bluuebunny/crossref_metadata_2025 huggingface dataset:
Segregación de género: narrativas de mujeres desde la academia.
Authors: Sanhueza Díaz Lilian , Fernández Darraz Cecilia , Montero Vargas Luis
Published: April 2021

Este artículo analiza las narrativas de mujeres insertas en la academia respecto de las desventajas que enfrentan en relación a sus pares hombres. Para tal efecto, se desarrollaron tres grupos de discusión con participación de académicas y administrativas. Con el fin de contextualizar los relatos, se analizaron datos cuantitativos sobre brechas de género en educación de pre y post grado en Chile. Las preguntas formuladas para realizar este trabajo fueron: ¿cuáles son las narrativas que las mujeres construyen en torno a las prácticas de dominación en la academia? ¿Cómo explican la posición de desventaja que enfrentan? En el análisis realizado se constata la presencia de estructuras y simbolismos androcéntricos que reifican las relaciones tradicionales y estereotipos de género. Se visualizan fronteras simbólicas de género en un espacio laboral generizado y mercantilizado, que desvaloriza los aportes de las mujeres y promueve una concepción hegemónica-masculina del éxito y de la productividad.
Vulnerabilidad-resiliencia ante el proceso de riesgo-desastre: Un análisis desde la ecología política
Authors: Sandoval-Díaz José
Published: April 2021

Las nociones de vulnerabilidad y resiliencia se han instalado como categorías explicativas centrales del proceso de riesgo-desastre, tanto en lo académico como institucional. No obstante, ambas nociones se han configurado como significantes flotantes del campo discursivo de la gestión de riesgo de desastres, presentando distintos supuestos, expresiones, énfasis y formas relacionales. A partir de esto el presente trabajo busca analizar, en un primer momento la construcción del discurso de la vulnerabilidad-resiliencia en el campo académico-institucional, para posteriormente, explorar la producción de la vulnerabilidad y la emergencia de la resiliencia local, bajo el prisma del capitaloceno de corte extractivista de Chile. A modo de conclusión afirmamos la importancia de incorporar en la discusión de la reducción de riesgo de desastre, tanto el esclarecimiento conceptual, como la relación dialéctica diferencial entre vulnerabilidad-resiliencia a escala glocal, comprendiendo que el fortalecimiento de capacidades debe ir acompañado de la reducción de las injusticias espaciales y ambientales.
Los límites de la participación: un análisis de la política de participación ciudadana en Chile (2011-2018)
Authors: Carrasco Soto Sebastián
Published: April 2021

La crisis de representación a la que se ha enfrentado el sistema político chileno durante los últimos años ha generado cambios en el funcionamiento de la política formal. Uno de ellos ha sido la incorporación de canales para la participación de la ciudadanía en los asuntos públicos. En ese contexto, el presente artículo estudia el proceso de implementación de la participación ciudadana institucional y analiza su impacto en los procesos de toma de decisión. Aplicando una metodología de estudio de caso, se concluye que en Chile se ha ido construyendo un discurso participativo que no se corresponde con la experiencia empírica en materia de participación. La política pública se ha ido implementando paulatinamente en los organismos del gobierno central. No obstante, ha sido  escasamente incidental, e incluso instrumentalizada por designios políticos. Esto plantea un cuestionamiento teórico en torno al rol de la participación en la democracia.
Las largas trayectorias de cuidado remunerado de las familias peruanas en Córdoba, Argentina
Authors: Magliano María José , Zenklusen Denise
Published: April 2021

Este artículo se propone analizar las trayectorias de mujeres peruanas en el sector de los cuidados remunerados y sus continuidades generacionales. En base a un trabajo cualitativo longitudinal con mujeres migrantes de origen peruano que viven en barrios urbanos relegados de la ciudad de Córdoba (Argentina), y retomando los aportes teóricos de la perspectiva interseccional, indaga en la articulación entre migraciones, generaciones y trabajos de cuidado remunerados. El artículo muestra, primero, la centralidad de esos trabajos en las experiencias migratorias de mujeres peruanas, pioneras en muchos casos de la migración a Córdoba; segundo, el modo en que esos trabajos son heredados por sus hijas y las dificultades que estas jóvenes enfrentan para acceder y moverse hacia otros rubros del mercado de trabajo. Como conclusión, reflexiona sobre los alcances generacionales de la segregación laboral en las sociedades contemporáneas y la reproducción de desigualdades sociales asociadas a los trabajos de cuidado.
Bewertung der Wahrnehmung von Medizinstudenten über medizinische Genetik während des Kurses und des Berufslebens, in einem Universitätszentrum von Belém, Pará, Amazônia
Authors: Martins Carlos Henrique Lopes , Lima Gabriela Elenor dos Santos , Dendasck Carla Viana , Oliveira Ciane Martins de , Oliveira Euzébio de
Published: April 2021

