Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Issue 5, 2022

Topic Russian North genetics

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Issue 6, 2021

Topic Parkinson’s disease

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Issue 1, 2022

Topic Red king crab nuclease applications

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Issue 2, 2022

Topic Oncolytic viruses

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Issue 3, 2022

Topic Listeria-macrophage interaction protein

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Issue 4, 2022

Topic Neonatal encephalopathy

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New articles

Kalinkin AI, Sigin VO, Nemtsova MV, Strelnikov VV

Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of female mortality. The development of prognostic models based on multiomics data is the main goal of precision oncology. Aberrant DNA methylation in BC is a diagnostic marker of carcinogenesis. Despite the existing factors of BC prognosis, introduction of methylation markers would make it possible to obtain more accurate prognostic scores. The study was aimed to assess DNA methylation signatures in various BC subtypes for clinical endpoints and patients' clinicopathological characteristics. The data on methylation of CpG dinucleotides (probes) and clinical characteristics of BC samples were obtained from The Cancer Genome Atlas Breast Cancer database. CpG dinucleotides associated with the selected endpoints were chosen by univariate Cox regression method. The LASSO method was used to search for stable probes, while further signature construction and testing of the clinical characteristics independence were performed using multivariate Cox regression. The dignostic and prognostic potential of the signatures was assessed using ROC analysis and Kaplan–Meier curves. It has been shown that the signatures of selected probes have a significant diagnostic (AUC 0.76–1) and prognostic (p < 0.05) potential. This approach has made it possible to identify 47 genes associated with good and poor prognosis, among these five genes have been described earlier. If the genome-wide DNA analysis results are available, the research approach applied can be used to study molecular pathogenesis of BC and other disorders.

Received: 2022-10-18

Published online: 2022-11-25

DOI: 10.24075/brsmu.2022.056

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VIEWS 61

Andreevskaya SN, Smirnova TG, Chernousova LN, Larionova EE, Kiseleva EA, Ergeshov A

Fluoroquinolones are the main group of drugs used for treatment of multidrug resistant tuberculosis (MDR-TB). The study was aimed to assess the diversity of mutation in the gyrA gene and to evaluate the association of gyrA mutations with the phenotypic resistance to levofloxacin and the general drug resistance profile of the pathogen. The study involved assessment of diagnostic materials obtained from 2836 patients with pulmonary tuberculosis. TB-BIOCHIP-2 and AmplitubeFQ-RV kits were used for identification of the gyrA mutations. Phenotypic drug susceptibility of M. tuberculosis (MTB) was defined using the BACTEC MGIT 960 test system. It was shown that mutations D94G (41.63%; 95% CI: 38.03–45.32%) and A90V (21.32%; 95% CI: 18.44–24.50%) prevailed in MBT, although some isolates carrying these mutations were obtained from the newly diagnosed patients with pulmonary tuberculosis. It was found that mutation D94A was not strongly associated with the phenotypic resistance to fluoroquinolones. Fluoroquinolone resistance was usually associated with multiple drug resistance (93.52%; 95% CI 91.43–95.12%). In 2.31% (95% CI 1.78–3.00%) of cases, genotypic heteroresistance to fluoroquinolones was detected: mixed populations included 2–4 MTB pools with various structure of the gyrA QRDR. The results obtained lead to the conclusion that resistance to fluoroquinolones that is usually associated with the existing MDR arises in the modern MTB population. MTB carrying gyrA mutations D94G and A90V seems to be the most promising in evolutionary terms.

Received: 2022-10-10

Published online: 2022-10-31

DOI: 10.24075/brsmu.2022.054

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Ermakova DM, Dolgushina NV, Menzhinskaya IV, Lomova NA, Vtorushina VV

Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, β2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%); p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy.

