bluuebunny/crossref_metadata_2025 huggingface dataset:
Mudas de tamarindos irrigadas com diferentes tipos e proporções de água
Authors: Queiroga Ranieri Antunes de , Pereira Junior Ednaldo Barbosa , Moreira Joserlan Nonato , Santos Ranniery Felix dos , Lima Filho Pedro , Oliveira Filho Francisco de Sales , Bezerra Diego Ernani Leite , Ferreira Neto João , Brito Filho José de Sousa
Published: August 2021

As precipitações pluviométricas irregulares e a elevada evapotranspiração são características da região semiárida do Nordeste Brasileiro. O conjunto dessas variáveis fazem da água um fator limitante para agricultura irrigada, o que torna a reutilização necessária, principalmente em locais sob condições de crescente escassez. Este trabalho teve o objetivo de avaliar o desenvolvimento de mudas de tamarindos e sua influência nos atributos químicos do solo, em função dos diferentes tipos e proporções de águas. A pesquisa foi desenvolvida no setor de produção de mudas localizado no Instituto Federal da Paraíba, Campus Sousa. Utilizou-se o delineamento de blocos inteiramente casualizados, com cinco tratamentos e quatro repetições. Os tratamentos resultaram das seguintes combinações: T1 = 100 % Poço Artesiano (PA), T2 =100 % Ar-Condicionado (AC), T3 = Combinação 50% Ar Condicionado + 50% Poço Artesiano (AC+PA), T4 = Combinação 50 % Efluente Agroindustrial + 50 % Ar Condicionado (EA+AC) e T5 = 100 % Efluente Agroindustrial (EA). As mudas de tamarindo foram produzidas em sacos plásticos, utilizando Neossolo Flúvico e esterco na proporção (2:1) como substrato. Foram avaliadas as seguintes variáveis: altura de planta, diâmetro de caule, número de folhas, massa verde e seca da parte aérea e raiz, comprimento da raiz e influência nos atributos do solo (pH, P, K, Na e MO). A combinação de 50% das águas de ar condicionado e 50% efluente agroindustrial se mostrou adequada na produção de mudas de Tamarindo.  O efluente agroindustrial é recomendável para irrigação de plântulas de tamarindo, apesar dos elevados teores de sódio e cloreto. O uso da água de ar condicionado  mostrou-se viável na produção  de mudas de tamarindos.
Ensino e aprendizagem impulsionados pelo pensamento computacional
Authors: Franco Karine Serpa , Ferreira Alessandra Teles Sirvinskas , Madeira Lucianne Fragel , Gomes Suzete Araujo Oliveira , Pinto Sergio Crespo Coelho da Silva
Published: August 2021

Pensamento Computacional (PC) é uma estratégia utilizada no processo ensino/aprendizagem, envolvendo resolução de problemas, de forma a desenvolver o pensamento crítico e criativo, de forma autônoma, interdisciplinarmente. O presente artigo apresenta uma análise reflexiva sobre o tema, fundamentando-se em literaturas que abordam o PC e seus desdobramentos. Tem como objetivo discutir os benefícios decorrentes do desenvolvimento do PC na educação básica, bem como descrever brevemente algumas estratégias já em uso para que o PC possa ser ensinado, beneficiando, assim, alunos, professores e a sociedade. Concluímos que ao desenvolver o PC o aluno passa a ser sujeito construtor de conhecimento, de forma crítica, criativa, polivalente, flexível e inovadora, e que isso pode se dar através de estratégias diversas, seja pelo ensino da robótica, programação em blocos, narrativas digitais, games, com atividades sem o uso de tecnologias, ou de forma transversal dentro das disciplinas.
O uso da Hidroxicloroquina no decorrer da pandemia da COVID-19: um estudo de revisão bibliográfica
Authors: Silva Amanda Brito , Galbraith Beatriz Bonfadini de Sá , Borges Camila Lopes Rieke , Costa Daniel Pereira de Rezende Sarmento , Bines Danilo , Lopes Gabriela Carreiro Kubitschek , Bekierman Hannah Barboza Vianna , Porto Helena Ferreira Bruzzi , Seabra Júlia Moraes de Andrade , Santos Julia Vieira , Cabral Michel Vladimir de Sousa , Saugo Pedro Henrique , Andrade Victor Gonçalves de , Azevedo Pedro Leite
Published: August 2021

A COVID-19 é uma doença infecciosa causada pelo SARS-CoV-2, apresenta elevada taxa de transmissão e têm resultado em milhares de óbitos registrados em todo o mundo. Atualmente, ainda não existem estudos clínicos que comprovem a eficácia de medicamentos específicos contra o SARS-Cov-2. No entanto, experiências anteriores com vírus semelhantes indicaram potencial de efetividade para determinados fármacos, dentre eles, o uso da Hidroxicloroquina (HCQ). No início da pandemia da COVID-19, a Organização Mundial da Saúde e o Ministério da Saúde orientaram a utilização da HCQ como opção terapêutica. No entanto, não se conhecia exatamente o seu papel na infecção viral pelo SARS-CoV-2, além dos seus reais benefícios in vivo. Portanto, o objetivo deste estudo foi realizar uma revisão bibliográfica sobre o uso da HCQ em casos de COVID-19, e discutir os resultados encontrados nos trabalhos que realizaram testes in vitro e in vivo, a fim de investigar a sua eficácia terapêutica. A revisão foi realizada utilizando descritores em base de dados informatizados. A eficácia antiviral da HCQ contra o SARS-CoV-2 in vitro foi descrita por diversos autores, inibindo a replicação do vírus e mediando a tempestade de citocinas por meio de seus efeitos imunomoduladores. No entanto, análises in vivo em organismos complexos não evidenciaram efeito na redução da carga viral, bem como nenhum benefício clínico ao paciente. Desta forma, apesar dos resultados preliminares in vitro terem se mostrado positivos e promissores, as evidências de ensaios clínicos randomizados apontaram que a HCQ não provocou os mesmos efeitos in vivo contra a COVID-19.
As perspectivas de Viktor Frankl e Erich Fromm sobre o amor e a humanidade
Authors: Silva Flávio Luiz Honorato da , Caldas Ana Raquel Alencar , Araújo Lucas Daniel Regis de , Silva Leandro Honorato da , Rodrigues Sarah Xavier Vasconcelos de Fialho , Ribeiro Maria Gabriela Costa
Published: August 2021