Die Disziplin Genetik spielt eine grundlegende Rolle in der akademischen und beruflichen Ausbildung von Medizinstudenten. Daher ist es notwendig, dass ihre Wahrnehmung während der Basis-, Klinischen und Boarding-Zyklen des Kurses regelmäßig oder gut ist, so dass ein gutes professionelles Verhalten basieren und Impulse für die Gesundheit des Patienten konditionieren kann. Das Hauptziel der Studie ist es, die Wahrnehmung der Studenten der Medizinischen Fakultät für Medizinische Genetik während des Kurses und des Berufslebens in einem Universitätszentrum von Belém, Pará, Amazônia zu bewerten. Dies ist eine quantitative Forschung, bei der ein Fragebogen von den Forschern mit offenen und geschlossenen Fragen erstellt wurde. Die gesammelten Daten wurden analysiert und in Diagrammen und Tabellen tabelliert, die über Microsoft Excel 2017 entwickelt wurden. Wir befragten 120 Studenten vom 1. bis 12. Semester des Kurses, wobei 90% erklärten, dass sie Schwierigkeiten im Verlauf des Kurses hatten, 62,5% hatten ihr Wissen nach der Realisierung des gleichen erweitert, aber 75% waren der Ansicht, dass die Disziplin nicht ausreichte, um die gesamte Länge des Fachs zu adressieren. Es wird daher vorgeschlagen, dass die Studierenden einen größeren Kontakt mit dem Fach haben können, entweder in Form von Kursen oder außerschulischen Praktika.
ОБЛІК, АУДИТ ТА УПРАВЛІННЯ КРЕДИТОРСЬКОЮ ЗАБОРГОВАНІСТЮ
Authors: Бондаренко Ольга , Матвєєва Ольга , Ковальова Валерія
Published: April 2021

У даній статті досліджено теоретичні та практичні питання щодо визначення сутності кредиторської заборгованості, її руху в господарській діяльності; розглянуто основні методи проведення аудиту кредиторської заборгованості згідно до Міжнародних стандартів; особливості ефективного управління поточними зобов’язаннями підприємства; аналіз поточної кредиторської заборгованості; облік кредиторської заборгованості. Визначено місце поточних зобов’язань у діяльності підприємства. Повна та достовірна інформація забезпечує прийняття управлінських рішень щодо кредиторської заборгованості на підприємстві. Особливе місце в кредиторський заборгованості займають численні розрахунки з постачальниками і підрядниками. Ефективне управління кредиторською заборгованістю належить до необхідних умов успішної діяльності, оскільки воно створює передумови для швидкого розвитку бізнесу і збільшення фінансових можливостей підприємства.
Faktor-Faktor Yang Mempengaruhi Tax Avoidance (Study Empiris Pada Perusahaan Manufaktur Sektor Industri Dasar Dan Kimia Tahun 2014-2018
Authors: Warseno Warseno , Suseno Silpi Intan , Febriani Widya
Published: April 2021

This study aims to determine the effect of Profitability, Leverage, Firm Size and Institutional Ownership on Tax Avoidance in Manufacturing Companies in the Basic and Chemical Industrial Sector in 2014-2018. The variables used in this study are profitability, leverage, company size and institutional ownership, while the dependent variable used is tax avoidance which uses an effective tax rate proxy. The analysis technique used in this study is multiple linear regression analysis where previously the data were tested using a classic assumption test consisting of normality test, multicollinearity test, autocorrelation test and heteroscedasticity test. The results showed that partially Profitability affects tax Avoidance. Simultaneously Profitability, Leverage, Firm Size and Institutional Ownership affect tax avoidance. The contribution of the dependent variable in explaining the independent variable is only 12.6%.
Analisis Faktor Faktor Yang Mempengaruhi Kebijakan Deviden Pada Perusahaan Manufaktur Yang Terdaftar Di BEI 2012-2016
Authors: Debataraja Ristionom , Debataraja Mintauli , Jamaludin Putri Apriliani
Published: April 2021

Dividend are payments made by a corporate to shareholder members which is depend on the dividend policy of each company. The objective of this research is to analyze the influence of cash ratio, debt to equity ratio and return on asset to dividend policy from sample of companies. The population of this research is manufacture companies which listed in Bursa Efek Indonesia (BEI), there is 24 companies. Research sample using purposive sampling of companies for periode ended 2012 – 2016. Analyzed by using the two tail linear regression method. The result show, debt to equity ratio and return on asset had a positive and significant effect to dividend policy. It proved by significant t value lower than 5% significances.
Perancangan Sistem Laporan Pengeluaran Dana Bantuan Operasional Sekolah (Bos) Pada Upt Satuan Pendidikan SMP Negeri 6 Tangerang
Authors: Rachmat Achmad , Indriana Sari , Rosa Amelia
Published: April 2021

School Operational Assistance (BOS) is a government program that is basically to provide funding for non-personnel operating costs for junior high schools (SMP) as implementing compulsory education programs. In supporting the management of School Operational Assistance (BOS) funds at schools, an information system has been created that can assist in managing BOS funds. The School Operational Assistance Management (BOS) Management Information System was created because inaccurate and incomplete data were often found at the UPT Education Unit of SMP Negeri 6 Tangerang. Causing financial statements every month to be not timely. Therefore this financial statement system was made to support the data to be accurate and complete and the financial statements also become timely. To illustrate the model design and system design using the Unified Modeling Language (UML). The results of this study are a financial reporting system that is designed using the PHP programming language,

MySQL database, and laptops are code editors. For testing the system using the Blackbox method, in order to test the functionality of the system.
Tertiary education in EU countries
Authors: Poráčová Janka , Zahatňanská Mária , Nagy Melinda , Konečná Mária , Mydlárová Blaščáková Marta , Sedlák Vincent , Tkáčová Renáta
Published: April 2021

