bluuebunny/crossref_metadata_2025 huggingface dataset:
A influência da atividade física para a prevenção e tratamento da osteoporose: revisão integrativa
Authors: Silva Barbara Beatriz Lira da , Alves Ana Klara Rodrigues , Pereira Raquel de Brito , Rodrigues Sandra Luiza Gouvêa , Santo Júnior Jales Gomes Espírito , Nogueira Fábio Dias , Alves Francisco Robson de Oliveira , Veras Iris Lopes , Silveira Eugênia Mirza de Queiroz Ferreira Barboza da , Melo Larissa Galeno , Castro Rhauanna Mylena dos Santos , Santos Tito Cacau Sousa , Azevedo Daline da Silva , Lima Ana Caroliny de Barros Soares , Mello Gustavo Wilson de Sousa
Published: September 2021

Objetivo: O presente estudo teve como objetivo verificar qual a influência da atividade física na prevenção e tratamento da osteoporose. Métodos: Revisão integrativa da literatura, realizado através de uma busca nas bases de dados Pubmed e Scielo usando os cruzamentos dos descritores em inglês “Osteoporosis”, “Prevention”, “Physical exercise”, utilizando o operadorador booleano “and”. Para a avaliação do problema de pesquisa e sua estratificação foi utilizada a estratégia PVO. Quanto a construção deste artigo, aplicou-se o seguinte questionamento: Como a atividade física influência na prevenção e no tratamento da osteoporose? Quanto aos critérios de inclusão foram incluídos artigos escritos na língua inglesa e portuguesa; publicados entre os anos 2015 a 2020. Após leitura seletiva dos textos, foram selecionados 19 artigos que atendessem ao objetivo do estudo. Resultados e Discussão: O exercício pode melhorar ou manter a massa óssea em todas as idades e estudos demonstram que o exercício pode melhorar a função física, qualidade de vida, dor e vitalidade em mulheres pós-menopáusicas osteoporóticas e osteopênicas. Esses exercícios específicos devem ser dinâmicos, exceder um limite de intensidade e frequência de deformação, impor um padrão de carga incomum nos ossos e ser apoiados por energia nutritiva ilimitada. Conclusão: O exercício pode melhorar ou manter a massa óssea em todas as idades e também pode melhorar a função física, qualidade de vida, dor e vitalidade. Os exercícios devem ser dinâmicos, exceder um limite de intensidade e frequência de deformação, impor um padrão de carga incomum nos ossos e ser apoiados por energia nutritiva ilimitada.
Zona Franca de Manaus: instabilidade do modelo e alternativas para o aproveitamento de seu real potencial
Authors: Queiroz Iris Rodrigues , Silva Claudenira Alves da , Oliveira Jean Serrão de
Published: September 2021

Em 1957, foi criado o modelo de desenvolvimento econômico para o estado do Amazonas denominado Zona Franca de Manaus (ZFM) por meio da 3.173/57, que posteriormente foi revogada pelo Decreto-Lei 288/63. Como, constitucionalmente, a ZFM não pode ser deslocada para outro lugar, mas nada impede que seja implantado um modelo semelhante em outras regiões do país ou seja alterado os tributos que são concedidos ao modelo o objetivo geral da pesquisa é propor alternativas para os entraves enfrentado pelo modelo ZFM que está deixando de se fortalecer frente a burocracia do governo federal e estadual. Para o desenvolvimento da pesquisa foi necessário realizar um estudo bibliográfico para o embasamento teórico da ZFM, incentivos fiscais, Processo Produtivo Básico (PPB) e Pesquisa, Desenvolvimento e Inovação (PD&I), além da pesquisa em campo para ter um suporte técnico e especializado para elaborar as propostas aos entraves enfrentados pelo modelo ZFM. Ao final da pesquisa conclui-se que os objetivos foram alcançados porque foi proposto alternativas para a melhor aplicação do modelo, entre as sugestões do estudo há: garantir que não se emitam normas infraconstitucionais que firam a constituição, ou seja, garantir à ZFM sua existência com vantagens competitivas e comparativas até o ano de 2073; revisar todos os marcos regulatórios para concessão de área, aprovação do projeto e acompanhamento industrial; demostrar aos ministérios da economia a dinâmica econômica produzida na ZFM cria impedância financeira, entre outras.
Burnout em trabalhadores de enfermagem de hospitais: estudo de tendências
Authors: Dorneles Ademir Jones Antunes , Dalmolin Graziele de Lima , Facin Mariane Buligon
Published: September 2021

Objetivo: conhecer a tendência da produção científica brasileira sobre burnout em trabalhadores de enfermagem no ambiente hospitalar. Método: Revisão narrativa com busca sistemática de teses e dissertações; realizada no período entre setembro de 2020 e março de 2021, a partir do Catálogo de Teses e Dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), com a combinação das palavras-chaves: “burnout AND "hospital" AND enfermagem”. Resultados: Foram incluídos 37 estudos, entre os anos de 2005 e 2019; evidenciaram-se três categorias temáticas: burnout e organização do trabalho, fatores associados ao burnout e estratégias e ações para prevenir o burnout. Observou-se que existem fatores correlacionados ente o burnout, a enfermagem e o ambiente hospitalar destacando-se entre eles, a baixa realização no trabalho, a exaustão profissional e o clima ético negativo; que investir. Conclusão/Considerações Finais: investir na prática de enfermagem em ambientes de trabalho éticos e positivos contribuirá na melhoria da qualidade da assistência de enfermagem e na redução de doenças laborais, como o burnout.
Inteligência Artificial no diagnóstico de doenças neurodegenerativas: uma revisão sistemática de literatura
Authors: Brito Emilayne Nicácio Dias , Figueiredo Bárbara Queiroz de , Souto Diego Nunes , Nogueira Júlia Fernandes , Melo Ana Luísa de Castro , Silva Iorrane Tavares da , Oliveira Iuri Pimenta , Almeida Marcelo Gomes de
Published: September 2021

