Search

The article presents ceramic materials from the excavations on the Pashenkovo Russian medieval settlement of the Golden Horde period, located in the Middle Don. The site is located on the territory of the village of Pashenkovo in the Khokholskiy district of the Voronezh region. The main purpose of the study is to determine the chronology of Russian pottery from the Pashenkovo settlement based on the technical and morphological features of the ceramics and a comparative analysis with materials from other sites, located on the territory of the Middle and Upper Don. All analyzed ceramic material from the Pashenkovo settlement comes from the filling of the pit and the layers above it, which represent a single complex. Individual finds from the territory of the site made it possible to tentatively date it within the XIV century. The analyzed pottery consisted of more than one thousand fragments, which included fragmented upper profile parts, walls and bottoms of pots. As a result of the work carried out on the archaeological site, a pre-Mongol ceramic tradition was identified, which has complete parallels in the Upper Don and Ob regions. The greatest similarity in technical and morphological characteristics, and sometimes complete identity, is found with the pottery from the Semiluki settlement, located 45 km upstream of the Don river on its right bank. Based on the obtained data, the authors propose to date the pottery assemblage of the Pashenkovo settlement within the second half of XIII-first half of XIV century.

Summary: Neuroblastoma exhibits significant inter- and intra-tumor genetic heterogeneity and varying clinical outcomes. Extrachromosomal DNAs (ecDNAs) may drive this heterogeneity by independently segregating during cell division, leading to rapid oncogene amplification. While ecDNA-mediated oncogene amplification is linked to poor prognosis in various cancers, the effects of ecDNA copy-number heterogeneity on intermediate phenotypes are poorly understood. Here, we leverage DNA and RNA sequencing from the same single cells in cell lines and neuroblastoma patients to investigate these effects. By analyzing ecDNA amplicon structures, we reveal extensive intercellular ecDNA copy-number heterogeneity. We also provide direct evidence of how this heterogeneity influences the expression of cargo genes, including MYCN and its downstream targets, and the overall transcriptional state of neuroblastoma cells. Our findings highlight the role of ecDNA copy number in promoting rapid adaptability of cellular states within tumors, underscoring the need for ecDNA-specific treatment strategies to address tumor formation and adaptation.

The second part of an interdisciplinary expert consensus on tissue banking is presented. An analysis and attempt was made to systematize some of the terms and definitions used by tissue bank specialists in the process of their work and presented in the Federal laws and orders of the Ministry of Health of the Russian Federation regulating medical activities in the field of tissue donation and their clinical use.

Introduction. Bovine respiratory syncytial virus (Pneumoviridae: Orthornavirae, Orthopneumovirus; Bovine orthopneumovirus, Bovine respiratory syncytial virus, BRSV) is one of causative agents of respiratory diseases in animals. The study of the occurrence and genetic diversity of this pathogen is of particular importance. Objective. To study the frequency of virus in animals using RT-PCR and genetic heterogeneity of isolates based on determining the complete nucleotide sequence of glycoprotein G gene. Materials and methods. A 381-bp region of glycoprotein F gene was used for identification of virus genome, while complete nucleotide sequences of G gene were used for phylogenetic analysis. Phylogenetic trees were constructed using the maximum likelihood method in MEGA 7.0 software. Results. During outbreaks of respiratory diseases, BRSV RNA was detected in animals of all ages in samples of lungs, nasal secretions, pulmonary lymph nodes. Complete nucleotide sequences of glycoprotein G gene, 771 bp in length were obtained for five isolates and 789 bp in length ‒ for two isolates. Nucleotide similarity between them was 87–100%. Phylogenetic analysis assigned the isolates to subgroups II and III, each of which included two isolates. A separate clade formed by K18 isolate from animals imported from Canada and sequences from vaccines containing the attenuated «375» strain. Conclusion. The virus genome was identified in cows and heifers (20.0 and 14.3%), in calves up 1 month of age (3.05%), and in calves from 1 to 6 months of age (6.7%). Complete G gene nucleotide sequence analysis is a useful tool for studying the molecular epidemiology of BRSV on particular territories.

IntroductionThe development of next-generation tissue-engineered medical devices such as tissue-engineered vascular grafts (TEVGs) is a leading trend in translational medicine. Microscopic examination is an indispensable part of animal experimentation, and histopathological analysis of regenerated tissue is crucial for assessing the outcomes of implanted medical devices. However, the objective quantification of regenerated tissues can be challenging due to their unusual and complex architecture. To address these challenges, research and development of advanced ML-driven tools for performing adequate histological analysis appears to be an extremely promising direction.MethodsWe compiled a dataset of 104 representative whole slide images (WSIs) of TEVGs which were collected after a 6-month implantation into the sheep carotid artery. The histological examination aimed to analyze the patterns of vascular tissue regeneration in TEVGs in situ. Having performed an automated slicing of these WSIs by the Entropy Masker algorithm, we filtered and then manually annotated 1,401 patches to identify 9 histological features: arteriole lumen, arteriole media, arteriole adventitia, venule lumen, venule wall, capillary lumen, capillary wall, immune cells, and nerve trunks. To segment and quantify these features, we rigorously tuned and evaluated the performance of six deep learning models (U-Net, LinkNet, FPN, PSPNet, DeepLabV3, and MA-Net).ResultsAfter rigorous hyperparameter optimization, all six deep learning models achieved mean Dice Similarity Coefficients (DSC) exceeding 0.823. Notably, FPN and PSPNet exhibited the fastest convergence rates. MA-Net stood out with the highest mean DSC of 0.875, demonstrating superior performance in arteriole segmentation. DeepLabV3 performed well in segmenting venous and capillary structures, while FPN exhibited proficiency in identifying immune cells and nerve trunks. An ensemble of these three models attained an average DSC of 0.889, surpassing their individual performances.ConclusionThis study showcases the potential of ML-driven segmentation in the analysis of histological images of tissue-engineered vascular grafts. Through the creation of a unique dataset and the optimization of deep neural network hyperparameters, we developed and validated an ensemble model, establishing an effective tool for detecting key histological features essential for understanding vascular tissue regeneration. These advances herald a significant improvement in ML-assisted workflows for tissue engineering research and development.

