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This article presents a literature review on the molecular mechanisms of the inner ear damage and current approaches to restoring its cellular structures. The search for sources was carried out in the RSCI, Scopus, PubMed and Google Scholar databases. The advantages and limitations of various approaches to cochlear hair cell regeneration, as well as prospects for their development, are discussed. Particular attention is paid to discoveries in the field of gene therapy for inner ear diseases. Представлен обзор литературы о молекулярных механизмах повреждения внутреннего уха и современных подходах к восстановлению его клеточных структур. Поиск источников проведен в базах данных РИНЦ, Scopus, PubMed, Google Scholar. Рассматриваются преимущества и ограничения разных подходов к регенерации нейроэпителия улитки, а также перспективы их развития. Особое внимание уделено открытиям в области генной терапии заболеваний внутреннего уха.
The aim of this study was to develop a quantitative method for assessing the ultrastructure of cardiomyocyte mitochondria in the right atrial appendage of patients with chronic heart failure (CHF). A single-center prospective study included 39 patients aged 67 [58; 71] years who underwent coronary artery bypass grafting. The inclusion criteria were as follows: heart failure with a left ventricular ejection fraction of <50%, atherosclerotic plaques in two or more large coronary arteries of 70% or greater, and the cardiac team's decision to perform coronary artery bypass grafting. To perform electron microscopy, biopsy samples were collected from the right atrial appendage during coronary artery bypass grafting. Two calculated parameters were used for the analysis: "total area of interfibrillar mitochondria" and "ratio of outer to inner membrane length". Based on these, the total index was calculated by the formula: the "total area of interfibrillar mitochondria" / the "ratio of outer to inner membrane length". The median values of the calculated parameters characterizing the ultrastructure of cardiomyocyte mitochondria in the right atrial appendage were as follows: 43.7 [35.9; 54.3]% for the "total area of interfibrillar mitochondria", 31 [25; 37]% for the "ratio of outer to inner membrane length", and 1.4 [0.95; 2.00] for the total index accounting for both ultrastructural characteristics of mitochondria: the "total area of interfibrillar mitochondria" / the "ratio of outer to inner membrane length".To assess the clinical significance of the proposed total index, associations between the obtained values and atrial fibrillation (AF) were studied. Mitochondrial ultrastructural changes were more pronounced in patients with both AF and CHF. However, some parameters had no statistically significant differences: the total area of interfibrillar mitochondria was lower in patients with AF (42% vs 49%, p=0.224), and the ratio of outer to inner membrane length was higher in patients with AF (35% vs 31%, p=0.125). The total index was significantly lower in patients with AF (0.96 vs 1.75, p=0.021). ROC analysis was performed to identify a connection between total index and AF, and AUC was 0.773 (p=0.021). The proposed total index for analyzing cardiomyocyte micrographs, calculated as the "total area of interfibrillar mitochondria" / the "ratio of outer to inner membrane length", provides a comprehensive characterization of mitochondria that accounts not only for their number and size but also for their internal structure.
The aim of the study was to evaluate the possibilities and limitations of using the immunohistochemical detection of Iba-1 protein for morphofunctional analysis of microglia under different conditions. In the study we used brain samples from Wistar rats at different ages: 7 days of postnatal development (n=18), 14 days of postnatal development (n=18), 4-6 months (n=22); the brain samples from 3-6-month-old SHR (spontaneously hypertensive rats) male rats (n=4); human cerebral cortex samples (n=10). Rabbit polyclonal antibodies against calcium-binding protein Iba-1 (Biocare Medical, USA) were used to detect microglia immunohistochemically followed by light and confocal laser microscopy. A previously developed original technique was applied to simultaneously detect microglial cells and amyloid plaques. Iba-1 protein in microglial cells was shown to be present in grey and white matter in all cerebral regions under study. Microglial cells in different regions were noted to be characterized by pronounced structural and functional features when stained for Iba-1. In addition to microglial cells, in the rat brain there were found other Iba-1-immunopositive macrophages, which were tissue cerebral macrophages differing from microgliocytes by specific morphology and localization. Iba-1 protein was demonstrated to be present in microglial cells in all investigated stages of postnatal development that makes Iba-1 an appropriate marker for comparative ontogenetical studies of microglial cells. The localization of Iba-1 in the bodies and processes of microgliocytes enables to more clearly identify the complex ramified cell morphology and make three-dimensional reconstructions. In the brain of spontaneously hypertensive rats (SHR line rats) the Iba-1-immunopositive microglia were shown to have a number of structural and functional features indicating the moderate activation of microglia. 48 h after ischemic injury, an anomalously great number of large Iba-1-immunopositive cells with amoeboid morphology were detected in the gray matter of the striatum in an ipsilateral hemisphere near the injured area in the rat brain. Microglial cells in human cerebral cortex were noted to be localized in the majority of the detected amyloid plaques and characterized by amoeboid morphology indicating their severe activation. The presented findings suggest Iba-1 protein to be a reliable and universal microglial marker. The immunohistochemical detection of the protein enables to identify and analyze qualitatively and quantitatively microglial cells in different brain regions in human and laboratory animals under normal and pathological conditions. The limitations of using Iba-1 as a marker of microglia include the inability to determine the microglial activation vector and the difficulty in distinguishing between microglia and infiltrating macrophages of the brain in pathology. In such cases, it is necessary to improve the technology for detecting microglia that can be based on using a multi-marker analysis.