Introdução: Inteligência Artificial (IA) é um ramo da ciência da computação que se propõe a desenvolver sistemas que simulem a capacidade humana de percepção de um problema, identificando seus componentes para, com isso, resolver problemas e propor/tomar decisões. Objetivo: ampliar conhecimentos e categorizar aplicações do uso da IA para o diagnóstico, tratamento e prognóstico de doenças neurodegenerativas, uma vez que, atualmente, seu uso se torna amplamente aplicável e essencial para contornar as etapas da moléstia. Metodologia: Trata-se de uma pesquisa descritiva do tipo revisão integrativa da literatura realizada através do acesso online nas bases de dados National Library of Medicine (PubMed MEDLINE), Scientific Electronic Library Online (Scielo), Google Scholar, Biblioteca Virtual em Saúde (BVS), Web of Science e EBSCO Information Services, nos meses de junho e julho de 2021. Resultados e discussão: Nos últimos anos, os dados obtidos por redes neurais, aprendizagem profunda e outros métodos matemáticos estão se desenvolvendo a uma velocidade sem precedentes. Eles têm sido amplamente utilizados no campo da análise de imagens, e demostraram grande potencial na análise de imagens médicas no diagnóstico de Doença de Alzheimer, Doença de Parkinson, esclerose múltipla, sendo a aplicação destes métodos podem melhorar ainda mais a capacidade de análise de dados de imagem multimodais complexos e melhorar a eficiência desses diagnósticos.  Conclusão: com a inteligência artificial, os distúrbios neurodegenerativos podem ser investigados em um nível mais profundo, fornecendo uma visão geral abrangente da doença e abrindo caminhos para a aplicação da medicina de precisão para essas patologias.
Warming sea surface temperatures fuel summer epidemics of eelgrass wasting disease
Authors: Groner ML , Eisenlord ME , Yoshioka RM , Fiorenza EA , Dawkins PD , Graham OJ , Winningham M , Vompe A , Rivlin ND , Yang B , Burge CA , Rappazzo B , Gomes CP , Harvell CD
Published: September 2021

Seawater temperatures are increasing, with many unquantified impacts on marine diseases. While prolonged temperature stress can accelerate host-pathogen interactions, the outcomes in nature are poorly quantified. We monitored eelgrass wasting disease (EWD) from 2013-2017 and correlated mid-summer prevalence of EWD with remotely sensed seawater temperature metrics before, during, and after the 2015-2016 marine heatwave in the northeast Pacific, the longest marine heatwave in recent history. Eelgrass shoot density declined by 60% between 2013 and 2015 and did not recover. EWD prevalence ranged from 5-70% in 2013 and increased to 60-90% by 2017. EWD severity approximately doubled each year between 2015 and 2017. EWD prevalence was positively correlated with warmer temperature for the month prior to sampling while EWD severity was negatively correlated with warming prior to sampling. This complex result may be mediated by leaf growth; bigger leaves may be more likely to be diseased, but may also grow faster than lesions, resulting in lower severity. Regional stressors leading to population declines prior to or early in the heatwave may have exacerbated the effects of warming on eelgrass disease susceptibility and reduced the resilience of this critical species.
Hubungan Antara Pengetahuan, Sikap dan Praktik Personal Hygiene Organ Genitalia Eksterna Terhadap Kejadian Keputihan Patologis
Authors: Cahyaningtyas Widia A. A. , Nainggolan Sudung , Simanjuntak Tigor P.
Published: September 2021

Abstrak

Keputihan (leukorea, flour albus, vaginal discharge) adalah sekret berlebihan dari vagina selain darah haid, dan tidak disebabkan neoplasma atau penyakit sistemik. Keputihan merupakan masalah kesehatan reproduksi dialami hampir 75%  perempuan didunia, paling tidak sekali selama hidupnya. Kurangnya pengetahuan, sikap, dan praktik dalam perawatan vagina diyakini berpengaruh terhadap kejadian keputihan patologis tersebut. Penelitian ini bertujuan untuk mengetahui hubungan pengetahuan, sikap, dan praktik personal hygiene organ genital eksterna terhadap kejadian keputihan patologis pada mahasiswi Fakultas Kedokteran Universitas Kristen Indonesia. Penelitian ini menggunakan desain penelitian analitik korelasional pada 98 mahasiswi. Terdapathubungan yang bermakna (p= 0,000) dan korelasi positif antara tingkat pengetahuan, sikap dan praktik personal hygiene dengan kejadian keputihan patologis.

 

Kata Kunci : keputihan, pengetahuan, sikap, praktik, personal hygiene.

