bluuebunny/crossref_metadata_2025 huggingface dataset:
TVN SA jako podmiot gospodarczy. Zarys zagadnienia na przykładzie analizy fundamentalnej i próby wyceny spółki w latach 2009–2015
Authors: Maksimowicz Daiwa
Published: December 2020

Media to istotny sektor polskiej gospodarki. Wkraczając na rynek kapitałowy, zyskują dodatkowe źródła dochodów, ale również prestiż w środowisku biznesowym. Indeks WIG-Media warszawskiej Giełdy Papierów Wartościowych notuje obecnie 13 spółek. Jego wartość została pomniejszona w wyniku wycofania z obrotu akcji jednego z największych koncernów medialnych – Grupy TVN. O jego rzeczywistej randze traktuje analiza fundamentalna i próba wyceny spółki zawarte w niniejszym artykule.
Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential
Authors: Raman Lennart , Van der Linden Malaïka , De Vriendt Ciel , Van den Broeck Bliede , Muylle Kristoff , Deeren Dries , Dedeurwaerdere Franceska , Verbeke Sofie , Dendooven Amélie , De Grove Katrien , Baert Saskia , Claes Kathleen , Menten Björn , Offner Fritz , Van Dorpe Jo
Published: December 2020

Shallow-depth sequencing of cell-free DNA, an inexpensive and standardized approach to obtain molecular information on tumors non-invasively, has been insufficiently explored for the diagnosis of lymphoma and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively- recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non-HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed. At diagnosis, liquid biopsies showed detectable copy number alterations in 84.2% of HL patients (88.6% for classical HL) and 74.1% of DLBCL patients. Of the DLBCL patients, copy number profiles between liquid-solid pairs were highly concordant (r=0.815±0.043); and, compared to tissue, HL liquid biopsies had abnormalities with higher amplitudes (P=0.010). This implies that tumor DNA is more abundant in plasma. Additionally, 39.5% of HL and 13.6% of DLBCL cases had a significantly elevated number of plasma Epstein-Barr virus DNA fragments, achieving a sensitivity of 100% compared to the current standard. A longitudinal analysis determined that, when detectable, copy number patterns were similar across (re)staging moments in refractory or relapsed patients. Further, the overall profile anomaly correlated highly with the total metabolic tumor volume (P<0.001). To conclude, as a proof of principle, we demonstrate that liquid biopsy-derived copy numbers can aid diagnosis: e.g., by differentiating HL from DLBCL, random forest modeling is represented by an area under the receiver operating characteristic curve of 0.967. This application is potentially useful when tissue is difficult to obtain or when biopsies are small and inconclusive.
Drug abuse and drug addiction among students of University of Rajshahi
Authors: Tahjiba Faiqua
Published: December 2020

Objectives: The aim of this study was to investigate the actual condition of the students of University of Rajshahi (RU) regarding drug abuse and addiction. Using case study method the research was conducted with four objectives: (a) to find out how respondents began drug abuse; (b) to discover the causes of their drug addiction; (c) to understand the process of their drug abuse; and (d) to find out the economic, social and health effects of drug abuse. Methods: Case study method was used in this research. Through snowball sampling 18 drug- addicted students of RU were selected as respondents. In-depth interview with a schedule was used to collect data from the respondents in January 2019. Results: Findings of the study show that the causes of drug addiction included curiosity, frustration, friends’ request, neglect from family and friends etc. The drugs which they usually abused were Yaba, Phensydyle, Ganja (Weed), Chuani etc. Their average monthly expenditure for collecting drugs was in between Taka 8,000-10,000. They collected those drugs from rickshaw pullers at different points within the campus and from Mizaner Mor, Budhpara slum and other places outside the campus. The respondents opined that drugs were available if sufficient money could be spent. The respondents had senior and junior fellow students and local boys as companions while taking drugs. Most of them faced physical problems after taking drugs, and some of them tried to get rid of this curse of drug addiction. Conclusion: The findings of this research show that the rate of drug addiction among the students of RU was quite alarming. Therefore, all stakeholders including the students, guardians, teachers, university authority, the law makers and law enforcing agencies, researchers, civil society, NGO’s and the state must come forward together to combat this formidable foe.
KEWENANGAN MAJELIS KEHORMATAN NOTARIS DALAM PERSPEKTIF HUKUM ADMINISTRASI NEGARA
Authors: Iryadi Irfan
Published: December 2020

