Georgy Lebedev

Ultraconserved elements (UCEs) are genomic sequences exhibiting exceptional evolutionary conservation across vertebrate taxa, yet their biological functions remain poorly understood. Here, we investigated the functional and expression characteristics of human protein-coding genes containing UCEs. Observed UCE distributions across Gene Ontology and manually curated, mutually exclusive functional groups of genes were compared with 1000 randomized UCE datasets that preserved natural UCE clustering. UCEs are preferentially located within genes involved in multilayered regulation, including transcription, chromatin organization, RNA processing, and ubiquitin-mediated protein regulation, whereas genes associated with membrane, extracellular, structural, transport, and metabolic functions are relatively UCE-poor. Within enriched groups, UCE accumulation is concentrated in multifunctional developmental regulators rather than in constitutive cellular machinery. Compared with length-matched UCE-free controls, UCE-rich genes showed higher and broader expression across 68 adult tissues and significantly higher prenatal expression in all seven organs examined. This expression excess was greatest in the developing brain and cerebellum and was most pronounced during early prenatal development. UCE-rich transcription factors are specifically enriched in developmental and chromatin-regulatory programs, including HOX-related embryonic patterning. These findings indicate that UCEs preferentially mark genes involved in several levels of cellular regulation and link ultraconservation to multilayered gene regulation and early human development.

Digitalization of healthcare is becoming an integral part of providing medical care to the population. The introduction of artificial intelligence (AI) in medicine leads to the formation of “digital thinking” and public trust in digital healthcare. The purpose of this literature review was to summarize the data related to AI in general and to the study of sarcoidosis – a multiorgan granulomatosis of unknown origin. The most widely represented works are on image recognition, which use different approaches. In pulmonology, this is work with fluorograms, radiographs and computed tomograms. At the same time, comprehensive work is underway on radiomics – comparing image diagnostic data with laboratory and functional data. Programs have been created that recognize speech, analyze the texts of conclusions, the results of tissue diagnostics and even patient auscultation data. In sarcoidosis, the creation of systems to support medical decision-making has been underway since the 1990s, with priority given to Russian phthisiologists, pulmonologists, and mathematicians. In international practice, deep learning has been most fully studied for the diagnosis of pulmonary sarcoidosis. Radiomics was mainly used to differentiate sarcoidosis from malignant tumors. Work is underway to differentiate sarcoidosis and normal data in pulmonary and cardiac sarcoidosis, and for remote self-monitoring of patients. Literature analysis has shown that in clinical medicine, the success of AI is possible only in close cooperation with an expert physician or a multidisciplinary committee of physicians.

Significance. The relevance of the topic is substantiated by the dissonance between the objectively proven advantages of remote patient monitoring and the subjective factors hindering its implementation in practice. Even technically advanced systems risk remaining unclaimed without solving the problem of physician's motivation, which will limit the potential for digital transformation of healthcare. Purpose. To identify the main physician's motivation factors to use remote patient monitoring in medical practice, as well as barriers preventing its implementation. To propose a set of measures based on the identified factors and barriers aimed at different participants in the remote monitoring ecosystem. Material and methods. To achieve this research goal, an analysis of scientific literature and data on the implementation and use of remote patient monitoring and other telemedicine technologies was carried out. Information was searched and analyzed in publicly available electronic databases: Medline, PubMed, Google Scholar, e-Library. Results. Physician's motivation to use remote monitoring is quite balanced and pragmatic, and is primarily determined by the clinical benefit to the patient and the increased effectiveness of their own work. A set of measures based on this motivation structure has been developed including targeted recommendations for all participants and stakeholders, aimed at strengthening these key factors. Conclusion. The implementation of remote patient monitoring is rather a comprehensive organizational transformation of the healthcare system than a technical project. Its successful implementation requires coordinated efforts by all participants: from developers creating high-quality and user-friendly products to changing working processes of clinics, updating normative regulation and government funding, as well as the willingness of doctors and patients themselves to switch to a new format of interaction. Keywords. remote patient monitoring; telemedicine; physician's motivation; implementation barriers

