bluuebunny/crossref_metadata_2025 huggingface dataset:
Метафорическая репрезентация лжи и обмана (на материале современной российской прессы)
Authors: Małecki Łukasz
Published: March 2021

Метафоре отводится роль одного из наиболее продуктивных средств формирования вторичных наименований в создании языковой картины мира, которая обладает свойством навязывать говорящим на определенном языке специфичный взгляд на мир. Современная когнитивная лингвистика считает метафору не тропом, призванным украсить речь и сделать образ более понятным, а формой мышления. В коммуникативной деятельности метафора – важное средство воздействия на интел-лект, чувства и волю адресата. В настоящее время в повседневной коммуникации отмечается повышенная агрессивность высказываний, активное использование кон-фронтационных стратегий и тактик речевого поведения, напр., всевозможных угроз, игнорирования, дискредитации, наклеивания ярлыков, оскорбления, а также обмана. Обман, несомненно, принадлежит к наиболее значимым социальным явлениям, но одновременно он отличается и высокой степенью абстрактности. Абстрактность семантического наполнения обмана, в свою очередь, побуждает обращаться к лек-сике с более конкретным значением. Настоящая статья посвящена рассмотрению метафоры в качестве средства вербализации лжи и обмана в современном русском языке. Объект исследования – метафора, функционирующая в языке современной русскоязычной газеты, в свою очередь предмет – метафора, очерчивающая языковую реализацию лжи и обмана, являющаяся ярким средством вербализации оценки, в частности и в печатных СМИ. Материалом исследования послужили русскоя-зычные газетно-публицистические тексты ведущих высокотиражных печатных изданий, напр.: «Новая газета», «Независимая газета», «Вести», «Российская газета», «Коммерсантъ» и др. В результате анализа фактического материала, отобранного из современной русскоязычной печати, возможным является выделение несколь-ких схем, метафорических моделей, которые вскрывают механизм метафориче-ского описании обмана и его разновидностей. В большей степени оказываются востребованными конфликтные, агрессивно воздействующие метафоры обмана (криминальные и милитарные), метафоры водной стихии (гидронимные), а также экономические, морбиальные и антропоморфные. Обман, ложь, фейк чаще всего характеризуются как сущности, неподконтрольные человеку, независимые от него, хотя им вербализованные в речи с моделированием целой системы схем. Кроме этого, в русскоязычной печати обман и его разновидности воспринимаются как самостоятельные, всепроникающие, нередко мистические сущности, перед которыми человек оказывается слабым и бессильным существом, характеризующие человека как пассивного, невластного над своей деятельностью, склонного к зависимости от неких более могущественных сил.
Media aesthetic component in special projects of the “Arguments and Facts” edition
Authors: Simakova Svetlana , Topchii Irina
Published: March 2021

The article examines the special projects of the publication “Arguments and Facts”, which are a polycode journalistic text, determines the role of the media aesthetic component in creating a publicistic image. The theoretical basis of the research was the works of M. A. Berezhnoy, M. V. Zagidullina, E. Kats. The case method made it possible to characterize the main features of a polycode media text in terms of media aesthetic potential: interactivity, conceptual design, and organization of space. Together they allow you to create a coherent, convincing, expressive image, to establish contact with the addressee.
МЕТОДИ ПРОФІЛАКТИКИ ПРОФЕСІЙНОЇ ДЕФОРМАЦІЇ ОСОБИСТОСТІ ПЕДАГОГА
Authors: Холковська Ірина , Вацьо Михайло
Published: March 2021

The article analyzes literature sources on the problem of prevention of professional deformity of the teacher's personality. The tasks of preventing professional deformities of the teacher's personality are defined. The essence of types of prevention of occupational deformity is revealed: primary, secondary, tertiary. It is noted that the prevention of professional deformity of the individual has a complex character and is implemented in two main areas: non-specialized psychological and pedagogical assistance, which consists in psychological and pedagogical support, the organization of optimal conditions that ensure the comfortable functioning of specialists, their development and prevention of the influence of undesirable factors of the professional environment; specialized psychological assistance, which consists in psychological counseling, psychological correction, psychological rehabilitation.
The effectiveness of the methods that make up the program of socio-mass primary psychological and pedagogical prevention of professional deformity; the program of pre-crisis psychological prevention; the program of rapid prevention; the program of individual prevention is analyzed.
The presented model of prevention of professional deformity of the teacher's personality, which provides for a complex impact on the macro-level (work with objective factors of professional deformation), meso-level (work with objective-subjective factors of professional deformation), micro-level (work with subjective factors of professional deformation) in order to restore and improve the psychophysiological health of teachers, harmonization of their relations with students and colleagues, prevention of professional destruction, development of the desire for self-actualization, mastering the methods of mental self-regulation, formation of the ability to self-development and development of stress-resistant behavior skills.
ПОЗААУДИТОРНА РОБОТА ЯК ЗАСІБ ФОРМУВАННЯ ГРОМАДЯНСЬКОСТІ МАЙБУТНІХ УЧИТЕЛІВ
Authors: Задворняк Людмила
Published: March 2021

