bluuebunny/crossref_metadata_2025 huggingface dataset:
NILAI-NILAI TASAWUF DALAM TRADISI KEAGAMAAN KOMUNITAS ABOGE
Authors: Nugroho Muhamad Yusuf Amin , Hidayat Muhtar S.
Published: February 2021

Tujuan penelitian ini adalah untuk mengetahui bagaimana tradisi keagamaan dan nilai-nilai tasawuf dalam tradisi keagamaan Aboge di Desa Mudal, Kecamatan Mojotengah, Kabupaten Wonosobo; juga pemahaman penganut Aboge di desa tersebut. Pendekatan yang digunakan dalam penelitian ini adalah kualitatif, yang tujuannya adalah menggali dan mendeskripsikan makna dalam sebuah realita. Dengan menggunakan studi kasus penelitian ini bermaksud memahami memahami fenomena-fenomena sosial dari sudut perspektif partisipan.

Berdasar penelitian yang sudah dilaksanakan kami menemukan tradisi keagamaan Aboge di Desa Mudal, yakni Suronan, Ruwahan dan Sadranan, Puasa, dan Ngubeng jagad. Tradisi  tersebut bukan hanya dalam rangka pelestarian tradisi nenek moyang, melainkan di dalamnya terkandung nilai-nilai luhur. Nilai-nilai tersebut berkaitan dengan tiga hal, yakni menyangkut hubungan manusia dengan alam, hubungan manusia dengan sesamanya, dan hubungan manusia dengan Sang Pencipta. Dengan kata lain, tradisi keagamaan masyarakat Aboge di Desa Mudal sangat kental dengan kandungan nilai-nilai tasawuf. Inti tasawuf adalah upaya melatih diri dari pengaruh negatif kehidupan dunia, sehingga tercermin akhlak yang mulia dan dekat dengan Tuhan. Tradisi keagamaan yang dijalankan oleh komunitas Aboge pada dasarnya memiliki tujuan bertasawuf tersebut.  Dalam menjalankan tradisi keagamaannya, diperlukan perlengkapan yang khusus yang disebut ubarampe. Ubarampe tidak hanya properti tetapi merupakan simbol yang mengandang ajaran moral. Meski begitu, pengetahuan anggota komunitas aboge di desa Mudal tentang makna ritual dan tradisi masih sangat rendah. Hanya sekitar 50 persen penganut Aboge di Desa Mudal yang paham bahwa dalam tradisi-tradisi keagamaan yang mereka jalani terdapat nilai-nilai tasawuf.
Manejo de pacientes com transtorno de personalidade borderline: Uma revisão integrativa
Authors: Lonsdale Jamylla Santos , Vasconcelos Gilberto Loiola de , Rosa Aline da , Oliveira Aline Vitoria de , Bezerra Ana Caroline Carvalho , Pimentel Barbara Previtalli , Costa Lara Benatti Braga , Pinto Maria Luísa Nunes Ribas , Fajardo Maria Vitória Moura , Nunes Thaynan Oliveira
Published: February 2021

Objetivo: O Transtorno de Personalidade Borderline (TPB) é uma doença multifatorial com influências genéticas e ambientais. O presente estudo procura elucidar opções de manejo terapêutico dos pacientes portadores desta condição com base em evidências clínicas recentes. Métodos: Através de fórmula de busca composta por Descritores em Ciências da Saúde, foi realizada busca nas bases de dados PubMed e Biblioteca Virtual de Saúde (BVS), tendo sido eleitos 11 estudos para revisão bibliográfica, todos ensaios clínicos controlados indexados nos últimos 10 anos. Resultados: Dentre os trabalhos selecionados, 63,6% sugerem a psicoterapia como tratamento mais efetivo do TPB e 9% sugerem que a terapia combinada, exemplificada pela associação entre psicoterapia e terapêutica medicamentosa, tem maior índice de efetividade do que a terapia psicológica isolada. Conclusão: A terapêutica individualizada e multifatorial parece ser a mais eficaz no controle do TPB. Há necessidade de maiores estudos com melhor rigor metodológico.
Ready to use implementation of project’s data portal with catalogue for findability, common services (SFTP,OPeNDAP) and persistent identifier for accessibility and interoperability
Authors: Paglialonga Lisa , Schirnick Carsten
Published: February 2021