Significance. In recent years, much attention has been paid to the development of telemedicine and digital technologies in the field of healthcare. One of the most promising areas is remote health monitoring, which is a tool that helps improve patient adherence to medical recommendations and maintain a healthy lifestyle. Purpose. To identify the factors contributing to and hindering the effective use of remote monitoring technologies in clinical practice, with an emphasis on their impact on patient behavior and compliance with medical recommendations. Material and methods. To achieve the stated objective of the study, an analysis of scientific literature and data on the topic of using remote health monitoring was conducted. The search and analysis of information was carried out in publicly available electronic databases: Medline, PubMed, Google Scholar, Elibrary. Results. An analysis of theoretical research and technological solutions in the field of remote monitoring was carried out and a number of factors have been identified, the combined effect of which provides increased patient adherence to therapy and improved clinical outcomes when using remote monitoring systems, as well as a number of factors limiting the use of remote monitoring technologies as a tool to increase patient adherence to therapy. Conclusions. Remote monitoring has been shown to improve clinical and economic outcomes by reducing hospitalizations, improving quality of life, and reducing costs for both patients and the healthcare system as a whole. Keywords: remote monitoring; information technology; digitalization of healthcare; artificial intelligence; Internet of Things; telemedicine, adherence to therapy.

Introduction. Respiratory diseases are number one in the structure of general morbidity of the population of the Russian Federation. The main complication of respiratory diseases is respiratory failure, which may be treated with long-term oxygen therapy (LTOT) and respiratory support (RS): non-invasive mechanical lung ventilation (NIV) and invasive mechanical lung ventilation (IV). International medical experience indicates a widespread enough implementation of respiratory support and oxygen therapy at home (RS and OT at home) for patients including whose requiring palliative medical care.Aim. The purpose of the study was to evaluate the clinical results of implementation of respiratory support and oxygen therapy at home.Materials and methods. The study included 98 patients with chronic respiratory failure (CRF). All patients used RS and OT at home according to the Study Protocol. All patients were divided into 3 groups: LTOT - 47 patients, NIV in combination or with-out LTOT - 43 patients, IV in combination or without LTOT - 8 patients. The estimated parameters of the patients' condition were measured at the initiating visit and three subsequent control sessions. The planned duration of the Study was 9 months.Results. During the Study, a statistically significant decrease in the severity of symptoms of respiratory failure was noted (CAT and mMRC scales) as well as an improvement in the quality of life and the general condition of the patient (SF-36 questionnaire and Karnovsky scale). During the study, 38 patients required hospitalization: in 8 cases hospitalization was associated with an exacerbation of CRF. The number of successful outcomes was 87 cases.Conclusion. The Study showed that RS and OT at home is an effective and safe medical technology for patients with CFR, which reduces the manifestation of symptoms, improves the quality of life, reduces the number of hospitalizations associated with exacerbation of respiratory failure, reduces mortality, and demonstrates the effectiveness of using a modern respiratory equipment at home, as well as telemedicine technologies.

RNA polymerase III (Pol III) transcribes tRNA genes using type II promoters. The internal control regions contain a Box A and a Box B, which are recognized by TFIIIC. The 5′-flanking regions of tRNA genes clearly play a role in the regulation of transcription, but consensus sequences in it have been found only in some plants and S. pombe; although, the TATA binding protein (TBP) is a component of the TFIIIB complex in all eukaryotes. Archaea utilize an ortholog of the TBP. The goal of this work is the detection of the positions of intragenic and extragenic promoters of Pol III, which regulate the transcription of tRNA genes in eukaryotes and archaea. For this purpose, we analyzed textual and some structural, mechanical, and physicochemical properties of the DNA in the 5′-flanking regions of tRNA genes, as well as in 30 bp at the beginning of genes and 60 bp at the end of genes in organisms possessing the TBP or its analog (eukaryotes, archaea) and organisms not possessing the TBP (bacteria). Representative tRNA gene sets of 11 organisms were taken from the GtRNAdb database. We found that the consensuses of A- and B-boxes in organisms from all three domains are identical; although, they differ in the conservativism of some positions. Their location relative to the ends of tRNA genes is also identical. In contrast, the structural and mechanical properties of DNA in the 5′-flanking regions of tRNA genes differ not only between organisms from different domains, but also between organisms from the same domain. Well-expressed TBP binding positions are found only in S. pombe and A. thaliana. We discuss possible reasons for the variability of the 5′-flanking regions of tRNA genes.

