bluuebunny/crossref_metadata_2025 huggingface dataset:
EL DISEÑADOR Y LA TECNOLOGÍA EN EL ECUADOR
Authors: Suárez Stalin
Published: June 2021

En una sociedad que se sustenta en el avance industrial, es innegable que las decisiones sociales, económicas y políticas involucran consideraciones científicas y de ingeniería, pero lamentablemente las personas que practican esta importante actividad no participan mayormente en los asuntos públicos, de allí la importancia de que las sociedades de ingeniería, y seminarios como el presente traten estos asuntos, con un objetivo fundamental cual es el de orientar, dar ideas, y aún presentar posibles soluciones que puedan ser recogidas por quienes tienen en sus manos el estructurar el presente y el futuro del país en beneficio de las grandes mayorías populares.
Developing Students’ Speaking Skills through Flipped Classroom Model
Authors: Sudarmaji Imam , Amaliyah Anwar Ariskha Ananda , Mulyana Agus
Published: June 2021

The aim of this study was to examine the impact of implementing flipped classroom model on students’ speaking skills. This research used quantitative method, the number of the sample were 34 of senior high school students which was taken purposively by using quasi-experimental research with before and after design. The whole online flipped classroom model was carried out, since the limitation to hold the actual face-to-face meeting at school, which still allow the students to interact face-to-face with each other and the teacher virtually through a group chat and video conferencing to discuss the material given and practicing to use spoken English during the class sessions. Pre-class activity was held using a group chat by giving instruction to the students to study the material before the actual class session and during the class session the whole class were meet face-to-face through video conferencing. A speaking test was carried before and after the implementation of flipped classroom model to assess the students’ speaking performance. Among the experimental group, the result showed the fully online flipped classroom model not only engage them with the English material but also significantly improved their speaking performance.  Furthermore, the students were become more confident to speak in English during the class session.
The Effect of Self-assessment on the Development of EFL Reading Comprehension Skills
Authors: TAKARROUCHT Kenza
Published: June 2021

Using self-assessment as part of reading courses is key to improving reading comprehension skills. This study aims at exploring how self-assessment develops EFL students’ reading comprehension skills. It was conducted with a sample of 40 students enrolled in the English Department, University of Algiers 2 during the first semester of the academic year 2020/2021. To collect data, an embedded mixed-methods research paradigm was used which involved collecting both quantitative and qualitative data.  The quantitative data were test scores collected as part of a pre-experiment. The pre-experiment involved administering a pre and post reading test and implementing a treatment. The treatment implemented was a self-assessment of reading strategies checklist. The qualitative data were   obtained by means of an open-ended interview on participants’ reading strategies. Quantitative data were analysed by calculating the mean score and the t-test, while qualitative data were analysed using content analysis. The findings indicated that self-assessment helped the students to increase test scores and to develop their reading strategies. It enabled them to plan, monitor, and evaluate their reading process by implementing different strategies and techniques. Drawing on these findings, it is suggested that English teachers use self-assessment of reading strategies as part of reading courses, since it can improve students’ reading comprehension skills and strategy use.
Questionários de avaliação da sobrecarga do cuidador informal: Revisão integrativa
Authors: Correia Elaine Trevezanuto , Santos Fernanda Gatez Trevisan dos , Rodrigues Thamires Fernandes Cardoso da Silva , Zulin Aline , Radovanovic Cremilde Aparecida Trindade
Published: June 2021

Objetivo: Identificar na literatura, os questionários de avaliação da sobrecarga em cuidadores informais. Método: Revisão integrativa, conduzida nas estratégias de busca: CINAHL, Biblioteca Virtual em Saúde, Web of Science e Scopus (Elsevier). Por meio da seguinte questão de pesquisa: Quais são os questionários de avaliação da sobrecarga do cuidador informal disponíveis na literatura? Utilizou-se o software RAYYAN® para importar os dados. Resultados: detectaram-se nas bases 292 obras, destas quatorze contemplaram a revisão. Os estudos utilizaram 44 instrumentos de avaliação, os quais analisaram a depressão, ansiedade, qualidade de vida entre outros, elementos que se relacionam direta ou indiretamente a sobrecarga do cuidador informal. Os resultados foram apresentados em forma de tabela e os questionários mais utilizados para avaliar a sobrecarga do cuidador informal dentre os 44 identificados na pesquisa. Conclusão: Identificou-se inúmeros instrumentos que avaliaram indiretamente a sobrecarga do cuidador informal, entretanto apenas seis questionários destinados à avaliação da sobrecarga do cuidador informal.
Práticas de cuidado em um CAPS-AD: Sobre a abstinência e redução de danos
Authors: Tavares Diogo Henrique , Silva Aline Basso da , Pavani Fabiane Machado , Nunes Cristiane Kenes , Franchini Beatriz , Rodrigues Cândida Garcia Sinott  Silveira
Published: June 2021