Background The Philippines has a shortage and uneven distribution of healthcare workers (HCWs). Job satisfaction is an important element to HCW retention and attracting new HCWs into the health system.Objective This study measured HCWs’ intent to stay and HCWs’ satisfaction after implementation of multiple interventions intended to strengthen the primary care system, and determine factors significantly associated with HCWs’ intent to stay.Methodology This is a serial cross-sectional study in urban, rural and remote primary care sites in the Philippines. All physicians, nurses, midwives, dentists, community health workers and support staff were invited to participate. Baseline HCWs’ intent to stay and satisfaction were obtained using a self-administered questionnaire prior to implementation of interventions. The same survey was again conducted in the years 2021 and 2022, corresponding to 5 and 6 years after initial implementation for the urban site, and 2 and 3 years for the rural and remote sites. We used multiple logistic regression to determine factors associated with intent to stay.Results There were 430 survey respondents (89.4% response rate) for year 2021, and 417 survey respondents (97.4% response rate) for year 2022. The urban and rural sites had significant increase in several HCW satisfaction domains, while the remote site had significant decrease in several HCW satisfaction domains. There was no significant difference in the intent to stay in the three sites. Factors that decreased intent to stay included length of employment, job involvement and employment as a nurse, while factors that increased intent to stay included job satisfaction, enjoyment and working in the urban site.Conclusion HCW satisfaction improved in the urban site and rural site, while HCW satisfaction declined in the remote site. Intention to stay of primary care HCWs did not significantly change.

Summary: The tobacco hornworm is a laboratory model that is particularly suitable for analyzing gut inflammation, but a physiological reference standard is currently unavailable. Here, we present a surface atlas of the healthy hornworm gut generated by scanning electron microscopy and nano-computed tomography. This comprehensive overview of the gut surface reveals morphological differences between the anterior, middle, and posterior midgut, allowing the screening of aberrant gut phenotypes while accommodating normal physiological variations. We estimated a total resorptive midgut surface of 0.42 m2 for L5d6 larvae, revealing its remarkable size. Our data will support allometric scaling and dose conversion from Manduca sexta to mammals in preclinical research, embracing the 3R principles. We also observed non-uniform gut colonization by enterococci, characterized by dense biofilms in the pyloric cone and downstream of the pylorus associated with pore and spine structures in the hindgut intima, indicating a putative immunosurveillance function in the lepidopteran hindgut.

Remote electronic voting (REV) as technology is gradually taking root in the political practice in Russia. As the technology is legally and chronologically new, it is both interesting and necessary to explain its implementation, as well as to identify the technological basis of the REV and, therefore, questions about the potential illegal use of this technology. This study aims at identifying the elements of the analysis of the implementation and legitimation of REV in cities and villages across Russia. The research is based on qualitative sociological and general logical methods: in general, the author uses the dialectical-materialistic approach, as well as the tools of comparative politics. A series of expert interviews were conducted in 10 regions of Russia. The results of the study showed that the Central Election Commission of the Russian Federation, the regional election commissions of the subjects of the Russian Federation, as well as regional and municipal authorities where the REV is being held, are at this stage looking for specific technologies to legitimize electronic voting. These practices will differ not only when comparing different regions, but also, most often, within one subject. One of the most significant differences will be noticeable with the introduction of REV in highly urbanized massifs and rural areas. Urban areas are characterized by the wide usage of political technologies to attract voters to electronic voting and legitimize it. Significantly larger budgets are invested in propaganda materials, including large, printed products (billboards, advertising at bus stops, and public transport). The idea of electronic voting is being promoted in social networks, mainly through VK, Telegram, Odnoklassniki, and WhatsApp. The rural areas, meanwhile, are characterized by activities aimed at personal contact with the voters and the use of informal connections. At the same time, today messages in social networks also reach rural residents, although most often it is not a purposeful activity, but a background capture of the audience. Concerning the improvement of the technological basis and the expansion of the geography of the REV, we can further elaborate on its legitimization and implementation, including in the context of the issues identified in this study.

Introduction. African swine fever virus (ASF) is a large, enveloped virus with an icosahedral capsid morphology and a double-stranded DNA genome ranging in size from 170 to 190 kb. The replication cycle proceeds in two phases, the early phase lasting 46 hours and the late 820 hours after infection. The adaptation of the ASF virus to growth in continuous cell lines makes efficient and reliable genetic analysis and more accurate interpretation of its results. Objective. Adaptation of a new isolate of the ASF virus to growth in a continuous cell line by the method of accelerated passages and preliminary genetic analysis of the resulting strain. Materials and methods. For virus isolation and passaging of the ASF virus, a porcine leukocyte cell culture (PL) and continuous cell cultures of porcine origin (ST, PK, PPK-66b) were used with Eagle MEM and HLA essential media with 10% porcine or fetal serum. Results. The article presents data on the isolation and analysis of the changes in the reproductive properties of a new African swine fever (ASF) virus isolate in the process of adaptation to growth in a continuous piglet kidney cell culture clone b (PPK-66b). The current state of the problem of cultivation of the ASF virus, the features of its reproduction, and the basis of the genetic differentiation of its isolates are described in detail. Understanding the uniqueness of the nature of the ASF virus determined the approaches to the processes of its cultivation and adaptation. In this regard, the results of studies of cultural properties, and analysis of the nucleotide sequence of 6 genes of the new isolate, as well as phylogenetic analysis of these genes with already known strains and isolates of the ASF virus are presented. Conclusion. A new strain obtained in the process of cell adaptation of ASVF/Znaury/PPK-23 ASF virus by the accelerated passaging method reaches a high level of reproduction in 72 hours with an accumulation titer of 7.07 lg HAdE50/cm3. Primary genetic analysis allowed to establish the main phylogenetic relationships of the newly isolated strain with previously known variants of the current ASF panzootic.

In plant hormone signaling, transcription factor regulatory networks (TFRNs), which link the master transcription factors to the biological processes under their control, remain insufficiently characterized despite their crucial function. Here, we identify a TFRN involved in the response to the key plant hormone auxin and define its impact on auxin-driven biological processes. To reconstruct the TFRN, we developed a three-step procedure, which is based on the integrated analysis of differentially expressed gene lists and a representative collection of transcription factor binding profiles. Its implementation is available as a part of the CisCross web server. With the new method, we distinguished two transcription factor subnetworks. The first operates before auxin treatment and is switched off upon hormone application, the second is switched on by the hormone. Moreover, we characterized the functioning of the auxin-regulated TFRN in control of chlorophyll and lignin biosynthesis, abscisic acid signaling, and ribosome biogenesis.

It is shown in this work that, with strong focusing of a beam with optical vortex and circular polarization, three energy flows take place in the focal plane: direct longitudinal, reverse longitudinal and azimuthal transverse flows. Calculations are made analytically using the Richards–Wolf formalism and by numerical simulation. Moreover, the energy rotation at different lengths from the optical axis occurs in different directions. Therefore, the focal plane intersects along the optical axis only part of the initial beam energy per unit time. The same energy part (other things being equal) intersects the focal plane along the positive direction of the optical axis when an optical vortex with cylindrical polarization is focused. The difference is that, if an optical vortex is present, then the transverse energy flux at the focus rotates around the optical axis. If an optical vortex is not present (a beam with only cylindrical polarization), then the average transverse flow in the focal plane is zero, though, in some regions in the focal plane, the flow is directed towards the optical axis and, in other regions, away from it. This behavior of the transverse energy flow at the focus (flow direction towards the optical axis and away from the optical axis) of a cylindrical vector beam can be deemed another kind of Hall effect.