As perspectivas de pensamentos da Logoterapia e Análise Existencial de Frankl e a Psicanálise de Freud, apesar de visões diferentes de ser humano e mundo, há muito em comum, principalmente quando as influências do humanismo e existencialismo afetam os pensamentos de psicanalistas. Esse trabalho tem como objetivo apresentar os pressupostos teóricos sobre o amor e humanidade de Viktor Emil Frankl e Erich Fromm considerados dois humanistas. O artigo busca indicar, apesar das divergências entre as duas abordagens psicológicas, posições em comum principalmente semelhanças de pensamentos, ou seja, concordâncias de ideias em benefício de um bem comum da saúde mental do indivíduo na terapia. Foram utilizadas pesquisas bibliográficas em livros e artigos em bases de dados, por meio dos fundamentos teóricos dos pensamentos de Viktor Emil Frankl e de Erich Fromm. Averiguou-se que, mesmo de escolas divergentes em relação aos conceitos de ser humano e mundo, as duas abordagens apresentam, de acordo com os pensadores, perspectivas que convergem em relação aos construtos de amor e humanidade.
Perfil epidemiológico das principais doenças veiculadas por alimentos
Authors: Araújo Bruna Silva , Duailibi Sandra Rojas , Rachid Lorena
Published: August 2021

A incidência de surtos veiculados por alimentos tem ganhado uma proporção elevada e estima-se que tenha mais casos não notificados. O objetivo do estudo é elucidar o perfil epidemiológico dos surtos de DVA no Brasil com base nos dados do Manual Integrado de Vigilância, Prevenção e Controle de Doenças Transmitidas por Alimentos. Assim, o estudo está estruturado pela apresentação dos elementos de investigação das DVA, as principais categorias e os locais de produção dos elementos envolvidos nos surtos e por fim, a relação dos principais micro-organismos encontrados nas análises dos surtos notificados e seus efeitos à saúde humana. Trata-se de um estudo descritivo, epidemiológico, documental com abordagem quantitativa e com as variáveis analisadas: alimentos e surtos 2016 e 2017, sinais e sintomas 2016 e 2017, perfil epidemiológico dos doentes 2016 e 2017, surtos e regiões do Brasil 2016 e 2017 e Micro-organismos veiculado aos alimentos 2016 e 2017. Ao analisar o local de produção dos alimentos, verificou-se que os surtos ocorrem em sua maioria nas residências e estabelecimentos comerciais. Desta forma, fica evidente a necessidade de mais estudos e de se buscar alternativas públicas para mudança comportamental da população e a inclusão de nutricionistas nos estabelecimentos comerciais e industriais.
Associação entre o fator neurotrófico derivado do encéfalo (BDNF) e o transtorno depressivo: uma revisão de literatura
Authors: Santos Thayná Bertolini dos , Souza Vytor Hugo Staut de , Lopes Noéli Cristina Gouveia , Ferreira Flávia Albuquerque , Leite Cleber Queiroz , Silva Messias Genézio Santana da , Santos Brian França dos
Published: August 2021

Objetivos: O presente trabalho teve por objetivo, reunir e sistematizar os principais estudos disponíveis, que esclarecessem a íntima relação entre os níveis de Fator Neurotrófico Derivado do Encéfalo (BDNF) com o transtorno depressivo. Metodologia: Foram selecionados 30 trabalhos relacionados com o BDNF e transtorno depressivo de plataformas intexadoras, publicadod entre os anos de 2017 – 2021, sendo que, o foco foram artigos que apresentassem contribuições para o tema associando as duas condições. Resultados e Discussão: Diversos trabalhos que relacionam o BDNF ao transtorno depressivo demonstram uma relação entre níveis diminuídos desse polipeptídeo em pacientes com a patologia quando comparado com indivíduos saudáveis, servindo mesmo como biomarcador da doença, ademais, houve aumento dos níveis do citado fator quando realizados os tratamentso específicos para a depressão. Outros autores relacionam o aumento dos níveis do BDNF com a realização de atividades físicas e restrição calórica e aventam a possibilidade de tal atividade ser considerada como tratamento adjuvante ao convencional. Por fim, outros trabalhos se detêm nas alterações genéticas e epigenéticas rastreáveis através de análise genômica podem interferir na expressão do BDNF e servir como fatores de risco aumentado para desenvolvimento de desordens neuropsiquiátricas. Conclusão: Há evidêcias suficientes para embasar a fala de que o BDNF está relacionado e pode ser uma ferramenta promissora para o diagnóstico e futuras abordagens da patologia, porém são necessários novos estudos para consolidar os achados já demonstrados anteriormente, bem como determinar os níveis de BDNF a serem considerados como preditores de doença.
Injúria renal aguda na Unidade de Terapia Intensiva em um hospital do interior amazônico
Authors: Silva Jamyle Balla da , Melo Cilene Aparecida de Souza , Barros Thiago Gonçalves
Published: August 2021