This document describes the GEOMAR data portal used by the data management team to make data openly accessible that do not fit into a specialized repository.
POMEN IZOBRAŽEVANJA VARNOSTNIH SIL ZA STABILIZACIJO AFGANISTANA:
NATOV PROJEkT OPISMENJEVANJA IN VLOGA SLOVENSkE VOJSkE
Authors: ERZNOŽNIK BLAŽKA
Published: February 2021

Uspeh tranzicije odgovornosti za varnost v Afganistanu je odvisen od zmogljivo- sti afganistanskih varnostnih sil. Za razvoj zmogljivih in profesionalnih sil pa je ključen Natov projekt opismenjevanja, saj se pripadnikov ne da profesionalizirati, če ne znajo brati in pisati. Opismenjevanje je tako nujnost, hkrati pa tudi dodana vrednost operacije Isaf, saj pomembno prispeva k boljši prihodnosti mlade afgani- stanske generacije, ki je odraščala v razmerah, v katerih je bil dostop do izobraževa- nja močno omejen. V projekt so bili vključeni tudi pripadniki Slovenske vojske (SV) in namen besedila je predstaviti tudi njihovo vlogo in izkušnje na terenu.

Opismenjevanje je popolnoma nesporna oblika podpore, ki pomembno prispeva k dolgotrajni stabilnosti Afganistana in predstavlja družbeno koristnost oboroženih sil (OS), ne pomeni pa takojšnje rešitve konflikta. Kljub izboljšanju razmer je splošna varnostna situacija v državi še vedno krhka in pomeni glavno oviro za napredek.

The success of the security transition in Afghanistan depends on the capacity of the Afghan National Security Forces. The NATO Literacy project is critical for the deve- lopment of a capable and professional force, since it cannot be professionalized if its members do not have the basic ability to read and write. The elimination of illiteracy is therefore not only a necessity but also an added value, contributing importantly to a better future for the young generations of Afghans, raised under a regime, where the access to education was highly limited. Members of the Slovenian Armed Forces (SAF) also took part in the project and the aim of this article is to present their role and their field experience.
Literacy training is a completely noncontroversial way of cooperation, which is essential for the long term stability of Afghanistan and represents the usefulness of the armed forces in the society. However, it does not represent an immediate conflict resolution. Despite the improvement of conditions, the overall security situation remains fragile and represents the main obstacle for progress.
Yuriy Vasiliyevich Gulyayev is 85
Authors: Doberstein S. A.
Published: February 2021

Yuriy Vasiliyevich Gulyayev is 85
IMPEDANCE MATCHING OF A HF ANTENNA-FEEDER PATH WITH
THE APPLICATION OF VARIOUS OPTIMIZATION METHODS
Authors: Pavlov A. P. , Kashchenko I. E.
Published: February 2021

The paper provides information on the algorithm of calculation of parameters of the matching network of HF radio-transmitting devices. One of the main advantages of this algorithm is the possibility of the use of various methods of optimization that allows estimating their efficiency. As the main methods of optimization are used: Nelder – Mead method, method of the golden ratio, method of patterns. For verification works of an algorithm of calculation of parameters of the matching network the simulation model of the matching network considering construction features of the real matching network of HF range is created. In conclusion, the results of imitating modeling of an algorithm with the use of various methods of optimization and comparative analysis this result is introduced.
Quantitative Content Parameter in the Standardization of Veratrum Aqua, Veratrum Lobelianum Bernh. Based Drug
Authors: Melnik E. V. , Belova M. V. , Tyurin I. A. , Ramenskaya G. V.
Published: February 2021

Introduction. According to the XIV Edition of the Russian Federation State Pharmacopoeia, the quality control of the «Veratrum Lobelianum rhizome and roots» herbal substance is carried out through the determination of the alkaloid sum by means of the titration-based method. There are no selective and sensitive instrumental methods for the quantitative analysis of veratrum aqua active ingredients either. Veratrum aqua is produced from the mentioned above herbal substance. Therefore, the study of veratrum aqua alkaloid composition is relevant, as well as the development of a modern analytical method for individual alkaloid determination that can be implemented in veratrum aqua standardization.

Aim. To develop an approach to the quantitative analysis in Veratrum Aqua standardization.

