bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal rich club organization in end-stage renal disease patients before dialysis initiation and undergoing maintenance hemodialysis
Authors: Ma Shaohui , Zhang Ming , Liu Yang , Ding Dun , Li Peng , Ma Xueying , Liu Hongjuan , Mu Junya
Published: November 2020

Background: End-stage renal disease (ESRD) patients are at a substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there isn’t an uncontested result whether cognition was improved or worsened during dialysis.Methods: To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), predialysis ESRD patients (predialysis group), and maintenance hemodialysis ESRD patients (HD group). All ESRD patients performed six blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K+, and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in the HD group and predialysis group.Results: Neuropsychological analysis showed the HD group exhibited better cognitive function than the predialysis group, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the predialysis group and HD group than the HCs. Besides, a lower normalized clustering coefficient was found in the predialysis group relative to the HCs and HD group. For the GLM analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in the predialysis group.Conclusions: Our study revealed that dialysis had a limited effect on cognitive improvement.
Protein synthesis inhibitors stimulate MondoA transcriptional activity by driving an accumulation of glucose 6-phosphate
Authors: Wilde Blake R , Kaadige Mohan R , Guillen Katrin P , Butterfield Andrew , Welm Bryan E , Ayer Don
Published: November 2020

BACKGROUND Protein synthesis is regulated by the availability of amino acids, the engagement of growth factor signaling pathways and ATP levels sufficient to support translation. Crosstalk between these inputs is extensive, yet other regulatory mechanisms remain to be characterized. For example, the translation initiation inhibitor Rocaglamide A (RocA) induces Thioredoxin Interacting Protein (TXNIP). TXNIP is a negative regulator of glucose uptake, thus its induction by RocA links translation to the availability of glucose. MondoA is the principal regulator of glucose-induced transcription and its activity is triggered by the glycolytic intermediate, glucose 6-phosphate (G6P). MondoA responds to G6P generated by cytoplasmic glucose and mitochondrial ATP (mtATP), suggesting a critical role in the cellular response to these energy sources. TXNIP expression is entirely dependent on MondoA, therefore, we investigated how protein synthesis inhibitors impact its transcriptional activity.METHODS We investigated how translation regulates MondoA activity using cell line models and loss-of-function approaches. We examined how protein synthesis inhibitors effect gene expression and metabolism using RNA-sequencing and metabolomics, respectively. The biological impact of RocA was evaluated using cell lines and Patient-Derived xenograft Organoid (PDxO) models. RESULTS We discovered that multiple protein synthesis inhibitors, including RocA, increase TXNIP expression in a manner that depends on MondoA, a functional electron transport chain and mtATP synthesis. Furthermore, RocA increases mtATP and G6P levels and TXNIP induction depends on interactions between the Voltage-Dependent Anion Channel (VDAC) and hexokinase, which generates G6P. RocA treatment impacts the regulation of ~1200 genes and ~250 of those genes are MondoA-dependent. RocA treatment is cytotoxic to Triple Negative Breast Cancer cell lines and shows preferential cytotoxicity against ER- PDxO breast cancer models. Finally, RocA-driven cytotoxicity is partially-dependent on MondoA or TXNIP.CONCLUSIONS Our data suggest that protein synthesis inhibitors rewire metabolism, resulting in an increase in mtATP and G6P, the latter driving MondoA-dependent transcriptional activity. Further, MondoA is a critical component of the cellular transcriptional response to RocA. Our functional assays suggest that RocA or similar translation inhibitors may show efficacy against ER- breast tumors and that the levels of MondoA and TXNIP should be considered when exploring these potential treatment options.
A Cross-Sectional Study On The Practice Of Wet Nursing Among Muslim Mothers
Authors: Rahim Norsyamlina Che Abdul , Hamjah Salasiah Hanin , Majid Latifah Abdul , Kusrin Zuliza , Hashim Nurhidayah Muhammad , Saidon Rafeah , Bahari Nora’inan , Ilias Muhamad Zariff , Ahmad Noor Ani
Published: November 2020

