bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSESSMENT OF THE RIVERS’ MAXIMUM RUNOFF IN THE COASTAL TERRITORY OF PRIMORSKY REGION IN THE VIEW OF FLOODS HAZARD
Authors:   Pacific Geographical Institute FEB RAS, Gorbatenko L.
Published: July 2021

The temporal patterns and spatial features of the maximum runoff in the coastal territory of Primorsky Region in view of the floods hazard for the period from the beginning of observations to 2018, are considered. The indicator of exceeding the hazardous water level, determined by the territorial divisions of the Hydrometeorology Department of the Russian Federation, used as a criterion for identifying the most flood-prone areas. Except for the Kazachka river, all the considered watercourses are characterized by the predominance of supreme value of runoff in summer-autumn season. There is no dependence between the amplitudes of intra-annual average daily, inter-annual fluctuations of the maximum water levels and the morphometric characteristics of catchments for the rivers on the coast of Primorsky Region. But generally it is obvious that amplitudes grow with increasing a river size. The temporal dynamics of the absolute values of the maximum runoff, its anomalies and long-term water cycles of the rivers in the coastal zone of Primorsky Region are not synchronous, except for a group of neighboring rivers on the east coast, as well as the Razdolnaya river in three gaging stations. The rivers of the coast region are characterized by a complex spatial differentiation of hazardous phenomena associated with high water levels. Their recurrence differs on closely located rivers. An increase in the frequency of floods in recent years has been observed only on certain rivers as the Razdolnaya river at Novogeorgievka settlement and the Rakovka river at Opyitny settlement. The territories of the catchments of the Razdolnaya, Borisovka and Tsukanovka rivers are exposed to the greatest threats of exceeding the hazardous water levels
CONCEPTUALIZATION OF SOCIAL AND RELIGIOUS SECURITY OF THE RUSSIAN FEDERATION IN POLITICAL STUDIES
Authors:   Transbaikal State University, Romanova N. , Kononov S. ,   Far Eastern Higher Combined Arms Command School named after Marshal of the Soviet Union K.K. Rokossovsky, Shevchenko M. ,   Transbaikal State University, Shevchenko Yu. ,   Transbaikal State University
Published: July 2021

The article is devoted to an attempt to analyze and compare the concepts of social security of the regions of the Russian Federation, including the concept of “unity” and the concept of “regionality”. The authors of the article seek to resolve the contradiction between these concepts using the simulation of social security of the Russian Federation on the basis of the complementary principle and synthesis of the concepts of “unity” and “regionality”. The result of the article is the a dynamic model formation of social security of Russian regions, under which the process of continuous designing of regulatory and value ideas, instilled in the regional community, through the impact of its society surrounding it, as well as social agreements aimed at achieving conjunction within the social framework of Russian regions. The second result is to determine the social security of Russian regions, as a process in which, depending on the situational influence of objective and subjective factors, or centrifugal or regional trends are dominated.The third result is the statement of the fact that, for a long time, despite the significant difference in the civilization nature of the regions, the Russian social framework maintains integrity, which indicates the predominance of unifying trends and the absence of the desire among Russian regions to the exit from the All-Russian social space
APPROACHES TO THE VALUATION AND REVALUATION OF FIXED ASSETS ACCORDING TO RUSSIAN AND INTERNATIONAL STANDARDS
Authors:   Transbaikal State University, Gonin V. , Panchenko E. ,   Transbaikal State University, Kibireva E. ,   Transbaikal State University, Nomokonova O. ,   Transbaikal State University
Published: July 2021

Questions of valuation and revaluation of fixed assets in a market environment inevitably arise. This is due to the increased role of assessing the effectiveness of asset management. The harmonization of national and international accounting standards allows us to consider the assessment and revaluation processes, both from the point of view of the accounting system and from the point of view of the financial consequences of the procedures performed. The purpose of the study is to study the historical background and systematize approaches to the assessment and revaluation of fixed assets according to Russian and international standards. To achieve this goal, the following tasks are set: to study the methods and historical aspect of revaluation; to study the conceptual framework of revaluation and impairment; to systematize the general provisions of the methodology for assessing the value of fixed assets during revaluation and impairment. The object of the study is fixed assets. In the course of the study, the history of revaluation of the cost of fixed assets is considered, the conceptual apparatus of the cost of fixed assets is analyzed in relation to the procedures for revaluation and impairment testing, the methodology of revaluation and impairment is considered. The paper concludes that it is necessary to introduce into the practice of accounting and management procedures for assessing the value of fixed assets and revaluing them, which will allow us to obtain reliable information when analyzing the impact of cost changes on the indicators used in determining the effectiveness of activities
Small-Scale Business Leadership in Ethiopia: An Assessment of Financial Bureau Opportunities in Yayu Woreda
Authors: Narayan Singh Satya
Published: July 2021