Materials and methods. Two analytical methods were developed: one for the veratrum alkaloid determination in veratrum aqua samples by means of high performance liquid chromatography coupled with tandem mass-spectrometry (HPLC-MS/MS), another – for jervine, the main veratrum aqua alkaloid, quantitation by means of HPLC with diode-array detector (HPLC-DAD).

Results and discussion. Three main alkaloids, namely jervine, protoveratrine A and protoveratrine B, were identified in veratrum aqua. Jervine was found to be the most abundant one, hence it was chosen for the further development of a more affordable HPLC-DAD method. This method was validated for specificity, linearity, accuracy and precision. Jervine concentrations were measured in seven veratrum aqua samples produced by different manufacturers.

Conclusion. The highest jervine concentration among the examined samples was found to be 170 µg/ml, the lowest – 136 µg/ml. It is proposed to implement the following quantitative content parameter in veratrum aqua standardization: «Quantitative test. Jervine content should be not lessthan 136 µg/ml». This parameter is to be determined by HPLC-DAD.
Aspectos comportamentais do parasitoide Cotesia flavipes produzido em laboratório no litoral norte paraibano
Authors: Silva Roberto Balbino da , Aquino Italo de Sousa , Borges Pericles de Farias , Barbosa Alex da Silva , Medeiros Geovergue Rodrigues de , Melo Thiago de Sousa
Published: February 2021

Dentre os múltiplos aspectos que perpassam pelo controle biológico e sustentável na cultura da cana-de-açúcar (Saccharum officinarum), este estudo privilegia os aspectos comportamentais de Cotesia flavipes produzidas em laboratório no litoral norte paraibano, mais especificamente no município de Mamanguape, com o objetivo de avaliar o comportamento da produção em laboratório para melhor desempenho em campo. Os experimentos foram desenvolvidos no Laboratório de Produção Massal de Controle Biológico (LPMCB) da Associação de Plantadores de Cana da Paraíba (ASPLAN) e realizados em delineamento inteiramente casualizado, em salas climatizadas com temperaturas de 21, 25 e 29 ºC, umidade relativa do ar variando de 70±10% e fotofase de 12 horas. Foram utilizadas 34 lagartas (repetição) para cada temperatura, avaliando-se as seguintes variáveis biológicas: durações de ovo-larva; duração de pupa; adultos; quantidade de casulos por lagarta, viabilidade de pupas; razão sexual nas três temperaturas e a eficiência entre manipuladores masculino e feminino. Os resultados obtidos no presente estudo enaltecem que os aspectos comportamentais de parasitoides produzidos em laboratório apresentam diferenças entre as temperaturas controladas. Infere-se que a amostra de parasitoide apresenta padrões aceitáveis para os parâmetros analisados.
Avaliação do Programa de Tratamento do Tabagismo do Sistema Único de Saúde brasileiro em um munícipio do sudoeste de Minas Gerais
Authors: Reis Ciro Luiz Fernandes , Oliveira Viviani de , Carvalho Cristopher Mateus , Reis Leonardo Frasson , Ribeiro Maria Inês Lemos Coelho
Published: February 2021