Tertiary education provided by universities and other higher education institutions play an essential role in society, by fostering innovation, increasing economic development and growth, and improving more generally the well-being of citizens. Some European universities are among the most prestigious in the world. Many commentators predict that in the coming years there will be increased demand for highly skilled people. Driven by digital technology, jobs are becoming more flexible and complex. This has resulted in a growing number of employers seeking staff with the necessary capacities to manage complex information, think autonomously, be creative, use resources in a smart and efficient manner, as well as communicate effectively. Education is an essential part of any modern, successful and rich country. EU countries are no exception. The need for a university-educated workforce is increasing every year by employers.  Educated graduates and workers are also needed in other areas of society, e.g. in healthcare, in the economic, social, legal, education, etc. One of the EU's main challenges is to ensure that policy developments are monitored to take account of the considerable geographical diversity in the EU. The territorial dimension of EU policy is increasingly recognized, as growth and job creation depend on making the best use of all resources while ensuring the coordinated and sustainable use of shared resources. This section provides an overview of some of the main EU policy developments that have a territorial impact.
Welcome
Authors: Toth Péter
Published: April 2021

This new decade began with a pandemic. It has shattered our everyday lives, our usual social life. A health emergency was introduced, and schools were ordered to close, and education was suddenly confronted with a new reality: it has become necessary to study and teach at home, using alternative teaching and learning forms and methods. This situation has been a giant challenge for students, teachers, researchers, and society as a whole; it took almost days to adapt to the new circumstances.
Korelasi antara Derajat Dehidrasi Menurut WHO dengan Rasio Vena Cava Inferior/Aorta Abdominal Menggunakan Ultrasonografi pada Anak Penderita Diare
Authors: Herman Teddy Marzuki , Murtala Bachtiar , Latief Nikmatia , Asriyani Sri , Zainuddin Andi Alfian , Ganda Idham Jaya
Published: April 2021

Penelitian ini bertujuan menilai hubungan antara derajat dehidrasi menurut WHO dengan rasio vena cava inferior / aorta abdominal berdasarkan ultrasonografi pada anak penderita diare. Penelitian ini merupakan penelitian cross sectional terhadap 46 anak penderita diare yang masuk ke IGD pediatrik RSUP Dr. Wahidin Sudirohusodo Makassar dari bulan Oktober 2018 sampai Desember 2018. Penilaian derajat dehidrasi menurut WHO dilakukan oleh dokter anak sesaat setelah dilakukan pemeriksaan ultrasonografi untuk mengukur rasio vena cava inferior/aorta abdominal. Hasil penelitian menunjukkan terdapat korelasi kuat antara derajat dehidrasi menurut WHO dengan rasio IVC/aorta abdominal (p0,001, r=-0,637). Semakin berat derajat dehidrasi menurut WHO, semakin rendah rasio IVC/aorta abdominal.
Hubungan Aktivitas Fisik terhadap Tinggi Badan pada Mahasiswa Fakultas Kedokteran Umum Universitas YARSI yang Berumur Kurang dari atau Sama dengan 20 Tahun
Authors: Savitri Adinda , Zulhamidah Yenni , Widayanti Etty
Published: April 2021

Latar Belakang: Penelitian sebelumnya telah menemukan hubungan antara ukuran tinggi badan pendek dengan tingkat pendidikan dan produktivitas manusia di masa depan. Beberapa penelitian telah menemukan bahwa aktivitas fisik berkorelasi dengan optimalisasi pertumbuhan massa mineral tulang yang dicapai pada awal usia 20 tahun, selanjutnya akan mempengaruhi pertumbuhan tinggi badan. Tujuan dari penelitian ini adalah untuk membuktikan hipotesis tentang hubungan antara aktivitas fisik dengan tinggi pada remaja usia lanjut. Metode: Desain penelitian yang digunakan dalam penelitian ini adalah kuantitatif korelasional dengan pendekatan Cross Sectional. Populasi sampel yang digunakan adalah mahasiswa kedokteran tahun pertama dan kedua Universitas YARSI yang berusia ? 20 tahun. Penentuan intensitas aktivitas fisik harian menggunakan kuesioner dan Global Physical Activity Questionnaire (GPAQ). Tinggi diperoleh dengan pengukuran tinggi badan responden secara langsung dan dikategorikan ke dalam tiga kelompok berdasarkan kurva CDC 2000. Data dianalisis dengan uji statistik Pearson Chi Square. Hasil: Analisis bivariat menunjukkan bahwa tidak ada hubungan antara aktivitas fisik pada remaja dengan tinggi badan dengan nilai P (P = 0,992 5%), tetapi ditemukan hubungan antara aktivitas fisik selama periode prapubertas dengan tinggi badan dengan nilai P (P = 0,045 5%). Simpulan: Aktivitas fisik yang dilakukan selama masa remaja tidak memiliki hubungan dengan tinggi badan, tetapi aktivitas fisik yang dilakukan selama periode prapubertas memiliki hubungan terhadap tinggi badan.
Gambaran Proses Pembelajaran E-learning Mahasiswa Fakultas Kedokteran Universitas YARSI Jakarta
Authors: Asiah Nur
Published: April 2021

