bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood-Based ATN Biomarkers of Alzheimer’s Disease: A Meta-Analysis
Authors: Koychev Ivan , Jansen Katrin , Dette Alina , Shi Liu , Holling Heinz
Published: November 2020

Background: The Amyloid Tau Neurodegeneration (ATN) framework was proposed to define the biological state underpinning Alzheimer’s disease (AD). Blood-based biomarkers offer a scalable alternative to the costly and invasive currently available biomarkers. Objective: In this meta-analysis we sought to assess the diagnostic performance of plasma amyloid (Aβ40, Aβ42, Aβ42/40 ratio), tangle (p-tau181), and neurodegeneration (total tau [t-tau], neurofilament light [NfL]) biomarkers. Methods: Electronic databases were screened for studies reporting biomarker concentrations for AD and control cohorts. Biomarker performance was examined by random-effect meta-analyses based on the ratio between biomarker concentrations in patients and controls. Results: 83 studies published between 1996 and 2020 were included in the analyses. Aβ42/40 ratio as well as Aβ42 discriminated AD patients from controls when using novel platforms such as immunomagnetic reduction (IMR). We found significant differences in ptau-181 concentration for studies based on single molecule array (Simoa), but not for studies based on IMR or ELISA. T-tau was significantly different between AD patients and control in IMR and Simoa but not in ELISA-based studies. In contrast, NfL differentiated between groups across platforms. Exosome studies showed strong separation between patients and controls for Aβ42, t-tau, and p-tau181. Conclusion: Currently available assays for sampling plasma ATN biomarkers appear to differentiate between AD patients and controls. Novel assay methodologies have given the field a significant boost for testing these biomarkers, such as IMR for Aβ, Simoa for p-tau181. Enriching samples through extracellular vesicles shows promise but requires further validation.
Magnetoelastic buckling properties of type-II superconducting thin strip subjected to perpendicular magnetic field and parallel distributed uniform mechanical load
Authors: Ma Yuanyuan , Feng Wenjie , Yan Zhen
Published: November 2020

The buckling analyses of type-II superconducting strip under applied perpendicular magnetic field and/or distributed uniform mechanical load are investigated in this paper. Based on the Bean critical state model, the electromagnetic body force is firstly given. Then, based on the classical plate theory and two-point initial value method, the critical buckling states of the superconducting strip with different boundary conditions are analyzed. Numerical results show the effects of both the thickness and boundary conditions of superconducting strip on the corresponding critical buckling loads. The present work should be helpful to the research and application of superconducting thin strips.
Propagation effect of the lightning vertical electric field along the actual ground surface and the revision of errors on ToA-based lightning location systems
Authors: Zhang Yuanyuan , Meng Fanhui , Liu Zhao , Xing Manman , Pang Huaji , Deng Meng
Published: November 2020

A satellite remote imaging data is used to describe the actual ground surface around east of Shandong, based on Barrick’s formulations and Wait’s formulations, and considering the time errors due to elongation of the propagation path caused by mountains, this paper comprehensively analyzes the lightning vertical electric field over the actual ground surface. Furthermore, its effects on time-of-arrival (ToA)-based lighting location systems (LLS) are discussed in details and results show that wave-shape and time-delay of the electromagnetic fields can be significantly affected when they propagate over actual ground surface. The time-delay of the field waveform becomes longer with the increasing roughness, but subtle effect on field peak. After analyzing the actual ground surface around district of Qingdao, this paper reveals the relation between azimuth, observation distance and time-delay. The location error caused by actual ground surface is about several kilometers around the district of Qingdao, and the revised stroke points which are evaluated by the improved actual ground surface propagation model are closer to the actual lightning strike points.
Red raspberry (Rubus idaeus) consumption restores the impaired vasoconstriction and vasorelaxation response in the aorta of the obese Zucker rat, a model of the Metabolic Syndrome
Authors: VandenAkker Natalie E. , Vendrame Stefano , Tsakiroglou Panagiotis , Klimis-Zacas Dorothy
Published: November 2020

Metabolic Syndrome (MetS) increases the risk of cardiovascular disease. Whole red raspberry (WRR) consumption on vascular function was investigated in the obese Zucker rat (OZR), model of MetS. Male OZR and their lean littermates (LZR) were placed on a control (C) or an 8% w/w WRR-enriched diet for 8 weeks. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation were measured in aortic rings in the presence or absence of L-N-monomethyl-arginine (L-NMMA) and mefenamic acid (MFA). Phe-induced vasoconstriction was lower in the OZR-C compared to LZR-C (p < 0.05). The WRR diet partially restored aortic response in the OZR-WRR aorta (p < 0.05) compared to OZR- C. The OZR-WRR group pre-treated with L-NMMA increased compared to OZR-C (p < 0.05). Pre-treatment with L-NMMA, maximal relaxation response was higher in the OZR compared to the LZR (p < 0.05). With L-NMMA, maximal relaxation response in OZR-WRR (p < 0.05) was lower compared to the OZR-C. Prostacyclin I2 concentration was higher in the OZR compared to the LZR (p < 0.05) and was attenuated in the OZR-WRR (p < 0.05). Aortic expression of eNOS and COX-2 were downregulated in the OZR-WRR (p < 0.05). In conclusion, WRR restores the impaired vascular tone of the OZR by enhancing Phe-induced vasoconstriction and attenuating Ach-induced vasorelaxation.
The impact of “omics” technologies for grapevine (Vitis vinifera) research
Authors: Fischer Nicolas , Efferth Thomas
Published: November 2020

