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Abstract In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.

At the 15th Congress of Anthropologists and Ethnologists of Russia, held in St. Petersburg at the end of June 2023, special attention was paid to the discussion of topical theoretical and practical problems related to scientific reflections and social practices of the institute of mentoring in the cultures of the Rus-sian North. The report presented by the authors of this article at the Congress outlined the scientific results of research on the traditional institution of mentoring in the Old Believer societies of Karelians, Komi, Russian Ust-Tsilems, the “institute of grandmothers” in Kenozerye and Onega Pomorie, the ritual “mentoring” functions of Nenets shamans and Zyryan sorcerers, public practices of the spiritual guidance of the laity in the parochial community of the North Russian mir-zemstvo. The central place in the article is given to the presentation of the scientific results of the analysis of the forms, methods and directions of the mentoring activities of the Kenozerskiy National Park, which, relying on the ethno-cultural heritage of the traditional societies of the Ozernyy district, acts as a reference methodological school-laboratory, implementing a wide range of mentoring research and educational practices aimed at transformation of local territories into a socio-cultural space of creative dialogue and cooperation between the Park and local communities, training of leaders and activists of territorial public self-government (TPS), elaboration of regional strategy and local programs of spatial development of the Northern macro-region.

For the sustainable development of territories, it is important to pay special attention to transport infrastructure, which directly affects the level of efficiency and competitiveness of the state (region) economy and forms the creation of a rational logistics system. Transport activates the work of the real sector of the economy (economic entities), carries out freight and passenger transportation, and is one of the significant sectors of the national economy, providing employment to the population, tax revenues to the budget system of the Russian Federation, investment attraction and GDP growth. The Arctic zone of the Russian Federation is strategically significant from the perspective of geopolitics and geo-economics in the modern world (1215% of the country’s GDP, 25% of exports). In the article, the object of study is the Western and Central Arctic of the Russian Federation, including six of the eight subjects belonging to the Arctic territories. The methodological framework of the study is based on review and analysis of regulatory documents and scientific literature that determine trends and prospects for improving territories within the development of transport infrastructure. The information base is regional statistical information. The study and assessment of the level of transport infrastructure development of the studied region is carried out. Economic analysis is conducted using statistical methods that allow identifying the main reasons associated with the ineffective operation of transport infrastructure at the meso-level. Tables and figures are used to visualize the research results. This makes it possible to conduct a comparative analysis of territories by the level of transport infrastructure development, to identify leaders and outsiders to substantiate proposals for stimulating key areas, basing on the review of regulatory documents aimed at increasing the efficiency of functioning of this area.

Introduction. The World Health Organization considers the values of antibody titers in the hemagglutination inhibition assay as one of the most important criteria for assessing successful vaccination. Mathematical modeling of cross-immunity allows for identification on a real-time basis of new antigenic variants, which is of paramount importance for human health. Materials and methods. This study uses statistical methods and machine learning techniques from simple to complex: logistic regression model, random forest method, and gradient boosting. The calculations used the AAindex matrices in parallel to the Hamming distance. The calculations were carried out with different types and values of antigenic escape thresholds, on four data sets. The results were compared using common binary classification metrics. Results. Significant differentiation is shown depending on the data sets used. The best results were demonstrated by all three models for the forecast autumn season of 2022, which were preliminary trained on the February season of the same year (Auroc 0.934; 0.958; 0.956, respectively). The lowest results were obtained for the entire forecast year 2023, they were set up on data from two seasons of 2022 (Aucroc 0.614; 0.658; 0.775). The dependence of the results on the types of thresholds used and their values turned out to be insignificant. The additional use of AAindex matrices did not significantly improve the results of the models without introducing significant deterioration. Conclusion. More complex models show better results. When developing cross-immunity models, testing on a variety of data sets is important to make strong claims about their prognostic robustness.

Pragmalinguistic analysis of media texts with a destructive component (violence, suicide, revenge, reprisals) is presented. A feature of the media content under study is: 1) the presence of a digital communicator – a digital platform (blog, messenger, social network, video, etc.) for broadcasting and replicating the communication process by the participants themselves (representatives of generation Z); 2) the place and role of a digital communicator in the implementation of a given destructive behavioral model. The transformation of axiosphere was revealed: there were axiological shifts in the conceptual field "LIFE-DEATH". Due to it we were able to identify the potential activity of the destructive vector of the homo digitalis behavioral model. The "axiologeme" is interpreted by us as a speech signal of hidden influence. In the text it acts as a lexical unit with code evaluation, which forms positive, neutral or negative associations: death (negative in psychological and emotional terms; neutral (logical conclusion of the life way) from the point of view of Christian morality in objective reality, neutral in virtual reality, as it is possible to reboot and positive (receiving bonuses: likes, discussions, comments). The development of influence plans ("positive-approving, neutral-indifferent or negativedisapproving") for the described events allowed us to identify the author's assessment of the media text with a destructive component. Positive-approving plan – 36.4%, negative-disapproving - 46.1%, and neutral-indifferent – 18.5%. These data reflect the prospects for the preservation/non-preservation of the axiosphere of Russian linguaculture.

Introduction. This paper is devoted to identifying the role of family and children in the value system of Kaliningrad university students. This aspect is important both in connection with the current demographic situation, as well as with the decision to declare 2024 the Year of the Family in Russia. Materials and methods. In 2023, a survey was conducted among students of Kaliningrad universities, which was attended by 241 people aged 18-24 years. The questionnaire consisted of six “open” questions. Students were asked to give their own definition of the concept of “values”; to name the most significant values; to describe the ideal family model; to determine the role of children in general and in their own life strategies; to explain the reasons for wanting or not wanting to have children. This type of survey was designated as an express interview. The methodological basis of the study was the concept of demographic well-being, according to which demographic processes must be considered simultaneously at the macro and micro levels. In this research, the focus was on the micro level. Results. The study revealed that the majority of respondents perceive values as basic attitudes that define a person’s life, are expressed in spiritual and material things and are passed on to the next generations. The most important values are recognized as family, friendship, money, love, freedom and health. Talking about the ideal family, the survey participants described the relationships they would like to see in the family. Only a few people consider the ideal families in which they grew up and live. The majority of respondents intend to have children in the future, although some make a reservation that there must be appropriate conditions for this. At the same time, a significant proportion of young people were identified who expressed a fundamental reluctance to have children. Discussion. Based on the conducted research, it was revealed that the family is the most significant category in the students’ value system. The ideal is a complete family without financial problems, whose members live in an environment of mutual understanding, support and love. For most respondents, children seem to be a necessary part of the family. Some survey participants expressed unwillingness to perform parental functions. The conducted research has demonstrated the importance of analyzing demographic processes at the micro level, that is, from a human perspective, taking into account his values and life attitudes.

Background. The process of storing sperm in a deeply frozen state causes structural and functional disorders of spermatozoa, which reduces their fertilizing ability. The main mechanism of the negative effect of cryopreservation on spermatozoa is the development of oxidative stress. Molecular hydrogen has some advantages as a potential antioxidant molecule - it is a selective effect on certain reactive oxygen species, the ability to overcome cell membranes, the absence of toxic effects. Purpose. To study the effect of molecular hydrogen on the functional status of native and deconserved sperm cells of breeding bulls. Materials and methods. The object of the study was the ejaculates of bulls before cryopreservation and after defrosting. The native sperm diluted with the "BioXcell" diluent, the native sperm diluted with the "BioXcell" diluent enriched with molecular hydrogen, the sperm after deep freezing and the sperm after deep freezing pretreated with molecular hydrogen were studied. The intensity of free radical processes and the activity of antioxidant enzymes were determined in spermatozoa. Results. After cryopreservation of sperm, the processes of lipid peroxidation in spermatozoa are significantly activated. The content of malondialdehyde, diene and triene conjugates increases. The use of molecular hydrogen to correct the quality of sperm production after cryopreservation gave positive results. A decrease in the concentration of primary and intermediate products of lipid peroxidation was noted. The activity of superoxide dismutase and catalase in spermatozoa significantly increases. Conclusion. Molecular hydrogen has the potential as a new and effective antioxidant, the widespread use of which is possible for veterinary purposes. Sponsorship information. The study was funded by the Russian Science Foundation grant No. 23-26-00205.

