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Objective: to compare the efficacy and toxicity of aflibercept and bevacizumab in combination with fOLfIRI in secondline therapy for patients with metastatic colon cancer.Materials and methods. we performed a retrospective analysis of data on patients with metastatic colon cancer treated in 9 clinics in the Russian federation. The inclusion criteria were as follows: metastatic or locally advanced colon cancer; treatment with bevacizumab or aflibercept plus fOLfIRI in the second-line therapy. The primary outcome measure was progression-free survival (PfS). Secondary outcome measures included objective response rate and incidence of adverse events.Results. A total of 271 patients with metastatic colon cancer who received second-line therapy with bevacizumab (n = 81) or aflibercept (n = 190) between 2014 and 2018 were selected for this study. Study groups were matched for main prognostic signs. The objective response rate was 18.1 % in the bevacizumab group and 20.5 % in the aflibercept group (p = 0.7). The median PfS was 5 months (95 % confidence interval 3.8–6.1) in the aflibercept group and 7 months (95 % confidence interval 0.81–2.1) in the bevacizumab group (hazard ratio 1.4; 95 % confidence interval 0.99–2.1; p = 0.04). multivariate regression analysis demonstrated that the type of the targeted drug independently had no effect on PfS (hazard ratio 1.3; 95 % confidence interval 0.9–1.9; p = 0.2). we observed no statistically significant differences in the incidence of complications of any grades between the groups (58 % vs 72 %, p = 0.1). Patients receiving aflibercept were more likely to develop grade III–Iv arterial hypertension (2 % vs 9.5 %) and diarrhea (0 % vs 5.4 %), whereas thrombotic complications were more common in the bevacizumab group (10 % vs 1.8 %).Conclusion. we observed no significant differences in objective response rate and PfS between patients with metastatic colon cancer receiving bevacizumab or aflibercept in combination with fOLfIRI as second-line therapy. The toxicity profiles were different. Our findings can be used for choosing an optimal targeted drug for second-line treatment.

Objective: to identify factors associated with efficacy of an aflibercept-chemotherapy combination in patients with metastatic colon cancer.Materials and methods. This retrospective multicenter study was conducted in 20 clinics from 15 regions of the Russian Federation. The main efficacy outcome was progression-free survival (PFS). We performed univariate and multivariate analysis to assess the impact of various factors of PFS.Results. Two hundred and fifty-seven patients received aflibercept-containing chemotherapy; of them, 175 participants (68.1 %) received it as a second-line therapy. The objective response rate and median PFS were 18.7% and 5 months (95% confidence interval (CI) 4.2—5.8) respec -tively. The following factors were found to have a positive effect of PFS at multivariate analysis: grade I—II adverse events to aflibercept therapy (hazard ratio (HR) 0.58; 95 % CI 0.38—0.89; p = 0.01), therapy for concomitant diseases (HR 0.47; 95 % CI 0.29—0.76; p = 0.002), and ECOG performance status of 0 (HR 0.53; 95 % CI 0.34—0.81; p = 0.004). Patient with all 3 factors present had median PFS of 9 months, whereas patients without them demonstrated PFS of only 3 months (HR 1.9; 95 % CI 1.5—2.6; p

Currently, treatment and diagnostics of neuroendocrine tumors are associated with a number of problems, including absence of a registry for these diseases. The article considers the main approaches and problems of immunohistochemical diagnostics of neuroendocrine tumors.

BRCA1 and BRCA2 may contribute in pancreatic cancer (PC) risk, however the selection criteria for BRCA1 testing are poorly defined. The analysis of Russian founder mutation BRCA1 5382insC in 150 PC patients identified 2 carriers. BRCA2 full-length sequencing of 8 DNA samples revealed 1 mutated allele (BRCA2 5197_5198delTC). All 3 carriers of BRCA1/2 mutations reported personal or familial history of BRCA-related cancers. Thus, BRCA1/2 testing is particularly