The present research paper highlights small-scale business leadership in Ethiopia to assess the financial bureau in Yayu Woreda of Ilu Abba Bora Zone of Oromia regional state of Ethiopia. The other allied purpose relates to evaluating the budgetary performance of the Yayo Woreda finance office in the Ilu Abba Bora Zone. The sampling technique is based on simple random sampling, and scientifically there were 100 samples of respondents taken from approximately one thousand and three hundred and seventy-three employees in the woreda. The representative samples were included one head office person, the council head of the budget and finance committee, plus the committee members from the Audit Office, Auditor general, deputy auditor general, Audit manager, and the audit team of consolidated financial statements. Additionally, three employees were also included from each sector, such as planners, accountants, and internal auditors, to control appropriate utilization of limited resources and auditing performance for the allocated budget at the woreda finance office. The descriptive survey design was employed in this study, and appropriate data collection methods were used through questionnaires and interviews. However, the secondary data is extracted from the final report and oversight of the written books and brochures. The data were analyzed and interpreted while using an appropriate methodology of concurrent concern. The study established that the budget implementation and its performance have a negative relationship to some extent. It is recommended that the woreda must have to enhance its manpower, particularly in the budget process, to improve budgetary performance, particularly in the aspect of small-scale business leadership.
The Impact of Regulations on Small Firm Characteristics
Authors: Kaya Halil D.
Published: July 2021

Regulations are shown to have a significant impact on entrepreneurial activity, especially on startups by smaller firms. Higher compliance costs are shown to deter small firms entering a new industry. In this study, using state-level regulation data in the U.S., we examine whether different types of regulations (including “health and safety regulations”, “employment regulations”, “tax code”, “licensing regulations”, “environmental regulations”, and “zoning regulations”) in each state deter smaller firms to do business in that state. We also examine whether each type of regulation deters firms to do business in certain industries or to operate in more or fewer states. Besides size, operational area, and industry, we also examine whether each type of regulation deters younger firms to do business in each state. Our results show that “health and safety regulations”, “employment regulations”, “tax code”, “licensing regulations”, and “environmental regulations” in a state affect firm size and industry, but do not affect operational area and firm age. In the states with high scores in these areas, there are fewer single-employee firms but more 2-20 employee firms when compared to the other states. Also, in the states with a high score in “environmental regulations”, we find fewer firms with 51 to 100 employees when compared to the other states. On the other hand, “zoning regulations” affect firm age and industry, but not operational area and firm size. In the states with high scores in “zoning regulations”, we find fewer firms that are established less than a year ago. Finally, in the states with high scores in regulations, generally, we find that more firms are in the “Business” industry and fewer firms are in the “Writing” industry. Overall, we show how each type of regulation deter certain types of firms operating in each state. This is important because if a state wants to attract certain types of firms (i.e., younger, or older firms, larger or smaller firms, or firms in certain industries), the officials in that state need to improve the corresponding regulations first.
Development of E-banking in Bangladesh: A Survey Study
Authors: Alam Md. Jahangir , Jesmin Farhana , Faruk Mohammad , Md. Nur-Al-Ahad
Published: July 2021

E-Banking is being grownup speedily in Bangladesh. The recent exceptional advancement in data technology and smartphones’ convenience has brought important changes in banks’ services in Bangladesh. Notably, banks are presently competitory to supply complete banking services via smartphones or through on-line platforms. Such digital banking services cut back long queues within the bank’s counter to withdraw cash/ to deposit cash to their accounts. However, very little is thought concerning security and customers’ feedback concerning such services, that is investigated during this paper. a lot of significantly, this paper tried to look at E-banking’s current standing, potential future opportunities, and challenges, notably in Bangladesh. To serve our functions, we have a tendency to interviewed one hundred fifty folks directly connected with such digital banking services, as well as bankers, users, and alternative people. Our study finds many barriers in E-banking service channels, as well as technological breakdown, infrastructural limitations, temporal arrangement problems, legal risks and name risks, etc. Our analysis conjointly finds that customers are not equally pleased with digital services, and that they demanded to scale back the extent of uncertainty related to digital banking services.
The Stability of The Financial System: a Comparison of Developed and Less Developed Countries
Authors: Kaya Halil D.
Published: July 2021

In this study, we examine the relationship between the development level of a country and stability of its financial system. We look at seven measures of stability. These are Bank z-score, Bank non-performing loans to gross loans, Bank capital to total assets, Bank credit to bank deposits, Regulatory capital to risk-weighted assets, Liquid assets to deposits and short term funding, and Provisions to non-performing loans. First, we compare developed and less developed countries’ stability measures. Do developed countries have more stable financial systems than less developed countries or is the opposite true? When we compare high-income countries to low- and middle-income countries, we find that low- and middle-income countries have better “stability” values in five measures. For the other two measures, we do not find any significant difference between the two groups. Then, we look at how high-income OECD countries differ from high-income non-OECD countries in terms of their financial system’s stability. When we compare high-income OECD-member countries to high-income Non-OECD-member countries, we find that high-income Non-OECD-member countries have better “stability” values in four measures. For the other three measures, we do not find any significant difference between the two groups. We conclude that developed countries, especially OECD members, are under greater risk when facing an economic/financial crisis.
Global Competitiveness of the Economy and Intellectual Capital Index: Case of EU Countries and Ukraine
Authors: Shkola Viktoriia Y. , Troyan Maria Y. , Domashenko Maryna D. , Vavilichev Mykola D.
Published: July 2021

