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Purpose. To develop a mathematical approach to quantitative assessment of the effectiveness of digital marketing of territories. To determine the tasks of digital marketing of territories and directions for increasing its effectiveness. Methodology. The research uses general and special methods of cognition: content analysis to substantiate the use of quantitative indicators for evaluating marketing effectiveness; induction and deduction for the development of a mathematical approach to evaluating the effectiveness of digital marketing of territories; analysis and synthesis to coordinate projects under conditions of a dynamic transformation of marketing processes. Findings. The mathematical formalization of quantitative evaluation effectiveness of marketing territories is developed, provided that the possibility of implementing project approach and conditions for coordination of projects is ensured. The tasks to be solved by the digital marketing of territories and directions for increasing its effectiveness are defined, and its advantages are detailed. The scheme is proposed for the implementation of territory marketing, taking into account the direct impact of information tools on the result and the reverse impact of an inappropriate result on the choice of information tools, which dictates the need to ensure the adaptability of marketing to dynamic changes in external and internal influences. Originality. The synergistic mutual influence of territory marketing and digital technologies, the synergistic mutual influence of business activities in the territorial location and the marketing of territories is established. It is established that the factor that determines the dynamic change in marketing plans is also a significant level of uncertainty due to the dynamic change in the level of threats and the dynamic nature of the introduction of the latest technologies. Practical value. The mathematical approach of quantitative assessment effectiveness of digital marketing territories and the determination of its tasks and directions for increasing efficiency determine the practical value of the study.

Diffuse astrocytomas is the major cause of mortality in pediatric neurooncology. Pediatric diffuse astrocytomas are clinically and biologically heterogeneous, they consist of distinct subtypes driven by various molecular events. Our aim was to reveal if the surrogate molecular signatures reflecting molecular alterations underlying diffuse astrocytomas could be of prognostic value. The surrogate molecular signature was determined by IHC with antibodies to IDH1R132H, p53, BRAF V600E, H3K27trimethylated, ATRX and by cytogenetics with identification of deletion CDKN2A and FGFR2 fusion. As a result, we obtained 6 groups of diffuse astrocytomas with different surrogate molecular signatures, which we designated as H3K27mut, ALT, IDH1mut, BRAFmut-PXA, BRAF mut/FGFR2, MYB. A total of 62 patients (29 male, 33 female, mean age 10,6 years, range 0–18 years) were analyzed. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Republic of Belarus). These surrogate molecular signatures were associated with significantly different outcomes, i.e. BRAFmut/FGFR2, MYB groups show a significantly good prognosis with 100% overall survival and relapse-free survival of 89 ± 11% and 100%. Groups H3K27mut, ALT, IDH1mut, BRAFmut-PXA display extremely poor outcomes with EFS equal to 0%, 20 ± 17%, 44 ± 17%, 18 ± 12% respectively, and OS equal to 23 ± 19%, 37 ± 20%, 40 ± 17%, 53 ± 19% respectively. The recognition of subtypes of pediatric diffuse astrocytomas based on surrogate molecular signature revealed close correlations with biological parameters and clinical outcomes and may therefore, be predictive of response to standard treatment protocols.

More than 20–25 % of patients with acute leukemia underwent transplantation of HSC from HLA-identical sibling or unrelated donor had relapse.Therefore, the purpose of this study was to evaluate the influence of different factors on the risk of post-transplantation relapse in children and teenagers with acute lymphoblastic leukemia (ALL).The gender, the age of a donor at the time of transplantation; the gender, the age of a recipient at the time of transplantation; the type, the number of relapses of previous HSCTs; the type of conditioning; the type of transplantation; the source of stem cells; transplant parameters; the acute (aGVHD) and chronic (cGVHD) graft-versus-host disease or its absence; the KIRalloreactivity of donor NK cells were estimated as risk factors for the disease relapse in our study.We established that the recipient’s age of less than 4 years at the time of transplantation (p = 0.0042); the time of relapse (very early and early) (p = 0.0047); the absence of aGVHD (p = 0.0183) or cGVHD (p = 0.0384) have been the important factors for the disease relapse of patients with ALL after allogeneic HSC transplantation.