Objetivo: analisar as práticas de cuidado ao usuário de drogas em um CAPS ad sobre a perspectiva da abstinência e redução de danos. Método: pesquisa qualitativa, desenvolvida em um serviço de saúde no interior localizado na fronteira entre Rio Grande do Sul/ Brasil e Uruguai. Os dados foram coletados com seis profissionais entre abril e setembro de 2017 por meio de entrevista semiestruturada como fonte de coleta de dados e análise de conteúdo para a sistematização dos achados. Resultados: A partir da análise, as informações foram organizadas em quatro categorias temáticas: Os testes toxicológicos e as finalidades de sua utilização; Acolhimento e os testes rápidos para IST’s e toxicológicos; A abstinência comprovada como critério de encaminhamento para a UAT; e As Consequências perante a imposição da abstinência no processo de reabilitação. Conclusão: É necessário refletir o processo de cuidado que inclua ações de redução de danos, excluindo o foco do tratamento na abstinência.
Detecção de dois tipos tumorais distintos em cavidade bucal de Cão: Relato de caso
Authors: Pereira Geovanna Santos , Carvalho Monique Resende , Abdalla Samira Lessa , Silva Marta Fernanda Albuquerque da , Gomes Lianna Ghisi , Spiller Paulo Roberto , Faria Eduardo Ferreira , Dall’Acqua Priscila Chediek , Paula Eric Mateus Nascimento de , Martini Andresa de Cássia
Published: June 2021

A cavidade bucal representa o quarto local mais frequente de neoplasias, sendo responsáveis por aproximadamente 5% dos tumores em cães. Sua ocorrência é maior em animais com idade média a avançada, sendo também observada em animais jovens. O objetivo desse relato foi realizar a descrição de dois tipos tumorais distintos identificados na cavidade bucal de um cão, dando ênfase para realização de exame histopatológico individual, para diferentes massas em uma mesma região anatômica. Foi avaliado um cão da raça Golden Retriever e ao exame específico da cavidade bucal foi observado halitose, doença periodontal grau III e presença de neoformação em mucosa jugal da maxila e mucosa mandibular, ambas do lado esquerdo. O animal foi encaminhado para realização de exérese de massa, através de técnica cirúrgica clássica e os fragmentos encaminhados para análise histopatológica, que evidenciou melanoma melanocítico em mucosa mandibular e mastocitoma na mucosa jugal da maxila, ambas do lado esquerdo. O pós-operatório consistiu na limpeza da cavidade bucal duas vezes ao dia com periogard®, durante dez dias, stomorgyl 20®, 3 comprimidos, SID, por 7 dias, maxicam® 2 mg, 2 comprimidos, SID, durante 3 dias e tramadol 50 mg, 2 comprimidos, BID, por 5 dias, todos por via oral.  Ao 10° dia do pós- operatório o animal retornou para avaliação, onde observou-se boa cicatrização no local de exérese das lesões, nessa ocasião foi realizada uma sessão de eletroquimioterapia com sulfato de bleomicina, na região da cicatriz cirúrgica. Aos 30 dias do pós- operatório o animal encontrava-se bem, com boa alimentação e sem recidiva de lesões em cavidade bucal. Esse estudo reforça a necessidade do diagnóstico e adoção terapêutica rápidas, para manutenção da qualidade e aumento na expectativa de vida do paciente que apresenta neoplasia em cavidade bucal. A realização de exame histopatológico individual, em diferentes massas em uma mesma região anatômica é imprescindível, a fim de identificar o tipo tumoral corretamente e estabelecer o tratamento, que pode contemplar exérese cirúrgica clássica ou ainda utilizar de terapias adjuvantes, como a eletroquimioterapia.
Laboratory findings in imaging diagnostic tests in patients infected with COVID-19 – A study review
Authors: Souza Caio Robert Rodrigues Martins de , Santos Danilo Lopes , Melo Larissa Maria Freire de , Alves Lumar Lucena , Silva Luiz André Santos , Santana Natália Jamille Alves de , Santos Míriam Clécia de Oliveira , Carvalho Thatyane Gama , Santos Jonas Prata Estevão dos , Oliveira Tereza Tizar Alves , Lucena Ingridy Evangelista Viana , Oliveira Raphaella Ingrid Santana
Published: June 2021

Purpose: This study disseminates the diagnosis of COVID-19 emphasizing the importance of imaging tests in medical interpretation and identification of its complications, besides demonstrating the contribution to patient care. Methodology: The study was conducted based on a literature review, in addition to the acquired results of imaging tests from clinical patients at a Public Hospital of the State of Sergipe, Brazil, to point the scoring system in thorax radiography and compare to computed tomography (CT). Results: The imaging tests are not indicated for patients with mild symptoms and suspected COVID-19 infection, except for risk of disease progression, being indicated in the complementary diagnosis of COVID-19 positive patients. Studies show that thorax radiography is more used because it has low cost and easy access. However, its use has limitations due to the low sharpness of the images and impossibility of visualization of some lesions. Computed tomography, on the other hand, can be used as a pulmonary monitoring and evolution test in patients with COVID-19 worsening and/or persistent homeostatic changes. Nevertheless, this test is not indicated for acute cases without aggravating symptoms. Conclusion: The high degree of dissemination of SARS-CoV-2 and the collapse of health systems demonstrated the importance of the science in health. In addition, the importance of laboratory tests in the diagnosis of virus infection and imaging tests in the early diagnosis of SARS-CoV-2 pneumonia has been shown as efficient complementarity in the evolution and clinical interpretation of patients, highlighting the importance of radiography and CT exams.
A Lei nº 13.415 e suas contribuições no contexto da formação cidadã da juventude no Ensino Médio
Authors: Vasconcelos Ada Raquel da Fonseca , Queiroz Nágila Maria Barroso de , Souza Érica de Souza e , Falcão Nádia Maciel
Published: June 2021