The aim of the study was to identify the regulatory potential of ascorbic acid and HOO• radicals in the formation of extracellular DNA networks and the internalization activity of mononuclear cells from rat blood and spleen. The isolated mononuclear cells from rat blood and spleen were exposed to ascorbic acid (10 and 50 μM), hydroperoxyl radicals (HOO•), and their combination. The following parameters were assessed: membrane toxicity (using the trypan blue exclusion test), internalization activity with latex particles (endocytosis), extracellular DNA networks formation, intracellular reactive oxygen species production kinetics (flow cytometry with the intracellular fluorescent probe dihydrorhodamine 123, DHR123), tryptophan fluorescence, glycated protein levels, and cellular redox balance (NAD+ and NADH). Ascorbic acid at the concentrations of 10 and 50 μM suppressed the formation of extracellular DNA networks. At a concentration of 50 μM, it exerted a membrane-toxic effect, reduced tryptophan fluorescence, increased glycated protein levels, and shifted the redox balance toward oxidation (increased NAD+ and decreased NADH). HOO• radicals at concentrations ≥200 μM demonstrated concentration-dependent effects: stimulation of endocytosis, increased formation of extracellular DNA networks, and elevated intracellular production of reactive oxygen species. At a concentration of 600 μM, HOO• radicals reduced tryptophan fluorescence and depleted both NAD+ and NADH levels. The stimulatory effects on endocytosis and extracellular DNA network formation in response to HOO• radicals were the most pronounced in splenic mononuclear cells.The analysis of the combined action of HOO• radicals and ascorbic acid showed that ascorbic acid at a concentration of 10 μM protected cells from the membrane-toxic effects of HOO• radicals and reduced the formation of extracellular DNA networks induced by HOO• radicals. The ascorbic acid at a concentration of 50 μM enhanced the membrane-toxic effect of HOO• radicals and reduced the internalization activity of mononuclear cells. HOO• radicals at concentrations ≥200 μM stimulated the internalization activity of mononuclear cells and the intracellular generation of reactive oxygen species, whereas HOO• radicals at 600 μM caused a decrease in both oxidized and reduced coenzyme levels and increased the formation of extracellular DNA networks. Ascorbic acid at a concentration of 10 μM exhibited antioxidant properties and protected cells from the damaging effects of HOO• radicals, while at 50 μM it acted as a synergistic pro-oxidant, enhancing the membrane-toxic effect of the radicals and reducing the internalization activity of cells.
The aim of the study was to assess the efficiency of the mandibular bone defect regeneration by administering mesenchymal stem cells (MSC) from the Bichat's fat pad (B-MSC), as well as the osteoblasts differentiated from them, according to the morphological findings. The experimental study was carried out on male Wistar rats (n=120) aged 2 months, weighing 250-300 g. B-MSCs and the osteoblasts differentiated from them were used for the regeneration of rat mandibular bone defects formed by a round bur. In the control group, the defect was not filled, the defect was healing under the blood clot. The biopsy specimens were histologically examined on days 14, 30, and 90 after the injury formed. The infiltration of the bone defect site by inflammatory cells was revealed for all study groups 14 days after the injury. The groups with cell administration showed the resorption of bone trabeculae (B-MSC and osteoblast groups) and a large number of capillaries (an osteoblast group). On day 30 after the injury, the preparations of the groups with cell administration demonstrated a large number of capillaries (B-MSC and osteoblast groups) and primitive bone trabeculae with osteoblasts (an osteoblast group). Active osteoclastic resorption and inflammatory infiltration were revealed in the control group. The groups with cell administration 90 days after the injury, in contrast to the control group, were found to have the formation of spongy mature bone tissue (B-MSC and osteoblast groups), the presence of bone mineralization and myeloid bone marrow (an osteoblast group) in the bone defect zone. It indicated high regenerative potential of the cells used when replacing a bone defect and the significant reduction of a regeneration period.