Civic education of students, aimed at the development of citizenship as an integrative quality of personality, is one of the pressing problems of the modern Ukrainian state, which combines: internal freedom and respect for state power, love for the Motherland and desire for peace, self-esteem and discipline, manifestation of patriotic feelings and culture of interethnic communication. The social significance of the problem of citizenship development is determined by the need of society in the social activity of students and the need to educate them in the qualities included in the concept of "citizenship". The article reveals the essence and content of the concepts "extracurricular activities", "citizenship"; the socio-historical preconditions and theoretical and pedagogical aspects of the development of citizenship of student youth in the process of extracurricular educational work are substantiated. The article is devoted to topical issues of organization of extracurricular activities of students of pedagogical institutions of higher education as a means of formation and development of their citizenship. The main forms and directions of organization of extracurricular activities of higher education seekers are considered, its potential in the formation of citizenship of future teachers is determined. The process of educating a young person is carried out in various areas of his environment: family, school, team, media and more. They are designed to promote the development of the individual, involving him in civic values, which are revived in modern Ukrainian society by humanistic universal ideals of freedom, goodness, humanism, human dignity, citizenship and patriotism. Purposeful and effectively organized extracurricular activities have a huge potential for the formation of citizenship of future teachers through the development of their pedagogical and creative abilities, self-realization, self-expression and self-development. Various forms of extracurricular work have great potential for shaping the worldview of future teachers, as they unite those who have different interests, which creates conditions for their effective communication. Clearly organized extracurricular activities allow to create conditions for self-realization of students of a pedagogical institution of higher work. This is possible through their participation in various amateur activities, competitions, charity events, etc. The effectiveness of extracurricular activities to form a certain worldview of the younger generation using the potential of extracurricular activities is an integral component of the vocational education system.
Дослідження про мілітарний сегмент гетьманського двору в ранньомодерній Україні
Authors: Федорук Андрій
Published: March 2021

Рецензія на книгу: Олексій Сокирко. На варті булави. Надвірні війська українських гетьманів середини XVII – другої половини XVIII ст.: науково-популярне видання. – К.: Темпора, 2018. – 184 с.: іл.
Adaptive system for visualization of the electromagnetic scattering field of aircraft
Authors: Kurbanismailov Z. M. , Tarlanov A. T. , Matyash E. D. , Karbova E. S.
Published: March 2021

The space industry has always set ambitious tasks to create unique equipment, including control equipment. Ensuring electromagnetic compatibility (EMC)  of  such systems is carried out at all stages of the life cycle of an aircraft (AC), starting from its development, including testing and stages of  operation. Digital technology is characterized by high noise immunity.  However, any modern technical system in the aggregate contains sensors, communication lines and receiving  antennas sensitive to the effects of external interfering signals that propagate both through wires and over the air. Hence, the relevance of ensuring the EMC of integrated technical systems that perform the functions  of  measurement, data processing and the formation of control actions, both digital and analog, is obvious. The electromagnetic compatibility of a sophisticated aircraft or spaceship technical system with other systems is a prerequisite for their sustainable operation. Aerospace technology, where both highly sensitive measurements and energetic control effects are closely combined in the dense layout of an aircraft, requires a solution to the EMC problem. This paper shows the need for effective technology to control the electromagnetic radiation created in the surrounding space, both by subsystems of aircraft and by the whole object. A method for visualizing 3D electromagnetic field both in space and in time is considered.
CIDADES SAUDÁVEIS E SUSTENTÁVEIS
Authors: Pereira Spinieli André Luiz , De Paula Souza Letícia
Published: March 2021

O desenvolvimento das cidades fez com que a estrutura urbana se tornasse apta a configurar espaços de exclusões, desigualdades e desprezos ao bem-estar e à qualidade de vida de seus habitantes. Têm-se buscado medidas práticas que objetivem garantir o direito ao ambiente urbano saudável, equilibrado e acessível, sobretudo para os grupos vulneráveis, dentre os quais destacamos as pessoas com deficiência, que são vítimas dos problemas de inacessibilidade e exclusão socioespacial. Adotando-se o método dedutivo, a partir de uma abordagem descritiva e documental de direitos humanos e urbanismo, este trabalho tem como finalidade apresentar criticamente o novo modelo de cidade sustentável e saudável, bem como sua proposta de inversão da lógica de exclusão das pessoas com deficiência, que, atingidas pela ausência de infraestrutura urbana adequada, têm seus direitos humanos violados. Por meio dos novos meios de se pensar o urbanismo, entende-se que as cidades saudáveis e sustentáveis se encontram em constante vínculo com o direito à acessibilidade urbana para pessoas com deficiência. Como direito instrumental, essa categoria permite que a cidade seja usufruída por todos em tom de igualdade, assim como abre vias para que seja utilizada como meio para a realização da inclusão social e do direito à cidade.
Corto Circuito: preservación histórica y cultural de una ciudad
Authors: Agudelo Guisao Daniela , Palacios Mena Angie Lizeth
Published: March 2021