Introduction. Epizootological monitoring of the area contamination with the causative agent of tularemia implies the collection and analysis of a variety of field specimens. The analysis of such objects is time- and labour-consuming. In this context, simple and fast diagnostic techniques are needed to analyze specimens under resource-limited conditions. Aim. To study the possibility of using immunomagnetic separation for accelerated detection of Francisella tularensis cells in soil samples using immunochromatography. Materials and methods. Immunomagnetic particles (IMPs) were produced by using monoclonal antibodies to lipopolysaccharide (LPS) of the tularemia causative agent. Soil specimens weighing 1 g with preliminary introduced inactivated F. tularensis 15/10 cells were used in the study. The samples were suspended in an extraction buffer (EB) and filtered. Tularemia cells were separated by IMP suspension. The particles were washed, resuspended in EB and heated at 100C for 5 minutes. The supernatant was analyzed with test strips based on F. tularensis IC-test kit. Results. A combination of the immunomagnetic separation method and the IC test to detect F. tularensis cells identified up to 1 106 cells of the tularemia pathogen in analyzed soil samples, while 1 107 cells were detected in soil washouts in the absence of immunomagnetic separation. Conclusion. The developed technique combining immunomagnetic separation and IC tests opens up prospects for express diagnostics of soil sample contamination in tularemia foci. The analysis takes about 3 hours, and its sensitivity is 1 106 cells/g of soil. The technique is simple, not requiring sophisticated expensive equipment. It can be easily adapted for testing other specimen types (water, grain, etc.). In addition, separated bacterial cells can be used for F. tularensis detection by other methods.

Abstract Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.

Introduction. Rabbit hemorrhagic disease is an acute highly contagious infection associated with two genotypes of pathogenic Lagovirus. Antibodies to major capsid protein (Vp60) are protective. The aim of the work ‒ is an evaluation of antigenic and immunogenic activity of virus-like particles (VLPs) based on recombinant major capsid proteins of both genotypes of rabbit hemorrhagic disease virus (RHDV) (recVP60-GI1 and recVP60-GI2). Materials and methods. Baculovirus-expressed VLPs were evaluated using electron microscopy and administered to clinically healthy 1.53 month old rabbits in a dose of 50 g. Rabbits were challenged with 103 LD50 of virulent strains Voronezhsky-87 and Tula 21 days post immunization. Serum samples were tested for the presence of RHDV-specific antibodies. Results. VLPs with hemagglutination activity forming VLP 3040 nm in size were obtained in Hi-5 cell culture. Specific antibody titers in rabbits measured by ELISA were 1 : 200 to 1 : 800 on 21th day post immunization with VLPs. Immunogenic activity of recVP60-GI1 VLPs was 90 and 40%, while it was 30 and 100% for recVP60-GI2 VLPs after the challenge with RHDV genotypes 1 and 2 respectively. The immunogenicity of two VLPs in mixture reached 100%. Discussion. VLPs possess hemagglutinating, antigenic and immunogenic activity, suggesting their use as components in substances designed for RHDV specific prophylaxis in rabbits. Results of the control challenge experiment demonstrated the need to include the antigens from both RHDV genotypes in the vaccine. Conclusion. Recombinant proteins recVP60-GI1 and recVP60-GI2 form VLPs that possess hemagglutinating an antigenic activity, and provide 90100% level of protection for animals challenged with RHDV GI1 and GI2 virulent strains.

The relevance of this study is caused by the need for import substitution of software in the field of design, modeling and optimization of the gas and oil processing. Almost all software for modeling used at oil and gas entities are the developments of the USA, Canada, Great Britain and other countries. In the current conditions of sanctions risks on using imported software for modeling technological processes, the development and rapid adaptation of engineering mathematical models of all basic oil refining processes are an extremely urgent task. These models will further become the basis of Russian import-substituting software products. Over the course of 30 years, the National Research Tomsk Polytechnic University has been researching the processes of the motor fuels production. On the basis of these studies the reliable mathematical models have been developed for technologies such as catalytic reforming of gasoline, isomerization of the hydrocarbons pentane-hexane fraction, catalytic cracking of vacuum distillate and mixed petroleum feedstock, hydroprocessing of petroleum fractions, compounding of high-octane gasolines, and others. Distinctive features of the developed mathematical models are related to following: firstly, they are built on the basis of real industrial data on the operation units at various refineries and, secondly, they take into account the main fundamental physical and chemical laws of reaction mechanisms, the catalyst deactivation as well as the macrokinetic factors of motor fuel production processes. The solution of multicriteria problem of optimizing the technology of preparation of motor fuels (gasoline and diesel fuels) is possible using the method of mathematical modeling on a physical and chemical basis. This approach takes into account the thermodynamics and kinetics of hydrocarbon conversions on the catalyst surface, as well as the non-stationarity of the processes due to coking, aging and poisoning by harmful impurities of the catalyst, changes in the chemical composition of the feedstock. The aim of this study is to develop the technical solutions aimed at improving the efficiency of multi-stage gasoline production using the engineering models of oil refining processes. The method of research is based on using the mathematical modelling method for multi-stage processes of petroleum feedstock refining. The group and individual composition of various petroleum fractions determined by chromatographic methods, were used as an initial data. Results. The effect of the component composition of the processed feedstock of catalytic reforming on the qualitative and quantitative properties of the components of commercial gasoline was estimated and predicted. The use of the catalytic cracking model showed that when processing the feedstock with a lower content of aromatic hydrocarbons and resins the coke content on the catalyst is lower by 0,15 % wt. This leads to increasing the catalyst activity and the desired product yields by 6,7 % and 4,9 wt. % in comparison with the feedstock with higher content of resins and aromatics.The maximum gasoline yield for two types of the feedstocks (55,4 and 56,5 % wt.) which is achieved at 536,0 and 534,0 °C was determined according to their hydrocarbon compositions. The predictive calculations with an assessment of how the composition of the catalytic cracking gasoline influences the formulation and commercial quality of the commercial gasoline using the lighter catalytic cracking feedstock, were performed. The possibility of increasing the amount of the catalytic cracking gasoline into the commercial gasoline formula is shown. The cost of motor fuel production in this case is reduced from 0,1 to 1,0 %.

Summary: Neuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although clinical risk-defining genomic alterations exist in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography and mutational signatures derived from all variant classes, we identified co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is associated with differences in the mutational processes driving these scenarios, linking risk-defining pathognomonic variants to distinct molecular processes. Whereas high-risk MYCN-amplified neuroblastomas were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas were marked by footprints of chromosome mis-segregation and TOP1 mutational activity. Furthermore, analysis of subclonal mutations uncovered differential activity of these processes through neuroblastoma evolution. Thus, clinical heterogeneity of neuroblastoma patients can be linked to differences in the mutational processes that are active in their tumors.