The aim of the study was to evaluate the applicability of radioimmunoconjugates (RIC) of nanobodies against PD-L1 and HER2/ neu for the diagnosis and therapy of malignant tumors. The nanobodies to human biomarkers PD-L1 and HER2/neu were conjugated with radionuclides 68Ga and 177Lu using the chelating agent DOTA. RIC biodistribution was studied in experimental models on F1 (DBA/2xBALB/c) mice, which were inoculated with genetically modified CT26 murine carcinoma cells expressing human PD-L1 or HER2/neu. RICs containing the isotope 68Ga and intended for tumor detection were administered to animals intravenously at a dose of 1.0-1.2 MBq. In 0.5, 1.5, and 4 h the radioactivity accumulation in specific tumors carrying human biomarkers was assessed using direct dosimetry compared with control tumors. RICs containing 177Lu were administered for therapy at a dose of 0.8-1.6 MBq, and studied similarly for 96 h after administration. Results. After RICs containing 68Ga were administered to mice, the greatest difference between specific and control tumors was observed in 1.5 h. At the same time, there was a multiple excess of the specific tumor radioactivity over the blood and muscle tissue radioactivity, which should provide high contrast imaging. After administering RICs containing 177Lu to mice, the radioactivity in specific tumors persisted for 48 h producing a long-term effect of the radioisotope on the tumor. With the introduction of all RICs, there was a rapid elimination of radioactivity from the blood through urine, which was associated with the use of nanobodies with a molecular weight of 13 kDa and not containing sites of interaction with Fc receptors. There were found the significant accumulation and long-term retention of radioactivity in the kidneys. The work revealed a dependence of the radioactivity biodistribution on the isotope used: the time-normalized radioactivity of some organs and tissues, including tumors, after the administration of RICs containing 68Ga appeared to be higher than after administering the RICs of the same specificity, but containing 177Lu radioisotopes. The findings indicated the functional suitability of the pairs of RIC nanobodies with 68Ga and 177Lu radioisotopes for theranostics of malignant tumors expressing PD-L1 and HER2/neu biomarkers.
The aim of the study was to evaluate the efficiency of the KANU-Net 2D architecture based on U-Net in medical segmentation tasks of 2D brain MRI images on BraTS dataset with a limited number of training samples. The experiments were carried out using the subsamples containing 50, 100, and 150 images. The study described the data preprocessing steps, including normalization, gamma correction, cropping, and augmentation. A combination of Dice loss and BCE loss was used as a loss function. The network was optimized using AdamW. The network operation performance was evaluated using Accuracy and Dice coefficient for each region and its mean Dice. KANU-Net 2D was experimentally demonstrated to achieve competitive performance comparable to current SOTA models of convolutional neural networks when trained on small samples. Specifically, the mean Dice coefficient reached 0.851 when using 100 training samples. The conducted studies showed KANU-Net 2D network to outperform the Med-DANet segmentation model both in terms of a mean value and region classes. The model effectiveness for different tumor regions highlighted the ability of the KAN-based (Kolmogorov-Arnold network) approach to adapt to various image characteristics in medical segmentation tasks. The obtained results demonstrated the undeniable promise of applying KAN for medical image segmentation in small samples and can lay the foundation for further research in this field.
The aim of this study was to study the role of transmission electron microscopy (TEM) in assessment of the phenotype of astrocytes obtained with the directed differentiation technique from induced pluripotent stem cells (iPSCs) from a healthy donor and from a patient with a hereditary form of Parkinson's disease (PD). Monolayer astrocyte cultures differentiated from iPSCs from a healthy donor and a PD patient having the G2019S mutation in the LRRK2 gene were used in the study. The obtained glial cultures were characterized using real-time PCR and immunocytochemical staining for glia-specific genes and proteins. TEM was used to examine astrocyte ultrastructure. PCR analysis and immunocytochemical staining demonstrated that cell lines received from a healthy donor and a PD patient expressed the required pattern of glia-specific genes and synthesized astrocyte-specific proteins. However, some glia-specific genes were expressed at reduced levels by mutant cells. One of the most typical ultrastructural features of astrocytes received from iPSCs from a PD patient was destructive changes in mitochondria, including mitochondrial clearing, swelling, and cristae destruction. In many cells, mitochondria were completely absent after a long culturing. Another characteristic feature of cells with a mutation in the LRRK2 gene was the accumulation of vacuoles with contents of varied electron density. Distinct changes in the ultrastructure of nuclei, protein-synthesizing organelles, and cytoskeletal elements were also seen in cultured astrocytes with a PD-associated LRRK2 mutation. Here, the morphometric study did not reveal any differences in the average cell area, nuclear area, cytoplasm area, or nuclear-cytoplasmic ratio between astrocytes of the control line and the PD mutation line. Reprogramming and obtaining of astrocytes from iPSCs received from a donor with a PD-associated mutation in the LRRK2 gene allow to assess the nature and dynamics of pathological morphochemical and ultrastructural changes caused by the mutation during gliogenesis. The use of combined techniques (PCR, immunocytochemistry, TEM) to compare cell cultures differentiated from iPSCs allow to assess, on the one hand, general culture parameters, such as the dynamics of culture differentiation based on changes in the expression level of specific genes and immunocytochemical markers, and on the other hand, morphofunctional changes at the level of individual cells. TEM demonstrates significant potential for studying cell cultures differentiated from iPSCs. This technique is instrumental for phenotyping the resulting cells based on their ultrastructure, assessing the degree of their morphological maturity, and identifying minor ultrastructural changes in cells, both pathological and differentiation-associated. The results of this TEM-based study indicate a pronounced decrease in mitochondrial viability and other ultrastructural abnormalities, thus confirming the idea of a significant role of astroglia in the development of the neurodegenerative process in the LRRK2-associated PD; hence, astroglia can be a basis for development of new approaches as well as for searching pharmacological targets in the pathogenetic therapy of the disease.