Animal behavior can serve as an important indicator of welfare for zoo inhabitants. The maternal behaviors exhibited by lynx and puma in captivity are crucial not only for the survival and well-being of their cubs but also provide valuable insights for species conservation programs. We analyzed the motor activity of a male and female Siberian lynx and a male and female puma during the period when they were raising their kittens, which had not yet left the shelter at the time of observation. Our ethological monitoring revealed both similarities and differences in behavior across species and sexes. We found that males of both species exhibited passive behaviors more frequently than females. Overall motor activity was higher during the evening observation periods. Notably, the male lynx spent significantly less time in the shelter compared to the other studied animals, likely due to his close cohabitation with the female and their kittens. In contrast, the male puma was kept nearby but separately from the female and her offspring. Abnormal behaviors were observed in nearly all animals, except for the female lynx. The female puma exhibited the highest level of abnormal activity, frequently carrying her kitten in her mouth for extended periods, which suggests a high level of stress. The intraspecific Shorygin indices of behavioral similarity between male and female lynxes and pumas were relatively low, at 42% and 45%, respectively. In comparison, our previous research indicated that the behavioral similarity index between male and female Eurasian lynxes without offspring was 87%. This suggests that the presence of kittens significantly increases the differences in time budgets between males and females.

Background. Intensive milk production technology creates a number of factors that can put an animal into a state of technological stress. The effect of stress is reflected in nonspecific resistance, which represents the body's ability to resist the effects of adverse factors by maintaining protective forces at the proper level. Neutrophils are one of the first protective cellular barriers that are rapidly mobilized when exposed to stress factors. To decipher the changes taking place in response to the action of stressors, the involvement of various evaluation tools is required. One of the possible methodological approaches is the use of various visualization methods that provide access to spatio-temporal information at the level of individual organelles and Purpose. The study of the morpho-functional state of neutrophils under technological stress in cattle by laser interference and electron scanning microscopy. Materials and methods. The work was carried out on 30 clinically healthy highly productive black-and-white cows. A combination of impacts was considered as technological stress: the rearrangement of animals and the change of service personnel. Neutrophils were analyzed by laser interference and electron scanning microscopy. Results. A change in the morphological structure and functional activity of neutrophils after the action of technological stress is shown. The analysis of interferograms revealed an increase in the heterogeneity of neutrophils due to the appearance of degeneratively altered cell forms with an increase in the number of functionally active neutrophils. Electron scanning microscopy revealed the appearance of NEToses and neutrophils with emptied granules and vacuolization of the cytoplasm after technological stress. Conclusion. The revealed morphofunctional changes in neutrophils prove the strain of adaptation mechanisms under technological stress. This circumstance must be taken into account in order to prevent disruption of the adaptive capabilities of the organism of highly productive animals.

The article discusses information security in the system of an industrial enterprise. Attention is focused on the need to implement a continuous information security process to protect all information assets from leaks, theft and unauthorized disclosure, the main provisions of information security management standards are analyzed. Objective: To optimize the methods of software protection of modern industrial enterprises, as well as to reduce threats and vulnerabilities related to information security at enterprises. Method or methodology of the work: In the process of investigating the problem, analytical methods of analysis were used. Results: The need to use ISO/IEC 27001 standards and the PDCA (Plan-Do-Check-Act) model at industrial enterprises of high-tech sectors of the economy in order to reduce threats and losses of information security, identify critical factors that negatively affect business processes and the enterprises themselves. Practical implications: The results obtained can be used as a theoretical basis for existing assessments of information security tools and automated security systems at high-tech industrial enterprises in modern economic conditions.

Combination steam ovens, or combi steamers, have entered all spheres of food production, including the meat industry. Their rational use requires a scientific and practical foundation. This research featured the changes in mean volume temperature and temperature gradient that occur in meat products (one-dimensional bodies with different nutrient compositions) during heat treatment in dry air and a steam-air mix. The research involved two samples of meat products with different moisture and fat contents. The chicken fillet sample had a moisture content of 74.5% and a fat content of 1.9% while the pork shoulder sample had a moisture content of 55.1% and a fat content of 29.4%. Shaped as a one-dimensional cylinder and a plate, the samples were subjected to heating at the temperature range of 160–240°C in a Unox-203G steam-convection oven (Italy). Dry air and a steam-air mix with a humidity of 80–85% served as a heating medium. The temperature was measured using thermocouples attached to a Sosna-004 meter. The research revealed some patterns in the mean volume temperature and temperature gradient. The temperature gradient involved three stages during processing in a steam-air mix and four stages when treated with dry air. The change in the mean volume temperature for the steam-air mix could be described by a power law equation; the dry air treatment was described using a linear equation. When heated in dry air, the rate of change in the temperature gradient was constant at first but started to decrease at a certain stage. The change rate in the mean volume temperature remained low for 5 min and started to increase onwards, maintaining its value until the end of the process. When heated in a steam-air mix, the change rate in the temperature gradient dropped to its minimum in 4–5 min and started to grow. The mean volume temperature demonstrated a high change rate during the first 5 min and went down. The chicken fillet with its low fat content warmed up faster by 13–26% when processed in a steam-air mix and by 9–23% when treated in dry air. The plate-shaped products needed longer heat treatment. The composition and form had no significant effect on the nature of the change in the temperature gradient and mean volume temperature. The obtained dependencies made it possible to select the optimal temperature and humidity conditions for convective frying of meat products.

The study is focused on revealing and analysis of external influences that affect the process of teaching the Russian language for specific purposes - business/professional communication to bilingual learners. The analysis is correlated with the description of external factors that cause a shift of emphasis from teaching the language of profession to teaching business communication. This comprehensive analysis makes it possible to build a uniform teaching course model based on a holistic approach. The study defines the general strategy of training, formulates tasks and outlines approaches to their solution, as well as delineates the contours of a branched out multi-component practical training course.

Historical education in the system of higher educations is designed to solve not only teaching, but also upbringing tasks. Therefore, it is called upon to quickly and effectively overcome challenges which the historical education faces with the help of a specific political situation and social need. The modern situation is particularly acute in this regard. The concept of teaching Russian history to individuals of non-historical specialties and fields, which are implemented in higher education organisations, adopted in 2023, also testifies to this. The renewal of the content of historical education in the country requires the introduction of innovations in the field of the methodology of teaching. The methodological basis of history teaching in Russia has a long tradition, formed within the framework of several directions. Modern researchers of the problem note the special importance of the technological approach, which has become widespread in educational institutions of the country. However, it is not enough for today. The methodology of teaching history should precisely reflect the changes in the content of the discipline. At the same time, the range of methodological techniques in the teacher's arsenal may not change significantly. It is even possible to appeal to the experience of pre-revolutionary and Soviet methodology. But the question of the content of the methodological base and its objective orientation is core.

Introduction. The COVID-19 pandemic, etiologically related to SARS-CoV-2, was the longest-lasting pandemic for an acute respiratory disease and had a significant impact on demography, economics and politics globally. Experiences with this pandemic are significant for the sustainable development of human society. A detailed analysis of these experiences in epidemic control should include details of the pathogen evolution down to the regional level. The aim of the study was to establish the regularities of the COVID-19 epidemic process in connection with the change of the pathogen genetic variants on the territory of Primorsky Krai. Materials and methods. A retrospective epidemiological analysis of COVID-19 incidence and dynamics of circulation of SARS-CoV-2 genetic variants during the pandemic of this disease (11.03.2020–05.05.2023) in Primorsky Krai was carried out. Data was gathered from the Department of Rospotrebnadzor in Primorsky Krai, the Centre of Hygiene and Epidemiology in Primorsky Krai, as well as the G.P. Somov Research Institute of Epidemiology and Microbiology of the Russian Federation and Russian Platform for Aggregation of Information on Virus Genomes (VGARus). In particular, 1055 nucleotide sequences of full-length SARS-CoV-2 genomes from Primorsky Krai, among which 553 were sequenced at the G.P. Somov Research Institute of Epidemiology and Microbiology were included in analysis. Results. When analyzing the epidemic dynamics of COVID-19 in Primorsky Krai (2020–2023), 7 rises in incidence with different clinical and epidemiological symptoms depending on the genetic variants of the pathogen were identified. At the beginning of the pandemic in Primorsky Krai, as well as throughout Russia, Wuhan-like variants of SARS-CoV-2 were predominant, though later, Delta and Omicron genetic variants were in the majority. By the end of April — beginning of May 2023, the proportion of Omicron sub-variants (XBB.1.9.2 and XBB.1.16) in Primorsky Krai was higher than the Russian average and comparable to that in neighboring countries (Republic of Korea and Japan). Conclusion. Due to the ongoing evolution of SARS-CoV-2, the possibility of the emergence of new pathogens, the peculiarities of the geographical location as well as political and economic importance of Primorsky Krai, it is necessary to consistently improve regional capabilities for operational molecular virological monitoring.

Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the cellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The objective of the work is to create nanocomposites consisting of TiO2 nanoparticles, antisense oligonucleotides, and photoactive groups and to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in the cellular system. Materials and methods. Influenza virus A/Aichi/2/68 (A/H3N2), N-succinimide ether of p-azidotetrafluorobenzoic acid, TiO2 nanoparticles, and oligodeoxyribonucleotides have been used in the work. The antiviral activity of the proposed nanocomposites has been studied on the MDCK cells infected with the A/H3N2 virus. Results and discussion. Unique nanocomposites have been created, which consist of three functional components, i.e., titanium dioxide nanoparticles, antisense oligonucleotides, and the photoactive tetrafluoroarylazide group, respectively, providing penetration into cells, selective interaction with target nucleic acids, and photomodification of the targets. A significant antiviral site-specific action of the nanocomposites has been demonstrated against the influenza A virus in the cellular system, which exceeds the effect of the analogous samples that contain no photoactive groups. Conclusion. The biological activity of the created nanocomposites has been demonstrated by the example of highly effective suppression of influenza A virus replication in the cellular system. The results indicate the prospects of using the proposed drugs to affect target nucleic acids inside cells.

Abstract Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98–99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary.

Abstract Low‐grade epilepsy‐associated tumors (LEATs) are a common cause of drug‐resistant epilepsy in children. Herein, we demonstrate the feasibility of using tumor tissue derived from stereoelectroencephalography (sEEG) electrodes upon removal to molecularly characterize tumors and aid in diagnosis. An 18‐year‐old male with focal epilepsy and MRI suggestive of a dysembryoplastic neuroepithelial tumor (DNET) in the left posterior temporal lobe underwent implantation of seven peri‐tumoral sEEG electrodes for peri‐operative language mapping and demarcation of the peri‐tumoral ictal zone prior to DNET resection. Using electrodes that passed through tumor tissue, we show successful isolation of tumor DNA and subsequent analysis using standard methods for tumor classification by DNA, including Glioseq targeted sequencing and DNA methylation array analysis. This study provides preliminary evidence for the feasibility of molecular diagnosis of LEATs or other lesions using a minimally invasive method with microscopic tissue volumes. The implications of sEEG electrodes in tumor characterization are broad but would aid in diagnosis and subsequent targeted therapeutic strategies.

The results of a study of accepting new conditions in the educational process by students of various forms of university education during the COVID-19 pandemic are presented. The urgency of the problem is due to significant qualitative changes in the educational process associated with the emergency transition to the use of distance learning technology the importance of assessing the dynamics of students’ personal acceptance of the transformations that have occurred. The sample consisted of 1,571 undergraduate and graduate students from universities in 8 federal districts of the Russian Federation, including full-time students (79.2%), part-time students (16.6%) and students of evening classes (4.2%). The main method of analyzing the levels of acceptance of new conditions in the organization of the educational process by among the respondents was a survey. The survey questions were compiled on the basis of focus group interviews with the students of all the three forms of university education ( n = 26). Using Spearman’s rank correlation coefficient, the probable association of the phase of ‘acceptance’ of the learning format using distance learning technology was shown. The results showed that the process of accepting changes among the part-time students was faster than among the full-time students and students of evening classes. A qualitative analysis of signs of acceptance of changes associated with the use of a learning format based on distance learning technology, made it possible to establish that the stages ‘denial’ and ‘aggression’ expressed at the beginning of the pandemic were replaced by the stage ‘acceptance’ for the majority of students. The data obtained can be useful for understanding how university students of various forms of education experience significant qualitative changes in the educational process.

The article discusses the problems and prospects for development of the logistics sector in Russia. The concept of blockchain, its main functions and tasks are described. The principles of operation of the system and examples of companies already using this technology are given. Now, in Russia, logistics support for cargo delivery has low quality and economic efficiency indicators. Logistics is in search of new technologies that will simplify and automate the process of accumulating and using data related to document flow, cargo tracking and information storage. Logistics chains can include dozens of links; the more nodes in the chain, the more difficult it is to control them and the more information appears. At the same time, interactions between producers, carriers and consumers are becoming less transparent. Blockchain technologies can solve these problems by reducing the cost of transportation, making information impossible to hack and falsify, and optimizing processing and query times. Purpose: to consider the main problems and challenges arising in the field of logistics that blockchain technologies can solve. Results: obtaining information on how blockchain technology can be applied in logistics, as well as identifying opportunities and prospects for its use. Practical implications: deciding on the implementation of blockchain technology in logistics operations and using its advantages to assess efficiency and competitiveness.

The study is devoted to the study of the relationship between the structure of the economy and the level of pollution of European cities in the context of the environmental imperative. Based on comparative statistical analysis, the level of pollution in European cities in 2013 and 2023 was considered and cities with the most and least favorable environmental situation were defined. Studied cities were divided into 7 groups by pollution index; stable trend of their location was determined through carrying out a cartographic analysis: groups of the most polluted cities are located mainly in the southeast of Europe and the least - in the northwest. Five types of cities with different trends in pollution index dynamics were identified. Based on a comprehensive synthetic analysis of cities with maximum improvement and deterioration of the environmental situation, the main factors of multidirectional dynamics are described - activity of environmental policy, sectoral structure transformation of urban economy. Main spatial trends in the environmental situation of European cities were identified: cities with positive dynamics of pollution index predominantly concentrated in the southeast, with a negative - in the east. The analysis showed that 2/3 of the largest cities in Europe improved their ecological condition mainly due to the effectiveness of environmental measures, the green political movement, the development of the tertiary and quaternary sectors in their economy.

The impact of nano-selenium supplementation on lipid metabolism, liver enzymes, renal function, and protein levels in male lambs was investigated in this study during a 60-day period. Lambs were divided into two groups - control and experimental, which were administered nanoselenium orally at a dosage of 0.5 mg/ kg of feed once a day, daily. Each group consisted of five male lambs. According to the findings, cholesterol levels dropped significantly at days 45 (P 0.01) and 60 (P 0.05), whereas triglyceride levels significantly rose at days 15 and 30 (P 0.01). Throughout the trial, the levels of uric acid and creatinine were constant. At days 15 and 60, aspartate aminotransferase (AST) levels were significantly decreased (P 0.05), while at days 45 and 60, alkaline phosphatase (ALP) levels declined (P 0.01 and P 0.05, respectively). At days 15 and 30, albumin levels dropped significantly (0.05), but day 60 saw an increase in globulin levels significantly (P 0.05). The drop in AST and ALP levels might be a sign that liver function has possibly improved. However, the drop in albumin levels and rise in globulin levels raise the possibility that taking nano-selenium supplements may affect how proteins are metabolized. The findings of this study concluded that the effects of nano-selenium supplementation on lipid metabolism, liver enzymes, renal function, and protein levels in male lambs were time-dependent. In addition to possible improvements in liver function based on decreased AST and ALP levels and changes in albumin and globulin levels, the study also noticed an initial transient increase in triglyceride levels that was followed by a decline in cholesterol levels. To determine the time-dependent changes in liver function, liver enzymes, as well as renal function in response to nano-selenium supplementation in male lambs was objective of this study.