 

Relationship Between Knowledge, Attitudes and Personal Practices of External Genitalia Hygiene Against Pathological Leucorrhoea

 

Abstract

Vaginal discharge (leukorrhea, flour albus, vaginal discharge) is excessive discharge from the vagina other than menstrual blood, and is not caused by neoplasms or systemic disease. Leucorrhoea is a reproductive health problem that affects nearly 75% of women in the world, at least once in their lifetime. Lack of knowledge, attitude, and practice in vaginal care is believed to have an effect on the incidence of pathological vaginal discharge. This study aims to determine the relationship between knowledge, attitudes, and personal hygiene practices of external genital organs on the incidence of pathological vaginal discharge in students of the Faculty of Medicine, Christian University of Indonesia. This study used a correlational analytical research design on 98 female students of the Faculty of Medicine, Christian University of Indonesia. It was found a significant relationship (p = 0.000) and a positive correlation between the level of knowledge, attitudes and personal hygiene practices with the incidence of pathological vaginal discharge.

 

Keywords: leucorrhoea, knowledge, attitude, practice, personal hygiene.
The content of plant pigments in bottom sediments of Batorino Lake and their spectral pigment indices
Authors: Zhukava Hanna A. , Smolskaya Volha S. , Vishnevetskaya Ekaterina A. , Karosienė Jūratė
Published: September 2021

Studies on the Batorino Lake were aimed at assessing the quantitative and qualitative characteristics of the autotrophic component of bottom sediments, as well as searching for their relationships with the data of spectral analysis of the pigment composition. The content of total chlorophyll a (without correction for the presence of phaeopigments) was relatively low – 12.7 ± 10.2 µg/g wet weight of bottom sediments. The content of carotenoids averaged 10.24 ± 4.89 µg/g wet weight of bottom sediments. It has been shown that pigment indices: Е450 /Е480, Е480/Е664, Е430/Е664, Е430/Е412, characterise the structural indicators of bottom sediments and reflect the long-term trends in the development of primary producers in water ecosystems, primarily phytoplankton. During the preliminary analysis, auxiliary pigment indices for controlling the purity of the extract and the clarity of the prescribed spectrum were calculated: Е664/Е720, Е430/Е720, Е530/Е720, Е412/Е720, Е430/Е530, Е664/Е530, Е412/Е664. A close inverse relationship was revealed between Е430/Е664 index and the amount of chlorophyll a at different depths of bottom sediments (r = – 0.7), as well as an average correlation between the Е430/ Е412 index and the proportion of phaeopigments (r = – 0.56).
Some aspects of biological effect of emodin on plants
Authors: Kakhanouski Aliaxandr I. , Yurin Vladimir M. , Kakhanouskaya Katsiaryna Yu.
Published: September 2021

Emodin, a secondary metabolite of many plants, has a wide spectrum of biological action on various groups of organisms, but the mechanisms of its action on plants are practically not studied. There is an assumption that emodin plays a certain role in allelopathy, getting into the soil with fallen leaves in the form of glycosides, which break down into emodin aglycones and are stored in the ecosystem. The aim of the study was to establish the effects of emodin on growth processes and its effect on heme-containing enzymes. It was found that emodin has an inhibitory effect on the root system of Allium cepa, and also promotes the activation of catalase activity in the roots. When studying the direct action of emodin on the activity of the catalase enzyme in vitro, it was found that the activity of the catalase enzyme decreases under the action of emodin. When studying the possible mechanisms of inactivation, it was found that emodin can interact with heme. Further detailing of the patterns of biological action of emodin will expand the scope of its application in plant protection, crop production, and also determine its role in plant ecology and physiology.
A precarização do Direito do Trabalho a partir de influências da Revolução Industrial sobre os entregadores por aplicativos no Brasil
Authors: Fernandes Lima Geórgia
Published: September 2021

O presente artigo objetiva uma abordagem acerca da temática da precarização do Direito do Trabalho a partir de influências da Revolução Industrial para com entregadores por aplicativos. Esta realidade vem ocorrendo pela falta de proteção regulamentada trabalhista a esses entregadores. Neste artigo é realizado um levantamento do histórico tratando das sucessivas Revoluções Industriais, dando-se ênfase a da “Indústria 4.0”, que se consolidou pela expansão das inovações tecnológicas. Em seguida, analisa-se a nova organização do trabalho com o surgimento das plataformas digitais, que geraram a atual terminologia do Gig Economy. Neste escopo, é abordado, também, o histórico do surgimento do conceito de “delivery” até chegar ao atual modelo, destacando-se os entregadores por aplicativos da iFood®, Rappi® e Uber Eats®. Ao mesmo tempo, o presente texto trata dos impactos nas relações de trabalho, destacando-se a precarização dos direitos trabalhistas, considerando que os entregadores por aplicativos não possuem proteção regulamentada na Consolidação das Leis do Trabalho (CLT). Finalmente, é estabelecida uma discussão sobre a necessidade de regulamentação protetiva, com o intuito de provocar uma reflexão sobre as tomadas de decisão para a regulamentação do trabalho dos entregadores por aplicativos.
State national security policy and intellectual property issues
Authors: Zaikivskyi Oleksandr , Onistrat Oleksandr
Published: September 2021

