bluuebunny/crossref_metadata_2025 huggingface dataset:
Espólios de Michel Foucault para a Análise do Discurso
Authors: Santos Ana Paula da Silva , Estevam Humberto Marcondes , Marques Welisson
Published: December 2020

Quais são as contribuições de Michel Foucault para a Análise do Discurso? Quem trouxe Foucault para o interior da AD? Quando e como isso se deu? As respostas a essas três indagações servem de norte para a escrita deste artigo, de base epistemológico-reflexiva. Assim, buscaremos analisar, a partir de uma retomada aos textos fundadores da disciplina e, em especial, à tese de Jean-Jacques Courtine – autor que articula a perspectiva foucaultiana no interior da AD –, espólios deixados pelo filósofo e que vivamente orientam inúmeros trabalhos inscritos sob esse viés de pesquisas na atualidade em nosso país. Para concluir, apresentamos um breve recenseamento realizado sobre Grupos de Pesquisa no Brasil, cadastrados no CNPq, cujas atividades se orientam por esta perspectiva teórica.
Simbionte – Ética da computação
Authors: Lemos André Souza , Marques Welisson
Published: December 2020

Neste trabalho se encontra uma conexão entre a educação matemática e a arquitetura do conhecimento da computação, na noção de sistema formal. O que contamos aqui é a história do fracasso do bloqueio da simbiose de sistemas de pensamento heterogêneos. Essa é a história da computação, como momento talvez culminante de um projeto de unificação dos sistemas de pensamento. Partimos da transição observável entre a produção de autoevidência, convenção da matemática escolar clássica, e a realização da máquina de calcular. Num segundo momento caminhamos na direção da construção do conhecimento teoremático, que se prolonga na noção de máquina configurável. Essa é a experiência comum dos sistemas computacionais. O trabalho então se debruça sobre a terceira etapa, que corresponde à conexão possível entre o ideal de formalização matemática e o conceito de linguagem computacional, que está na origem do conhecimento da ciência da computação, e que desemboca no último estágio do percurso: o campo problemático dos sistemas autorreferentes, em que a tentativa de consubstanciar a recusa à simbiose dos sistemas de pensamento heterogêneos entra em uma deriva que a fará fracassar. O desenvolvimento conceitual assim engendrado acaba funcionando como conexão com o exterior do pensamento. Um exterior que impõe a consideração de que, à semelhança da psicanálise, o que resta do fracasso da computação como disciplina é uma ética.
Fechamento de fístula oroantral com a utilização de corpo adiposo de bichat: revisão narrativa da literatura
Authors: Palhano José Martí Luna , Cordeiro Annyelle Anastácio , Gregório Beatriz de Aguiar , Dias Brenno Anderson Santiago , Sousa Flávia Regina Galvão de , Gregório Juliana de Aguiar , Figueiredo Lanna Lidia Monteiro , Deus Larissa Alves Assunção de , Silva Maria Alice Pereira , Silva Maria Isabel Araújo André da , Rodrigues Matheus Andrade , Veríssimo Matheus Harllen Gonçalves , Paiva Paulina Renata da Silva , Pereira Pauliny Anaiza de Almeida , Lima Ramon Rodrigues de
Published: December 2020

A comunicação oroantral, também conhecida como fístula oroantral, é uma problemática que ocorre frequentemente no âmbito odontológico, principalmente durante extrações de molares e pré-molares, em que há o íntimo contato com o seio Maxilar, causando o desenvolvimento de uma fístula oroantral. Objetivos: Análise de diversos trabalhos científicos já feitos para que se possa ter maior aquiescência das informações e conteúdo sobre a temática.  Metodologia: Foi feito uma análise bibliográfica de 14 trabalhos, em língua inglesa e portuguesa, durante o período de 2015 a 2020, através das bases de dados: Pubmed, SCIELO, ScienceDirect e LILACS. Resultados: com isso, 85% dos trabalhos apresentaram a efetividade da utilização do corpo adiposo de bichat no tratamento para a comunicação oroantral; e 15% focaram na utilização de enxertos de tecido duro. Considerações finais: O uso do corpo adiposo de Bichat para o fechamento de fístula oroantral persiste em ser um procedimento mais eficaz, no que se diz respeito ao melhoramento do prognóstico do paciente e técnica menos invasiva desenvolvida pelo cirurgião-dentista.
Reuni como política de expansão das universidades federais e os cortes do Governo Federal
Authors: Melo Emilly Coelly Pedrosa de , Santos Stefany Thyene Albuquerque dos , Rodrigues Janine Marta Coelho , Aragão Wilson Honorato
Published: December 2020

O presente trabalho visa refletir  sobre uma política pública educacional, mostrando seus respectivos resultados, evidenciando problemas públicos, destacando seus atores e classificando a política escolhida nas tipologias dos seguintes teóricos de: Lowi, Wilson, Gormley, Gustafsson, Bozeman e Pandey. A política pública que iremos discutir neste trabalho é o Programa de Apoio a planos de Reestruturação e Expansão Acadêmica das Universidades Federais (REUNI), criado no governo ex presidente Luiz Inácio Lula da Silva, em 2007, o objetivo desta política pulica voltada para área de educação era criar condições para a ampliação do acesso e permanência na educação superior. Após estudos observamos que a maioria das universidades Federais se localizavam nas capitas e os estudantes de baixa renda oriundo dos interiores não conseguiam o acesso ao ensino superior, nem tão pouco tinham condições de se manter nas capitais, então o foco maior desta política é a interiorização das universidades federais e ifes como ampliação de vagas acesso e permanência nos cursos superiores.
THE EUROPEAN UNION AND THE PARIS AGREEMENT
Authors: Natalie Miranda , Patricia Sherene , Patricia Sherene , Silveria Erlyn , Dameria Ellya , Sitanggang Tiolas , Michelle Valerie
Published: December 2020