Despertó interés por parte de estudiantes pertenecientes al programa de Comunicación Audiovisual y Digital y al semillero de investigación, “Memoria y Región” de la Fundación Universitaria del Área Andina por investigar el fenómeno que surgió a partir del evento cultural pereirano, Corto Circuito, el cual consta de cinco instituciones educativas y culturales en el centro de Pereira, que se unen para ofrecer una noche desbordada de arte, cultura y ciudad.Inicialmente, se propuso realizar cuatro productos audiovisuales para Corto Circuito, que homenajeen sus 15 años de realización, donde se narre su historia y funcionamiento actual, también productos de promoción que fortalezcan y aumenten la asistencia. A partir de esta idea, se realizaron entrevistas semiestructuradas a los gestores de cada institución, artistas y a una fundadora, con el fin de obtener información de primera mano de las personas que son la base sólida de este y recopilarla en los productos.
La cuarta revolución industrial 4.0 y la perspectiva de la profesión del contador público al futuro
Authors: Gil Cumaco Mateo , Urrea López Diego Fernando
Published: March 2021

El mundo actual se encuentra viviendo un sin número de cambios significativos los cuales ha afectado a la humanidad en todas sus vivencias, una de ellas es la Revolución Industrial 4.0 la cual ha generado cambios relevantes fomentado que los nuevos profesionales contables exploren otros campos de acción y se puedan evidenciar en el mundo digital y tecnológico como una profesión cambiante y perdurable en el tiempo, por tal motivo, es de gran importancia realizar un ejercicio investigativo del Contador Público y la perspectiva que este tiene frente a este nuevo mundo de la revolución Industrial.
Maduración biológica de patinadores entre 8 y 16 años de las ciudades de Pereira y Cartago
Authors: García Zapata Natalia , Sánchez García Alejandra , Rodas Domínguez Laura Marcela , Gómez Rodas Alejandro
Published: March 2021

Introducción:El patinaje de velocidad es un deporte de iniciación temprana que clasifica categorías según edad cronológica provocando que competencias y entrenamientos no estén acordes al desarrollo biológico. El objetivo de esta investigación será determinar las características de la maduración biológica en patinadores entre los 8 y 16 años de las ciudades de Pereira y Cartago.Métodos: Estudio cuantitativo observacional analítico con muestra no probabilística intencionada de 60 patinadores. Se realizará predicción de velocidad pico de crecimiento mediante ecuación de regresión lineal propuesta por Mirwald y colaboradores a partir de medidas antropométricas.Resultados esperados: Conocimiento acerca de procesos de crecimiento y desarrollo biológico en patinadores de 8 – 16 años y establecimiento de baremos comparativos con otras con otras poblaciones.Impactos esperados: Mejoramiento y adecuación de la dosificación de las intensidades volúmenes y densidades de entrenamiento acordes a los procesos de crecimiento y desarrollo de deportistas en formación.
J’écris ensemble : quelques propositions
Authors: Giguère Nicholas
Published: March 2021

Dans sa réponse littéraire aux articles du numéro spécial des Cahiers de la Société bibliographique du Canada, « Œuvrer ensemble. Les rouages collectifs dans la chaîne du livre», Giguère traque dans ses derniers retranchements le mythe du génie solitaire seul responsable de ses forfaits littéraires; un mythe persistant, mais désormais intenable pour les historiens du livre. Giguère propose en fait que le « je » écrit toujours en collaboration avec d’autres agents.
“French-English Translation in Canada” by Maynard Gertler
Authors: Panofsky Ruth
Published: March 2021

“French-English Translation in Canada” is the transcript of a talk given by Montreal publisher Maynard Gertler to an unidentified audience in 1976. When Gertler founded Harvest House in 1959, his aim was to issue the first English-language translations of the works of Québécois writers in inexpensive, accessible editions. The talk is a document of enduring value that provides incisive analysis of contemporary Canadian publishing and presents the challenges facing a domestic publisher who was committed to issuing French works in English translation.
Isolation and identification of different compounds from Citrus assamensis leaf
Authors: Shahriar Mohammad Shahriar , Bhuiyan Mohiuddin Ahmed , Rana Md Sohel
Published: March 2021

Six coumarins, one benzene, one flavone, one acridone, one limonoid, one triterpene and two phytosterol derivatives were isolated from the methanol, ethanol and chloroform leaf extracts of Citrus assamensis. Extensive spectroscopic studies, including high field 1H NMR and 13C NMR analyses, allowed the identification of thirteen known compounds as bergapten (1), umckalin (2), citropten (3), 4-hydroxybenzaldehyde (4), bergamottin (5), β-amyrin (6), umbeliferone (7), scopoletin (8), citrusinol (9), citracridone-III (10), limonin (11), stigmasterol (12), and β-sitosterol (13). The identity of these compounds was confirmed by comparison with published data as well as co-TLC with authentic samples.