BACKGROUND: Grapevine (Vitis vinifera L.) as basis for winemaking is one of the most economically important plants in modern agriculture. As requirements in viticulture are increasing due to changing environments, terroir and pests, classical agriculture techniques reach their limits. OBJECTIVE: We summarize the impact of modern “omics” technologies on modern grapevine breeding and cultivation, as well as for dealing with challenges in viniculture caused by environmental or terroir changes and pests and diseases. In this review, we give an overview on current research on the influence of “omics” technologies on modern viticulture. RESULTS: Considerable advances in bioinformatics and analytical techniques such as next generation sequencing or mass spectrometry fueled new molecular biological studies. Modern “omics” technologies such as “genomics”, “transcriptomics”, “proteomics” and “metabolomics” allow the investigation on a large-scale data basis and the identification of key markers. Holistic understanding of genes, proteins and metabolites in combination with external biotic and abiotic factors improves vine and wine quality. CONCLUSION: The rapid evolution in wine quality was only enabled by the progress of modern biotechnological methods developing enology from a handcraft to science.
Systemic therapy a risk factor for glaucoma development and progression
Authors:   Bryansk Regional Hospital, Bryansk, Russian Federation, Getmanova A.M. , Brezhnev A.Yu. ,   Kursk State Medical University, Kursk, Russian Federation, Kuroyedov A.V. ,   Mandryka Military Clinical Hospital, Moscow, Russian Federation,   Pirogov Russian National Research Medical University, Moscow, Russian Federation, Baranov V.I. ,   Kursk State Medical University, Kursk, Russian Federation, Dvornikov A.S. ,   Pirogov Russian National Research Medical University, Moscow, Russian Federation
Published: November 2020

The prevalence of multimorbidity defined as the presence of two or more chronic diseases increases with ageing. Multimorbidity which is associated with a decline in the quality of life and functional abilities results in the increase in the rate of various physiological disorders and hospital treatment and, therefore, growing healthcare costs. Glaucoma treatment, in particular, in elderly patients, is often accompanied by systemic comorbidities and the intake of multiple systemic drugs. Some systemic agents are known to affect the development of glaucoma (i.e., corticosteroids, some of cardiovascular drugs etc.). However, the data on the effect of systemic medications on the levels of intraocular pressure (IOP) and glaucoma progression remain controversial. Understanding the mechanisms of the effects of systemic medications on IOP levels is of crucial importance. Hence, well-designed prospective randomized controlled studies are required to evaluate these effects. This review paper summarizes published data on the effects of common systemic drugs on IOP levels as well as the risks of the development and progression of primary open-angle glaucoma.Keywords: glaucoma, systemic medications, risk factors, comorbidity, polypharmacy.For citation: Getmanova A.M., Brezhnev A.Yu., Kuroyedov A.V. et al. Systemic therapy a risk factor for glaucoma development and progression. Russian Journal of Clinical Ophthalmology. 2020;20(4):191–196. DOI: 10.32364/2311-7729-2020-20-4-191-196.
Retinoblastoma. Part 2. Treatment strategies for intraocular retinoblastoma
Authors:   N.N. Petrov National Medical Research Center of Oncology, St. Petersburg,  Russian Federation, Ivanova S.V. , Kuleva S.A. ,   N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation, Sadovnikova N.N. ,   St. Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation, Komissarov M.I. ,   St. Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation, Chistyakova M.N. ,   St. Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation, Khokhlova A.V. ,   N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation, Shchegoleva N.A. ,   K.A. Rauchfuss St. Petersburg Children’s City Multidisciplinary Clinical Center of High Medical Technologies, St. Petersburg, Russian Federation
Published: November 2020

Retinoblastoma is one of the most common retinal tumors in young children. Current early diagnostic and treatment strategies focus on the possibility to implement eye-preserving therapies. The 5-year overall survival for children with retinoblastoma is now 100%. First-line eye removal is recommended in extensive intraocular seeding and poor visual prognosis. The volume of adjuvant therapy is based on the histological risk factors for disease progression. This paper discusses the algorithms to determine risk factors and further systemic treatment strategy in several large study groups. Eye and even vision preservation is now possible in at least 65–75% of retinoblastoma patients. The paper also describes in detail the methods of locally administering chemotherapy which are considered eye-preserving treatment options, i.e., selective intra-arterial chemotherapy and intravitreal chemotherapy. Various physical methods of eye-preserving treatment which underwent significant development over the past decade are highlighted. In conclusion, the authors emphasize that retinoblastoma survivors, their siblings and offspring should be carefully monitored.Keywords: children, retinoblastoma, enucleation, polychemotherapy, selective intra-arterial chemotherapy, intravitreal chemotherapy, laser photocoagulation, transpupillary thermotherapy, cryotherapy, brachytherapy, monitoring.For citation: Ivanova S.V., Kuleva S.A., Sadovnikova N.N. et al. Retinoblastoma. Part 2. Treatment strategies for intraocular retinoblastoma. Russian Journal of Clinical Ophthalmology. 2020;20(4):197–203. DOI: 10.32364/2311-7729-2020-20-4-197-203.
The Effect of Solution-Focused Brief Approach on Adolescent Subjective Well-Being: An Experimental Study
Authors: ATEŞ Bünyamin
Published: November 2020

The aim of this study is to examine the effect of solution-focused brief approach based on subjective well-being improvement program on adolescents' subjective well-being levels. The study group con-sisted of 36 adolescents with low subjective well-being pre-test scores. The research is a study based on true experimental design with pre-test which has experimental-control-placebo group, post-test and follow-up test measurements. In this study, Adolescent Subjective Well-Being Scale and Personal In-formation Form were used as data collection tools. Kruskal Wallis H Test for Independent Samples, Mann Whitney U Test for Independent Samples and Wilcoxon Signed Rank Test for Paired Samples were used to analyze data. According to obtained results, it was determined that there was a signifi-cant increase in subjective well-being post-test scores of adolescents in the experimental group compa-red to the pre-test scores, control and placebo groups. It was observed that the increase in the post-test scores of the adolescents in the experimental group was preserved in the follow-up measurements. In the control and placebo groups, no significant difference was found between the pre-test, post-test, and follow-up test scores.
Possibility to use erythrocyte antigens and feather coloration genes to determine resistance to non-plastic diseases
Authors: Livoschenko L. P. , Livoschenko Y. M.
Published: November 2020