Background: Breastfeeding and wet nursing have been synonymous since ancient times. The practice of wet nursing of another woman’s child in Malaysia is on the rise due to the emergence of awareness among the public about the importance and advantages of breast milk. However, problems arise when there is no systematic system to record and trace the milk mother and milk child data, especially for Muslim participants as milk kinship could affect their relationship status in Islam. Therefore, this study aims to determine the practice of wet nursing among Muslim mothers in Selangor. Simultaneously, this study intends to provide the authorities with an accurate picture of the more aggressive compilation of steps to prevent duplication of consanguinity in wet nursing. Methods: This cross-sectional study was conducted on 100 women who had breastfed another child in Selangor. Data were obtained using a validated questionnaire (Cronbach alpha=0.8) and processed using the SPSS software. Results: Results showed 43.0% of respondents had at least breastfed one someone else’s child. Meanwhile, there were 3.0% of the respondents were nursing seven to ten other children. A total of 237 children have been breastfed by the respondents (n = 100). Of these, 21.5% children were breastfed less than five times, while 78.5% children were breastfed less than five times. Most mothers recorded their milk child background data, and this shows that the community is aware of the importance of data documentation and it indirectly proves that the authorities should act on these current needs. Conclusions: This study shows that there is a wet nursing practice in the society. Obviously, a phenomenon, trend and practice in the society has the ground and basis as to why it existed and is upheld. Researches related to wet nursing and matters connected to it should continue so as to bring about much good to society.
Factors affecting birthweight decline in recent Japan based on birth certificates
Authors: Kato Noriko , Sauvaget Catherine , Yoshida Honami , Yokoyama Tetsuji , Yoshiike Nobuo
Published: November 2020

Background: Birthweight has been declining consistently for >30 years in Japan. This rapid rise in low birthweight in infants is the worst among the Organization for Economic Co-operation and Development countries.Objective: To contribute to the literature and provide new information to clarify the risk factors associated with birthweight decline in Japan.Methods: We used population-based birth certificate data from vital statistics records with prior permission and retrieved 40,968,266 birth certificates of neonates born between 1980 and 2004 to analyze time trends using linear regression analysis for examining whether the decline in birthweight could be explained by obstetrical variables such as gestational age and multiple gestations.Results: From 1980 to 2004, we observed a decline in mean birthweight with a yearly effect of -8.07 g, which became steeper after 1985, persisted until 1999, and plateaued thereafter. After adjusting for gestational age, neonatal gender, birth order, multiple gestations, and fathers’ age, the yearly effect between 1980 and 2004 reduced to -5.13 g. Conclusion: Recent decreases in birthweight among Japanese neonates were not explained fully by trends in gestational age, neonatal gender, birth order, multiple gestations, and fathers’ age. Thus, additional factors such as pre-pregnancy maternal body mass index and maternal diet should be considered.
The use of dried tube specimens of Plasmodium falciparum in an External Quality Assessment program to evaluate health worker performance for malaria rapid diagnostic testing in healthcare centers in Togo
Authors: DORKENOO Monique Ameyo , Kouassi Kafui Codjo , Koura Adjane K. , Adams Martin L , Gbada Komivi , Katawa Gnatoulma , Yakpa Kossi , Charlebois Remi , Milgotina Ekaterina , Merkel Michele O , Aidoo Michael
Published: November 2020

Background: The use of rapid diagnostic tests (RDTs) to diagnose malaria is common in Sub-Saharan African laboratories, remote primary health facilities and in the community. Currently, there is a lack of reliable methods to ascertain health worker competency to accurately use RDTs in the testing and diagnosis of malaria. Dried tube specimens (DTS) have been shown to be a consistent and useful method for quality control of malaria RDTs, however, its application in National Quality Management programs has been limited.Methods: A P. falciparum strain was grown in culture and harvested to create DTS of varying parasite density (0, 100, 200, 500 and 1,000 parasites/µL). Using the dried tube specimens as quality control material, a proficiency testing (PT) program was carried out in 80 representative health centers in Togo. Health worker competency for performing malaria RDTs (mRDTs) was assessed using five blinded DTS samples, and the DTS were tested in the same manner as a patient sample would be tested by multiple testers per health center. Results: All the DTS with 100 parasites/µl and 50% of DTS with 200 parasites/µl were classified as non-reactive during the pre-PT quality control step. Therefore, data from these parasite densities were not analyzed as part of the PT dataset. PT scores across all 80 facilities and 235 testers was 100% for 0 parasites/µl, 63% for 500 parasites/µl and 93% for 1,000 parasites/µl. Overall, 59% of the 80 healthcare centers that participated in the PT program received a score of 80% or higher on a set of 0, 500 and 1,000 parasites/ µl DTS samples. Sixty percent of health workers at these centers recorded correct test results for all three samples. Conclusions: The use of DTS for a malaria PT program was the first of its kind ever conducted in Togo. The ease of use and stability of the DTS illustrates that they this type of samples can be considered for the assessment of staff competency. The implementation of quality management systems, refresher training and expanded PT at remote testing facilities are essential elements to improve the quality of malaria diagnosis.
Aqueous alteration without initial water: Possibility of organic-induced hydration of anhydrous silicates in meteorite parent bodies
Authors: Hirakawa Naoki , Kebukawa Yoko , Furukawa Yoshihiro , Kondo Masashi , Nakano Hideyuki , Kobayashi Kensei
Published: November 2020

