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The system of professional training of officers of the Ministry of Internal Affairs of Russia is meant to ensure the competence of a specialist and his high professional readiness for implementing the law-enforcement functions by means of a deep theoretical training, practical orientation of the training process, and introduction of students to values of the profession. The primary focus is on the formation of students’ competencies at all levels, which act as an important guide for organizing the activities of managers and teachers, as well as the desired result of mastering the content of education, which is shown in the ability to apply variably formed knowledge and skills depending on the situation. Professional readiness, in addition to the accumulated competencies and practical experience in their application, includes a personal component that characterizes the officer’s attitude towards the processes and phenomena, formed through the perception of professionally and personally important information, understanding of an environmental context, development of his attitude towards the phenomena of society in the process of the reflexive activity. The teacher’s function is transformed from an active translator of professionally significant information into a subject supporting accumulation of the personal experience in a planned person-centered environment that provides for a partner model of cooperation and reflexivity of relations between the subjects of joint activity. The goal of the research is to analyze the methodological basis of the process of professional becoming of officers from the Ministry of Internal Affairs of Russia, and to identify significant characteristics of the process of planning the educational environment based on pedagogical support in the formation of personal experience. Such methods as a comparative analysis of methodological approaches in organizing the person-centered education, the study of independent characteristics, search of static information, method of expert assessment were applied. The methodological approaches in organizing the professional becoming of a specialist have been studied, the role of pedagogical support in the professional becoming of a specialist has been substantiated; the relations between the effectiveness of professional development and organization of pedagogical support of this process have been detected.

The aim of the study was to evaluate a prognostic significance of immunohistochemical parameters in serous ovarian carcinomas and their statistical relationships after neoadjuvant treatment to assess the development of tumor resistance to platinum-containing adjuvant polychemotherapy regimens. Material and Methods. An immunohistochemical study of tumor tissue was carried out in patients with high-grade serous ovarian cancer (stage IIIC–IV). The age of the patients ranged from 49–72 years. There were 59 patients who were sensitive and 22 patients who were resistant to platinum-containing adjuvant polychemotherapy. In the tissue of ovarian tumors obtained during surgery after noadjuvant polychemotherapy, we studied immunohistochemical indicators of proliferative activity (Ki67), expression of the DNA excision repair protein ERCC1 and proteins of the ABC transporter family – Pgp and BCRP, as well as statistical relationships between these indicators (Spearman’s rank correlation coefficient). Results. After effective neoadjuvant polychemotherapy, more pronounced signs of activity in the processes of proliferation, DNA repair and xenobiotic efflux were noted in serous ovarian carcinomas, which subsequently demonstrated resistance to platinum-containing polychemotherapy regimens compared to tumors that retained platinum sensitivity. Moreover, in 40 % of cases or more, there was a coincidence in the ranges of values of the studied parameters in tumors with different sensitivity to platinum drugs. The expression of transporter proteins greater than 60 % for BCRP and 65 % for Pgp was shown to precede the development of resistance to adjuvant treatment with carboplatin. In the studied groups, differences in the number and significance of statistical relationships between the variables were observed. The most significant differences were noted for the Ki67 – BCRP correlation, which had the opposite direction in groups with different sensitivity to adjuvant treatment with carboplatin. Conclusion. A comprehensive immunohistochemical analysis of highgrade serous ovarian carcinomas after neoadjuvant polychemotherapy, which further demonstrated different sensitivity to platinum-containing adjuvant regimens, was carried out, and the prognostic value of the studied parameters was assessed. The revealed critical levels of Pgp and BCRP expression in tumor tissue may have a prognostic value regarding the effect of adjuvant polychemotherapy. The results of the correlation analysis suggest a relationship between the development of platinum resistance and changes in the nature of the regulatory relationships between proliferative activity and transport processes in tumor tissue.

ABSTRACTThe main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far-Eastern subtype. A 3.8 Å resolution reconstruction reveals the structural integrity of the envelope E proteins, specifically the E protein ectodomains. The comparative study shows a high structural similarity to the previously published structures of the TBEV European subtype strains Hypr and Kuutsalo-14. A fraction of inactivated virions exhibits asymmetric features including the deformations of the membrane profile. We propose that the heterogeneity is caused by inactivation and perform a local variability analysis on the small parts of the envelope protein shell to reveal membrane curvature features possibly induced by the inactivation. The results of this study will have implications for the design of novel vaccines against diseases caused by flaviviruses.