Objetivo: Identificar e analisar a injúria renal aguda na unidade de terapia intensiva em um hospital do interior amazônico. Metodologia: Trata-se de um estudo observacional, descritivo, prospectivo, transversal com abordagem quantitativa de uma amostra de 30 indivíduos, realizada no período de maio a junho de 2021 em um hospital de referência no interior amazônico.  Resultados: Observou-se que o sexo prevalente foi masculino (63%), e que 57% tinham mais de 55 anos. Prevaleceu o tempo de internação de até 7 dias (70%). O principal diagnóstico de admissão foi TCE/politrauma. Ratificou-se a HAS e DM como principais fatores de risco e que mais de 50% da amostra apresentou alterações glicêmicas e pressóricas durante a internação. Notou-se que 70% dos pacientes precisaram de VM e 63,40% de DVA. Os estágios 2 e 3 do KDIGO estiveram presentes em 70% da amostra. A principal medida terapêutica foi hidratação venosa e houve 40% de morte ao final deste estudo. Conclusão: Constatou-se que indivíduos que tinham alguma doença crônica de base e que tinham hábitos de vida não saudáveis obtiveram pior score na classificação KDIGO e apresentaram desfecho desfavorável. Portanto, compreender o perfil dos indivíduos atendidos no serviço pode favorecer melhor atendimento médico, com maior rapidez diagnóstica e permitir otimização terapêutica, afim de reduzir os impactos na morbimortalidade induzidos pela injúria renal aguda na unidade de terapia intensiva.
Tempo de reação motora no diabetes mellitus tipo 2: revisão integrativa da literatura
Authors: Gervásio Flávia Martins , Veloso Aline Helena Nascimento , Brito Luíza Rodrigues de Assis , Farias Alexandre Barroso de , Oliveira Franassis Barbosa de
Published: August 2021

Altos níveis glicêmicos prejudicam principalmente o sistema nervoso periférico, causando danos sensitivos e motores. Medidas neuromotoras de tempo de reação (TR) mostraram-se um eficiente indicador de prejuízo funcional em diferentes populações. O presente estudo objetivou identificar e analisar nas literaturas nacional e internacional o comportamento do TR no diabetes mellitus 2 (DM2) e os principais fatores intervenientes. Trata-se de uma revisão integrativa, conduzida nas bases de dados LILACS, BIREME, SCOPUS, Cochrane e Pubmed no período de julho e agosto de 2020. Ao final foram selecionados 14 artigos todos na língua inglesa. Os resultados mostram que o TR no DM2 associado à neuropatia foi significativamente maior em comparação a outras populações. Portanto, a medida do TR é uma alternativa viável no diagnóstico das disfunções neurológicas do DM2, uma vez que se mostrou sensível à mudança da velocidade dos impulsos nervosos, mostrando-se lentificada. Esta avaliação pode ser aplicada como medida diagnóstica e preventiva no tratamento destes pacientes, com efeito aos casos graves como úlceras e amputações, triados previamente. Estudos futuros podem investigar possível padronização instrumental e metodológica, além da validação de um produto nacional que explore o TR na população brasileira.
An evaluation of MorphInd's morphological annotation scheme for Indonesian
Authors:   Prihantoro
Published: August 2021

MorphInd 2 ( Larasati et al., 2011 ) is a state-of-the-art morphological analyser for Indonesian. To date, there has not been any comprehensive evaluation of the morphological annotation scheme which MorphInd implements. My evaluation of this annotation scheme reveals a number of significant drawbacks. Some analytical features encoded in MorphInd's tagset seem not to reflect features actually present in Indonesian morphology, while certain common features in the analysis of Indonesian are absent. Likewise, the Part of Speech (pos) hierarchy in the MorphInd tagset does not reflect the usual pos hierarchy used by Indonesian reference grammars. Moreover, the MorphInd output does not link morphological tags to the corresponding morpheme. Finally, a number of issues which might problematise text/corpus querying in the annotation's layout are observable, particularly relating to affixes, reduplication, and the affix–reduplication interface.
Early use of cytokine adsorption in treatment of COVID-19 associated respiratory distress syndrome
Authors: Rybalko A. S. , Voronin A. V. , Vagulin A. O. , Saryglar A. S. , Zabolotskaya L. V. , Perekhodov S. N. , Karpun N. A. , Chaus N. I. , Evdokimov E. A.
Published: August 2021

Introduction. It is the recommendations for treatment of sepsis and septic shock combined with rheumatologists’ recommendations for monoclonal antibodies therapy that guide severe COVID-19 management in ICU. However, those recommendations may not be fully applied to patients with acute respiratory distress-syndrome associated with SARS-CoV-2, as there exists a difference in pathogenesis between sepsis and virus-associated pneumonias. Monoclonal antibodies therapy may contribute to cytokine cascade severity and promote lung injury. Cytokine storm aggravates the course of the disease. At present, there are two groups of methods described in literature for cytokine storm control and therapy: pharmacological and extracorporeal approaches.Materials and methods. We have performed a retrospective analysis of five COVID-19 patients with acute respiratory syndrome. Cytokine adsorption start criteria were respiratory insufficiency and IL-6 levels greater than 500 pg/ml. Adsorption therapy was initiated within 24 hours of ICU admission and continued for 48–120 hours in hemoperfusion mode on Multifiltrate machine (Fresenius Medical Care). The length of a single session of CytoSorb (Cytosorbents Inc.) therapy was 24 hours.Results. All patients demonstrated SpO2/FiO2 ratio growth and IL-6 concentration decrease by the end of hemoadsorption. We noted lymphocyte count rise as well as IgM и IgG SARS-CoV-2 antibodies titer substantial increase.Conclusions. Our observations suggest that the early start of hemoadsorption associates with gas-exchange stabilization and hinders respiratory distress progression. Hemoadsorption allows for pro-inflammatory cytokines concentrations decrease and prevents secondary lung injury. According to our data, hemoadsorption is beneficial to form a coronavirus infection specific immune response. Further research is needed for a detailed study of the results we here describe.
Current understanding of pathophysiological mechanisms of peripartal cardiomyopathy
Authors: Kazantseva V. D. , Khidirova L. D. , Kokoulina N. A.
Published: August 2021

