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BackgroundThe Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors.ResultsPerformance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic.ConclusionsResults show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead.

Aim. To analyze the experience of Chazov National Medical Research Center of Cardiology in patient selection for left ventricular assist device (LVAD) implantation. Materials and methods. 901 patients, whose documents were sent to Chazov National Medical Research Center of Cardiology from regional medical and prophylactic institutions, were screened as selection for LVAD implantation. Firstly, all patients underwent transthoracic echocardiography performed according to the extended protocol with a comprehensive assessment of the left and right ventricle size and function. Patients who underwent the screening procedure underwent further examination including both laboratory and instrumental diagnostic methods. In addition, the polyclinic database of patients diagnosed with chronic heart failure (CHF) and dilated cardiomyopathy was also analyzed. Results. Among 901 screened patients 7.9% were suitable candidates for LVAD implantation and only 23 (2.6%) patients underwent surgery. Among those not eligible for surgery: 208 (29%) patients were not on optimal medical therapy, 15% of patients had indications for other surgical treatment of CHF, 12% of patients had severe right ventricular failure, 9.8% had severe comorbidities, 6.8% of patients refused surgery. Conclusions. The main problems of selection for LVAD implantation were: low awareness of doctors about the introduction of new treatment methods, poor quality of transthoracic echocardiography, a large percentage of patients not receiving basic therapy for CHF, untimely referral of patients for other types of surgical treatment.

A cubic pyrochlore with the composition Bi1.865Co1/2Fe1/2Ta2O9+Δ (space group Fd-3m, a = 10.5013(8) Å) was synthesized from oxide precursors using solid-phase reactions. These ceramics are characterized by a porous microstructure formed by randomly oriented grains of an elongated shape with a longitudinal size of 0.5–1 µm. The electronic state of cobalt and iron ions in oxide ceramics was studied by NEXAFS and XPS spectroscopy. The parameters of the XPS spectra of Bi4f, Bi5d, Ta4f, Co2p, and Fe2p ionization thresholds for a complex pyrochlore were compared with the parameters of the corresponding oxides of the transition elements. The energy position of the XPS-Ta4f and -Ta5p spectra is shifted towards lower energies compared to the binding energy in tantalum(V) oxide by 0.75 eV. According to XPS spectroscopy, bismuth and tantalum cations have the corresponding effective charge of +3 and +(5-δ). The NEXAFS-Fe2p spectrum of ceramics coincides with the spectrum of Fe2O3 in its main spectrum characteristics and indicates the content of iron ions in the oxide ceramics in the form of octahedral Fe(III) ions, and according to the character of the Co2p spectrum, cobalt ions are predominantly in the Co(II) state.

Abstract Motivation Alignment of reads to a reference genome sequence is one of the key steps in the analysis of human whole-genome sequencing data obtained through Next-generation sequencing (NGS) technologies. The quality of the subsequent steps of the analysis, such as the results of clinical interpretation of genetic variants or the results of a genome-wide association study, depends on the correct identification of the position of the read as a result of its alignment. The amount of human NGS whole-genome sequencing data is constantly growing. There are a number of human genome sequencing projects worldwide that have resulted in the creation of large-scale databases of genetic variants of sequenced human genomes. Such information about known genetic variants can be used to improve the quality of alignment at the read alignment stage when analysing sequencing data obtained for a new individual, for example, by creating a genomic graph. While existing methods for aligning reads to a linear reference genome have high alignment speed, methods for aligning reads to a genomic graph have greater accuracy in variable regions of the genome. The development of a read alignment method that takes into account known genetic variants in the linear reference sequence index allows combining the advantages of both sets of methods. Results In this paper, we present the minimap2_index_modifier tool, which enables the construction of a modified index of a reference genome using known single nucleotide variants and insertions/deletions (indels) specific to a given human population. The use of the modified minimap2 index improves variant calling quality without modifying the bioinformatics pipeline and without significant additional computational overhead. Using the PrecisionFDA Truth Challenge V2 benchmark data (for HG002 short-read data aligned to the GRCh38 linear reference (GCA_000001405.15) with parameters k = 27 and w = 14) it was demonstrated that the number of false negative genetic variants decreased by more than 9500, and the number of false positives decreased by more than 7000 when modifying the index with genetic variants from the Human Pangenome Reference Consortium.

