatomy and topography of the root canal system at all stages and by all available methods.Conclusions. In case of sufficient duration of observation, absence of symptoms, absence of periapical changes (radiologically) – repeated treatment for the purpose of endodontic treatment of the "missed" root canal is not justified. If there are changes in the periapical tissues, repeated endodontic intervention should be performed. In this case, preference should be given to endodontic re-treatment using a microscope.

Currently, the Russian economy is undergoing active processes of digital transformation and system integration in all areas of production and economic activity. At the same time, the agro-industrial complex and agriculture lag behind the leading industries in terms of the level of digitalisation. This opens up large-scale prospects for the implementation of information technology projects, but also dictates the need to introduce additional measures to accelerate the development and implementation of digital technologies. The growing popularity of system integration is explained by a number of advantages: reducing the time for information exchange, decision-making and goods circulation, eliminating duplication of functions and the overall economic effect for each of the participants due to a wider and more comprehensive integration of computer systems. To support such initiatives, the study proposes a mechanism for the system integration of the resource subsystem of agricultural, processing and marketing enterprises in the region using a theoretical and methodological basis. Achieving the highest level of system integration is expected through the integration of information systems on a platform framework, as well as the addition of digital services of financial operators with the connection of economic entities of the agro-industrial complex. The developed mechanism reflects the algorithm of strategically significant events with a target orientation towards expanding the scale of system integration of enterprises in the agro-industrial complex. Its implementation will provide an opportunity for global planning in industries and provision of recommendations to market participants, including those based on artificial intelligence technologies.

The unprecedented impact of external shocks on the Russian economy threatens with a long-term recession, the avoidance of which requires the initiation of successive shifts in the technological, reproductive, sectoral, social structure, united by a single imperative of neo-industrial development. At the same time, structural changes in the economies of technologically advanced countries today are moving in line with the post-industrial transformation, the result of which is an increase in labor productivity and added value. In the Russian economy, the protracted deindustrialization requires the formation of a methodology and theory of neo-industrial development based on its own technologies and resources to counteract external shocks. The purpose of the study is to analyze approaches and theoretical provisions to the study of the possibilities of neo-industrial development of the Russian economy in the face of external shocks. Methods: literary review of Russian and foreign publications and materials, comparison and critical analysis of scientific theories. The results represent the structured content of the approach to the study of the neo-industrial transformation of the Russian economy in the context of external shocks, presented in comparison with the metho-dology of post-industrial development; the theories associated with it are criticized. The theoretical provisions of regulated structural shifts of the neo-industrial type, which are necessary to overcome de-industrialization and avoid post-shock recession, are considered. Conclusions. Theories describing the movement of the modern economy from an industrial to a post-industrial type objectively describe structural changes and technological transition in advanced countries, but do not offer forms and institutions to overcome the deindustrialization of the Russian economy due to its specifics. Nevertheless, the methodology of neo-industrial development includes approaches to the theoretical substantiation of the accelerated innovation and technological development necessary for the development of industry in the face of external shocks.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is an aggressive hematological disease. Modern polychemotherapy protocols allow achieving a 5-year overall survival of 60–90 % in different age groups, however, relapses and refractory forms of T-ALL remain incurable. Over the past decades, the pathogenesis of this variant of leukemia has been studied in many trials, and it has been found that various signaling pathways are involved in the multi-step process of leukemogenesis. This opens the way for targeted therapy.In this review, we provide an update on the pathogenesis of T-ALL, opportunities for introducing targeted therapies, and issues that remain to be addressed.

Works on the study of the stress-strain state of the shell of an equal slope with an ellipse at the base have not been widely performed. The present paper is a part of a series of articles on the analysis of the geometry and stress state of torses of an equal slope with a directrix ellipse by various methods under different loads and support conditions. The derivation of the differential equations of equilibrium of the momentless theory of shells for determining internal forces in the torse with a directrix ellipse under the action of internal pressure is presented. The analytical results are compared with results obtained by the finite element method (FEM) and the variational difference method (VDM). The advantages and disadvantages of three calculation methods are determined, and it is established that VDM results are more accurate compared to FEM, but FEM-based software is a more powerful tool to perform the structural analysis.