The aim of the study. To analyze literature data in order to study the pathophysiological mechanisms of development of peripartum cardiomyopathy. Research methods and materials. A review of modern Russian and foreign, mainly English-speaking, literature on the pathogenetic mechanisms of IPAH development was carried out. We took into account publications not older than 6 years, published in specialized medical journals and guidelines. Results. According to the data of modern studies devoted to the peculiarities of the development of peripartum cardiomyopathy, much attention is paid to the risk factors of the disease, in particular the age-related obstetric history, pregnancy with twins or more, and arterial hypertension. In addition, the significance of genetic predisposition, inflammatory syndrome has been proven, and the vasculo-hormonal theory is being studied. Difficult issues of the etiopathogenesis of the disease, including myocarditis, the role of the prolactin-cathepsin-prolactin 16 kDa system, and malnutrition are discussed.Conclusion. Pathophysiological mechanism of development of peripartum cardiomyopathy. appears as a complex combination of inflammatory changes in the myocardium with the participation of a cardiotoxic subfragment – prolactin 16 kDa, which causes damage and dysfunction of the endothelium under hemodynamic stress against the background of possible genetic changes, which leads to damage to cardiomyocytes and a decrease in myocardial contractility.
Profiles and genetic determinants of antimicrobial resistance in pathogens causing community-acquired urinary tract infections in reproductive-age women
Authors: Khusnutdinova T. A. , Shipitsyna E. V. , Krysanova A. A. , Savicheva A. M.
Published: August 2021

Objective. To characterize the profiles and genetic determinants of antibiotic resistance in pathogens of community-acquired urinary tract infections (UTI) in women of reproductive age in St. Petersburg (Russia).Materials and methods. The study included strains of microorganisms obtained from 145 women of reproductive age with diagnosed with a UTI. Antibiotic susceptibility was evaluated by disk diffusion method; the interpretation of the results was carried out in accordance with the EUCAST criteria. Strains of uropathogenic enterobacteria were tested by PCR for the presence of beta-lactamase genes: beta-lactamase genes encoding enzymes of the AmpC group (MOX, CMY, LAT, BIL, DHA, ACC, MIR, ACT, FOX), TEM, SHV, OXA‑1, ESBL genes of the CTX–M group, genes of carbapenemases (KPC, OXA‑48) and metal-beta-lactamases (VIM, IMP, NDM).Results. Most cases (81 %) of UTIs in women in St. Petersburg were due to enterobacteria, with Escherichia coli highly prevailing (66 %). Fosfomycin, meropenem and nitrofurantoin had the highest in vitro activity against uropathogenic Enterobacteriaceae. High rates of resistance to betalactam antibiotics were found (from 16 % to cefotaxime to 28 % to amoxicillin/clavulanic acid). The genes of TEM-beta-lactamases were found in 31 isolates (26.7 %), SHV – in 17 (14.6 %), CTX–M type – in 15 (12.9 %), DHA – in 2 (1.7 %). The other beta-lactam resistance genes (MOX, CMY, LAT, BIL, ACC, MIR, ACT, FOX, KPC group, OXA-like group, VIM, IMP, NDM) were not detected.Conclusion. Microbiological and molecular analysis of the structure of beta-lactam resistance is important for the effective of epidemiological control of antimicrobial resistance in pathogens causing urinary tract infections.
Situation on tuberculosis in world and Russia at present stage. Prospects of improvement of actions for elimination of burden of tuberculosis from epidemiologist’s point of view
Authors: Shelkova E. S.
Published: August 2021

Situation on tuberculosis (TB) in the world according to World Health Organization and in the Russian Federation. Factors, having impact on TB burden level. The specific prevention of TB in all age and social groups is a priority and cost-effective way to actually reduce the burden of TB at the present stage in the presence of a vaccine that has shown its effectiveness in organizing anti-epidemic measures between 1961 and 1992. Recovery of the National calendar of preventive inoculations and the Calendar of inoculations according to epidemic indications on TB is an important step in ensuring national security and improvement of a demographic situation in the country.
Biomarkers in patients after chemotherapy
Authors: Akildzhonov F. R. , Buziashvili J. I. , Stilidi I. S. , Asymbekova E. U. , Artamonova E. V.
Published: August 2021