The aim of the study was to develop a novel approach to treatment of non-healing wounds by using a portable Biogan bioprinter and an ink based on fibrin-gelatin hydrogel and spheroids derived from mesenchymal stromal cells (MSCs) from adipose tissue in a model of ischemic pig wound. To simulate the wound, titanium sealing rings were used, which mechanically compressed the skin to create a local ischemic wound. A day after, the rings were removed, and the epidermis of the skin was excised. The wound was treated one day and 2 weeks after the wound infliction. For this purpose, a combined ink was applied to the wound surface using a portable Biogan bioprinter (the prototype was developed by the authors). An adapted passive mixer allowed uniform mixing of the bioink based on a fibrin-gelatin hydrogel and spheroids derived from human adipose MSCs. Wound closure rates were assessed over 36 days, followed by histological analysis. The use of inks based on fibrin-gelatin hydrogel and spheroids from adipose MSCs significantly accelerated healing, as evidenced by the reduction in the wound area compared to the control group and hydrogel-only group, as well as the complete restoration of all skin layers by day 36. The therapeutic effect of the developed approach was due to the spheroids in the bioinks and not to the hydrogel. The use of the developed mixer did not reduce the cell viability and ensured convenient ink application to the wound surface.
The article provides an overview of data on the prevalence, conservative, and surgical treatment of chronic suppurative otitis media, which remains one of the most common and socially significant diseases of the otorhinolaryngological structures, accompanied by a high frequency of complications and persistent hearing loss. The evolution of treatment methods is traced, and special attention is given to the prospects for the use of tissue engineering constructs and tissue engineering in general. The possibilities of creating three-layer grafts are highlighted, taking into account the achievements of scientific and technological progress. It has been shown that classical methods of surgical correction of defects of the eardrum, including the use of autografts (temporal fascia, cartilage), do not always allow to achieve a sustainable anatomical and functional result, especially in large and persistent perforations. There is a tendency of active development of the direction of regenerative medicine and tissue engineering, allowing to create biocompatible grafts with specified properties, to introduce mesenchymal stem cells, as well as to use growth factors to stimulate reparative processes. The review analyzes data on the effectiveness of classical and innovative tympanoplasty methods, as well as the prospects for using 3D bioprinting, collagen matrices, and cellular technologies to restore the integrity of the eardrum. Special attention is paid to the results of clinical and experimental studies that demonstrate a significant increase in the frequency of successful closure of perforations when using tissue engineering constructs and growth factors compared to traditional methods. The article discusses unresolved issues related to the optimization of technologies, the standardization of protocols, and the need for further multicenter studies to widely implement innovative approaches in clinical practice. В статье представлен обзор данных о распространенности, консервативном и хирургическом лечении хронического гнойного среднего отита, который остается одним из наиболее распространенных и социально значимых заболеваний оториноларингологических структур, сопровождается высокой частотой осложнений и стойкой тугоухостью. Прослежена эволюция методов лечения и сделан особый акцент на перспективах применения тканеинженерных конструкций и тканевой инженерии в целом. Отмечены возможности создания трехслойных трансплантатов с учетом достижений научно-технического прогресса. Показано, что классические методы хирургической коррекции дефектов барабанной перепонки, включая использование аутотрансплантатов (височная фасция, хрящ), не всегда позволяют добиться устойчивого анатомического и функционального результата, особенно при больших и стойких перфорациях. Прослеживается тенденция активного развития направления регенеративной медицины и тканевой инженерии, позволяющих создавать биосовместимые трансплантаты с заданными свойствами, внедрять мезенхимальные стволовые клетки, а также использовать факторы роста для стимуляции репаративных процессов. В обзоре проанализированы данные об эффективности классических и инновационных методов тимпанопластики, а также перспективы применения 3D-биопечати, коллагеновых матриц и клеточных технологий для восстановления целостности барабанной перепонки. Особое внимание уделено результатам клинических и экспериментальных исследований, демонстрирующих значительное повышение частоты успешного закрытия перфораций при использовании тканеинженерных конструкций и факторов роста по сравнению с традиционными методами. Обсуждаются нерешенные вопросы, связанные с оптимизацией технологий, стандартизацией протоколов и необходимостью дальнейших многоцентровых исследований для широкого внедрения инновационных подходов в клиническую практику.