Kewenangan badan tata usaha negara tentunya harus didasari pada asas legalitas. Asas ini berlaku agar badan tata usaha negara itu tidak bertindak diluar kewenangannya, termasuk Majelis Kehormatan Notaris. Namun eksistensi Majelis Kehormatan Notaris sebagai badan tata usaha negara masih diragukan legalitasnya. Bahkan masih juga terdapat kontradiksi pemahaman menyangkut kewenangannya sebagaimana dimaksud dalam Pasal 66 ayat (1) Undang-Undang Nomor 2 Tahun 2014. Disamping itu, masih ada juga yang menyamakan prosedur kewenangan Majelis Kehormatan Notaris dengan prosedur kewenangan Majelis Pengawas Notaris. Untuk kepentingan itu, maka artikel ini sengaja ditulis sebagai upaya untuk menelaah kewenangan Majelis Kehormatan Notaris dalam perspektif hukum administrasi negara. Metode penelitian yang digunakan adalah penelitian hukum normatif. Hasil penelitian menunjukkan bahwa Majelis Kehormatan Notaris itu memang mempunyai legalitas sebagai badan tata usaha negara dengan sumber kewenangan distribusi. Esensi dari kewenangan Majelis Kehormatan Notaris itu adalah untuk melakukan pembinaan kepada notaris menyangkut pemeriksaan dalam ranah tanggung jawab jabatan melalui kontruksi hukum administrasi dengan instrumen perizinan, bukan tanggung jawab individu melalui sarana hukum pidana. Tujuannya adalah untuk menjaga wibawa jabatan notaris dengan cara mendahulukan proses pemeriksaan dalam ranah tanggung jawab jabatan sebelum pemeriksaan tanggung jawab individu.
PRODUÇÃO SOBRE ASSÉDIO SEXUAL NO PERÍODO DE 2010 A 2019: UM ESTUDO BIBLIOMÉTRICO
Authors: Sartori Farencena Gisela , Kocourek Sheila , Moro da Silva Andreia , Henri Dorion Eric Charles
Published: December 2020

O assédio sexual é uma forma de violência que atinge, diariamente, muitas mulheres. Como uma prática recorrente, espera-se que a temática também venha recebendo atenção por parte dos pesquisadores. Assim, este estudo tem como objetivo analisar a produção científica sobre o assédio sexual entre os anos de 2010 e 2019, mais especificamente no que se refere à Administração e áreas afins. Para isso, foi realizado um estudo bibliométrico em duas bases de dados: da ANPAD (Associação Nacional de Pós-Graduação e Pesquisa em Administração), fazendo uma breve análise dos trabalhos encontrados; e Web of Science, onde foram analisados o perfil geral das publicações (principais áreas que pesquisam o tema, ano, autores, idiomas e países) e as características dos dez artigos mais citados na referida base. A partir dos artigos encontrados nas bases, foi possível perceber que o assédio sexual no local de trabalho foi uma forte tendência de pesquisa no período analisado, mas há carência de estudos dessa forma de assédio em organizações públicas.
Palavras-Chave: Assédio sexual. Produção científica. Bibliométrico.
 
Abstract: Sexual harassment is a form of violence that daily affects many women. As a recurring practice, it is expected that the theme will also receive attention from researchers. Thus, this study aims to analyze the scientific production on sexual harassment between the years 2010 and 2019, more specifically with regard to Administration and related areas. For this, a bibliometric study was carried out in two databases: from ANPAD (National Association of Graduate Studies and Research in Administration), making a brief analysis of the works found; and Web of Science, where the general profile of the publications (main areas that research the theme, year, authors, languages and countries) and the characteristics of the ten most cited articles in that database were analyzed. From the articles found in the databases, it was possible to perceive that sexual harassment in the workplace was a strong research trend in the analyzed period, but there is a lack of studies on this form of harassment in public organizations.
Keywords: Sexual harassment. Scientific production. Bibliometric.
Telegram Bot Implementation in Academic Information Services with The Forward Chaining Method
Authors: Rianto Rianto , Rahmatulloh Alam , Firmansah Teguh Anugrah
Published: December 2020

Academic information is an important information for students in assisting academic activities, every effort has been developed to improve academic services. With the continuous development of various mobile devices or smartphones, the traditional way of Short Message Service (SMS) has been replaced by instant messaging applications that make the communication process more real-time. So this research will try to use technology in instant message as a means of academic service information, it is expected academic information can be delivered more quickly and up-to-date. Telegram as one of the instant messaging application that offers various advantages in its feature than other instant messaging application. The most popular feature and is being developed on telegram is the bot feature, where a third party or user can develop bot features according to user requirements. Thus telegram can help overcome various problems such as academic information seeking problems. For that made the application of lecture information service using Telegram Bot. The making of this information service application is built with Rational Unified Process (RUP) process model, Forward Chaining method and using Python Telepot Framework for Telegram Bot API for application to run via Telegram instant message. With the making of this application, facilitate communication and delivery of academic information to lecturers, students, and the academic community.
Development of Belajar Astronomi: an Astronomy Learning Application for Kids
Authors: Muharram Riza Miftah , Budiman Ade Surya
Published: December 2020