BackgroundProlgolimab is the first Russian PD-1 inhibitor approved for the first-line treatment of unresectable or metastatic melanoma and advanced non-small cell lung cancer. It was approved in two weight-based regimens of 1 mg/kg Q2W and 3 mg/kg Q3W, but because of re-evaluation of weight-based dosing paradigm, studying of a fixed-dose regimen was considered perspective.MethodsWe conducted a multicenter, single-arm, open-label efficacy, pharmacokinetics, and safety study to obtain data that would allow the approval of the new flat dosing regimen of prolgolimab in patients with previously untreated unresectable or metastatic melanoma (BCD-100-8/FLAT, NCT05783882). The primary objective was to prove the non-inferiority of prolgolimab 250 mg Q3W versus prolgolimab 1 mg/kg Q2W for the treatment of patients with unresectable or metastatic melanoma in terms of ORR according to RECIST 1.1. Patients from the MIRACULUM study (BCD-100-2/MIRACULUM, NCT03269565) comprised a historical control group.ResultsOne hundred fourteen patients received prolgolimab 250 mg Q3W, and 61 patients received prolgolimab (Prolgo) 1 mg/kg Q2W (historical control). Objective response was achieved by 33.3% [95% confidence interval (CI): 24.8, 42.8] of patients in the Prolgo 250 mg group compared with 32.8% (95% CI: 21.3, 46.0) of patients in the Prolgo 1 mg/kg group. Risk difference was 0.00, 95% CI (−0.12; NA), p = 0.0082. Both regimens were well tolerated, and safety profiles were comparable. The pharmacokinetic analysis (PK) showed that the regimen with the fixed dose of 250 mg Q3W was characterized by higher PK parameters. The immunogenicity study did not detect binding antibodies to prolgolimab in any of the subjects.ConclusionThe obtained results showed that the selected fixed dosing regimen of prolgolimab 250 mg Q3W is characterized by efficacy and safety parameters comparable to that observed for the 1 mg/kg Q2W regimen.

PurposeBevacizumab-related imaging abnormality (BRIA), appearing as areas of restricted diffusion on magnetic resonance imaging (MRI) and representing atypical coagulative necrosis pathologically, has been observed in patients with brain tumors receiving radiotherapy and bevacizumab. We investigated the role of cumulative radiation dose in BRIA development in a voxel-wise analysis.MethodsPatients (n = 18) with BRIA were identified. All had high-grade gliomas or brain metastases treated with radiotherapy and bevacizumab. Areas of BRIA were segmented semi-automatically on diffusion-weighted MRI with apparent diffusion coefficient (ADC) images. To avoid confounding by possible tumor, hypoperfusion was confirmed with perfusion imaging. ADC images and radiation dose maps were co-registered to a high-resolution T1-weighted MRI and registration accuracy was verified. Voxel-wise normal tissue complication probability analyses were performed using a logistic model analyzing the relationship between cumulative voxel equivalent total dose in 2 Gy fractions (EQD2) and BRIA development at each voxel. Confidence intervals for regression model predictions were estimated with bootstrapping.ResultsAmong 18 patients, 39 brain tumors were treated. Patients received a median of 4.5 cycles of bevacizumab and 1-4 radiation courses prior to BRIA appearance. Most (64%) treated tumors overlapped with areas of BRIA. The median proportion of each BRIA region of interest volume overlapping with tumor was 98%. We found a dose-dependent association between cumulative voxel EQD2 and the relative probability of BRIA (β0 = -5.1, β1 = 0.03 Gy-1, γ = 1.3).ConclusionsBRIA is likely a radiation dose-dependent phenomenon in patients with brain tumors receiving bevacizumab and radiotherapy. The combination of radiation effects and tumor microenvironmental factors in potentiating BRIA in this population should be further investigated.

This article discusses the urgent aspects of online learning didactics. They are comprised of, for instance, organization and methods of organized learning, main principles of actions aimed at practical orientation; their objective is combination of the methods of distance learning, formation of efficient skills of students with social mediation, analysis of reasons of errors and their correction, pursuance of success in relevant areas. Organized online learning also provides opportunity for students to use all advantages of digital technologies: flexibility, individual distribution of learning duration, compatibility with other forms of occupation. In addition to digital know-how, organization of learning and independent work of distant students can develop self-discipline, sustainability of acquired skills. Students can use various digital sources of information available under various conditions in addition to that organized under the management of distance learning teacher.

Introduction. Radiomics is a rapidly developing field in oncology visualization aimed at searching for prognostically effective imaging features associated with specific genetic events that determine various characteristics of the disease course. According to numerous studies, the presence of IDH mutations in glial tumors determines a longer overall survival. Despite the fact that biopsy is considered to be the «gold standard» for brain tumors differential diagnosis, it is though quite difficult to perform due to the complexity of surgical access, common cases of the repeat procedure impossibility, serious complications and mortality.Aim: a search for imaging features providing prognostic data on the presence of certain mutations and gene expression in gliomas, obtained using traditional pulse sequences and characterized by the absence of restrictions on applicability depending on the tumors visible morphological features.Material and methods: retrospective analysis of 49 eligible patients' primary brain MRI data between 2021 and 2023 from Almazov National Medical Research Centre (n = 31) and Napalkov Oncological Centre (n = 18) with glial tumors and subsequently identified status of the target variable; preprocessing of MR images using the histogram matching; regions of interest determination and semi-automated slice-by-slice segmentation with subsequent extraction of radiomics features; search for predictive radiomics features regarding the status of target variable using statistical analysis tools.Results. Dependence Entropy was found to be highly effective as a predictor of IDH mutations (area under the ROC-curve – 0.766 [0.627–0.880]).Conclusions. We determined a target variable for the development of a predictive model (IDH status), a pulse sequence (T2-Tirm), a tool for initial imaging data preprocessing (histogram matching), regions of interest (tumor-associated T2-Tirm-hyperintensity including cystic and/or necrotic lesions). As a result, a statistically significant relationship between the Dependence Entropy feature and IDH status of glial tumors was found. In the course of further work it is planned to increase the size of a database, improve the accuracy of the existing statistical model, search for relevant radiomic features extracted using other traditional pulse sequences, create a comprehensive predictive radiogenomics model and develop a software.