Early evolution of Solar System small bodies proceeded through interactions of mineral and water. Melting of water ice accreted with mineral particles to the parent body results in the formation of secondary minerals, the so-called aqueous alteration. Formation of phyllosilicates from anhydrous silicates is a typical alteration effect recorded in primitive meteorites. In addition to mineral and water, organic matter could have been also a significant component in meteorite parent bodies. However, the role of organic matter in the alteration of silicates is not well understood. We conducted a heating experiment of anhydrous silicate (olivine) with a mixture of organic compounds which simulated primordial organic matter in the Solar System. Dissolution and precipitation features were confirmed on the olivine surface after heating at 300 °C for 10 days, and proto-phyllosilicates were formed in the precipitation area. Magnesite was also detected as concomitant mineral phase. These minerals could be the evidence of aqueous alteration and carbonation of olivine induced by water generated through decomposition of the organic compounds with hydroxy groups. Our result showed that the in-situ formation of hydrated silicates through a mineral-organic interaction without the initial presence of water. It further implies that formation of phyllosilicates on the olivine surface in contact with organic matter can occur in meteorite parent bodies which formed inside the H2O snow line but accreted with organic matter, initially without water. Water formed through decomposition of organic matter could be one candidate for hydrous silicate formation, for example in ordinary chondrites from S-type asteroids inside the H2O snow line. Although the origin of water in ordinary chondrites is under debate, water generation from organic matter may also explain the D-rich water in ordinary chondrites because primordial organic matter is known to be D-rich.
A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs.
Authors: Flossmann Gabriele , Wurmser Christine , Pausch Hubert , Tenghe Amabel , Dodenhoff Jörg , Dahinten Günther , Götz Kay-Uwe , Russ Ingolf , Fries Ruedi
Published: November 2020

Background: Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts. Results: A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10 -43 ). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 ( BMP15 , Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10 -83 ) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth. Conclusion: Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.
A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling
Authors: Sun Suofeng , Gao Jing , Zhou Shen , Li Yuan , Wang Yu , Jin Li , Li Jian , Liu Bowei , Zhang Bingyong , Han Shuangyin , Ding Hui , Li Xiuling
Published: November 2020

Background: Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.Methods: qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.Results: Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188-9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC.Conclusions: Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.
Loss of MIG-6 results in endometrial progesterone resistance via ERBB2
Authors: Yoo Jung-Yoon , Kim Tae Hoon , Shin Jung-Ho , Marquardt Ryan , Mueller Ulrich , Fazleabas Asgerally , Young Steven , Lessey Bruce , Yoon Ho-Geun , Jeong Jae-Wook
Published: November 2020

Female subfertility is highly associated with endometriosis. Although the exact etiology of endometriosis-related infertility remains to be determined, endometrial progesterone resistance has recently been suggested as a crucial element in the development of endometrial diseases. Here, we report that MIG-6, a progesterone-induced gene, is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. In an endometriosis mouse model with a fluorescent reporter used to identify lesions, an increase of endometriosis development and implantation failure were observed in mice with Mig-6 deficient endometrium compared to controls. MIG-6 is known to inhibit ERBB2, which we found overexpressed in the endometrium from uterine-specific Mig-6 knock-out mice (Pgrcre/+Mig-6f/f; Mig-6d/d). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduced Erbb2 ablation in Mig-6d/d mice (Mig-6d/dErbb2d/d mice). The additional knockout of Erbb2 rescued all phenotypes seen in Mig-6d/d mice including endometrial progesterone resistance, infertility, and endometriosis lesion development. Transcriptomic analysis showed that genes differentially expressed in Mig-6d/d mice reverted to their normal expression amounts in Mig-6d/dErbb2d/d mice. Together, our results demonstrate that MIG-6-induced ERBB2 overexpression causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility and that ERBB2 targeting reverses these effects.
Granulocyte-Macrophage Colony-Stimulating Factor and CAR-T Technology for Solid Tumors in Experiment
Authors: Zaytsev Daniil Vladislavovich , Zaikova E.K. , Golovkin A.S. , Bulatov E.R. , Valiullina A.Kh. , Mirgayazova R.M. , Daks A.A. , Zaritskey A.Yu. , Petukhov A.V.
Published: November 2020