Pendahuluan: Pandemi covid-19 telah menuntut pergutuan tinggi untuk melaksanakan pembelajaran online. Tujuan penelitian ini adalah untuk mengetahui gambaran proses pembelajaran secara e-learning pada mahasiswa Fakultas Kedokteran Universitas YARSI Jakarta pada bulan September-November 2020. Metode: Desain penelitian bersifat cross sectional dengan cara pengumpulan data melalui kuesioner. Data yang terkumpul berasal dari 220 orang mahasiswa semester V yang sedang mengikuti Blok Endokrin, Metabolik dan Nutrisi. Pertanyaan yang diajukan terdiri dari pertanyaan terbuka dengan jawaban singkat dan pertanyaan pilihan ganda. Hasil: Hasil penelitian menunjukkan 40% mahasiswa menyatakan penyampaian materi kuliah diserap dengan baik, 48% mahasiswa mempersiapkan materi sebelum e-learning, 47% mahasiswa memiliki pengaturan waktu yang baik dan 36% mahasiswa berkonsentrasi selama 2-3 jam. Keluhan kesehatan terbanyak adalah kekakuan leher dan otot serta pusing (40%). Sebanyak 47% mahasiswa menyatakan mudah mendapatkan materi kuliah. Metode belajar secara berkelompok merupakan pilihan utama (69%), meskipun 56% mahasiswa lebih menyukai tatap muka langsung dibandingkan e-learning. Simpulan: E-learning pada mahasiswa FK YARSI Jakarta berlangsung lancar dengan penyerapan materi yang baik dan kemudahan mengakses materi. Kemandirian mahasiswa terlihat berupa persiapan, pengaturan kegiatan harian dan sistem belajar kelompok, meskipun terdapat keluhan kesehatan, terbatasnya konsentrasi dan tatap muka langsung yang lebih disukai dibandingkan e-learning.
Effects of Charge Compensation on the Thermoelectric Properties of (La1-zCez)0.8Fe4-xCoxSb12 Skutterudites
Authors: Jang Kyung-Wook , Cha Ye-Eun , Choi Deok-Yeong , Kim Sunuk , Seo Won-Seon , Lee Kyu Hyoung , Kim Il-Ho
Published: April 2021

La/Ce-partially double-filled and Co-charge-compensated (La1−zCez)0.8Fe4−xCoxSb12 skutterudites were synthesized, and their thermoelectric properties were studied by varying the filling ratio and charge compensation. X-ray diffraction analysis revealed that the matrix phase was skutterudite and a secondary phase was determined to the marcasite FeSb2. However, the formation of marcasite could be inhibited by increasing the Co content. Rare-earth antimonides, including LaSb2 and CeSb2, which were formed in fully filled La1−zCezFe4−xCoxSb12, were not found after La/Ce partial filling. La/Ce filling and Co substitution were confirmed by the decrease in lattice constants, from 0.9137 to 0.9099 nm, with increasing Ce and Co contents. Electrical conductivity showed negative temperature dependence, indicating metallic or degenerate semiconductor characteristics. Intrinsic conduction resulted in the maximum Seebeck coefficient at temperatures between 723 and 823 K. As the Co-substitution and Ce-filling contents increased, the Seebeck coefficient increased, while electrical and thermal conductivities decreased. This was considered to be due to difference in the valences of La3+ and Ce3+/4+ and the increase in carrier concentration caused by Co charge compensation. However, because they had similar atomic masses and ionic radii, the effects of the La/Ce filling ratio were not significant. Instead, Co charge compensation had the dominant effect on thermoelectric properties. The maximum Seebeck coefficient of 165.4 µVK-1 was obtained for (La0.25Ce0.75)0.8Fe3CoSb12 at 823 K, and the highest electrical conductivity of 2.27 × 105 S m-1 was achieved for (La0.75Ce0.25)0.8Fe4Sb12. (La0.25Ce0.75)0.8Fe3CoSb12 exhibited the lowest thermal conductivity of 2.15 W m-1K-1 at 523 K and (La0.75Ce0.25)0.8Fe3.5Co0.5Sb12 showed the highest power factor of 2.53 mW m-1 K-2 at 723 K. The maximum dimensionless figure of merit, ZTmax = 0.71, was achieved at 723 K for (La0.75Ce0.25)0.8Fe3CoSb12.
Patterns ofPhysisand the Self-MakingKosmosin Heraclitus
Authors: Decker Jessica Elbert
Published: April 2021

Contemporary Western thinkers recognise the destructive effects of long-standing attitudes of mastery over nature and the dualistic and hierarchical thinking that informs them. Heraclitus’ metaphysical position is ideal for reframing these traditional stances for several reasons: first, Heraclitus’ concept of identity is dynamic and relies on a sophisticated understanding of opposites that recognises ambiguity; secondly, his philosophical position produces a model of truth as multiple rather than univocal; and finally, in Heraclitus’ self-making kosmos, human beings are not separate from the processes of physis but inextricably entangled in them. Heraclitus’ philosophy offers relevant avenues for reimagining contemporary philosophical issues, particularly theories of identity, the multiplicity of truth, and the proper ethical human relation to nature.
IMPACTO AMBIENTAL ASOCIADO A LA IMPLEMENTACIÓN Y EJECUCIÓN DEL PROYECTO DE MEDIANA MINERÍA RÍO BLANCO
Authors:   Universidad Politécnica Salesiana, Moreno Farfán Raúl Andrés
Published: April 2021