The paper presents the design of a damper based on a multilayer magnetorheological elastomer that has high load capacity, up to 500 N. The damper is able to operate in all vibration control modes, depending on its control signal. The damper cooling system is presented. Vibration tests were carried out and the damper amplitude-frequency characteristics were obtained. The transition process of damper displacement with a control step signal was analyzed.

BACKGROUND: Lacrimal glands and lacrimal pathways are one of the main undesirable targets during radionuclide therapy using I-131, namely, in 24% of cases, secondary lacrimal pathways obliteration occurs [1]. In the legislation of the Russian Federation in the field of atomic energy use, there are a number of administrative documents obliging to keep records and control of individual radiation doses with the provision of data to the unified system for monitoring individual radiation doses of citizens. At the same time, statistical analysis does not include systematic accounting and control of individual doses of internal radiation to patients, in particular, to the lacrimal apparatus, when using nuclear medicine methods for therapeutic purposes. AIM: To develop a software and hardware preventive complex — a system for accounting and monitoring dose loads on lacrimal pathways during radioiodotherapy. MATERIALS AND METHODS: GE Discovery NM/CT 670 imaging systems, GE Discovery NM 630, the Xeleris 4 DR Workstation nuclear Medicine Workstation and the I-131-based radioisotope were used. To exclude the ingress of radioisotope into lacrimal pathways, the use of vasoconstrictive drugs and the use of tear point obturators were considered. The client part of the web service was implemented based on the React JavaScript library. The development of the Backend component was carried out in the Python programming language. RESULTS: To assess the risk of complications, a method was developed that takes into account the following parameters: age, gender, total administered activity to the patient, the presence of current lacrimation at the time of hospitalization, the presence of menopause (for women) and the accumulation index I-131 in lacrimal pathways. The primary data (anamnesis and prescribed treatment) are entered by the patient's attending physician in the questionnaire during the initial examination. At 72 hours after the introduction of radioisotope, using a molecular imaging system, a medical physicist determines the index of accumulation of radioisotope in lacrimal pathways. Based on the data obtained, the overall risk level of secondary obliteration of the lacrimal tract is determined and, depending on the result obtained, appropriate recommendations are made to the patient. Since the described process is quite time-consuming in a clinical setting, an intelligent medical decision support system has been developed that allows automating the process and minimizing the likelihood of errors. CONCLUSION: The development of a software and hardware preventive complex will make it possible to prescribe preventive methods with greater efficiency at all stages of the course of treatment in order to minimize the occurrence of adverse events (such as secondary obliteration of the tear ducts), which in turn will improve the quality of life of patients.

The vortex ring states are observed when the rotor is flowed at positive angles of attack. For the main rotor, these conditions are realized during a steep descent of the helicopter at low speeds. The rotor vortex ring states are affected by significant phenomena related to the behavior of its aerodynamics, including negative phenomena. The latter is, firstly, referred to decrease in rotor thrust, increase in the required power, pulsations of thrust and torque, unsteady flapping blade motion, etc. In terms of helicopter piloting, it means a sharp loss of altitude, increase in the control force, a high level of vibration, defocusing attenuation of rotor spinning cone, as well as controllability deterioration. All these factors determine the relevance of research on these modes and the importance of solving a problem of defining their boundaries. Recently, due to the rapid development of computer technologies and computational models, it has become practical to perform numerical research of the rotor aerodynamics in vortex ring states. The paper presents the study results of Ka-226T helicopter coaxial rotor aerodynamics in steep descent modes in the field of vortex ring states. The angles of rotor attack αВ = 90...30° and the range of vertical descent velocities Vу = 0...26 m/s are considered. The original nonlinear bladed vortex model of the rotor developed at the Moscow Aviation Institute (MAI) was used. The total and distributed aerodynamic rotor characteristics were calculated. The shapes of the vortex wake and the rotor flow patterns were analyzed. The boundaries of the vortex ring states in velocity coordinates “Vx − Vу” were constructed according to various criteria reflecting the known features of these states. The results obtained significantly complement the existing experience of experimental and numerical research in this field.