Introdução: Na década de 1980, surgiram as primeiras medidas contra o tabagismo pelo Ministério da Saúde brasileiro. A partir de 2002, o Programa de Tratamento do Tabagismo (PTT) foi implementado no Sistema Único de Saúde (SUS), fornecendo tratamento gratuito nas Estratégias de Saúde da Família (ESFs). Objetivos: Avaliar e descrever o PTT, aplicado em um município da região sudoeste de Minas Gerais, a partir de seus usuários, bem como traçar o perfil sociodemográfico desses indivíduos. Materiais e métodos: Trata-se de um estudo observacional, tipo transversal, com abordagem quantitativa e qualitativa, cuja coleta de dados ocorreu entre março de 2019 e março de 2020 por meio da aplicação de questionário sistematizado aos profissionais das ESFs alvo e a 52 usuários do PTT inscritos no programa. Resultados: Foi observado que a maioria dos pacientes pertencia ao sexo feminino e que 68% desses obtiveram sucesso na cessação do tabagismo após sua submissão ao PTT, sendo a terapia em grupo avaliada pelos usuários como o melhor tratamento. Foi apontada associação significativa (p<0,05) entre o desfecho clínico e o tipo de tratamento empreendido, a quantidade de cigarros fumados por dia e o número de enfermidades. Segundo o relato dos profissionais, adaptações se fizeram necessárias segundo a realidade local do município com fins a melhorar os resultados do PTT. Conclusão: A pesquisa demonstrou que o PTT apresentou eficácia em promover a cessação do tabagismo. No entanto, mais estudos se fazem necessários com fins a avaliar a eficácia desse programa em outras realidades.
Influência de constante iluminação, melatonina e geldanamicina sob o testículo de rato por mais de 60 dias
Authors: Costa Marcos Aurélio Santos da , Lira Anna Carolina Lopes de , Guedes Geovanna Hachyra Facundo , Gomes José Anderson da Silva , Carvalho Jennyfer Martins de , Oliveira Maria Luísa Figueira de , Silva Maria Eduarda da , Gonzaga Bárbara Silva , Novis Pedro Vinícius Silva , Britto Diana Babini Lapa de Albuquerque , Tenório Bruno Mendes , Maia Carina Scanoni , Medeiros Juliana Pinto de , Tenorio Fernanda das Chagas Angelo Mendes
Published: February 2021

A melatonina (N-acetil-5-metoxitriptamina) é um hormônio secretado pela glândula pineal. Nos homens, a melatonina afeta a regulação reprodutiva de três maneiras principais. Primeiro, ele regula a secreção de GnRH e LH. Em segundo lugar, regula a síntese de testosterona e a maturação testicular. Terceiro, como um potente representante do radical livre que é tanto lipofílico quanto hidrofílico. O testículo de mamíferos é um órgão suscetível a agentes tóxicos ambientais e terapêuticos que comprometem a espermatogênese, o presente estudo teve como objetivo analisar a influência da iluminação constante, melatonina e geldanamicina sob o testículo de ratos tratados por 60 dias. Os machos foram divididos aleatoriamente em 4 grupos, cada um composto por 5 animais, sendo eles: Grupo I - ratos controle (não tratados); Grupo II - ratos submetidos à iluminação constante por 60 dias; Grupo III - ratos submetidos à iluminação constante por 60 dias e tratados com melatonina por 60 dias; Grupo IV - ratos submetidos à iluminação constante por 60 dias, tratados com melatonina e geldanamicina por 60 dias. A exposição à iluminação constante afeta o desenvolvimento do epitélio germinativo, bem como a diminuição do peso dos testículos, células de Leydig, Sertoli e testosterona. O tratamento com melatonina e geldanamicina tem um efeito protetor contra a iluminação constante, reduzindo os danos testiculares quando tomados em conjunto.
The therapeutic effects of Agrimonia eupatoria L.
Authors: Paluch Z , Biriczová L , Pallag G , Carvalheiro Marques E , Vargová N , Kmoníčková E
Published: February 2021

Agrimonia eupatoria L. is an herb of the Rosaceae family, widely used in traditional (folk) medicine for its beneficial effects. Its water extracts (infusions and decoctions) are used in the treatment of airway and urinary system diseases, digestive tract diseases, and chronic wounds. Phytochemical analyses of Agrimonia eupatoria L. identified a variety of bioactive compounds including tannins, flavonoids, phenolic acids, triterpenoids and volatile oils possessing antioxidant, immunomodulatory and antimicrobial activities. The authors review the available literature sources examining and discussing the therapeutic and pharmacological effects of Agrimonia eupatoria L. at the molecular level in vitro and in vivo.
Mothers’ Physical Activity in the New Millennium: A Systematic Review of the Literature
Authors: Juwono Ignatius Darma , Kun Bernadette , Demetrovics Zsolt , Szabo Attila
Published: February 2021

Background. Physical activity is essential for health, especially in an increasingly sedentary world. Being a parent involves responsibilities that could interfere with mothers’ physical activity. Research suggests that mothers are especially vulnerable to physical inactivity. Health promoters invest substantial effort in facilitating the physical activity of women with children.

Methods. The scope of this systematic literature review is to synthesize research efforts on mothers’ physical activity and supporting interventions. Three databases were scrutinized in this review (Medline, Scopus, and PsycINFO). Articles published between 2000–2020 were selected in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Fifty-four eligible articles were included after screening 3708 articles.

