Репозиторий Университета

© Springer Science+Business Media, LLC, part of Springer Nature 2020. DNA mutations govern cancer development. Cancer mutation profiles vary dramatically among the individuals. In some cases, they may serve as the predictors of disease progression and response to therapies. However, the biomarker potential of cancer mutations can be dramatically (several orders of magnitude) enhanced by applying molecular pathway-based approach. We developed Oncobox system for calculation of pathway instability (PI) values for the molecular pathways that are aggregated mutation frequencies of the pathway members normalized on gene lengths and on number of genes in the pathway. PI scores can be effective biomarkers in different types of comparisons, for example, as the cancer type biomarkers and as the predictors of tumor response to target therapies. The latter option is implemented using mutation drug score (MDS) values, which algorithmically rank the drugs capacity of interfering with the mutated molecular pathways. Here, describe the mathematical basis and algorithms for PI and MDS values calculation, validation and implementation. The example analysis is provided encompassing 5956 human tumor mutation profiles of 15 cancer types from The Cancer Genome Atlas (TCGA) project, that totally make 2,316,670 mutations in 19,872 genes and 1748 molecular pathways, thus enabling ranking of 128 clinically approved target drugs. Our results evidence that the Oncobox PI and MDS approaches are highly useful for basic and applied aspects of molecular oncology and pharmacology research.

© 2019, SICOT aisbl. Background: Rupture of the anterior cruciate ligament (ACL) is one of the most common sports injuries of the knee joint. Today, we have a large number of approaches to arthroscopic reconstruction of the anterior cruciate ligament that lead to successful outcomes and allow the patients to return to a significant level of activity post-operatively. Nevertheless, the return to competitions rate stays relatively low. The functional state is thought to be dependent on rotational and anteroposterior stability of the knee. These data encourage search for methods of additional stabilization of the knee joint, one of them being extra-articular tenodesis, or reconstruction of anterolateral ligament of the knee. The aim of the study: To evaluate medium-term results of combined simultaneous arthroscopic reconstruction of anterior cruciate ligament and anterolateral ligament of the knee joint in sportsmen and to access the probability of return to competitions. Materials and methods: The surgeries were performed in 2014–2015 in 50 patients who fulfilled the entry criteria: 20 patients (including 10 professional sportsmen) underwent arthroscopic ACL reconstruction together with reconstruction of anterolateral ligament—group 1 (main group), and 30 patients (including 10 professional sportsmen) underwent arthroscopic ACL reconstruction—group 2 (control group). Results: Group 1: All patients of group 1 were able to return to the pre-operative sports level in two years after the surgery. The mean Tegner Lysholm score was 72.6 ± 6.45 (hereinafter, SE—standard error) before the surgery and 97.4 ± 1.18 after the surgery. The mean IKDC score was 63.1 ± 4.8% before the surgery and 96.3 ± 1.8% after the surgery. Group 2: 20 of 30 patients (66.7%) returned to the pre-operative level of activity and returned to competitions (if they were professional sportsmen) in a year after the surgery. Five of ten patients (50%) (professional sportsmen) returned to competitions. Fifteen of 20 patients (75%) (amateur sportsmen) also returned to competitions. The mean pre-operative Tegner Lysholm score was 69.6 ± 3.5, and the mean post-operative score was 92.1 ± 3.9. The mean pre-operative IKDC score was 73.4 ± 3.2%, and the mean post-operative score was 90.3 ± 3.7%. Conclusion: The results of the study show that more patients with higher functional demands and more professional sportsmen returned to sports. Despite the results of our and other foreign studies, a need remains for studies that will compare outcomes of ALL reconstruction with the same surgical technique in homogenous groups of patients.

© 2019 American Chemical Society. Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Arbitrary and involuntary movements were studied from the position of the new chaos—self-organization theory. Analysis of organization of tappingrams and tremorograms within the framework of N. A. Bernstein “repetition without repetitions” hypothesis leads to the Eskov—Zinchenko effect. In this case, there is no statistical stability for samples of parameters of electromyograms of any movements obtained in a row, i.e. fj(xi)≠fj+1(xi) with the probability p≥0.97. In this paper, the basic problem of motion physiology, stochastic instability establishment mechanisms, is solved in the analysis of muscle electromyogram parameters under conditions of permanent static force. Statistical instability of electromyograms within the framework of the Eskov—Zinchenko effect is proven.

© 2018, Media Sphera Publishing Group. All rights reserved. Objective. To study the efficacy of various methods of non-drug therapy of diseases manifested by vertigo and dizziness in neurological practice. Material and methods. Referral and final diagnoses were compared after neurovestibular examination of 599 patients (177 men and 422 women), aged 25 to 79 years (mean age 55 years), with various causes of vertigo. Patients underwent vestibular rehabilitation, trainings on the stabiloplatform with biological feedback (biofeedback), repositioning maneuvers in patients with benign paroxysmal positional vertigo (BPPV). Severity of dizziness on a Visual analogue scale of dizziness (VAS-d) and balance on stabilography before and after a course of vestibular rehabilitation was analyzed. Results. Before neurovestibular examination, the diagnoses of vertebrobasilar insufficiency (44%), hypertensive or atherosclerotic encephalopathy (35%), cervical spondyloarthrosis (8%), autonomic dystonia (11%)) are often considered mistakenly as the causes of vertigo and dizziness. After neurovestibular examination, the diagnoses were as follows: BPPV (39%), phobic postural vertigo (29%), Ménière’s disease (14%), vestibular neuritis (11%), multisensory dizziness in elderly (5%). The effectiveness of repositioning maneuvers in BPPV was 90,2% after the first session and 100% after the second session. After a course of vestibular exercises and trainings on the stabiloplatform with biofeedback, there was the marked improvement in indicators of stabilography and VAS-d in patients with vestibular neuritis, Meniere’s disease, phobic postural vertigo (p<0.05). Vestibular rehabilitation was most effective if started within the first month after vestibular neuritis. There was the high efficacy of complex rehabilitation, including vestibular exercises and trainings on stabilographic platform with biofeedback, in patients with Meniere’s disease. In the rehabilitation of patients with phobic postural vertigo, better results were achieved when vestibular exercises were combined with trainings on stabilographic platform with biofeedback and psychotherapy. Conclusion. The results demonstrated the low accuracy of diagnosis of diseases manifested by vertigo and dizziness and high efficacy of non-drug therapy in most cases, especially BPPV, vestibular neuritis, Meniere’s disease, postural phobic vertigo.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Mainly, intracoronary thrombosis is the cause of acute coronary syndrome. The structure of the atherosclerotic plaque plays an important role in the development of the mechanism of intracoronary thrombosis. Currently, there are various radiological methods for diagnosis of atherosclerotic plaques of the coronary arteries. The current review reveals the theme of "indirect" signs of instability of atherosclerotic plaques, their combinations and occurrence, detected by computed tomography. Retrospective studies have shown the feasibility of these signs of plaques in the assessment of the prognosis of acute coronary events. The review compares the results of computed tomography (CT) and intravascular ultrasound, which is the gold standard in the diagnosis of atherosclerotic plaque morphology.

© 2018 ABC-press Publishing House. All rights reserved. Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.