Este artigo tem como objetivo analisar a Lei nº 13.415, de fevereiro de 2017 e as suas contribuições no contexto da formação cidadã da juventude no Ensino Médio. Para isso, recorreu-se à pesquisa bibliográfica e documental, a partir de um conjunto de referenciais, leis e decretos que permitiu uma análise mais profunda para o entendimento dos processos que levaram à construção da atual contrarreforma do Ensino Médio no país, articulada às categorias Trabalho e Educação; bem como aos desafios que se apresentam para o fortalecimento das políticas educacionais para a juventude brasileira.
Avaliação dos fatores de risco para fatura osteoporótica em mulheres pós menopausa
Authors: Alves Breno William Santana , Pereira Francisco de Assis , Silva Ronald Bispo Barreto da , Alves Neto José Seabra , Cruz Amanda Raquel Costa
Published: June 2021

Objetivo: avaliar os fatores de risco para osteoporose e fratura por fragilidade em mulheres idosas. Métodos: Estudo descritivo, observacional e transversal com amostra de conveniência realizado em um serviço ambulatorial, privado, vinculado à Universidade Tiradentes, na cidade de Aracaju-SE.  Resultados: A casuística do estudo foi composta por 102 mulheres pós menopausa. Os três fatores de risco para osteoporose que apresentaram maior frequência em nossa amostra foram sedentarismo (70,6%), uso de corticoide (17,6%), menopausa precoce (15,3%), todas as participantes possuíam pelo menos três fatores de risco. Todas as participantes do estudo têm indicação de densitometria óssea, porém 68 (66,7%) referiram ter sido submetidas ao exame e destas, 32 (31,4%) referiram ter o diagnóstico de osteoporose densitométrica. Em relação à queda, 43 (42,2%) participantes relataram já ter apresentado pelo menos um episódio no último ano. Conclusões: Nossos resultados demonstram que a população feminina e idosa, embora apresente maiores risco para osteoporose e fratura por fragilidade, ainda é negligenciada em nosso meio, demonstrando que há necessidade de programas de promoção de saúde e na prática médica rotineira para detecção dos fatores de risco para osteoporose e bem com de fraturas nos grupos de indivíduos mais propensos a apresentarem estas condições clínicas.
Fratura orbitária provocada por projetil de borracha: Relato de caso
Authors: Oliveira Mirlany Mendes Maciel , Borges Amanda Bárbara , Acioly Rodrigo da Franca , Souza Dennis Dinelly de , Carvalho Daniel do Carmo , Silva Bruno Araújo da
Published: June 2021

Os projeteis de borracha são utilizados, geralmente por entidades policiais e de segurança privada, na busca de um melhor controle de manifestações, tumultos ou rebeliões. Consideradas armas menos letais que as armas de fogo, tais artifícios podem causar lesões corporais devastadoras, com consequências estéticas, funcionais e sociais inimagináveis ao alvo. A utilização deste instrumento deve seguir recomendações criteriosamente na busca de evitar e/ou minimizar danos. As lesões balísticas que acometem a região maxilofacial consistem em um desafio para o cirurgião Bucomaxilofacial, em virtude do seu alto grau de complexidade, devendo ser realizado a identificação anatômica dos tecidos danificados, o entendimento das limitações desse tipo de lesão, a preservação de tecidos esqueléticos e moles. Desta maneira a conscientização do potencial lesivo deste instrumento deve ser prioridade na busca de minimizar lesões advindas do mesmo.  O objetivo deste artigo é relatar o caso clínico de fratura orbitária causada por projétil de borracha, bem como discutir o potencial de morbidade deste instrumento.
A utilização dos massageadores perineais e dilatadores vaginais como métodos de tratamento fisioterapêutico nas Disfunções Pélvicas: Vaginismo e Dispareunia
Authors: Nagamine Bruna Pereira , Silva Karla Camila Correia da
Published: June 2021

Os massageadores perineais são recursos manuais terapêuticos que são realizados através de deslizamentos e liberações miofasciais na região pélvica, estimulando o relaxamento da musculatura e provocando um efeito inibitório nas tensões musculares, e os dilatadores vaginais amolecem os tecidos e promovem consciência corporal. O objetivo do presente artigo é demonstrar como os dos massageadores perineais e dilatadores vaginais podem ser eficazes no tratamento do vaginismo e da dispareunia, a partir das pesquisas realizadas através das plataformas digitais: Scielo, Pubmed e PEDro. Conclui-se que diante das patologias vaginismo e dispareunia os massageadores perineais e dilatadores vaginais podem ser eficazes no tratamento por diminuindo a percepção da dor e a tensão muscular, recuperando o tônus e promovendo a dessensibilização da musculatura do assoalho pélvico.
Climatology and variability of the start, end, and length of the frost-free season across Iran
Authors: Kiany MSK , Masoodian SA , Balling Jr RC
Published: June 2021

Climate change can manifest in many ways, including impacts on the start, end, and duration of the frost-free season. We examined the climatology and variability of the first fall frost day (FFFD), last spring frost day (LSFD), and length of the frost-free season (LFFS) across Iran for the period 1978-2017. Trend analysis revealed that FFFD shifted later by 6.4 d over the study period while LSFD shifted earlier by slightly over 2 wk, and LFFS is now >3 wk longer than it was only 4 decades ago. Since land-use changes around meteorological stations may affect the temperature measured at these stations (especially the magnitudes of nocturnal cooling rates), atmospheric thickness changes, which reflect temperature changes and are independent of station-based measurements, were used as a secondary dataset to investigate minimum temperature trends. The analysis revealed a very strong relationship between frost-related indices and atmospheric thickness. Sequential Mann-Kendall statistical analysis revealed abrupt changes in the applied frost-related indices, minimum temperatures, and atmospheric thicknesses. The first abrupt changes in FFFD and LFFS occurred around 1996, which matched the timing of abrupt changes in atmospheric thickness over Iran. Interestingly, seasonal trend analyses of minimum temperature over the Northern Hemisphere using Era5 reanalysis data indicated consistent regional patterns of warming over the last 4 decades. The results suggest that the increase in LFFS is largely driven by regional-scale warming as opposed to local urbanization and/or land-use changes. Our results document an important and ongoing change of potentially considerable interest to agriculturalists in Iran and elsewhere.
Tracking young-of-the-year gray seals Halichoerus grypus to estimate fishery encounter risk
Authors: Murray KT , Hatch JM , DiGiovanni RA , Josephson E
Published: June 2021