Stress-related anxiety disorders and anxiety-like behavior in post-traumatic stress disorder (PTSD) are associated with altered neurocircuitry pathways, neurotransmitter systems, and the activities of monoamine and glucocorticoid-metabolizing enzymes. Resveratrol, a natural polyphenol, is recognized for its antioxidant, anti-inflammatory, and antipsychiatric properties. Previous studies suggest that resveratrol reduces anxiety-like behavior in animal PTSD models by downregulating key enzymes such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and monoamine oxidases (MAOs). However, the underlying mechanisms remain unclear. In this study, we explored the efficacy of resveratrol in treating stress-induced anxiety using a chronic predator stress model in rats. Resveratrol was administered intraperitoneally at 100 mg/kg following a 10-day stress exposure, and anxiety behavior was assessed with an elevated plus maze. Our results indicated that stress-related anxiety correlated with increased activities of brain MAO-A, MAO-B, and hepatic 11β-HSD-1, alongside elevated oxidative stress markers in the brain and liver. Resveratrol treatment improved anxiety behavior and decreased enzyme activities, oxidative stress, and hepatic damage. We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol’s potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.

Background. Improving the quality of dental care for patients with sensorineural hearing loss is one of the most important problems in dentistry at present. The special status of patients with sensorineural hearing loss makes this contingent the most defenseless in such an issue as dental education. In this regard, these patients have an unsatisfactory level of hygienic dental knowledge. In addition, they have low motivation to improve their level of knowledge, and also lack motivation to not only maintain, but also strengthen their oral health. Regular and proper oral hygiene ensures 85-90% of dental health. The purpose of the research is to study the effectiveness of using a modern, adapted, proposed by us, method of brushing teeth in patients with sensorineural hearing loss. Materials and methods. To study the effectiveness of our proposed method of brushing teeth, 150 people with varying degrees of hearing loss were selected. A study of dental status was carried out, a questionnaire was carried out, an index assessment of hard dental tissues was carried out, a modern, adapted method of brushing teeth was tested. Results. When analyzing this method of brushing teeth, it was revealed that for patients with sensorineural hearing loss, it is not so much the amount of information that is important, but the amount of information learned with the possibility of its correct implementation in practice. Conclusions. Our research has shown that the adapted method of brushing teeth makes it possible to easily remember information and control the quality of teeth brushing at each stage.

Introduction/Justification: The use of artificial intelligence using convolutional neural networks in clinical practice is recent. Thus, a growing need exists to validate software performance in different tasks in different diseases. Objectives: To evaluate the performance of artificial intelligence software to determine metabolic tumor burden in the primary staging of rectal cancer. Materials and Methods: A cross-sectional retrospective analysis was conducted on 51 histology-proven rectal cancer patients (35% females; mean age = 61 years) who underwent a staging 18F-FDG PET/CT. Whole-body metabolic tumor burden parameters (wbMTV and wbTLG) were quantified semi-automatically and through AI algorithm (Syngovia VB60; Siemens Healthineers Medical Solutions). The AI software's ability to correctly identify and classify the primary lesion, regional lymph nodes, and distant metastases was evaluated. In addition, the intraclass correlation coefficient (ICC) was applied to evaluate concordance between the AI-based software and the semiautomatic software in determining wbMTV and wbTLG. Values above 0.7 were considered to indicate substantial agreement. Resultados: The AI and semiautomatic tumor burden metrics correlated strongly for both wbMTV (ICC = 1.00; 95% CI = 0.94 - 0.99; P < 0.0000) and wbTLG (ICC = 1.00; 95% CI = 0.80 – 0.90; P < 0.0000). Additionally, the AI software's ability to correctly identify lesions compared to the documented staging was better for the identification of distant metastasis (78,57% of patients), mildly adequate to identify regional lymph nodes (50,00%) and had poor performance for identification of the primary lesion (5,76%). On the other hand, the time spent calculating these metrics was less by AI than by the semiautomatic method, especially in patients with advanced disease. Conclusion: The determination of whole-body metabolic tumor burden on 18F-FDG PET/CT with artificial intelligence software is challenging because of the physiologic bowel activity. However, deep learning may have the ability to overcome these challenges and may therefore improve the primary staging of rectal cancer.

IntroductionThe plasticity of the nervous system plays a crucial role in shaping adaptive neural circuits and corresponding animal behaviors. Understanding the mechanisms underlying neural plasticity during development and its implications for animal adaptation constitutes an intriguing area of research. Sea urchin larvae offer a fascinating subject for investigation due to their remarkable evolutionary and ecological diversity, as well as their diverse developmental forms and behavioral patterns.Materials and methodsWe conducted immunochemical and histochemical analyses of serotonin-containing (5-HT-neurons) and dopamine-containing (DA-positive) neurons to study their developmental dynamics in two sea urchin species: Mesocentrotus nudus and Paracentrotus lividus. Our approach involved detailed visualization of 5-HT- and DA-positive neurons at gastrula-pluteus stages, coupled with behavioral assays to assess larval upward and downward swimming in the water column, with a focus on correlating cell numbers with larval swimming ability.ResultsThe study reveals a heterochronic polymorphism in the appearance of post-oral DA-positive neuroendocrine cells and confirms the stable differentiation pattern of apical 5-HT neurons in larvae of both species. Notably, larvae of the same age exhibit a two- to four-fold difference in DA neurons. An increased number of DA neurons and application of dopamine positively correlate with larval downward swimming, whereas 5-HT-neurons and serotonin application induce upward swimming. The ratio of 5-HT/DA neurons determines the stage-dependent vertical distribution of larvae within the water column. Consequently, larvae from the same generation with a higher number of DA-positive neurons tend to remain at the bottom compared to those with fewer DA-positive neurons.DiscussionThe proportion of 5-HT and DA neurons within larvae of the same age underlies the different potentials of individuals for upward and downward swimming. A proposed model illustrates how coordination in humoral regulation, based on heterochrony in DA-positive neuroendocrine cell differentiation, influences larval behavior, mitigates competition between siblings, and ensures optimal population expansion. The study explores the evolutionary and ecological implications of these neuroendocrine adaptations in marine species.

Breda Cushen,1,&ast; Mariko Siyue Koh,2,&ast; Trung N Tran,3 Neil Martin,3,4 Ruth Murray,5 Thendral Uthaman,6 Celine Yun Yi Goh,5,6 Rebecca Vella,7 Neva Eleangovan,5,6 Lakmini Bulathsinhala,5,6 Jorge F Maspero,8,9 Matthew J Peters,10 Florence Schleich,11 Paulo Pitrez,12 George Christoff,13 Mohsen Sadatsafavi,14 Carlos A Torres-Duque,15,16 Celeste Porsbjerg,17 Alan Altraja,18 Lauri Lehtimäki,19 Arnaud Bourdin,20 Christian Taube,21 Nikolaos G Papadopoulos,22,23 Csoma Zsuzsanna,24 Unnur Björnsdóttir,25 Sundeep Salvi,26 Enrico Heffler,27 Takashi Iwanaga,28 Mona al-Ahmad,29 Désirée Larenas-Linnemann,30 Job FM van Boven,31 Bernt Bøgvald Aarli,32,33 Piotr Kuna,34 Cláudia Chaves Loureiro,35,36 Riyad Al-lehebi,37 Jae Ha Lee,38 Nuria Marina,39 Leif Bjermer,40 Chau-Chyun Sheu,41,42 Bassam Mahboub,43 John Busby,44 Andrew Menzies-Gow,45 Eileen Wang,46 David B Price5,6,47 On behalf of ISAR Inventory Study Group1Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland; 2Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Respiratory Medicine, University of Leicester, Leicester, UK; 5Optimum Patient Care Global, Cambridge, UK; 6Observational Pragmatic Research Institute, Singapore, Singapore; 7Optimum Patient Care, Brisbane, Queensland, Australia; 8Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 9University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 10Department of Thoracic Medicine, Concord Hospital, Sydney, Australia; 11CHU Sart-Tilman, GIGA I3, University of Liege, Liège, Wallonia, Belgium; 12Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil; 13Faculty of Public Health, Medical University, Sofia, Bulgaria; 14Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada; 15CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 16Universidad de La Sabana, Chia, Colombia; 17Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark; 18Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 19Allergy Centre, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 20PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 21Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 22Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 23Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 24Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary; 25Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland; 26Pulmocare Research and Education Foundation, Pune, India; 27Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 28Kindai University Hospital, Osakasayama, Japan; 29Microbiology Department, College of Medicine, Kuwait University, Kuwait, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 30Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 31University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Clinical Pharmacy & Pharmacology, Groningen, the Netherlands; 32Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; 33Department of Clinical Science, University of Bergen, Bergen, Norway; 34Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland; 35Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 36Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 37Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia, Alfaisal University, Riyadh, Saudi Arabia; 38Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 39Pneumology Service, Biocruces, Cruces University Hospital, Barakaldo, Spain; 40Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; 41Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 42Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 43Rashid Hospital, Dubai Health Authority (DHA), Dubai, United Arab Emirates; 44Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK; 45Lung Division, Royal Brompton & Harefield Hospital, London, UK; 46Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health and University of Colorado School of Medicine, Denver and Aurora, CO, USA; 47Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK&ast;These authors contributed equally to this workCorrespondence: David B Price, Observational and Pragmatic Research Institute (OPRI) Pte Ltd, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR’s Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised.Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting > 90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases.Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.Keywords: Asia-Pacific, biologics, COVID-19, Europe, ISAR, International Severe Asthma Registry, oral corticosteroids, Registry, Middle East, Severe Asthma, Latin America, USA