Introduction. Bovine coronaviruses (BCoVs) are causative agents of diarrhea, respiratory diseases in calves and winter cow dysentery. The study of genetic diversity of these viruses is topical issue. The purpose of the research is studying the genetic diversity of BCoV isolates circulating among dairy cattle in Siberia. Materials and methods. Specimens used in this study were collected from animals that died or was forcedly slaughtered before the start of the study. The target for amplification were nucleotide sequences of S and N gene regions. Results. Based on the results of RT-PCR testing, virus genome was present in 16.3% of samples from calves with diarrheal syndrome and in 9.9% with respiratory syndrome. The nucleotide sequences of S gene region were determined for 18 isolates, and N gene sequences - for 12 isolates. Based on S gene, isolates were divided into two clades each containing two subclades. First subclade of first clade (European line) included 11 isolates. Second one included classic strains Quebec and Mebus, strains from Europe, USA and Korea, but none of sequences from this study belonged to this subclade. 6 isolates belonged to first subclade of second clade (American-Asian line). Second subclade (mixed line) included one isolate. N gene sequences formed two clades, one of them included two subclades. First subclade included 3 isolates (American-Asian line), and second subclade (mixed) included one isolate. Second clade (mixed) included 8 sequences. No differences in phylogenetic grouping between intestinal and respiratory isolates, as well as according to their geographic origin were identified. Conclusion. The studied population of BCoV isolates is heterogeneous. Nucleotide sequence analysis is a useful tool for studying molecular epidemiology of BCoV. It can be beneficial for choice of vaccines to be used in a particular geographic region.

Abstract Background Methicillin resistant Staphylococcus aureus (MRSA) is a major burden for hospitals globally. However, in the Netherlands, the MRSA prevalence is relatively low due to the ‘search and destroy’ policy. Routine multiple-locus variable-number of tandem repeat analysis (MLVA) of MRSA isolates supports outbreak detection. However, whole genome multiple locus sequence typing (wgMLST) is superior to MLVA in identifying (pseudo-)outbreaks with MRSA. The present study describes a pseudo-outbreak of MRSA at the bacteriology laboratory of a large Dutch teaching hospital. Methods All staff members of the bacteriology laboratory of the Elisabeth-TweeSteden hospital were screened for MRSA carriage, after a laboratory contamination with MRSA was suspected. Clonal relatedness between the index isolate and the MRSA isolates from laboratory staff members and all previous MRSA isolates from the Elisabeth-TweeSteden hospital with the same MLVA-type as the index case was examined based on wgMLST using whole genome sequencing. Results One of the staff members was identified as the probable source of the laboratory contamination, because of carriage of a MRSA possessing the same MLVA-type as the index case. Eleven other isolates with the same molecular characteristics were found in the database, of which seven were retrospectively suspected of contamination. Clonal relatedness was found between ten isolates, including the isolate found in the staff member and the MRSA found in the index patient with a maximum of eleven alleles difference. All isolates were epidemiologically linked through the laboratory staff member, who had worked on all these cultures. Conclusions The present study describes a MRSA pseudo-outbreak over a 2.5-year period due to laboratory contamination caused by a MRSA carrying laboratory staff member involving nine patients. In case of unexpected bacteriological findings, the possibility of a laboratory contamination should be considered.

Here, combining diagnostic imaging modalities and in vivo assays, Windfelder and colleagues established tobacco hornworm larvae Manduca sexta as an alternative high-throughput platform to study the innate immunity of the gut and host-pathogen interactions. Using the platform, the authors identify mediators of gut inflammation, differentiate pathogens from gut mutualist bacteria, and demonstrate pharmacological interventions.

The relevance of the research is caused by the need of catalytic reforming modernization by selecting and varying feed on the basis of an existing enterprise, as well as at the stage of its design. The main aim of the research is to analyze the influence of raw materials from a gas condensate field on the qualitative and quantitative characteristics of the product. Objects: feed from three gas condensate reservoirs in Western and Eastern Siberia. Methods: determination of individual and group hydrocarbon composition by capillary gas chromatography method; mathematical modeling to study the impact of feed varying. Results. A mathematical model of semi-regenerative catalytic reforming was developed. The feed composition impact on the reformate yield and quality was studied using the mathematical model. The feed used is degassed condensate from three different gas condensate fields in Western and Eastern Siberia. The degassed condensate was obtained by standard separation in the research laboratory «GasInformPlast». The paper introduces the index of raw materials, indicating the predominance of a certain hydrocarbon group in the compositions of three degassed condensates. It was revealed that use of the feed from gas condensate fields with a minimum content of paraffin hydrocarbons and a high value of naphthenic and aromatic hydrocarbons leads to increase in the yield of aromatic hydrocarbons by 20 % wt.; increase in reformate yield by 3 % wt.; increase in octane number by 7–8 points; increased coking by 0,5 % wt. The change in the composition of gasoline fractions during gas condensate field operation for five years is analyzed using the mathematical model. It was established that increase in the life of the deposit has negative effect on the catalytic reforming system due to the increase in aromatic compounds in its composition.

This review presents the current state of the problem of development and application of the specific prevention of African swine fever (ASF) with a brief description of its etiology and pathogenesis. The unique nature of the ASF virus (ASFV) determines some limitations and the complexity of solving the problem of vaccine development. Such situation stimulated the development of highly specific diagnostic methods for rapid and accurate detection of the ASFV. In this regard, results of studies, including our own, concerning the comparative analysis of the genome of vaccine and virulent strains of the ASFV, as well as immunodiagnostic approaches to determine causes of high virulence and low protective activity of the ASFV, are briefly presented. Special attention is given to the issue related to the development of safe and effective vaccines against ASF. In this context disadvantages and possible advantages of live attenuated (LAV) and recombinant (RV) vaccines are considered in details. Results of recent studies on the assessment of the immunogenicity of genetically modified vaccines (GMV) which developed in various laboratories around the world are presented. The obtained data indicate that ASF vaccination is currently the most promising measure to stop the spread of this disease in our country and in the world, however, previous experience with ASF vaccination has revealed some problems in its development and application. The significant contribution of foreign researchers to the study of the basics of virulence of this pathogen and the study of its genes functions are noted. The possible further expansion of ASF in Europe and Asia in bordering Russia territories, as well as the established fact of the persistence of ASFV in wild boar population indicate a constant threat of its re-introduction into our country. In conclusion, the importance of developing a safe effective vaccine against ASF and the assessing of the possible risks of creating the artificial sources of the infection in nature as a result of its use is emphasized.