El crecimiento económico de un país se basa en el desarrollo de distintas esferas económicas y constituye una prioridad para los gobiernos mundiales. En Ecuador la minería constituye un recurso natural que se explota cada vez con mayor fuerza. Sin embargo, el auge de la minería puede traer consigo un impacto ambiental negativo. El objetivo de la presente investigación es describir el posible impacto ambiental asociado a la implementación y ejecución del proyecto de mediana minería Río Blanco y plantear una propuesta de diseño y estabilización de relaves. Para esto se realizó una investigación básica, descriptiva y explicativa, basada en la revisión documental y el trabajo de campo. Como principal resultado se puede señalar la identificación de dos problemas fundamentales como fueron las balsas de flotación y el conflicto social. Se concluye que el proyecto de mediana minería Rio Blanco, a pesar de crear condiciones favorables desde el punto de vista de creación de puestos de trabajo y de crecimiento económico de la zona, representa un riesgo ecológico y ambiental elevado. Se diseñó una propuesta de intervención para lograr la integración y restauración ambiental de la zona de acción minera, basada en una propuesta de diseño y estabilización de depósitos de relaves. Se concluye que la actividad minera constituye un sector de desarrollo local y regional; sin embargo, la actividad debe relazarse basado en planes que garanticen una explotación sostenida sin que se perjudique el ambiente que rodee al área de explotación.
The Nuclear Farnesoid X Receptor Reduces p53 Ubiquitination and Inhibits Cervical Cancer Cell Proliferation
Authors: Huang Xiaohua , Wang Bin , Chen Runji , Zhong Shuping , Gao Fenfei , Zhang Yanmei , Niu Yongdong , Li Congzhu , Shi Ganggang
Published: April 2021

The role of farnesoid X receptor (FXR) in cervical cancer and the underlying molecular mechanism remain largely unknown. Therefore, this study aimed to assess the mechanism of FXR in cervical cancer. Western blot, qRT-PCR, and immunohistochemistry demonstrated that FXR was significantly reduced in squamous cell carcinoma tissues, although there were no associations of metastasis and TNM stage with FXR. In Lenti-FXR cells obtained by lentiviral transfection, the overexpression of FXR reduced cell viability and colony formation. Compared with the Lenti-Vector groups, the overexpression of FXR induced early and late apoptosis and promoted G1 arrest. With time, early apoptosis decreased, and late apoptosis increased. In tumor xenograft experiments, overexpression of FXR upregulated small heterodimer partner (SHP), murine double minute-2 (MDM2), and p53 in the nucleus. Co-immunoprecipitation (Co-IP) showed that SHP directly interacted with MDM2, which is important to protect p53 from ubiquitination. Nutlin3a increased MDM2 and p53 amounts in the Lenti-Vector groups, without effects in the Lenti-FXR groups. Silencing SHP reduced MDM2 and p53 levels in the Lenti-FXR groups, and Nutlin3a counteracted these effects. Taken together, these findings suggest that FXR inhibits cervical cancer via upregulation of SHP, MDM2, and p53.
The Regulation and Function of Histone Crotonylation
Authors: Ntorla Angeliki , Burgoyne Joseph Robert
Published: April 2021

Histone crotonylation is a newly identified epigenetic modification that has a pronounced ability to regulate gene expression. It belongs to an expanding group of short chain lysine acylations that also includes the extensively studied mark histone acetylation. Emerging evidence suggests that histone crotonylation is functionally distinct from histone acetylation and that competition for sites of modification, which reflects the cellular metabolic status, could be an important epigenetic mechanism that regulates diverse processes. Here, we discuss the enzymatic and metabolic regulation of histone crotonylation, the “reader” proteins that selectively recognise this modification and translate it into diverse functional outcomes within the cell, as well as the identified physiological roles of histone crotonylation, which range from signal-dependent gene activation to spermatogenesis and tissue injury.
Shear-Regulated Extracellular Microenvironments and Endothelial Cell Surface Integrin Receptors Intertwine in Atherosclerosis
Authors: Mo Fan-E
Published: April 2021

Mechanical forces imposed by blood flow shear stress directly modulate endothelial gene expression and functional phenotype. The production of extracellular matrix proteins and corresponding cell-surface integrin receptors in arterial endothelial cells is intricately regulated by blood flow patterns. Laminar blood flow promotes mature and atheroresistant endothelial phenotype, while disturbed flow induces dysfunctional and atheroprone endothelial responses. Here, we discuss how hemodynamic changes orchestrate the remodeling of extracellular microenvironments and the expression profile of the integrin receptors in endothelial cells leading to oxidative stress and inflammation. Targeting the interaction between matrix proteins and their corresponding integrins is a potential therapeutic approach for atherosclerosis.
Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma
Authors: Lou Qi , Zhao Minyi , Xu Quanhui , Xie Siyu , Liang Yingying , Chen Jian , Yuan Lisha , Wang Lingling , Jiang Linjia , Mou Lisha , Lin Dongjun , Zhao Meng
Published: April 2021

Bone marrow mesenchymal stem/stromal cells (BMSCs) can be transformed into tumor-associated MSCs (TA-MSCs) within the tumor microenvironment to facilitate tumor progression. However, the underline mechanism and potential therapeutic strategy remain unclear. Here, we explored that interleukin 17 (IL-17) cooperating with IFNγ transforms BMSCs into TA-MSCs, which promotes tumor progression by recruiting macrophages/monocytes and myeloid-derived suppressor cells (MDSCs) in murine melanoma. IL-17 and IFNγ transformed TA-MSCs have high expression levels of myelocyte-recruiting chemokines (CCL2, CCL5, CCL7, and CCL20) mediated by activated NF-κB signaling pathway. Furthermore, retinoic acid inhibits NF-κB signaling, decreases chemokine expression, and suppresses the tumor-promoting function of transformed TA-MSCs by prohibiting the recruitment of macrophages/monocytes and MDSCs in the tumor microenvironment. Overall, our findings demonstrate that IL-17 collaborating with IFNγ to induce TA-MSC transformation, which can be targeted by RA for melanoma treatment.
Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy
Authors: Wang Tian , Li Yiming , Guo Miao , Dong Xue , Liao Mengyu , Du Mei , Wang Xiaohong , Yin Haifang , Yan Hua
Published: April 2021