Gastrointestinal stromal tumors (GISTs) are the most common subtype of soft tissue sarcomas, with diagnosis based on a combination of clinical presentation, anatomical localization of the tumor, histological and immunohistochemical (IHC) studies. This paper explores the potential of artificial intelligence (AI) technologies for the automated detection of mitotic figures in histological images of GISTs. A literature review on the application of AI in morphological diagnostics of various tumors is presented. A test dataset of 220 digitized histological slides annotated in CVAT was created as part of the study. A convolutional neural network, YOLOv11, trained over 300 epochs, was used to analyze mitotic activity. Model performance evaluation showed that its accuracy was limited due to the small size of the training dataset. Future work will focus on expanding the dataset and improving the accuracy of pathological mitosis detection. Гастроинтестинальные стромальные опухоли (ГИСО) являются наиболее распространенным подтипом сарком мягких тканей, диагностика которых основывается на сочетании клинической картины, анатомической локализации опухоли и гистологического и иммуногистохимического (ИГХ) исследований. В данной работе рассматривается возможность применения технологий искусственного интеллекта (ИИ) для автоматизированного выявления митозов в гистологических изображениях ГИСО. Проведен обзор литературы по использованию ИИ в морфологической диагностике различных опухолей. В рамках исследования создан тестовый датасет из 220 оцифрованных гистологических стеклопрепаратов, размеченных на платформе CVAT. Для анализа митотической активности применена сверточная нейронная сеть YOLOv11, обученная на 300 эпохах. Оценка эффективности модели показала, что точность ее работы ограничена из-за небольшого количества обучающих данных. В будущем планируется расширение датасета и повышение качества распознавания патологических митозов.
The aim of the present study was to improve the differential diagnosis accuracy of retinal diseases combining a transformer model to classify the biomarkers on OCT images and the large language model DeepSeek-V3. Two datasets were collected and annotated: a training set (3288 central retinal OCT images annotated for 8 biomarkers) and a validation set (50 clinical cases from octcases.com). For biomarker classification, we compared ResNet, DenseNet, EfficientNet, and Vision Transformer (ViT-Tiny-Patch16-224) architectures. The ViT-Tiny model demonstrated the highest performance, its F1 macro - 0.84±0.03. An integration algorithm was developed to combine predicted biomarker labels with clinical history data via the DeepSeek-V3 LLM API. Combining OCT biomarkers and the medical history significantly improved the diagnostic accuracy: Top-1 Accuracy - 78%, Top-3 Accuracy - 94%, MRR - 84%, representing 10-44% improvement over using either data type alone. The suggested approach enabled to automate the detection of biomarkers on OCT images and enhance the differential diagnosis accuracy of eye diseases, reducing the image interpretation time and supporting clinical decision-making.