Non-plastic diseases are a problem in both medical and veterinary practice. These include lymphoid leukemia (LL) and Marek's disease (CM). It should be noted that HM causes losses to poultry three times higher than LL. CM is a highly contagious viral neoplastic disease of chickens. It is known that the degree of resistance of different breeds and lines of chickens to Marek's disease (CM) and lymphoid leukemia (LL) is not the same. To date, little attention has been paid to the role of erythrocyte antigenic factors in the bird's response to morbidity. There is a relationship between the incidence among vaccinated birds and the natural susceptibility to HM birds of certain breeds and lines. The effect of protective reactions in chickens associated with erythrocyte antigenic factors in poultry selected for resistance to non-plastic diseases is still unclear. The objects of the study were chickens and 11-day-old embryos of poultry from one of the farms of Ukraine. The studies were performed on Rhode Island, Leghorn D4 and P-37 chickens. Standard strains of Rouse's sarcoma virus (HRV) were used in the study. Embryos of 11 days of incubation were infected with Rouse virus on the chorio-allantoic membrane (САМ). The results of the studies proved that the resistance to HRV had a significantly opposite correlation only with the presence of B16 antigen and the absence of X31. In chickens of the P-37 line we noted a probable difference in the number of birds of different genetic groups at loci B18 and E 8. Among birds of this line of genotypes rs and ss no individuals with locus E8 were found, while among chickens with genotype rr rarely found a bird with a locus B18. In hens of line D-4 with genotype rr, the frequency of the A12 locus was set more often than in genotypes rs and ss. As for the frequency of the B33 locus, the opposite pattern was observed. Tumor regression was probably more common in birds with antigenic factor B1 and in the absence of B33. Hypersensitivity to non-plastic diseases of chickens carrying B2, B21, B29, X50 antigens has been established. The bird, more resistant to neoplasms, had an increased number of antigens B3, B18, C26. and research in this direction continues. It is assumed that the plumage color gene (s), if present in homozygous form, is an inhibitor of sensitivity. The experiments used embryos and chickens with different plumage color: red, black, white with a yellow tinge, pure white. Their ratio is approximately 2:1:1 or 3 parts “colored” and 1 part white. It was found that among the “colored” embryos were more stable than sensitive. In fact, the resulting cleavage was close to expected.
The content of total protein and protein fractions in cows during pregnancy and their diagnostic value
Authors: Stravsky Ya. S. , Boltyk N. P. , Sachuk R. M. , Serheyev V. I. , Rushchynska T. M.
Published: November 2020

The aim of the article was to study the content of total protein and protein fractions in the blood of cows during pregnancy and determine their diagnostic value. The studies were performed as follows. Within 7 days after insemination on the principle of analogues selected a group of 100 cows. Pregnancy was diagnosed by rectal examination of cows 60 days after insemination. In experimental animals, starting from the 25th to the 29th day after insemination, blood samples for morphological and biochemical studies were taken monthly before delivery. The total protein content in the serum was determined by the biuret reaction, protein fractions – nephelometric method. Depending on the course of labor and the postpartum period, cows were divided into two groups. The first group included 30 animals with a physiological course of the postpartum period. The second group was formed of 30 cows with subinvolution of the uterus. According to this goal, the dynamics of total protein, albumin, alpha-, beta- and gammaglobulins in the blood of cows with physiological course of pregnancy and prone to the development of subinvolution of the uterus from the first to 9 months of pregnancy. It was found that in clinically healthy cows the onset of pregnancy is characterized by a high (0.89) albumin-globulin ratio, which in the fourth month of pregnancy decreases to 0.78, in the fifth or sixth months increases to 0.85, followed by a decrease to 0.78 before childbirth. In cows prone to uterine subinvolution, a significant difference in albumin content was found in the first month of pregnancy (47.07 ± 1.21 vs. 41.02 ± 1.26 %). In the third to fifth months of pregnancy, there was an increase in the proportion of albumin in the protein to 44.62 ± 0.88 % and a new decrease in the seventh to ninth months to 41.96 ± 0.3 %. In the first month of pregnancy, the albumin-globulin ratio was 0.7, with a tendency to increase in the fifth to sixth months of pregnancy to 0.8, and decrease to 0.72 before calving. Analyzing the dynamics of alpha-globulins in clinically healthy cows, we noted two peaks of decrease in their percentage - in the third month of pregnancy (from 16.02 ± 0.08 to 15.14 ± 0.06 %) and in the fifth month , 96 ± 0.48 %) and a consistent increase in the seventh to ninth months of pregnancy (up to 17.22 ± 0.13 %). And in cows prone to the development of uterine subinvolution, with a slightly higher percentage at the beginning of pregnancy (16.02 ± 0.08 to 17.08 ± 0.05 %), we did not notice significant changes in the percentage of this globulin, except for a significant increase in seventh to ninth month of pregnancy (up to 18.01 ± 0.24 – 19.01 ± 0.32 %). It is proposed to use the albumin-globulin ratio at 6, 7, 8, 9 months of gestation as a prognostic factor in the detection of cows prone to uterine subinvolution.
Perfil de los usuarios del servicio de salud bucal en Comendador Levy Gasparian/RJ
Authors: Melo Renata Patrícia Pereira de , Silva Natália Leal da , Machado Fátima Lúcia Cartaxo , Souza Rafael de
Published: November 2020