Keywords: state policy, national security, intellectual property

National security (“NS”) of Ukraine is achieved through a balancedstate policy in accordance with accepted doctrines, strategies, concepts and programsin such areas as political, economic, social, military, environmental, scientific andtechnological, information, etc.However, many theoretical and practical issues concerning the definition of thecontent, challenges, tasks and mechanisms of implementation of effective functions ofpublic policy and management decisions for the further development of social processesstill remain insufficiently studied. Therefore, the main tasks of the NS system subjectsare constant monitoring of the impact on NS of processes taking place in variousfields (including intellectual property), forecasting, identifying and assessing possiblethreats, destabilizing factors and conflicts, their causes and occurrence consequences.In particular, the impact on NS (especially on defence capabilities) of the significantdevelopment of intellectual property and the full use of intellectual property rights isnot taken into account at all.State NS policy should include measures to prevent the emergence and neutralizationof sources of threats to NS under the influence of the development of intellectualproperty.Theoretical aspects of the state policy of National Security and Defence of Ukraine(“NSDU”) development are considered. The necessity of current problems definition inthis sphere and the inclusion of intellectual property questions in these processes isinvestigated. It is determined that the effective implementation of the state NS policyis impossible without a comprehensive analysis of intellectual property issues impacton the sphere of the NSDU. The importance of further research on the development ofa unified approach to improving the protection of intellectual property and its determinationas a component of NSDU, the development of appropriate recommendationsto address issues of intellectual property in this area and to neutralize sources ofthreats under the influence of intellectual property in the structure of NSDU.
Application of Principal Component Analysis of Sows' Behavioral Indicators of the Welfare Quality® Protocol to Determine Main Components of Behavior
Authors: Friedrich Lena , Krieter Joachim , Kemper Nicole , Czycholl Irena
Published: September 2021

Understanding behavior is important in terms of welfare assessments to be able to evaluate possible changes in behavior among different husbandry systems. The present study applied principal component analysis (PCA) to reveal relationships between behavioral indicators to identify the main components of sows' behavior promoting feasibility of welfare assessments by providing possibilities for variable reduction and aggregation. The indicators of the Welfare Quality®protocol's principle to assess behavior were repeatedly applied by two observers on 13 farms in Northern Germany. This included Qualitative Behavior Assessments (QBA) to evaluate animals' body language using 20 pre-defined adjectives, assessments of social and exploratory behavior, stereotypies, and human–animal relationship tests. Two separate PCA were performed with respect to the QBA: (1) adjectives were included as independent variables and (2) adjectives were pre-aggregated using the calculation rules of the Welfare Quality®protocol for fattening pigs since a calculation for sows does not yet exist. In both analyses, two components described sows' behavior. Most variance was explained by the solution with adjectives as independent variables (51.0%). Other behavioral elements not captured as indicators by the protocol may still be important for all-inclusive welfare assessments as the required variance of 70% was not achieved in the analyses. Component loadings were used to determine components' labels as (1) “satisfaction of exploratory behavior” and (2) “social resting”. Both components reflected characteristics of sows' natural behavior and can subsequently be used for variable reduction but also for development of component scores for aggregation. As defined for PCA, component 1 explained more variance than component 2. PCA is useful to determine the main components of sows' behavior, which can be used to enhance feasibility of welfare assessments.
Effects of the SUMO Ligase BCA2 on Metabolic Activity, Cell Proliferation, Cell Migration, Cell Cycle, and the Regulation of NF-κB and IRF1 in Different Breast Epithelial Cellular Contexts
Authors: Shi Yuhang , Castro-Gonzalez Sergio , Chen Yuexuan , Serra-Moreno Ruth
Published: September 2021

Breast cancer-associated gene 2 (BCA2) is an E3 ubiquitin and SUMO ligase with antiviral properties against HIV. Specifically, BCA2 (i) enhances the restriction imposed by BST2/Tetherin, impeding viral release; (ii) promotes the ubiquitination and degradation of the HIV protein Gag, limiting virion production; (iii) down-regulates NF-κB, which is necessary for HIV RNA synthesis; and (iv) activates the innate transcription factor IRF1. Due to its antiviral properties, ectopic expression of BCA2 in infected cells represents a promising therapeutic approach against HIV infection. However, BCA2 up-regulation is often observed in breast tumors. To date, the studies about BCA2 and cancer development are controversial, stating both pro- and anti-oncogenic roles. Here, we investigated the impact of BCA2 on cellular metabolic activity, cell proliferation, cell migration, and cell cycle progression. In addition, we also examined the ability of BCA2 to regulate NF-κB and IRF1 in transformed and non-tumor breast epithelial environments. Despite the fact that BCA2 promotes the transition from G1 to S phase of the cell cycle, it did not increase cell proliferation, migration nor metabolic activity. As expected, BCA2 maintains its enzymatic function at inhibiting NF-κB in different breast cancer cell lines. However, the effect of BCA2 on IRF1 differs depending on the cellular context. Specifically, BCA2 activates IRF1 in ER+breast cell lines while it inhibits this transcription factor in ER–breast cancer cells. We hypothesize that the distinct actions of BCA2 over IRF1 may explain, at least in part, the different proposed roles for BCA2 in these cancers.
Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond
Authors: Jeong Wonyoung , Jho Eek-hoon
Published: September 2021

Wnt signaling plays crucial roles in development and tissue homeostasis, and its dysregulation leads to various diseases, notably cancer. Wnt/β-catenin signaling is initiated when the glycoprotein Wnt binds to and forms a ternary complex with the Frizzled and low-density lipoprotein receptor-related protein 5/6 (LRP5/6). Despite being identified as a Wnt co-receptor over 20 years ago, the molecular mechanisms governing how LRP6 senses Wnt and transduces downstream signaling cascades are still being deciphered. Due to its role as one of the main Wnt signaling components, the dysregulation or mutation of LRP6 is implicated in several diseases such as cancer, neurodegeneration, metabolic syndrome and skeletal disease. Herein, we will review how LRP6 is activated by Wnt stimulation and explore the various regulatory mechanisms involved. The participation of LRP6 in other signaling pathways will also be discussed. Finally, the relationship between LRP6 dysregulation and disease will be examined in detail.
Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients
Authors: Jiang Quan , Chen Lingli , Chen Hao , Tang Zhaoqing , Liu Fenglin , Sun Yihong
Published: September 2021

