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Background. During the COVID-19 pandemic, annual adult check-ups have been postponed, resulting in cancer screening disruption.The aim of the study was to evaluate changes in the incidence and stage distribution of malignancies included in the screening program during the COVID-19 pandemic using the Arkhangelsk Regional Cancer Registry (ARRC).Material and Methods. We assessed the changes of the incidence rates and stage distribution for the colon, rectum, lung, breast, cervix, uterine body, ovary, prostate and kidney cancers over the periods 2018–19 and 2020–21. Results. A total of 12354 cases with 9 cancers were selected: 6680 for the period 2018–19 and 5674 (-15.1 %) for the period 2020-21. The most significant decrease in crude and age-standardized incidence rates was registered in patients with lung (-18.0–18.1 %), rectum (-25.1–25.9 %) and cervix (-33.6–36.9 %) cancers, p˂0.001. The decrease was not significant in patients with breast, uterine body, and kidney cancers. The proportion of patients with stage I decreased in lung cancer (-20.0 %, from 14.8 % to 11.8 %), rectum (-20.2 %, from 20.9 % to 16.7 %), and uterine cervix (-37.1 %, from 53.2 % to 33.5 %). In prostate and kidney cancers, the proportion of patients with stage I increased by 30 % (from 19.5 % to 25.4 %) and 17.6 % (from 45.9 % to 54.0 %), respectively. A significant reduction in the proportion of early stages during the COVID-19 pandemic was observed in lung and cervical cancer.Conclusion. Postponed health checkups due to COVID-19 pandemic disruptions have led to substantial reductions in new cancers being diagnosed, mainly for cervical, lung, colon and rectal cancers. No significant changes were observed for other cancers. Further analysis of mortality and survival of cancer patients is required.

In birch-dominated areas, allergies to pollen from trees of the order Fagales are considered to be initiated by the major birch pollen allergen Bet v 1. However, the sensitizing activity of Bet v 1-homologs in Fagales pollen might be underestimated. Allergen-specific T-cells are crucial in the sensitization process. The T-cell response to major allergens from alder, hazel, oak, hornbeam, chestnut, beech, and chestnut pollen has not yet been analyzed. Here, we characterized the cellular cross-reactivity of major allergens in Fagales pollen with Bet v 1.T-cell-lines (TCL) were established from allergic individuals with Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1, and Que a 1, and tested for reactivity with Bet v 1 and synthetic overlapping 12-mer peptides representing its primary sequence. Aln g 1-specific TCL was additionally tested with Aln g 1-derived peptides and all allergens. IgE-competition experiments with Aln g 1 and Bet v 1 were performed.T-cell-lines initiated with Fagales pollen allergens varied strongly in their reactivity with Bet v 1 and by the majority responded stronger to the original stimulus. Cross-reactivity was mostly restricted to the epitope Bet v 1The cellular cross-reactivity of major Fagales pollen allergens with Bet v 1 was unincisive, particularly for Aln g 1, most akin to Bet v 1. Our results indicate that humoral and cellular responses to these allergens are not predominantly based on cross-reactivity with the major birch pollen allergen but suggest a Bet v 1-independent sensitization in individuals from birch tree-dominated areas.

Internal tandem duplication is the most common form of mutation in FMS-like tyrosine kinase 3 (FLT3) in different haematological malignancies, highlighting in acute myeloid leukaemia (AML) and is associated with increased risk of relapse and reduced overall survival. A major breakthrough in the treatment of FLT3-mutated AML has been achieved through the use of highly selective FLT3 tyrosine kinase inhibitors, both in monotherapy and in combination with standard intensive cytotoxic chemotherapy. The desire to improve the outcomes of patients with AML, including those with relapse and refractory disease, has led to attempts to use non-standard therapeutic options. Enhancement of the antileukemic effects of the second-generation FLT3 inhibitor Gilteritinib may be achieved through synergy with the hypomethylating agent 5-azacytidine and the selective Bcl-2 inhibitor Venetoclax. Thus, targeted triple therapy is a promising option in the treatment of patients with FLT3-mutated AML. This study sought to evaluate the effectiveness of “triple therapy” regimen in 4 patients with relapsed/refractory FLT3 mutated AML. We found that the use of this combination showed rapid response with good safety and frequently allowed subsequent transplant and achieve durable clinical benefit.

Electrical injuries are a serious problem around the world. Patients with extensive, high-voltage electric burns belong to the group of severely burned. Timely and adequate treatment, which includes intensive anti-shock measures in the first days after injury, with simultaneous active surgical tactics, is decisive for saving life for such victims. The provision of specialized, high-tech medical care for these complex patients is optimal in conditions of a burn department / center of a multidisciplinary medical organization. However, knowledge of the basic principles of providing emergency and urgent medical care to victims with electrical trauma even before admission to the burn hospital is the key to their further successful treatment.

Abstract Developments in missile proliferation are analyzed, including the main drivers, trends, and actors. The increasing complexity of the global missile proliferation landscape is shown. They key areas of technological development are identified, as well as several types of missile proliferators, to substantiate the importance of missile proliferation in the context of international security. Existing and prospective mechanisms are discussed with respect to arms control, nonproliferation, and multilateral risk reduction measures. It is stressed that the existing mechanisms are aimed primarily at reducing the risks associated with creating delivery vehicles for weapons of mass destruction whereas the greatest importance is now attached to the potential use of conventionally armed missiles. It is proposed to concentrate efforts on “soft arms control” in order to lay a foundation for a gradual increase in controllability in the absence of real prospects for verifiable and intrusive multilateral measures.

