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Introduction. The concept of appropriateness of professional self-determination is analyzed, approaches to its analysis and measurement are described. Theoretical analysis. The significance of self-assessment of appropriateness of professional self-determination as a condition of sustainability to frequent stresses and prevention of professional burnout, including emotional exhaustion and depersonalization of personnel. Еmpirical analysis. The empirical study presents the results of the validation of the “Appropriateness of professional self-determination” Scale, developed by the author of the article. The empirical research base includes 396 workers, 277 men and 119 women. The performed in the study verification of the factor structure of the Scale confirmed its two-factor structure (subscale “Compliance of personal qualities of the job`s demands” (Cronbach`s α = 0.82) and subscale “Compliance of job of personal qualities” (Cronbach`s α. = 0.63)). The factor structure of the Scale was confirmed by the results of confirmatory factor analysis (RMSEA = 0.061, CFI = 0.964, TLI = 0.906). It was found that male workers and female workers evaluate their own appropriateness of professional self-determination in the same way. Negative correlations of appropriateness of professional self-determination with professional burnout, frequency of stresses and positive correlations with job satisfaction were revealed. Conclusion. The results of the study confirm the validity of the Appropriateness of Professional self-determination Scale, contribute the theoretical reflection of professional self-determination.

With the development of next-generation sequencing (NGS) technologies it became possible to simultaneously analyze millions of variants. Despite the quality improvement, it is generally still required to confirm the variants before reporting. However, in recent years the dominant idea is that one could define the quality thresholds for "high quality" variants which do not require orthogonal validation. Despite that, no works to date report the concordance between variants from whole genome sequencing and their gold-standard Sanger validation. In this study we analyzed the concordance for 1756 WGS variants in order to establish the appropriate thresholds for high-quality variants filtering. Resulting thresholds allowed us to drastically reduce the number of variants which require validation, to 4.8% and 1.2% of the initial set for caller-agnostic (DP, AF) and caller-dependent (QUAL) thresholds, respectively. [ABSTRACT FROM AUTHOR]

A pseudogene is a non-functional copy of a protein-coding gene. Processed pseudogenes, which are created by the reverse transcription of mRNA and subsequent integration of the resulting cDNA into the genome, being a major pseudogene class, represent a significant challenge in genome analysis due to their high sequence similarity to the parent genes and their frequent absence in the reference genome. This homology can lead to errors in variant identification, as sequences derived from processed pseudogenes can be incorrectly assigned to parental genes, complicating correct variant calling. In this study, we quantified the occurrence of variant calling errors associated with pseudogenes, generated by the most popular germline variant callers, namely GATK-HC, DRAGEN, and DeepVariant, when analysing 30x human whole-genome sequencing data (n = 13,307). The results show that the presence of pseudogenes can interfere with variant calling, leading to false positive identifications of potentially clinically relevant variants. Compared to other approaches, DeepVariant was the most effective in correcting these errors. [ABSTRACT FROM AUTHOR]

The extracellular matrix is an organized three-dimensional network of protein-based molecules and other macromolecules that provide structural and biochemical support to tissues. Depending on its biochemical and structural properties, the extracellular matrix influences cell adhesion and signal transduction and, in general, can influence cell differentiation and proliferation through specific mechanisms of chemical and mechanical sensing. The development of body tissues during ontogenesis is accompanied by changes not only in cells but also in the composition and properties of the extracellular matrix. Similarly, tumor development in carcinogenesis is accompanied by a continuous change in the properties of the extracellular matrix of tumor cells, called 'oncomatrix', as the tumor matures, from the development of the primary focus to the stage of metastasis. In this paper, the characteristics of the composition and properties of the extracellular matrix of tumor tissues are considered, as well as changes to the composition and properties of the matrix during the evolution of the tumor and metastasis. The extracellular matrix patterns of tumor tissues can be used as biomarkers of oncological diseases as well as potential targets for promising anti-tumor therapies. [ABSTRACT FROM AUTHOR]