This research aims to analyze indicators of competitiveness of Ukraine economy in contrast to consistent indicators of the EU counties’ economies in context of forward-looking perspective on integration Ukraine into the EU, as well as examine the national index of intellectual capital considering each of its dimensions (human capital, market capital, process capital and renewal capital) within three pillars: Education, R&D, New Business, and explore the potential for growth of Ukraine’s economic competitiveness global given its innovation aspects. The study uses a mixed approach, including factorial analysis and descriptive statistics, using a sample of 27 the EU economies and Ukraine’s economy. The study shows Ukraine has significant innovative potential, high level of higher education and training. It is a crucial competitive advantage, providing successful economic development and accelerating integration Ukraine into the EU. Only through developing of advanced technologies and implementing them in all sphere, stable pace of economic growth and welfare of the nation can be achieved in the conditions of globalization. The restraining factors are corruption, political instability, inflation, and ineffective state policy. In order to be more innovative and, hence, competitive, Ukraine needs to focus more on the structural and comprehensive reforms of institutional environment, concerning the ethical behavior of companies, the protection of property and intellectual property rights, transparency in the adoption of state decisions, the independence of the judiciary, the efficiency of the use of the state budget, public trust in politicians etc. Future studies may explore the opportunities for enhancing innovation performance based on the management of intellectual capital in more detail, using larger sample sizes.
Periodic and non-periodic stacking in molybdenite (MoS2) revealed by STEM
Authors: Yang Yiping , He Hongping , Xian Haiyang , Xi Jiaxin , Wu Xiao , Chen Aiqing , Zhu Jianxi , Xu Huifang
Published: July 2021

Polytypism is a typical feature of layered minerals with differences only in stacking sequences. There is no obvious “phase” boundary among different polytypes, although the frequency of polytypes occurrence is related to its crystallization environment. In the past decades, X-ray studies of molybdenite specimens from a variety of geological environments have revealed that most molybdenite crystals contain both 2H1 (hexagonal) and 3R (rhombohedral) polytypes. However, the stacking sequences of these molybdenite polytypic intergrowths and their formation mechanism are not well understood. Here, we report stacking faults and domains of long-period polytypes identified by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) in a molybdenite sample from a carbonatite vein in the Huanglongpu Mo-Pb ore deposit in Qinling orogenic belt, Northern China. Several layers of disordered domains intergrown with ordered 2H1 domain were recognized based on the contrast in HAADF image with one-dimensional lattice fringes. In addition, a 30-layer long-period polytype was unambiguously identified by a STEM image. The stacking sequences of 4-, 6-, and 8-layer disordered domains and the 30-layer long-period polytype were further examined using HRSTEM images at the atomic resolution. A 2H3 polytype with three repetitions was also discovered in the sample. We propose that non-equilibrium conditions related to the fluctuation of fluid composition during crystallization resulted in the oscillation of 2H1 and 3R polytypes and intergrowth of various disordered domains. More broadly, our study demonstrates that HAADF-STEM imaging method may be applicable for studying other disordered layered crystals and twinned minerals.
PENGARUH KINERJA LINGKUNGAN, PENGUNGKAPAN LINGKUNGAN, DAN PROFITABILITAS TERHADAP TINGKAT PENGEMBALIAN SAHAM: STUDI EMPIRIS DI BURSA EFEK INDONESIA
Authors: Wiweko Hidayah
Published: July 2021

ABSTRAK Tujuan dilakukan penelitian ini adalah untuk mengetahui pengaruh kinerja lingkungan, pengungkapan lingkungan dan profitabilitas terhadap return saham. Variabel independen dalam penelitian ini adalah kinerja lingkungan, pengungkapan lingkungan dan profitabilitas. Variabel dependen dalam penelitian ini adalah return saham. Populasi dalam penelitian ini adalah sektor manufaktur yang memperoleh peringkat PROPER dan terdaftar di Bursa Efek Indonesia (BEI) tahun 2015-2018 sebanyak 42 perusahaan. Sampel dalam penelitian ini diambil dengan menggunakan metode purposive sampling. Analisis data menggunakan statistik deskriptif, uji asumsi klasik, analisis regresi berganda dan pengujian hipotesis. Hasil penelitian ini menunjukkan bahwa variabel kinerja lingkungan, pengungkapan lingkungan dan profitabilitas berpengaruh signifikan terhadap return saham.Kata Kunci: return saham, kinerja lingkungan, pengungkapan lingkungan, profitabilitas ABSTRACT The purpose of this research is to determine the effect of environmental performance, environmental disclosure and profitability on stock return. The independent variables in this study are environmental performance, environmental disclosure, profitability. The dependent variable in this study is stock return. The population in this study is the manufacturing sector which received a PROPER rating and was listed on the Indonesia Stock Exchange (IDX) in 2015-2018 as many as 42 companies. The sample in this study was taken using a purposive sampling method. Data analysis uses descriptive statistics, classic assumption tests, multiple regression analysis and hypothesis testing. The results of this study indicate that environmental performance, environmental disclosure and profitability variables have a significant effect on stock returns.Keywords:   stock return, environmental performance, environmental disclosure, profitability
VERGİ DAİRESİ ÖZELİNDE TİCARET SİCİLİ KAYITLARINDA “ÜÇÜNCÜ KİŞİ”
Authors: KARAAHMETOĞLU İsmail Özgün
Published: July 2021