The study examines how the US Cold War cinema employed linguistic means to construct images of the USSR and American communists. The research relevance is determined by: the need to study the techniques of creating the enemy image as one of the crucial issues in international relations; and the importance of the topic amidst the aggravation of Russia- US relations. The study aims at analysing the usage of linguistic means in such practices of constructing/deconstructing the images of ‘enemy number one’ as dehumanisation of the enemy, its normalisation, domestication, and rehumanisation. The research novelty lies in the fact that, for the first time, the language as a resource for constructing enemy images in the Cold War films is analysed. The material for the study makes American films of the 1940s-1960s, in which contaminated speech for depicting Soviet characters is extensively used. Particular attention is paid to the means of creating speech portraits of Soviet characters. The research methods used are descriptive, linguistic, and sociolinguistic methods, and discourse analysis. The authors conclude that linguistic means (primarily linguistic competences and accent) were instrumental for creating enemy images in the cinematic Cold War. Linguistic otherness served as a means of emphasising second-rate culture, which in turn was intended to mark political foreignness. Linguistic means helped fulfil functions of the enemy image: showing its otherness; depriving it of the linguistic abilities as an essential attribute of humanity, helping dehumanise it; emphasizing its civilisational inferiority; and making the enemy comical. Finally, attention is drawn to the fact that the cinematic image of ‘enemy number one’ contributed to the hierarchisation of languages; everything Russian was associated with communism and therefore perceived as inferior and hostile.

Abstract Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultrasound as the stimulus. By engineering a hyper-efficient dCas12a and effector under a heat shock promoter, we demonstrate a system that can be inducibly activated through thermal energy produced by ultrasound absorption. This system allows versatile thermal induction of gene activation or base editing across cell types, including primary T cells, and enables multiplexed gene activation using a single guide RNA array. In mouse models, localized temperature elevation guided by high-intensity focused ultrasound effectively triggers reporter gene expression in implanted cells. Our work underscores the potential of ultrasound as a clinically viable approach to enhance cell and gene-based therapies via precision genome and epigenome engineering.

The design of multi-storey buildings is a natural trend in the development of a modern metropolis. Obtaining exact solutions when studying their own and forced oscillations within the framework of a continuous homogeneous medium model (continuum mechanics) with an infinite number of degrees of freedom is often difficult to implement. Therefore, in the article (as part of the modernization of the finite element method), the model of a multi-storey building is discretized and endowed with a finite number of degrees of freedom placed in the middle of the finite elements at the nodes (the mass of finite elements is also placed there), which elastically interact with the finite elements of the model that do not have mass. It is believed that the elements of a multistorey building work only for bending, which is fully justified by comparing the frequencies of its bending and longitudinal oscillations. The resolving system of differential equations of oscillations of a multi-storey building, in which expressions for energies (potential, kinetic and Rayleigh) are written in quadratures, is obtained using Lagrange equations of the second kind. In the article, the problems of free oscillations of 3- and 100-storey buildings are solved using Green’s functions, stiffness, mass, compliance matrices, etc. The approximate results obtained in the article, when compared with the little-known approximate results obtained by other methods, as well as exact results (direct and indirect methods of boundary elements), showed a good correspondence.

Background. Voluntary control of goal-directed behavior and mental activity in preschool children plays a key role in knowledge acquisition and future academic achievement. Studies of voluntary control have mainly concerned 6-8-year- old children; much less is known about the ability to exercise voluntary control at early ages. Due to the high prognostic value of the level of development of voluntary control and heterogeneous development of their individual components, it seems actually useful to study age-related changes of these components in children from 3-4 to 4-5 years old. Objective. To compare age-related changes in executive functions (EF) in children age 3-4 years (mean age: 3.5±0.2 yrs; n = 49; 31 boys) and 4-5 years (mean age: 4.5±0.3 yrs; n = 70; 35 boys). Design. To assess the different components of EF we used: 1) a qualitative group and individual testing procedure based on the principles of Luria’s theory of the dynamic localization and organization of higher mental functions; and 2) a computerized testing procedure which included the Bourdon-Wiersma cancellation test, the “Hearts and Flowers” conflict test (the Dots task), and the Corsi block-tapping test. Results. The results showed that different components of voluntary control developed at different rates (heterochronically): there were significant progressive changes from 3-4 to 4-5 years for working memory, assimilation of instructions, switching between separate actions, selective concentration on a target or task, and the distribution of attention. Some other components of EF did not show significant positive dynamics during this period. Conclusion. The results indicate the importance of applying the activity theory approach to the development of cognitive processes in preschool age.

Abstract In this proof-of-concept study, we used a systems perspective to conceptualize and investigate treatment-related dynamics (temporal and cross-sectional associations) of symptoms and elements related to the manifestation of a common functional somatic syndrome (FSS), Globus Sensations (GS). We analyzed data from 100 patients (M = 47.1 years, SD = 14.4 years; 64% female) with GS who received eight sessions of group psychotherapy in the context of a randomized controlled trial (RCT). Symptoms and elements were assessed after each treatment session. We applied a multilevel graphical vector-autoregression (ml GVAR) model approach resulting in three separate, complementary networks (temporal, contemporaneous, and between-subject) for an affective, cognitive, and behavioral dimension, respectively. GS were not temporally associated with any affective, cognitive, and behavioral elements. Temporally, catastrophizing cognitions predicted bodily weakness (r = 0.14, p

Abstract Background Trypanosomatids are parasitic flagellates well known because of some representatives infecting humans, domestic animals, and cultural plants. Many trypanosomatid species bear RNA viruses, which, in the case of human pathogens Leishmania spp., influence the course of the disease. One of the close relatives of leishmaniae, Leptomonas pyrrhocoris, has been previously shown to harbor viruses of the groups not documented in other trypanosomatids. At the same time, this species has a worldwide distribution and high prevalence in the natural populations of its cosmopolitan firebug host. It therefore represents an attractive model to study the diversity of RNA viruses. Results We surveyed 106 axenic cultures of L. pyrrhocoris and found that 64 (60%) of these displayed 2–12 double-stranded RNA fragments. The analysis of next-generation sequencing data revealed four viral groups with seven species, of which up to five were simultaneously detected in a single trypanosomatid isolate. Only two of these species, a tombus-like virus and an Ostravirus, were earlier documented in L. pyrrhocoris. In addition, there were four new species of Leishbuviridae, the family encompassing trypanosomatid-specific viruses, and a new species of Qinviridae, the family previously known only from metatranscriptomes of invertebrates. Currently, this is the only qinvirus with an unambiguously determined host. Our phylogenetic inferences suggest reassortment in the tombus-like virus owing to the interaction of different trypanosomatid strains. Two of the new Leishbuviridae members branch early on the phylogenetic tree of this family and display intermediate stages of genomic segment reduction between insect Phenuiviridae and crown Leishbuviridae. Conclusions The unprecedented wide range of viruses in one protist species and the simultaneous presence of up to five viral species in a single Leptomonas pyrrhocoris isolate indicate the uniqueness of this flagellate. This is likely determined by the peculiarity of its firebug host, a highly abundant cosmopolitan species with several habits ensuring wide distribution and profuseness of L. pyrrhocoris, as well as its exposure to a wider spectrum of viruses compared to other trypanosomatids combined with a limited ability to transmit these viruses to its relatives. Thus, L. pyrrhocoris represents a suitable model to study the adoption of new viruses and their relationships with a protist host.