Results. The results suggest that mothers exhibit lower levels of physical activity than the recommended level for adults. Lack of time, focus on childcare, limited knowledge, and insufficient spousal support emerge as the primary barriers to physical activity in mothers with children. Interventions trying to overcome these barriers vary in methods, evaluations, and effectiveness. Positive changes in mothers’ physical activity may emerge if interventions focus on increasing self-efficacy, problem-solving, goal setting, and other cognitive factors.

Conclusion. Future interventions integrating internet-based applications and involving spouses and/or partners might help mothers to increase their physical activity.

Keywords: exercise, health behavior, motherhood, sedentary, women.
Increased Exercise Effort after Artificially-Induced Stress: Laboratory-Based Evidence for the Catharsis Theory of Stress
Authors: Szabo Attila , Tóth Eliza , Kósa Lili , Laki Ádám , Ihász Ferenc
Published: February 2021

Background. Evolution prepared humans to deal with physical challenges. Today, people encounter psychosocial stress more than physical stress. However, the physiological response to the contemporary forms of stress is still preserved as the biological evolution’s vestigial heritage. This laboratory investigation aimed to determine whether brief mental stress triggers greater innate (instinctual) effort to ‘let off steam’ than a non-challenging control condition.

Method. Using a counterbalanced within-participants laboratory design, 29 young men walked/jogged at voluntary (self-paced) effort after two conditions: a) artificially-induced mental stress comprised by the Stroop Color-Word Task, which lasted for five minutes, and b) a control session, also lasting for five minutes, in which the participants watched a video depicting the world’s ten tallest buildings.

Results. The increased arousal after mental stress was carried over into the walk or jog period, and participants worked harder, but they did not perceive exerting greater effort in contrast to the control condition.

Conclusions. These results suggest that a ‘flight or fight’ response to psychosocial stress is manifested in the form of subliminal catharsis. While larger-scale studies with more impactful stressors are needed, these preliminary results support the catharsis theory. They might open new research avenues to provide people more physical opportunities for letting off steam before the necessity of treatment with chemical substances or other behavioral therapies.

Keywords: cognitive stress, exercise, mental stress, flight or fight, physical activity, psychosocial stress.
Deletion of Mea6 in Cerebellar Granule Cells Impairs Synaptic Development and Motor Performance
Authors: Wang Xin-Tai , Zhou Lin , Cai Xin-Yu , Xu Fang-Xiao , Xu Zhi-Heng , Li Xiang-Yao , Shen Ying
Published: February 2021

The cerebellum is conceptualized as a processor of complex movements. Many diseases with gene-targeted mutations, including Fahr’s disease associated with the loss-of-function mutation of meningioma expressed antigen 6 (Mea6), exhibit cerebellar malformations, and abnormal motor behaviors. We previously reported that the defects in cerebellar development and motor performance of Nestin-Cre;Mea6F/Fmice are severer than those of Purkinje cell-targeted pCP2-Cre;Mea6F/Fmice, suggesting that Mea6 acts on other types of cerebellar cells. Hence, we investigated the function of Mea6 in cerebellar granule cells. We found that mutant mice with the specific deletion ofMea6in granule cells displayed abnormal posture, balance, and motor learning, as indicated in footprint, head inclination, balanced beam, and rotarod tests. We further showed that Math1-Cre;Mea6F/Fmice exhibited disrupted migration of granule cell progenitors and damaged parallel fiber-Purkinje cell synapses, which may be related to impaired intracellular transport of vesicular glutamate transporter 1 and brain-derived neurotrophic factor. The present findings extend our previous work and may help to better understand the pathogenesis of Fahr’s disease.
Transcriptome Analysis of Dnmt3l Knock-Out Mice Derived Multipotent Mesenchymal Stem/Stromal Cells During Osteogenic Differentiation
Authors: Yang Chih-Yi , Lu Rita Jui-Hsien , Lee Ming-Kang , Hsiao Felix Shih-Hsian , Yen Ya-Ping , Cheng Chun-Chun , Hsu Pu-Sheng , Tsai Yi-Tzang , Chen Shih-Kuo , Liu I-Hsuan , Chen Pao-Yang , Lin Shau-Ping
Published: February 2021