Journal of Bangladesh Academy of Sciences, Vol. 44, No. 2, 85-93, 2020
Versatility of Latissimus Dorsi Free Flap-a Prospective Study
Authors: Islam Abu Faisal Md Ariful , Khan Mohammad Rabiul Karim , Sumi Sharmin Akter , Khan Mohammad Hedayet Ali , Kalam Md Abul
Published: March 2021

Introduction: Free flaps offer a great variable of available tissues to cover larger, multifocal or multistructural defects. The choice among different free flap is dependent upon their recipient site requirement. Reconstruction with latissimus dorsi flap is now versatile tool in coverage. It can resurface large wound with reliable vascularity, consistent anatomy ,long pedicle length, opportunity for tailoring of flap. It has less donor site morbidity and has very little post-operative complications.

Objective: To evaluate the versatility of free Latissimus dorsi flap for soft tissue reconstruction.

Materials and methods: A prospective, observational study design was used in Department of Plastic Surgery of Dhaka Medical College and Hospital. Here 20 patients with soft tissue defect of variable sizes over lower limb, head neck and trunk underwent coverage with microvascular surgery. The study was carried out from July 2017 to June 2018.

Result: Regarding the age distribution, the mean age was 35.65with an SD of + 10.81. The lowest age was 20years and the highest age was 56 years, Male female ratio was 3:2.The major cause (65.0%) of soft tissue defect of the samples was RTA. The flap was used to reconstruct the soft tissue defect over lower leg in 13 (65%)cases, on scalp 05 (25%) cases and over anterior trunk in two cases. The mean flap dimension was 229.25cm2 and its range was between 120 – 384 cm2. The standard myocutaneous flap was harvested in 80% cases, chimeric (10%) and partial Latissimus muscle flap in two cases. The donor site in all the 20 (100%) cases was closed primarily. The outcome of reconstruction was excellent in 16(80%), good in 02 (10%) cases and poor in 02 (10%) cases. There was no significant complication during the three months postoperative period.

Conclusion: The Latissimus dorsi flap is a versatile option for resurfacing the soft tissue defect in different areas of the body with variable flap components and with minimal donor site morbidity.

J Dhaka Medical College, Vol. 28, No.2, October, 2019, Page 142-152
Perfil de mães de recém-nascidos pré-termo em um município do semiárido cearense
Authors: Otaviano Maria Danara Alves , Silva Maria Adelane Monteiro da , Sousa Francisca Júlia dos Santos , Mesquita Anna Larissa Moraes , Portela Tainá de Jesus Alves , Brandão Maria Girlane Sousa Albuquerque , Sousa Francisca Erandielly Lopes
Published: March 2021

Objetivo: Delinear o perfil socioeconômico e obstétrico de mães com filhos pré-termo em um município do semiárido cearense. Métodos: Trata-se de um estudo descritivo, documental, retrospectivo, com abordagem quantitativa. A fonte utilizada para a coleta foi a base de dados de um município da região norte do Estado do Ceará, alimentada a partir de entrevistas aplicadas a todas as puérperas que deram à luz nas maternidades locais no ano de 2015. As informações foram processadas usando o software EPI INFO 6.0 e o programa Excel 2007. Os dados foram analisados por meio de estatística descritiva. Os princípios da Resolução nº 466/2012, aprovados pelo Comitê de Ética sob número de protocolo 1.590.501, foram respeitados. Resultados: O perfil socioeconômico das puérperas no ano de 2015 foi de 74,6% na faixa etária de 20 a 35 anos e 45,7% com renda menor que um salário-mínimo 37,8% com ensino médio completo. Quanto ao perfil obstétrico, 88,1% tinha de 1 a 3 gestações e 51,1% realizou sete ou mais consultas de pré-natal. O tipo de parto prevalente foi à cesárea (69,8%). As intercorrências evidenciadas foram: infecção urinária, ameaça de parto prematuro e infecção vaginal, associada a parto prematuro. As puérperas de menor renda apresentaram maiores porcentagens de infecção do trato urinário e infecção vaginal. Conclusões: As características encontradas em mulheres com parto prematuro neste estudo não diferem dos achados da literatura, contudo, evidenciou-se a relação da infecção urinária com a prematuridade e a influência das condições socioeconômicas neste desfecho neonatal.
Efeitos fotobiomoduladores das luzes vermelha, azul e verde sobre o colágeno durante o processo de cicatrização de queimaduras cutâneas: uma revisão integrativa
Authors: Souza Alana Olivia Nascimento de , Catão Maria Helena Chaves de Vasconcelos
Published: March 2021

Introdução: A cicatrização de feridas é um mecanismo que envolve uma sequência de eventos moleculares com o objetivo de reparo tecidual. Neste sentido, destaca-se o uso fototerapia LED e laser devido as suas características bioestimulantes para a célula durante o processo de reparo. Objetivo: realizar uma revisão de literatura com o intuito de observar o efeito fotobiomodulador das luzes vermelha, azul e verde sobre o colágeno durante o processo de cicatrização de queimaduras. Metodologia: trata-se de uma revisão de literatura do tipo integrativa, realizada nas bases de dados Pubmed, Web of Science e Lilacs.  Resultados: entre os 1721 estudos encontrados, somente 18 artigos, publicados entre os anos de 2011 a 2020, foram utilizados dos resultados. Conclusão: A fotobiomodulação das luzes vermelha, azul e verde no processo de reparo de queimaduras cutâneas mostrou resultados satisfatórios principalmente em relação a produção de colágeno, angiogênese, redução da inflamação, redução do tamanho da lesão e estímulo de fibroblastos.
Imagining the Commoning Library: Alter-Neoliberal Pedagogy in Informational Capitalism
Authors: Soudias Dimitris
Published: March 2021