The current level of annual incidental bycatch of gray seals Halichoerus grypus in the New England sink gillnet fishery is the highest for all marine mammal species in the USA. One way to evaluate the risk of bycatch is to examine the risk of encounter between an animal and fishing gear based on the animal’s habitat use in relation to fishing activity. Here we used satellite telemetry deployed on 30 gray seal pups in 2019 and 2020 to measure the risk of encounter with large-mesh sink gillnet fishing effort throughout the Gulf of Maine and southern New England. We estimated relative encounter risk within 30 min grid cells in each calendar quarter based on the overlap of seal presence and fishing effort, and then validated the expected risk based on bycatch events reported by independent observers on board fishing vessels. The relative risk of seals encountering gillnet fishing gear was highest off southeastern Massachusetts in spring. Patterns in the estimated encounter risk fit our expectation that relatively high levels of habitat use and fishing effort correspond to increased encounter risk. The approach taken here can be used to identify times and areas of high encounter risk to justify altered fishing practices for purposes of avoidance, or to target observer monitoring intended to characterize and quantify bycatch. Mitigation strategies will need to be continuously monitored and updated to incorporate new information as conflicts with fisheries and gray seals are likely to continue.
TEKNOLOGI INFORMASI DALAM MENDOKUMENTASIKAN TUTUR BAHASA NGADHA YANG MENGAJARKAN KODE ETIK TEKS LOKAL
Authors: Batarius Patrisius , Vianey Watu Yohanes , Samane Ignatius P. A. N
Published: June 2021

This research is an answer to the concern about the extinction of the local text code of ethics in an area. These codes of ethics teach the noble values ​​of the local area. The area taken in this study is Ngada in the central part of Flores Island, NTT Province. Research and documentation of Ngadha speech which teaches a code of ethics for local texts is widely carried out. However, this is only known by some people who speak Ngadha. The community in general knows the local language spoken from the local customary activities that have been passed down from generation to generation. Current generations and future generations do not know the meaning and speech of their own local language which contains the education of Pancasila values. Information technology is currently one of the solutions in documenting and publishing Ngadha speech. There are 160 Ngadha language sayings which have Pancasila educational values. These data are collected from interviews that have been written in book form and translated into Indonesian. A website is created to document digitally for further dissemination which is equipped with a literal and figurative meaning. It is hoped that, now and in the future, both elementary and secondary school children will know the meaning and value of Ngadha language speech. Educators can teach local wisdom values ​​in the form of texts to students. Another goal, for academic interests, both in the field of information technology and philosophy, is the moral responsibility of academics in documenting local content in Ngadha language.
SISTEM PAKAR DIAGNOSA PENYAKIT TANAMAN KELAPA SAWIT BERBASIS ANDROID
Authors: Surianti Surianti , Banyal Nur Ain
Published: June 2021

The lack of farmers' knowledge about various palm oil palm plant diseases and how to prevent plant is not attacked by the disease even with the lack of knowledge has led to mistakes in dealing with diseases that attack the oil palm plantations. On the other hand, to meet experts who are experts in the field of agriculture plant oil palm is very difficult, it is necessary for the right technology to solve the problem of oil palm plantations.  One way to overcome this problem by building a plant disease expert system palm, to facilitate the farmers know the oil palm plant diseases. There are various methods in an expert system, but here using certainty factor.  This study resulted in an expert system that can be used as a means for diagnosing the disease of oil palm trees are diseased, in the application development using Android SDK android studio and used to run android emulator on a computer or pc
IMPLEMENTASI SISTEM PENGOLAHAN PENILAIAN DATA SISWA SMP NEGERI 1 SEPATAN TIMUR
Authors: Nurninawati Euis , Wulandari Ayu
Published: June 2021

Dalam membangun dan mengembangkan sistem guna memberikan penilaian hasil studi siswa, menguji kelayakan sistem informasi penilaian berbasis website, serta membantu guru dalam memberikan nilai siswa. SMP Negeri 1 Sepatan Timur dalam mengolah data nilai hasil belajar siswa masih menggunakan sistem manual yaitu mengerjakan dengan Microsoft excel kemudian dikumpulkan ke bagian kurikulum baru setelahnya diberikan kepada wali kelas dalam bentuk lembaran kertas. Terkait hal tersebut maka dibutuhkan suatu sistem informasi pengolahan data nilai hasil belajar siswa secara efektif dan efisien. Tujuan dari penelitian ini adalah untuk mengembangkan sistem pengolahan penilaian data siswa berbasis website, Metode yang digunakan dalam penelitian ini adalah metode pengumpulan data, metode analisa, metode perancangan, metode pengembangan dan metode pengujian, Penelitian ini menghasilkan sebuah sistem informasi yang dibuat menggunakan bahasa pemrograman PHP dan MySQL sebagai databasenya. Dari hasil penelitian dapat disimpulkan bahwa sistem penilaian berbasis website dapat dikembangkan untuk membantu guru dalam proses penilaian dan memberikan informasi nilai hasil studi siswa. Sistem informasi penilaian berbasis website dapat mempermudah guru dalam memberikan deskripsi atau catatan untuk setiap aspek mata pelajaran, serta membantu guru dalam perhitungan nilai sehingga menjadi lebih cepat dan akurat dibandingkan dengan perhitungan nilai secara manual. Diharapkan dengan akses informasi yang diberikan kepada siswa dan wali murid dapat membantu dan memantau siswa atau anaknya, Maka penerapan nilai siswa disekolah SMP Negeri 1 Sepatan Timur Kabupaten Tangerang sangat perlu untuk meningkatkan mutu pelayanan penilaian yang baik untuk siswa.
Hepatolienal syndrome in practice of therapist
Authors: Znoyko O. O. , Nosova A. V.
Published: June 2021