Multipotent mesenchymal stem/stromal cells (MSCs) exhibit great potential for cell-based therapy. Proper epigenomic signatures in MSCs are important for the maintenance and the subsequent differentiation potential. The DNA methyltransferase 3-like (DNMT3L) that was mainly expressed in the embryonic stem (ES) cells and the developing germ cells plays an important role in shaping the epigenetic landscape. Here, we report the reduced colony forming ability and impairedin vitroosteogenesis inDnmt3l-knockout-mice-derived MSCs (Dnmt3lKO MSCs). By comparing the transcriptome between undifferentiatedDnmt3lKO MSCs and the MSCs from the wild-type littermates, some of the differentially regulated genes (DEGs) were found to be associated with bone-morphology-related phenotypes. On the third day of osteogenic induction, differentiatingDnmt3lKO MSCs were enriched for genes associated with nucleosome structure, peptide binding and extracellular matrix modulation. Differentially expressed transposable elements in many subfamilies reflected the change of corresponding regional epigenomic signatures. Interestingly, DNMT3L protein is not expressed in cultured MSCs. Therefore, the observed defects inDnmt3lKO MSCs are unlikely a direct effect from missing DNMT3L in this cell type; instead, we hypothesized them as an outcome of the pre-deposited epigenetic signatures from the DNMT3L-expressing progenitors. We observed that 24 out of the 107 upregulated DEGs inDnmt3lKO MSCs were hypermethylated in their gene bodies of DNMT3L knock-down ES cells. Among these 24 genes, some were associated with skeletal development or homeostasis. However, we did not observe reduced bone development, or reduced bone density through agingin vivo. The stronger phenotypein vitrosuggested the involvement of potential spreading and amplification of the pre-deposited epigenetic defects over passages, and the contribution of oxidative stress duringin vitroculture. We demonstrated that transient deficiency of epigenetic co-factor in ES cells or progenitor cells caused compromised property in differentiating cells much later. In order to facilitate safer practice in cell-based therapy, we suggest more in-depth examination shall be implemented for cells before transplantation, even on the epigenetic level, to avoid long-term risk afterward.
SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy
Authors: Ferreras C. , Pascual-Miguel B. , Mestre-Durán C. , Navarro-Zapata A. , Clares-Villa L. , Martín-Cortázar C. , De Paz R. , Marcos A. , Vicario J. L. , Balas A. , García-Sánchez F. , Eguizabal C. , Solano C. , Mora-Rillo M. , Soria B. , Pérez-Martínez A.
Published: February 2021

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus’ complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA– memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA– memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA– subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available “off-the-shelf” to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.
The Chromatin Remodeling Protein BRG1 Regulates SREBP Maturation by Activating SCAP Transcription in Hepatocytes
Authors: Kong Ming , Zhu Yuwen , Shao Jing , Fan Zhiwen , Xu Yong
Published: February 2021

Sterol response element binding protein (SREBP) is a master regulator of cellular lipogenesis. One key step in the regulation of SREBP activity is its sequential cleavage and trans-location by several different proteinases including SREBP cleavage activating protein (SCAP). We have previously reported that Brahma related gene 1 (BRG1) directly interacts with SREBP1c and SREBP2 to activate pro-lipogenic transcription in hepatocytes. We report here that BRG1 deficiency resulted in reduced processing and nuclear accumulation of SREBP in the murine livers in two different models of non-alcoholic steatohepatitis (NASH). Exposure of hepatocytes to lipopolysaccharide (LPS) and palmitate (PA) promoted SREBP accumulation in the nucleus whereas BRG1 knockdown or inhibition blocked SREBP maturation. Further analysis revealed that BRG1 played an essential role in the regulation of SCAP expression. Mechanistically, BRG1 interacted with Sp1 and directly bound to the SCAP promoter to activate SCAP transcription. Forced expression of exogenous SCAP partially rescued the deficiency in the expression of SREBP target genes in BRG1-null hepatocytes. In conclusion, our data uncover a novel mechanism by which BRG1 contributes to SREBP-dependent lipid metabolism.
Human Atrial Fibrillation Is Not Associated With Remodeling of Ryanodine Receptor Clusters
Authors: Munro Michelle L. , van Hout Isabelle , Aitken-Buck Hamish M. , Sugunesegran Ramanen , Bhagwat Krishna , Davis Philip J. , Lamberts Regis R. , Coffey Sean , Soeller Christian , Jones Peter P.
Published: February 2021