The Paris Agreement has undoubtedly impacted on other more personal environmental policies in each country worldwide. We are trying to explain the dynamics (changes and debates) that occur in the policy-making process by the actors and stakeholders in the Paris Agreement. For instance, with the Trump dismantling policy to leave the Paris Agreement that we called the free-riding strategy that affects not only the members within the Paris Agreement but also the environmental sector globally. We also contemplate the alternatives way to solve the environmental  problem through the Paris Agreement, and a solution to the problem occurs within the members by considering the consequences under international law

 

Keywords: Paris Agreement, Environmental Issue, European Union, President Trump
Fabrication and Electromagnetic wave absorption Properties of Co-Cu-substituted Ni-Zn Spinel Ferrite-epoxy Composites
Authors: Yoo Ji-Eun , Kang Young-Min
Published: December 2020

Spinel ferrites (Ni0.5Zn0.5)1-x-yCoxCuyFe2O4, (x = 0 and y = 0, x = 0.2 and y = 0, x = 0.1 and y = 0.1, x = 0 and y = 0.2) were prepared by sol-gel method and post-annealed at 1100 oC. The grain growth of the sample is very sensitive to the Cu substitution y. The average grain size of the non-doped sample (x = 0, y = 0) was ~400 nm and it increased to ~3 μm at the sample with x = 0 and y = 0.2. The real and imaginary parts of permittivities (ε', ε") and permeabilities (μ', μ") were measured on the spinel ferrite powder-epoxy (10 wt%) composite samples by a network vector analyzer in the frequency range of 0.1 ≤ f ≤ 15 GHz. The μ' and μ" depend on Co substitution x and the ε' is sensitive to Cu doping y. Reflection loss (RL), which implies electromagnetic (EM) wave absorption properties, were analyzed based on the complex permeability, permittivity spectra. In the RL map plotted as functions of sample thickness (d) and frequency (f), the intensive EM absorbing area (RL < -30 dB) shifted to a high frequency region with increasing Co substitution. This can be attributed to a permeability spectra shift, due to the increase in ferromagnetic resonance frequency produced by the Co substitution. The samples with x = 0.1 and y = 0.1, x = 0.2 and y = 0 also exhibited a very broad-ranged EM wave absorbing performance with a d < 3 mm, indicated by RL < -10 dB being satisfied in the frequency range 7~14 GHz.
Effect of Electrolyte Anion on Electrochemical Behavior of Nickel Hexacyanoferrate Electrode in Aqueous Sodium-Ion Batteries
Authors: Park Sungjun , Chun Sang-Eun
Published: December 2020

Nickel hexacyanoferrate (NiHCF) has a three-dimensional open framework structure, excellent long-cycling stability and rate performance as a cathode for aqueous sodium-ion batteries. However, the specific capacity of NiHCF is lower than that of present cathodes for aqueous batteries. A sodium-ion electrolyte was explored to achieve optimum capacity with NiHCF. Powder-type NiHCF was fabricated by coprecipitation with the atomic composition K0.065Ni1.44Fe(CN)6·4.4H2O. The presence of Fe vacancies in the atomic composition is attributable to the inclusion of coordinating and zeolitic water during coprecipitation. Two sodium-ion electrolytes, 1 M Na2SO4 and 1 M NaNO3, were employed to analyze the electrochemical behavior of the NiHCF electrode. Identical redox potentials to 0.58 V (vs. NHE) were measured in both electrolytes. However, a lower overpotential was observed in NaNO3 compared to Na2SO4 as a result of the smaller interfacial charge transfer resistance. The lower charge transfer resistance in the NaNO3 solution produced a higher specific capacity of 57 mAh g-1 (1 C-rate) and the superior capacity retention of 46.6% at 20 C-rate. The anion in the aqueous electrolyte changed the charge transfer resistance at the electrode/electrolyte interface, confirming the electrolyte anion has a crucial effect on the charge capacity and rate performance of NiHCF.
Small molecules combined with narrowband UVB therapy for psoriasis patients
Authors: Khotko A. A. , Kruglova L. S.
Published: December 2020

Psoriasis is a heterogeneous disease characterized by a wide range of clinical manifestations. Patients with psoriasis and psoriatic arthritis have an increased risk of developing comorbid conditions, therefore, when prescribing therapy, it is necessary to take into account aspects of polypharmacy and the risks of developing infections. Apremilast is effective for the treatment of patients with psoriasis and comorbid comorbidity. To increase the effectiveness of apremilast therapy (achieving PASI 90 and PASI 100), it is possible to use a combination with narrow-band medium-wave phototherapy. The combined method allows achieving clear or almost clear skin in the vast majority of patients and is highly safe, as evidenced by the absence of severe side effects. The method is safe when used in patients with impaired glucose tolerance, diabetes mellitus, increased body weight and the risk of infections.
Health and growth indices in children with cow’s milk protein allergy depending on oral tolerance development
Authors: Galimova A. A. , Emelyashenkov E. E. , Makarova S. G. , Murashkin N. N. , Fisenko A. P. , Ereshko O. A. , Zubkova I. V. , Snovskaya M. A. , Chumbadze T. R. , Yasakov D. S. , Gordeeva I. G. , Kozhevnikova O. V.
Published: December 2020

Relevance. Dairy-free diet is the basis of cow’s milk allergy (CMA) patient’s management. Duration of the diet is individual, but some children don’t develop tolerance.

The aim of the study was to investigate health and growth indices in children with CMA depending on tolerance development by the age of five. Materials and methods. 153 children from 1 to 18 months with diagnosed CMA were included in the prospective study (76.5% with IgE-mediated form). The tolerance was determined after 6–12 months of a milk-free diet and at the age of 5 using an open challenge test. Anthropometry indices (Anthro Plus), levels of specific IgE (Immuno CAP 250) and IgG4 (ELISA) to dietary proteins and the presence of allergic diseases in children also were assessed.