The article is a variant of an interdisciplinary educational dialogue between an infectious disease doctor and a therapist and aims to increase the awareness of therapists in terms of diagnosis and treatment of therapeutic and infectious diseases occurring with the presence of hepatolienal syndrome. The most common pathology is briefly presented, algorithms for differential diagnostic search are given.
Ribozyme-Mediated Downregulation Uncovers DNA Integrity Scanning Protein A (DisA) as a Solventogenesis Determinant in Clostridium beijerinckii
Authors: Ujor Victor Chinomso , Lai Lien B. , Okonkwo Christopher Chukwudi , Gopalan Venkat , Ezeji Thaddeus Chukwuemeka
Published: June 2021

Carbon catabolite repression (CCR) limits microbial utilization of lignocellulose-derived pentoses. To relieve CCR in Clostridium beijerinckii NCIMB 8052, we sought to downregulate catabolite control protein A (CcpA) using the M1GS ribozyme technology. A CcpA-specific ribozyme was constructed by tethering the catalytic subunit of Escherichia coli RNase P (M1 RNA) to a guide sequence (GS) targeting CcpA mRNA (M1GSCcpA). As negative controls, the ribozyme M1GSCcpA–Sc (constructed with a scrambled GSCcpA) or the empty plasmid pMTL500E were used. With a ∼3-fold knockdown of CcpA mRNA in C. beijerinckii expressing M1GSCcpA (C. beijerinckii_M1GSCcpA) relative to both controls, a modest enhancement in mixed-sugar utilization and solvent production was achieved. Unexpectedly, C. beijerinckii_M1GSCcpA–Sc produced 50% more solvent than C. beijerinckii_pMTL500E grown on glucose + arabinose. Sequence complementarity (albeit suboptimal) suggested that M1GSCcpA–Sc could target the mRNA encoding DNA integrity scanning protein A (DisA), an expectation that was confirmed by a 53-fold knockdown in DisA mRNA levels. Therefore, M1GSCcpA–Sc was renamed M1GSDisA. Compared to C. beijerinckii_M1GSCcpA and _pMTL500E, C. beijerinckii_M1GSDisA exhibited a 7-fold decrease in the intracellular c-di-AMP level after 24 h of growth and a near-complete loss of viability upon exposure to DNA-damaging antibiotics. Alterations in c-di-AMP-mediated signaling and cell cycling likely culminate in a sporulation delay and the solvent production gains observed in C. beijerinckii_M1GSDisA. Successful knockdown of the CcpA and DisA mRNAs demonstrate the feasibility of using M1GS technology as a metabolic engineering tool for increasing butanol production in C. beijerinckii.
Dynamic Responses of Female Volunteers in Rear Impact Sled Tests at Two Head Restraint Distances
Authors: Carlsson Anna , Horion Stefan , Davidsson Johan , Schick Sylvia , Linder Astrid , Hell Wolfram , Svensson Mats Y.
Published: June 2021

The objective of this study was to assess the biomechanical and kinematic responses of female volunteers with two different head restraint (HR) configurations when exposed to a low-speed rear loading environment. A series of rear impact sled tests comprising eight belted, near 50th percentile female volunteers, seated on a simplified laboratory seat, was performed with a mean sled acceleration of 2.1 g and a velocity change of 6.8 km/h. Each volunteer underwent two tests; the first test configuration, HR10, was performed at the initial HR distance ∼10 cm and the second test configuration, HR15, was performed at ∼15 cm. Time histories, peak values and their timing were derived from accelerometer data and video analysis, and response corridors were also generated. The results were separated into three different categories, HR10C (N = 8), HR15C (N = 6), and HR15NC (N = 2), based on: (1) the targeted initial HR distance [10 cm or 15 cm] and (2) whether the volunteers’ head had made contact with the HR [Contact (C) or No Contact (NC)] during the test event. The results in the three categories deviated significantly. The greatest differences were found for the average peak head angular displacements, ranging from 10° to 64°. Furthermore, the average neck injury criteria (NIC) value was 22% lower in HR10C (3.9 m2/s2), and 49% greater in HR15NC (7.4 m2/s2) in comparison to HR15C (5.0 m2/s2). This study supplies new data suitable for validation of mechanical or mathematical models of a 50th percentile female. A model of a 50th percentile female remains to be developed and is urgently required to complement the average male models to enhance equality in safety assessments. Hence, it is important that future protection systems are developed and evaluated with female properties taken into consideration too. It is likely that the HR15 test configuration is close to the limit for avoiding HR contact for this specific seat setup. Using both datasets (HR15C and HR15NC), each with its corresponding HR contact condition, will be possible in future dummy or model evaluation.
Propofol Mediated Protection of the Brain From Ischemia/Reperfusion Injury Through the Regulation of Microglial Connexin 43
Authors: Zhang Tingting , Wang Yanyan , Xia Qin , Tu Zhiyi , Sun Jiajun , Jing Qi , Chen Pei , Zhao Xuan
Published: June 2021