Along with the rapid development of molecular genetic testing, immunotherapy and targeted antitumor therapy in Oncology, the risk of cardiotoxicity associated with chemotherapy remains a keystone that directly affects the survival and quality of life of patients after therapy. Elevated levels of troponin, BNP/NT-proBNP, myeloperoxidase, and D-dimer have been associated with increased all-cause mortality in cancer patients and have been shown in numerous studies to predict the risk of heart failure and myocardial damage associated with chemotherapy. Specifi diagnostic algorithms are particularly important for risk stratifiation, monitoring, and long-term follow-up of cancer patients receiving chemotherapy. Biomarkers are the basis for diagnosing acute and chronic heart diseases. However, their role in the timely detection and monitoring of cardiotoxicity is not well understood. Thus, clinicians should identify adverse effects at an early stage, seeking to take appropriate preventive measures before the occurrence of a permanent or irreversible dysfunction of the heart. In dynamic cardiology, biomarkers are a key tool for risk assessment, diagnosis, and monitoring of cancer-related cardiotoxicity and cancer therapy. The complex interaction of such branches of medicine as oncology, oncotherapy and cardiology indicates the need for a multi-disciplinary cardio-oncological approach to ensure optimal quality of treatment
Intensification of High-Quality Brewing Processes
Authors: Romanova Zoriana M. , Loiko Serhii M. , Romanov Mykola S. , Kosogolova Ludmila O. , Khlynovskiy Mikhail D.
Published: August 2021

Brewing is a complex process that involves many stages and successive operations. The issues of intensifying the brewing processes are of great importance in improving the ways to obtain a high-quality finished beer product and maintain high standards of its quality in the future. The relevance of the subject matter is conditioned by the stable demand for high-quality beer products in society and the urgent need to create effective technologies for the production of high-quality beer, taking into account the introduction of the latest technologies for the intensification of brewing processes. The purpose of the study is to determine the main factors that are important from the standpoint of intensifying the processes of quality brewing, in the context of assessing the prospects for their subsequent consideration when planning the beer production processes. The leading approach of this study is a combination of a systematic analysis of the peculiarities of brewing processes in the context of searching for opportunities for its intensification, with an analytical study of real options for intensifying the brewing processes, from the standpoint of maintaining high-quality standards of finished beer and increasing the overall production rate. The main results obtained in the course of this study should be considered the substantiation of the main factors of the brewing processes intensification in the context of creating a mathematical model for calculating the possibilities of its implementation in the activities of breweries to increase the rate of brewing high-quality beer. The prospects for further research are determined by the preservation of a stable demand for high-quality beer products, combined with an increase in the need to intensify the processes of its production, in accordance with the set standards for the quality of beer production.
Inertial navigation for divers
Authors: Mac Manus Lorcán , Brown Melvin
Published: August 2021

The Study Group investigated the possibility of a small standalone dead-reckoning system making use of cheaply available accelerometer, gyroscope and magnetic field sensors. The Study Group captured data using an Android device strapped to a skateboard to simulate the type of movements a diver might make underwater. Different modes of movement were evident from filtered versions of the sensor outputs, indicating that a pedometry-based solution ought to be feasible. The Study Group then formulated and investigated the feasibility of a generic dead-reckoning system. Although sensors provide more data than is strictly necessary, significant errors arise from imperfect calibration and from noise for which the Study Group derived estimates of the resulting drift in position over time. The accuracy of practical numerical integration schemes in the context of rotating frames was investigated, and a Kalman filter used to reduce error in the orientation data by combining accelerometer and gyroscopic data.
Design, Preparation, and Bioactivity Study of New Fusion Protein HB-NC4 in the Treatment of Osteoarthritis
Authors: Wang Yaya , Li Lian , Wei Qiang , Chai Rongrong , Yao Qingqiang , Liang Chen , Wang Fuwen , Li Yan
Published: August 2021

Osteoarthritis (OA) is now becoming the main disease that affects public health. There is no specific medicine used for OA in clinical application until now. Recently, several studies demonstrated that OA is closely related to the complement system, and some complement regulators such as N-terminal non-collagenous domain 4 (NC4) aimed at alleviating OA have shown a promising therapeutic effect. However, targeting ability is the main limitation for NC4. In this study, a fusion protein named heparin-binding domain-N-terminal non-collagenous domain 4 (HB-NC4) was proposed to solve this problem, which could provide a better way for OA treatment. First, HB-NC4 plasmid was constructed using ClonExpress II one-step ligation kit method. And Escherichia coli BL21 was utilized to express the fusion protein, Ni2+-sepharose, and a desalting gravity column were introduced to purify HB-NC4. The results showed that 0.84 mg HB-NC4 could be obtained from a 1 L culture medium with a purity higher than 92.6%. Then, the hemolytic assay was introduced to validate the anti-complement activity of HB-NC4; these results demonstrated that both HB-NC4 and NC4 had a similar anti-complement activity, which indicated that heparin-binding (HB) did not affect the NC4 structure. Targeting ability was investigated in vivo. HB-NC4 showed a higher affinity to cartilage tissue than NC4, which could prolong the retention time in cartilage. Finally, the destabilization of the medial meniscus (DMM) model was applied to investigate HB-NC4 pharmacodynamics in vivo. The results indicated that HB-NC4 significantly slowed cartilage degradation during the OA process. In summary, compared with NC4, HB-NC4 had better-targeting ability which could improve its therapeutic effect and prolonged its action time. It could be used as a new complement regulator for the treatment of OA in the future.
Lnc-GD2H Promotes Proliferation by Forming a Feedback Loop With c-Myc and Enhances Differentiation Through Interacting With NACA to Upregulate Myog in C2C12 Myoblasts
Authors: Chen Rui , Lei Si , She Yanling , Zhou Shanyao , Shi Huacai , Li Cheng , Jiang Ting
Published: August 2021