Learning process should be an interesting process, especially for kids in elementary school. There are many methods has delivered to make the kids going fun to learn any new thing. Information and Communication Technolgy (ICT) could been involved to the learning process. ICT-based learning tools that used to help teachers and parents are developed in this research.   Astronomy is one of the fields of science which is generally taught in schools as a part of natural science subject. In this study, authors developed an astronomy learning application’s named Belajar Astronomi that comes as a supplement study material for elementary students. This Astronomy Learning application is designed to be a tool for students to study astronomy independently. Belajar Astronomi’s application developed with the Visual Basic programming language in Microsoft Visual Studio 2010 using Waterfall methods, to make sure Its functionality and usefulness. The application is equipped with images, text, and videos that can help students to learn astronomy more easily, Its also equipped with quizzes as training materials that can help students in sharpening their knowledge in Astronomy subject.
Prevalência e fatores associados à violência conjugal
Authors: Lopes Raquel Ferreira , Almeida Thayse Gomes de , Tavares Núbia Vanessa da Silva , Melo Jéssica da Silva , Santos Jaqueline Maria Silva dos , Vasconcelos Eveline Lucena , Trindade Ruth França Cizino da
Published: December 2020

Objetivo: investigar a prevalência e fatores associados à violência doméstica. Metodologia: Estudo quantitativo de natureza exploratória, de corte transversal e descritivo. Realizado em nove unidades básicas de saúde dos oito distritos sanitários do município de Maceió-Al. Participaram da pesquisa 247 mulheres usuárias de nove unidades de atenção básica de saúde, residentes no município de Maceió – Al, na faixa etária entre 18 a 49 anos de idade. Foi utilizado o instrumento Abuse Assesment Screen (AAS) para detecção da violência e um formulário estruturado para caracterização dos dados sócio demográficos das entrevistadas. Resultados: entre as 247 entrevistadas, foi detectado prevalência de 43,72% de violência doméstica. Houve associação significativa entre violência física com renda familiar e idade do parceiro, tabagismo, uso de álcool e violência na infância. Conclusão: os dados mostraram alta prevalência de violência doméstica, em sua maioria praticada pelo parceiro íntimo. Faz-se necessário maiores investimentos em capacitações com os profissionais das unidades básicas de saúde para reconhecer e lidar com a violência doméstica.
Estudo cienciométrico da dinâmica comportamental das publicações referentes ao tratamento da COVID-19 no primeiro semestre de 2020
Authors: Bellotto Ghabriel Luiz , Anschau Bruna Spironello , Moereira Camilla Scott , Silva Juliane Toffoli , Teixeira Kádima Nayara
Published: December 2020

A primeira infecção causada pelo novo coronavírus ocorreu na China, em dezembro de 2019.  Desde então, a busca por tratamentos para a COVID-19 tornou-se alvo de pesquisas internacionais.  Apesar dos estudos terem iniciado logo após o surto viral na China, era esperado o aumento das publicações desses estudos pelo mundo todo após a declaração da Organização Mundial de Saúde sobre o estado pandêmico da doença. Dessa forma, este estudo teve como objetivo analisar a dinâmica das publicações científicas sobre o tratamento da COVID-19 no primeiro semestre de 2020. Para a coleta de dados utilizou-se a plataforma MEDLINE por meio da PubMed; os descritores adotados foram: “COVID-19 and Treatment”
e “SARS-CoV-2 and Treatment”, restringindo o período de publicação de 01/01/2020 a 30/06/2020. Dados mostraram que em janeiro de 2020, fase inicial da pandemia, o número de
publicações sobre o tema foi ínfimo em relação a junho, com a pandemia totalmente disseminada. O maior crescimento no número de publicações ocorreu entre fevereiro e março (8,3 vezes maior). No que se refere ao número de países envolvidos em publicações, observa-se que em janeiro, três países estavam envolvidos; enquanto, em maio havia 41 países. No período analisado, a China liderou com 152 publicações, seguida pelos Estados Unidos (141). Isso pode ser resultado do surgimento dos primeiros casos da doença e  do caráter socioeconômico de ambos, que apesar dos distintos regimes políticos, têm a pesquisa científica como ponto importante para a continuidade do desenvolvimento.
Efeito imediato da técnica finger kazoo em pacientes com afecções laríngeas: estudo de casos
Authors: Rossa Aline Medianeira Tolfo , Bastilha Gabriele Rodrigues , Christmann Mara Keli , Cielo Carla Aparecida
Published: December 2020

Objetivo: Verificar as modificações vocais perceptivoauditivas após a técnica vocal finger kazoo em três mulheres com afecções laríngeas. Métodos:  Três mulheres adultas com respectivo diagnóstico médico de: sulco vocal estria maior (S1), nódulos vocais (S2), e microweb laríngeo (S3) realizaram três séries de 15 repetições do finger kazoo com 30 s de repouso passivo entre as séries. Dois juízes realizaram análise vocal perceptivoauditiva antes, imediatamente após a terapia, e cinco minutos após silêncio absoluto. Resultados: Soprosidade, astenia e instabilidade diminuíram imediatamente após a execução do finger kazoo em S1 e S3 e soprosidade e instabilidade diminuíram em S2. Após cinco minutos de silêncio, todos os parâmetros diminuíram, com exceção da tensão em S1; a rouquidão, soprosidade e instabilidade diminuíram em S2; e todos os parâmetros, com exceção da tensão, pioraram em S3. Conclusões: O finger kazoo executado em uma sessão de três séries de 15 repetições ocasionou melhora de parâmetros perceptivoauditivos nas três mulheres com afecção laríngea em ambos os momentos pós-terapia, com exceção da paciente com microweb que apresentou melhora imediatamente após a realização da técnica e piora após cinco minutos de silêncio.
Short Term Methylphenidate Treatment Does Not Increase Myocardial Injury in the Ischemic Rat Heart
Authors: SEELEY S , D’SOUZA M , STOOPS T , RORABAUGH B
Published: December 2020