The ascent of neoliberalism and informational capitalism has been largely successful in privatizing and re-regulating state-subject-market relations in ways that treat them “as if” they are a market situation. Here, we observe both the increasing commodification of digital forms of knowledge, as well as the commodification of the access to this knowledge. As predominantly non-commercial spaces, libraries serve the vital function of deflecting these developments. In this article, I argue for going one step further and imagining libraries as institutionalized and pedagogical spaces that can negotiate and transgress their institutional limits vis-à-vis public and private resources, discourses, policies, and technologies for the purpose of furthering the commons. In so doing, libraries serve as alter-neoliberal pedagogies, which democratize the construction and deconstruction of knowledge, as well as the access to them. Here, alternative literacies, ways of learning, and ways of being can be prefigured in practice. In imagining these conceptual potentialities of academic and public libraries, this article sets forth an initial agenda toward the commoning library.
THE EFFECT OF STORY TELLING METHOD ON SOCIAL STUDIES LEARNING RESULTS OF CLASS IV ELEMENTARY SCHOOLS
Authors: Sahara Annisa Elva , Supratno Haris , Rochmania Desty Dwi
Published: March 2021

Adding insights about the results of the pretest-posttest as well as the influence of when or without using the storytelling method on social studies learning results in grade IV elementary schools is the purpose of this study. The research design used was a quasi-experimental design with a pretest-posttest design, non equivalent control group design. Where examining two groups, that is the experimental class and the control class in one class. Grade IV elementary school students, that is group A and group B are the population in this study. Sampling technique is a technique used in determining research samples. The test of student social studies learning results (cognitive) that has been tested for validity by experts is a research instrument. The test analysis used is the normality test and hypothesis testing. The results showed that there was a significant influence in the use of storytelling methods on social studies learning results. The results of the t-test show that learning without using the method of storytelling is in the control class with tcount (7,786)> ttable (2.131). The same from the t test on learning using the story telling method, is in the experimental class with tcount (10.647)> t table (2.131). This proves that there is a positive influence on the use of storytelling methods on social studies learning results in grade IV elementary schools. The use of the storytelling method can help teachers in providing creative learning, giving students freedom in conveying their ideas and creativity in understanding the material and being presented in learning that is not boring will make students interested in the learning that takes place so that the material can be conveyed well.
The Emerging Roles of Axonemal Glutamylation in Regulation of Cilia Architecture and Functions
Authors: Yang Wen-Ting , Hong Shi-Rong , He Kai , Ling Kun , Shaiv Kritika , Hu JingHua , Lin Yu-Chun
Published: March 2021

Cilia, which either generate coordinated motion or sense environmental cues and transmit corresponding signals to the cell body, are highly conserved hair-like structures that protrude from the cell surface among diverse species. Disruption of ciliary functions leads to numerous human disorders, collectively referred to as ciliopathies. Cilia are mechanically supported by axonemes, which are composed of microtubule doublets. It has been recognized for several decades that tubulins in axonemes undergo glutamylation, a post-translational polymodification, that conjugates glutamic acid chains onto the C-terminal tail of tubulins. However, the physiological roles of axonemal glutamylation were not uncovered until recently. This review will focus on how cells modulate glutamylation on ciliary axonemes and how axonemal glutamylation regulates cilia architecture and functions, as well as its physiological importance in human health. We will also discuss the conventional and emerging new strategies used to manipulate glutamylation in cilia.
ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC
Authors: Chang Ruimin , Xiao Xiaoxiong , Fu Yao , Zhang Chunfang , Zhu Xiaoyan , Gao Yang
Published: March 2021

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.
Guidelines for Regulated Cell Death Assays: A Systematic Summary, A Categorical Comparison, A Prospective
Authors: Hu Xi-min , Li Zhi-xin , Lin Rui-han , Shan Jia-qi , Yu Qing-wei , Wang Rui-xuan , Liao Lv-shuang , Yan Wei-tao , Wang Zhen , Shang Lei , Huang Yanxia , Zhang Qi , Xiong Kun
Published: March 2021

Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.
Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment
Authors: Liu Jinlong , Wang Yuchen , Qiu Zhidong , Lv Guangfu , Huang Xiaowei , Lin He , Lin Zhe , Qu Peng
Published: March 2021