Results. 50.3% of children developed tolerance to cow’s milk protein after 6–12 months of a milk-free diet. By the age of 5 63.3% of patients had complete tolerance of dairy products. Partially formed tolerance was observed in 22.9%. 13.8% of patients still had clinical reactions to cow’s milk proteins. Patients with persistent CMA typically had IgE-mediated form, lower growth indices and multiple allergic pathology.

Conclusion. The consideration of tolerance development predictors can allow to personalize the management of CMA. Additional researches are needed to clarify the causes of growth indices decline in children with persistent CMA.
Prevention and therapy of acne-like rash in cancer patients receiving therapy with EGFR receptor inhibitors
Authors: Kruglova L. S. , Korolyova I. A. , Shatokhina E. A.
Published: December 2020

Cancer chemotherapy advanced dramatically. The success in the management of a broad spectrum of malignancies was achieved due to the development of targeted chemotherapeutic drugs, such as inhibitors of the epidermal growth factor receptor (iEGFR). The most common dermatologic side effect of iEGFR therapy is an acneiform rash that occurs in 60–80 % of patients. This adverse event develops during the first 2 weeks of treatment with iEGFR. Diagnostics of acneiform rash may be complicated because of different interpretations by oncologists and dermatologists. Acneiform rash is frequently associated with pain and itch. Skin toxicity affects a patient’s quality of life, including physical and psychological well-being, emotional and social adaptation, may lead to dose reduction and iEGFR discontinuation. The degree of acneiform rash correlates with an iEGFR effectiveness, which is currently confirmed by different data. Thus, the prevention and prompt management of dermatologic adverse events is a pressing issue because they influence the anti-cancer treatment prognosis. This article reviews the current recommendations on the prevention and management of iEGFR associated acneiform rash. The authors present their own clinical case of a patient with acneiform rash during panitumumab (monoclonal antibody against EGFR) therapy.
Lichen planus of anogenital region: clinical spectrum and approaches to therapy
Authors: Smirnova I. O. , Parygina O. V. , Petunova Ya. G. , Shin N. V. , Zhelonkina A. O.
Published: December 2020

Lichen planus is among the most common chronic anogenital noninfectious dermatoses both in male and female. The disease is characterized by clinical polymorphism, frequent involvement of skin and oral mucosa and protracted course. Typical, hypertrophic and erosive forms are distinguished. Erosive variant is commonly encountered in women and has a prominent tendency for scarring. The most common anogenital form in men is the typical lichen planus, which usually resolves completely. Vulvovagino-gingival and penogingival lichen planus are rare severe disease forms. Evolutional and biological heterogeny of clinical manifestations complicates the disease diagnosis. Lichen planus pathogenesis remains unclear. Pronounced scarring tendency in anogenital cases is believed to be the consequence of epithelial-mesenchimal transition. High-quality clinical trials of various therapeutic modalities in anogenital lichen planus are lacking. Management of such patients is mostly based on case series reports, practical experience and general principles of dermatologic treatment. This review focuses on contemporary views on clinical presentation, pathogenesis, diagnosis and approach to therapy of anogenital lichen planus.
Maintenance acne therapy: prophylactic efficacy of fixed combination of adapalene and benzoyl peroxide
Authors: Kruglova L. S. , Gryazeva N. V.
Published: December 2020

Acne is a chronic disease and even reliable therapies do not completely ensure absence of relapses. Acne relapses have a negative psychological impact on patients, as they feel unable to control the disease and achieve complete and long-lasting recovery. Supportive therapy is necessary to prolong the remission of acne achieved with initial successful treatment and to minimize the risk of relapse. According to the literature sources, the most justified as a maintenance therapy is the use of topical retinoids, which have been shown to be effective in the prevention of exacerbations of acne. In the present study 54 patients were involved who after the active therapy used a fixed combination of adapalene 0.1% / BPO 2.5% as maintenance treatment. Only 1 patient (2.9%) with moderate acne and 2 patients (5.8%) with severe acne had a relapse within 6 months of maintenance therapy. The absence of adverse events during the course of treatment was recorded, as well as high adherence of patients to the treatment. During the period of post-treatment observation (6 months after maintenance therapy), among the patients without exacerbations during maintenance therapy, a relapse occurred in 2 (7.1%) patients of group 1 (n = 28) and 2 (8.7%) patients of group 2 (n = 23). The obtained data indicates that maintenance therapy with Effezel® gel can extend the achieved effectiveness of the treatment and prevent the development of relapses.
Tanaman Berkhasiat untuk Pengobatan Malaria di Indonesia Berdasarkan Etnofarmasi
Authors: Mufidah Farah , Zuhrotun Ade
Published: December 2020

Malaria merupakan penyakit yang umum terjadi pada negara-negara tropis termasuk Indonesia. Penyakit malaria disebabkan oleh Plasmodium sp. yang ditandai dengan beberapa gejala seperti demam dan nyeri sendi. Hal ini dapat dipengaruhi oleh berbagai faktor yaitu sanitasi yang buruk, migrasi, tingkat kepadatan penduduk, faktor pekerjaan, dan resistensi Plasmodium sp. terhadap obat-obat. Pengobatan konvensional malaria saat ini yaitu Chloroquine (Chloroquine Phosphateâ), Mefloquine (Lariamâ), Quinine (Quinineâ), Primaquine (Primakuinâ), Pyrimethamine (Pirimetaminâ). Namun, beberapa etnik masyarakat wilayah di Indonesia masih mengonsumsi tanaman herbal yang sudah ada dan didapatkan secara turun temurun. Dari 44 tanaman pengobatan malaria berdasarkan etnofarmasi diketahui tanaman terbaik yaitu Caesalpinia crista  (L.) dengan nilai IC50 0,09 µg/mL dan tanaman dengan efektifitas terbaik yaitu Tithonia diversifolia (Hemsl.) dengan nilai ED50 200 mg/Kg. Adanya kandungan diterpen dan sesquiterpen pada bagian tanaman tersebut memberikan ekstrak memiliki aktivitas antimalaria yang baik.
Antibacterial Activity Of Tangerine Powder (Citrus reticulata Blanco.) Against Caries-Causing Bacteria (Streptococcus mutans)
Authors: Sriarumtias Framesti Frisma , Najihudin Aji , Rantika Nopi , Nengsih Rita
Published: December 2020