Cerebral ischemia/reperfusion (I/R) injury is a serious condition that leads to increased apoptosis of microglial and neurons in the brain. In this study, we identified that Cx43 expression level is significantly increased in the microglial cells during I/R injury. Using anin vitromodel (hypoxia/reoxygenation-H/R injury), we observed that H/R injury leads to an increase in activation of microglial cells and increase in levels of pro-inflammatory markers such as IL-1β, IL-6, and TNF-α. Additionally, we could also observe significant increase in phosphorylation of Cx43 and Cav3.2 levels. To assess the role of H/R injured microglial cells on neuronal population, we cultured the neurons with conditioned media (MCS) from H/R injured microglial cells. Interestingly, we observed that microglial H/R injury significantly decreased Map2 expression and affected neuronal morphology. Further, we aimed to assess the effects of propofol on cerebral H/R injury, and observed that 40 μM propofol significantly decreased Cx43, Cx43 phosphorylation, and CaV3.2 levels. Additionally, propofol decreased apoptosis and increased Map2 expression levels in H/R injured neurons. Using silencing experiments, we confirmed that siCx43 could significantly improve the propofol’s rescue after H/R injury in both microglia and neurons. We further developed anin vivoMCAO (middle cerebral artery occlusion) rat model to understand the effect of propofol in I/R injury. Interestingly, propofol treatment and downregulation of Cx43 significantly decreased the infract volume and apoptosis in these MCAO rats. Thus, this study clearly establishes that propofol protects the brain against I/R injury through the downregulation of Cx43 in microglial cells.
The Interdisciplinary Stem Cell Institute’s Use of Food and Drug Administration-Expanded Access Guidelines to Provide Experimental Cell Therapy to Patients With Rare Serious Diseases
Authors: Khan Aisha , Bellio Michael A. , Schulman Ivonne H. , Levi Allan D. , Longsomboon Bangon , Brooks Adriana , Valasaki Krystalenia , DiFede Darcy L. , Pujol Marietsy V. , Yavagal Dileep R. , Bates Karen E. , Si Ming-Sing , Kaushal Sunjay , Green Barth A. , Anderson Kimberly D. , Guest James D. , Burks Stephen Shelby , Silvera Risset , Santamaria Andrea J. , Lalwani Anil , Dietrich W. Dalton , Hare Joshua M.
Published: June 2021

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.
Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis And Post Kala-azar Dermal Leishmaniasis (PKDL)
Authors: Volpedo Greta , Pacheco-Fernandez Thalia , Holcomb Erin A. , Cipriano Natalie , Cox Blake , Satoskar Abhay R.
Published: June 2021

Leishmaniasis is a neglected tropical disease that affects 12 million people worldwide. The disease has high morbidity and mortality rates and is prevalent in over 80 countries, leaving more than 300 million people at risk of infection. Of all of the manifestations of this disease, cutaneous leishmaniasis (CL) is the most common form and it presents as ulcerating skin lesions that can self-heal or become chronic, leading to disfiguring scars. This review focuses on the different pathologies and disease manifestations of CL, as well as their varying degrees of severity. In particular, this review will discuss self-healing localized cutaneous leishmaniasis (LCL), leishmaniasis recidivans (LR), mucocutaneous leishmaniasis (MCL), anergic diffuse cutaneous leishmaniasis (ADCL), disseminated leishmaniasis (DL), and Post Kala-azar Dermal Leishmaniasis (PKDL), which is a cutaneous manifestation observed in some visceral leishmaniasis (VL) patients after successful treatment. The different clinical manifestations of CL are determined by a variety of factors including the species of the parasites and the host’s immune response. Specifically, the balance between the pro and anti-inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease. Depending upon the immune response,Leishmaniainfection can also transition from one form of the disease to another. In this review, different forms of cutaneousLeishmaniainfections and their immunology are described.
The Role of Primary Cilia in Thyroid Cancer: From Basic Research to Clinical Applications
Authors: Ma Cheng-Xu , Ma Xiao-Ni , Li Ying-Dong , Fu Song-Bo
Published: June 2021

Primary cilia (PC) are microtubule-based organelles that are present on nearly all thyroid follicle cells and play an important role in physiological development and in maintaining the dynamic homeostasis of thyroid follicles. PC are generally lost in many thyroid cancers (TCs), and this loss has been linked to the malignant transformation of thyrocytes, which is regulated by PC-mediated signaling reciprocity between the stroma and cancer cells. Restoring PC on TC cells is a possible promising therapeutic strategy, and the therapeutic response and prognosis of TC are associated with the presence or absence of PC. This review mainly discusses the role of PC in the normal thyroid and TC as well as their potential clinical utility.
PV Cell Parameter Extraction Using Data Prediction–Based Meta-Heuristic Algorithm via Extreme Learning Machine
Authors: Li Bing , Chen Huang , Tan Tian
Published: June 2021