The tumor microenvironment (TME) is composed of tumor cells, blood/lymphatic vessels, the tumor stroma, and tumor-infiltrating myeloid precursors (TIMPs) as a sophisticated pathological system to provide the survival environment for tumor cells and facilitate tumor metastasis. In TME, TIMPs, mainly including tumor-associated macrophage (TAM), tumor-associated dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs), play important roles in repressing the antitumor activity of T cell or other immune cells. Therefore, targeting those cells would be one novel efficient method to retard cancer progression. Numerous studies have shown that traditional Chinese medicine (TCM) has made extensive research in tumor immunotherapy. In the review, we demonstrate that Chinese herbal medicine (CHM) and its components induce tumor cell apoptosis, directly inhibiting tumor growth and invasion. Further, we discuss that TCM regulates TME to promote effective antitumor immune response, downregulates the numbers and function of TAMs/MDSCs, and enhances the antigen presentation ability of mature DCs. We also review the therapeutic effects of TCM herbs and their ingredients on TIMPs in TME and systemically analyze the regulatory mechanisms of TCM on those cells to have a deeper understanding of TCM in tumor immunotherapy. Those investigations on TCM may provide novel ideas for cancer treatment.
SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis
Authors: Galeano-Otero Isabel , Del Toro Raquel , Khatib Abdel-Majid , Rosado Juan Antonio , Ordóñez-Fernández Antonio , Smani Tarik
Published: March 2021

Angiogenesis is a multistep process that controls endothelial cells (ECs) functioning to form new blood vessels from preexisting vascular beds. This process is tightly regulated by pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which promote signaling pathways involving the increase in the intracellular Ca2+ concentration ([Ca2+]i). Recent evidence suggests that store-operated calcium entry (SOCE) might play a role in angiogenesis. However, little is known regarding the role of SARAF, SOCE-associated regulatory factor, and Orai1, the pore-forming subunit of the store-operated calcium channel (SOCC), in angiogenesis. Here, we show that SOCE inhibition with GSK-7975A blocks aorta sprouting, as well as human umbilical vein endothelial cell (HUVEC) tube formation and migration. The intraperitoneal injection of GSK-7975A also delays the development of retinal vasculature assessed at postnatal day 6 in mice, since it reduces vessel length and the number of junctions, while it increases lacunarity. Moreover, we find that SARAF and Orai1 are involved in VEGF-mediated [Ca2+]i increase, and their knockdown using siRNA impairs HUVEC tube formation, proliferation, and migration. Finally, immunostaining and in situ proximity ligation assays indicate that SARAF likely interacts with Orai1 in HUVECs. Therefore, these findings show for the first time a functional interaction between SARAF and Orai1 in ECs and highlight their essential role in different steps of the angiogenesis process.
Targeting Endosomal Recycling Pathways by Bacterial and Viral Pathogens
Authors: Yong Xin , Mao Lejiao , Shen Xiaofei , Zhang Zhen , Billadeau Daniel D. , Jia Da
Published: March 2021

Endosomes are essential cellular stations where endocytic and secretory trafficking routes converge. Proteins transiting at endosomes can be degraded via lysosome, or recycled to the plasma membrane, trans-Golgi network (TGN), or other cellular destinations. Pathways regulating endosomal recycling are tightly regulated in order to preserve organelle identity, to maintain lipid homeostasis, and to support other essential cellular functions. Recent studies have revealed that both pathogenic bacteria and viruses subvert host endosomal recycling pathways for their survival and replication. Several host factors that are frequently targeted by pathogens are being identified, including retromer, TBC1D5, SNX-BARs, and the WASH complex. In this review, we will focus on the recent advances in understanding how intracellular bacteria, human papillomavirus (HPV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijack host endosomal recycling pathways. This exciting work not only reveals distinct mechanisms employed by pathogens to manipulate host signaling pathways, but also deepens our understanding of the molecular intricacies regulating endosomal receptor trafficking.
m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer
Authors: Zhao Huaying , Xu Yue , Xie Yilin , Zhang Lan , Gao Ming , Li Shenglei , Wang Feng
Published: March 2021

N6 methyladenosine (m6A) RNA methylation regulators play an important role in the development of tumors. However, their function in esophageal cancer (EC) has not been fully elucidated. Here, we analyzed the gene expression data of 24 major m6A RNA methylation regulators from 775 patients with EC from TCGA dataset. The present study showed the aberrations of m6A regulators in genome were correlated to prognosis in human ECs. Meanwhile, 17 m6A regulators showed increased expression in EC samples, including YTHDC1, IGF2BP2, FTO, METTL14, YTHDF3, RBM15, WTAP, HNRNPA2B1, HNRNPC, ALKBH5, YTHDF2, METTL16, IGF2BP3, VIRMA, RBM15B, YTHDF1, KIAA1429, HAKAI, and ZC3H13. Among them, we found HNRNPC, YTHDC2, WTAP, VIRMA, IGF2BP3, and HNRNPA2B1 were significantly correlated to worse outcomes and advanced stage in EC. Furthermore, we showed levels of m6A regulators is correlated with the expression of Immuno-regulators (Immunoinhibitors, Immunostimulators, and MHC molecules) and immune infiltration levels in EC. Bioinformatics further confirm m6A regulators were involved in regulating RNA splicing, RNA stability, and cell proliferation. Our study showed m6A regulators are promising targets and biomarkers for cancer immunotherapy in EC.
Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?
Authors: Rorabaugh Boyd R.
Published: March 2021