Dental caries is caused by Streptococcus mutans, which lives in the oral cavity and causes plaque on the teeth. Dental caries treatment involves restoration or filling of tooth tissue that has been perforated due to dental caries. The purpose of this study was analyze the effectivity of  tangerine juice powder in preventing the emergence of dental caries caused by Streptococcus mutans. The experimental method was used in this study started by making a powder from tangerine jiuce using freeze drying method, followed by testing the antibacterial activity using the disc diffusion method. In addition, the minimum inhibitory concentration (MIC) was also sought by measuring the diameter of the clear zone. The results showed that tangerine powder has antibacterial activity, with a minimum inhibitory concentration of 10%. The highest activity of tangerine powder to inhibit the growth of Streptococcus mutans bacteria was observed at   concentration of 25% with an inhibition zone diameter of 15.8 mm, and is classified as having moderate inhibitory power. According to the result of this study is that tangerine juice powder has a good antibacterial activity against Streptococcus mutans and can be developed into a pharmaceutical ingredients to prevent dental caries.
Toksisitas Subkronis Ekstrak Etanol Propolis Dengan Parameter Konsentrasi Glukosa, Kolesterol dan Trigliserida Pada Darah Tikus
Authors: Hasan Akhmad Endang Zainal , Husnawati Husnawati , Abrar Tommy
Published: December 2020

Propolis merupakan salah satu bahan alam yang dimanfaatkan oleh masyarakat, antara lain sebagai antibakteri, hepatoprotektor, anestesi lokal, antikanker dan antioksidan. Penelitian ini bertujuan menentukan tingkat toksisitas subkronis ekstrak etanol 70% propolis (EEP) pada tikus Sprague Dawley terhadap glukosa, kolesterol dan trigliserida darah selama 28 hari. Ekstrak propolis diberikan sebanyak 1 ml secara oral pada tikus jantan dan betina sebanyak 60 ekor dan 10 ekor sebagai kontrol. Ekstrak diberikan dalam dosis 0,3 mg/kg bobot badan (BB), 2,1 mg/kg BB, 14,7 mg/kg BB, 102,9 mg/kg BB, dan 720,3 mg/kg BB sebanyak 5 kali dalam seminggu selama 28 hari. Konsentrasi glukosa darah tikus jantan dan betina pada hari ke-28 adalah 79,85 – 97,49 mg/dL dan 61,88 – 90,26 mg/dL. Konsentrasi kolesterol darah tikus jantan dan betina pada hari ke-28 adalah 100,42 – 116,25 mg/dL dan 118,63 – 132,78 mg/dL. Konsentrasi trigliserida darah tikus jantan dan betina pada hari ke-28 adalah 128,64 – 142,37 mg/dL dan 110,95 – 128,58 mg/dL. Pemberian ekstrak etanol 70% propolis sampai dosis 720,3 mg/kg bb selama 28 hari tidak mengakibatkan abnormalitas terhadap nilai glukosa, kolesterol dan trigliserida darah tikus Sprague Dawley.  Semua parameter pada hari ke-28 tidak menunjukkan perbedaan yang signifikan secara statistika dibandingkan dengan kelompok normal.  Ekstrak etanol 70% propolis pada penelitian ini tidak menimbulkan pengaruh toksik pada konsentrasi glukosa, kholesterol dan trigliserida selama pengujian subkronis 28 hari.  Uji ANOVA pada hari ke-28 tidak menunjukkan perbedaan nyata dibandingkan dengan kelompok normal.
Aktivitas Gel Ekstrak Etanol Daun Pucuk Merah (Syzygium myrtifolium) Terhadap Penyembuhan Luka Bakar Tikus Sprague-Dawley
Authors: Indriani Lusi , Almasyhuri Almasyhuri , Pratama Aldryan Racka
Published: December 2020

Luka bakar adalah bentuk kerusakan jaringan yang disebabkan kontak dengan sumber panas seperti api, air panas, bahan kimia, listrik, dan radiasi. Gejalanya berupa sakit, bengkak, merah, melepuh karena permeabilitas pembuluh darah meningkat. Salah satu tanaman yang diduga berpotensi sebagai obat luka bakar adalah daun pucuk merah, yang mengandung beberapa senyawa metabolit sekunder seperti alkaloid, flavonoid, kalkon, tanin, dan terpenoid. Penelitian ini bertujuan untuk mengetahui aktivitas gel ekstrak etanol daun pucuk merah pada luka bakar tikus putih jantan Sprague-Dawley. Kelompok perlakuan terdiri dari formula 1 (ekstrak daun pucuk merah 2%), formula 2 (ekstrak daun pucuk merah 4%), formula 3 (ekstrak daun pucuk merah 6%), Bioplacenton sebagai kontrol positif dan basis gel sebagai kontrol negatif. Hasil penelitian menunjukkan bahwa gel ekstrak daun pucuk merah memberikan efek sebagai obat luka bakar, dimana proses penyembuhan ditandai dengan penurunan diameter luka yang lebih cepat pada tikus. Formula 3 menunjukkan persentase penyembuhan luka bakar yang paling efektif yaitu 99,81% sembuh setelah 17 hari.
Vart är äldreomsorgen på väg?
Authors: Siverskog Anna , Jönson Håkan
Published: December 2020