Due to the developing resistance and intolerance to antiretroviral drugs, there is an urgent demand for alternative agents that can suppress the viral load in people living with human immunodeficiency virus (HIV). Recently, there has been increased interest in agents of marine origin such as, in particular, fucoidans to suppress HIV replication. In the present study, the anti-HIV-1 activity of fucoidans from the brown algae Alaria marginata, Alaria ochotensis, Laminaria longipes, Saccharina cichorioides, Saccharina gurianovae, and Tauya basicrassa was studied in vitro. The studied compounds were found to be able to inhibit HIV-1 replication at different stages of the virus life cycle. Herewith, all fucoidans exhibited significant antiviral activity by affecting the early stages of the virus–cell interaction. The fucoidan from Saccharina cichorioides showed the highest virus-inhibitory activity by blocking the virus’ attachment to and entry into the host’s cell, with a selectivity index (SI) > 160.

Introduction. The article is devoted to the problem of institutional boundaries blurring triggered by the disintegration of traditional institutions, the emergence of new educational formats. The aim is to institutionally analyse the international experience in adult education, explore traditional and new forms, and identify key vectors of change. Materials and Methods. The methodological framework is an ecosystem approach, comparative, institutional and thematic content analyses of scientific publications. In the first step, the authors analysed statistical data and identified three groups of countries according to the level of adult involvement in lifelong learning. In the second step, the authors conducted a socio-historical review of institutional forms of adult education in different countries. Results. The analytical review allowed the authors to identify traditional and new institutional forms, as well as their representation in different countries. It was proved that traditional institutions are being replaced by new formats due to the development of digital technologies and the EdTech industry. Traditional institutions are characterized by internal stability, clear boundaries and hierarchy. They are being replaced by flexible, hybrid institutional structures based on digital communication networks with horizontal links. Roles and statuses of participants in the learning process, instructional design, learning pathways, procedures, assessment technologies, which are the key vectors of institutional transformation, have changed. Discussion and Conclusion. Having analysed historical experience and international best practices in adult education, the authors substantiate a possible evolutionary scenario of institutional changes. The results obtained contribute to the development of scientific ideas about the relationship between the labour market, EdTech industry and institutional forms in adult education to synchronize supply and demand. The study can be used to develop social policy measures for training different population groups and create a national ecosystem of lifelong adult education.

Abstract Background Protists of the family Trypanosomatidae (phylum Euglenozoa) have gained notoriety as parasites affecting humans, domestic animals, and agricultural plants. However, the true extent of the group's diversity spreads far beyond the medically and veterinary relevant species. We address several knowledge gaps in trypanosomatid research by undertaking sequencing, assembly, and analysis of genomes from previously overlooked representatives of this protistan group. Results We assembled genomes for twenty-one trypanosomatid species, with a primary focus on insect parasites and Trypanosoma spp. parasitizing non-human hosts. The assemblies exhibit sizes consistent with previously sequenced trypanosomatid genomes, ranging from approximately 18 Mb for Obscuromonas modryi to 35 Mb for Crithidia brevicula and Zelonia costaricensis. Despite being the smallest, the genome of O. modryi has the highest content of repetitive elements, contributing nearly half of its total size. Conversely, the highest proportion of unique DNA is found in the genomes of Wallacemonas spp., with repeats accounting for less than 8% of the assembly length. The majority of examined species exhibit varying degrees of aneuploidy, with trisomy being the most frequently observed condition after disomy. Conclusions The genome of Obscuromonas modryi represents a very unusual, if not unique, example of evolution driven by two antidromous forces: i) increasing dependence on the host leading to genomic shrinkage and ii) expansion of repeats causing genome enlargement. The observed variation in somy within and between trypanosomatid genera suggests that these flagellates are largely predisposed to aneuploidy and, apparently, exploit it to gain a fitness advantage. High heterogeneity in the genome size, repeat content, and variation in chromosome copy numbers in the newly-sequenced species highlight the remarkable genome plasticity exhibited by trypanosomatid flagellates. These new genome assemblies are a robust foundation for future research on the genetic basis of life cycle changes and adaptation to different hosts in the family Trypanosomatidae.

Introduction. The WHO regularly updates influenza vaccine recommendations to maximize their match with circulating strains. Nevertheless, the effectiveness of the influenza A vaccine, specifically its H3N2 component, has been low for several seasons. The aim of the study is to develop a mathematical model of cross-immunity based on the array of published WHO hemagglutination inhibition assay (HAI) data. Materials and methods. In this study, a mathematical model was proposed, based on finding, using regression analysis, the dependence of HAI titers on substitutions in antigenic sites of sequences. The computer program we developed can process data (GISAID, NCBI, etc.) and create real-time databases according to the set tasks. Results. Based on our research, an additional antigenic site F was identified. The difference in 1.6 times the adjusted R2, on subsets of viruses grown in cell culture and grown in chicken embryos, demonstrates the validity of our decision to divide the original data array by passage histories. We have introduced the concept of a degree of homology between two arbitrary strains, which takes the value of a function depending on the Hamming distance, and it has been shown that the regression results significantly depend on the choice of function. The provided analysis showed that the most significant antigenic sites are A, B, and E. The obtained results on predicted HAI titers showed a good enough result, comparable to similar work by our colleagues. Conclusion. The proposed method could serve as a useful tool for future forecasts, with further study to confirm its sustainability.

Background. The intensification of animal husbandry leads to a violation of the adaptive capabilities of the body, a decrease in productivity and natural resistance of animals. The study of nonspecific factors of protection of the cow's body will allow us to develop ways to increase the immune status and as additional information can be used in breeding work for the selection of highly resistant parent pairs. Purpose. The study of the cellular and humoral link of nonspecific resistance in the development of a stress reaction in cattle after the action of technological stress on the body of cows. Materials and methods. The work was carried out on 20 clinically healthy highly productive black-and-white cows. The stressor for the cows was the regrouping, the change of attendants, the conduct of veterinary and sanitary manipulations. The total number of leukocytes, leukogram, bactericidal and lysozyme activity of the blood serum of cows were studied by standard clinical and laboratory methods and the morphology of leukocytes on a scanning electron microscope before and 3, 14, 30 days after technological stress. Results. On days 3-14 after stress, leukocytosis, neutrophilia, monocytosis and lymphopenia were detected relative to the initial level. When using high-resolution microscopy using a scanning electron microscope, the appearance of NEToses in the blood of cows after technological stress was detected. A decrease in the bactericidal activity of serum on the 3rd day after stress with its subsequent increase was established, on the contrary, an increase in lysozyme on the 3rd day was accompanied by its subsequent decrease by 30 days after the technological stress relative to the initial level. Conclusion. The data obtained indicate that the body's defenses are a dynamic physiological indicator, which must be considered as a general resistance of the cattle body to stressors in order to prevent the disruption of the body's adaptive capabilities.