Traumatic optic neuropathy (TON) refers to optic nerve damage caused by trauma, leading to partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged as a promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes as nanosized vesicles for the delivery of PACAP38 loaded via the exosomal anchor peptide CP05 (EXOPACAP38). EXOPACAP38 showed greater uptake efficiency in vitro and in vivo than PACAP38. The results showed that EXOPACAP38 significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXOPACAP38 significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXOPACAP38 can be used as a treatment option and may have therapeutic implications for patients with TON.
Therapeutic Potential of GABAergic Signaling in Myelin Plasticity and Repair
Authors: Reyes-Haro Daniel , Cisneros-Mejorado Abraham , Arellano Rogelio O.
Published: April 2021

Oligodendrocytes (OLs) produce myelin to insulate axons. This accelerates action potential propagation, allowing nerve impulse information to synchronize within complex neuronal ensembles and promoting brain connectivity. Brain plasticity includes myelination, a process that starts early after birth and continues throughout life. Myelin repair, followed by injury or disease, requires new OLs differentiated from a population derived from oligodendrocyte precursor cells (OPCs) that continue to proliferate, migrate and differentiate to preserve and remodel myelin in the adult central nervous system. OPCs represent the largest proliferative neural cell population outside the adult neurogenic niches in the brain. OPCs receive synaptic inputs from glutamatergic and GABAergic neurons throughout neurodevelopment, a unique feature among glial cells. Neuron-glia communication through GABA signaling in OPCs has been shown to play a role in myelin plasticity and repair. In this review we will focus on the molecular and functional properties of GABAA receptors (GABAARs) expressed by OPCs and their potential role in remyelination.
Predicting Recurrent Venous Thromboembolism in Patients With Deep-Vein Thrombosis: Development and Internal Validation of a Potential New Prediction Model (Continu-8)
Authors: Nagler Michael , Van Kuijk Sander M. J. , Ten Cate Hugo , Prins Martin H. , Ten Cate-Hoek Arina J.
Published: April 2021

Background: Previous prediction models for recurrent thromboembolism (VTE) are often complicated to apply and have not been implemented widely.

Aim: To develop and internally validate a potential new prediction model for recurrent VTE that can be used without stopping anticoagulant treatment for D-dimer measurements in patients with provoked and unprovoked DVT.

Methods: Cohort data of 479 patients treated in a clinical care pathway at Maastricht University Medical Center were used. Predictors for the Cox proportional hazards model (unprovoked DVT, male gender, factor VIII levels) were derived from literature and using forward selection procedure. The scoring rule was internally validated using bootstrapping techniques and the predictive ability was compared to existing prediction models.

Results: Patients were followed for a median of 3.12 years after stopping anticoagulation treatment (IQR 0.78, 3.90). Sixty-four of 479 patients developed recurrent VTE (13%). The scoring rule consisted of unprovoked DVT (yes: 2 points), male sex (yes: 1 point), and factor VIII > 213 % (yes: 2 points) and was categorized into three groups [i.e., low risk (score 0), medium risk (scores 1, 2, or 3) and high risk (scores 4 and 5)]. The concordance statistic was 0.68 (95% CI: 0.61, 0.75).

Conclusion: The discriminative ability of the new Continu-8 score was adequate. Future studies shall verify this score in an independent setting without stopping anticoagulation treatment.
Long Non-coding RNA: A Key Regulator in the Pathogenesis of Diabetic Cardiomyopathy
Authors: Guo Yaoyao , Feng Xiaohui , Wang Dan , Kang Xiaonan , Zhang Lu , Ren Huihui , Yuan Gang
Published: April 2021

In recent years, diabetes mellitus has become a global issue with increasing incidence rate worldwide. Diabetic cardiomyopathy (DCM), one of the important complications of diabetes, refers to patients with type 1 and type 2 diabetes who have ventricular hypertrophy, fibrosis and even diastolic dysfunction. The pathogenesis of DCM is related to oxidative stress, inflammatory response, apoptosis, autophagy, myocardial fibrosis and, diabetic microangiopathy. Long non-coding RNAs (lncRNA) is a non-coding RNA with a length longer than 200 nucleotides which lack the ability of protein coding. With the development of molecular technology, massive evidence demonstrates that lncRNA play a critical role in the molecular mechanism of DCM. Moreover, it can also be used as potential diagnostic markers for DCM. In this review, we intend to summarize the pathological roles and molecular mechanism of lncRNA in the progression of diabetic cardiomyopathy, which may provide promising diagnosis and treatment strategies for DCM.
Experimental Methods for the Quantitative Assessment of the Volume Fraction of Movable Shale Oil: A Case Study in the Jimsar Sag, Junggar Basin, China
Authors: Luo Xia , Zhao Zhongying , Hou Lianhua , Lin Senhu , Sun Feifei , Zhang Lijun , Zhang Yan
Published: April 2021