La salud de los dientes y la cavidad oral afecta la calidad de vida de las personas, ya que interfiere con la capacidad de comer, comunicarse, estética y prevenir otras enfermedades. El objetivo de esta investigación es identificar el perfil de los usuarios de los servicios de salud bucal en las unidades básicas de salud en el municipio de Comendador Levy Gasparian/RJ. La población del estudio estaba compuesta por todos los usuarios del servicio dental del municipio y el tamaño de la muestra para la recolección utilizaba una muestra no paramétrica del tipo para mayor comodidad. La investigación se llevó a cabo utilizando el enfoque cuantitativo y el análisis de datos utilizando Estadísticas Descriptivas. Para facilitar el análisis y la compresión, se construyeron gráficos con datos univariados y bidata. Los resultados mostraron que las mujeres, los jóvenes, los ancianos, las personas de la raza amarilla y los pacientes con Educación Superior representan grupos que menos utilizan los servicios dentales del municipio y las estrategias que atraen a este tipo de audiencias pueden aumentar el acceso al servicio. Las unidades cercanas al centro urbano del municipio recibieron un mayor número de participantes.
Perfil dos usuários do serviço de saúde bucal em Comendador Levy Gasparian/RJ
Authors: Melo Renata Patrícia Pereira de , Silva Natália Leal da , Machado Fátima Lúcia Cartaxo , Souza Rafael de
Published: November 2020

A saúde dos dentes e da cavidade oral afeta a qualidade de vida das pessoas, pois interfere na capacidade de comer, comunicar-se, na estética e na prevenção de outras doenças. O objetivo da pesquisa é identificar o perfil dos usuários dos serviços de saúde bucal das unidades básicas de saúde do município de Comendador Levy Gasparian/RJ. A população do estudo foi composta por todos os usuários do serviço odontológico do município e o tamanho da amostra para coleta utilizou uma amostragem não paramétrica do tipo por conveniência. A pesquisa foi executada usando a abordagem quantitativa e a análise dos dados por meio da Estatística Descritiva. Para facilitar a análise e compressão foram construídos gráficos com dados univariados e bivariados. Os resultados demonstraram as mulheres, os jovens, os idosos, pessoas da raça amarela e pacientes com Ensino Superior representam grupos que menos usam os serviços odontológicos do município e estratégias que atraiam tais públicos podem aumentar o acesso ao serviço. As unidades próximas ao centro urbano do município receberam um número maior de participantes.
Walka z uchylaniem się od opodatkowania w Republice Czeskiej po wdrożeniu ATAD
Authors: Hrabčák Ladislav , Radvan Michal
Published: November 2020

Temat uchylania się od opodatkowania jest szeroko omawiany w środowisku akademickim. Biorąc pod uwagę kontekst postępującej globalizacji oraz rozwój handlu międzynarodowego, można stwierdzić, że ten problem nabrał charakteru globalnego. W związku z tym różne państwa członkowskie UE podejmują rozmaite działania, by zapobiegać uchylaniu się od opodatkowania bądź całkowicie je wyeliminować. Jedną z inicjatyw podjętych przez Unię Europejską jest Dyrektywa Rady (UE) 2016/1164 z dnia 12 lipca 2016 r. ustanawiająca przepisy mające na celu przeciwdziałanie praktykom unikania opodatkowania, które mają bezpośredni wpływ na funkcjonowanie rynku wewnętrznego. W artykule omówiono kwestię wdrożenia tej dyrektywy w Republice Czeskiej. Dokonano oceny skuteczności walki z uchylaniem się od opodatkowania w Czechach po wdrożeniu ATAD, a jednocześnie zweryfikowano następujące hipotezy: 1) Czechy adekwatnie zharmonizowały swój porządek prawny zgodnie z literą odpowiednich dyrektyw, 2) walka z uchylaniem się od opodatkowania w Republice Czeskiej jest obecnie bardziej efektywna.
浅谈发电机氢气露点上升的原因
Authors: 李 继华
Published: November 2020

某核电厂的发电机采用“水-氢-氢”冷却方式冷却发电机腔室，发电机定子线圈采用水冷却方式，定子铁芯及转子采用氢气进行冷却，以防止发电机内部产生热应力及局部过热。氢气露点超标会危害发电机定子绕组的绝缘强度且能加快转子护环应力腐蚀速度。另外，湿度超标又使得氢气纯度降低，对机组运行有极大危害。文章旨在分析发电机露点上升的原因，并提出一系列的解决措施。
新形势下创新水利工程档案管理的途径
Authors: 马 翠芝
Published: November 2020

所谓的水利工程档案也就是在进行水利工程建设与管理的各个阶段产生的有着一定存储价值的历史记录与资料，有着很多的形式，比如说图表、声像以及文字等。这些资料使国家以及相关单位、部门实施工作的真实的记录，对于进行科学研究，维护社会利益都有重要的作用。社会在快速的发展，水利领域也在不断的进步，水利工程项目管理也迎来了更多的挑战。现代水利工程建设的特点就是项目规模大、数量也比较多，而且参与的单位有很多，建设的周期也比较长，有些工程更是需要多年的时间进行建设，很多年以后才能投入使用，这些情况大大的增加了水利工程档案管理的难度。
10kV配电网无功优化自动化控制系统设计
Authors: 张 黎
Published: November 2020