Summary: The tobacco hornworm is used extensively as a model system for ecotoxicology, immunology and gut physiology. Here, we established a micro-computed tomography approach based on the oral application of the clinical contrast agent iodixanol, allowing for a high-resolution quantitative analysis of the Manduca sexta gut. This technique permitted the identification of previously unknown and understudied structures, such as the crop or gastric ceca, and revealed the underlying complexity of the hindgut folding pattern, which is involved in fecal pellet formation. The acquired data enabled the volume rendering of all gut parts, the reliable calculation of their volumes, and the virtual endoscopy of the entire alimentary tract. It can provide information for accurate orientation in histology uses, enable quantitative anatomical phenotyping in three dimensions, and allow the calculation of locally effective midgut concentrations of applied chemicals. This atlas will provide critical insights into the evolution of the alimentary tract in lepidopterans.

Two linked gear wheels in a micromachine can be simultaneously rotated in opposite directions by using a laser beam that has in its section areas the spin angular momentum (SAM) of the opposite sign. However, for instance, a cylindrical vector beam has zero SAM in the focus. We alter a cylindrical vector beam so as to generate areas in its focus where the SAM is of opposite signs. The first alteration is adding to the cylindrical vector beam a linearly polarized beam. Thus, we study superposition of two rotationally symmetric beams: those with cylindrical and linear polarization. We obtain an expression for the SAM and prove two of its properties. The first property is that changing superposition coefficients does not change the shape of the SAM density distribution, whereas the intensity changes. The second property is that maximal SAM density is achieved when both beams in the superposition have the same energy. The second perturbation is adding a spatial carrier frequency. We study the SAM density of a cylindrical vector beam with a spatial carrier frequency. Due to periodic modulation, upon propagation in space, such a beam is split into two beams, having left and right elliptic polarization. Thus, in the beam transverse section, areas with the spin of different signs are separated in space, which is a manifestation of the spin Hall effect. We demonstrate that such light beams can be generated by metasurfaces, with the transmittance depending periodically on one coordinate.

Oxidative stress is involved in a wide range of age-related diseases. A critical role has been proposed for mitochondrial oxidative stress in initiating or promoting these pathologies and the potential for mitochondria-targeted antioxidants to fight them, making their search and testing a very urgent task. In this study, the mitochondria-targeted antioxidants SkQ1, SkQ3 and MitoQ were examined as they affected isolated rat liver mitochondria and yeast cells, comparing SkQ3 with clinically tested SkQ1 and MitoQ. At low concentrations, all three substances stimulated the oxidation of respiratory substrates in state 4 respiration (no ADP addition); at higher concentrations, they inhibited the ADP-triggered state 3 respiration and the uncoupled state, depolarized the inner mitochondrial membrane, contributed to the opening of the mPTP (mitochondrial permeability transition pore), did not specifically affect ATP synthase, and had a pronounced antioxidant effect. SkQ3 was the most active antioxidant, not possessing, unlike SkQ1 or MitoQ, prooxidant activity with increasing concentrations. In yeast cells, all three substances reduced prooxidant-induced intracellular oxidative stress and cell death and prevented and reversed mitochondrial fragmentation, with SkQ3 being the most efficient. These data allow us to consider SkQ3 as a promising potential therapeutic agent to mitigate pathologies associated with oxidative stress.

Alveolar rhabdomyosarcoma is a clinically challenging disease due to the lack of druggable targets. Here the authors show preclinical evidence for ATR inhibitors as a therapeutic option for alveolar rhabdomyosarcoma.

Classical cryptosystems proposed by Robert McEliece (1978) and Harold Niederreiter (1986) and their modern variations are studied. A detailed review of five code-based public key cryptosystems has been presented. It is shown that some of the modern interpretations of the classical McEliece and Niederreiter cryptosystems have significant issues. In particular, it has been established that the XGRS cryptosystem based on extended Reed-Solomon codes does not provide the declared level of security against the information set decoding attack, and also has a number of inaccuracies. It is shown that the time of key generation and decryption in modern cryptosystems is quite large, and the public and private keys take up a large amount of memory. The inaccuracies of the considered schemes revealed in this work can be used to improve and adjust the systems, as well as to build a more accurate assessment of their security level and efficiency. The presented cryptosystems can be considered as standards for post-quantum cryptography and can be used to protect data after development of powerful quantum computers.

It is generally accepted that mycobiota diversity in urban greenhouses is poorer than in natural ecosystems, but our knowledge on this field of research is fragmentary. Here, we present the results of a long-term study of aphyllophoroid macrofungi (Basidiomycota) forming fruitbodies on non-native sub/tropical woody and herbaceous plants in the greenhouses of Saint Petersburg, Moscow, and Ekaterinburg botanical gardens located in the hemiboreal vegetation subzone of Eastern Europe. Over 20 years of research, fruitbodies of 58 species of aphyllophoroid fungi have been identified. Fungal species that developed on the wooden structures of greenhouses and building materials made of local wood are discussed separately. The list of fungi on non-native substrates is dominated by saprobes (93.1% of total list) as well as mycorrhizal with basidiomata on plants (8.6%). Phytopathogens have the lowest number (7.0%), and ¾ of species are widespread locally. Non-native plants are dominated by native fungal species (78.9%), while the percentage of non-native species is low (21.1%). In the three surveyed cities, the area of the studied greenhouses is 2.8 ha, and not a single species of fungi has been found twice on the same substrate. Half of the identified species are characterized by a single specimen (29 species/50.9%). Hymenochaete rheicolor was discovered in Russia for the first time and its known distribution is discussed. Only six (Antrodia gossypium, Hyphodontia arguta, Lyomyces sambuci, Peniophora cinerea, Ramariopsis kunzei, and Trechispora farinacea) local species (10.5%) were collected in all the three cities. The α-diversity of mycobiota (mean number of species per site, Shannon Index, and Menhinick Index) in the Ekaterinburg’s greenhouses is 1.2–3.0 times lower compared to suburban forest parks and old-growth natural forests, while β-diversity (Whittaker Index, Jaccard Index, and Morisita–Horn Index), on the contrary, is 2.1–7.7 times higher. With the plants’ age, the probability of detecting fungi on them increases significantly. In greenhouses, phytopathogenic aphyllophoroid macrofungi are collected on woody plants only, but the probability of their development is not related to the plants’ age.

Abstract Magnetic resonance imaging (MRI) is the key whole-body imaging technology for observing processes within a living object providing excellent resolution and contrast between soft tissues. In the present work, we exploited the non-destructive properties of MRI to track longitudinally the dynamic changes that take place in developing pupae of the Emperor Moth (Saturnia pavonia) during the last days before eclosion. While in diapause pupae, body fluid was almost homogeneously distributed over the internal compartments, as soon as wings, legs, flight muscles and the head region were fully developed, a significant redistribution of water levels occurred between thoracic and abdominal regions. During the last two days before eclosion, the developing moths transferred substantial amounts of liquid into the gut and the labial gland, and in case of females, into developing eggs. Concomitantly, the volume of the air sacs increased drastically and their expansion/compression became clearly visible in time-resolved MR images. Furthermore, besides ventilation of the tracheal system, air sacs are likely to serve as volume reservoir for liquid transfer during development of the moths inside their pupal case. In parallel, we were able to monitor noninvasively lipid consumption, cardiac activity and haemolymph circulation during final metamorphosis.