Received: 2022-09-07

Published online: 2022-10-31

DOI: 10.24075/brsmu.2022.048

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VIEWS 129

Nuralieva NF, Yukina MYu, Troshina EA, Zhukova OV, Petrov VA, Volnukhin VA

There is evidence in the literature about more frequent association of vitiligo with autoimmune endocrine diseases (AEDs) compared to general population. No full-fledged studies aimed at assessing the prevalence of AEDs in the Russian cohort of adult vitiligo patients have been conducted. The study was aimed to assess the prevalence of AEDs in the cohort of Russian adult vitiligo patients. Patients with vitiligo monitored in two clinics, the Endocrinology Research Centre (Clinic 1; n = 39) and the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology (Clinic 2; n = 26), were enrolled. Along with clinical examination, screening laboratory tests were performed in all patients in order to reveal AEDs. The majority of patients (more than 95% of cases) had nonsegmental vitiligo. Among patients monitored in Clinic 1, AEDs were diagnosed in 85% of cases: isolated AEDs accounted for 39%, while multiple AEDs were found in 46% of cases. Autoimmune thyroid diseases were diagnosed in 69% of cases. Autoimmune adrenal insufficiency was found in 28% of patients, type 1 diabetes mellitus in 21%, hypoparathyroidism in 13%, hypergonadotropic hypogonadism in 10%, endocrine ophthalmopathy in 10% of patients. Among patients monitored in Clinic 2, AEDs were diagnosed in four patients (15% of cases): three patients had primary hypothyroidism in the outcome of autoimmune thyroiditis, one patient had Graves' disease. Thus, the prevalence of AEDs in patients with vitiligo may vary between 15–85%. Vitiligo is most often associated with autoimmune thyroid diseases (15–69%). Vitiligo patients should undergo annual screening aimed at detection of autoimmune endocrine disorders, especially thyroid diseases.

Received: 2022-09-29

Published online: 2022-10-29

DOI: 10.24075/brsmu.2022.055

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VIEWS 135

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Popular articles

Voroshilina ES, Khayutin LV, Kudryavtseva EV, Kovalev VV, Plotko EE

Detecting high risk of preterm birth (PB) early makes its prevention possible. The aim of the work was to develop a mathematical predictive model for assessing the risk of preterm birth based on a quantitative analysis of the vaginal microbiota in the first trimester of pregnancy. The study included 199 pregnant women, i.e. 41 pregnancies that ended in preterm birth, and 158 — in term birth. Vaginal microbiota was analyzed in all patients in the 1st trimester of pregnancy by quantitative real-time PCR (qPCR). The method of dicriminant analysis was used to develop a predictive model. A method for predicting PB was developed with the calculation of the PRIMA prognostic index (Premature Birth. Index Of Microbiological Analysis). If the value of PRIMA > 0 – the risk of premature birth is low, if PRIMA < 0 – the risk is high. The sensitivity and specificity of the method are respectively 70.7% and 79.75%, the effectiveness is 77.89%. Evaluation of vaginal microbiota in the 1st trimester makes it possible to identify a high-risk group of PB and perform timely preventive measures.

Received: 2022-04-28

Published online: 2022-06-19

DOI: 10.24075/brsmu.2022.032

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VIEWS 507

Ganin IP, Kaplan AYa

The P300-based brain–computer interfaces (P300 BCI) allow the user to select commands by focusing on them. The technology involves electroencephalographic (EEG) representation of the event-related potentials (ERP) that arise in response to repetitive external stimulation. Conventional procedures for ERP extraction and analysis imply that identical stimuli produce identical responses. However, the floating onset of EEG reactions is a known neurophysiological phenomenon. A failure to account for this source of variability may considerably skew the output and undermine the overall accuracy of the interface. This study aimed to analyze the effects of ERP variability in EEG reactions in order to minimize their influence on P300 BCI command classification accuracy. Healthy subjects aged 21–22 years (n = 12) were presented with a modified P300 BCI matrix moving with specified parameters within the working area. The results strongly support the inherent significance of ERP variability in P300 BCI environments. The correction of peak latencies in single EEG reactions provided a 1.5–2 fold increase in ERP amplitude with a concomitant enhancement of classification accuracy (from 71–78% to 92–95%, p < 0.0005). These effects were particularly pronounced in attention-demanding tasks with the highest matrix velocities. The findings underscore the importance of accounting for ERP variability in advanced BCI systems.

Received: 2022-05-04

Published online: 2022-06-21

DOI: 10.24075/brsmu.2022.033

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VIEWS 452

Special Project Author's Work

Secrets of a quality research study and a good manuscript

At the end of 2015, Bulletin of RSMU saw an important change in its typographic design and content. We formulated new editorial policies and established strict ethical standards for submitted manuscripts in accordance with the guidelines of reputable international bodies. As a result, about a quarter of the submitted works have been rejected, the primary reason being the author trying to submit a previously published article. Sometimes authors believe that by making slight changes to the introduction, excluding a few people from the study, performing a new statistical analysis, and thus obtaining totally new results they will turn their old manuscript into a novel work. That is why we would like to talk about scientific integrity, honesty, plagiarism, and self-plagiarism in our special project “Author’s work”.

American physicist Richard P. Feynman, a Nobel laureate, was always very scrupulous about the quality of a research study. During his commencement address at the California Institute of Technology in 1974, he talked about scientific integrity and honesty and warned young researchers “not to fool” themselves. A must-read for anyone who believes he/she is a true scientist.

In 1918, Russian physiologist Ivan Pavlov, a Nobel laureate, delivered two lectures: on the mind in general and the Russian mind in particular; on those mind qualities that determine the success of a research work and on how these qualities are present in the Russian mind. Pavlov's thoughts are an effective vaccine against poor intellectual work.