Background. Cytokines are considered as important factors that enhance the efficacy of CAR-T cell therapy. Besides, they are key elements of the pathogenesis of cytokine release syndrome and neurotoxicity in applying the CAR-T technology. However, cytokine effects in the context of CAR-T therapy have not yet been properly studied. Aim. To quantitatively assess cytokine secretion using multiplex assay with co-incubation of anti-CD19 CAR-T lymphocytes with epithelial HeLa and A431 cell lines expressing CD19 on their surface. Materials & Methods. T-lymphocytes were transduced with the lentiviral vector containing anti-CD19-CAR gene. CAR expression was tested based on GFP reporter using flow cytometry. To confirm a specific CAR-T cell activation response to tumor antigen, the levels of interleukin-2, interferon-γ, and tumor necrosis factor-α were measured by means of immunoassay. Cytotoxic activity of CAR-T lymphocytes obtained was examined with their direct co-culturing with target cells. The levels of cytokines isolated prior to and after incubation of targets with CAR-T cells were compared using multiplex assay. Results. The level of some proinflammatory cytokines (interleukin-6, interleukin-1β, interferon-γ) (P < 0.01) increased. The difference in the levels of anti-inflammatory cytokines (interleukin-4, interleukin-10) was inconsiderable, and in the HeLa cell line experiment it was insignificant (p > 0.05). The concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) was many times higher after incubation with CAR-T lymphocytes (p < 0.01). Conclusion. The trial revealed multiple enhancement of GM-CSF, one of the key elements of the pathogenesis of cy tokine release syndrome and CAR-T-associated neurotoxicity. The results of further studies of GM-CSF can contribute to improving the efficacy of CAR-T therapy with considerably lower toxicity.
Aldehyde Dehydrogenase as a Marker of Early Mesenchymal Progenitor Cells in Donor Bone Marrow Stroma
Authors: Vetoshkin Konstantin Aleksandrovich , Isaeva N.V. , Butolina M.A. , Minaeva N.V. , Zorina N.A. , Khorobrykh M.N. , Zmeeva Yu.S.
Published: November 2020

Aim. To analyze the growth rate of mesenchymal stromal cell (MSC) culture depending on the aldehyde dehydrogenase-positive (ALDH+) cell count. Materials & Methods. The study involved bone marrow mesenchymal cell cultures of 10 donors (5 men and 5 women) with median age of 34.5 years (range 14-38 years). Nucleated cells were obtained by density gradient centrifugation. MSCs were cultivated according to the conventional protocol using platelet-rich donor plasma. Stromal cell identification and ALDH+ cell counting were performed by laser flow cytometry according to the criteria of the International Society for Cell Therapy. Results. The growth rate of MSC cultures and ALDH+ cell counts are maximum at primary and passage No. 1, becoming significantly lower by passage No. 3. The relationship between MSC culture growth rate and ALDH+ cell count was revealed. The older the donor, the lower MSC culture growth rate and ALDH+ cell count in bone marrow stroma. Conclusion. The data obtained indicate the relationship between bone marrow MSC culture growth rate, donor’s age, and ALDH+ cell count. ALDH-expressing cells proved to confer MSC population renewal. Based on the results acquired, we assume that the studied ALDH marker can serve as an objective criterion for placing mesenchymal cell elements into the category of early progenitor cells.
Bendamustine in the Treatment of Relapsed/Refractory Hodgkin’s Lymphoma: Literature Review and Clinical Experience
Authors: Shklyaev Stanislav Sergeevich , Falaleeva N.A. , Bogatyreva T.I. , Terekhova A.Yu. , Danilova M.A.
Published: November 2020

Aim. To assess the efficacy of bendamustine combined with dexamethasone in the treatment of relapsed/refractory Hodgkin’s lymphoma (HL). Materials & Methods. The article provides an updated review of literature as well as the data of prospective observational clinical trial in 47 HL patients (17 men and 30 women aged 20-65 years, median age 36 years) with relapses after standard and high-dose chemotherapy with autologous hematopoietic stem cell transplantation. The therapy regimen included 120 mg/m2 of bendamustine IV on Days 1 and 2 and 20 mg of dexamethasone IV from Day 1 to Day 4. Retreatment was administered 21 days after the start of the previous one. Radiotherapy was applied only to the regions of massive relapsed lesions and bone destructions with pain syndrome. Results. From April 2011 to September 2017 all 47 patients received 149 bendamustine + dexamethasone therapy regimens with the overall response of 57 % (complete response 27 %, partial response 30 %). Disease progression on therapy was reported in 20 (43 %) patients, its incidence was the highest after the first (n = 8) or the second cycle (n = 4). In the group of 27 patients with overall response 19 (70 %) patients showed new relapses. In these cases the treatment-free period was from 8 to 31 months (median 11 months). The repeated administration of 57 bendamustine + dexamethasone therapy regimens in 12 out of 47 patients achieved clinical effect for 4-36 months (median 6 months). After the first failure of bendamustine-based therapy 13 patients were treated with brentuximab vedotin and nivolumab, the new salvage therapy drugs. With median follow-up of 22 months (range 1-69 months) median overall survival (OS) and time to the next progression were 35 and 10 months, respectively, in all patients. Multivariate analysis showed that OS was unfavorably affected only by B-symptoms on bendamustine + dexamethasone administration (p = 0.046), and the time to the next progression was shorter in the presence of B-symptoms (p = 0.017) and in histological variant “nodular sclerosis type II” (p = 0.006). Conclusion. Bendamustine + dexamethasone therapy is a relatively low-toxic and effective method of life prolongation in HL patients with chemotherapy-refractory tumors and recurrent relapses, provided no B-symptoms occur by the start of antitumor therapy.
Chronic Myeloid Leukemia: Role of Allogeneic Hematopoietic Stem Cell Transplantation in the Era of Tyrosine Kinase Inhibitors
Authors: Morozova Elena Vladislavovna , Vlasova Yu.Yu. , Barabanshchikova M.V. , Mamaev N.N. , Barkhatov I.M. , Alyanskii A.L. , Darskaya E.L. , Vladovskaya M.V. , Bondarenko S.N. , Moiseev I.S. , Afanasyev B.V.
Published: November 2020