Good fixation of filigree specimens for micro-CT examinations is often a challenge. Movement artefacts, over-radiation or even crushing of the specimen can easily occur. Since different specimens have different requirements, we scanned, analysed and compared 19 possible fixation materials under the same conditions in the micro-CT. We focused on radiodensity, porosity and reversibility of these fixation materials. Furthermore, we have made sure that all materials are cheap and easily available. The scans were performed with a SkyScan 1173 micro-CT. All dry fixation materials tested were punched into 5 mm diameter cylinders and clamped into 0.2 ml reaction vessels. A voxel size of 5.33 μm was achieved in a 180° scan in 0.3° steps. Ideally, fixation materials should not be visible in the reconstructed image, i.e., barely binarised. Besides common micro-CT fixation materials such as styrofoam (-935 Hounsfield Units) or Basotect foam (-943 Hounsfield Units), polyethylene air cushions (-944 Hounsfield Units), Micropor foam (-926 Hounsfield Units) and polyurethane foam, (-960 Hounsfield Units to -470 Hounsfield Units) have proved to be attractive alternatives. Furthermore, more radiopaque materials such as paraffin wax granulate (-640 Hounsfield Units) and epoxy resin (-190 Hounsfield Units) are also suitable as fixation materials. These materials often can be removed in the reconstructed image by segmentation. Sample fixations in the studies of recent years are almost all limited to fixation in Parafilm, Styrofoam, or Basotect foam if the fixation type is mentioned at all. However, these are not always useful, as styrofoam, for example, dissolves in some common media such as methylsalicylate. We show that micro-CT laboratories should be equipped with various fixation materials to achieve high-level image quality.

Background Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde‐treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next‐generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether–treated BHVs. Methods and Results Ten ethylene glycol diglycidyl ether–treated BHVs excised because of SVD, and 5 calcified aortic valves (AVs) replaced with BHVs because of calcific AV disease were collected and their proteomic profile was deciphered. Then, BHVs and AVs were interrogated for immune cell infiltration, microbial contamination, distribution of matrix‐degrading enzymes and their tissue inhibitors, lipid deposition, and calcification. In contrast with dysfunctional AVs, failing BHVs suffered from complement‐driven neutrophil invasion, excessive proteolysis, unwanted coagulation, and lipid deposition. Neutrophil infiltration was triggered by an asymptomatic bacterial colonization of the prosthetic tissue. Neutrophil elastase, myeloblastin/proteinase 3, cathepsin G, and matrix metalloproteinases (MMPs; neutrophil‐derived MMP‐8 and plasma‐derived MMP‐9), were significantly overexpressed, while tissue inhibitors of metalloproteinases 1/2 were downregulated in the BHVs as compared with AVs, together indicative of unbalanced proteolysis in the failing BHVs. As opposed to other proteases, MMP‐9 was mostly expressed in the disorganized prosthetic extracellular matrix, suggesting plasma‐derived proteases as the primary culprit of SVD in ethylene glycol diglycidyl ether–treated BHVs. Hence, hemodynamic stress and progressive accumulation of proteases led to the extracellular matrix degeneration and dystrophic calcification, ultimately resulting in SVD. Conclusions Neutrophil‐ and plasma‐derived proteases are responsible for the loss of BHV mechanical competence and need to be thwarted to prevent SVD.

This article provides a brief overview of the term sustainable development and its brief characteristics. The author considers the details of the ongoing changes in the current macroeconomic context of the global pandemic. The author concludes that only a few indicators have improved their dynamics in 2020-2021. In the future, inertial development is predicted for most of the key areas of sustainable development. Therefore, the article shows that achieving the SDGs on a global scale by 2030 is nothing more than an indicative and currently unattainable goal.

Neuroblastoma is a devastating tumour in children. Here, the authors analyse multi-region patient samples using genomics and transcriptomics, revealing temporal and spatial heterogeneity and questioning the reliability of single-biopsy based diagnostics.

Abstract Background Histone acetylation and deacetylation seem processes involved in the pathogenesis of Ewing sarcoma (EwS). Here histone deacetylases (HDAC) class I were investigated. Methods Their role was determined using different inhibitors including TSA, Romidepsin, Entinostat and PCI-34051 as well as CRISPR/Cas9 class I HDAC knockouts and HDAC RNAi. To analyze resulting changes microarray analysis, qRT-PCR, western blotting, Co-IP, proliferation, apoptosis, differentiation, invasion assays and xenograft-mouse models were used. Results Class I HDACs are constitutively expressed in EwS. Patients with high levels of individual class I HDAC expression show decreased overall survival. CRISPR/Cas9 class I HDAC knockout of individual HDACs such as HDAC1 and HDAC2 inhibited invasiveness, and blocked local tumor growth in xenograft mice. Microarray analysis demonstrated that treatment with individual HDAC inhibitors (HDACi) blocked an EWS-FLI1 specific expression profile, while Entinostat in addition suppressed metastasis relevant genes. EwS cells demonstrated increased susceptibility to treatment with chemotherapeutics including Doxorubicin in the presence of HDACi. Furthermore, HDACi treatment mimicked RNAi of EZH2 in EwS. Treated cells showed diminished growth capacity, but an increased endothelial as well as neuronal differentiation ability. HDACi synergizes with EED inhibitor (EEDi) in vitro and together inhibited tumor growth in xenograft mice. Co-IP experiments identified HDAC class I family members as part of a regulatory complex together with PRC2. Conclusions Class I HDAC proteins seem to be important mediators of the pathognomonic EWS-ETS-mediated transcription program in EwS and in combination therapy, co-treatment with HDACi is an interesting new treatment opportunity for this malignant disease.

In this study, we delve into the impact of genotoxic anticancer drug treatment on the chromatin structure of human cells, with a particular focus on the effects of doxorubicin. Using Hi-C, ChIP-seq, and RNA-seq, we explore the changes in chromatin architecture brought about by doxorubicin and ICRF193. Our results indicate that physiologically relevant doses of doxorubicin lead to a local reduction in Hi-C interactions in certain genomic regions that contain active promoters, with changes in chromatin architecture occurring independently of Top2 inhibition, cell cycle arrest, and differential gene expression. Inside the regions with decreased interactions, we detected redistribution of RAD21 around the peaks of H3K27 acetylation. Our study also revealed a common structural pattern in the regions with altered architecture, characterized by two large domains separated from each other. Additionally, doxorubicin was found to increase CTCF binding in H3K27 acetylated regions. Furthermore, we discovered that Top2-dependent chemotherapy causes changes in the distance decay of Hi-C contacts, which are driven by direct and indirect inhibitors. Our proposed model suggests that doxorubicin-induced DSBs cause cohesin redistribution, which leads to increased insulation on actively transcribed TAD boundaries. Our findings underscore the significant impact of genotoxic anticancer treatment on the chromatin structure of the human genome.