Methylphenidate is commonly used for the treatment of attention deficit hyperactivity disorder. The cardiovascular safety of methylphenidate has been a subject of debate with some studies indicating that methylphenidate increases the likelihood of experiencing a myocardial infarction. However, it is unknown whether methylphenidate worsens the extent of injury during an ischemic insult. The purpose of this study was to determine whether short term exposure to methylphenidate increases the extent of myocardial injury during an ischemic insult. Male and female rats received methylphenidate (5 mg/kg/day) or saline for 10 days by oral gavage. Hearts were subjected to 20 min of ischemia and 2 h of reperfusion on a Langendorff isolated heart apparatus on day 11. Cardiac contractile function was monitored via an intraventricular balloon and myocardial injury was assessed by triphenyltetrazolium chloride staining. Methylpheni-date significantly increased locomotor activity in male and female rats, confirming absorption of this psychostimulant into the central nervous system. Male hearts had significantly larger infarcts than female hearts, but methylphenidate had no impact on infarct size or postischemic recovery of contractile function in hearts of either sex. These data indicate that methylphenidate does not increase the extent of injury induced by an ischemic insult.
Fogyasztói szokások vizsgálata kvantitatív módszerekkel a magyarországi tejtermékpiacon
Authors: Szabó-Szentgróti Eszter , Szigeti Orsolya , Tóth Katalin , Borbély Csaba , Szakály Zoltán
Published: December 2020

Számos tanulmány és kutatás szól a tejtermékek egészségvédő szerepéről, és hogy fogyasztásuk hozzátartozik a kiegyensúlyozott és egészséges táplálkozáshoz. Az említett pozitív élettani hatások miatt nem mindegy, hogy mennyit és milyen formában fogyasztunk ezekből a termékekből, ugyanakkor a mai (élelmiszer) fogyasztási szokások átalakulóban vannak és rapid módon változnak. A tanulmány célja volt, hogy a fogyasztási gyakoriságon túl felmérje a tejtermékfogyasztók tipikus csoportjait és a fogyasztási szokásokat. A reprezentatív megkérdezés országos szintű volt, amelyben 503 fő vett részt 18-75 éves korig. A statisztikai elemzések során 95%-os konfidencia szint mellett 0,05 vagy annál alacsonyabb érték lett meghatározva szignifikáns kapcsolatnak. A faktorextrakció főkomponens elemzéssel történt, az adatok alkalmasságának vizsgálata Kaiser-Meyer-Olkin (KMO) és Bartlett teszt segítségével készült. A faktorok száma a Kaiser kritériummal lett meghatározva, továbbá Varimax rotáció lett alkalmazva. A klaszterek számának meghatározása két lépcsőben történt (1. Ward-féle módszer, 2. K-közép módszer). Megállapítható volt, hogy leggyakrabban folyadéktejet, joghurtot, tejfölt és túrót fogyasztunk, továbbá elmondható, hogy a hazai fogyasztó még mindig nincs tisztában a vaj és a margarin közti különbséggel. A nők átlagosan gyakrabban fogyasztanak folyadéktejet és tejfölt, mint a férfiak. A magasabb jövedelemmel rendelkezők gyakrabban fogyasztanak érlelt sajtokat. A magukat egészségtudatosnak vélő válaszadók gyakrabban esznek joghurtot, túrót és érlelt sajtot. A klaszteranalízis során három klasztert sikerült azonosítani: a „Tömegtermék fogyasztó”-t, az „Innovációra nyitott”-at és a „Hipokrita lokálpatrióták”-at. A három klaszter esetében meghatároztuk azokat a jellemzőket, amelyek segítségével egy kampány során megszólíthatók.
The circumstances of the origin and history of the development of the church schism of the Belarusian diaspora in the first half of the 1980s
Authors: Slesarau Aliaxandr V.
Published: December 2020

The article describes the history of the origin and development of the intra-confessional conflict that engulfed the Belarusian Autocephalous Orthodox Church (BAOC) in the first half of the 1980s. For the first time, a conclusion is drawn regarding the decisive role of the ideological prerequisites for the emergence of a split, rooted in the difference in approaches to understanding the principles of church governance. If the highest church leadership was characterised by a commitment to the ideas of the key role of hierarchy (clericalism), then representatives of parishes and Belarusian sociopolitical organisations insisted on the obligation to implement the principle of collegiality. The conflict developed as a result of the structural and administrative division of the BAOC, mutual compromise of opponents, a significant reduction in the financial possibilities of parishes and the disintegration of the Belarusian diaspora. Unlike the Ukrainian Autocephalous Orthodox Church in exile, divided and weakened by internal contradictions, the BAOC was unable to expand its activities in Belarus in the late 1980s and 1990s.
On some properties of the lattice of totally σ-local formations of finite groups
Authors: Safonov Vasilly G. , Safonova Inna Nikolaevna
Published: December 2020