Many Swedish municipalities approve home-care services for persons above a particular age without individual need assessment (FBH) and following a change in the Social Service Act 2018, this policy is likely to increase. How can this development be understood in relation to larger trends within Swedish eldercare policy and practice? This article is based on an interview study with 50 representatives for municipal social services and aims to explore argument for and against FBH, and how these arguments represent differences in views on eldercare. Toulmin’s model of argumentation was used to sort data and Bacchi’s What’s the Problem Represented to be approach was used to relate findings to the development of eldercare. A striking finding was that arguments for and against FBH in several cases were based on the same warrants: user participation, independence and efficient use of resources. FBH was however also presented as a means to base services on trust, and to avoid the intrusive and blunt character of needs assessments. Arguments against FBH suggested that evaluated needs rather than age should be the foundation of services. A conclusion of the study is that FBH introduces a partly new concept of needs that is based on self-evaluation of older persons. This development could in one sense be regarded as empowering, but in another sense as part of the ongoing marketization of eldercare, where services are defined as commodities.
Overcoming Energetic Barriers in Acetogenic C1 Conversion
Authors: Katsyv Alexander , Müller Volker
Published: December 2020

Currently one of the biggest challenges for society is to combat global warming. A solution to this global threat is the implementation of a CO2-based bioeconomy and a H2-based bioenergy economy. Anaerobic lithotrophic bacteria such as the acetogenic bacteria are key players in the global carbon and H2cycle and thus prime candidates as driving forces in a H2- and CO2-bioeconomy. Naturally, they convert two molecules of CO2viathe Wood-Ljungdahl pathway (WLP) to one molecule of acetyl-CoA which can be converted to different C2-products (acetate or ethanol) or elongated to C4 (butyrate) or C5-products (caproate). Since there is no net ATP generation from acetate formation, an electron-transport phosphorylation (ETP) module is hooked up to the WLP. ETP provides the cell with additional ATP, but the ATP gain is very low, only a fraction of an ATP per mol of acetate. Since acetogens live at the thermodynamic edge of life, metabolic engineering to obtain high-value products is currently limited by the low energy status of the cells that allows for the production of only a few compounds with rather low specificity. To set the stage for acetogens as production platforms for a wide range of bioproducts from CO2, the energetic barriers have to be overcome. This review summarizes the pathway, the energetics of the pathway and describes ways to overcome energetic barriers in acetogenic C1 conversion.
FAIM Is Regulated by MiR-206, MiR-1-3p and MiR-133b
Authors: Coccia Elena , Masanas Marc , López-Soriano Joaquín , Segura Miguel F. , Comella Joan X. , Pérez-García M. José
Published: December 2020

Apoptosis plays an important role during development, control of tissue homeostasis and in pathological contexts. Apoptosis is executed mainly through the intrinsic pathway or the death receptor pathway, i.e., extrinsic pathway. These processes are tightly controlled by positive and negative regulators that dictate pro- or anti-apoptotic death receptor signaling. One of these regulators is the Fas Apoptotic Inhibitory Molecule (FAIM). This death receptor antagonist has two main isoforms, FAIM-S (short) which is the ubiquitously expressed, and a longer isoform, FAIM-L (long), which is mainly expressed in the nervous system. Despite its role as a death receptor antagonist, FAIM also participates in cell death-independent processes such as nerve growth factor-induced neuritogenesis or synaptic transmission. Moreover, FAIM isoforms have been implicated in blocking the formation of protein aggregates under stress conditions or de-regulated in certain pathologies such as Alzheimer’s and Parkinson’s diseases. Despite the role of FAIM in physiological and pathological processes, little is known about the molecular mechanisms involved in the regulation of its expression. Here, we seek to investigate the post-transcriptional regulation of FAIM isoforms by microRNAs (miRNAs). We found that miR-206, miR-1-3p, and miR-133b are direct regulators of FAIM expression. These findings provide new insights into the regulation of FAIM and may provide new opportunities for therapeutic intervention in diseases in which the expression of FAIM is altered.
LncRNA DHRS4-AS1 Inhibits the Stemness of NSCLC Cells by Sponging miR-224-3p and Upregulating TP53 and TET1
Authors: Yan Fei , Zhao Wei , Xu Xiaoyue , Li Chenchen , Li Xiaoyou , Liu Siwen , Shi Lin , Wu Yuan
Published: December 2020

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. This study aimed to examine the roles of DHRS4-AS1/miR-224-3p signaling in the cancer cell stemness of NSCLC. Real-time PCR showed that DHRS4-AS1 was downregulated in cancerous tissues, and bioinformatics analysis revealed that high DHRS4-AS1 expression indicated a good prognosis for NSCLC patients. Sphere and colony formation assays showed that DHRS4-AS1 overexpression significantly suppressed NSCLC cell colony formation and stem cell-like properties. DHRS4-AS1 also abrogated the expression of OCT4, SOX2, CD34, and CD133, markedly inhibited the expression of epithelial-mesenchymal transition (EMT)-related factors, N-cadherin, ZEB1, and Vimentin, and increased E-cadherin expression in spheres. Furthermore, luciferase reporter assays and real-time PCR analysis demonstrated that DHRS4-AS1 and miR-224-3p were antagonistically repressed in NSCLC cells. RNA immunoprecipitation (RIP) analysis revealed that DHRS4-AS1 interacted with miR-224-3p. DHRS4-AS1 partially reversed the miR-224-3p-decreased TP53 and TET1, resulting in the inhibition of tumor growth in vivo. Finally, TP53 and TET1 were antagonistically regulated by DHRS4-AS1 and miR-224-3p in NSCLC cells. In conclusion, TP53- and TET1-associated DHRS4-AS1/miR-224-3p axis is an essential mechanism by which NSCLC modulates cancer cell stemness.
Establishment and Characterization of a Topotecan Resistant Non-small Cell Lung Cancer NCI-H460/TPT10 Cell Line
Authors: Lei Zi-Ning , Teng Qiu-Xu , Zhang Wei , Fan Ying-Fang , Wang Jing-Quan , Cai Chao-Yun , Lu Kimberly W. , Yang Dong-Hua , Wurpel John N. D. , Chen Zhe-Sheng
Published: December 2020