The immune microenvironment plays a critical role in tumor biology. As a critical feature of cancers, stemness is acknowledged as a contributor to the development of drug resistance in gastric cancers (GCs). Long non-coding RNAs (lncRNAs) have been revealed to participate in this process. In this study, we aimed to develop a stemness-related lncRNA signature (SRLncSig) with guiding significance for immunotherapy. Three cohorts (TCGA, Zhongshan, and IMvigor210) were enrolled for analysis. A list of stemness-related lncRNAs (SRlncRNAs) was collected by co-expression strategy under the threshold of coefficient value >0.35 and p-value < 0.05. Cox and Lasso regression analysis was further applied to find out the SRlncRNAs with prognosis-predictive value to establish the SRLncSig in the TCGA cohort. IPS and TIDE algorithms were further applied to predict the efficacy of SRLncSig in TCGA and Zhongshan cohorts. IMvigor210 was composed of patients with clinical outcomes of immunotherapy. The results indicated that SRLncSig not only was confirmed as an independent risk factor for GCs but also identified as a robust indicator for immunotherapy. The patient with a lower SRLncSig score was more likely to benefit from immunotherapy, and the results were highly consistent in three cohorts. In conclusion, our study not only could clarify the correlations between stemness and immunotherapy in GC patients but also provided a model to guide the applications of immunotherapy in clinical practice.
Pathogen Metagenomics Reveals Distinct Lung Microbiota Signatures Between Bacteriologically Confirmed and Negative Tuberculosis Patients
Authors: Ding Li , Liu Yanmin , Wu Xiaorong , Wu Minhao , Luo Xiaoqing , Ouyang Hui , Xia Jinyu , Liu Xi , Ding Tao
Published: September 2021

Understanding the dynamics of lung microbiota in tuberculosis patients, especially those who cannot be confirmed bacteriologically in clinical practice, is imperative for accurate diagnosis and effective treatment. This study aims to characterize the distinct lung microbial features between bacteriologically confirmed and negative tuberculosis patients to understand the influence of microbiota on tuberculosis patients. We collected specimens of bronchoalveolar lavage fluid from 123 tuberculosis patients. Samples were subjected to metagenomic next-generation sequencing to reveal the lung microbial signatures. By combining conventional bacterial detection and metagenomic sequencing, 101/123 (82%) tuberculosis patients were bacteriologically confirmed. In addition toMycobacterium tuberculosis,Staphylococcus aureus,Kluyveromyces lactis, andPyricularia pennisetigenawere also enriched in the bacteriological confirmation group. In contrast,Haemophilus parainfluenzaewas enriched in the bacteriologically negative group. Besides, microbial interaction exhibits a different state between bacteriologically confirmed and negative tuberculosis patients.Mycobacterium tuberculosiswas confirmed correlated with clinical characteristics such as albumin and chest cavities. Our study comprehensively demonstrates the correlation between unique features of lung microbial dynamics and the clinical characteristics of tuberculosis patients, suggesting the importance of studying the pulmonary microbiome in tuberculosis disease and providing new insights for future precision diagnosis and treatment.
Case Report: BMPR2-Targeted MinION Sequencing as a Tool for Genetic Analysis in Patients With Pulmonary Arterial Hypertension
Authors: Takashima Tomoya , Brisset Sophie , Furukawa Asuka , Taniguchi Hirohisa , Takeyasu Rika , Kawamura Akio , Tamura Yuichi
Published: September 2021

Background: Mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2) represent a major genetic cause of pulmonary arterial hypertension (PAH). Identification of BMPR2 mutations is crucial for the genetic diagnosis of PAH. MinION nanopore sequencer is a portable third-generation technology that enables long-read sequencing at a low-cost. This nanopore technology-based device has not been used previously for PAH diagnosis. This study aimed to determine the feasibility of using MinION nanopore sequencing for the genetic analysis of PAH patients, focused on BMPR2.

Methods: We developed a protocol for the custom bioinformatics pipeline analysis of long reads generated by long-PCR. To evaluate the potential of using MinION sequencing in PAH, we analyzed five samples, including those of two idiopathic PAH patients and a family of three members with one affected patient. Sanger sequencing analysis was performed to validate the variants.

Results: The median read length was around 3.4 kb and a good mean quality score of approximately 19 was obtained. The total number of reads generated was uniform among the cases and ranged from 2,268,263 to 3,126,719. The coverage was consistent across flow cells in which the average number of reads per base ranged from 80,375 to 135,603. We identified two polymorphic variants and three mutations in four out of five patients. Certain indel variant calling-related errors were observed, mostly outside coding sequences.