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a radical method of chronic myeloid leukemia (CML) treatment. In the 1990s CML became the most frequent indication for allo-HSCT worldwide. CML treatment drastically changed after tyrosine kinase inhibitors (TKI) had been introduced into clinical practice. However, despite considerable progress achieved in treatment, low survival rate is observed in patients with CML either diagnosed at an advanced stage or characterized with resistance, TKI intolerance, and loss of response. For such patients allo-HSCT remains the only and the best treatment solution. The present article discusses current views on the importance of allo-HSCT for CML treatment in the era of extensive use of TKIs.
Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Treatment with and without the Use of Granulocyte Colony-Stimulating Factor in Post-Transplantation Period
Authors: Gritsaev S.V. , Kostroma I.I. , Zhernyakova A.A. , Zapreeva I.M. , Chebotkevich V.N. , Bessmeltsev S.S. , Chechetkin A.V.
Published: November 2020

Background. There exist different data on how the administration of granulocyte colony-stimulating factor (G-CSF) after autologous hematopoietic stem cell transplantation (auto-HSCT) affects the duration of post-transplantation agranulocytosis in multiple myeloma (MM) patients. Aim. To study the effect of G-CSF, administered after auto-HSCT to MM patients, on the duration of neutrophil engraft-ment, febrile neutropenia rate, and hospitalization duration. Materials & Methods. The trial included 36 MM patients aged 42-69 years (median 59 years), 16 of which were not treated with G-CSF (1st group), and 20 patients received a single injection of 6 mg pegylated G-CSF on Day +4 or Day +5 (2nd group). Results. Patients of the 1st group were significantly younger than patients of the 2nd group: median 55.5 and 61 years, respectively (p = 0.006). There were no differences with respect to the number of patients who previously received lenalidomide, the overall and very good partial response rate, the number of the first and repeated auto-HSCTs, and the number of melphalan conditioning regimens. The patients who received G-CSF engrafted neutrophils on day 11 (median) after auto-HSCT, i.e. earlier than patients without G-CSF administration who engrafted neutrophils on day 13 (p = 0.006). In the 1st group intravenous antibiotics were administered for a longer time than in the group with G-CSF: median 13 and 11 days, respectively (p = 0.04). In 2 patients from the group without G-CSF sepsis was diagnosed. G-CSF administration led to a shorter hospital stay: median 16 and 18 days in the 1st and 2nd groups, respectively (p = 0.08). There were no differences in the number of patients with febrile neutropenia. Conclusion. G-CSF administration improves the course of the post-transplantation period in MM patients. The final decision on the feasibility of G-CSF administration after auto-HSCT can be made after more clinical observations are available.
Early Response and Long-Term Outcomes of Ruxolitinib Therapy in Myelofibrosis: Multicenter Retrospective Study in 10 Centers of the Russian Federation
Authors: Lomaia E.G. , Siordiya N.T. , Senderova O.M. , Ochirova O.E. , Zhalsanova E.B. , Furtovskaya A.Yu. , Dimov G.P. , Pozina M.G. , Li O.Yu. , Trizna K.B. , Mikhalev M.A. , Sokurova E.V. , Otmorskaya A.A. , Khazieva A.S. , Ust’yantseva V.V. , Rogovaya Yu.D. , Zaritskey A.Yu.
Published: November 2020