The issue of differentiation of socio-economic development indicators is relevant for the regions of the Russian Federation. An important condition for the effective and stable development of territories is a favorable demographic situation. This requires a competent and thoughtful demographic policy that will ensure population reproduction and economic development of the constituent entities of the Russian Federation. The study area is the Arkhangelsk Oblast, partly included in the Arctic zone of the Russian Federation, which is of strategic interest to Russia due to its geopolitical, geo-economic position in the modern world. The aim of the work is to analyze the changes in the qualitative and quantitative composition of the population of the Arkhangelsk Oblast, determined by the processes of fertility, mortality, migration, as well as the socio-economic situation and state policy. To analyze the demographic situation, the paper uses traditional methods of analysis (comparison, relative and average values, graphic method). The paper presents the territorial differentiation of the demographic situation in the regions of the Northwestern Federal Okrug. The information base is national and regional statistical information for the last 10 years. The article discusses the interim results of the implementation of the national project “Demography” in the Arkhangelsk Oblast. The results of the study can be useful for state authorities and local governments that manage the regional development of territories within the framework of the national project “Demography”.

over. The disease is associated with impaired function, pain, disability, reduced quality of life and requires total joint replacement in severe cases. There is no clear understanding of the causes of the disease, however, the pathogenesis is well studied. Intra-articular injection of synovial fluid prostheses including hyaluronic acid is one of the approaches to restore the properties of synovial fluid. Stabilometry that is a rare use in orthopaedics, and no use in this aspect was added to the traditional treatment effectiveness assessment. The objective was to explore biomechanical changes in patients with Kellgren-Lawrence grade II-III gonarthrosis who underwent a series of three knee injections of synovial fluid prosthesis over a period of 6 months. Material and methods An open prospective non-comparative study was performed for 30 patients with unilateral gonarthrosis at a mean age of 60 (56; 63) years. The effect of intra-articular injections of a sterile mannitol heat-stabilized biopolymer synovial fluid prosthesis on the biomechanics was evaluated in two samples using WOMAC score (overall and ≥ 30). Biomechanics was assessed in the form of stabilometry. Standardized stabilography and questionnaires were used at 3 follow-up visits: at 0 month (before administration), at 3 and 6 months. Results General sample showed no cases of true drift of the stabilogram parameters, decreased area of the statokinesiogram, and the WOMAC ≥ 30 sample demonstrated an additional improvement in the speed parameters of vertical oscillation at 6 months, a decreased area of the statokinesiogram at 3 months and at 6 months, decreased energy costs at 6 months (p < 0.05). Discussion Positive changes in stabilometry indicated a decreased pain and fatigue reactions in a vertical static position in gonarthrosis during the treatment. Most effects were statistically significant in moderate and severe dysfunction and pain. Intra-articular injection of synovial fluid prosthesis objectively improved the physiometric parameters of the support reaction. Conclusion Three intra-articular injections of a synovial fluid prosthesis based on mannitol-stabilized hyaluronic acid used in gonarthrosis Kellgren-Lawrence grade II-III showed improved body posture parameters of maintaining upright posture and reduced energy consumption in moderate and severe knee pain according to dynamic stabilometry for at least 6 months.

The article presents experiment findings to verify the educational activities program in the field of COVID-19 vaccine prevention for students. The study was conducted at the Moscow State University of Psychology and Education, the analytical sample size is N = 780. Five aspects (as measuring scales) of attitudes towards vaccination against COVID-19 were identified: the benefits of vaccination against coronavirus for a person and society; denial of the coronavirus danger and hope for natural immunity; fear of the side effects of vaccination against coronavirus and distrust of vaccination safety information; confidence in the serious negative consequences of the coronavirus vaccine; disbelief in the proven effectiveness of Russian vaccines at the international level. A comparative analysis of the effectiveness of 4 strategies for influencing student's attitudes to vaccination against COVID-19 was carried out: lectures only (CG), lectures in combination with seminars / webinars in the traditional format (EG1), with discussions of real life cases related to vaccination and its effects (EG2), with holding student's debates (EG3). There are no gender differences between groups. There are differences in age, but the mean difference does not exceed 2 years. At the ascertaining stage, there are no differences on the scales; at the control stage, differences are revealed. On all 5 scales, positive and negative effects in the whole sample are almost equally likely. It was not possible to single out a fundamentally best strategy for educational influence. In general, the effectiveness of educational activities is somewhat greater when conducting lectures in combination with various kinds of seminars compared to lectures alone, but the effectiveness is low everywhere. Cohen's d standard effect sizes do not exceed 0,44. Slightly higher is efficiency when conducting lectures in combination with traditional seminars / webinars or case studies. The student's debates holding strategy did not meet expectations. A number of significant correlations were found between various aspects of attitudes towards vaccination with natural science literacy, logical thinking, verbal intelligence, the degree of fear of COVID-19, personal and situational anxiety. All correlations are weak, but their direction is as expected.

Vibrational and structural properties have an enormous influence on optoelectronic properties of hybrid halide perovskites CH3NH3PbX3 (X = I, Br, Cl), which are perspective materials for different photovoltaic applications. Here, we report results of the first high-resolution optical spectroscopy measurements of large CH3NH3PbBr3 single crystals in wide frequency (20–20 000 cm−1) and temperature (5–300 K) ranges. Fit of polarized far-infrared reflection spectra using Lorentz model of damped oscillators revealed parameters of three phonons at room temperature and 38 phonons at 10 K. An analysis of mid-infrared transmission spectra gave evidence of a strong anharmonicity in this hybrid perovskite. A splitting of some lines observed in the orthorhombic phase was presumably assigned to the tunneling of the CH3NH3+ cation molecule between several potential energy minima. The temperature behavior of the transmission spectra near the fundamental absorption edge was tentatively explained by the competition between two different exciton transitions in CH3NH3PbBr3. Positions of spectral lines and of the absorption edge measured at cooling and heating the sample demonstrate hysteresis loops in the vicinities of phase transitions around 237, 155, and 149 K, thus revealing the first-order nature of all three phase transitions in CH3NH3PbBr3.

Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission and are implicated in various neurological disorders. In this review, we discuss the role of the two fastest iGluRs subtypes, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, in the pathogenesis and treatment of Parkinson’s disease, epilepsy, and amyotrophic lateral sclerosis. Although both AMPA and kainate receptors represent promising therapeutic targets for the treatment of these diseases, many of their antagonists show adverse side effects. Further studies of factors affecting the selective subunit expression and trafficking of AMPA and kainate receptors, and a reasonable approach to their regulation by the recently identified novel compounds remain promising directions for pharmacological research.

Prielbrusye National Park is one of the most popular tourist destinations in Russia. In recent years internal tourism development, stimulated by restrictive measures (due to the COVID pandemic and geopolitical situation), resulted in significant growth of tourist flow to the national park’s territory. A surge in anthropogenic load on the park’s geosystems might degrade them and lead to environmental pollution. This research involved chemical studies of natural waters and snow from the south slope of the Elbrus and audit of the most popular tourist trails. The results have shown that in the snow alongside mountain hiking pistes to the Elbrus all the way up to 4,720 m above sea level (a.s.l.) oil stains concentration is up to 38 times higher than maximum acceptable concentration (MAC). Content analysis of heavy metals in snow cover on the Elbrus slopes and in the river Baksan has shown a significant rise in lead load over the period of 2015–2021 from the trace levels to 1.5 MAC, which is the result of increased anthropogenic load on the south slope of the Elbrus mountain. Ground observation of tourist trails has brought to light numerous patches of vegetation trampling, width extension and branching of the main trail, as well as campfire sites. The research results can be used as a rationale to take measures to reduce recreational load, to improve local geosystems’ condition and to develop a plan of action on nature conservation within the park’s territory.

Objective. To analyze three methods of cleaning and disinfection of removable plate prostheses (protected by patents) available for elderly and senile persons with psychoneurological diseases living in boarding schools. Materials and methods. Technologies of application of the following methods of cleaning and disinfection of removable plate prostheses are described: 1) using an ultrasonic dispersant UZDN-A with a complex of individual reagents; 2) using the ozonizer-sterilizer « Ozon-stom»; 3) with the help of an ultrasonic washing machine «Retona» and an original complex of domestic reagents. Results. Their positive and negative aspects are revealed; it is established: that each method carried out according to the instructions gives 100% disinfection of removable dentures; the most rational method of ultrasonic treatment with the use of a washing machine of the «Retona» type; for the removal of old and dense deposits of plaque, the method with the use of a dispersant UZDN-A is preferable; the method of ozonation for the elderly and senile people suffering from neuropsychiatric diseases can only be used with the participation of medical staff. Conclusion. The considered methods of cleaning and disinfection of removable plate prostheses can be applied to a greater or lesser extent for the elderly and senile in residential homes of psycho-neurological profile, with complete success can be applied to this category of persons living in a family or in residential homes for the elderly without diseases of this profile. According to the volume of positive aspects, the method of cleaning removable plate prostheses using a washing machine of the “Retona” type and the original complex of domestic reagents is most preferable.