Conclusion: We have shown the ability of this portable nanopore sequencer to detect BMPR2 mutations in patients with PAH. The MinION nanopore sequencer is a promising tool for screening BMPR2 mutations, especially in small laboratories and research groups.
Modified GAN Augmentation Algorithms for the MRI-Classification of Myocardial Scar Tissue in Ischemic Cardiomyopathy
Authors: Sharma Umesh C. , Zhao Kanhao , Mentkowski Kyle , Sonkawade Swati D. , Karthikeyan Badri , Lang Jennifer K. , Ying Leslie
Published: September 2021

Contrast-enhanced cardiac magnetic resonance imaging (MRI) is routinely used to determine myocardial scar burden and make therapeutic decisions for coronary revascularization. Currently, there are no optimized deep-learning algorithms for the automated classification of scarred vs. normal myocardium. We report a modified Generative Adversarial Network (GAN) augmentation method to improve the binary classification of myocardial scar using both pre-clinical and clinical approaches. For the initial training of the MobileNetV2 platform, we used the images generated from a high-field (9.4T) cardiac MRI of a mouse model of acute myocardial infarction (MI). Once the system showed 100% accuracy for the classification of acute MI in mice, we tested the translational significance of this approach in 91 patients with an ischemic myocardial scar, and 31 control subjects without evidence of myocardial scarring. To obtain a comparable augmentation dataset, we rotated scar images 8-times and control images 72-times, generating a total of 6,684 scar images and 7,451 control images. In humans, the use of Progressive Growing GAN (PGGAN)-based augmentation showed 93% classification accuracy, which is far superior to conventional automated modules. The use of other attention modules in our CNN further improved the classification accuracy by up to 5%. These data are of high translational significance and warrant larger multicenter studies in the future to validate the clinical implications.
Integrated Household Appliance Scheduling With Modeling of Occupant Satisfaction and Appliance Heat Gain
Authors: Zhao Zehua , Luo Fengji , Zhang Yongxi , Ranzi Gianluca , Su Sheng
Published: September 2021

With the prevalence of building automation and Internet-of-Things technologies, home energy management has become an active area in recent years. This paper proposes an integrated, multi-objective Home Energy Management System (HEMS), which optimally schedules controllable electric household appliances to balance three objectives: 1) home energy cost; 2) the occupant’s use satisfaction of controllable appliances; and 3) the occupant’s thermal comfort. In particular, the HEMS models the coupling operational relationship between the non-thermostatically controlled appliances and the air conditioner by investigating the impact of heat gains released by the appliances on the indoor temperature. An advanced multi-objective optimizer is applied to solve the home energy management model. Simulations are conducted to validate the proposed method.
UNC93B1 Is Widely Expressed in the Murine CNS and Is Required for Neuroinflammation and Neuronal Injury Induced by MicroRNA let-7b
Authors: Klammer Markus G. , Dzaye Omar , Wallach Thomas , Krüger Christina , Gaessler Dorothea , Buonfiglioli Alice , Derkow Katja , Kettenmann Helmut , Brinkmann Melanie M. , Lehnardt Seija
Published: September 2021

The chaperone protein Unc-93 homolog B1 (UNC93B1) regulates internalization, trafficking, and stabilization of nucleic acid-sensing Toll-like receptors (TLR) in peripheral immune cells. We sought to determine UNC93B1 expression and its functional relevance in inflammatory and injurious processes in the central nervous system (CNS). We found that UNC93B1 is expressed in various CNS cells including microglia, astrocytes, oligodendrocytes, and neurons, as assessed by PCR, immunocyto-/histochemistry, and flow cytometry. UNC93B1 expression in the murine brain increased during development. Exposure to the microRNA let-7b, a recently discovered endogenous TLR7 activator, but also to TLR3 and TLR4 agonists, led to increased UNC93B1 expression in microglia and neurons. Microglial activation by extracellular let-7b required functional UNC93B1, as assessed by TNF ELISA. Neuronal injury induced by extracellular let-7b was dependent on UNC93B1, as UNC93B1-deficient neurons were unaffected by the microRNA’s neurotoxicity in vitro. Intrathecal application of let-7b triggered neurodegeneration in wild-type mice, whereas mice deficient for UNC93B1 were protected against injurious effects on neurons and axons. In summary, our data demonstrate broad UNC93B1 expression in the murine brain and establish this chaperone as a modulator of neuroinflammation and neuronal injury triggered by extracellular microRNA and subsequent induction of TLR signaling.
Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling
Authors: Tian Lianlian , Zhao Jun-Long , Kang Jian-Qin , Guo Shi-bo , Zhang Nini , Shang Lei , Zhang Ya-Long , Zhang Jian , Jiang Xun , Lin Yan
Published: September 2021

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.
Active Carbon Flux of Mesozooplankton in South China Sea and Western Philippine Sea
Authors: Ge Ruping , Chen Hongju , Zhuang Yunyun , Liu Guangxing
Published: September 2021

The active carbon flux mediated by diel vertical migration (DVM) of zooplankton is an important component of the downward carbon flux in the ocean. However, active fluxes transported by zooplankton DVM are poorly known in the South China Sea (SCS) and the Western Philippine Sea (WPS). In this study, active carbon fluxes in the SCS and WPS were evaluated on the basis of the data of mesozooplankton community and DVM at two stations of these areas. The mesozooplankton community in the SCS was obviously different from that in the WPS, and higher species number and abundance in the SCS were observed, which may be related to the higher chlorophyll a (Chl a) concentration and the wide gradients of temperature and salinity in this sea. Moreover, shallow depth Chl a maximum and strong thermocline were detected in the SCS, causing lower migration amplitudes of mesozooplankton in the SCS than those in the WPS. However, the migrant biomass of mesozooplankton in the SCS was 98.40 mg C m–2, higher than that in the WPS at 25.12 mg C m–2. The mesozooplankton active carbon flux in the SCS (4.64 mg C m–2⋅d–1) was also higher than that in the WPS (1.80 mg C m–2⋅d–1). The mesozooplankton active fluxes were equivalent to 8.3 and 8.1% of the total flux (active flux plus passive flux) of the SCS and WPS, respectively, and they play an important role in the biological pump functioning in the two regions.
A Consortium of Rhizosphere-Competent Actinobacteria Exhibiting Multiple Plant Growth-Promoting Traits Improves the Growth of Avicennia marina in the United Arab Emirates
Authors: El-Tarabily Khaled A. , Sham Arjun , Elbadawi Alaa A. , Hassan Amira H. , Alhosani Bashaer K. K. , El-Esawi Mohamed A. , AlKhajeh Abdulmajeed S. , AbuQamar Synan F.
Published: September 2021