Aim. To assess the efficacy of targeted therapy with ruxolitinib in patients with myelofibrosis in real clinical practice in Russia. To determine the prognostic value of spleen reduction in the early stages of ruxolitinib treatment and its effect on overall survival. Materials & Methods. The present retrospective study was based on the data of 10 centers of Russia. It included 56 myelofibrosis (primary or post-polycythemic and post-throm-bocythemic) patients who received ruxolitinib. The median age of patients was 56 years (range 26-76 years). Most of them (59 %) were considered intermediate-1 risk according Results. By the start of data collection most of patients (79 %) had been treated with ruxolitinib. In no case therapy was withdrawn for the reason of drug toxicity. On ruxolitinib constitutional symptoms were reversed in 70 %, 87 %, and 98 % of patients by months 1, 3 and 6, respectively. In 36 % and 46 % of patients by months 3 and 6, respectively, > 50 % decrease in spleen size was observed. Overall, in 31 % and 27 % of cases the size of the spleen decreased by less than 25 % by months 3 and 6, respectively. The factors affecting the changes in spleen size have not been identified. The probability of overall survival by years 2 and 5 of follow-up was 97 % and almost 70 %, respectively. This parameter was significantly affected by the extent of spleen size reduction by month 3 of follow-up as well as by its initial size. Conclusion. Ruxolitinib shows high efficacy for both decrease of general myelofibrosis symptoms and reduction in spleen size. The extent of spleen reduction is an important prognostic factor. It seems, that in patients with insufficient spleen reduction an increase in drug dose is advisable. If it is not possible, alternative methods of treatment should be sought.
Pharmacokinetics, Safety, and Tolerance of Anagrelide, the First Domestic Generic, Compared with Reference Drug
Authors: Zyryanov S.K. , Chistyakov V.V. , Butranova O.L. , Stepanova E.S. , Potanina O.G. , Abramovich R.A.
Published: November 2020

Background. Anagrelide is used for the treatment of essential thrombocythemia. This drug selectively affects thrombocytes without inducing pronounced myelosuppression, which provides a satisfactory safety profile. Aim. To compare pharmacokinetics and to assess bioequivalence of two anagrelide drugs for oral administration in healthy volunteers. Materials & Methods. Open, randomized, two-period, twosequence, crossover study comparing pharmacokinetics and bioequivalence of anagrelide included 30 volunteers. The participants received a single dose of either test or reference drug, depending on the study period. Serial blood samples for pharmacokinetic analysis were collected within 12 hours after drug administration. Plasma anagrelide concentration was measured by high-performance liquid chromatography/mass spectrometry. Pharmacokinetic parameters were analyzed by non-compart-mental method. ANOVA analysis of variance was used for assessing the difference between the mean values of the AUC0-t, AUC0_ and Cmax pharmacokinetic parameters at 5 % significance level. Results. The mean values of maximum concentration (С ) after a single dose of anagrelide were 12.68 ± 2.99 ng/mL and 12.46 ± 3.15 ng/mL for test and reference drugs, respectively. Relative bioavailability was 1.16 ± 0.18. The AUC0-12 mean values calculated by anagrelide concentrations after a single dose of test and reference drugs were 30.38 ± 7.0 ng • h/mL and 28.78 ± 7.50 ng • h/mL, respectively, and the AUC0_ mean values were 31.13 ± 7.15 ng • h/mL and 29.55 ± 7.61 ng • h/mL, respectively. The assessment of main vital functions and laboratory parameters did not reveal any effect of the drugs on the health status of trial participants. Conclusion. Pharmacokinetic profile of the test drug (generic anagrelide) did not considerably differ from that of reference drug, which indicates in vivo bioequivalence of it. The assessment of drug safety yielded satisfactory tolerance; no serious adverse events have been reported.
Quality of Life of Hematologists in the Russian Federation According to the RAND SF-36 Questionnaire
Authors: Tsyba Nikolai Nikolaevich , Ionova T.I. , Lazareva Olga Veniaminovna , Nikitina T.P. , Porfir’eva N.M. , Petrova A.N. , Garmaeva T.Ts. , Turkina A.G.
Published: November 2020

Medical profession is notable for its enormous social value and associated with no less responsibility. At the same time, society’s requirements for doctors constantly increase. The regulation of medical activities in various disciplines becomes more and more stringent. The aim of the present article was to study the quality of life of 104 hematologists working in different regions of the Russian Federation. For this purpose, the Russian-language version of RAND SF-36 health survey questionnaire was used. Young doctors aged 35-44 years showed lowest scores on mental health inventory which may indicate negative emotional status and a low level of positive emotions. Compared to relatively healthy respondents, hematologists show a low level of emotional role functioning that may also indicate negative emotional status which in turn negatively affects the quality of health care delivery and appears to be a contributing factor in burnout syndrome. Compared to relatively healthy respondents, hematologists show higher pain scores which may indicate a specific attitude of doctors to pain due to their professional approach. Similar quality of life indicators indirectly suggest that hematologists in different regions of the Russian Federation regard their professional activities as a priority, and it affects their quality of life. Both the results obtained and the literature review prove the relevance of the study of human resources and development of programs aimed at continuity of personnel in the health care system. The quality of life of doctors in different disciplines should become the object of comprehensive sociological, clinical, and sanitation studies which will permit to design a program to improve the quality of life of the medical professionals.
Molecular genetic methods of analysis to identify the species affiliation of the raw material composition in food products
Authors: Yurova E. A. , Zhizhin N. A. , Filchakova S. A.
Published: November 2020