Throughout this paper, all groups are finite. Let $σ=\{σ_i{}|i\in I\}$ be some partition of the set of all primes $\Bbb{P}$. If $n$ is an integer, $G$ is a group, and $\mathfrak{F}$ is a class of groups, then $σ(n)=\{σ_i{}|σ_i{}\cap \pi(n)\ne \emptyset\}$, $σ(G)=σ(|G|)$, and $σ(\mathfrak{F})=\cup _G{}_\in{}_\mathfrak{F}σ(G)$. A function $f$ of the form  $f\colon σ\to$ {formations of groups} is called a formation σ-function. For any formation $σ$-function $f$ the class $LF_σ(f)$ is defined as follows:

$LF_{\sigma}(f)=(G$ is a group $|G=1$ или $G\ne1$ and $G/O_σ{}'_i{}_,{}_σ{}_i{}(G)\in f(σ_i{})$ for all $σ_i{}\in σ(G))$.

If for some formation $σ$-function $f$ we have $\mathfrak{F}=LF_{\sigma}(f)$, then the class $\mathfrak{F}$ is called $σ$-local definition of $\mathfrak{F}$. Every formation is called 0-multiply $σ$-local. For $n$ > 0, a formation $\mathfrak{F}$ is called $n$-multiply $σ$-local provided either $\mathfrak{F}=(1)$ is the class of all identity groups or $\mathfrak{F}=LF_{\sigma}(f)$, where $f(σ_i{})$ is $(n – 1)$-multiply $σ$-local for all $σ_i{}\in σ(\mathfrak{F})$. A formation is called totally $σ$-local if it is $n$-multiply $σ$-local for all non-negative integer $n$. The aim of this paper is to study properties of the lattice of totally $σ$-local formations. In particular, we prove that the lattice of all totally $σ$-local formations is algebraic and distributive.
EARLY WARNING OF INSOLVENCY IN THE EUROPEAN UNION LAW
Authors:   University of Opole, Opole, Poland, ADAMUS RAFAŁ
Published: December 2020

Rapid diagnosis of the risk of an entrepreneur’s insolvency is of great importance for the socio-economic environment. This issue is of particular importance in the context of the financial crisis caused by the COVID-19 pandemic. The insolvency resulting in the announced bankruptcy brings a lot of harm to the debtors themselves (their shareholders), creditors and the entire economy. A much better solution is the restructuring of the debtor. For the purposes of predicting insolvency can be used Artificial Intelligence although traditional methods are also in use. For these reasons, in European Union law, the Restructuring Directive focuses on the anticipation of debtor’s insolvency. The text refers to possible directions for the implementation of the directive in national laws. The aim of the study is to analyze the available methods of early warning against insolvency. As a result of the research, the ways of implementing the Directive were proposed.
RISKS OF FOREIGN TRADE PARTICIPANTS IN THE FIELD OF CALCULATION AND ADMINISTRATION OF CUSTOMS PAYMENTS
Authors:   Financial University under the Government of the Russian Federation, Moscow, Russian Federation, KOSTIN ALEKSEY
Published: December 2020

Purpose of research. The article deals with the problems of forming a business environment in foreign trade, taking into account the construction of a risk-based compliance management model by controlling state bodies. The purpose of the study is to establish and identify the features of identifying risks of participants in foreign economic activity and the state in the calculation and administration of customs payments, respectively. This is necessary not only for the administration of customs duties and taxes, but also for determining the main directions for the development of foreign trade activities of the Russian Federation. Conclusions. As a result of the research, the author comes to the conclusion that risk management occupies a special place in the system of managing the compliance of foreign trade activities with the criteria established by state regulatory (customs, tax) authorities. However, in addition to managing tax and customs risks, which according to current legislation are recognized as violations of the rules established by law, it is necessary to change the system for evaluating the effectiveness and efficiency of the Supervisory authorities themselves. Currently, the relationship between the risk management system and the violations of customs and other legislation themselves is mostly reduced to the implementation of the customs authorities ' fiscal task. According to the majority of importers, the application of the risk management system has a single goal - to increase the costs of participants in foreign economic activity associated with cross-border movement of goods. On the part of participants in foreign economic activity, it is necessary to restructure the strategy of interaction with regulatory authorities. In these circumstances, the key areas of such interaction are the development of the Institute of authorized economic operators, its sub-Institute of authorized exporters, as well as the creation of a self-regulating organization in the field of foreign trade that represents the interests of not only Russian exporters, but also importers.
SPATIAL DEVELOPMENT STRATEGY OF RUSSIA: ASSESSMENT OF IMPLEMENTATION PROSPECTS
Authors:   Academy of Public Administration, Mytischi, Russian Federation, ALIEV ADIK , SURTAEVA OLGA ,   Siberian Federal University, Krasnoyarsk, Russian Federation, SAVELYEV ANDREY ,   FOK LLC
Published: December 2020