Background. The sodium-dependent phosphate transporter NaPi2b is expressed in a number of tumors and serves as a target for monoclonal antibody therapy. The NaPi2b transporter has a large extracellular domain containing 4 cysteines and an MX35 epitope recognized by the corresponding monoclonal antibodies. Aim. To study the recognition of the MX35 epitope in cysteine mutants C303 and C350 of the sodium-dependent phosphate transporter NaPi2b by monoclonal antibodies in ovarian cancer cells. Material and methods. Ovarian cancer cells of the OVCAR-8 line were transfected with plasmids encoding mutant forms of the NaPi2b transporter. The recognition of these forms by monoclonal antibodies was studied by Western blot and flow cytometry. Statistical analysis of flow cytometry data was performed using Pearsons Chi-squared test with Yates correction. Results. Western blot analysis of lysates of OVCAR-8 cells expressing the wild-type NaPi2b transporter demonstrated the presence of a specific signal only in samples without the addition of dithiothreitol, while in all samples with NaPi2b cysteine mutants, even without the addition of dithiothreitol, no specific signal from monoclonal antibodies was detected. The flow cytometry results showed that proportion of OVCAR-8 cells with positive staining of the MX35 epitope with antibodies is less when expressing the NaPi2b mutants compared to the wild type. Conclusion. Cysteines C303 and C350 are involved in disulfide bonds formation, which is of key importance for the formation of the conformation of the extracellular domain of the sodium-dependent phosphate transporter NaPi2b, which ensures the MX35 epitope recognition by monoclonal antibodies.

Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.

The analysis of the state and direction of development of equipment and technology for grinding materials in the Russian and foreign cement industry is carried out. The equipment used for grinding with ball mills, vertical mills and press-roll grinders is considered. The effectiveness of the use of ball mills and their advantage over other grinding units used in large-capacity production is shown. One of the main directions for the development of the efficiency of the grinding process in ball drum mills has been determined. It consists in the development of intra-mill devices that are aimed at destroying stagnant zones in the feed, intensifying the work of grinding bodies and creating conditions within the mill classification of the crushed material. The design and principle of operation of a ball drum mill equipped with an inclined inter-chamber partition is described. It ensures the transverse-longitudinal movement of grinding bodies in the mill body. The advantages of using an inclined inter-chamber partition are given, which include a reduction in the weight of the mill load and the hydraulic resistance of partition, improved aspiration, reduced power consumption and provision of transverse-longitudinal movement.

The article provides a literary review on the redistribution of route networks, and also shows the possibilities of applying different approaches to the redistribution of route networks of SPB GUP "Passazhiravtotrans" from the point of view of opening a new bus fleet. The author substantiates the importance of using mathematical modeling in general for this purpose and modeling based on the concept of machine learning and the "digital twin", in particular, as perspective.

Pediocin-like bacteriocins are among the natural antimicrobial agents attracting attention as scaffolds for the development of a new generation of antibiotics. Acidocin A has significant structural differences from most other members of this subclass. We studied its antibacterial and cytotoxic activity, as well as effects on the permeability of E. coli membranes in comparison with avicin A, the typical pediocin-like bacteriocin. Acidocin A had a more marked tendency to form an alpha-helical structure upon contact with detergent micelles, as was shown by CD spectroscopy, and demonstrated considerably less specific mode of action: it inhibited growth of Gram-positive and Gram-negative strains, which were unsusceptible to avicin A, and disrupted the integrity of outer and inner membranes of E. coli. However, the peptide retained a low toxicity towards normal and tumor human cells. The effect of mutations in the pediocin box of acidocin A (on average, a 2–4-fold decrease in activity) was less pronounced than is usually observed for such peptides. Using multiplex analysis, we showed that acidocin A and avicin A modulated the expression level of a number of cytokines and growth factors in primary human monocytes. Acidocin A induced the production of a number of inflammatory mediators (IL-6, TNFα, MIG/CXCL9, MCP-1/CCL2, MCP-3/CCL7, and MIP-1β) and inhibited the production of some anti-inflammatory factors (IL-1RA, MDC/CCL22). We assumed that the activity of acidocin A and similar peptides produced by lactic acid bacteria might affect the functional state of the human intestinal tract, not only through direct inhibition of various groups of symbiotic and pathogenic bacteria, but also via immunomodulatory effects.

Early (preclinical) diagnosis of Parkinsons disease (PD) is a major challenge in modern neuroscience. The objective of this study was to experimentally evaluate a diagnostic challenge test with monoiodotyrosine (MIT), an endogenous inhibitor of tyrosine hydroxylase. Striatal dopamine was shown to decrease by 34% 2 h after subcutaneous injection of 100 mg/kg MIT to intact mice, with the effect not being amplified by a further increase in the MIT dose. The selected MIT dose caused motor impairment in a neurotoxic mouse model of preclinical PD, but not in the controls. This was because MIT reduced striatal dopamine to the threshold of motor symptoms manifestation only in PD mice. Therefore, using the experimental mouse model of preclinical PD, we have shown that a MIT challenge test may be used to detect latent nigrostriatal dysfunction.

Today, in modern Russia, the decrease in wear resistance and contact fatigue endurance of locomotive and waggon wheels is the main and most expensive problem in the railway industry. In this scient...

Последовательно развивается недавно предложенная схема матричного расширения бездисперсионных интегрируемых систем для общего случая многомерных иерархий, в основном для размерности $d\geqslant 4$. Представлены расширенные пары Лакса, уравнения Лакса-Сато, матричные уравнения на фоне векторных полей и схема одевания. Обсуждаются построение решений, редукции и связи с геометрией. Отдельно рассмотрен случай абелева расширения, для которого уравнения Римана-Гильберта схемы одевания решаются явно и дают аналог формулы Пенроуза в искривленном пространстве.