Received in revised 08.08.2020 Methods based on the analysis of proteins and DNA molecules are more and more used to assess the composition of food products. Proteins research methods include immunological, electrophoretic and chromatographic ones. The analysis of DNA molecules is most often used to identify the species affiliation of food components. This is due to the stability of their structure compared to proteins, as well as their presence in most biological tissues. The results of studies evaluating methodological approaches for the application of the PCR diagnostic method to identify the composition of food products and the possibility of their use for monitoring dairy products have been shown. The objects of research were samples of cow, goat, sheep milk, as well as milk samples of different animal species mixed in various ratios. DNA was extracted from milk samples according to a unified technique for the separation of DNA molecules in milk and dairy products. The work also considers the possibility of using the PCR diagnostic method to identify the raw material origin of the product. To evaluate the measurement methods, artificially created samples of raw milk were used, which were cow, goat and sheep milk, a mix of three types of milk in different ratios. As a result of the research, the main method has been chosen as the real time PCR method, which has reliability, high sensitivity, sufficient rapidity, with the possibility of using it for dairy multicomponent products with a complex structural matrix, as well as products that have undergone deep technological processing.
Optimization of fatty acid composition of cottage cheese bagel
Authors: Efremova A. A. , Lyulkovich V. S. , Naumova N. L.
Published: November 2020

The triglyceride composition of the fat base of margarine used in the technology of flour confectionery products (FCP) includes up to 70 % monounsaturated acids, up to 25 % saturated ones. It has been established that for a more complete assimilation of FCP, a fat-intensive product should contain these fatty acids in equal proportions and should not contain trans-isomers of fatty acids, the main source of which are partially hydrogenated vegetable oils. Trans fats contained in margarines can cause the development of many diseases. It is known that the fat of sunflower flour is represented by unsaturated acids: linoleic (≈70 %) and oleic (≈18 %), which are of great physiological importance. The aim of the research was to optimize the fatty acid composition of cottage cheese bagel through the use of flour from sunflower seeds. The nutritional value of raw materials has been investigated. Tests of several variants of modification of cottage cheese bagel recipe in the process of baking laboratory samples have shown the advantage of sunflower flour in comparison with wheat flour in terms of the amount of fat, proteins, dietary fiber. The possibility of replacing 15 % of wheat flour with flour from sunflower seeds with a decrease in margarine by 19.8 % in bagel technology has been established. The product of the modified prescription composition contain more polyunsaturated fatty acids (by 28.4 %), of which linoleic - by 29.9 %, γ-linolenic - by 50 %, docosahexaenoic - by 20 %, eicosatrienic - by 35 %; less saturated fatty acids (by 6.2 %), of which caprylic - by 14.0 %, lauric - by 13.9 %, capric - by 10.7 %, myristic - by 9.6 %, butyric - by 9.1 %, palmitic - by 6.7 %; fewer transisomers of fatty acids (by 8.7 %), of which transisomers of oleic acid - by 9.6 %, linolenic - by 33.3 %. The proposed development has good consumer properties, and is characterized by a high content of protein (by 11.6 %) and dietary fiber (by 7.2 %).
Study of rheological properties of gels based on Thorny Skate cartilage broth (Raja radiata) in the technology of natural fish culinary products -aspic fish, in jelly, fish jellies and potions
Authors: Shokina Yu. V. , Kuchina Yu. A. , Novozhilov M. P. , Popov M. M. , Shokin G. O.
Published: November 2020

The paper deals with methodological approaches to study the rheological properties of gelatin gels based on the thorny skate cartilage broth ( Raja radiate ), which is an aqueous extract of chondroitin sulfate, depending on the manufacturing technology. It is shown that the use of modern instrumental methods for studying the rheological properties of gels and methodological approaches typical of physical and colloidal chemistry allows to obtain the most complete and objective information about the mechanisms of formation of key consumer properties of fish products and the main directions of improving the technology of its manufacture. The influence of gelatin concentration in the range from 0.5 to 5.0 % in chondroitin sulfate-containing broths from the thorny skate cartilage on kinematic and dynamic viscosity of broths, as well as on the strength, melting point and shear stress indices of gels based on these broths was studied. As control samples, aqueous solutions of gelatin in concentrations from 0.5 to 5.0 % and gels based on them were used in the studies. The analysis of the results of the study showed that the broths prepared on the basis of the thorny skate cartilage have increased relative to the control samples the values of kinematic and dynamic viscosity, the increase in indicators is characterized by a directly proportional dependence on the concentration of gelatin in the broth. Gelatin gels based on chondroitin sulfate-containing broths made from the thorny skate cartilage have increased strength, which has a positive effect on the organoleptic evaluation and consumer properties of the finished culinary products.
La Cooperación Cultural como movilizadora del desarrollo sostenible
Authors: Caballero Poveda Francys Lorena , Diaz Donado Astrid Isabel
Published: November 2020