In the present study, the roles of a novel long non-coding RNA (lncRNA), lnc-GD2H, in promoting C2C12 myoblast proliferation and differentiation and muscle regeneration were investigated by quantitative polymerase chain reaction, western blotting, Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine (EdU), immunofluorescence staining, luciferase reporter, mass spectrometry, pulldown, chromatin immunoprecipitation, RNA immunoprecipitation assay, wound healing assays, and cardiotoxin (CTX)-induced muscle injury assays. It was observed that lnc-GD2H promoted myoblast proliferation as evidenced by the enhancement of the proliferation markers c-Myc, CDK2, CDK4, and CDK6, percentage of EdU-positive cells, and rate of cell survival during C2C12 myoblast proliferation. Additional experiments confirmed that c-Myc bound to the lnc-GD2H promoter and regulated its transcription. lnc-GD2H promoted cell differentiation with enhanced MyHC immunostaining as well as increased expression of the myogenic marker genes myogenin (Myog), Mef2a, and Mef2c during myoblast differentiation. Additional assays indicated that lnc-GD2H interacted with NACA which plays a role of transcriptional regulation in myoblast differentiation, and the enrichment of NACA at the Myog promoter was impaired by lnc-GD2H. Furthermore, inhibition of lnc-GD2H impaired muscle regeneration after CTX-induced injury in mice. lnc-GD2H facilitated the expression of proliferating marker genes and formed a feedback loop with c-Myc during myoblast proliferation. In differentiating myoblasts, lnc-GD2H interacted with NACA to relieve the inhibitory effect of NACA on Myog, facilitating Myog expression to promote differentiation. The results provide evidence for the role of lncRNAs in muscle regeneration and are useful for developing novel therapeutic targets for muscle disorders.
Genetic Mechanism for the Cyclostome Cerebellar Neurons Reveals Early Evolution of the Vertebrate Cerebellum
Authors: Sugahara Fumiaki , Pascual-Anaya Juan , Kuraku Shigehiro , Kuratani Shigeru , Murakami Yasunori
Published: August 2021

The vertebrate cerebellum arises at the dorsal part of rhombomere 1, induced by signals from the isthmic organizer. Two major cerebellar neuronal subtypes, granule cells (excitatory) and Purkinje cells (inhibitory), are generated from the anterior rhombic lip and the ventricular zone, respectively. This regionalization and the way it develops are shared in all extant jawed vertebrates (gnathostomes). However, very little is known about early evolution of the cerebellum. The lamprey, an extant jawless vertebrate lineage or cyclostome, possesses an undifferentiated, plate-like cerebellum, whereas the hagfish, another cyclostome lineage, is thought to lack a cerebellum proper. In this study, we found that hagfish Atoh1 and Wnt1 genes are co-expressed in the rhombic lip, and Ptf1a is expressed ventrally to them, confirming the existence of r1’s rhombic lip and the ventricular zone in cyclostomes. In later stages, lamprey Atoh1 is downregulated in the posterior r1, in which the NeuroD increases, similar to the differentiation process of cerebellar granule cells in gnathostomes. Also, a continuous Atoh1-positive domain in the rostral r1 is reminiscent of the primordium of valvula cerebelli of ray-finned fishes. Lastly, we detected a GAD-positive domain adjacent to the Ptf1a-positive ventricular zone in lampreys, suggesting that the Ptf1a-positive cells differentiate into some GABAergic inhibitory neurons such as Purkinje and other inhibitory neurons like in gnathostomes. Altogether, we conclude that the ancestral genetic programs for the formation of a distinct cerebellum were established in the last common ancestor of vertebrates.
Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease
Authors: Larkin Benjamin P. , Nguyen Long T. , Hou Miao , Glastras Sarah J. , Chen Hui , Wang Rosy , Pollock Carol A. , Saad Sonia
Published: August 2021

Background

Maternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring.

Methods

Female C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint.

Results

Offspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress.

Conclusion

Gestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.
Ventral Telencephalic Patterning Protocols for Induced Pluripotent Stem Cells
Authors: Krajka Victor , Naujock Maximilian , Pauly Martje G. , Stengel Felix , Meier Britta , Stanslowsky Nancy , Klein Christine , Seibler Philip , Wegner Florian , Capetian Philipp
Published: August 2021

The differentiation of human induced pluripotent stem cells (hiPSCs) into specific cell types for disease modeling and restorative therapies is a key research agenda and offers the possibility to obtain patient-specific cells of interest for a wide range of diseases. Basal forebrain cholinergic neurons (BFCNs) play a particular role in the pathophysiology of Alzheimer’s dementia and isolated dystonias. In this work, various directed differentiation protocols based on monolayer neural induction were tested for their effectiveness in promoting a ventral telencephalic phenotype and generating BFCN. Ventralizing factors [i.e., purmorphamine and Sonic hedgehog (SHH)] were applied at different time points, time intervals, and concentrations. In addition, caudal identity was prevented by the use of a small molecule XAV-939 that inhibits the Wnt-pathway. After patterning, gene expression profiles were analyzed by quantitative PCR (qPCR). Rostro-ventral patterning is most effective when initiated simultaneously with neural induction. The most promising combination of patterning factors was 0.5 μM of purmorphamine and 1 μM of XAV-939, which induces the highest expression of transcription factors specific for the medial ganglionic eminence, the source of GABAergic inter- and cholinergic neurons in the telencephalon. Upon maturation of cells, the immune phenotype, as well as electrophysiological properties were investigated showing the presence of marker proteins specific for BFCN (choline acetyltransferase, ISL1, p75, and NKX2.1) and GABAergic neurons. Moreover, a considerable fraction of measured cells displayed mature electrophysiological properties. Synaptic boutons containing the vesicular acetylcholine transporter (VACHT) could be observed in the vicinity of the cells. This work will help to generate basal forebrain interneurons from hiPSCs, providing a promising platform for modeling neurological diseases, such as Alzheimer’s disease or Dystonia.
CO2 Metallothermal Reduction to Graphene: The Influence of Zn
Authors: Luchetta Carolina , Oliveira Munsignatti Erica C. , Pastore Heloise O.
Published: August 2021