Ticaret sicili, özünde ticari işletmeye dair hususların kaydı ile varlıkları hakkında aleniyetin sağlanması suretiyle kamu nezdinde bilhassa üçüncü kişilerin bilgi sahibi olmasına yarayan ve ispatına hizmet eden resmi sicildir. Ticaret sicili kayıtları tescile tabi tutulan hususun hukuken varlık kazanıp kazanmaması bakımından kurucu ya da açıklayıcı; üçüncü kişilerin iyi niyetli sayılıp sayılmaması açısından ise olumlu ya da olumsuz etki gösterebilir. Hatta görüşüne güven ilkesi çerçevesinde tescil kaydı ile ilan edilen durum arasında farklılık bulunması hâlinde, tescil edilmiş olan gerçek durumu bildikleri ispat edilmediği sürece, üçüncü kişilerin ilan edilen duruma güvenleri korunmaktadır. Bunların haricinde tescile tabi hususun hem incelenmesinde başvurulacak kriterlerin belirlenmesinde hem de ticaret sicili müdürlüğüne belirli şartlarda üçüncü kişilerin başvurması neticesinde ortaya çıkan durumlar açısından ticaret sicili kaydındaki üçüncü kişiler özellik arz etmektedir. Bu bağlamda ticaret sicili kayıtlarının üçüncü kişilere doğrudan ya da dolayısıyla etkilerinin doktrinde geniş çerçeveli araştırmalara konu olduğuna tanık olmaktayız. Oysaki ticaret sicilinin etkilerinin muhatabı olan/olacak üçüncü kişinin kim olduğuna dair herhangi bir yasal düzenleme yapılmamıştır. Bu yüzden bu konudaki hukuki boşluğun ticaret sicili kayıtlarında üçüncü kişinin belirlenmesine dair birtakım kıstaslar ortaya konularak doldurulması gerekmektedir. Bunun için vergi dairesi özelinde ticaret sicili kayıtlarında ‘üçüncü kişi’ kavramı irdelenecektir.
Mastitis periductal y absceso subareolar de la mama
Authors: Bonilla Sepulveda Óscar Alejandro
Published: July 2021

La mastitis se define como la inflamación del seno asociada o no a infección. La mastitis lactacional es la enfermedad inflamatoria de la mama más común; sin embargo, no deben olvidarse los procesos inflamatorios no asociados a la lactancia, clínicamente similares y a veces indistinguibles, pero con una evolución crónica y recurrente, con formación de absceso subareolar. Con frecuencia se encuentra infección bacteriana polimicrobiana, fuertemente asociada al tabaquismo. El retraso en el diagnóstico puede conllevar daño en la función o la estructura mamaria y secuelas permanentes. La similitud clínica con el cáncer localmente avanzado y con el carcinoma inflamatorio de la mama hace necesario que deban ser excluidos. El tratamiento definitivo requiere drenaje y resección quirúrgica de la fistula para reducir el riesgo de recurrencia. En esta revisión se exponen los aspectos más relevantes y actualizados sobre la enfermedad con el objetivo de proporcionar elementos para su abordaje diagnóstico y terapéutico.
Water, sanitation, and hygiene (WASH) in healthcare facilities of 14 low- and middle-income countries: to what extent is WASH implemented and what are the ‘drivers’ of improvement in their service levels?
Authors: Kmentt Laura , Cronk Ryan , Tidwell James Benjamin , Rogers Elliott
Published: July 2021

Prevention and control of healthcare-associated infections through the provision of water, sanitation, and hygiene (WASH) in healthcare facilities (HCF) is inadequate in low- and middle-income countries (LMICs), resulting in high patient morbidity and mortality, additional costs, and increased risk of antibiotic resistance. There is little evidence describing factors leading to improved WASH conditions in LMICs. We aim to identify the extent to which WASH is implemented in HCFs in LMICs and understand the ‘drivers’ of improvement in their service levels. WASH service levels in 14 LMICs were descriptively analysed, and potential drivers of service-level differences were explored using univariable and multivariable mixed-model logistic regression analyses. Descriptive analysis showed a lack of adequate water quality, sanitation, hand, and environmental hygiene, and waste disposal. We found that the presence of infection prevention and control protocols (IPCPs), having an IPC/WASH focal person at the facility, and conducting WASH training for staff were associated with higher levels of WASH services. This study demonstrates a lack of basic WASH services in HCF in LMICs. We show that there are potential interventions, such as implementing IPCPs, identifying WASH leaders in HCF, and conducting training that may lead to service improvements.
Hydrological probabilistic forecasting based on deep learning and Bayesian optimization algorithm
Authors: Bai Haijun , Li Guanjun , Liu Changming , Li Bin , Zhang Zhendong , Qin Hui
Published: July 2021