Next-generation sequencing technologies have not only defined a breakthrough in medical genetics, but also been able to enter routine clinical practice to determine individual genetic susceptibilities. Modern technological developments are routinely introduced to genetic analysis overtaking the established approaches, potentially raising a number of challenges. To what extent is the advantage of new methodologies in synthetic metrics, such as precision and recall, more important than stability and reproducibility? Could differences in the technical protocol for calling variants be crucial to the diagnosis and, by extension, the patient's treatment strategy? A regulatory review process may delay the incorporation of potentially beneficial technologies, resulting in missed opportunities to make the right medical decisions. On the other hand, a blind adoption of new technologies based solely on synthetic metrics of precision and recall can lead to incorrect conclusions and adverse outcomes for the specific patient. Here, we use the example of a patient with a WHO-diagnosed desmoplastic/nodular SHH-medulloblastoma to explore how the choice of DNA variant search protocol affects the genetic diagnostics outcome. [ABSTRACT FROM AUTHOR]

99mTc is a well-known radionuclide that is widely used and readily available for SPECT/CT (Single-Photon Emission Computed Tomography) diagnosis. However, commercial isotope carriers are not specific enough to tumours, rapidly clear from the bloodstream, and are not safe. To overcome these limitations, we suggest immunologically compatible recombinant proteins containing a combination of metal binding sites as 99mTc chelators and several different tumour-specific ligands for early detection of tumours. E1b protein containing metal-binding centres and tumour-specific ligands targeting integrin αvβ3 and nucleolin, as well as a short Cys-rich sequence, was artificially constructed. It was produced in E. coli, purified by metal-chelate chromatography, and used to obtain a complex with 99mTc. This was administered intravenously to healthy Balb/C mice at an activity dose of about 80 MBq per mouse, and the biodistribution was studied by SPECT/CT for 24 h. Free sodium 99mTc-pertechnetate at the same dose was used as a reference. The selectivity of 99mTc-E1b and the kinetics of isotope retention in tumours were then investigated in experiments in C57Bl/6 and Balb/C mice with subcutaneously transplanted lung carcinoma (LLC) or mammary adenocarcinoma (Ca755, EMT6, or 4T1). The radionuclide distribution ratio in tumour and adjacent normal tissue (T/N) steadily increased over 24 h, reaching 15.7 ± 4.2 for EMT6, 16.5 ± 3.8 for Ca755, 6.7 ± 4.2 for LLC, and 7.5 ± 3.1 for 4T1. [ABSTRACT FROM AUTHOR]

Natural compounds, including diterpenoids, play a critical role in various biological processes and are recognized as valuable components in cancer treatment. Isocyanides multicomponent reactions (IsMCRs) are one of the effective methods to obtain adducts at the carboxyl group with a peptide-like substituent. In this study, dehydroabietic acid and levopimaric acid diene adducts as the starting scaffolds were modified by the multicomponent Passerini (P-3CR) and Ugi (U-4CR) reactions to afford α-acyloxycarboxamides and α-acylaminocarboxamides. A group of twenty novel diterpene hybrids was subjected to NCI in vitro assessment, and a consistent structure–activity relationship was established. Eleven of the synthesized derivatives inhibited the growth of cancer cells of 4 to 39 cell lines in one dose assay, and the most active were derivatives 3d, 9d, and 10d holding a fragment of 1a,4a-dehydroquinopimaric acid. They were selected for a five-dose analysis and demonstrated a significant antiproliferative effect towards human cancer cell lines. The outstanding cytotoxic activity was observed for the P-3CR product 3d with growth inhibitory at submicromolar and micromolar concentrations (GI50 = 0.42–3 μM) against the most sensitive cell lines. The U-4CR products 9d and 10d showed selective activity against all leukemia cell lines with GI50 in the range of 1–17 µM and selectivity indexes of 5.49 and 4.72, respectively. Matrix COMPARE analysis using the GI50 vector showed a moderate positive correlation of compound 3d with standard anticancer agents that can influence kinase receptors and epidermal growth factor receptors (EGFRs). The ADMET analysis acknowledges the favorable prognosis using compounds as potential anticancer agents. The obtained results indicate that these new hybrids could be useful for the further development of anticancer drugs, and 1a,4a-dehydroquinopimaric acid derivatives could be recommended for in-depth studies and the synthesis of new antitumor analogs on their basis. [ABSTRACT FROM AUTHOR]

The subjects of the transport space are developing new tasks, which are due to the accelerated introduction of digital technologies in the economic and social spheres. The article is devoted to the consideration of issues related to the need for digitalization of port equipment and seaports in general. The main advantages and disadvantages of digital transformation are highlighted. Also, the article contains examples of the use of digital technologies in Russian and foreign seaports. Conclusion is made about the need to improve the efficiency of seaports through digital transformation and interaction of subjects within the new digital space.