CO2 is the most important greenhouse gas involved in climate change; it has been a concern for many years and will remain as such in the years to come. CO2 adsorption and CO2 utilization have been studied as methods to mitigate the concentration of the gas in the atmosphere by sequestering and transforming it into a value-added product, capable of being commercialized. With those aims in mind, CO2 reduction into 3D graphene was studied using a Zn–Mg mixture. The results show that Mg is the only reducing agent, and Zn acted as a porogen during graphene formation as the energy released by the reaction between CO2 and Mg is enough to evaporate Zn. Thus, Zn vapor increases graphene porosity and increases the contact of CO2 with Mg, yielding larger masses of graphene. A relationship between the Zn–Mg ratio and the reaction yield was found.
Inflammatory Amplification: A Central Tenet of Uterine Transition for Labor
Authors: Leimert Kelycia B. , Xu Wendy , Princ Magdalena M. , Chemtob Sylvain , Olson David M.
Published: August 2021

In preparation for delivery, the uterus transitions from actively maintaining quiescence during pregnancy to an active parturient state. This transition occurs as a result of the accumulation of pro-inflammatory signals which are amplified by positive feedback interactions involving paracrine and autocrine signaling at the level of each intrauterine cell and tissue. The amplification events occur in parallel until they reach a certain threshold, ‘tipping the scale’ and contributing to processes of uterine activation and functional progesterone withdrawal. The described signaling interactions all occur upstream from the presentation of clinical labor symptoms. In this review, we will: 1) describe the different physiological processes involved in uterine transition for each intrauterine tissue; 2) compare and contrast the current models of labor initiation; 3) introduce innovative models for measuring paracrine inflammatory interactions; and 4) discuss the therapeutic value in identifying and targeting key players in this crucial event for preterm birth.
Thermoresponsive Copolymer Nanovectors Improve the Bioavailability of Retrograde Inhibitors in the Treatment of Leishmania Infections
Authors: Craig Evan , Calarco Anna , Conte Raffaele , Ambrogi Veronica , d’Ayala Giovanna Gomez , Alabi Philip , Sello Jason K. , Cerruti Pierfrancesco , Kima Peter E.
Published: August 2021

Clinical manifestations of leishmaniasis range from self-healing, cutaneous lesions to fatal infections of the viscera. With no preventative Leishmania vaccine available, the frontline option against leishmaniasis is chemotherapy. Unfortunately, currently available anti-Leishmania drugs face several obstacles, including toxicity that limits dosing and emergent drug resistant strains in endemic regions. It is, therefore, imperative that more effective drug formulations with decreased toxicity profiles are developed. Previous studies had shown that 2-(((5-Methyl-2-thienyl)methylene)amino)-N-phenylbenzamide (also called Retro-2) has efficacy against Leishmania infections. Structure–activity relationship (SAR) analogs of Retro-2, using the dihydroquinazolinone (DHQZ) base structure, were subsequently described that are more efficacious than Retro-2. However, considering the hydrophobic nature of these compounds that limits their solubility and uptake, the current studies were initiated to determine whether the solubility of Retro-2 and its SAR analogs could be enhanced through encapsulation in amphiphilic polymer nanoparticles. We evaluated encapsulation of these compounds in the amphiphilic, thermoresponsive oligo(ethylene glycol) methacrylate-co-pentafluorostyrene (PFG30) copolymer that forms nanoparticle aggregates upon heating past temperatures of 30°C. The hydrophobic tracer, coumarin 6, was used to evaluate uptake of a hydrophobic molecule into PFG30 aggregates. Mass spectrometry analysis showed considerably greater delivery of encapsulated DHQZ analogs into infected cells and more rapid shrinkage of L. amazonensis communal vacuoles. Moreover, encapsulation in PFG30 augmented the efficacy of Retro-2 and its SAR analogs to clear both L. amazonensis and L. donovani infections. These studies demonstrate that encapsulation of compounds in PFG30 is a viable approach to dramatically increase bioavailability and efficacy of anti-Leishmania compounds.
Miniature Erupting Volcano-Shaped Mitral Valve Aneurysm Secondary to Streptococcus agalactiae ST1656 Endocarditis: A Case Report
Authors: Yamamoto Hiroyuki , Yamada Hiroyuki , Maeda Takahiro , Goto Mieko , Ikeda Yoshihiko , Takahashi Takashi
Published: August 2021

Mitral valve aneurysm (MVA) is a rare but life-threatening valvular pathologic entity most commonly associated with infective endocarditis (IE) of the aortic valve (AV). We describe a diabetic patient with ruptured anterior MVA secondary to capsular genotype V Streptococcus agalactiae (GBS) harboring novel ST1656 IE without AV involvement. Our patient presented with manifestations of various serious systemic and intracardiac complications, requiring early surgery, but ultimately died from non-cardiogenic causes. This case emphasizes the importance of treating MVA as a dangerous sequela of IE, of performing transesophageal echocardiography to make its accurate diagnosis and institute early surgical intervention, and of considering GBS as a rare but important causative agent of IE in elderly patients with comorbidities.
Confronting Missing Ecological Data in the Age of Pandemic Lockdown
Authors: Hossie Thomas J. , Gobin Jenilee , Murray Dennis L.
Published: August 2021