Modern forensic odontology is undergoing a digital transformation associated with the introduction of 3D technologies and the creation of specialized digital databases. These innovations radically change traditional approaches to personal identification, providing increased accuracy, speed and objectivity of analysis. The use of 3D scanning, CAD/CAM systems, computed tomography, and 3D printing makes it possible to create highly detailed digital models of the maxillofacial region that can be used to identify individuals in cases of mass disasters, criminal investigations, and when working with severely damaged remains. Despite the obvious advantages, the integration of these technologies faces challenges of standardization, implementation costs, and cybersecurity. A systematic search and analytical review of scientific literature published over the past 10 years (2014-2024) was conducted. Relevant publications were searched in international electronic databases (PubMed, Cochrane Library, Scopus, Web of Science) and in Russian scientific electronic libraries (eLibrary, CyberLeninka). The inclusion criteria were: focus on the application of 3D technologies (3D scanning, CAD/CAM, 3D printing) and/or digital databases in the context of forensic dentistry; description of specific clinical cases or research techniques; the presence of an analysis of advantages, limitations and prospects. Articles that did not contain original data were excluded, as well as publications that were not available in full text. As part of the study, 20 publications were selected from the proposed 254 that meet the specified inclusion criteria. Современная судебная одонтология переживает цифровую трансформацию, связанную с внедрением 3D-технологий и созданием специализированных цифровых баз данных. Эти инновации кардинально меняют традиционные подходы к идентификации личности, обеспечивая повышенную точность, скорость и объективность анализа. Использование 3D-сканирования, CAD/CAM-систем, компьютерной томографии и 3D-печати позволяет создавать высокодетализированные цифровые модели челюстно-лицевой области, которые могут использоваться для установления личности в случаях массовых катастроф, криминальных расследований и при работе с сильно поврежденными останками. Несмотря на очевидные преимущества, интеграция этих технологий сталкивается с проблемами стандартизации, затрат на внедрение и обеспечения кибербезопасности. Проведен аналитический обзор научной литературы, опубликованной за последние 10 лет (2014—2024 гг.). Поиск релевантных публикаций осуществлялся в международных электронных базах данных (PubMed, Cochrane Library, Scopus, Web of Science) и в российских научных электронных библиотеках (eLibrary, CyberLeninka). Критериями включения являлись фокус на применении 3D-технологий (3D-сканирование, CAD/CAM, 3D-печать) и/или цифровых баз данных в контексте судебной стоматологии; описание конкретных клинических случаев или исследовательских методик; наличие анализа преимуществ, ограничений и перспектив. Исключались статьи, не содержащие оригинальных данных, а также публикации, недоступные в полном тексте. В рамках исследования из предложенных 254 отобрано 20 публикаций, отвечающих указанным критериям включения.
The aim of the study was to analyze the influence of various pipelines for preprocessing raw functional magnetic resonance imaging (fMRI) data on the accuracy of classification of subjects into schizophrenia patients and healthy controls using machine learning methods, and to give recommendations for optimizing the data preprocessing pipeline for this task. The study used fMRI data from 72 subjects acquired on a Siemens Magnetom Verio 3T MRI scanner (Siemens Healthineers, Germany) at the National Research Centre "Kurchatov Institute". Seven different preprocessing pipelines were used on each dataset. Feature vectors for classification were constructed from each preprocessed dataset. We applied the following three algorithms for feature vector construction: ReHo, FCM, and FHR. Classification was performed using 15 machine learning methods from the scikit-learn package for each feature set and each preprocessing pipeline. The final accuracy was determined as the maximum accuracy among all machine learning methods. No single optimal preprocessing pipeline for all feature vector construction algorithms was found. Smoothing increased accuracy for the voxel metrics ReHo and FHR, but not for the regional metric FCM. Spatial smoothing was the only preprocessing step that affected classification accuracy for the FHR method. The FHR feature set without smoothing demonstrated accuracy close to chance level. The steps of frequency filtering and median normalization substantially increased the accuracy for both the ReHo and FCM methods, both with and without smoothing. The steps of inhomogeneity correction and slice timing correction did not increase accuracy for the FCM feature set but did improve it by several percent for the ReHo feature set. Application of ICA filtering changed accuracy within a range of 5%, in either a positive or negative direction. Based on the obtained results, the following recommendations can be given for fMRI data preprocessing pipelines for binary classification of subjects into schizophrenia patients and healthy controls using machine learning methods and taking into account the feature vector construction algorithm. The most suitable for the ReHo metric pipeline includes motion correction, normalization, inhomogeneity correction, slice timing correction, frequency filtering, median normalization, and spatial smoothing. The most suitable for the FCM metric pipeline includes motion correction, normalization, inhomogeneity correction, slice timing correction, frequency filtering, and median normalization. Spatial smoothing is the most important factor for the FHR metric. The ICA filtering step does not provide a clear benefit and should therefore be applied with caution.