Elements of micromachines can be driven by light, including structured light with phase and/or polarization singularities. We investigate here a paraxial vector Gaussian beam with an infinite number of polarization singularities residing evenly on a straight line. The intensity distribution is derived analytically and the polarization singularities are shown to exist only in the initial plane and in the far field. The azimuthal angle of the polarization singularities is shown to increase in the far field by π/2. We obtain the longitudinal component of the spin angular momentum (SAM) density and show that it is independent of the azimuthal angle of the polarization singularities. Upon propagation in free space, an infinite number of C-points is generated, where polarization is circular. We show that the SAM density distribution has a shape of four spots, two with left and two with right elliptic polarization. The distance to the transverse plane with the maximal SAM density decreases with decreasing distance between the polarization singularities in the initial plane. Generating such alternating areas with positive and negative SAM density, despite linear polarization in the initial plane, manifests the optical spin Hall effect. Application areas of the obtained results include designing micromachines with optically driven elements.

We consider sharp focusing of an axial superposition of two optical vortices with identical topological charges, but different amplitudes and circular polarizations of different signs. The ratio of the amplitudes of the two beams is a parameter. When this parameter changes, the polarization state of the superposition changes from linear polarization to right-hand circular polarization. Based on the Richards–Wolf theory, exact expressions are obtained for the longitudinal components of the spin angular momentum (SAM) density and orbital angular momentum (OAM) density at the focus of the considered superposition. It follows from these expressions that the sum of the total longitudinal components of the SAM and OAM is conserved upon focusing, and also that, due to the spin-orbit conversion, the total longitudinal component of the SAM decreases during focusing, while the total longitudinal component of the OAM increases by the same amount. By changing the ratio of the amplitudes of the constituent beams from 1 to 0, one can change the value of the spin-orbit conversion from zero (for linear polarization) to a maximum (for circular polarization). Also, by changing this parameter, one can control the spin Hall effect at the focus, which takes place at the focus of the considered beam. This study can be applied for controlling the rotation velocity of microparticles trapped in the focus.

The study considers the solution of a number of problems of supersonic and hypersonic gas dynamics using a model that takes into account the dissociation and ionization of air. The results of verification and validation of the developed numerical method using various difference schemes (the Roe scheme, Rusanov scheme, AUSM scheme) for discretizing convective flows are presented. The formulation of the mathematical model for high-temperature air uses the presence of equilibrium chemical reactions of dissociation and ionization. For this purpose, at high incoming flow velocities, the Kraiko model is applied, which includes equilibrium chemical reactions in air at high temperatures. To discretize the basic equations, the finite volume method on an unstructured grid is applied. One of the features of the constructed mathematical model is the implementation of the transition between physical and conservative variables. Relationships are given, with the help of which the transition from conservative variables to physical ones and vice versa is carried out when using the high-temperature air model. To ensure the stability of numerical calculations, an entropy correction is introduced. The decrease in entropy in the solution of hyperbolic equations is excluded by introducing an artificial viscosity according to Neumann, as well as by using the Godunov method with an exact solution of the Riemann problem and methods based on the approximate solution of the problem of the decay of an arbitrary discontinuity. A number of problems of supersonic gas dynamics (supersonic flow in a channel with a straight step and supersonic flow around a sphere) are numerically solved taking into account high-temperature effects. The criteria for the accuracy of numerical calculations related to the location of shock-wave structures are discussed. The calculated shock-wave structure of the flow is compared with the data available in the literature, as well as with calculations using the perfect gas model. Some results of numerical calculations are compared with the available experimental data. The shock-wave flow patterns obtained in the framework of the inviscid model, which takes into account the effect of viscosity and its dependence on temperature, and the turbulent flow model are compared. On the basis of numerical simulation data, the influence of viscous effects on the flow characteristics in a channel with a straight step and hypersonic flow around a sphere is considered. The influence of various numerical factors on the shape of the bow shock and the presence of fluctuations in the solution behind the shock is emphasized. As part of the work, a computational module was prepared for the commercial package Ansys Fluent, implemented with the help of user programming tools. The prepared module expands the standard capabilities of commercial software focused on solving computational gas dynamics problems, and is available to Ansys Fluent users for solving hypersonic aerodynamics problems. The developed means of numerical simulation can be useful in the design and optimization of hypersonic aircraft.

An amendment to this paper has been published and can be accessed via the original article.

Having DNA-binding profiles for a sufficient number of genome-encoded transcription factors (TFs) opens up the perspectives for systematic evaluation of the upstream regulators for the gene lists. Plant Cistrome database, a large collection of TF binding profiles detected using the DAP-seq method, made it possible for Arabidopsis. Here we re-processed raw DAP-seq data with MACS2, the most popular peak caller that leads among other ones according to quality metrics. In the benchmarking study, we confirmed that the improved collection of TF binding profiles supported a more precise gene list enrichment procedure, and resulted in a more relevant ranking of potential upstream regulators. Moreover, we consistently recovered the TF binding profiles that were missing in the previous collection of DAP-seq peak sets. We developed the CisCross web service (https://plamorph.sysbio.ru/ciscross/) that gives more flexibility in the analysis of potential upstream TF regulators for Arabidopsis thaliana genes.

We present a C++ header-only parallel sparse matrix library, based on sparse quadtree representation of matrices using the Chunks and Tasks programming model. The library implements a number of sparse matrix algorithms for distributed memory parallelization that are able to dynamically exploit data locality to avoid movement of data. This is demonstrated for the example of block-sparse matrix–matrix multiplication applied to three sequences of matrices with different nonzero structure, using the CHT-MPI 2.0 runtime library implementation of the Chunks and Tasks model. The runtime library succeeds to dynamically load balance the calculation regardless of the sparsity structure.

Abstract Invasive coronary angiography remains the gold standard for diagnosing coronary artery disease, which may be complicated by both, patient-specific anatomy and image quality. Deep learning techniques aimed at detecting coronary artery stenoses may facilitate the diagnosis. However, previous studies have failed to achieve superior accuracy and performance for real-time labeling. Our study is aimed at confirming the feasibility of real-time coronary artery stenosis detection using deep learning methods. To reach this goal we trained and tested eight promising detectors based on different neural network architectures (MobileNet, ResNet-50, ResNet-101, Inception ResNet, NASNet) using clinical angiography data of 100 patients. Three neural networks have demonstrated superior results. The network based on Faster-RCNN Inception ResNet V2 is the most accurate and it achieved the mean Average Precision of 0.95, F1-score 0.96 and the slowest prediction rate of 3 fps on the validation subset. The relatively lightweight SSD MobileNet V2 network proved itself as the fastest one with a low mAP of 0.83, F1-score of 0.80 and a mean prediction rate of 38 fps. The model based on RFCN ResNet-101 V2 has demonstrated an optimal accuracy-to-speed ratio. Its mAP makes up 0.94, F1-score 0.96 while the prediction speed is 10 fps. The resultant performance-accuracy balance of the modern neural networks has confirmed the feasibility of real-time coronary artery stenosis detection supporting the decision-making process of the Heart Team interpreting coronary angiography findings.