The article is devoted to the peculiarities of the formation and development of library management of the Chuvash Autonomous Region. The purpose of the article is to consider the state of library management in Chuvashia in the 20s of the twentieth century and the main activities of reading huts and libraries in raising the educational and cultural level of the population in the period under review. The article is written on the basis of a thorough analysis of a wide range of literature on the topic, statistical collections, the study and selection of materials from central and local state archives, most of which are introduced into scientific circulation for the first time. It was revealed that in the years under study, many methods of mass work were developed and tested in practice, which, being improved at subsequent stages in connection with new tasks, have been used and used by libraries to this day: thematic book exhibitions, review evenings, literary evenings, evenings for discussion of new works of fiction, long-term mass campaigns to promote relevant books and libraries among the population, etc. It is concluded that libraries and reading rooms during the period under study gradually gained experience in cultural and educational work: from the mechanical issuance of books, passive service of readers to the search for methods of active work among the masses. By the mid-1920s, libraries and reading rooms began to switch to more organized and planned work.

Layered silicates, such as serpentine and vermiculite, have properties that make it possible to use materials based on them as components of environmental technologies. The possibility of soil remediation in industrially contaminated area, formed due to the long-term exposure to emissions from copper-nickel production (Monchegorsk, Murmansk region), was studied. Two materials were used as ameliorants in our study: expanded vermiculite and granular serpentine sorbent, a waste after using the purification technology of highly concentrated solutions from metals. These materials have a high sorption activity to several metals, a high specific surface area, the ability to retain moisture, and are available in quantities sufficient to work on the remediation of large areas. A study of the physicochemical properties of industrially polluted soil and ameliorants, direct phytotoxicity testing of podzol and its mixtures with expanded vermiculite and the serpentine sorbent (test plants - common oat Avna satva L. and red clover Trifolium pratnse L.) were carried out. The study results showed that the proposed materials were effective additives for increasing the pH of acidic soil, sorption and precipitation of Al and potentially toxic metals - Cu, Ni, Pb, Fe, and improving the soil hydrophysical and agrochemical characteristics. A positive response of test plants to the introduction of ameliorants into industrially contaminated soil was noted.

Background. The phenomenon of multilingualism and its impact on child development are in the spotlight of latter-day psychology, and of utmost importance both for theory and practice. Language development is a strong predictor of psychological readiness for school and further academic success. At the same time, children's mastery of written and oral speech in school education in a multilingual environment has several distinctive features. This study was dedicated to examining the influence of executive functions on the development of the vocabulary aspects of speech (both active and passive vocabulary) of mono- and bilingual children growing up in a bilingual environment. Objective. We aimed to analyze the relationship between bilingualism and language development (vocabulary and verbal fluency) and determine which executive functions may help overcome the resulting difficulties at preschool age. Design. Both monolingual and bilingual children participated in the study (n = 137 and n = 81, respectively). The children’s ages ranged from 6 to 7 years (M = 78.7 months, SD = 5.87). Two independent General Linear Models (GLM) were built to define which executive functions influenced the vocabulary and verbal fluency of the mono- and bilingual subjects (controlling for age, gender, and non-verbal intelligence as well). Results. The results confirmed that bilingualism is negatively related to language development, but showed that verbal working memory significantly helps bilinguals compensate for difficulties in developing vocabulary and verbal fluency. Conclusion. The study demonstrated that the ability to preserve and reproduce verbal information was of more significance for children's vocabulary and verbal fluency than their language group (mono- or bilingual).

Purpose. To study the level of vitamin D and the levels of antimicrobial peptides in the blood of children suffering from gastroesophageal reflux disease with nasopharyngeal symptoms, to find out how they depend on the composition of refluxate in LFR and how they affect microbial colonization in the nasopharynx. Materials and methods. The clinical study was conducted on the basis of the ENT and the Gastroenterology Departments of the Municipal Non-Commercial Enterprise “City Children's Hospital no. 5" of Zaporizhia City Council. By clinical examination and pH monitoring in the esophagus, the following groups of children 3 to 6 years were established: the 1st group of 22 children with gastroesophageal reflux disease with nasopharyngeal signs, the 2nd group of 22 children with gastroesophageal reflux disease without nasopharyngeal signs. Children were assigned to 1st group on the basis of the presence of clinical manifestations that indicated like a high GER. For children with nasopharyngeal manifestations of GERD, there are not only complaints specific to GERD, as well as symptoms that may indicate LFR: cough after eating and morning hoarseness, redness of the larynx and swelling of the vocal cords.The control group (the 3rd group) consisted of 22 children without pathology from the gastrointestinal tract and ENT systems. The children were tested for the levels of 25(ОН)D3, 1,25(ОН)2D, vitamin D binding protein (DBP), α­defensins 1–3 and cathelicidins. Microbial contamination of the mucous membrane of the nasopharyngeal zone was carried out. As far as the distribution differed from normal one (p