近年来，我国社会综合国力得到了全面的提升，为各个领域的发展壮大带来了良好的机遇，在这种形势下社会的发展与民众的生活都对电力能源的供应提出了更高的要求。针对配电网实施无功优化能够有效的提升电能的质量、增强电压稳定性、控制线损、降低碳排放，可以说是电力生产企业良好发展的重要基础。配电网的无功补偿其实质就是借助专门电容器所给予的容性无功抵偿电网中的运行的感性无功促进功率参数的不断提升，最终实现无功优化的效果。就现如今实际情况来看，我国针对无功优化所实施的研究已经达到了较为成熟的状态，全球大部分的专业人士针对补偿容量计算、补偿位置确定的研究工作投入了大量的精力。因为配电网测量仪器仪表存在一定的弊端，借助专业的统计学知识，结合配网短路电路符合分布情况，年无功符合曲线以及日符合曲线确定无功补偿容量以及补偿位置的判断是当前最为常用的一种方法。因为配电线路的负荷往往都是与时间和季节的更替存在直接的关联性，所以针对配电网运行的补偿电容器切实的运用静态补偿方法，可以有效的实现无功过补的目的，而在其他时间段进行无功欠补是无法实现无功优化的效果的。针对这个问题，国内一些专业人士指出了统计多个时段无功优化的方法，选择不同的时间段来进行电容的补偿，但是这种方法实践运用具有一定的局限性。
开发利用好水资源保障城镇发展需求
Authors: 李 新甲
Published: November 2020

1996年桐城撤县设市，随着城镇建设规模的扩张，经济建设的步伐加快，也带动了生产、生活用水总量的不断攀升。因此，对水资源的开发利用和管理，已成为市域经济持续、稳定、健康发展的重要因素。文章将通过对桐城市水资源可供总量的分析，研究水资源供需矛盾，探索有限的水资源合理利用途径，从而实现桐城市水资源的优化配置。
电磁流量计的典型故障及其解决方案
Authors: 张 建明 , 安 康
Published: November 2020

从德国化工测量与调节技术标准化委员会，调查统计汇总出的8种电磁流量计典型故障, 简单的分析一下故障的原因和表象，分析出此故障引起的后果，结合自己的经验和推理，找到故障处理的方法。并从实际使用和试验中，提出流量测量的优化方案。特别从气泡产生的原理和造成的后果，强调安装位置的重要性。
Responsibilities of the Marketing Authorisation Holders in Respect of GMP Compliance (Review)
Authors: Meshkovskiy A. P. , Pyatigorskaya N. V. , Aladysheva Z. I. , Beregovykh V. V. , Pyatigorskiy A. M. , Nikolenko N. S. , Marshalova M. M. , Belyaev V. V.
Published: November 2020

Introduction. The article is focused on differences in quality assurance-related obligations and responsibilities between Marketing Authorisation Holders (MAHs) and manufacturing authorisation holder (manufacturers) in pharmaceutical industry. In case of outsourcing and technical agreements there is a need to differentiate responsibilities related to quality assurance between the above mentioned categories.

Text. The guidelines for the pharmaceutical sector of the European Union (EU) provide guidance on the responsibilities of the MAHs in relation to the GMP rules, which are scattered throughout the various chapters of the GMP and its appendices. In addition, certain provisions on this topic are contained in the EU directives. With this in mind the European Medicines Agency (EMA) issued in January 2020 a draft Reflection paper on Good manufacturing practice and Marketing Authorisation Holders. The draft clarifies that while certain activities of an MAH may be delegated to the manufacturer, MAH retains ultimate responsibility for the performance of a medicinal product, its safety, quality and efficacy. The important obligation of MAH in this context is to facilitate GMP compliance by establishing a robust two-way communication system with national competent authorities, manufacturing sites, Qualified Persons (QPs) certifying batches before release, and other interested parties. The MAH ought to communicate to manufacturing personnel, normally through QPs, production processes and related quality control procedures, including subsequent variations, described in registration dossiers.

Conclusion. A general one conclusion: in view of rapid developments in the EU GMP Guide, the Eurasian Economic Union GMP requirements ought to be updated. In respect of specific responsibilities of MAH pertaining to GMP compliance the EMA draft Reflection paper merits attention as a guidance regarding separation of obligations and responsibilities between MAH and personnel of manufacturing sights.
Study of Biologically Active Solid-phase Systems Based on Halogen-substituted Nitrobenzofuroxans by the IR Spectroscopy Method
Authors: Khuziakhmetova A. N. , Gorelova E. G. , Yusupova L. M. , Kurmaeva A. A.
Published: November 2020

Introduction. Biologically active compounds 4,6-dinitro-5,7-dichlorobenzofuroxan (4,6-DNDHBFO) and 5-nitro-4,6-dichlorobenzofuroxan (5-NDHBFO) effectively in-hibit ultra-resistant microorganisms: Staphylococcus aureus, pathogenic fungi – Aspergillius niger, Coniophora cerebella, Candida albicanas and other microor-ganisms. Mixed systems based on 4,6-DNDHBFO and 5-NDHBFO exhibit high potentiated synergistic activity against Aspergillius niger. Currently, there are no full-fledged studies about the mechanism of synergism of 5-NDHBFO and 4,6-DNDHBFO in a solidphase system. The results of the study of solid-phase sys-tems 5-NDHBFO – 4,6-DNDHBFO by IR spectroscopy will make it possible to establish the nature of the interaction between the components of the binary mix-ture.

Aim. Experimental study of the intermolecular interaction of 5-NDHBFO with 4,6-DNDHBFO by the IR spectroscopy method.

Materials and methods. The intermolecular interaction of 5-NDHBFO with 4,6-DNDHBFO at different ratios in a solid-phase system was studied by the IR spectroscopy method.

Results and discussion. Based on the results of the study, the physico-chemical interaction of 5-NDHBPO with 4,6-DNDHBFO in solid-phase systems was revealed. Shifts and changes in the intensities of the characteristic frequencies of functional groups involved in the formation of intermolecular bonds between 5-NDHBPO and 4,6-DNDHBPO were revealed.