The issue of the evacuation of persons belonging to the special contingent during the Great Patriotic War was unavailable for a long time due to the inability to access the NKVD documents. The situation changed in the post-Soviet period after the declassification of the Gulag documentation, when scientists were able to thoroughly study the problem of moving prisoners in the general evacuation process. Consideration of this topic in the context of social and micro-history allows us to shift the focus from the economic dimension of evacuation processes to the motives and behavior of people in the extreme conditions of forced relocation. The examples cited by the authors confirm the thesis that evacuation was not a well-organized and well-regulated process and the plans for it changed during the war. Obviously, relocation of prisoners was not a priority task of the Soviet government, but it could not afford wasteful negligence of the potential labor opportunities that a colossal number of prisoners could offer. One of the serious problems was a significant number of prisons and corrective labor camps in the European part of the USSR’s territory that was occupied by the enemy in the first months of the war. The effectiveness of evacuation was more dependent on the actions of the local leadership of penitentiary institutions and the NKVD than on the directives of the central government. Specific features of evacuation of prisoners include restriction of freedom and being under escort at the time of transportation, which led to significant losses, for example, during the enemy air raids, as well as spontaneous character of providing food and medical care and lack of prospects for prisoners to change their social status and position at the place of their new location. To reduce the number of evacuated prisoners, at the beginning of the war the authorities went to the length of releasing those prisoners who were convicted of minor crimes (usually sentenced to 1 year or less). During the evacuation, the guards used extreme measures against the escorted prisoners, up to execution, most often in situations when further movement was difficult. Determining the exact number of prisoners who died during evacuation remains an open question.

This article contributes to a better understanding of theoretical models and empirical evidence revealing the impact of social inclusion of non-formal education on professional and personal development in the context of five generations. Based on the typology of peculiar generations in the non-formal education market, including their interest and motivation, we have identified the differences between the benefits and the barriers to social inclusion in order to overcome social inequalities and digital inequities. Due to the fact that all generations use non-formal education, but its contribution to social inclusion differs from generation to generation, our research questions are as following: What is the impact of non-formal education on social inclusion? How do non-formal education practices differ across generations? The article critically engages with non-formal education as a resource of social inclusion highlighting the low level of inclusion of five generations. To show the specificity of five generations’ social inclusion we develop a data collection method including a questionnaire survey of the population based on the typology of generations. As such, the research shows that today inclusion through non-formal education, mobility in the labor market due to retraining, as well as inclusion in new social ties, study groups, adaptation to new challenges do have generational characteristics.

The relevance of the research is due to the development and widespread introduction of digital technologies in a wide context of socio-cultural and economic processes, the inevitable digital transformation of the processes of education, upbringing and development of the younger generation. The teacher is seen as the main agent of digital literacy, the vehicle to pass on digital culture. The teacher acts as the main subject of two processes: one of digital transformation of the educational environment; the other of the retraining for the digital economy at the level of general education. The objective of the research is to assess the digital competence of teachers in educational organizations of Saratov and the Saratov region as well as their readiness to create a digital educational environment. The research reveals modern Russian and foreign scientific approaches explaining the essence of digital competence as a meta-subject competence, its specifics in relation to teachers’ activities. The authors identify the content of four components of teachers’ digital competence and six ways according to which it can be formed and developed among educators. The article provides a systematic approach revealing the leading functions of a teacher in the educational context, when the latter is created with the help of digital tools. The essential indicators are singled out. They are used to propose a system of levels according to which digital competence is built: they are basic, optimal, advanced. The authors conducted an online survey of teachers of Saratov and the Saratov region, had conversations with them and observed their work (N = 1500). Basing on the data, the article presents an analytical report on the real state of how and to what extent teachers’ digital competence is formed depending on their professional experience. The assessment of the degree of teachers’ readiness to create a digital educational environment is given. On the basis of pedagogical modeling, the article proposes the ways and methods to solve the problem of interest at different stages of the professional life cycle.

The article is devoted to the search for new approaches and forms of control over the assimilation of students’ knowledge at the initial stage within the framework of a worldview approach to teaching Russian as a foreign language. Based on the analysis of existing forms and types of control, a conclusion was made about their incomplete compliance with the goals of teaching live communication in Russian. The main problem is the lack of motivation to form an oral or written statement. The thematic principle for the organization of control over the assimilation of listening / speaking skills is outdated, it does not reflect the specifics of modern interpersonal communication, including socially conditioned one. Based on this conclusion, the article outlines approaches to the creation of an expanded comprehensive control system aimed, on the one hand, at testing (control) skills of free communication, and, on the other hand, at psychological stimulation (psychological boost) of communication.

Relevance of the article is due to changes in the activities of inpatient social services in connection with the introduction of the quarantine regime in 2020-2022. Adaptation to new conditions of life, communication and activity in the pandemic and post-pandemic world has led to the design of new technologies for leisure, communication, development and participation of residents of residential homes for the elderly and disabled, neuropsychiatric boarding homes. The purpose of the article is to analyze the experience in implementation and scientific monitoring of the project «Conquer your Height» on the organization of intellectual team games online in the conditions of pandemic and post-pandemic restrictions on the basis of stationary social service institutions. Research methods: systematic and comparative approach, questionnaire survey met-hod, expert surveys and discussions, methodology for the study of subjective well-being, methodology for the study of professional burnout. Results. Within the framework of the partnership of the «Autonomous Non-profit Organization for the elderly and disabled "Old Age is a joy", Rostov-on-Don», the Social Technologies Department of the Southern Federal University and ten inpatient social service institutions of the Rostov region (residential homes for the elderly and disabled and neuropsychiatric boarding homes), the project «Conquer your Height» was implemented in 2022. The essence of the project was to organize a series of intellectual team games in the style of «What? Where? When?» in an online format in conditions of inpatient social services during quarantine and forced isolation. In order to objectively and reasonably assess the effectiveness of the project, its positive effects for participants, employees and institutions, scientific monitoring was carried out (at the entrance and at the exit). Conclusions. During the involvement in the project, cognitive and social activity, subjective well-being and self-esteem of residents of residential or boarding homes, the intensity and quality of communications between beneficiaries and specialists have increased; there is an increase in solidarity, improvement of the socio-psychological climate, information and methodological infrastructure and socio-cultural environment of institutions, growth of professional self-esteem and reduction of the risks of burnout of specialists.

The research examines the proposals of the “Cornwall Consensus” in the context of their possible application in Latin America. The authors argue that these proposals could contribute to the development of a new economic development strategy for the post-liberal period. It is likely that the “Cornwall Consensus” proposals become dominant in shaping the global agenda on the new economic paradigm. Although it is important to mention that nowadays there also also “Beijing” and “Delhi” consensuses those are linked to the Chinese and Indian models of economic liberalization and constitute an alternative to the “Washington Consensus”. The article analyzes the effectiveness of the “Washington Consensus” adjustment mechanism, carries out a comparative analysis of the Latin American economies that pursued both liberal and statist development models. Then the article examines the main recommendations and ideas of the “Cornwall Consensus”, the prospects of adapting the Latin American region to the proposals of a new development model against the background of existing experience in implementing the recommendations of the “Washington Consensus”, its consequences and existing “post-neoliberal” alternatives. The authors conclude that, despite the adaptability of the Latin American economies, the question remains whether the proposals of the “Cornwall Consensus” can contribute to the revival of the development policy in Latin America aimed at creating a new type of “welfare state”? The study concludes that the proposals of the “Cornwall Consensus” could contribute to the formulation of a new development policy, since the “welfare state” in its Latin American version, regardless of whether “neoliberal” or “progressive”, has exhausted itself.