The purpose of the article is to provide a comprehensive theoretical analysis of the implementation of the Spatial Development Strategy of the Russian Federation for the period up to 2025 (hereinafter referred to as the Strategy), on the basis of which it is envisaged to compare such concepts as «federal district», «macroregion» and «aspect of regional studies - zoning», since in theoretical terms, the overlap and confusion of the boundaries of the application of these concepts is seen. This approach is dictated by the need to identify the balanced development of the regions of the Russian Federation and the observed transformation of the spatial organization of the economy and social sphere. Questions remain: will the implementation of the Strategy entail an increase in the number of officials, increased bureaucratization and an increase in additional ineffective budget spending in the country, which is, therefore, extremely high. The article also examines practical issues related to assessing the feasibility of implementing the results of the Strategy contained in such innovations as the formation of agglomerations, the identification of promising industries for each region for future economic specialization and the creation of macroregions. They touch upon a number of problems of a legal, financial, managerial nature and coordination support of this government document, which await their solution in the future. In the course of the study, the conclusions were obtained that the Strategy is a strategic planning document. It provides for large-scale reform and innovative development of the production sector, social economy, management, environmental and a number of other equally significant tasks of the country's territorial modernization.
Biotechnology and Biomaterial-Based Therapeutic Strategies for Age-Related Macular Degeneration. Part II: Cell and Tissue Engineering Therapies
Authors: Jemni-Damer Nahla , Guedan-Duran Atocha , Fuentes-Andion María , Serrano-Bengoechea Nora , Alfageme-Lopez Nuria , Armada-Maresca Félix , Guinea Gustavo V. , Perez-Rigueiro José , Rojo Francisco , Gonzalez-Nieto Daniel , Kaplan David L. , Panetsos Fivos
Published: December 2020

Age-related Macular Degeneration (AMD) is an up-to-date untreatable chronic neurodegenerative eye disease of multifactorial origin, and the main causes of blindness in over 65 y.o. people. It is characterized by a slow progression and the presence of a multitude of factors, highlighting those related to diet, genetic heritage and environmental conditions, present throughout each of the stages of the illness. Current therapeutic approaches, mainly consisting on intraocular drug delivery, are only used for symptoms relief and/or to decelerate the progression of the disease. Furthermore, they are overly simplistic and ignore the complexity of the disease and the enormous differences in the symptomatology between patients. Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, Due to the wide impact of the AMD and the up-to-date absence of clinical solutions, different treatment options have to be considered. Cell therapy is a very promising alternative to drug-based approaches for AMD treatment. Cells delivered to the affected tissue as a suspension have shown poor retention and low survival rate. A solution to these inconveniences has been the encapsulation of these cells on biomaterials, which contrive to their protection, gives them support, and favor their retention of the desired area. We offer a two-papers critical review of the available and under development AMD therapeutic approaches, from a biomaterials and biotechnological point of view. We highlight benefits and limitations and we forecast forthcoming alternatives based on novel biomaterials and biotechnology methods. In this second part we review the preclinical and clinical cell-replacement approaches aiming at the development of efficient AMD-therapies, the employed cell types, as well as the cell-encapsulation and cell-implant systems. We discuss their advantages and disadvantages and how they could improve the survival and integration of the implanted cells.
Experimental Testing and Numerical Modeling of Robust Unreinforced and Reinforced Clay Masonry Infill Walls, With and Without Openings
Authors: da Porto Francesca , Donà Marco , Verlato Nicolò , Guidi Giovanni
Published: December 2020

This paper presents an overview of the experimental results obtained by combined in-plane/out-of-plane (IP/OOP) tests carried out on robust clay masonry infill walls. The combined tests were carried out on eight full-scale one-bay, one-story infilled reinforced concrete (RC) frames, plus one reference RC bare frame. In four cases, the masonry walls fully fill the RC frame: two walls are made of unreinforced masonry (URM), whereas the other two are made of reinforced masonry (RM), with both vertical and horizontal reinforcement. Each pair of specimens was tested up to different levels of IP drift before carrying out the OOP tests. Four other specimens, still made of URM and RM walls, are characterized by the presence of a central opening, and in one case, the effect of a lintel is analyzed. On the basis of the tests carried out, an analytical model was developed for the analysis of the OOP behavior. It was used to calibrate IP damage degradation models based on the experimental results to define limits for the applicability of well-known flexural and arching mechanism models for the evaluation of the OOP capacity of the infill walls and to evaluate the efficiency of vertical reinforcement. In this work, the experimental campaign is presented, and the results of both experimental tests and numerical analyses are discussed.
Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
Authors: Wang Nan , Xie Gang , Liu Chao , Cong Wei , He Shipeng , Li Yinghua , Fan Li , Hu Hong-Gang
Published: December 2020