Obtaining accurate runoff prediction results and quantifying the uncertainty of the forecasting are critical to the planning and management of water resources. However, the strong randomness of runoff makes it difficult to predict. In this study, a hybrid model based on XGBoost (XGB) and Gaussian process regression (GPR) with Bayesian optimization algorithm (BOA) is proposed for runoff probabilistic forecasting. XGB is first used to obtain point prediction results, which can guarantee the accuracy of forecast. Then, GPR is constructed to obtain runoff probability prediction results. To make the model show better performance, the hyper-parameters of the model are optimized by BOA. Finally, the proposed hybrid model XGB-GPR-BOA is applied to four runoff prediction cases in the Yangtze River Basin, China and compared with eight state-of-the-art runoff prediction methods from three aspects: point prediction accuracy, interval prediction suitability and probability prediction comprehensive performance. The experimental results show that the proposed model can obtain high-precision point prediction, appropriate prediction interval and reliable probabilistic prediction results on the runoff prediction problems.
CuO as efficient photo catalyst for photocatalytic decoloration of wastewater containing Azo dyes
Authors: Ramesh Martha
Published: July 2021

Cupric oxide nanoparticles (CuO NPs) were prepared via a chemical precipitation method using the precursor of copper (II) nitrate trihydrate. X-ray diffraction analysis confirms that the CuO NPs were a monoclinic crystal structure. The energy band gap of CuO NPs was found to be about 1.76 eV. The obtained CuO NPs were used as a photo catalyst to decolorize various dyes, such as methylene blue (MB), acid yellow 23 (AY 23) and reactive black 5 (RB 5), with a low concentration in the presence of visible light. The results show that the highest decolorization achieved was 67.8% and 66.3% for RB-5 dye and AY-23 dye, while 43.5% for MB dye from aqueous solution at 5 h illumination. The obtained CuO NPs were used as a photo catalyst to decolorize various dyes, RB-5, AY-23 and MB dye obeys pseudo first order kinetics with values of −0.112, −0.174 and −0.201 h−1, respectively.
METAPHORICAL MODELS WITH THE HUMAN SUBJECTIVE ZONE IN THE POETRY OF A. MARIENGOFF AND S. YESENIN
Authors: KUPCHIK Elena V.
Published: July 2021

This article analyzes the metaphorical models with the subject “human” and “part of the body” in the poetry of A. Mariengof and S. Yesenin. The object of the research is comparative paths in which metaphorical models are realized. Based on the consideration of metaphors and comparisons, metaphorical models are isolated and characterized, reflecting the connection between two conceptual areas. The comparison of metaphorical models in the poetry of A. Mariengof and S. Yesenin is carried out, the features of similarity and difference are highlighted. It was revealed that both poets pay considerable attention to a person as a subject of figurative comparisons. The model “human — being” is represented by comparisons with different representatives of the fauna, the semantics of images of which in poetic systems do not coincide. The most important for the authors figurative correspondences of a person, the most significant for each poet, subjects and objects of comparison are determined. The model “human — plant” occupies an important place in the figurative world of S. Yesenin, A. Mariengof mainly uses comparisons with objects of inanimate nature. Models with the subject “part of the body” are characterized by a variety of comparison subjects, especially in the poetry of A. Mariengof. The somatic vocabulary which is used by the authors is considered. Cases of combination in the realizations of metaphorical models of high and low are noted. Figurative correspondences through which poets characterize themselves are identified.
TITLE AS A FIGURATIVE AND SYMBOLIC CENTER OF BORIS PASTERNAK’S POETRY COLLECTION “OVER THE BARRIERS”
Authors: RAZUMKOVA Nadezhda V.
Published: July 2021

This article, based on my report at the international conference dedicated to the 130th anniversary of B. L. Pasternak (China, Hangzhou, Zhejiang University, 8-10 November 2020), is aimed at studying the nature of the relationship between the title of the collection and the texts of the poems included in it. The relevance of the work is determined by the anthropocentric orientation of modern linguistics, which focuses on the linguistic personality and the world picture of the creative individual. The theoretical section discusses the methodological foundations of the research, reveals conceptual categories, highlights a complex of factors that affect the perception and understanding of Pasternak’s lyrics. The practical part of this article contains the results of a contextual analysis of the lyric works titles. The symbolic meanings of the title-trope are presented, the associative features of which correlate with the idea of overcoming limitations in the broad sense of the word. In poetic texts, the referent of the key sign is manifested by lexemes: body (intimate space), courtyard (home space), sleep (border space), street and canals (segments of urban space), railway (technogenic space), weather conditions (obstacles in the perception of the environment), ice (natural shackles that are temporary) etc. The conclusions are formulated in the following judgments: 1) the title, which is considered to be global and local “ad hoc” connectivity, makes the entire collection complete, strengthens its internal unity due to the motive of overcoming space-time boundaries; 2) the formula “over the barriers” symbolizes the boundaries both in personal and biographical terms and in the philosophical and psychological sense, emphasizes the complexity and significance of the poet’s creative quests.
Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies
Authors: Sahebnasagh Adeleh , Saghafi Fatemeh , Negintaji Sina , Hu Tingyan , Shabani-Borujeni Mojtaba , Safdari Mohammadreza , Ghaleno Hassan Rezai , Miao Lingchao , Qi Yaping , Wang Mingfu , Liao Pan , Sureda Antoni , Simal-Gándara Jesus , Nabavi Seyed Mohammad , Xiao Jianbo
Published: July 2021