The article considers phonetic variants of English proper names that comprise homographic groups, and some impairments during their registration in pronouncing dictionaries. The authors present the results of lexicographic and comparative analysis of units extracted from two pronouncing dictionaries: “Cambridge English Pronouncing Dictionary” by D. Jones and “Longman Pronunciation Dictionary” by J. Wells using the continuous sampling method. Particular attention is focused on the methods of registration and completeness of phonetic notation of homographs pronunciation. A number of peculiarities are noted in recording semantics, phonetic-and-orthographic variations in some homogroups in British and American English. Clear inconsistency and insufficiency of lexicographic parametrization of both homographic proper names and their national and social pronunciation variants, as well as the meanings of common and proper names are revealed. The conclusion is made about the accuracy of “Cambridge English Pronouncing Dictionary” in terms of registering several British and American variants of onyms pronunciation, supplemented by additional comments on the phonetic variants and meanings of numerous types of proper names (anthroponyms, toponyms, ergonyms). The data obtained are required for differentiating the meanings of proper names, correct use of onyms and appellatives in oral speech, as well as for compiling dictionaries and reference books.

The relevance of the research is caused by the necessity to determine the residual resource of the equipment with a sufficient degree of accuracy and in various circumstances. The development of mathematical models for assessing the mechanisms of damage accumulation and the actual state of the equipment will allow predicting the development of changes in the state of the object, considering the established patterns of damage mechanisms, and determining the moment of occurrence of the limit state. The aim of the research is to propose a method for assessing the residual resource of heat exchangers, considering expert intuitive-logical analysis of the problem with a quantitative assessment of judgments and processing of results. Objects: heat exchangers, expert conclusions on heat exchangers used in oil refining. Methods: Kullback–Leibler informative model, showing the degree of informativeness of individual parameters to the degree of discrepancy between the two classes of objects, diagnosing residual resource for the development of corrosion damage, diagnosing residual resource of equipment related to changed parameters of its technical condition. Results. The paper sets the task to assess the service life of the heat exchanging equipment after diagnosing on the allowed technical parameters depending on the total effect of the parameters of the technical condition of the equipment for oil and gas processing and petrochemistry. 10 technical and technological indicators of heat exchangers were selected, and the evaluation was performed by using such an indicator as the residual service life of heat exchangers. The authors developed a mathematical model, calculated diagnostic coefficients and informativeness of the indicator for each period accepted by the expert. An algorithm for estimating the residual service life of heat exchangers based on the Kullback informativeness measure is proposed. Estimates of the residual resource, out of the constructed model are shown. Conclusions about the rationality of using the proposed algorithm for solving problems of this type are made.

The influence of structural features of three serpentine-group minerals (antigorite, chrysotile, and lizardite) on the hydration of heat-treated materials and the formation of magnesium silicate binder has been studied. Initial serpentine samples have been fired in the interval 550–800 °C with a step of 50 °C; acid neutralization capacity (ANC) values have been determined for all samples. Antigorite samples (SAP) have exhibited a maximum reactivity at a temperature of 700 °C (ANC 7.7 meq/g). We have established that the acid-neutralizing capacity of chrysotile and lizardite samples in the temperature range of 650–700 °C differ slightly; the capacity varied in the interval of 19.6–19.7 meq/g and 19.6–19.7 meq/g, respectively. The samples obtained at optimal temperatures (antigorite—700 °C, lizardite, and chrysotile—650 °C) have been studied. Heat-treated serpentines have interacted with water vapor for a year; serpentine hydration has been investigated. The strength characteristics of the resulting binder agents were studied after 7, 28, 180, and 360 days. Upon hardening within 7 days, the strengths of the SAP and SCH samples have been almost the same (2.2 MPa), whereas this indicator for the SLH and SLK samples has been significantly lower (0.5 MPa). After hardening for over a year, the chrysotile sample SCH had the highest strength (about 8 MPa), whereas the strength of antigorite SAP was 3 MPa. The samples of initial, heat-treated, and hydrated heat-treated serpentines have been studied using XRD, differential scanning calorimetry, and surface texture analysis. The serpentine structure is crucial in destroying the mineral crystal lattice during heat treatment. In contrast to heat-treated chrysotile and lizardite, antigorite did not adsorb water. Structural features of chrysotile provided the highest compressive strength of the binding agent compared with antigorite and lizardite. The acid-neutralizing ability of lizardite was noticeably higher than antigorite, whereas its compressive strength was lower due to the layered mineral structure and impurities. We have established that the minerals’ structural features are crucial for the hydration of heat-treated serpentines; the structure determines material utilization in various environmental technologies.