Deep insights into the movability of the retained shale oil are of great significance to shale oil. Rock and crude oil samples were collected from well J174 in the Jimsar Sag, Junggar Basin. Rock samples were subjected to different extraction followed by analysis of the component in the extracts, and measurement of porosity in conjunction with nuclear magnetic resonance and high-pressure mercury injection analysis. The results of these analyses were used to establish an experimental method for quantitative assessment of movable shale oil. The extract content of the component varied among different extraction and between mud shale and non-mud shale samples. The saturated hydrocarbon in the extracts of the mud shale was similar to those of the non-mud shale after extraction with CHCl3 alone or after sequential extraction with nC6 + CHCl3. The aromatic hydrocarbon in the extract were significantly lower for the mud shale than for the non-mud shale after extraction with nC6, but the opposite was observed after sequential extraction with nC6 + CHCl3. The contents of the non-hydrocarbon in the extract were significantly lower for the mud shale than for the non-mud shale after extraction with nC6, but the opposite was observed after extraction with CHCl3 or nC6 + CHCl3. The contents of the asphaltene in the extract were not significantly different for the mud shale and non-mud shale after extraction with nC6, but the contents were higher for the mud shale than for the non-mud shale after extraction with nC6 + CHCl3 or CHCl3. The viscosity of the crude oil was negatively correlated with the saturated hydrocarbon, was positively correlated with the aromatic hydrocarbon and non-hydrocarbon, and was not correlated with the asphaltene. For the mud shale and non-mud shale, their porosity after extraction with nC6 or CHCl3 was higher than their original porosity. Moreover, their porosity after extraction with CHCl3 was higher than after extraction with nC6. The movable oil was significantly correlated with the lithology, with sandstone allowing for a higher fluid movability than mud shale and dolomite allowing for a higher fluid movability than siliceous rocks.
Effects of Microplastic Fibers on Soil Aggregation and Enzyme Activities Are Organic Matter Dependent
Authors: Liang Yun , Lehmann Anika , Yang Gaowen , Leifheit Eva F. , Rillig Matthias C.
Published: April 2021

Microplastic as an anthropogenic pollutant accumulates in terrestrial ecosystems over time, threatening soil quality and health, for example by decreasing aggregate stability. Organic matter addition is an efficient approach to promote aggregate stability, yet little is known about whether microplastic can reduce the beneficial effect of organic matter on aggregate stability. We investigated the impacts of microplastic fibers in the presence or absence of different organic materials by carrying out a soil incubation experiment. This experiment was set up as a fully factorial design containing all combinations of microplastic fibers (no microplastic fiber addition, two different types of polyester fibers, and polyacrylic) and organic matter (no organic matter addition, Medicago lupulina leaves, Plantago lanceolata leaves, wheat straw, and hemp stems). We evaluated the percentage of water-stable aggregates (WSA) and activities of four soil enzymes (β-glucosidase, β-D-celluliosidase, N-acetyl-b-glucosaminidase, phosphatase). Organic matter addition increased WSA and enzyme activities, as expected. In particular, Plantago or wheat straw addition increased WSA and enzyme activities by 224.77 or 281.65% and 298.51 or 55.45%, respectively. Microplastic fibers had no effect on WSA and enzyme activities in the soil without organic matter addition, but decreased WSA and enzyme activities by 26.20 or 37.57% and 23.85 or 26.11%, respectively, in the presence of Plantago or wheat straw. Our study shows that the effects of microplastic fibers on soil aggregation and enzyme activities are organic matter dependent. A possible reason is that Plantago and wheat straw addition stimulated soil aggregation to a greater degree, resulting in more newly formed aggregates containing microplastic, the incorporated microplastic fibers led to less stable aggregates, and decrease in enzyme activities This highlights an important aspect of the context dependency of microplastic effects in soil and on soil health. Our results also suggest risks for soil stability associated with organic matter additions, such as is common in agroecosystems, when microplastics are present.
Cprp—An Unusual, Repetitive Protein Which Impacts Pleuromutilin Biosynthesis in the Basidiomycete Clitopilus passeckerianus
Authors: de Mattos-Shipley Kate M. J. , Foster Gary D. , Bailey Andy M.
Published: April 2021

Interrogation of an EST database forClitopilus passeckerianusidentified a putative homolog to the unusual stress response gene from yeast;ddr48, as being upregulated under pleuromutilin production conditions. Silencing of this gene, namedcprp, produced a population of transformants which demonstrated significantly reduced pleuromutilin production. Attempts to complement aSaccharomyces cerevisiae ddr48mutant strain (strain Y16748) withcprpwere hampered by the lack of a clearly identifiable mutant phenotype, but interestingly, overexpression of eitherddr48orcprpinS. cerevisiaeY16748 led to a conspicuous and comparable reduction in growth rate. This observation, combined with the known role of DDR48 proteins from a range of fungal species in nutrient starvation and stress responses, raises the possibility that this family of proteins plays a role in triggering oligotrophic growth. Localization studiesviathe production of a Cprp:GFP fusion protein inC. passeckerianusshowed clear localization adjacent to the hyphal septa and, to a lesser extent, cell walls, which is consistent with the identification of DDR48 as a cell wall-associated protein in various yeast species. To our knowledge this is the first study demonstrating that a DDR48-like protein plays a role in the regulation of a secondary metabolite, and represents the first DDR48-like protein from a basidiomycete. Potential homologs can be identified across much of the Dikarya, suggesting that this unusual protein may play a central role in regulating both primary and secondary metabolism in fungi.
Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach
Authors: Tamkeen Naaila , AlOmar Suliman Yousef , Alqahtani Saeed Awad M. , Al-jurayyan Abdullah , Farooqui Anam , Tazyeen Safia , Ahmad Nadeem , Ishrat Romana
Published: April 2021