The COVID-19 pandemic profoundly affected research in ecology and evolution, with lockdowns resulting in the suspension of most research programs and creating gaps in many ecological datasets. Likewise, monitoring efforts directed either at tracking trends in natural systems or documenting the environmental impacts of anthropogenic activities were largely curtailed. In addition, lockdowns have affected human activity in natural environments in ways that impact the systems under investigation, rendering many widely used approaches for handling missing data (e.g., available case analysis, mean substitution) inadequate. Failure to properly address missing data will lead to bias and weak inference. Researchers and environmental monitors must ensure that lost data are handled robustly by diagnosing patterns and mechanisms of missingness and applying appropriate tools like multiple imputation, full-information maximum likelihood, or Bayesian approaches. The pandemic has altered many aspects of society and it is timely that we critically reassess how we treat missing data in ecological research and environmental monitoring, and plan future data collection to ensure robust inference when faced with missing data. These efforts will help ensure the integrity of inference derived from datasets spanning the COVID-19 lockdown and beyond.
Multi-Transcript Level Profiling Revealed Distinct mRNA, miRNA, and tRNA-Derived Fragment Bio-Signatures for Coping Behavior Linked Haplotypes in HPA Axis and Limbic System
Authors: Gley Kevin , Hadlich Frieder , Trakooljul Nares , Haack Fiete , Murani Eduard , Gimsa Ulrike , Wimmers Klaus , Ponsuksili Siriluck
Published: August 2021

The molecular basis of porcine coping behavior (CB) relies on a sophisticated interplay of genetic and epigenetic features. Deep sequencing technologies allowed the identification of a plethora of new regulatory small non-coding RNA (sncRNA). We characterized mRNA and sncRNA profiles of central parts of the physiological stress response system including amygdala, hippocampus, hypothalamus and adrenal gland using systems biology for integration. Therefore, ten each of high- (HR) and low- (LR) reactive pigs (n = 20) carrying a CB associated haplotype in a prominent QTL-region on SSC12 were selected for mRNA and sncRNA expression profiling. The molecular markers related to the LR group included ATP1B2, MPDU1, miR-19b-5p, let-7g-5p, and 5′-tiRNALeu in the adrenal gland, miR-194a-5p, miR-125a-5p, miR-7-1-5p, and miR-107-5p in the hippocampus and CBL and PVRL1 in the hypothalamus. Interestingly, amygdalae of the LR group showed 5′-tiRNA and 5′-tRF (5′-tRFLys, 5′-tiRNALys, 5′-tiRNACys, and 5′-tiRNAGln) enrichment. Contrarily, molecular markers associated with the HR group encompassed miR-26b-5p, tRNAArg, tRNAGlyiF in the adrenal gland, IGF1 and APOD in the amygdala and PBX1, TOB1, and C18orf1 in the hippocampus and miR-24 in the hypothalamus. In addition, hypothalami of the HR group were characterized by 3′-tiRNA enrichment (3′-tiRNAGln, 3′-tiRNAAsn, 3′-tiRNAVal, 3′-tRFPro, 3′-tiRNACys, and 3′-tiRNAAla) and 3′-tRFs enrichment (3′-tRFAsn, 3′-tRFGlu, and 3′-tRFVal). These evidence suggest that tRNA-derived fragments and their cleavage activity are a specific marker for coping behavior. Data integration revealed new bio-signatures of important molecular interactions on a multi-transcript level in HPA axis and limbic system of pigs carrying a CB-associated haplotype.
Combining Immunocytokine and Ex Vivo Activated NK Cells as a Platform for Enhancing Graft-Versus-Tumor Effects Against GD2+ Murine Neuroblastoma
Authors: Bates Paul D. , Rakhmilevich Alexander L. , Cho Monica M. , Bouchlaka Myriam N. , Rao Seema L. , Hales Joanna M. , Orentas Rimas J. , Fry Terry J. , Gilles Stephen D. , Sondel Paul M. , Capitini Christian M.
Published: August 2021

Management for high-risk neuroblastoma (NBL) has included autologous hematopoietic stem cell transplant (HSCT) and anti-GD2 immunotherapy, but survival remains around 50%. The aim of this study was to determine if allogeneic HSCT could serve as a platform for inducing a graft-versus-tumor (GVT) effect against NBL with combination immunocytokine and NK cells in a murine model. Lethally irradiated C57BL/6 (B6) x A/J recipients were transplanted with B6 bone marrow on Day +0. On day +10, allogeneic HSCT recipients were challenged with NXS2, a GD2+NBL. On days +14-16, mice were treated with the anti-GD2 immunocytokine hu14.18-IL2. In select groups, hu14.18-IL2 was combined with infusions of B6 NK cells activated with IL-15/IL-15Rα and CD137Lex vivo. Allogeneic HSCT alone was insufficient to control NXS2 tumor growth, but the addition of hu14.18-IL2 controlled tumor growth and improved survival. Adoptive transfer ofex vivoCD137L/IL-15/IL-15Rα activated NK cells with or without hu14.18-IL2 exacerbated lethality. CD137L/IL-15/IL-15Rα activated NK cells showed enhanced cytotoxicity and produced high levels of TNF-αin vitro, but induced cytokine release syndrome (CRS)in vivo. Infusing Perforin-/-CD137L/IL-15/IL-15Rα activated NK cells had no impact on GVT, whereas TNF-α-/-CD137L/IL-15/IL-15Rα activated NK cells improved GVT by decreasing peripheral effector cell subsets while preserving tumor-infiltrating lymphocytes. Depletion of Ly49H+NK cells also improved GVT. Using allogeneic HSCT for NBL is a viable platform for immunocytokines andex vivoactivated NK cell infusions, but must be balanced with induction of CRS. Regulation of TNFα or activating NK subsets may be needed to improve GVT effects.