While topotecan (TPT) is a first- and second-line chemotherapeutic drug in treating lung cancer, the development of drug resistance in tumors still reserves as a major obstacle to chemotherapeutic success. Therefore, a better understanding of the mechanisms of topotecan resistance is critical. In this study, the first topotecan-resistant human non-small cell lung cancer (NSCLC) cell line, termed NCI-H460/TPT10, was established from the parental NCI-H460 cell line. NCI-H460/TPT10 cells exhibited a 394.7-fold resistance to TPT, and cross-resistance to SN-38, mitoxantrone, and doxorubicin, compared to parental NCI-H460 cells. Overexpression of ABCG2 localized on the cell membrane, but not ABCB1 or ABCC1, was found in NCI-H460/TPT10 cells, indicating that ABCG2 was likely to be involved in topotecan-resistance. This was confirmed by the abolishment of drug resistance in NCI-H460/TPT10 cells after ABCG2 knockout. Moreover, the involvement of functional ABCG2 as a drug efflux pump conferring multidrug resistance (MDR) was indicated by low intracellular accumulation of TPT in NCI-H460/TPT10 cells, and the reversal effects by ABCG2 inhibitor Ko143. The NCI-H460/TPT10 cell line and its parental cell line can be useful for drug screening and developing targeted strategies to overcome ABCG2-mediated MDR in NSCLC.
Mutation Screening in the miR-183/96/182 Cluster in Patients With Inherited Retinal Dystrophy
Authors: Xu Shunbin , Coku Ardian , Muraleedharan Chithra K. , Harajli Ali , Mishulin Eric , Dahabra Chafic , Choi Joanne , Garcia William J. , Webb Kaylie , Birch David , Goetz Kerry , Li Weifeng
Published: December 2020

Inherited retinal dystrophy (IRD) is a heterogenous blinding eye disease and affects more than 200,000 Americans and millions worldwide. By far, 270 protein-coding genes have been identified to cause IRD when defective. However, only one microRNA (miRNA), miR-204, has been reported to be responsible for IRD when a point-mutation occurs in its seed sequence. Previously, we identified that a conserved, polycistronic, paralogous miRNA cluster, the miR-183/96/182 cluster, is highly specifically expressed in all photoreceptors and other sensory organs; inactivation of this cluster in mice resulted in syndromic IRD with multi-sensory defects. We hypothesized that mutations in the miR-183/96/182 cluster in human cause IRD. To test this hypothesis, we perform mutation screening in the pre-miR-183, -96, -182 in >1000 peripheral blood DNA samples of patients with various forms of IRD. We identified six sequence variants, three in pre-miR-182 and three in pre-miR-96. These variants are in the pre-miRNA-182 or -96, but not in the mature miRNAs, and are unlikely to be the cause of the IRD in these patients. In spite of this, the nature and location of these sequence variants in the pre-miRNAs suggest that some may have impact on the biogenesis and maturation of miR-182 or miR-96 and potential roles in the susceptibility to diseases. Although reporting on negative results so far, our study established a system for mutation screening in the miR-183/96/182 cluster in human for a continued effort to unravel and provides deeper insight into the potential roles of miR-183/96/182 cluster in human diseases.
Disorders of Sex Development in Individuals Harbouring MAMLD1 Variants: WES and Interactome Evidence of Oligogenic Inheritance
Authors: Li Lele , Gao Fenqi , Fan Lijun , Su Chang , Liang Xuejun , Gong ChunXiu
Published: December 2020

Mastermind-like domain-containing 1 (MAMLD1) has been shown to play an important role in the process of sexual development and is associated with 46,XY disorders of sex development (DSDs). However, the causative role of MAMLD1 variations in DSDs remains disputable. In this study, we have described a clinical series on children from unrelated families with 46,XY DSD harbouring MAMLD1 variants. Whole exome sequencing (WES) was performed for each patient. WES data were filtered using common tools and disease customisation algorithms, including comparison against lists of known and candidate MAMLD1-related and DSD-related genes. Lastly, we investigated the hypothesis that MAMLD1-related DSD may follow an oligogenic mode of inheritance. Forty-three potentially deleterious/candidate variants of 18 genes (RET, CDH23, MYO7A, NOTCH2, MAML1, MAML2, CYP1A1, WNT9B, GLI2, GLI3, MAML3, WNT9A, FRAS1, PIK3R3, FREM2, PTPN11, EVC, and FLNA) were identified, which may have contributed to the patient phenotypes. MYO7A was the most commonly identified gene. Specific gene combinations were also identified. In the interactome analysis, MAMLD1 exhibited direct connection with MAML1/2/3 and NOTCH1/2. Through NOTCH1/2, the following eight genes were shown to be associated with MAMLD1:WNT9A/9B, GLI2/3, RET, FLNA, PTPN11, and EYA1. Our findings provide further evidence that individuals with MAMLD1-related 46,XY DSD could carry two or more variants of known DSD-related genes, and the phenotypic outcome of affected individuals might be determined by multiple genes.
Gene Expression Analysis of the Pre-Diabetic Pancreas to Identify Pathogenic Mechanisms and Biomarkers of Type 1 Diabetes
Authors: Yip Linda , Fuhlbrigge Rebecca , Alkhataybeh Reem , Fathman C. Garrison
Published: December 2020