The release of Ca2+ by ryanodine receptor (RyR2) channels is critical for cardiac function. However, abnormal RyR2 activity has been linked to the development of arrhythmias, including increased spontaneous Ca2+ release in human atrial fibrillation (AF). Clustering properties of RyR2 have been suggested to alter the activity of the channel, with remodeling of RyR2 clusters identified in pre-clinical models of AF and heart failure. Whether such remodeling occurs in human cardiac disease remains unclear. This study aimed to investigate the nanoscale organization of RyR2 clusters in AF patients – the first known study to examine this potential remodeling in diseased human cardiomyocytes. Right atrial appendage from cardiac surgery patients with paroxysmal or persistent AF, or without AF (non-AF) were examined using super-resolution (dSTORM) imaging. Significant atrial dilation and cardiomyocyte hypertrophy was observed in persistent AF patients compared to non-AF, with these two parameters significantly correlated. Interestingly, the clustering properties of RyR2 were remarkably unaltered in the AF patients. No significant differences were identified in cluster size (mean ∼18 RyR2 channels), density or channel packing within clusters between patient groups. The spatial organization of clusters throughout the cardiomyocyte was also unchanged across the groups. RyR2 clustering properties did not significantly correlate with patient characteristics. In this first study to examine nanoscale RyR2 organization in human cardiac disease, these findings indicate that RyR2 cluster remodeling is not an underlying mechanism contributing to altered channel function and subsequent arrhythmogenesis in human AF.
Direct and Rapid Detection of Mycoplasma bovis in Bovine Milk Samples by Recombinase Polymerase Amplification Assays
Authors: Li Ruiwen , Wang Jinfeng , Sun Xiaoxia , Liu Libing , Wang Jianchang , Yuan Wanzhe
Published: February 2021

This study aimed to detetct Mycoplasma bovis (M. bovis) in bovine milk quickly and directly by developing and validating isothermal recombinase polymerase amplification (RPA) assays. Targeting the uvrC gene of M. bovis, an RPA assay based on the fluorescence monitoring (real-time RPA) and an RPA assay combined with a lateral flow strip (LFS RPA) were conducted. It took 20 min for the real-time RPA to finish in a Genie III at 39°C, and 15 min were required to perform the LFS RPA in an incubator block at 39°C, followed by the visualization of the products on the lateral flow strip within 5 min. Both of the two assays showed high specificity for M. bovis without any cross-reaction with the other tested pathogens. With the standard recombinant plasmid pMbovis-uvrC serving as a template, both RPA assays had a limit of detcion of 1.0 × 101 copies per reaction, equivalent to that of a real-time PCR assay. In the 65 milk samples collected from cattle with mastitis, the M. bovis genomic DNA was detected in 24 samples by both the real-time RPA and the LFS RPA assays. The developed RPA assays could detect M. bovis in bovine milk in an efficient, convenient, and credible manner as attractive and promising tools, and the assays would be helpful in the rapid response to M. bovis infection causing bovine mastitis.
QT Prolongation in Cancer Patients
Authors: Kim Peter , Masha Luke , Olson Amanda , Iliescu Cezar , Karimzad Kaveh , Hassan Saamir , Palaskas Nicolas , Durand Jean-Bernard , Leung Cheuk Hong , Lopez-Mattei Juan
Published: February 2021

Background: QT prolongation and torsades de pointes pose a major concern for cardiologists and oncologists. Although cancer patients are suspected to have prolonged QT intervals, this has not been investigated in a large population. The purpose of this study was to analyze the QT interval distribution in a cancer population and compare it to a non-cancer population in the same institution.

Methods: The study was a retrospective review of 82,410 ECGs performed in cancer patients (51.8% women and 48.2% men) and 775 ECGs performed in normal stem cell donors (47.9% women and 52.1% men) from January 2009 to December 2013 at the University of Texas MD Anderson Cancer Center. Pharmacy prescription data was also collected and analyzed during the same time period. Correction of the QT interval for the heart rate was performed using the Bazett and Fridericia formulas.