We present the results of Auroral Kilometric Radiation (AKR) measurements near the plasmapause on the ERG (Arase) satellite. The apogee of the satellite's orbit is located near the ecliptic plane, at latitudes ±30°. According to the generally accepted point of view, AKR observation is impossible in this region since it is shielded by the plasmasphere. Simultaneous measurements of AKR and local plasma density made it possible to determine that AKR in near-equatorial regions occur in plasma channels — density inhomogeneities elongated along magnetic field lines. AKR from sources located in the auroral magnetosphere is transferred by these channels to the equatorial region. This work analyzes the conditions for the capture and propagation of AKR in low plasma density channels. In the geometrical optics approximation, we have simulated the conditions for the radiation capture and propagation. The calculation results show that the proposed scheme for AKR capture into plasma channels can explain the measurement results — the radiation transfer from the auroral region to the near-equatorial region.

Aim. To assess the efficacy and safety of lenvatinib and pembrolizumab for the treatment of mismatch repair-proficient endometrial cancer (EC) in routine clinical practice in Russia.Materials and methods. This multicenter, retrospective, cohort study included patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between May 2020 and April 2023. Patients with histologically verified EC without microsatellite instability who received ≥1 course of pembrolizumab/lenvatinib therapy were included in the study. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed, the objective response rate and the toxicity profile of therapy were assessed.Results. The study included 100 patients. Median age was 65 (30–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (68 %); serous adenocarcinoma was diagnosed in 22 % of cases, other types of tumor – 10 % of cases. All patients had pMMR/microsatellite-stable tumors. The median progression-free survival was 7.75 months (95 % confidence interval 0.7–33.8), and a partial response to therapy was observed in 24 % of patients. Almost half of the patients (44 %) required dose reduction due to adverse events. The most common adverse events included fatigue (n = 26; 26 %), hypertension (n = 20; 20 %), and hypothyroidism (n = 14; 14 %).Conclusion. This study confirms the clinical efficacy of lenvatinib and pembrolizumab in patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR-tumors) in routine clinical practice.

This work was carried out in real clinical practice. Five clinical observations of anemia caused by vitamin B12 deficiency are presented, which demonstrate the difficulties of differential diagnosis. Differential diagnosis of B12‑deficiency anemia is carried out with folate deficiency anemia, hemolytic anemia, myelodysplastic syndrome, acute leukemia – erythromyelosis, aplastic anemia, myelocarcinomatosis, anemia due to copper deficiency. The relevance of the clinical problem is determined by the fact that B12‑deficiency anemia is one of the common anemias, the frequency of its detection varies in different age groups: after 60 years, vitamin B12 deficiency is found in one in 50 people, after 70 years – in every 15th. Currently, an increasingly common cause of megaloblastic anemia is vitamin B12 deficiency, which occurs while taking certain medications. Vitamin deficiency leads to a wide range of various disorders, primarily the occurrence of neurological manifestations, while there is insufficient awareness of clinicians about causes of its occurrence, nonspecific manifestations, diagnostic methods and effective therapy.

Abstract The T5 family of viruses are tailed bacteriophages characterized by a long non-contractile tail. The bacteriophage DT57C is closely related to the paradigmal T5 phage, though it recognizes a different receptor (BtuB) and features highly divergent lateral tail fibers (LTF). Considerable portions of T5-like phages remain structurally uncharacterized. Here, we present the structure of DT57C determined by cryo-EM, and an atomic model of the virus, which was further explored using all-atom molecular dynamics simulations. The structure revealed a unique way of LTF attachment assisted by a dodecameric collar protein LtfC, and an unusual composition of the phage neck constructed of three protein rings. The tape measure protein (TMP) is organized within the tail tube in a three-stranded parallel α-helical coiled coil which makes direct contact with the genomic DNA. The presence of the C-terminal fragment of the TMP that remains within the tail tip suggests that the tail tip complex returns to its original state after DNA ejection. Our results provide a complete atomic structure of a T5-like phage, provide insights into the process of DNA ejection as well as a structural basis for the design of engineered phages and future mechanistic studies.