Prenatal exposure to an adverse uterine environment can have long lasting effects on adult offspring through DNA methylation, histone acetylation, and other epigenetic effects that alter gene expression and physiology. It is well-known that consumption of CNS stimulants such as caffeine, nicotine, amphetamines, and cocaine during pregnancy can adversely impact the offspring. However, most work in this area has focused on neurological and behavioral outcomes and has been limited to assessments in young offspring. The impact of prenatal exposure to these agents on the adult cardiovascular system has received relatively little attention. Evidence from both animal and human studies indicate that exposure to CNS stimulants during the gestational period can negatively impact the adult heart and vasculature, potentially leading to cardiovascular diseases later in life. This review discusses our current understanding of the impact of prenatal exposure to cocaine, methamphetamine, nicotine, and caffeine on the adult cardiovascular system.
Mesoscopic Optical Imaging of the Pancreas—Revisiting Pancreatic Anatomy and Pathophysiology
Authors: Alanentalo Tomas , Hahn Max , Willekens Stefanie M. A. , Ahlgren Ulf
Published: March 2021

The exocrine-endocrine multipart organization of the pancreas makes it an exceedingly challenging organ to analyze, quantitatively and spatially. Both in rodents and humans, estimates of the pancreatic cellular composition, including beta-cell mass, has been largely relying on the extrapolation of 2D stereological data originating from limited sample volumes. Alternatively, they have been obtained by low resolution non-invasive imaging techniques providing little detail regarding the anatomical organization of the pancreas and its cellular and/or molecular make up. In this mini-review, the state of the art and the future potential of currently existing and emerging high-resolution optical imaging techniques working in the mm-cm range with μm resolution, here referred to as mesoscopic imaging approaches, will be discussed regarding their contribution toward a better understanding of pancreatic anatomy both in normal conditions and in the diabetic setting. In particular, optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) imaging of the pancreas and their associated tissue processing and computational analysis protocols will be discussed in the light of their current capabilities and future potential to obtain more detailed 3D-spatial, quantitative, and molecular information of the pancreas.
Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes
Authors: Bayliss Jacqueline , Ooi Geraldine J. , De Nardo William , Shah Yazmin Johari Halim , Montgomery Magdalene K. , McLean Catriona , Kemp William , Roberts Stuart K. , Brown Wendy A. , Burton Paul R. , Watt Matthew J.
Published: March 2021

Ectodysplasin A (EDA) was recently identified as a liver-secreted protein that is increased in the liver and plasma of obese mice and causes skeletal muscle insulin resistance. We assessed if liver and plasma EDA is associated with worsening non-alcoholic fatty liver disease (NAFLD) in obese patients and evaluated plasma EDA as a biomarker for NAFLD. Using a cross-sectional study in a public hospital, patients with a body mass index >30 kg/m2 (n=152) underwent liver biopsy for histopathology assessment and fasting liver EDA mRNA. Fasting plasma EDA levels were also assessed. Non-alcoholic fatty liver (NAFL) was defined as >5% hepatic steatosis and nonalcoholic steatohepatitis (NASH) as NAFLD activity score ≥3. Patients were divided into three groups: No NAFLD (n=45); NAFL (n=65); and NASH (n=42). Liver EDA mRNA was increased in patients with NASH compared with No NAFLD (P=0.05), but not NAFL. Plasma EDA levels were increased in NAFL and NASH compared with No NAFLD (P=0.03). Plasma EDA was related to worsening steatosis (P=0.02) and fibrosis (P=0.04), but not inflammation or hepatocellular ballooning. ROC analysis indicates that plasma EDA is not a reliable biomarker for NAFL or NASH. Plasma EDA was not increased in patients with type 2 diabetes and did not correlate with insulin resistance. Together, we show that plasma EDA is increased in NAFL and NASH, is related to worsening steatosis and fibrosis but is not a reliable biomarker for NASH. Circulating EDA is not associated with insulin resistance in human obesity.

Clinical Trial Registration

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000875505, identifier ACTRN12615000875505.
Not Only Environmental Conditions but Also Human Awareness Matters: A Successful Post-Crayfish Plague Reintroduction of the White-Clawed Crayfish (Austropotamobius pallipes) in Northern Italy
Authors: Manenti Raoul , Barzaghi Benedetta , Nessi Alessandro , Cioccarelli Sara , Villa Mauro , Ficetola Gentile Francesco
Published: March 2021