Type 1 Diabetes (T1D) occurs as a result of the autoimmune destruction of pancreatic β-cells by self-reactive T cells. The etiology of this disease is complex and difficult to study due to a lack of disease-relevant tissues from pre-diabetic individuals. In this study, we performed gene expression analysis on human pancreas tissues obtained from the Network of Pancreatic Organ Donors with Diabetes (nPOD), and showed that 155 genes were differentially expressed by ≥2-fold in the pancreata of autoantibody-positive (AA+) at-risk individuals compared to healthy controls. Only 48 of these genes remained changed by ≥2-fold in the pancreata of established T1D patients. Pathway analysis of these genes showed a significant association with various immune pathways. We were able to validate the differential expression of eight disease-relevant genes by QPCR analysis: A significant upregulation ofCADM2, and downregulation ofTRPM5, CRH, PDK4, ANGPL4, CLEC4D, RSG16, andFCGR2Bwas confirmed in the pancreata of AA+ individuals versus controls. Studies have already implicatedFCGR2Bin the pathogenesis of disease in non-obese diabetic (NOD) mice. Here we showed thatCADM2, TRPM5, PDK4, andANGPL4were similarly changed in the pancreata of pre-diabetic 12-week-old NOD mice compared to NOD.B10 controls, suggesting a possible role for these genes in the pathogenesis of both T1D and NOD disease. The loss of the leukocyte-specific gene,FCGR2B, in the pancreata of AA+ individuals, is particularly interesting, as it may serve as a potential whole blood biomarker of disease progression. To test this, we quantifiedFCGR2Bexpression in peripheral blood samples of T1D patients, and AA+ and AA- first-degree relatives of T1D patients enrolled in the TrialNet Pathway to Prevention study. We showed thatFCGR2Bwas significantly reduced in the peripheral blood of AA+ individuals compared to AA- controls. Together, these findings demonstrate that gene expression analysis of pancreatic tissue and peripheral blood samples can be used to identify disease-relevant genes and pathways and potential biomarkers of disease progression in T1D.
Can Invasiveness in Freshwater Fishes Be Predicted From Life-History Traits?
Authors: Copp Gordon H. , Fox Michael G.
Published: December 2020

We review a model we developed in 2007 to predict the invasion potential of an introduced population, based on the relationship between juvenile growth (mean total length at age 2) and mean age-at-maturity, and test the model with data from 75 non-native populations of pumpkinseedLepomis gibbosusin nine countries of Europe and western Asia. The database used to construct the model was derived from a mix of primary and secondary data collected between 1981 and 2016. Based on number of specimens collected or catch-per-unit-effort data, and/or comments by the original authors, populations were classifieda priorias “invasive” or “non-invasive.” The plot of the proposed model placed populations in three invasiveness categories (non-invasive, transitional, invasive). Of those predicted by the model to be invasive, only 57% were correct with regard to theira prioriclassification, a result that was not statistically significant. For populations predicted by the model to be non-invasive, 70% were correct with regard to theira prioriclassification when “transitional” were grouped with non-invasive (P= 0.0024), and 64% were correct when “transitional” were excluded from the test (P= 0.12). Applications of the model to two other non-native freshwater fishes (black bullheadAmeiurus melasand crucian carpCarassius carassius) are also discussed. The lack of stronger statistical support for the model may have been the result of using life-history traits from the populations after they were introduced, as the source populations were unknown, as well as to shortcomings in the dataset that could affecta prioriand modeled classifications. We conclude that such life-history models can be useful for predicting invasiveness status in non-native freshwater fishes, though the basis of the predictions, statistical or heuristic, will depend on the size and quality of the underlying life-history database.
CRISPR-Cas9-Mediated Mutagenesis of the Rubisco Small Subunit Family in Nicotiana tabacum
Authors: Donovan Sophie , Mao Yuwei , Orr Douglas J. , Carmo-Silva Elizabete , McCormick Alistair J.
Published: December 2020

Engineering the small subunit of the key CO2-fixing enzyme Rubisco (SSU, encoded by rbcS) in plants currently poses a significant challenge, as many plants have polyploid genomes and SSUs are encoded by large multigene families. Here, we used CRISPR-Cas9-mediated genome editing approach to simultaneously knock-out multiple rbcS homologs in the model tetraploid crop tobacco (Nicotiana tabacum cv. Petit Havana). The three rbcS homologs rbcS_S1a, rbcS_S1b and rbcS_T1 account for at least 80% of total rbcS expression in tobacco. In this study, two multiplexing guide RNAs (gRNAs) were designed to target homologous regions in these three genes. We generated tobacco mutant lines with indel mutations in all three genes, including one line with a 670 bp deletion in rbcS-T1. The Rubisco content of three selected mutant lines in the T1 generation was reduced by ca. 93% and mutant plants accumulated only 10% of the total biomass of wild-type plants. As a second goal, we developed a proof-of-principle approach to simultaneously introduce a non-native rbcS gene while generating the triple SSU knockout by co-transformation into a wild-type tobacco background. Our results show that CRISPR-Cas9 is a viable tool for the targeted mutagenesis of rbcS families in polyploid species and will contribute to efforts aimed at improving photosynthetic efficiency through expression of superior non-native Rubisco enzymes in plants.
THI Modulation of Genetic and Non-genetic Variance Components for Carcass Traits in Hanwoo Cattle
Authors: Chung Yoonji , Lee Seung Hwan , Lee Hak-Kyo , Lim Dajeong , van der Werf Julius , Lee S. Hong
Published: December 2020

The phenotype of carcass traits in beef cattle are affected by random genetic and non-genetic effects, which both can be modulated by an environmental variable such as Temperature-Humidity Index (THI), a key environmental factor in cattle production. In this study, a multivariate reaction norm model (MRNM) was used to assess if the random genetic and non-genetic (i.e., residual) effects of carcass weight (CW), back fat thickness (BFT), eye muscle area (EMA), and marbling score (MS) were modulated by THI, using 9,318 Hanwoo steers (N= 8,964) and cows (N= 354) that were genotyped on the Illumina Bovine SNP50 BeadChip (50K). THI was measured based on the period of 15–45 days before slaughter. Both the correlation and the interaction between THI and random genetic and non-genetic effects were accounted for in the model. In the analyses, it was shown that the genetic effects of EMA and the non-genetic effects of CW and MS were significantly modulated by THI. No significant THI modulation of such effects was found for BFT. These results highlight the relevance of THI changes for the genetic and non-genetic variation of CW, EMA, and MS in Hanwoo beef cattle. Importantly, heritability estimates for CW, EMA, and MS from additive models without considering THI interactions were underestimated. Moreover, the significance of interaction can be biased if not properly accounting for the correlation between THI and genetic and non-genetic effects. Thus, we argue that the estimation of genetic parameters should be based on appropriate models to avoid any potential bias of estimates. Our finding should serve as a basis for future studies aiming at revealing genotype by environment interaction in estimation and genomic prediction of breeding values.
Association of Fibroblast Growth Factor 23 With Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study
Authors: Zheng Kai , Lin Lingmin , Cui Pan , Liu Tao , Chen Lin , Yang Chunsheng , Jiang Wei
Published: December 2020