Main causes of secondary hypertrophic cardiomyopathy include acromegalic cardiomyopathy. Heart damage in patients with the acromegaly is mediated both by the direct action of growth hormone and insulin-like growth factor-1, and increased deposition of collagen and lymphomononuclear cells in the myocardium, which leads to architectural changes, disturbances in fluid and electrolyte balance, severe left ventricular myocardial hypertrophy, diastolic and systolic left ventricular dysfunction and chronic heart failure. This article presents the world's first described observation demonstrating the possibility of successful transfemoral aortic valve repair to a comorbid patient with severe aortic stenosis according to the potential risks caused by the active form of the acromegaly.

Co doped bismuth magnesium tantalate with a pyrochlore structure (sp. gr. Fd-3m) was synthesized for the first time using the standard ceramic method. Single phase Bi2Mg1−xCoxTa2O9 samples were found to be formed when x < 0.7 in the X-ray phase analysis. However, with a higher cobalt content in the samples, the impurity phase β-BiTaO4 (sp. gr. P-1) is detected, and its amount is proportional to the degree of cobalt doping. The formation of solid solutions is evidenced by a uniform increase in the unit cell parameter of the Co,Mg co doped bismuth tantalate phase with an increase in the content of cobalt ions in the samples from 10.5412(8) (x = 0.3) to 10.5499(8) Å (x = 0.7). The samples exhibit a porous microstructure consisting of chaotically oriented and partially fused elongated grains measuring 1–2 μm. The dependence of the ceramic grain size on the n(Mg)/n(Co) ratio was not determined. X-ray spectroscopy (ear dge X-ray bsorption ine tructure (NEXAFS) and X-ray photoelectron spectroscopy (XPS)) was used to study the charge state of ions in Bi2Mg1−xCoxTa2O9. The NEXAFS and XPS data showed that doping with cobalt and magnesium did not change the bismuth and tantalum oxidation states in pyrochlore; in particular, the ions maintained their oxidation states of Bi(+3), Mg(+2) and Ta(+5). The energy position of the peaks of the Ta4f-, Ta5p-, Ta4d spectra had a characteristic shift towards lower energies compared to the binding energy in pentavalent tantalum oxide Ta2O5. A shift towards lower energies is characteristic of a decrease in the effective positive charge; in particular, for the Ta4f and Ta4d spectra we presented, this energy shift was ΔE = 0.65 eV, and in the region of the Ta4d edge—0.55 eV. This in turn allowed for us to assume that tantalum atoms have the same effective charge +(5-δ). The oxidation state of cobalt ions was predominantly 2+ and partially 3+, according to NEXAFS spectroscopy data.

The paper presents the results of U-Pb isotope dating of zircons extracted from rocks of the southern part of the Baltic Shield (Early Riphean conglomerates and Paleoproterozoic secondary quartzites) and makes a comparison of these results with the ages of crystalline complexes of the East European Platform (EEP). The paper presents the study results on composition of quartzites from the Bol. Tyuters and Gogland islands. There has been discussion about tectonic and paleogeographical features in the period prior to the beginning of Riphean sedimentation in the northeastern part of the EEP. It is concluded that the conglomerates are composed of erosional products of mainly Paleoproterozoic and less frequently Archean crystalline complexes. At the same time, the rocks at the base of the generalized section of Riphean deposits (Gogland group), did not contain any zircons with ages referring to 200 million years prior to the inferred time (1640–1660 Ma) of the beginning of the conglomerate sequence formation. The rocks that compose the Gogland group and their underlying Paleoproterozoic basement rocks have significant differences. We associate these differences with the existence of pre-Riphean sheet-like deposits, comprising rocks of essentially quartz composition, in the southern Baltic Shield, in the upper levels of the peneplenized Paleoproterozoic basement structure. The deposits relics are only found on the Bol. Tyuters Island; in all other places, these deposits were completely eroded or underwent significant structural and material transformations. The absence of detrital zircon grains with ages ranging from 1.87 to 1.65 Ga in the clastic rocks of the Riphean basal horizons implies no noticeable Pre-Riphean and Early Riphean orogenic movements in the northeastern part of the EEP. Tectono-magmatic reactivation in this region occurred only in the middle of the Early Riphean.