Conclusion. The nature of the interaction between 4,6-DNDHBFO and 5-NDHBFO in the solid-phase system was established, leading to the appearance of a synergy effect. The interaction of 5-NDHBFO with 4,6-DNDHBFO in a bi-nary system is due to the formation of an intermolecular hydrogen bond. The in-teraction involves the proton of the 5-NDHBFO molecule, the oxygen of the fu-roxan ring of 4,6-DNDHBFO, as well as the halogen atom of 4,6-DNDHBFO at an equimolar ratio of the components of the solid-phase system.
Development of Radiopharmaceutical Composition for Radionuclide Diagnostics of Malignant Melanoma
Authors: Klementyeva O. E. , Bruskin A. B. , Lunyova K. A. , Bubenshchikov V. B. , Ternovskaya K. E. , Lunev A. S. , Kodina G. E.
Published: November 2020

Introduction. Skin cancers came first in Russia in numbers of oncological diseases. Melanoma, making up only a small part of these cases, leads to the most serious consequences. The nuclear medicine methods application is necessary at the stages of clarifying the diagnosis, searching for remote metastases and the treatment monitoring. The work is devoted to one of the stages of the radiopharmaceutical development for the diagnostics of malignant melanoma and its metastases based on the synthetic analog of α-melanocyte stimulating hormone (SAH) and radionuclide Tc-99m.

Aim. The selection of optimal conditions for the preparation of the SAH ∙ 99mTc complex and the study of the using possibility it as a diagnostic tool in in vitro experiments.

Materials and methods. Experimental work was carried out to optimize the conditions for obtaining the complex compound SAH ∙ 99mTc. The binding and internalization of this compound by B16-F0 melanoma cells has been studied.

Results and discussion. The results of labeling SAH with a 99mTc radionuclide under a wide range of conditions were obtained both by the direct method and using the intermediate complex. The target compound rapidly binds to B16-F0 melanoma cells. The degree of internalization is more than 85 %.

Conclusion. Based on the results of chemical experiments and data from in vitro experiments, optimal conditions for obtaining a complex compound SAH ∙ 99mTc with a radiochemical yield of more than 90 % were found. The mechanism of binding of this compound to malignant melanoma cells has been established.
Effect of Different Extractant Concentrations on the Content of Biologically Active Substances in Motherwort Tincture
Authors: Rogozhnikova E. P. , Mizina P. G. , Mardanly S. G.
Published: November 2020

Introduction. This article considers the ways to optimize the motherwort tincture formulation while reducing the content of ethyl alcohol in the finished product. Qualitative and quantitative tincture test items depending on extraction method used and extractant concentration have been studied.

Aim. To study the possibility of reducing the content of ethyl alcohol in motherwort tincture.

Materials and methods. Comparison of quantitative and qualitative test items of tincture samples prepared by percolation, maceration, fractional maceration, modified fractional maceration is carried out. Quantitative comparative test items: dry residue, ethyl alcohol content, microbiological purity, quantitation, qualitative reactions – the presence of phenolic compounds, flavonoids in the samples (qualitative reactions, HPLC), iridoids (TLC) was used.

Results and discussion. The developed method of modified fractional maceration consists in extracting herb materials with a more concentrated extractant (in the study, 80 %, 60 %, 40 % ethyl alcohol), then the subsequent extraction of herb materials with purified water. Comparison of the presence of different classes of biologically active substances in tinctures obtained by different technological methods and in infusions is carried out.

Conclusion. It has been established that the most rational method is to obtain a tincture by modified fractional maceration method with ethyl alcohol content NLT 35 % in the finished product. The obtained results can be used in pharmaceutical industry for drug production by extractive methods, as well as for studies on technology optimization for obtaining extractive drugs from medicinal herb materials.
Dificuldades apresentadas por pessoas com estoma intestinal durante autocuidado: revisão integrativa
Authors: Reis Bianca Leal , Brandão Euzeli da Silva , Tonole Renato , Moraes Érica Brandão de
Published: November 2020

Objetivo: identificar as dificuldades apresentadas durante o manejo da bolsa por adultos colostomizados/ileostomizados no ambiente domiciliar. Método: Revisão integrativa. Durante a busca, foram utilizados os descritores “ostomy” e “self care”, com o operador boleano “AND”, nas bases eletrônicas: National Library of Medicine (MEDLINE) via PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), The Cochrane Library, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus e Embase, considerando artigos publicados em qualquer idioma, recorte temporal de 2009 a 2020.  Resultados: Foram encontrados 266 estudos, após utilização dos critérios de inclusão, foram selecionados 04 artigos.   Entre as dificuldades destacam-se: retirada das fezes, limpeza da bolsa, recorte da placa, troca da bolsa, sendo esta última apontada em todos os estudos. Discussão: As dificuldades apontadas nos estudos selecionados revelam necessidade de intensificar as avaliações e orientações que devem ser realizadas junto aos estomizados nas fases pré, trans e pós operatórias. Tais ações devem ser preferencialmente desenvolvidas pelo enfermeiro estomaterapeuta. Conclusão: Destaca-se a importância da função educadora do enfermeiro especializado para êxito no autocuidado.
A Multidimensional Method for Pilot Workload Assessment and Diagnosis
Authors: Wang Zhen , Lu Yanyu , Fu Shan
Published: November 2020