The aim of the study was to histologically validate the diagnostic potential of new systemic inflammation biomarkers (MLR, SIRI, CAR, dNLR, ALB/dNLR) in assessing the severity of rheumatoid arthritis (RA) induced in warm-blooded animals with genetically determined resistance to hypoxia. An autoimmune RA model (experimental groups) was induced by subcutaneous injection of complete Freund's adjuvant into the right hind limbs of 8-month-old male rats of strains with high (HR/SmY) and low (LR/SmY) resistance to hypoxia. Rats in the control groups received only the solvent. After 35 days, blood was collected from the hearts of all the rats. To calculate the new inflammation biomarkers - CAR, ALB/dNLR, SIRI, dNLR, NC/LC, and MLR - the following laboratory parameters were used: ALB (albumin), CRP (C-reactive protein), MC (monocytes), LC (lymphocytes), and NC (neutrophils). The effectiveness of disease severity assessment using these biomarkers was determined based on histological examination of plantar sections of the tarsal and metatarsophalangeal joints of control and experimental rats. Genetically determined resistance to hypoxia is an important factor in the onset of the pathogenetic RA mechanisms. Low hypoxia resistance was associated with more severe connective tissue pathology compared to high resistance: LR/HR - 164 points/113 points, p≤0.05. The severity of pathomorphological RA changes (considering the organism's resistance to hypoxia), identified histologically (cartilage degeneration: LR/HR - 29 points/18 points, p≤0.01; general joint inflammation: LR/HR - 37 points/26 points, p≤0.01; osteolysis: LR/HR - 6 points/0 points, p≤0.01), was most effectively reflected by the following integral inflammation indices: CAR (LR/HR - 11.55·10-6 units/12.73·10-6 units), ALB/dNLR (LR/HR - 86.93 units/78.51 units), and SIRI (LR/HR - 0.14 units/ 0.19 units). The severity of pathomorphological RA signs depends on genetically determined resistance to hypoxia. For effective prediction of the disease, risk of complications, and treatment efficacy, it is advisable to use the new systemic inflammation biomarkers CAR, ALB/dNLR, and SIRI.
A neural interface is a set of tools that enable information exchange between the brain and an external device. Such systems are widely used in biomedicine, including the recovery of nervous system functions. This review summarizes the operating principles of neurointerfaces, reviews the materials used in their design, and presents examples of this technology's use in medicine, including chronic implantation. Нейронный интерфейс — это комплекс средств, предназначенный для обмена информацией между мозгом и внешним устройством. Данная система находит широкое применение в области биомедицины, в том числе при восстановлении функций нервной системы. В обзоре обобщены принципы работы нейроинтерфейсов, проанализированы виды материалов, использующихся для их создания, а также рассмотрены различные примеры применения данной технологии в медицине, в том числе при хронической имплантации.
The aim of the study was to estimate the efficiency of identifying bacterial agents in native cardiac valves affected by infective endocarditis using 16S rRNA metabarcoding. The study material involved 20 native cardiac valve samples from 16 patients. Sequencing was carried out in the Center for Collective Use "Genomics" (Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Russia) on a sequenator MiSeq (Illumina, USA) using MiSeq Reagent Kit v3 (2×300 bp; Illumina, USA). The study revealed major microorganisms (their portion in the sample under study was over 5% from all identified bacterial agents) belonging to Streptococcus (40% of all valves studied), Sphingomonas (35%), Pseudomonas (35%), Roseateles (25%), Phyllobacterium (25%), and Enterococcus (15%). Moreover, the studied valves were found to have rare cases of Ralstonia pickettii, as well as Bacillus and Klebsiella representatives. The findings demonstrated the efficiency of 16S rRNA metabarcoding in identifying bacterial agents compared to routine noninvasive diagnostic methods. Native cardiac valves isolated from the patients with infective endocarditis were characterized by numerous opportunistic pathogenic bacteria in negative blood cultures.
Chronic kidney disease (CKD), which often requires maintenance hemodialysis (MHD), represents a model of accelerated aging. Therefore, understanding the mechanisms underlying cerebral neurodegeneration (CND) and cognitive impairment (CI) in patients undergoing MHD is of particular importance. Brain damage in patients with end-stage CKD is considered a multicomponent process associated with the impact of cerebrovascular, neurodegenerative, and numerous dysmetabolic factors. Special attention is given to CND mechanisms mediated by the activation of microglia and astrocytes. The high prevalence of CI in the general population and especially among patients with end-stage CKD undergoing MHD determines the need to clarify CND risk factors and biomarkers. Furthermore, it is essential to explore therapeutic targets, as well as modifiable modern strategies and technologies aimed at slowing the CND progression. This review synthesizes data on the role of neuroglia and associated factors in the development of CND and CI in MHD patients. It presents the mechanisms and factors affecting neuroglia and involved in the pathogenesis of CND and CI. Particular focus is placed on chronic systemic inflammation, the effects of uremic toxins, and the activation of the cerebral renin-angiotensin-aldosterone system. The article studies such chronic systemic inflammatory factors associated with neuroglia as protein S100B, IL-1β, IL-6, TNF-α, and fibrinogen. Experimental and clinical data investigating the impact of uremic toxins (indoxyl sulfate, p-cresol sulfate, and imidazole propionate) on microglia and astrocytes, as well as the activation of the cerebral renin-angiotensin-aldosterone system, are analyzed. Potential further clinical research fields aimed at slowing the CND and CI progression in this patient population are highlighted.