To reliably evaluate the practical performance and to undertake optimal control of PV systems, a precise PV cell parameter extraction–based accurate modeling of PV cells is extremely crucial. However, its inherent high nonlinear and multimodal characteristics usually hinder conventional optimization methods to obtain a fast and satisfactory performance. Besides, insufficient current–voltage (I–V) data provided by manufacturers cannot guarantee high accuracy and flexibility of PV cell parameter extraction under various operation scenarios. Hence, this article proposes a novel parameter extraction strategy by data prediction–based meta-heuristic algorithm (DPMhA). An extreme learning machine (ELM) is adopted to predict output I–V data from measured data, which can provide a more reliable fitness function to meta-heuristic algorithms (MhAs). Consequently, MhAs can undertake a more stable search for optimal solution through extended I–V data; thus, PV cell parameters can be obtained with high accuracy and convergence rate. Its effectiveness is validated via three typical PV cell models, that is, single diode model (SDM), double diode model (DDM), and three diode model (TDM). Last, comprehensive case studies illustrate that the DPMhA can considerably enhance the accuracy and effectiveness compared with those without data prediction.
Mitochondrial Genomes of the United States Distribution of Gray Fox (Urocyon cinereoargenteus) Reveal a Major Phylogeographic Break at the Great Plains Suture Zone
Authors: Reding Dawn M. , Castañeda-Rico Susette , Shirazi Sabrina , Hofman Courtney A. , Cancellare Imogene A. , Lance Stacey L. , Beringer Jeff , Clark William R. , Maldonado Jesus E.
Published: June 2021

We examined phylogeographic structure in gray fox (Urocyon cinereoargenteus) across the United States to identify the location of secondary contact zone(s) between eastern and western lineages and investigate the possibility of additional cryptic intraspecific divergences. We generated and analyzed complete mitochondrial genome sequence data from 75 samples and partial control region mitochondrial DNA sequences from 378 samples to investigate levels of genetic diversity and structure through population- and individual-based analyses including estimates of divergence (FSTand SAMOVA), median joining networks, and phylogenies. We used complete mitochondrial genomes to infer phylogenetic relationships and date divergence times of major lineages ofUrocyonin the United States. Despite broad-scale sampling, we did not recover additional major lineages ofUrocyonwithin the United States, but identified a deep east-west split (∼0.8 million years) with secondary contact at the Great Plains Suture Zone and confirmed the Channel Island fox (Urocyon littoralis) is nested withinU. cinereoargenteus. Genetic diversity declined at northern latitudes in the eastern United States, a pattern concordant with post-glacial recolonization and range expansion. Beyond the east-west divergence, morphologically-based subspecies did not form monophyletic groups, though unique haplotypes were often geographically limited. Gray foxes in the United States displayed a deep, cryptic divergence suggesting taxonomic revision is needed. Secondary contact at a common phylogeographic break, the Great Plains Suture Zone, where environmental variables show a sharp cline, suggests ongoing evolutionary processes may reinforce this divergence. Follow-up study with nuclear markers should investigate whether hybridization is occurring along the suture zone and characterize contemporary population structure to help identify conservation units. Comparative work on other wide-ranging carnivores in the region should test whether similar evolutionary patterns and processes are occurring.
New Insights of Phospholipase A2 Associated Neurodegeneration Phenotype Based on the Long-Term Follow-Up of a Large Hungarian Family
Authors: Toth-Bencsik Renata , Balicza Peter , Varga Edina Timea , Lengyel Andras , Rudas Gabor , Gal Aniko , Molnar Maria Judit
Published: June 2021

Introduction

Phospholipase A2-associated Neurodegeneration (PLAN) is a group of neurodegenerative diseases associated with the alterations of PLA2G6. Some phenotype-genotype association are well known but there is no clear explanation why some cases can be classified into distinct subgroups, while others follow a continuous clinical spectrum.

Methods

Long-term neurological, and psychiatric follow-up, neuropathological, radiological, and genetic examinations, were performed in three affected girls and their family.

Results

Two 24-years old twins and their 22-years old sister harbored the p.P622S, and p.R600W mutation in PLA2G6. The age of onset and the most prominent presenting symptoms (gaze palsy, ataxia, dystonia, psychomotor regression indicated atypical neuroaxonal dystrophy (ANAD), however, optic atrophy, severe tetraparesis would fit into infantile neuroaxonal dystrophy (INAD). All siblings had hyperintensity in the globi pallidi and substantiae nigrae which is reported in ANAD, whereas it is considered a later neuroradiological marker in INAD. The slow progression, rigidity, bradykinesis, and the prominent psychiatric symptoms indicate PLA2G6-related dystonia-parkinsonism. Abnormal mitochondria, lipid accumulation and axonal spheroids were observed in the muscle and nerve tissue. Brain deposition appeared 6 years following the initial cerebellar atrophy. Mild MRI alterations were detected in the asymptomatic carrier parents.

Conclusion

The colorful clinical symptoms, the slightly discordant phenotype, and the neuroimaging data in the family supports the view that despite the distinct definition of age-related phenotypes in PLAN, these are not strict disease categories, but rather a continuous phenotypic spectrum. The mild MRI alterations of the parents and the family history suggest that even heterozygous pathogenic variants might be associated with clinical symptoms, although systematic study is needed to prove this.
Whole-Exome Sequencing for Identification of Genetic Variants Involved in Vitamin D Metabolic Pathways in Families With Vitamin D Deficiency in Saudi Arabia
Authors: Alharazy Shatha , Naseer Muhammad Imran , Alissa Eman , Robertson Margaret Denise , Lanham-New Susan , Chaudhary Adeel G.
Published: June 2021

Background

Numerous research studies have found an association between vitamin D (vitD) status and single-nucleotide polymorphisms (SNPs) in genes involved in vitD metabolism. It is notable that the influence of these SNPs on 25-hydroxyvitamin D [25(OH)D] levels might vary in different populations. In this study, we aimed to explore for genetic variants in genes related to vitD metabolism in families with vitD deficiency in Saudi Arabia using whole-exome sequencing (WES).