INTRODUCTION: Pilot workload assessment plays an important role on flight safety evaluation, interface design, and airworthiness certification. The design of an effective and reliable workload assessment method is a difficult problem in the human factors field.METHOD:
This study proposed to assess pilot workload from four dimensions: cognitive activity, control activity, stress, and flight performance. A set of physiological, behavioral, and flight parameters were recorded and combined hierarchically to achieve overall workload assessment. A simulated flight
experiment consisting of three flight phases (standard instrument departure, autopilot cruise, and nonprecision approach) was conducted to test the effectiveness of the proposed workload assessment method.RESULT: Experimental results determined the changes of each objective measure.
The overall workload index could significantly distinguish the difference in workload caused by changing task difficulty and the result was consistent with the NASA-TLX. The four workload dimensions provided detailed differences about workload: during nonprecision approach there were more
control activities and stress than in other flight phases; during autopilot cruise there were the least control activities and the highest flight performance. The correlation between workload dimensions provided extra diagnostic information: the cognitive and control activities in the approach
phase were more stressful than in the takeoff phase; the correlation between control activity and performance was higher in the approach phase than in the takeoff phase.CONCLUSION: This study proposed an effective pilot workload assessment method which could also provide detailed
and diagnostic information. It could be used as an auxiliary tool for the development and evaluation of pilot-cockpit interaction.Wang Z, Lu Y, Fu S. A multidimensional method for pilot workload assessment and diagnosis. Aerosp Med Hum Perform. 2020; 91(12):932939.
Fatigue Management Health Education Intervention Effects on Flight Attendants
Authors: Hu Chia-Jung , Lee Feng-Ping , Hong Rei-Mei
Published: November 2020

BACKGROUND: This study explored the impact of a fatigue management health education intervention (FMI) on flight attendants fatigue management knowledge, attitudes, behavioral intention, self-efficacy, and fatigue intensity.METHODS: A quasi-experimental pretest-posttest
design was used. The sample included 70 flight attendants of an international airline company in Taiwan. The experimental group (N 34) received an FMI, while the control group (N 36) had no intervention. Fatigue management knowledge, attitude, behavior intention, self-efficacy,
and fatigue intensity were assessed at baseline and 1 wk later. Single-factor analysis of covariance and Jensen Neman methods were used to assess the differences in outcomes between the two groups.RESULTS: Attitude and self-efficacy in the experimental group were significantly improved
after the FMI [standardized mean difference (SMD), 0.96; 1.98]. The intervention also reduced their fatigue intensity (SMD 6.05) and both knowledge and behavioral intention scores were increased in more than 80% of subjects in the experimental group.DISCUSSION: FMI can effectively
improve fatigue management knowledge, attitudes, behavioral intention, and self-efficacy and reduce fatigue intensity in flight attendants.Hu CJ, Lee FP, Hong RM. Fatigue management health education intervention effects on flight attendants. Aerosp Med Hum Perform. 2020; 91(12):911917.
Potential Involvement of the Ocular Glymphatic System in Optic Disc Edema in Astronauts
Authors: Wostyn Peter , De Winne Frank , Stern Claudia , Mader Thomas H. , Gibson Charles Robert , De Deyn Peter Paul
Published: November 2020

INTRODUCTION: A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities, including optic disc edema, optic nerve sheath distention, globe flattening, chorioretinal folds, hyperopic refractive error shifts, and nerve
fiber layer infarcts. A constellation of these neuro-ophthalmic findings has been termed spaceflight-associated neuro-ocular syndrome. An increased understanding of factors contributing to this syndrome is one of the top priorities for ESA and NASA because the length of missions is expected
to increase substantially in the future. As discussed in the present article, the very recent discovery of an ocular glymphatic clearance system can potentially help to unlock mechanisms underlying microgravity-induced optic disc edema. Observations pertaining to the ocular glymphatic pathway
provide supporting evidence for the hypothesis, originally proposed by our group, suggesting that the glymphatic outflow from the eye into the optic nerve may be impeded under prolonged microgravity conditions, leading to optic disc edema.Wostyn P, De Winne F, Stern C, Mader TH, Gibson
CR, De Deyn PP. Potential involvement of the ocular glymphatic system in optic disc edema in astronauts. Aerosp Med Hum Perform. 2020; 91(12):975977.
Cognitive Changes in a Commercial Pilot Secondary to an Olfactory Meningioma
Authors: Hong Michelle , Kreykes Amy J.
Published: November 2020

BACKGROUND: Olfactory meningiomas are typically benign, slow-growing intracranial tumors with subtle presentations that result in delayed diagnosis. To date, only a few published reports describe meningiomas in airmen. None specifically mention olfactory meningiomas or detail
the associated presence of cognitive impairment.CASE REPORT: This was a 55-yr-old commercial pilot with over 20 yr of flight experience who presented for a fitness-for-duty evaluation due to alarming performance at work and neurocognitive concerns. On examination, the patient had
an odd affect and anosmia. Imaging showed a large, frontal, midline intracranial mass consistent with an olfactory meningioma.DISCUSSION: Fitness-for-duty cases are often challenging and even more so when neurocognition is called into question. Symptoms may be subtle and gradual
in onset, making recognition and diagnosis difficult. Dementia, alcohol or substance misuse/abuse, and psychiatric diagnoses are often the first conditions considered when evaluating new cognitive impairment in a pilot. This case highlights the importance of keeping a broad differential, including
intracranial masses, conducting a thorough neurological examination, and the judicious use of brain imaging.Hong M, Kreykes AJ. Cognitive changes in a commercial pilot secondary to an olfactory meningioma. Aerosp Med Hum Perform. 2020; 91(12):966969.
REPRESENTATION OF FEMININITY IN MODERN UKRAINIAN NOVELS
Authors: Bashkyrova Olha
Published: November 2020