Gray mangrove (Avicennia marina) is the dominant vegetation distributed along the coast of the United Arab Emirates (UAE). Despite its performance as natural coastal guardians, very little is known about the reforestation projects to increase mangrove cover over the years in the UAE and in the Arabian Gulf. Plant growth-promoting actinobacteria (PGPA) were isolated from the mangrove rhizosphere sediments found in the UAE and were evaluated for their potential to produce plant growth regulators (PGRs) and to enhance mangrove growth under seawater irrigation conditions.In vitroscreening identified nine rhizosphere-competent actinobacterial isolates, in a naturally competitive environment, of whichStreptomyces coelicoflavus(Sc) showed a high phosphorus solubilizing activity. Moreover,Streptomyces polychromogenes(Sp),Streptomyces bacillaris(Sb), andStreptomyces ferrugineus(Sf) produced auxins, polyamines (PAs), and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, respectively. Although sediment inoculation with single isolates significantly improved the dry biomass of mangrove shoots (43.2–74.0%) and roots (40.8–75.9%), the consortium of isolates (Sc/Sp/Sb/Sf) caused a greater increase in the dry weight of shoots (82.1%) and roots (81.6%) compared with seawater-irrigated plants (control). In our greenhouse experiments, the levels of photosynthetic pigments,in plantaauxins, and PAs significantly increased in plant tissues inoculated withSc/Sp/Sb/Sf; whereas ACC contents were reduced. This was also evident as the maximum velocity of rubisco carboxylation (Vcmax) increased four-fold in plants treated with the mixture of isolates over control. To the best of our knowledge, this is the first study reporting culturable halotolerant, rhizosphere-competent PGPA inhabiting salty and arid ecosystems applied individually or in combination to promote mangrove growth under harsh conditions such as those found in the Arabian coastal areas.
Functional Characterization of the Cell Division Gene Cluster of the Wall-less Bacterium Mycoplasma genitalium
Authors: Martínez-Torró Carlos , Torres-Puig Sergi , Marcos-Silva Marina , Huguet-Ramón Marta , Muñoz-Navarro Carmen , Lluch-Senar Maria , Serrano Luis , Querol Enrique , Piñol Jaume , Pich Oscar Q.
Published: September 2021

It is well-established that FtsZ drives peptidoglycan synthesis at the division site in walled bacteria. However, the function and conservation of FtsZ in wall-less prokaryotes such as mycoplasmas are less clear. In the genome-reduced bacterium Mycoplasma genitalium, the cell division gene cluster is limited to four genes: mraZ, mraW, MG_223, and ftsZ. In a previous study, we demonstrated that ftsZ was dispensable for growth of M. genitalium under laboratory culture conditions. Herein, we show that the entire cell division gene cluster of M. genitalium is non-essential for growth in vitro. Our analyses indicate that loss of the mraZ gene alone is more detrimental for growth of M. genitalium than deletion of ftsZ or the entire cell division gene cluster. Transcriptional analysis revealed a marked upregulation of ftsZ in the mraZ mutant. Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics confirmed the overexpression of FtsZ in MraZ-deprived cells. Of note, we found that ftsZ expression was upregulated in non-adherent cells of M. genitalium, which arise spontaneously at relatively high rates. Single cell analysis using fluorescent markers showed that FtsZ localization varied throughout the cell cycle of M. genitalium in a coordinated manner with the chromosome and the terminal organelle (TMO). In addition, our results indicate a possible role for the RNA methyltransferase MraW in the regulation of FtsZ expression at the post-transcriptional level. Altogether, this study provides an extensive characterization of the cell division gene cluster of M. genitalium and demonstrates the existence of regulatory elements controlling FtsZ expression at the temporal and spatial level in mycoplasmas.
Whole-Genome Sequencing Elucidates the Epidemiology of Multidrug-Resistant Acinetobacter baumannii in an Intensive Care Unit
Authors: Mao Pu , Deng Xiaolong , Yan Leping , Wang Ya , Jiang Yueting , Zhang Rong , Yang Chun , Xu Yonghao , Liu Xiaoqing , Li Yimin
Published: September 2021