Augmented reality (AR) is a new tool in surgical treatment of craniofacial deformities, in particular, craniosynostosis. To clarify the indications for AR navigation system, technical capabilities of system, its advantages and disadvantages in surgery for craniosynostosis in children, as well as to compare these findings with literature data. In 2025, nine consecutive surgical interventions were performed using this method in patients with craniosynostosis at the Burdenko Neurosurgery Center. There were 7 boys (78%) and 2 girls (22%) aged 38.8 ± 54.7 (7-156) months. AR navigation allowed us to simulate results of preoperative virtual planning in reconstructive procedures. This ensured accuracy of interventions. AR navigation localized intracranial structures, such as endostoses and venous sinuses, whose visualization made surgery safer. This technique was valuable to mark craniotomy lines, control distraction device position and bone fragments, and assess conformity of final reconstruction with scheduled one. Preoperative modeling took 173.3±61.4 (90-240) min. Overall intraoperative time spent for AR navigation was 33.9±15.6 (15-60) min. The augmented reality system appears to be perspective in surgery for craniosynostosis enabling real time intraoperative neuronavigation. Further development of augmented reality techniques in craniosynostosis surgery will improve outcomes and make results more predictable and safe. Дополненная реальность представляет собой новый инструмент в хирургическом лечении краниофациальных деформаций, в частности в хирургии краниосиностозов. Уточнение показаний к использованию системы AR-навигации (Augmented Reality — дополненная реальность), клиническая оценка технических возможностей системы, анализ ее преимуществ и недостатков в хирургии краниосиностозов у детей, а также сопоставление полученных данных с литературными источниками. В ФГАУ НМИЦН им. ак. Н.Н. Бурденко в 2025 г. было последовательно проведено 9 хирургических вмешательств с применением указанного метода у пациентов с краниосиностозами в возрасте 38,8±54,7 (7—156) мес; 7 (78%) мальчиков и 2 (22%) девочки. Использование AR-навигации позволило смоделировать результаты предоперационного виртуального планирования во время реконструктивных операций, что обеспечило точность проведенных вмешательств. AR-навигация позволяла лоцировать интракраниальные структуры, такие как костные эндостозы, венозные синусы, визуализация которых делала оперативное вмешательство более безопасным. С помощью этой методики было возможно проводить разметку линий краниотомий, контролировать позиционирование дистракционных аппаратов и отдельных костных фрагментов, осуществлять оценку соответствия полученной реконструкции — запланированной. На предоперационное моделирование было затрачено 173,3±61,4 (90—240) мин. Средняя суммарная длительность интраоперационного использования AR-навигации составила 33,9±15,6 (15—60) мин. Система дополненной реальности представляется перспективной методикой в хирургии краниосиностозов, позволяющей осуществлять нейронавигацию по ходу операции в режиме реального времени. Дальнейшая разработка методик дополненной реальности в хирургии краниосиностозов позволит улучшить результаты лечения пациентов и сделать получаемый результат более предсказуемым и безопасным.
The aim of the study was to develop an optimal technique to predict the results of a bicycle ergometry test (BET) based on the parameters recorded during a six-minute walk test (6MWT) using machine learning methods. The study involved 56 patients who had experienced acute myocardial infarction and were undergoing the second stage of cardiac rehabilitation. The patients underwent a complete examination, including history taking, physical examination, anthropometric assessment, as well as a symptom-limited BET and 6MWT. During the 6MWT, we recorded the following: the distance covered, the heart rate, the blood pressure, the oxygen saturation, Borg rating of perceived exertion, the number of steps taken, and the electrocardiographic data. The algorithms for random forest, gradient boosting, k-nearest neighbors, and multiple linear regression were used to construct the machine learning models. The performance of the models was evaluated based on a determination coefficient, a mean absolute error, a mean square error, and a root mean square error. SHAP analysis was applied to interpret the findings. The gradient boosting model provided the best prediction quality with a high determination coefficient (R2 being around 0.99) and low error values for both target metrics: the distance walked in the 6MWT and the metabolic equivalent achieved during the BET. The significance analysis of features revealed the heart rate, age, and the body mass index to have the greatest impact on predicting the 6MWT distance, while for predicting the metabolic equivalent, the distance covered, the number of steps, and the body mass index were the most significant. The developed gradient boosting-based machine learning model demonstrated its high efficiency in predicting the results of the 6MWT-based BET. The suggested method can serve as a valuable auxiliary tool to plan cardiac rehabilitation programs, particularly in cases when BET is difficult or impossible to perform. The use of SHAP analysis helped to understand the contribution of each feature to the prediction, increasing the confidence in the model results.