Introduction. Liver cirrhosis (LC) is the final stage in the progression of chronic diffuse diseases. As common, late stages of LC do not respond to conservative treatment methods, so liver transplantation is the most effective method at this stage. Widespread use of transplantation in clinical practice is due to serious obstacles: a shortage of donor organs, transplant rejection, complications during the operation and the postoperative period, as well as the high cost of such an intervention. We consider bone marrow stem cell transplantation as a potential treatment for liver cirrhosis and additional clinical trials for efficacy and safety.The aim of the study was to assess the efficacy and safety of intraparenchymal transplantation of autologous MSCs from the bone marrow for the treatment of patients with cirrhosis of the liver caused by the hepatitis C virus (HCV-LC).Materials and methods. A pilot open-label non-randomized prospective study with the inclusion of 6 patients with HCV-LP. Autologous MSCs were transplanted intraparenchymally into the liver tissue at the rate of 1x106/kg body weight — 1 ml at 5 points.Results. By 6 months after transplantation, there has been a decrease in the level of bilirubin (from 36,4 μmol/L to 27 μmol/L, p=0.03), MELD scores (from 11,5 to 8, p=0.035), and an increase in platelet levels by 3 months (from 83x109 / l to 124,6x109/l, p=0,031) and 6 months (up to 119,5x109/l, p=0,031). By 6 months after transplantation, there has been no statistically significant result in changing on points on the Child-Pugh scale (p=0,181), cytolysis indicators (maintaining elevated levels of ALT (p=0,062) and AST (p=0,844)), replicative activity of the virus (рreservation of HCV RNA in the blood) (p=0,219 ). Moreover, introduction of MSCs by 6 months after transplantation did not lead to resolution of liver cirrhosis and inflammatory infiltration according to light microscopy data, as well as to resolution of sinusoidal capillarization (p=0,586) and PCI transdifferentiation into myofibroblasts (p>0,99) according to immunohistochemical studies. None of the procedures after the transplantation had an increase in body temperature, an increase in laboratory parameters, or changes in vital functions. One patient was admitted to hospital after 6 months. after MSC transplantation, deep vein thrombosis of the right leg was diagnosed.Conclusion. The positive effect of MSCs on the improvement of liver function was noted. There was no effect on the replicative activity of the virus. The continuing activity of the inflammatory process was observed. The used MSC transplantation technique is a safe procedure for patients with HCV-LC severity classes A and B and can be applied in clinical practice.

Age-related deterioration in female fertility is mainly associated with a decrease in the number and quality of ovarian follicles, which, in turn, leads to various endocrine disorders. In the present work, the steroidogenic activity of theca and granulosa layers from preovulatory follicles of laying hens of different ages was studied in vitro. Young hens aged 32-33 weeks with a long egg clutch and hens aged 74-76 weeks with a short egg clutch were used in the experiments. The granulosa and theca layers were isolated from the two largest preovulatory follicles F1 and F2 and cultured separately for 18 h. After culture, the concentration of sex steroid hormones in the media was determined by ELISA. The production of progesterone by the granulosa layer was 1.5-2.0 times higher in reproductively aged layers than in young layers. Concurrently, the secretory activity of granulosa cells increased with the development of follicles from the F2 stage to the F1 stage only in aged birds (from 74.0±7.5 to 97.0±10.9 pmol/mg tissue, P At the same time the ability of theca cells to secrete estradiol-17β was 1.6-2.3 times lower (P The findings indicate that the processes associated with ovarian aging modulate the steroidogenic activity of follicular cells in laying hens, with the age-related reduction in the egg clutch being related to an increase in the basal production of progesterone and testosterone in the two largest preovulatory follicles.

An urgent problem in the treatment of Crohn's disease in children is a loss of sensitivity or lack of response to prescribed anti-inflammatory therapy, which is manifested by a relapse or an increase in the degree of disease activity. This therapy includes glucocorticosteroids, immunosuppressants, salicylates, genetically engineered biological drugs, and enteral nutrition products. In this regard, new methods of treatment are being developed, one of which is the use of mesenchymal stem cells (MSC). There is experience in the world on the use of mesenchymal stem cells (MSCs) in adult patients with inflammatory bowel diseases (IBD). Clinical studies on the use of MSCs in children with IBD are in their infancy. The article describes a clinical case demonstrating the effectiveness of MSC administration in a patient with Crohn's disease. It demonstrates the short-term clinical efficacy of systemic administration of allogeneic MSCs in a patient with Crohn's disease as a combination treatment with standard therapy. The results of the study confirm that the use of MSCs with their powerful immunosuppressive, anti-inflammatory and regenerative potential can be one of the components of complex therapy for IBD in children.