Una perspectiva reciente del desarrollo humano según la que este es definido en términos de libertad, ha permitido considerar la cultura como una dimensión esencial para lograr el desarrollo de cualquier comunidad. En este sentido, la presente investigación estudia inicialmente la relación entre cultura y desarrollo para posteriormente centrarse en el análisis del papel que tiene la cooperación cultural internacional como agente movilizador de desarrollo humano sostenible, tomando como referente, el caso de la comunidad de Getsemaní (ubicada en el Centro histórico de Cartagena de Indias), con su patrimonio cultural inmaterial representado en sus manifestaciones de vida de barrio.
Todo el proceso fue guiado por una metodología de corte cualitativo que tuvo como principales técnicas de recolección de información, la revisión de fuentes documentales, entrevistas semiestructuradas a expertos culturales y un grupo focal conformado por diferentes actores de la comunidad de Getsemaní. Los resultados obtenidos revelan la percepción positiva y altas expectativas que autores consultados, expertos entrevistados y miembros de la comunidad en mención, tienen con respecto al papel que podría desempeñar la cooperación cultural, como un medio generador de desarrollo sostenible en Getsemaní. Las consideraciones finales reafirman cómo esta cooperación se perfila como un fuerte aliado de las comunidades a la hora de gestionar su desarrollo a través de la cultura, al considerar que esta puede dar el impulso necesario para dar a conocer y gestionar su patrimonio inmaterial a través de proyectos en los que sea la misma comunidad la protagonista, desde su diseño hasta su implementación.
The rise and fall of a strategic partnership: Brazilian-Russian relations within the BRICS framework
Authors:   St. Petersburg State University, Jeifets Victor , Jubran Bruno Mariotto ,   State Department of Planning, Administration and Budget of Rio Grande do Sul
Published: November 2020

This article analyzes the recent evolution of Brazilian-Russian relations, with an emphasis on their interaction within the BRICS group. The authors claim that beyond the changes and un- certainties in global world order throughout the second decade of the 21st century, the evolution of Brazilian foreign policy, following the internal political conjectures in Brasilia, impacted not only the bilateral relations with Moscow, but also affected qualitatively its participation in the informal grouping. Political turmoil started in the South American nation in 2013 and the eventual impeachment of Dilma Rousseff in 2016 clearly marked a fundamental change in Brazil’s global orientation. Brazil abandoned its autonomist and soft revisionist stance on global affairs that characterized the Lula da Silva (2003–2010) and Rousseff (2011–2016) presidencies, and embraced a pro-US perspective, which became even more pronounced after the rise of Jair Bolsonaro in 2019. The article also addresses some prospects on possible paths of cooperation between Brasilia and Moscow in the near future and implications for neighboring countries, especially Argentina and Venezuela (the Venezuelan crisis as a factor of BRICS development is also considered).
Explaining the security of the global South: Western and Non-Western approaches
Authors:   Moscow State Institute of International Relations of MFA of Russia (MGIMO University), Khudaykulova Alexandra
Published: November 2020

Dominant security theories, being mostly Western by their origin, are concentrated on the Western experience and security models, with minimal attempts to analyze the postcolonial security landscape of the global “South” which heavily affects the security agenda. The predominant part of modern conflicts (with some exceptions) take place precisely in the developing countries of the global South Western and non-Western approaches to security are distinguished by an expanded (comprehensive) understanding, but in both cases the emphasis is different. Various readings of security create a conflict of perception and, according to many non-Western experts, reflect the Western strategy to initiate a new colonization. At the same time, neither Western understanding nor alternative non-Western critical security theories can claim to be universal. The article describes the dynamics of theoretical approaches to the conceptualization of security, mainly in the context of the dominant Western school of International Relations, demonstrates and explains the marginality of non-Western security issues, and provides an overview of key security issues and threats to the developing world. In addition, relatively new Western concepts of security (humanitarian intervention, human security, responsibility to protect) are being analyzed, which cause strong opposition from the entire developing world and are perceived by non-Western societies as a direct threat. The weakness of the “postcolonial” states, their apparent inability to cope with internal development problems and disorders, and to ensure the safety of the population within their borders, serve as a reason for becoming an object of political influence and interference. At the same time, the West and the non-West are making efforts to speak the same political language of security because of the indivisibility of the current threats. However, the Western practice of world regulation is rejected by the developing world, especially by rising powers. Considering the weight and significance of “the rest of humanity” in such conditions, it is difficult to hope for a rational dialogue on global issues if the discourse, interests, and ambitions of the two poles differ considerably.