Fibroblast growth factor 23 (FGF23), which is involved in the regulation of vitamin D, is an emerging independent risk factor for cardiovascular diseases. Previous studies have demonstrated a positive association between FGF23 and stroke. In this study, we aimed to assess the association of FGF23 with ischemic stroke and its subtypes by applying a Mendelian randomization (MR) framework. Five genetic variants obtained from a genome-wide association study involving 16,624 European subjects were used as valid instruments of circulating FGF23 levels. MR was applied to infer the causality of FGF23 levels and the risk of ischemic stroke using data from the MEGASTROKE consortium. Subsequently, several MR analyses, including inverse-variance weighted meta-analysis, MR-Egger, weighted median estimate (WME), MR Pleiotropy Residual Sum and Outlier were performed. The heterogeneity test analysis, including Cochran’s Q, I2 test and leave-one-out analysis were also applied. Furthermore, potential horizontal/vertical pleiotropy was assessed. Lastly, the power of MR analysis was tested. Three validated variants were found to be associated with circulating FGF23 levels and were used for further investigation. We found that high expression level of FGF23 was not associated with any ischemic stroke. However, a causal association between genetically predicted FGF23 levels and the risk of large-artery atherosclerotic stroke (LAS) was significant, with an odds ratio of 1.74 (95% confidence interval = 1.08–2.81) per standard deviation increase in circulating FGF23 levels. Our findings provide support for the causal association between FGF23 and LAS, and therefore, offer potential therapeutic targets for LAS. The specific roles of FGF23 in LAS and associated molecules require further investigation.
Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis
Authors: Korniotis Sarantis , D’Aveni Maud , Hergalant Sébastien , Letscher Hélène , Tejerina Emmanuel , Gastineau Pauline , Agbogan Viviane A. , Gras Christophe , Fouquet Guillemette , Rossignol Julien , Chèvre Jean-Claude , Cagnard Nicolas , Rubio Marie-Thérèse , Hermine Olivier , Zavala Flora
Published: December 2020

Achieving immunoregulation via in vivo expansion of Foxp3+ regulatory CD4+ T cells (Treg) remains challenging. We have shown that mobilization confers to multipotent hematopoietic progenitors (MPPs) the capacity to enhance Treg proliferation. Transcriptomic analysis of Tregs co-cultured with MPPs revealed enhanced expression of genes stabilizing the suppressive function of Tregs as well as the activation of IL-1β–driven pathways. Adoptive transfer of only 25,000 MPPs effectively reduced the development of experimental autoimmune encephalomyelitis (EAE), a pre-clinical model for multiple sclerosis (MS). Production of the pathogenic cytokines IL-17 and GM-CSF by spinal cord-derived CD4+ T-cells in MPP-protected recipients was reduced while Treg expansion was enhanced. Treg depletion once protection by MPPs was established, triggered disease relapse to the same level as in EAE mice without MPP injection. The key role of IL-1β was further confirmed in vivo by the lack of protection against EAE in recipients of IL-1β–deficient MPPs. Mobilized MPPs may thus be worth considering for cell therapy of MS either per se or for enrichment of HSC grafts in autologous bone marrow transplantation already implemented in patients with severe refractory multiple sclerosis.
Diagnostic Value of T-SPOT.TB Assay for Tuberculous Peritonitis: A Meta-Analysis
Authors: Luo Ying , Xue Ying , Mao Liyan , Lin Qun , Tang Guoxing , Song Huijuan , Wang Feng , Sun Ziyong
Published: December 2020

Background:Tuberculous peritonitis (TP) is a common form of abdominal tuberculosis (TB). Diagnosing TP remains challenging in clinical practice. The aim of the present meta-analysis was to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and peritoneal fluid (PF) T-SPOT for diagnosing TP.

Methods:PubMed, EmBase, Cochrane, Scopus, Google scholar, China national knowledge internet, and Wan-Fang databases were searched for relevant articles from August 1, 2005 to July 5, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. Diagnostic parameters including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic curve was used to determine the area under the curve (AUC).

Results:Twelve studies were eligible and included in the meta-analysis. The analysis showed that the pooled sensitivity and specificity of PB T-SPOT in diagnosing TP were 0.91 (95% CI, 0.88–0.94) and 0.78 (95% CI, 0.73–0.81), respectively, while the pooled PLR, NLR, and DOR were 4.05 (95% CI, 2.73–6.01), 0.13 (95% CI, 0.07–0.23), and 37.8 (95% CI, 15.04–94.98), respectively. On the other hand, the summary estimates of sensitivity, specificity, PLR, NLR, and DOR of PF T-SPOT for TP diagnosis were 0.90 (95% CI, 0.85–0.94), 0.78 (95% CI, 0.72–0.83), 6.35 (95% CI, 2.67–15.07), 0.14 (95% CI, 0.09–0.21), and 58.22 (95% CI, 28.76–117.83), respectively. Furthermore, the AUC of PB T-SPOT and PF T-SPOT for TP diagnosis were 0.91 and 0.94, respectively.

Conclusions:Our results indicate that both PB T-SPOT and PF T-SPOT can be served as sensitive approaches for the diagnosis of TP. However, the unsatisfactory specificities of these two methods limit their application as rule-in tests for TP diagnosis. Furthermore, the standardization of the operating procedure of PF T-SPOT is further needed.