In Europe, invasive freshwater crayfish are not only changing freshwater ecosystems, but they are also leading to local extinctions of native freshwater crayfish. This is particularly evident for the populations of red swamp crayfish and spiny-cheek crayfish in northern Italy, which are threatening the last and isolated populations of the white-clawed crayfish. Here, we describe the steps that accompanied a successful reintroduction of the white-clawed crayfish in an Italian stream (Park Monte Barro) that, although isolated from other freshwater sites, suffered from an illegal introduction of the spiny-cheek crayfish in 2013. After the removal of presumably all the introduced spiny-cheek crayfish individuals, we started periodical surveys (twice a year) of the stream to confirm the absence of further introductions and to monitor environmental conditions. Prior to the reintroduction of the white-clawed crayfish that started in autumn 2018, we developed an intense dissemination activity to raise awareness of white-clawed crayfish features and importance among landowners surrounding the stream, including those suspected of the introduction of the spiny-cheek crayfish: we organized public meetings and we performed seven direct visits, house to house, to the local people providing information on good practices for white-clawed crayfish conservation. From 2018 to 2020, every autumn, we reintroduced a batch of 3-month-old white-clawed crayfish juveniles, and we developed a program for the monitoring of crayfish growth and density, water quality, and direct landowners’ disturbance of the site. We detected a significant increase of the white-clawed crayfish total length (TL) from the first reintroduction (October 2018) to June 2020. In 2020, crayfish were consistently larger than in the 2019 surveys; some of them were able to breed less than 2 years after the first reintroduction. In 2020, the estimated density of large crayfish reached 0.57 individuals/m2, which is lower than the density observed prior to extinction. We did not detect any case of human disturbance of the site. Our results underline that the reintroduction actions could be more effective when the stakeholders having the greatest potential impact on the species are identified, informed, and involved as primary caretakers of the activities.
Targeted RNA-Based Oxford Nanopore Sequencing for Typing 12 Classical HLA Genes
Authors: Johansson Tiira , Koskela Satu , Yohannes Dawit A. , Partanen Jukka , Saavalainen Päivi
Published: March 2021

Identification of human leukocyte antigen (HLA) alleles from next-generation sequencing (NGS) data is challenging because of the high polymorphism and mosaic nature of HLA genes. Owing to the complex nature of HLA genes and consequent challenges in allele assignment, Oxford Nanopore Technologies’ (ONT) single-molecule sequencing technology has been of great interest due to its fitness for sequencing long reads. In addition to the read length, ONT’s advantages are its portability and possibility for a rapid real-time sequencing, which enables a simultaneous data analysis. Here, we describe a targeted RNA-based method for HLA typing using ONT sequencing and SeqNext-HLA SeqPilot software (JSI Medical Systems GmbH). Twelve classical HLA genes were enriched from cDNA of 50 individuals, barcoded, pooled, and sequenced in 10 MinION R9.4 SpotON flow cell runs producing over 30,000 reads per sample. Using barcoded 2D reads, SeqPilot assigned HLA alleles to two-field typing resolution or higher with the average read depth of 1750x. Sequence analysis resulted in 99–100% accuracy at low-resolution level (one-field) and in 74–100% accuracy at high-resolution level (two-field) with the expected alleles. There are still some limitations with ONT RNA sequencing, such as noisy reads, homopolymer errors, and the lack of robust algorithms, which interfere with confident allele assignment. These issues need to be inspected carefully in the future to improve the allele call rates. Nevertheless, here we show that sequencing of multiplexed cDNA amplicon libraries on ONT MinION can produce accurate high-resolution typing results of 12 classical HLA loci. For HLA research, ONT RNA sequencing is a promising method due to its capability to sequence full-length HLA transcripts. In addition to HLA genotyping, the technique could also be applied for simultaneous expression analysis.
Selecting Classification Methods for Small Samples of Next-Generation Sequencing Data
Authors: Zhu Jiadi , Yuan Ziyang , Shu Lianjie , Liao Wenhui , Zhao Mingtao , Zhou Yan
Published: March 2021

Next-generation sequencing has emerged as an essential technology for the quantitative analysis of gene expression. In medical research, RNA sequencing (RNA-seq) data are commonly used to identify which type of disease a patient has. Because of the discrete nature of RNA-seq data, the existing statistical methods that have been developed for microarray data cannot be directly applied to RNA-seq data. Existing statistical methods usually model RNA-seq data by a discrete distribution, such as the Poisson, the negative binomial, or the mixture distribution with a point mass at zero and a Poisson distribution to further allow for data with an excess of zeros. Consequently, analytic tools corresponding to the above three discrete distributions have been developed: Poisson linear discriminant analysis (PLDA), negative binomial linear discriminant analysis (NBLDA), and zero-inflated Poisson logistic discriminant analysis (ZIPLDA). However, it is unclear what the real distributions would be for these classifications when applied to a new and real dataset. Considering that count datasets are frequently characterized by excess zeros and overdispersion, this paper extends the existing distribution to a mixture distribution with a point mass at zero and a negative binomial distribution and proposes a zero-inflated negative binomial logistic discriminant analysis (ZINBLDA) for classification. More importantly, we compare the above four classification methods from the perspective of model parameters, as an understanding of parameters is necessary for selecting the optimal method for RNA-seq data. Furthermore, we determine that the above four methods could transform into each other in some cases. Using simulation studies, we compare and evaluate the performance of these classification methods in a wide range of settings, and we also present a decision tree model created to help us select the optimal classifier for a new RNA-seq dataset. The results of the two real datasets coincide with the theory and simulation analysis results. The methods used in this work are implemented in the open-scource R scripts, with a source code freely available athttps://github.com/FocusPaka/ZINBLDA.