Objective of the study . Analysis of the treatment outcomes of patients with MLL rearrangements in the Republic of Belarus within protocols AML-MM-2000 and AML-MM-2006.Materials and methods . The study included 151 patients with newly diagnosed acute myeloid leukemia (AML) who were treated according to protocol AML-MM-2000 and AML-MM-2006. 11q23 abnormalities were detected in 40 (26.5 %) out of 151 patients.Results . The performed analysis of the survival outcomes of patients with 11q23 depending on the protocol showed that the probability of 5-year event-free survival (EFS) was significantly better (p = 0.0110) in children receiving treatment under protocol AML-MM-2006 (86 ± 13 %) compared with that of the patients included in protocol AML-MM-2000 (23 ± 12 %). Using protocol AML-MM-2006 allowed reducing the cumulative incidence of relapse (CIR) in this cohort from 46.2 ± 15.1 to 14.3 ± 14.3 % (p = 0.1609). EFS probability in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) was 100 %, whereas in the group without alloHSCT – 31 ± 12 %, p = 0.0359. The treatment outcomes of patients with t(1;11) are comparable to those with CBF leukemia. The risk of relapse in patients with t(10;11) is higher than in the rest of the 11q23 cohort (62.5 ± 19.2 % versus 21.9 ± 7.5 %; p = 0.0136). CIR in patients with t(9;11) decreased from 42.8 % in protocol AML-MM-2000 to 15.4 % in protocol AML-MM-2006 (p = 0.1411).Conclusion . For the described cohort of patients alloHSCT is the best option for post-remission therapy. The worst prognosis is determined in patients with t(10;11), whereas the presence of t(1;11) is a favorable prognostic factor. Using the arm with cladribine showed to be effective in patients with t(9;11). To obtain reliable outcomes, we consider it reasonable to continue the study with the use of cladribine in patients with t(9;11).

Introduction. The importance of the HCV-infection is determined by the wide spread, progressive course, the formation of liver cirrhosis (LC) and hepatocellular carcinoma. The mechanisms of the effect of the virus on hepatic cells, the processes of fibrogenesis and fibrolysis, mechanisms of the reverse development of the LC remain unexplored. There is no effective pathogenetic therapy. The aim of the study — determination of the effectiveness and safety of intrahepatic transplantation of mesenchymal stem cells (MSC) in chronic HCV-infection at the stage оf LC. Methods. A patient with HCV-LC who has a secondary hemorrhagic vaculities who underwent autologous MSC transplantation into the liver tissue. The liver biopsy specimens were studied in dynamics by light and electronic microscopy and by immunohistochemistry. Results. The transplantation and posttransplantation period proceeded without complications. After the introduction of MSC the features of the formed micronodular LC remained. In some parts of the samples, the septa looked thin, sometimes perforated, indicating a resorption in this place of fibrous tissue. There was a decrease in the degree of transdifferentiation of stellate cells into myofibroblasts, a decrease in the number of fibroblasts and fibroblasts, there were no immune reactions in the form of deposition of amorphous and fibrous masses of moderate electron density along the sinusoidal capillaries that were significantly expressed in the primary biopsy. These changes were combined with the appearance of hepatocyte heterogeneity in the density of the cytoplasmic matrix, the state and quantity of organelles and inclusions, and the structural improvement of intracellular organelles. Conclusion. Autologous transplantation of mesenchymal bone marrow stem cells reduces the degree of destructive changes in hepatocytes, the severity of fibrosis and contributes to the improvement of the morpho-functional state of the liver, and therefore, it can be recommended as an important component of medical interventions.

Eser, Sultan (Balikesir Author), Background In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights.Findings For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer., American Cancer Society Centers for Disease Control and Prevention Swiss Re Swiss Cancer Research foundation Swiss Cancer League Institut National du Cancer La Ligue Contre le Cancer Rossy Family Foundation US National Cancer Institute Susan G Komen Foundation

Secondary leukemias in children in most cases are acute myeloid leukemia (AML) cases induced by chemotherapy and/or radiotherapy and by other chemical mutagens after treatment of malignant neoplasms (MN) or acquired aplastic anemia (AAA). The purpose of this study was to evaluate the clinical and laboratory features of secondary AML. The study included 9 patients with secondary AML and 128 patients with de novo AML. The girls revealed secondary AML more often. The largest percentage of secondary AML cases was observed in the age group from 3 to 10 (age median: 11.5), the most frequently registered morphology was M1-M2, but statistically significant differences with de novo AML were not found (p > 0,05). When comparing the clinical manifestations, no significant differences were detected (p > 0,5). Meanwhile, the pathology of chromosome 7 with secondary AML was significantly the most prevalent (p ≤ 0,01).