Methods

This family-based WES study was conducted for 21 families with vitD deficiency (n = 39) in Saudi Arabia. WES was performed for DNA samples, then resulting WES data was filtered and a number of variants were prioritized and validated by Sanger DNA sequencing.

Results

Several missense variants in vitD-related genes were detected in families. We determined two variants in low-density lipoprotein 2 gene (LRP2) with one variant (rs2075252) observed in six individuals, while the other LRP2 variant (rs4667591) was detected in 13 subjects. Single variants in 7-dehydrocholesterol reductase (DHCR7) (rs143587828) and melanocortin-1 receptor (MC1R) (rs1805005) genes were observed in two subjects from two different families. Other variants in group-specific component (GC), cubilin (CUBN), and calcium-sensing receptor (CASR) gene were found in index cases and controls. Polymorphisms in GC (rs9016) and CASR (rs1801726) were found in the majority of family cases (94 and 88%), respectively.

Conclusion

In vitD-deficient families in Saudi Arabia, we were able to detect a number of missense exonic variants including variants in GC (rs9016), CUBN (rs1801222), CASR (rs1801726), and LRP2 (rs4667591). However, the existence of these variants was not different between affected family members and non-affected controls. Additionally, we were able to find a mutation in DHCR7 (rs143587828) and a polymorphism in LRP2 (rs2075252), which may affect vitD levels and influence vitD status. Further studies are now required to confirm the association of these variants with vitD deficiency.
Serum Antibodies Against the Oncogenic Merkel Cell Polyomavirus Detected by an Innovative Immunological Assay With Mimotopes in Healthy Subjects
Authors: Mazziotta Chiara , Lanzillotti Carmen , Torreggiani Elena , Oton-Gonzalez Lucia , Iaquinta Maria Rosa , Mazzoni Elisa , Gaboriaud Pauline , Touzé Antoine , Silvagni Ettore , Govoni Marcello , Martini Fernanda , Tognon Mauro , Rotondo John Charles
Published: June 2021

Merkel cell polyomavirus (MCPyV), a small DNA tumor virus, has been detected in Merkel cell carcinoma (MCC) and in normal tissues. Since MCPyV infection occurs in both MCC-affected patients and healthy subjects (HS), innovative immunoassays for detecting antibodies (abs) against MCPyV are required. Herein, sera from HS were analyzed with a novel indirect ELISA using two synthetic peptides mimicking MCPyV capsid protein epitopes of VP1 and VP2. Synthetic peptides were designed to recognize IgGs against MCPyV VP mimotopes using a computer-assisted approach. The assay was set up evaluating its performance in detecting IgGs anti-MCPyV on MCPyV-positive (n=65) and -negative (n=67) control sera. Then, the ELISA was extended to sera (n=548) from HS aged 18-65 yrs old. Age-specific MCPyV-seroprevalence was investigated. Performance evaluation indicated that the assay showed 80% sensitivity, 91% specificity and 83.9% accuracy, with positive and negative predictive values of 94.3% and 71%, respectively. The ratio expected/obtained data agreement was 86%, with a Cohen’s kappa of 0.72. Receiver-operating characteristic (ROC) curves analysis indicated that the areas under the curves (AUCs) for the two peptides were 0.82 and 0.74, respectively. Intra-/inter-run variations were below 9%. The overall prevalence of serum IgGs anti-MCPyV in HS was 62.9% (345/548). Age-specific MCPyV-seroprevalence was 63.1% (82/130), 56.7% (68/120), 64.5% (91/141), and 66.2% (104/157) in HS aged 18-30, 31-40, 41-50 and 51-65 yrs old, respectively (p>0.05). Performance evaluation suggests that our indirect ELISA is reliable in detecting IgGs anti-MCPyV. Our immunological data indicate that MCPyV infection occurs asymptomatically, at a relatively high prevalence, in humans.
Immunological and Pathological Landscape of Dengue Serotypes 1-4 Infections in Immune-Competent Mice
Authors: Rathore Abhay P. S. , Mantri Chinmay K. , Tan Meredith W. , Shirazi Roksana , Nishida Andrew , Aman Siti A. B. , Morrison Juliet , St. John Ashley L.
Published: June 2021

Dengue virus (DENV), a Flavivirus, causes a broad spectrum of disease in humans with key clinical signs including thrombocytopenia, vascular leakage and hemorrhaging. A major obstacle to understanding DENV immunity has been the lack of a validated immune-competent mouse model. Here, we report the infection profiles of human clinical isolates of DENV serotypes 1-4 in an immune-competent mouse model. We detected replicating DENV in the peritoneal cells, liver and the spleen that was generally resolved within 2 weeks. The DENV target cell types for infection were monocytes/macrophages, dendritic cells, endothelial cells, and we identified a novel DENV cellular target, fibroblast reticular cells of the spleen. We observed gross pathologies in the spleen and liver that are consistent with dengue disease, including hemorrhaging as well as transcriptional patterns suggesting that antiviral responses and tissue damage were induced. Key clinical blood parameters that define human DENV disease such as hemoconcentration, leukopenia and reduced number of platelets were also observed. Thus, immune-competent mice sustain replicating infection and experience signs, such as hemorrhaging, that define DENV disease in humans. This study thoroughly characterizes DENV1-4 infection in immune-competent mice and confirms the wild-type mouse model as a valid and reproducible system for investigating the mechanisms of DENV pathogenesis.