An investigation of innate immunity receptors sheds light on the mechanisms of inflammation and associated immune reactions. One of the key immune regulators is the TREM-1 receptor, which is involved in both inflammation and antitumor immune response. In this article, we have obtained a new ligand for the TREM-1 receptor. The peptide, named N3, is a part of the innate immune protein PGLYRP1/Tag7. It is responsible for activating the TREM-1 signaling pathway. Here, we have demonstrated that the N3 peptide acts like other TREM-1 receptor ligands: its binding results in a mild inflammation response and appearance of cytotoxic lymphocytes. We have shown that cytotoxic populations of lymphocytes in N3 peptide-treated PBMCs are similar to those treated with Tag7 or Hsp70. We also determined the part of the N3 peptide responsible for binding to TREM-1. The resulting peptide (N9) consists of nine amino acids and can be considered as a potential peptide that blocks TREM-1 signaling.

The problem on internal waves in a weakly stratified two-layer fluid is studied semi-analytically. We discuss the 2.5-layer fluid flows with exponential stratification of both layers. The long-wave model describing travelling waves is constructed by means of a scaling procedure with a small Boussinesq parameter. It is demonstrated that solitary-wave regimes can be affected by the Kelvin–Helmholtz instability arising due to interfacial velocity shear in upstream flow.

Serpentine heat treatment at temperatures of 650–750 °C yields magnesium–silicate reagent with high chemical activity. Precise and express control of roasting conditions in laboratory kilns and industrial aggregates is needed to derive thermally activated serpentines on a large scale. Color change in serpentines with a high iron content during roasting might be used to indicate the changes in chemical activity in the technological process. This study gives a scientific basis for the express control of roasting of such serpentines by comparing the colors of the obtained material and the reference sample. Serpentines with different chemical activity were studied by X-ray diffraction, Mössbauer spectroscopy, and optical spectroscopy. The color parameters were determined using RGB (red, green, blue), CIELAB (International Commission on Illumination 1976 L*a*b), and HSB (hue, brightness, saturation) color models. The color of heat-treated samples was found to be affected by changes in the crystallochemical characteristics of iron included in the structure of the serpentine minerals. The color characteristics given by the CIELAB model were in good coherence with the acid-neutralizing ability and optical spectra of heat-treated serpentines. Thus, in contrast to the long-term analysis by these methods, the control by color palette provides an express assessment of the quality of the resulting product.

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.

The search for and analysis of new ligands for innate immunity receptors are of special significance for understanding the regulatory mechanisms of immune response. Here we show that the major heat shock protein 70 (Hsp70) can bind to and activate TREM-1, the innate immunity receptor expressed on monocytes. The Hsp70–TREM-1 interaction activates expression of TNFα and IFNγ mRNAs in monocytes and stimulates IL-2 secretion by PBMCs. Moreover, incubation of PBMCs with Hsp70 leads to an appearance of cytotoxic lymphocyte subpopulations active against the MHC-negative tumor cells. In addition, both the CD4+ T-lymphocytes and CD14+ monocytes are necessary for the Hsp70 signal transduction and a consequent activation of the cytotoxic lymphocytes. We believe that data presented in this study will broaden the views on the involvement of Hsp70 in the antitumor immunity.