To assess the response of cells to antileukemic drugs in vitro in the concentration, similar to the therapeutic in blood, a diagnostic kit has been suggested to switch the panel of frozen-dried drugs that can help to compare the sensitivity of the patient`s leukemic cells to different preparations.

The article contains the scientific facts regarding the radiogenic leukemia risks in children after the exposure of low doses ionizing radiation, as well as the results of the main completed epidemiological childhood leukemia studies in Belarus after the Chernobyl accident, and a discussion of the necessity of further researches taking into account the recommendations of the Chernobyl Forum and World Health Organization.

We studied expression and functional activity of tumor cell P-gp in children with various leukemia variants and analyzed its prognostic role in acute lymphoblastic leukemia. Functional activity of P-gp increased in acute myeloid leukemia, relapses of acute lymphoblastic leukemia (in comparison with primary disease), and in a group of patients in whom no remission was attained. The survival of patients with acute lymphoblastic leukemia was lower in cases with increased expression and function of P-gp.

The article presents 8 cases of secondary acute myeloblastic leukemia in patients, undergoing the treatment for a malignant neoplasm or anplastic anemia acquired in childhood and 40 cases of de novo acute myeloblastic leukemia of the high risk group. The clinical laboratory characteristics, therapy and survival rate of secondary acute myeloblastic leukemia and de novo acute myeloblastic leukemia have been discussed in the article with the account of the literary up-to-date data.

The objective of this study was to investigate expression of drug resistance associated genes in CD34+ and CD34- leukemic subpopulations in childhood acute lymphoblastic leukemia (ALL).ALL samples with heterogeneous CD34 expression were separated into CD34-positive and CD34-negative subpopulations and mRNA levels of MDR1, LRP, BCRP and BCL-2 genes were compared.BCL-2 gene expression levels did not differ significantly between CD34+ vs CD34- subpopulations in most analyzed ALL cases. Oppositely, MDR1 gene hadtwo-fold differences in expression levels between subpopulations in the majority of ALL cases. In T-lineage ALL CD34- fractions had increased level of BCRP and LRP genes in comparison with CD34+ ones whereas in most of B-lineage ALL expression of these genes did not differ.It was not found the unique pattern of resistance related genes expression in CD34+ vs CD34- subpopulations. However, in majority of studied pediatric ALL cases with CD34 heterogeneous expression one of subpopulations (positive or negative) could have an advantage for survival through elevated expression of drug resistance related genes.

The acute-phase response alters the composition of carrier proteins in plasma, which may affect the blood deposition and transport of biomediators and drugs. The effect of the acute-phase response on the ligand binding ability of plasma was studied in leukemic children with and without systemic inflammation (sepsis and septic shock). To target different transport proteins, differentially charged fluorescent dyes were used: anionic ANS (8-anilinonaphthalene-1-sulfonate), uncharged Nile red, and cationic Quinaldine red. Human serum albumin was a principal carrier for ANS and competed for Nile red binding with lipoproteins. The synchro-scan fluorescence spectra of Nile red in plasma distinguished two species of the dye bound to serum albumin and to low-density and/or very low-density lipoproteins. The binding of Quinaldine red did not correlate with albumin and lipoprotein levels, and was probably determined by alpha(1)-acid glycoprotein. Compared with the control group, leukemia increased Quinaldine red binding by 65% and did not significantly affect the binding of other probes. Sepsis and septic shock did not change the binding of Quinaldine red, but progressively decreased ANS binding, finally by about 33%, and shifted Nile red distribution from serum albumin toward lipoproteins. These changes reflected a modified composition of the three principal transport proteins in plasma in the acute-phase response. Simple and rapid fluorescent tests developed in this study can be used to evaluate the acute-phase response and to optimize drug administration protocols in clinical practice.