:

In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, and EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low/moderate levels may favor tumorigenesis, while higher levels would exert antitumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this “doubleedged sword” in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.
Insights into the Mechanism of the Therapeutic Potential of Herbal
Monoamine Oxidase Inhibitors in Neurological Diseases
Authors: Mannan Ashi , Singh Thakur Gurjeet , Singh Varinder , Garg Nikhil , Kaur Amarjot , Singh Manjinder
Published: July 2021

:

Monoamine oxidase (MAO) is an enzyme that catalyzes the deamination of
monoamines and other proteins. MAO’s hyperactivation results in the massive generation of reactive
oxygen species, which leads to a variety of neurological diseases such as Alzheimer's disease,
Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and depression-like disorders.
Although synthetic MAO inhibitors are clinically available, they are associated with side effects
such as hepatotoxicity, cheese reaction, hypertensive crisis, and so on, necessitating the investigation
of alternative MAO inhibitors from a natural source with a safe profile. Herbal medications
have a significant impact on the prevention of many diseases; additionally, they have fewer
side effects and serve as a precursor for drug development. This review discusses the potential of
herbal MAO inhibitors as well as their associated mechanism of action, with an aim to foster future
research on herbal MAO inhibitors as a potential treatment for neurological diseases.
Lipidomics as Tools for Finding Biomarkers of Intestinal Pathology: From
Irritable Bowel Syndrome to Colorectal Cancer
Authors: Moreno Lorena Ortega , Sánchez Pilar Navarro , Abalo Raquel
Published: July 2021

:

Lipidomics is an emerging and promising omic that analyzes different lipid molecules in
a biological sample. It is considered as a branch of metabolomics, which is defined as the comprehensive
analysis of metabolites in a biological specimen. Nonetheless, in recent years lipidomics is
being considered a distinct discipline in the biomedicine field. Lipids play important roles in many
biological pathways and could work as biomarkers of disease or as therapeutic targets for treatment
diseases. The major lipidomics strategies are shotgun lipidomics and liquid chromatography coupled
with mass spectrometry. Gastrointestinal diseases such as irritable bowel syndrome or inflammatory
bowel disease are chronic diseases that need non-invasive biomarkers for prognosis and diagnosis.
Even more, patients with inflammatory bowel disease are at a significantly increased risk
of colorectal cancer, principally resulting from the pro-neoplastic effects of chronic intestinal inflammation.
Current screening methods utilized globally include sigmoidoscopy, or standard
colonoscopy but it is important to develop non-invasive and accurate screening tools to facilitate
early detection and precise staging of colorectal cancer. Disease progression and response to treatment
may benefit also from the application of these potential new tools. This review is focused on
studies that use lipidomics approaches to discover potential biomarkers for monitoring the mentioned
intestinal diseases and, particularly, tumour progression.
Identification of Gene Signature Associated with Type 2 Diabetes Mellitus
by Integrating Mutation and Expression Data
Authors: Cheng Liang , Zhu Zijun , Han Xudong
Published: July 2021

Background:

Type 2 Diabetes Mellitus (T2DM) is a chronic disease. The molecular diagnosis
should be helpful for the treatment of T2DM patients. With the development of sequencing
technology, a large number of differentially expressed genes were identified from expression data.
However, the method of machine learning can only identify the local optimal solution as the signature.

Objective:

The mutation information obtained by inheritance can better reflect the relationship between
genes and diseases. Therefore, we need to integrate mutation information to more accurately
identify the signature.

Methods:

To this end, we integrated Genome-Wide Association Study (GWAS) data and expression
data, combined with expression Quantitative Trait Loci (eQTL) technology to get T2DM predictive
signature (T2DMSig-10). Firstly, we used GWAS data to obtain a list of T2DM susceptible loci.
Then, we used eQTL technology to obtain risk Single Nucleotide Polymorphisms (SNPs), and combined
with the pancreatic β-cells gene expression data to obtain 10 protein-coding genes. Next, we
combined these genes with equal weights.

Results:

After Receiver Operating Characteristic (ROC), single-gene removal and increase method, gene
ontology function enrichment and protein-protein interaction network were used to verify the results showed
that T2DMSig-10 had an excellent predictive effect on T2DM (AUC=0.99), and was highly robust.

Conclusion:

In short, we obtained the predictive signature of T2DM, and further verified it.
Organic Cation Transporters are Involved in Fluoxetine Transport Across
the Blood-Brain Barrier In Vivo and In Vitro.
Authors: Wei Yang , Wang Min , Sun Yingying , Hu Bingying , He Zhisheng , Chen Shanshan , Qi Dake , An Hai
Published: July 2021

Background:

The research and development of drugs for the treatment of central nervous
system diseases faces many challenges at present. One of the most important questions to be
answered is, how does the drug cross the blood-brain barrier to get to the target site for pharmacological
action. Fluoxetine is widely used in clinical antidepressant therapy. However, the mechanism
by which fluoxetine passes through the BBB also remains unclear. Under physiological pH
conditions, fluoxetine is an organic cation with a relatively small molecular weight (<500), which
is in line with the substrate characteristics of organic cation transporters (OCTs). Therefore, this
study aimed to investigate the interaction of fluoxetine with OCTs at the BBB and BBB-associated
efflux transporters. This is of great significance for fluoxetine to better treat depression. Moreover,
it can provide a theoretical basis for clinical drug combination.