Studies on the mechanisms of activation of cytotoxic lymphocyte subpopulations are an important research direction in modern immunology. This study provides a detailed analysis of the effect of Tag7 (PGRP-S, PGLYRP1) on the development of lymphocyte subpopulations cytotoxic against MHC-negative tumor cells in a pool of peripheral blood mononuclear cells (PBMCs). The results show that Tag7 can bind to the TREM-1 receptor on the surfaces of monocytes, thereby triggering the expression of mRNA TNFα and IFNγ. The appearance of these cytokines in conditioned medium leads to IL-2 cytokine secretion by CD3+CD4+ lymphocytes. In turn, IL-2 facilitates unspecific activation of three cytotoxic cell subpopulations in the PBMC pool: NK (CD16+CD56+), CD3+CD4+ and CD3+CD8+. These subpopulations appear after a certain period of incubation with Tag7 and show toxicity against tumor cells.

Изменение общего содержания озона над станцией «Академик Вернадский» / «Фарадей» исследуется с 1996 года, после передачи Украине станции Британской Антарктической службы (БАС). В последние десятилетия отмечается заметное истощение озонового слоя над Антарктидой. Сравнение среднего годового хода общего содержания озона по измерениям на станции «Академик Вернадский» / «Фарадей» за периоды 1972 - 1994 гг. и 1995 - 2012 гг. показали, что озоновая дыра в период 1972-1994 гг. не проявлялась. В статье предлагается новый подход к классификации кривых годового хода общего содержания озона над Украинской Антарктической станцией (УАС) в последние десятилетия.

In present work, carbon nanomaterials (CNMs) are investigated as potential carriers of 68Ga, which is widely used in positron emission tomography (PET) in nuclear medicine. Sorption behavior of 68Ga was studied onto CNMs of various structures and chemical compositions: nanodiamonds (ND), reduced graphite oxide (rGiO) and multi-walled carbon nanotubes (MWCNT), as well as their oxidized (ND–COOH) or reduced (rGiO–H, MWCNT–H) forms. The physicochemical properties of the nanoparticles were determined by high resolution transmission electron microscopy, x-ray photoelectron spectroscopy, dynamic light scattering and potentiometric titration. The content of 68Ga in the solutions during the study of sorption was determined by gamma-ray spectrometry. The highest degree of 68Ga sorption was observed on ND and ND–COOH samples, and the optimal sorption conditions were determined: an aqueous solution with a pH of 5–7, m/V ratio of 50 μg/mL and a room temperature (25 °C). The 68Ga@ND and 68Ga@ND–COOH conjugates were found to be stable in a model blood solution—phosphate-buffered saline with a pH of 7.3, containing 40 g/L of bovine serum albumin: 68Ga desorption from these samples in 90 minutes was no more than 20% at 25 °C and up to 30% at 37 °C. Such a quantity of desorbed 68Ga does not harm the body and does not interfere with the PET imaging process. Thus, ND and ND–COOH are promising CNMs for using as carriers of 68Ga for PET diagnostics.

Investigation of interactions between a pro-inflammatory cytokine tumor necrosis factor (TNFα) and its receptor is required for the development of new treatments for autoimmune diseases associated with the adverse effects of TNFα. Earlier, we demonstrated that the innate immunity protein Tag7 (PGRP-S, PGLYRP1) can interact with the TNFα receptor, TNFR1, and block the transduction of apoptotic signals through this receptor. A complex formed between the Tag7 protein and the major heat shock protein Hsp70 can activate TNFR1 receptor and induce tumor cell death via either apoptotic or necroptotic pathway. In this study, we show that a 12-mer peptide, designated 17.1, which was derived from the Tag7 protein, can be regarded as a novel TNFα inhibitor, also is able to form a cytotoxic complex with the heat shock protein Hsp70. This finding demonstrates a new role for Hsp70 protein in the immune response. Also, this new inhibitory 17.1 peptide demonstrates an anti-inflammatory activity in the complete Freund’s adjuvant (CFA)-induced autoimmune arthritis model in laboratory mice. It appears that the 17.1 peptide could potentially be used as an anti-inflammatory agent.

In the paper some methodological approaches to forming spelling acquisition by Russian students in the English language for correct written speech and reading are described. It contains various types of creative exercises aimed at the elimination of the typical spelling mistakes.