Objective: analysis of domestic scientific literature to identify ways of applying the Beers criteria, frequency of prescriptions and the structure of potentially inappropriate medications (PIMs) in elderly patients.Material and methods. The search for publications was carried out in Google Scholar abstract database, as wel as in eLibrary and CyberLeninka information-bearing networks for the period from 2013 to 2023. In total, 34 articles were found, among which 18 sources used Beers criteria as a tool for identifying PIMs.Results. In inpatient therapeutic departments, the maximum frequency of PIMs prescriptions according to the Beers criteria was 66.6% of cases, in surgical departments – 70%, in psychiatric departments – 90.4%, and in outpatient treatment settings – 28%. Non-steroidal anti-inflammatory drugs at different diseases were the most prescribed group of PIMs in both inpatients and outpatients. Surgical hospitals took the leading position in prescribing these drugs; specifically, more than 2/3 of elderly patients (75%) received them. According to two studies describing clinical cases of drug-induced falls in patients, the Beers criteria were effective in identifying drugs that can provoke this condition. One of papers presented application of Beers criteria to assess the economic affordability of replacing PIMs with safer new generation drugs.Conclusion. An analysis of domestic literature data has shown various ways of applying the Beers criteria, the frequency of prescriptions, and the most common PIMs. This information will help healthcare workers to be more wary of such drugs and think over applying the Beers criteria in routine practice of geriatric patients, which will further prevent or reduce the number of adverse drug reactions.

Significance. Development of information technologies as an integral part of the technological progress has led to the transformation of society, accompanied by the emergence of new environments and interaction tools. In modern conditions, a digital twin concept is a natural consequence of the emergence and development of information space and information society. The purpose of the study is to justify the need to define the concept of a medical digital twin. Material and methods. In order to achieve this goal, relevant domestic and foreign sources of literature, as well as standardization documents valid within the territory of the Russian Federation were analyzed. The search for normative-legal acts and standardization documents was carried through the information and legal reference systems “Garant” and “ConsultantPlus”. Results. The authors have analyzed the existing official definitions of the concept of a “digital twin” and proposed an approach to define the concept “a digital twin for medical purposes”. Conclusion. There is a current urgent need to define a digital twin concept in relation to its use in medicine. Keywords. Digital twin; definition; GOST; standard; healthcare; medicine

The article describes a method for assessing the malignancy potential of thyroid nodules and their stratification according to the European Thyroid Imaging And Reporting Data System (Eu-TIRADS) scale based on ultrasound diagnostic images using an artificial intelligence system. The method is based on the use of transfer learning technology for multi-parameter models of convolutional neural networks and their subsequent fine tuning. It was shown that even on a small dataset consisting of 1129 thyroid ultrasound images classified by 5 Eu-TIRADS categories, the application of the method provides high training accuracy (Accuracy: 0.8, AUC: 0.92). This makes it possible to introduce and use this technology in clinical practice as an additional tool (‘second opinion’) for an objective assessment of the risk of malignancy in thyroid nodules for the purpose of their further selection for fine needle biopsy.

Recent developments in Digital Medicine approaches concern pharmaceutical product optimization. Artificial Intelligence (AI) has multiple applications for pharmaceutical products’ lifecycle, increasing development speed, quality of the products, and efficiency of the therapy. Here, we systematically review the overall approach for AI implementation in pharmaceutical products’ lifecycle. The published studies in PubMed and IEEE Xplore were searched from inception to March 2022. The papers were screened for relevant outcomes, publication types, and data sufficiency, and a total of 73 (1.2%) out of 6131 studies were retrieved after the selection. We extracted the data according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. All Artificial Intelligence systems could be divided into multiple overlapping categories by implementation. For the 177 projects found, the most popular areas of AI implementation are clinical trials and pre-clinical tests (34%). In second place are novel small molecule design systems, with 33% of the total. The third most popular scope for AI implementation is target identification for novel medicines. More than 25% of the systems provide this functionality. It is interesting that most of the systems specialize in only one area (102 systems—57%). None of the systems provide functionality for full coverage of the lifecycle and function in all categories of the tasks. This meta-analysis demonstrated that Artificial Intelligence solutions in pharmaceutical products’ lifecycle could find numerous implementations, and none of the available market solutions covers them all.