A4K14-citropin 1.1 is a structurally optimized derivative derived from amphibians' skin secreta peptide Citropin, which exhibits broad biological activities. However, the application of A4K14-citropin 1.1 as a cancer therapeutic is restricted by its structural flexibility. In this study, a series of all-hydrocarbon stapled peptides derivatives of A4K14-citropin 1.1 were designed and synthesized, and their chemical and biological characteristics were also investigated. Among them, A4K14-citropin 1.1-Sp1 and A4K14-citropin 1.1-Sp4 displayed improved helicity levels, greater protease stability, and increased antitumor activity compared with the original peptide, which establishes them as promising lead compounds for novel cancer therapeutics development. These results revealed the important influence of all-hydrocarbon stapling side chain on the secondary structure, hydrolase stability, and biological activity of A4K14-citropin 1.1.
Accelerator or Brake: Immune Regulators in Malaria
Authors: Cai Chunmei , Hu Zhiqiang , Yu Xiao
Published: December 2020

Malaria is a life-threatening infectious disease, affecting over 250 million individuals worldwide each year, eradicating malaria has been one of the greatest challenges to public health for a century. Growing resistance to anti-parasitic therapies and lack of effective vaccines are major contributing factors in controlling this disease. However, the incomplete understanding of parasite interactions with host anti-malaria immunity hinders vaccine development efforts to date. Recent studies have been unveiling the complexity of immune responses and regulators againstPlasmodiuminfection. Here, we summarize our current understanding of host immune responses againstPlasmodium-derived components infection and mainly focus on the various regulatory mechanisms mediated by recent identified immune regulators orchestrating anti-malaria immunity.
Profiling of H3K27Ac Reveals the Influence of Asthma on the Epigenome of the Airway Epithelium
Authors: McErlean Peter , Kelly Audrey , Dhariwal Jaideep , Kirtland Max , Watson Julie , Ranz Ismael , Smith Janet , Saxena Alka , Cousins David J. , Van Oosterhout Antoon , Solari Roberto , Edwards Michael R. , Johnston Sebastian L. , Lavender Paul
Published: December 2020

Background

Asthma is a chronic airway disease driven by complex genetic–environmental interactions. The role of epigenetic modifications in bronchial epithelial cells (BECs) in asthma is poorly understood.

Methods

We piloted genome-wide profiling of the enhancer-associated histone modification H3K27ac in BECs from people with asthma (n = 4) and healthy controls (n = 3).

Results

We identified n = 4,321 (FDR < 0.05) regions exhibiting differential H3K27ac enrichment between asthma and health, clustering at genes associated predominately with epithelial processes (EMT). We identified initial evidence of asthma-associated Super-Enhancers encompassing genes encoding transcription factors (TP63) and enzymes regulating lipid metabolism (PTGS1). We integrated published datasets to identify epithelium-specific transcription factors associated with H3K27ac in asthma (TP73) and identify initial relationships between asthma-associated changes in H3K27ac and transcriptional profiles. Finally, we investigated the potential of CRISPR-based approaches to functionally evaluate H3K27ac-asthma landscape in vitro by identifying guide-RNAs capable of targeting acetylation to asthma DERs and inducing gene expression (TLR3).

Conclusion

Our small pilot study validates genome-wide approaches for deciphering epigenetic mechanisms underlying asthma pathogenesis in the airways.
Hybrid Incompatibilities and Transgressive Gene Expression Between Two Closely Related Subspecies of Drosophila
Authors: Go Alwyn C. , Civetta Alberto
Published: December 2020

Genome-wide assays of expression between species and their hybrids have identified genes that become either over- or underexpressed relative to the parental species (i.e., transgressive). Transgressive expression in hybrids is of interest because it highlights possible changes in gene regulation linked to hybrid dysfunction. Previous studies inDrosophilathat used long-diverged species pairs with complete or nearly complete isolation (i.e., full sterility and partial inviability of hybrids) and high-levels of genome misregulation have found correlations between expression and coding sequence divergence. The work highlighted the possible effects of directional selection driving sequence divergence and transgressive expression. Whether the same is true for taxa at early stages of divergence that have only achieved partial isolation remains untested. Here, we reanalyze previously published genome expression data and available genome sequence reads from a pair of partially isolated subspecies ofDrosophilato compare expression and sequence divergence. We find a significant correlation in rates of expression and sequence evolution, but no support for directional selection driving transgressive expression in hybrids. We find that most transgressive genes in hybrids show no differential expression between parental subspecies and used SNP data to explore the role of stabilizing selection through compensatory mutations. We also examine possible misregulation through cascade effects that could be driven by interacting gene networks or co-option of off-targetcis-regulatory elements.
Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis
Authors: Gong Weiming , Guo Ping , Liu Lu , Guan Qingbo , Yuan Zhongshang
Published: December 2020