Spina Bifida (SB) is a congenital spinal cord malformation. Efforts to discern the key regulators (KRs) of the SB protein-protein interaction (PPI) network are requisite for developing its successful interventions. The architecture of the SB network, constructed from 117 manually curated genes was found to self-organize into a scale-free fractal state having a weak hierarchical organization. We identified three modules/motifs consisting of ten KRs, namely, TNIP1, TNF, TRAF1, TNRC6B, KMT2C, KMT2D, NCOA3, TRDMT1, DICER1, and HDAC1. These KRs serve as the backbone of the network, they propagate signals through the different hierarchical levels of the network to conserve the network’s stability while maintaining low popularity in the network. We also observed that the SB network exhibits a rich-club organization, the formation of which is attributed to our key regulators also except for TNIP1 and TRDMT1. The KRs that were found to ally with each other and emerge in the same motif, open up a new dimension of research of studying these KRs together. Owing to the multiple etiology and mechanisms of SB, a combination of several biomarkers is expected to have higher diagnostic accuracy for SB as compared to using a single biomarker. So, if all the KRs present in a single module/motif are targetted together, they can serve as biomarkers for the diagnosis of SB. Our study puts forward some novel SB-related genes that need further experimental validation to be considered as reliable future biomarkers and therapeutic targets.
System-Level Analysis of Alzheimer’s Disease Prioritizes Candidate Genes for Neurodegeneration
Authors: Brabec Jeffrey L. , Lara Montana Kay , Tyler Anna L. , Mahoney J. Matthew
Published: April 2021

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder. Since the advent of the genome-wide association study (GWAS) we have come to understand much about the genes involved in AD heritability and pathophysiology. Large case-control meta-GWAS studies have increased our ability to prioritize weaker effect alleles, while the recent development of network-based functional prediction has provided a mechanism by which we can use machine learning to reprioritize GWAS hits in the functional context of relevant brain tissues like the hippocampus and amygdala. In parallel with these developments, groups like the Alzheimer’s Disease Neuroimaging Initiative (ADNI) have compiled rich compendia of AD patient data including genotype and biomarker information, including derived volume measures for relevant structures like the hippocampus and the amygdala. In this study we wanted to identify genes involved in AD-related atrophy of these two structures, which are often critically impaired over the course of the disease. To do this we developed a combined score prioritization method which uses the cumulative distribution function of a gene’s functional and positional score, to prioritize top genes that not only segregate with disease status, but also with hippocampal and amygdalar atrophy. Our method identified a mix of genes that had previously been identified in AD GWAS including APOE, TOMM40, and NECTIN2(PVRL2) and several others that have not been identified in AD genetic studies, but play integral roles in AD-effected functional pathways including IQSEC1, PFN1, and PAK2. Our findings support the viability of our novel combined score as a method for prioritizing region- and even cell-specific AD risk genes.
Study on the Influence of mRNA, the Genetic Language, on Protein Folding Rates
Authors: Li Ruifang , Li Hong , Feng Xue , Zhao Ruifeng , Cheng Yongxia
Published: April 2021

Many works have reported that protein folding rates are influenced by the characteristics of amino acid sequences and protein structures. However, few reports on the problem of whether the corresponding mRNA sequences are related to the protein folding rates can be found. An mRNA sequence is regarded as a kind of genetic language, and its vocabulary and phraseology must provide influential information regarding the protein folding rate. In the present work, linear regressions on the parameters of the vocabulary and phraseology of mRNA sequences and the corresponding protein folding rates were analyzed. The results indicated that D2 (the adjacent base-related information redundancy) values and the GC content values of the corresponding mRNA sequences exhibit significant negative relations with the protein folding rates, but D1 (the single base information redundancy) values exhibit significant positive relations with the protein folding rates. In addition, the results show that the relationships between the parameters of the genetic language and the corresponding protein folding rates are obviously different for different protein groups. Some useful parameters that are related to protein folding rates were found. The results indicate that when predicting protein folding rates, the information from protein structures and their amino acid sequences is insufficient, and some information for regulating the protein folding rates must be derived from the mRNA sequences.
Efficacy and Safety of Adalimumab Biosimilars: Current Critical Clinical Data in Rheumatoid Arthritis
Authors: Lu XiaoQin , Hu Rui , Peng Lin , Liu MengSi , Sun Zhen
Published: April 2021

Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually expired, experiments on its biosimilars are constantly being implemented. In this review, we summarized clinical trials of seven biosimilars currently approved by the FDA and/or EMA for the treatment of rheumatoid arthritis, namely: ABP 501 (Amjevita/Amgevita/Solymbic), BI 695501 (Cyltezo), SB5 (Imraldi/Hadlima), GP2017 (Hyrimoz/Hefiya/Halimatoz), MSB11022 (Idacio), FKB327 (Hulio), and PF-06410293 (Abrilada). Overall, these biosimilars showed similar efficacy, safety, and immunogenicity to adalimumab. All biosimilar switching trials indicated that switching from adalimumab to a biosimilar does not have a significant impact on efficacy, safety, and immunogenicity.