Methods:

In vitro BBB model was developed using human brain microvascular endothelial cells
(hCMEC/D3), and the cellular accumulation was tested in the presence or absence of transporter inhibitors.
In addition, an in vivo trial was performed in rats to investigate the effect of OCTs on the
distribution of fluoxetine in the brain tissue. Fluoxetine concentration was determined by a validated
UPLC-MS/MS method.

Results:

The results showed that amantadine (an OCT1/2 inhibitor) and prazosin (an OCT1/3 inhibitor)
significantly decreased the cellular accumulation of fluoxetine (P <.001). Moreover, we
found that N-methylnicotinamide (an OCT2 inhibitor) significantly inhibited the cellular uptake of
100 and 500 ng/mL fluoxetine (P <.01 and P <.05 respectively). In contrast, corticosterone (an OCT3
inhibitor) only significantly inhibited the cellular uptake of 1000 ng/mL fluoxetine (P <.05).
The P-glycoprotein (P-gp) inhibitor, verapamil, and the multidrug resistance associated proteins
(MRPs) inhibitor, MK571, significantly decreased the cellular uptake of fluoxetine. However, intracellular
accumulation of fluoxetine was not significantly changed when fluoxetine was incubated
with the breast cancer resistance protein (BCRP) inhibitor Ko143. Furthermore, in vivo experiments
proved that corticosterone and prazosin significantly inhibited the brain-plasma ratio of fluoxetine
at 5.5 h and 12 h, respectively.

Conclusion:

OCTs might play a significant role in the transport of fluoxetine across the BBB. In
addition, P-gp, BCRP, and MRPs seemed not to mediate the efflux transport of fluoxetine.
Recent Advances in Mesoporous Silica Nanoparticles for Targeted Drug
Delivery Applications
Authors: Abu-Dief Ahmed M. , Nafady Ayman , Alsehli Mosa , Al-Enizi Abdullah
Published: July 2021

Nanotechnology provides the means to design and fabricate delivery vehicles capable of
overcoming physiologically imposed obstacles and undesirable side effects of systemic drug delivery.
This protocol allows maximal targeting effectiveness and therefore enhances therapeutic efficiency.
In recent years, Mesoporous Silica Nanoparticles (MSNPs) have sparked interest in
nanomedicine research community, particularly for their promising applications in cancer treatment.
The intrinsic physio-chemical stability, facile functionalization, high surface area, low toxicity,
and great loading capacity for a wide range of chemotherapeutic agents make MSNPs very appealing
candidates for controllable drug delivery systems. Importantly, the peculiar nanostructures
of MSNPs enabled them to serve as an effective drug, gene, protein and antigen delivery vehicle
for a variety of therapeutic regimens. For these reasons, in this review article, we underscore the recent
progress in the design and synthesis of MSNPs along with the parameters influencing their
characteristic features and activities. In addition, the process of absorption, dissemination and secretion
by injection or oral management of MSNPs are also discussed, as they are key directions for
potential utilization of MSNPs. Factors influencing the in vivo fate of MSNPs will also be highlighted,
with a main focus on particle size, morphology, porosity, surface functionality and oxidation.
Given that combining other functional materials with MSNPs may increase their biological
compatibility, monitor drug discharge, or improve absorption by tumor cells coated MSNPs; these
aspects are also covered and discussed herein.
Plasma Homocysteine and Prognosis of Patients with Recanalization after Acute Basilar Artery Occlusion: An Analysis from the Acute Basilar Artery Occlusion Study (BASILAR) Nationwide Prospective Registry
Authors: Sun Xiangrong , Yang Qian , Ju Xinyue , Wang Shenglin , Qiu Zhongming , Sang Hongfei , Zi Wenjie , Yang Qingwu , Jiang Guohui
Published: July 2021

Background:

Few studies have investigated the association between plasma Homocysteine
(Hcy) levels in patients with recanalization after acute Basilar Artery Occlusion (BAO).

Objective:

This study investigated the predictive value of Hcy on the clinical prognosis of patients
with recanalization after acute BAO.

Methods:

Altogether, 829 participants were recruited from the standard medical treatment plus endovascular
treatment group of the Acute Basilar Artery Occlusion Study (BASILAR). Hcy levels
were measured the morning after admission. The primary outcome was a combination of death and
major disability (modified Rankin Scale score 4-6) at 90 days, and the secondary outcome was the
mortality of patients with recanalization after acute BAO within 90 days. We used multivariable logistic
regression modeling to estimate the association between Hcy and prognosis in our participants
at 90 days.

Results:

Altogether, 647 patients were assessed, and 302 patients were included in this study. The
median was 12.88 μmol/L, and the mean Hcy concentration was 15.49 μmol/L. Elevated plasma
Hcy levels (Hcy >12.88 μmol/L) were associated with poor functional outcomes (adjusted odds ratio
1.922, 95% confidence interval (CI) 1.048-3.528, P=0.035), but not with mortality (adjusted
odds ratio 1.605, 95% CI 0.986-2.489, P=0.058). In further subgroup analysis, the conclusion was
consistent in all predefined subgroups.