This paper is devoted to researching the major aspects of the digital transformation of the logistical field. Provided are the suggestions for constructing logistical process stakeholder interaction models. One of the major trends in digital logistics is platform solutions that will come to replace specialized digital solutions. Based on this trend, authors provide the 3-level model of stakeholder interaction on the logistical platform which could form the foundation of a future platform solution architecture. The creation of the logistical platform is the next step in the digital transformation of logistics which aims to create a unified logistical ecosystem.

The article substantiates the need to apply training and retraining programs for personnel for permanent work in the Arctic using digital technologies, namely VR / AR / MR technologies. The geopolitical features of the Arctic zone, difficult climatic conditions do not allow directly practicing the development of professional competencies and, therefore, require the introduction of a multi-stage system of personnel training using technologies of approximate reality. Such requirements for the personnel training system predetermine the need to search for relevant digital technologies that can create conditions that are as close as possible to the conditions of professional activity in hard-to-reach Arctic regions. When forming a personnel training / retraining system for oil and gas enterprises, in addition to the specified specific working conditions, it is also necessary to take into account the sectoral features of oil and gas enterprises, which also forms a number of functional requirements for the selection of relevant digital tools, the main of which for personnel training can be considered immersive technologies. Based on the above, the paper analyzes the use of immersive technologies by oil and gas enterprises, a comparative analysis of the directions of using immersive technologies in personnel training at oil and gas enterprises, identifies the positive and negative aspects of using VR / MR / AR technologies.

Eight crows were taught to discriminate overlapping pairs of visual stimuli (A+ B-, B+ C-, C+ D-, and D+ E-). For 4 birds, the stimuli were colored cards with a circle of the same color on the reverse side whose diameter decreased from A to E (ordered feedback group). These circles were made available for comparison to potentially help the crows order the stimuli along a physical dimension. For the other 4 birds, the circles corresponding to the colored cards had the same diameter (constant feedback group). In later testing, a novel choice pair (BD) was presented. Reinforcement history involving stimuli B and D was controlled so that the reinforcement/nonreinforcement ratios for the latter would be greater than for the former. If, during the BD test, the crows chose between stimuli according to these reinforcement/nonreinforcement ratios, then they should prefer D; if they chose according to the diameter of the feedback stimuli, then they should prefer B. In the ordered feedback group, the crows strongly preferred B over D; in the constant feedback group, the crows' choice did not differ significantly from chance. These results, plus simulations using associative models, suggest that the orderability of the postchoice feedback stimuli is important for crows' transitive responding. (Contains 5 tables and 4 figures.)

The formation of global competences for learners at all levels of professional engineering and mining education as the basis for the successful career and social life has become increasingly urgent in modern fast-changing world. The solution to this problem involves several aspects: first, identification and description of the basic elements and the structure of the global competences within the competency-based approach; second, the interpretation of global competences and their components taking into account convergent and divergent global processes in all spheres of human activity. Third, the development of tools to facilitate the reform of education, to ensure the quality improvement of the educational process, procedures, evaluation of results and ensuring the growth of quality indicators of the results of education.

The article deals with a relatively recent, but dynamically developing branch of the economy-the digital economy. A brief historical review of the formation of this direction, its impact on the traditional economy. On the basis of statistical data, the analysis of the potential of its development and the impact of the digital economy on the structure of modern innovative firms.As a comparative model, an in-depth analysis of the effectiveness of the introduction of modern digital technologies is carried out on the example of the use of three-dimensional modeling of extended objects in the construction industry using multi-dimensional scanning produced by unmanned aerial vehicles (drones) equipped with laser scanning systems and automatic positioning systems with reference to the terrain by GPS coordinates.