The nosocomial pathogen Acinetobacter baumannii is a frequent cause of healthcare-acquired infections, particularly in critically ill patients, and is of serious concern due to its potential for acquired multidrug resistance. Whole-genome sequencing (WGS) is increasingly used to obtain a high-resolution view of relationships between isolates, which helps in controlling healthcare-acquired infections. Here, we conducted a retrospective study to identify epidemic situations and assess the percentage of transmission in intensive care units (ICUs). Multidrug-resistant A. baumannii (MDR-AB) were continuously isolated from the lower respiratory tract of different patients (at the first isolation in our ICU). We performed WGS, pulsed-field gel electrophoresis (PFGE), and multilocus-sequence typing (MLST) analyses to elucidate bacterial relatedness and to compare the performance of conventional methods with WGS for typing MDR-AB. From June 2017 to August 2018, A. baumannii complex strains were detected in 124 of 796 patients during their ICU stays, 103 of which were MDR-AB. Then we subjected 70 available MDR-AB strains to typing with WGS, PFGE, and MLST. Among the 70 A. baumannii isolates, 38 (54.29%) were isolated at admission, and 32(45.71%) were acquisition isolates. MLST identified 12 unique sequence types, a novel ST (ST2367) was founded. PFGE revealed 16 different pulsotypes. Finally, 38 genotypes and 23 transmissions were identified by WGS. Transmission was the main mode of MDR-AB acquisition in our ICU. Our results demonstrated that WGS was a discriminatory technique for epidemiological healthcare-infection studies. The technique should greatly benefit the identification of epidemic situations and controlling transmission events in the near future.
Rapid Detection and Quantification of Mycobacterium tuberculosis DNA in Paraffinized Samples by Droplet Digital PCR: A Preliminary Study
Authors: Antonello Maria , Scutari Rossana , Lauricella Calogero , Renica Silvia , Motta Valentina , Torri Stefania , Russo Cristina , Gentile Leonarda , Cento Valeria , Colagrossi Luna , Mattana Giordana , Codecasa Luigi Ruffo , Vismara Chiara , Scaglione Francesco , Veronese Silvio Marco , Bonoldi Emanuela , Bandera Alessandra , Gori Andrea , Mazzola Ester , Perno Carlo Federico , Alteri Claudia
Published: September 2021

Background: Rapid and reliable diagnosis of tuberculosis (TB) represents a diagnostic challenge in compartmentalized extrapulmonary TB infection because of the small number of mycobacteria (MTB) and the frequent lack of fresh samples to perform culture. Here, we estimate the performances of homemade droplet digital PCR (ddPCR)-based assays against culture in 89 biopsies, for those fresh and formalin-fixed and paraffin-embedded (FFPE) subsamples were available.

Methods: MTB diagnosis in fresh subsamples was performed by culture. Fresh subsamples were also analyzed for acid-fast bacilli smear-microscopy (AFB) and Xpert® MTB/RIF (Xpert). MTB examination was repeated in blind in the 89 FFPE subsamples by in-house ddPCR assays targeting the IS6110 and rpoB. Analytical sensitivity of ddPCR assays was evaluated using serial dilution of H37Rv strain. Limit of detection (LOD) was calculated by probit analysis. Results were expressed in copies/106 cells.

Results: IS6110 and rpoB ddPCR assays showed a good linear correlation between expected and observed values (R2: 0.9907 and 0.9743, respectively). Probit analyses predicted a LOD of 17 and 40 copies/106 cells of MTB DNA for IS6110 and rpoB, respectively. Of the 89 biopsies, 68 were culture positive and 21 were culture negative. Considering mycobacterial culture as reference method, IS6110 assay yielded positive results in 67/68 culture-positive samples with a median interquartile range (IQR) of 1,680 (550–8,444) copies/106 cells (sensitivity: 98.5%; accuracy: 98.9). These performances were superior to those reported by the rpoB assay in FFPE subsamples (sensitivity: 66.20%; accuracy: 74.1) and even superior to those reported by Xpert and AFB in fresh subsamples (sensitivity: 79.4 and 33.8%, respectively; accuracy: 84.3 and 49.4, respectively). When Xpert and AFB results were stratified according to mycobacterial load detected by rpoB and IS6110 ddPCR, bacterial load was lower in Xpert and AFB negative with respect to Xpert and AFB-positive samples (p = 0.003 and 0.01 for rpoB and p = 0.01 and 0.11 for IS6110), confirming the poor sensitivity of these methods in paucibacillary disease.

Conclusion: ddPCR provides highly sensitive, accurate, and rapid MTB diagnosis in FFPE samples, as defined by the high concordance between IS6110 assay and culture results. This approach can be safely introduced in clinical routine to accelerate MTB diagnosis mainly when culture results remain unavailable.
Upregulation of Translationally Controlled Tumor Protein Is Associated With Cervical Cancer Progression
Authors: Zhu Xiaoyu , Ren Ji , Xu Dianqin , Cheng Di , Wang Wei , Ren Jie , Xiao Ziwen , Jiang Hongmei , Ding Yan , Tan Yujie
Published: September 2021

Outside a few affluent countries with adequate vaccination and screening coverage, cervical cancer remains the leading cause of cancer-related deaths in women in many countries. Currently, a major problem is that a substantial proportion of patients are already at an advanced cancer stage when diagnosed. There is increasing evidence that indicates the involvement of translationally controlled tumor protein 1 (TPT1) overexpression in cancer development, but little is known about its implication in cervical cancer. We assessed the levels of TPT1 in surgical tissue and sera of patients with cervicitis, cervical intraepithelial neoplasia III, and cervical cancer, as well as in normal and cancerous cervical cell lines. Gene sets, pathways, and functional protein interactions associated with TPT1 were identified using the TCGA data cohort of cervical cancer. We found that the TPT1 expression was significantly increased in cervical cancer tissue compared to all nonmalignant cervical tissues, including samples of cervicitis, cervical intraepithelial neoplasia III, and normal controls. Serum level of TPT1 was also increased in cervical cancer patients compared to healthy subjects. Furthermore, elevated TPT1 expression was significantly correlated with lymph node metastasis and a low differentiation degree of the cancer. In the cancerous tissues and cell lines, selective markers of PI3K/AKT/mTOR pathway over-activation, apoptosis repression, and EMT were detected, and their interaction with TPT1 was supported by biometrics analyses. Our results, for the first time, demonstrate a strong correlation of upregulated TPT1 expression with cervical cancer progression, suggesting that TPT1 might provide a potential biomarker for cervical cancer progression.