The purpose of the present study is to determine the prevalence of genital mycoplasmas (M. genitalium, M. hominis, U. parvum, U. urealyticum) in pregnant women by molecular biological methods. Material/Methods: A prospective epidemiological study of 107 pregnant women hospitalized in the Clinic of Obstetrics and Gynecology, University Hospital-Pleven, Bulgaria, was conducted. Vaginal secretion samples were taken from all 107 pregnant women. A Polymerase chain reaction (PCR) assay was used to detect the genomic DNA of the bacteria in pregnant women. Results: The highest is the relative share of women in the age group from 20 to 35 years - 66 (64.68%), followed by women under 20 years - 27 (25.23%) and women over 35 years - 14 (13.08%). Detection of bacterial DNA was found in 85 (79.44%) of the cases, with present Ureaplasma spp. Colonization in 42 women (39.25%). Although no statistical dependence was found on open bacteria and age groups (p-value = 0.4688), it is noteworthy that the prevalence of Mycoplasma spp. and Ureaplasma spp. as a whole in the age group from 20 to 35 years, which has the highest birth rate, is more than twice higher than the group of up to 20 years and more than five times higher compared to the group over 35 years. Conclusions: Studies on the incidence of Mycoplasma spp. and Ureaplasma spp. in pregnant women is important for controlling the pregnancy, predicting the risk of developing maternal-fetal infection and discussing the options for timely treatment.

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility. We then compared the long-term patency and remodeling features of PCL and PHBV/PCL prostheses in a sheep carotid artery interposition model. The research findings verified that the drug coating of both types of prostheses improved their hemocompatibility and tensile strength. The 6-month primary patency of the PCL/Ilo/A prostheses was 50%, while all PHBV/PCL/Ilo/A implants were occluded at the same time point. The PCL/Ilo/A prostheses were completely endothelialized, in contrast to the PHBV/PCL/Ilo/A conduits, which had no endothelial cells on the inner layer. The polymeric material of both prostheses degraded and was replaced with neotissue containing smooth-muscle cells; macrophages; proteins of the extracellular matrix such as type I, III, and IV collagens; and vasa vasorum. Thus, the biodegradable PCL/Ilo/A prostheses demonstrate better regenerative potential than PHBV/PCL-based implants and are more suitable for clinical use.

This article provides a brief overview of the ongoing changes in the methodology for evaluating and selecting personnel in government agencies of the Russian Federation. The author analyzes the details of ongoing reforms in the current macroeconomic context. The article covers expected consequences of the planned unified approach to certification of civil servants in all state bodies of the Russian Federation using examples of existing business structures that already use the new methods. The author comes to the conclusion that disproportionate powers of managers in any departments and strictly formalized criteria for certification of civil servants, which came from the commercial sphere, will negatively affect the motivation of civil servants, the quality of their work with citizens, and lead to erosion of the civil service ethics. The ongoing reform may potentially result in a loss of public trust to state institutions.

MYCN amplification is common in neuroblastomas. Here the authors analyse the MYCN amplicon structure and its epigenetic regulation by integrating short- and longread genomic and epigenomic data and find two classes of MYCN amplicons in neuroblastomas, one driven by local enhancers and the other by hijacking of distal regulatory elements.

Fusion genes are a hallmarks of cancer, though breakpoint-position promiscuity restricts diagnostic detection. Here, the authors present FUDGE, a CRISPR-Cas9-based enrichment strategy for nanopore sequencing to identify target fusions irrespective of genomic breakpoint or fusion partner.

Ewing sarcoma is characterized by the fusion of EWSR1 and FLI1. Here, the authors show that EWSR1-FLI1 increases the activity of the developmental transcription factor SOX6, which promotes tumor growth but also increases sensitivity to oxidative stress.

Abstract Background Questionnaires to detect emotional and behavioral problems (EBP) in Preventive Child Healthcare (PCH) should be short which potentially affects validity and reliability. Simulation studies have shown that Computerized Adaptive Testing (CAT) could overcome these weaknesses. We studied the applicability (using the measures participation rate, satisfaction, and efficiency) and the validity of CAT in routine PCH practice. Methods We analyzed data on 461 children aged 10–11 years (response 41%), who were assessed during routine well-child examinations by PCH professionals. Before the visit, parents completed the CAT and the Child Behavior Checklist (CBCL). Satisfaction was measured by parent- and PCH professional-report. Efficiency of the CAT procedure was measured as number of items needed to assess whether a child has serious problems or not. Its validity was assessed using the CBCL as the criterion. Results Parents and PCH professionals rated the CAT on average as good. The procedure required at average 16 items to assess whether a child has serious problems or not. Agreement of scores on the CAT scales with corresponding CBCL scales was high (range of Spearman correlations 0.59–0.72). Area Under Curves (AUC) were high (range: 0.95–0.97) for the Psycat total, externalizing, and hyperactivity scales using corresponding CBCL scale scores as criterion. For the Psycat internalizing scale the AUC was somewhat lower but still high (0.86). Conclusions CAT is a valid procedure for the identification of emotional and behavioral problems in children aged 10–11 years. It may support the efficient and accurate identification of children with overall, and potentially also specific, emotional and behavioral problems in routine PCH.

Simultaneous inhibition of multiple molecular targets is an established strategy to improve the continuance of clinical response to therapy. Here, we screened 49 molecules with dual nanomolar inhibitory activity against BRD4 and PLK1, best classified as dual kinase-bromodomain inhibitors, in pediatric tumor cell lines for their antitumor activity. We identified two candidate dual kinase-bromodomain inhibitors with strong and tumor-specific activity against neuroblastoma, medulloblastoma, and rhabdomyosarcoma tumor cells. Dual PLK1 and BRD4 inhibitor treatment suppressed proliferation and induced apoptosis in pediatric tumor cell lines at low nanomolar concentrations. This was associated with reduced MYCN-driven gene expression as assessed by RNA sequencing. Treatment of patient-derived xenografts with dual inhibitor UMB103 led to significant tumor regression. We demonstrate that concurrent inhibition of two central regulators of MYC protein family of protooncogenes, BRD4, and PLK1, with single small molecules has strong and specific antitumor effects in preclinical pediatric cancer models.