The paper deals with the main tendencies of the artistic reception of women images in modern Ukrainian novels. The principles of modeling femininity in literature have been considered from the positions of the gender studies, postcolonial and psychoanalytic theory. It is proved that the peculiarities of this modeling are determined by stylistic and genre tendencies of the Ukrainian literature. The interpretation of feminine images typical for the national literary tradition (mother, family-keeper, demonic woman) has been demonstrated in numerous examples. These images correlate with the fundamental artistic principles of the turning points in history (actualization of the archetypes, attention to the irrational manifestations of human psychics). They display the ‘masculine’ literary tradition (representation of a woman as an external object), but at the same time demonstrate a new accent in the understanding of the gender roles (woman as a mentor of a man). The alternative types of the feminine identity represented by feminist and culturological women’s writing have been explored as well. Special attention has been paid to procreation as the main woman’s ability, which forms different models of feminine mentality – from the essentialist mother-type to the image of a child-free woman. The modeling of a feminine artistic worldview becomes an actual strategy in overcoming the postcolonial trauma. It is explained by the peculiarities of the postcolonial literatures, which fulfill their historical reflections in the local family stories. In this context, feminine conscience gets the status of a memory-keeper and shows the ability to trace the development of national history in its everyday dimensions. Based on the large-scale generalization of the last decades’ artistic practice, the researcher determines the main worldview intentions of modern novels, in particular the tendency to achieve gender parity, the full-fledged dialogue of men and women as the equal subjects of culture creation.
Отношение к нищим государства и общества в советское время (ATTITUDE TO THE POVERTY OF THE STATE AND SOCIETY IN SOVIET TIME)
Authors: Шляхтина (Shlyakhtina) Наталья Валерьевна (Natalia Valerievna)
Published: November 2020

Автор рассматривает социальную категорию нищих в религиозном контексте, а также в свете конкретной русской этнической традиции. В последнем случае нищие были близки группе «странников», богомольцев, которые посвятили свою жизнь паломничеству по святым местам. Между тем уже в начале XX в. немалое число нищих были просто бедняками, не имеющими дома и заработка. В советское время с нищенством начинают целенаправленно бороться, как с социально вредным явлением. Но при этом советская власть своими масштабными проектами – индустриализацией и особенно коллективизацией, борьбой с враждебными классами, порождала миллионы нищих. Она боролась с ними, как с врагами народа. Еще одна большая волна нищих появилась после Великой Отечественной войны, но и эти нищие не нашли должного сочувствия у власти. В целом, отношение к нищим в советское время можно охарактеризовать как репрессивное, вне традиции, вне религиозных норм, что служит обличением власти.
The author considers the social category of the poor in a religious context, as well as in the light of a specific Russian ethnic tradition. In the latter case, the poor were close to the category of “wanderers,” pilgrims who dedicated their lives to pilgrimage to holy places. Meanwhile, at the beginning of the XX century. a considerable number of beggars were simply poor people who did not have a home or income. In Soviet times, the authorities began to struggle with poverty in a deliberate way, as with a socially harmful phenomenon. But at the same time, the Soviet government with its large-scale projects - industrialization and especially collectivization, the struggle against hostile classes - generated millions of beggars. It fought with them, as with the enemies of the people. Another big wave of beggars appeared after World War II, but these beggars did not meet the proper sympathy of the government. In general, the attitude towards the poor in Soviet times can be described as repressive, outside of tradition, outside of religious norms, which serves as a denunciation of power.
Deep Learning on High-Throughput Transcriptomics to Predict Drug-Induced Liver Injury
Authors: Li Ting , Tong Weida , Roberts Ruth , Liu Zhichao , Thakkar Shraddha
Published: November 2020

Drug-induced liver injury (DILI) is one of the most cited reasons for the high drug attrition rate and drug withdrawal from the market. The accumulated large amount of high throughput transcriptomic profiles and advances in deep learning provide an unprecedented opportunity to improve the suboptimal performance of DILI prediction. In this study, we developed an eight-layer Deep Neural Network (DNN) model for DILI prediction using transcriptomic profiles of human cell lines (LINCS L1000 dataset) with the current largest binary DILI annotation data [i.e., DILI severity and toxicity (DILIst)]. The developed models were evaluated by Monte Carlo cross-validation (MCCV), permutation test, and an independent validation (IV) set. The developed DNN model achieved the area under the receiver operating characteristic curve (AUC) of 0.802 and 0.798, and balanced accuracy of 0.741 and 0.721 for training and an IV set, respectively, outperforming the conventional machine learning algorithms, including K-nearest neighbors (KNN), Support Vector Machine (SVM), and Random Forest (RF). Moreover, the developed DNN model provided a more balanced sensitivity of 0.839 and specificity of 0.603. Besides, we found the developed DNN model had a superior predictive performance for oncology drugs. Also, the functional and network analysis of genes driving the predictions revealed their relevance to the underlying mechanisms of DILI. The proposed DNN model could be a promising tool for early detection of DILI potential in the pre-clinical setting.
Optical Tweezers Exploring Neuroscience
Authors: Lenton Isaac C. D. , Scott Ethan K. , Rubinsztein-Dunlop Halina , Favre-Bulle Itia A.
Published: November 2020

Over the past decade, optical tweezers (OT) have been increasingly used in neuroscience for studies of molecules and neuronal dynamics, as well as for the study of model organisms as a whole. Compared to other areas of biology, it has taken much longer for OT to become an established tool in neuroscience. This is, in part, due to the complexity of the brain and the inherent difficulties in trapping individual molecules or manipulating cells located deep within biological tissue. Recent advances in OT, as well as parallel developments in imaging and adaptive optics, have significantly extended the capabilities of OT. In this review, we describe how OT became an established tool in neuroscience and we elaborate on possible future directions for the field. Rather than covering all applications of OT to neurons or related proteins and molecules, we focus our discussions on studies that provide crucial information to neuroscience, such as neuron dynamics, growth, and communication, as these studies have revealed meaningful information and provide direction for the field into the future.