Idiopathic pulmonary fibrosis (IPF) is a type of scarring lung disease characterized by a chronic, progressive, and irreversible decline in lung function. The genetic basis of IPF remains elusive. A transcriptome-wide association study (TWAS) of IPF was performed by FUSION using gene expression weights of three tissues combined with a large-scale genome-wide association study (GWAS) dataset, totally involving 2,668 IPF cases and 8,591 controls. Significant genes identified by TWAS were then subjected to gene ontology (GO) and pathway enrichment analysis. The overlapped GO terms and pathways between enrichment analysis of TWAS significant genes and differentially expressed genes (DEGs) from the genome-wide mRNA expression profiling of IPF were also identified. For TWAS significant genes, protein–protein interaction (PPI) network and clustering modules analyses were further conducted using STRING and Cytoscape. Overall, TWAS identified a group of candidate genes for IPF under the Bonferroni corrected P value threshold (0.05/14929 = 3.35 × 10–6), such as DSP (PTWAS = 1.35 × 10–29 for lung tissue), MUC5B (PTWAS = 1.09 × 10–28 for lung tissue), and TOLLIP (PTWAS = 1.41 × 10–15 for whole blood). Pathway enrichment analysis identified multiple candidate pathways, such as herpes simplex infection (P value = 7.93 × 10–5) and antigen processing and presentation (P value = 6.55 × 10–5). 38 common GO terms and 8 KEGG pathways shared by enrichment analysis of TWAS significant genes and DEGs were identified. In the PPI network, 14 genes (DYNLL1, DYNC1LI1, DYNLL2, HLA-DRB5, HLA-DPB1, HLA-DQB2, HLA-DQA2, HLA-DQB1, HLA-DRB1, POLR2L, CENPP, CENPK, NUP133, and NUP107) were simultaneously detected by hub gene and module analysis. In conclusion, through integrative analysis of TWAS and mRNA expression profiles, we identified multiple novel candidate genes, GO terms and pathways for IPF, which contributes to the understanding of the genetic mechanism of IPF.
Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma
Authors: Tombolan Lucia , Millino Caterina , Pacchioni Beniamina , Cattelan Manuela , Zin Angelica , Bonvini Paolo , Bisogno Gianni
Published: December 2020

Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.
Bioinformatics Analysis of Actin Molecules: Why Quantity Does Not Translate Into Quality?
Authors: Glyakina Anna V. , Galzitskaya Oxana V.
Published: December 2020

It is time to review all the available data and find the distinctive characteristics of actin that make it such an important cell molecule. The presented double-stranded organization of filamentous actin cannot explain the strong polymorphism of actin fibrils. In this work, we performed bioinformatics analysis of a set of 296 amino acid actin sequences from representatives of different classes of the Chordate type. Based on the results of the analysis, the degree of conservatism of the primary structure of this protein in representatives of the Chordate type was determined. In addition, 155 structures of rabbit actin obtained using X-ray diffraction analysis and electron microscopy have been analyzed over the past 30 years. From pairwise alignments and the calculation of root-mean-square deviations (RMSDs) for these structures, it follows that they are very similar to each other without correlation with the structure resolution and the reconstruction method: the RMSDs for 11,781 pairs did not exceed 3 Å. It turned out that in rabbit actin most of the charged amino acid residues are located inside the protein, which is not typical for the protein structure. We found that two of six exon regions correspond to structural subdomains. To test the double-stranded organization of the actin structure, it is necessary to use new approaches and new techniques, taking into account our new data obtained from the structural analysis of actin.
Teasaponin Ameliorates Murine Colitis by Regulating Gut Microbiota and Suppressing the Immune System Response
Authors: Yang Huan , Cai Rui , Kong Ziyan , Chen Ying , Cheng Chen , Qi Suhua , Gu Bing
Published: December 2020

Background: Dietary intervention is an exciting topic in current research of inflammatory bowel disease (IBD). The effect of teasaponin (TS) on IBD has not been fully elucidated. Here, we aim to investigate the intestinal anti-inflammatory activity of TS in a dextran sodium sulfate (DSS)-induced colitis mouse model and identify potential mechanisms.

Methods: We applied TS to mice with DSS-induced colitis and then monitored the body weight, disease activity index (DAI) daily. When sacrificed, the intestinal permeability was measured. The analysis of mucin and tight junction proteins was conducted. We detected the inflammatory cytokines, the immune cells and related inflammatory signaling pathways. In addition, the gut microbiota were analyzed by 16S rRNA sequencing and we also performed fecal microbiota transplantation (FMT).

Results: It showed that TS ameliorated the colonic damage by lowering the DAI, prolonging the colon length, reducing inflammatory cytokines and improving the mucus barrier. Parallel to down-regulation of the inflammatory cytokines, the fecal lipocalin 2, p-P65, p-STAT3, and neutrophil accumulation were also decreased in TS-treated mice. Microbiota characterization showed that Campylobacteria, Proteobacteria, Helicobacter, and Enterobacteriaceae were the key bacteria associated with IBD. In addition, TS could reverse the Firmicutes/Bacteroidetes (F/B) ratio and increase the beneficial bacteria, including Akkermansia and Bacteroides. TS ameliorated DSS-induced colitis by regulating the gut microbiota, and the gut microbiota could regulate gut inflammation.

Conclusions: These studies demonstrated that TS ameliorated murine colitis through the modulation of immune response, mucus barrier and gut microbiota, thus improving gut dysbiosis. In addition, the gut microbiota may play an important role in regulating the host's innate immune system, and the two coexist and are mutually beneficial. We provide a promising perspective on the clinical treatment of IBD.