Conclusion:

Our analysis suggests that elevated plasma Hcy levels have a predictive value for functional
outcomes in patients with recanalization after acute BAO during the 90-day follow-up period,
but not for mortality.
Longitudinal Functional Magnetic Resonance Spectroscopy Study in Subjects with Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Cho Soo-Hyun , Rhee Hak Y. , Oh Janghoon , Lee Jin S. , Park Soonchan , Shin Won C. , Paik Jong-Woo , Ryu Chang-Woo , Park Key C. , Jahng Geon-Ho
Published: July 2021

Background:

Longitudinal changes of brain metabolites during a functional stimulation
are unknown in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) subjects.

Objective:

This study was to evaluate the longitudinal changes of brain metabolites using proton
magnetic resonance spectroscopy (1H MRS) in response to treatment during a memory task in the
subjects of cognitive normal (CN), aMCI, and AD.

Methods:

We acquired functional magnetic resonance spectroscopy (fMRS) data from 28 CN elderly,
16 aMCI and 12 AD subjects during a face-name association task. We measured fMRS metabolite
ratios over 24 months in the 8-month apart, determined the temporal changes of the metabolites,
and evaluated the differences among the three groups under the three different conditions
(base, novel, repeat).

Results:

The results of comparisons for the three subject groups and the three-time points showed
that tNAA/tCho and tCr/tCho were statistically significant among the three subject groups in any
of the three conditions. The dynamic temporal change measurements for the metabolites for each
condition showed that Glx/tCho and Glu/tCho levels at the third visit increased significantly compared
with in the first visit in the novel condition in the AD group.

Conclusion:

We found declines in tNAA/tCho and tCr/tCho in the aMCI and AD subjects with increasing disease severity, being highest in CN and lowest in AD. The Glx/tCho level increased temporally in the AD subjects after they took an acetylcholine esterase inhibitor. Therefore, Glx may be suitable to demonstrate functional recovery after treatment.
Mesenchymal Stem Cells (MSCs) in Targeted Drug Delivery: Literature Review and Exploratory Data on Migrating and Differentiation Capacities of Bone MSCs into Hepatic Progenitor Cells
Authors: Zhu Xulong , Yan Tan , Cheng Chong , Ma Jia , Xiang Junxi , Lv Yi , Wang Jue , Huo Binliang , Zhang Feifei , Wu Shuhan , Bai Lu , Li Jianhui
Published: July 2021

Background and Objective:

Mesenchymal stem cells (MSCs), particularly bone MSCs
(BMSCs) offer great potentials for targeted therapeutic applications owing to their migratory and
differentiation capacities. Significant advances have been achieved in the differentiation of hepatocyte
or hepatocyte-like cells both in vitro and in vivo. However, there is limited knowledge on the
differentiation of BMSCs into bipotential hepatic progenitor cells or cholangiocyte. This study reviews
the potentials and advances in using MSCs as vehicles for targeted drug delivery and proposes
a new method for the induction of differentiation in rat BMSCs into hepatic progenitor cells in
vitro and assesses the differential and migratory capacities.

Methods:

The BMSCs of Sprague Dawley (SD) rats were harvested from the femur and the tibiae
of the rats. After isolation and culturing, BMSCs from Passage 1 were used for the study. The in
vitro differentiation of the hepatic progenitor cells was performed using a 2-step induction approach
after 5-day serum deprivation from the BMSCs and culturing in Dulbecco's modified eagle
medium. Spontaneous in vitro differentiation of BMSCs was examined in the absence of growth
factors for 15 days as control treatment. Hepatocytes differentiation was achieved by exposing the
culture to collagen type I-coated plates. Cholangiocytes differentiation was achieved with replating
the BMC-HepPCs on a layer of Matrigel. Immunofluorescence was conducted on twelve-well
plates to determine cell differentiations. Real-Time Quantitative Reverse Transcription PCR (qRTPCR)
was used to determine the total RNA extracted using the Trizol LS reagent. In the hepatocyte
differentiation group, after periodic acid-schiff (PAS) staining for glycogen, inverted microscope
was used to determine differentiations and undifferentiated BMC-HepPCs served as controls.
The amount of low-density lipoprotein (LDL) uptake by the BMSCs-derived hepatocytes was assessed
using fluorescence microscopy. The secretion of rat albumin was quantified using a quantitative
ELISA kit.

Results:

Differentiation induction is indicative of the sequential supplementation of sodium butyrate
and cytokines, which are involved in the embryonic development of the mammalian liver.
Hepatic progenitor cells, derived from bone marrow, can be differentiated bidirectionally in vitro
into both hepatocyte and cholangiocyte cell-lines. The differentiated cells, including hepatic progenitor
cells, hepatocytes, and bile duct-like cells, were identified and analyzed at mRNA and protein
levels.

Conclusion:

Our findings show that BMSCs can be utilized as novel bipotential hepatic progenitor
cells and thereby for hepatobiliary disease treatment or hepatobiliary tissue-engineering.