Aim. To study the changes of left ventricular (LV) contractile function in patients with severe mitral valve (MV) insufficiency with assessment of global longitudinal strain (GLS) indicators and LV myocardial function after the mitral transcatheter edge-to-edge repair (TEER) within 12-month follow-up.Material and methods. The study consisted of 43 patients with severe mitral regurgitation (MR) as follows: 23 patients with functional MR (FMR), 20 patients with degenerative MR (DMR). A comprehensive echocardiographic study, including speckle tracking echocardiography, was performed at baseline, 4-5 days, 6 and 12 months after TEER. Standard structural and functional indicators of the LV, LV GLS and myocardial performance parameters were assessed.Results. The early postoperative period (4-5 days) was characterized by a decrease in global constructive work (GCW) (FMR group — from 977 [684; 1253] to 857 [736; 1488] mm Hg%, (p=0,038); DMR group — from 1458 [1283; 1848] to 1350 [1010; 1488] mm Hg% (p=0,011)), an increase in global wasted work (GWW) (FMR group — from 177 [130; 280] to 336 [242; 388] mm Hg% (p=0,004); DMR group — from 128 [81; 172] to 216 [164; 279] mm Hg% (p=0,043)), which was accompanied by a decrease in myocardial efficiency (FMR group — from 81,5 [77; 87] to 76 [73; 79]%, (p=0,021); DMR group — from 90 [85; 93] to 82 [79; 85]% (p=0,018)). After 12-month follow-up, there was a significant increase in GCW relative to the initial values in both cohorts of patients as follows: FMR group — to 1128 [890; 1711] mm Hg% (p=0,048); DMR group — to 1818 [1478; 2034] mm Hg% (p

Background. Development of a methodological apparatus for constructing means to ensure the required level of probability of failure-free operation and survivability of self-healing specialized computers (SEVMs). During the research, an analysis of operating conditions and a selection of reliability indicators for computers of aerospace equipment was carried out. Requirements for computer backup methods are formulated. A comparative assessment of the detecting ability and hardware costs was carried out when implementing the majority redundancy method, the duplication method and the use of correcting codes. Materials and methods. The expediency of using the duplication method is substantiated to increase the probability of failure-free operation and survivability of self-healing central computers, using algebraic linear codes to identify a faulty backup channel. Unlike known codes, it is proposed to use an algebraic linear code, in which the values of the check bits correspond to the direct and inverse values of the information bits, which makes it possible to detect errors when reading information from the inverse outputs of the memory, correct single errors, detect double errors and control the logical inversion operation, necessary to represent a negative number in two's complement code, which makes it possible to adapt the code to control arithmetic and logical operations of the computer processor. An assessment was made of the probability of failure-free operation of a duplicated computer, with its general redundancy, with detection and correction of single errors in the backup memory channels and detection of errors in the backup channels of the processor ALU based on the proposed code, and an assessment of the probability of failure-free operation of the computer, with its separate redundancy, with error detection in the backup channels of the duplicated memory based on the Hamming code and error correction in the backup channels of the processor ALU based on the majority method. Results and conclusions. As a result of comparing the probabilities of failure-free operation, it was established that the general redundancy of the computer based on the proposed code, in comparison with the separate redundancy of the memory and ALU of the computer processor, allows for a gain in the probability of failurefree operation of the computer and its functional devices throughout the entire period of operation.

The article proposes a clarification to the interpretation of the composition of the poem by N.A. Nekrasov “Who Lives Happily in Russia.” In post-war Soviet editions, “Prologue” (“In what year — guess...”) was constantly published as part of the first part of the poem. The article argues for the need to print it before the whole poem, since in the last lifetime editions of the poet’s poems “Prologue” was “out of place” as a result of external circumstances. The fact is that the very division into parts in the poem appeared when the 5th part of the edition of 1869–1873. (containing the prologue and the first five chapters) was already typed and the changes had to be made to the finished layout.