Results: After QT correction for heart rate by the Fridericia formula (QTcF), the mean and 99% percentile QTc for cancer patients were 414 and 473 ms, respectively. These were significantly longer than the normal stem cell donors, 407 and 458 ms, p < 0.001, respectively. Among the cancer patients, the QTc was longer in the inpatient setting when compared to both outpatient and emergency center areas. The most commonly prescribed QT prolonging medications identified were ondansetron and methadone.

Conclusion: Our study demonstrates significantly longer QTc intervals in cancer patients, especially in the inpatient setting. Frequently prescribed QT prolonging medications such as antiemetics and analgesics may have a causative role in QT prolongation seen in our cancer hospital.
Strong Earthquakes Recurrence Times of the Southern Thessaly, Greece, Fault System: Insights from a Physics-Based Simulator Application
Authors: Kourouklas Christos , Console Rodolfo , Papadimitriou Eleftheria , Murru Maura , Karakostas Vassilios
Published: February 2021

The recurrence time,Tr, of strong earthquakes above a predefined magnitude threshold on specific faults or fault segments is an important parameter, that could be used as an input in the development of long-term fault-based Earthquake Rupture Forecasts (ERF). The amount of observational recurrence time data per segment is often limited, due to the long duration of the stress rebuilt and the shortage of earthquake catalogs. As a consequence, the application of robust statistical models is difficult to implement with a precise conclusion, concerningTrand its variability. Physics-based earthquake simulators are a powerful tool to overcome these limitations, and could provide much longer earthquake records than the historical and instrumental earthquake catalogs. A physics-based simulator, which embodies known physical processes, is applied in the Southern Thessaly Fault Zone (Greece), aiming to provide insights about the recurrence behavior of earthquakes withMw≥ 6.0 in the six major fault segments in the study area. The build of the input fault model is made by compiling the geometrical and kinematic parameters of the fault network from the available seismotectonic studies. The simulation is implemented through the application of the algorithm multiple times, with a series of different input free parameters, in order to conclude in the simulated catalog which showed the best performance in respect to the observational data. The detailed examination of the 254Mw≥ 6.0 earthquakes reported in the simulated catalog reveals that both single and multiple segmented ruptures can be realized in the study area. Results of statistical analysis of the interevent times of theMw≥ 6.0 earthquakes per segment evidence quasi-periodic recurrence behavior and better performance of the Brownian Passage Time (BPT) renewal model in comparison to the Poissonian behavior.
Tools for Comprehensive Assessment of Fluid-Mediated and Solid-State Alteration of Carbonates Used to Reconstruct Ancient Elevation and Environments
Authors: Ingalls Miquela , Snell Kathryn E.
Published: February 2021

Carbonates are ubiquitous in the rock record and provide a broad array of stable isotope-based paleoclimatic proxies (i.e., δ18O, δ13C, ∆17O, ∆47, ∆48) that provide information on stratigraphy, carbon cycling, temperature, hydrology, and the altitude of ancient land surfaces. Thus, carbonates are an essential archive of environmental and topographic histories of continental terranes. However, carbonate minerals are highly susceptible to post-depositional alteration of primary isotopic values via fluid-mediated and solid-state reactions. We propose a hierarchical suite of techniques to comprehensively assess alteration in carbonates, from essential and readily accessible tools to novel, high-resolution techniques. This framework provides a means of identifying preserved textures in differentially altered samples that contain high-value environmental information. To illustrate this progressive approach, we present a case study of Tethyan nearshore carbonates from the Paleocene Tso Jianding Group (Tibet). We demonstrate the utility of each technique in identifying chemical and crystallographic indicators of post-depositional alteration at progressively finer spatial scales. For example, secondary ionization mass spectrometry (SIMS) oxygen isotope maps of micrite and bioclasts reveal significant isotopic heterogeneity due to grain-scale water-rock exchange in textures that were labeled “primary” by optical inspection at coarser spatial resolution. Optical and cathodoluminescence microscopy should be the minimum required assessment of carbonate samples used in stable isotope analyses, but supplemented when necessary by SIMS, PIC mapping, and other yet untapped technologies that may allow distinction of primary and altered fabrics at finer spatial resolutions.
Case Report: Off Label Utilization of Topiramate and Metformin in Patients With BMI ≥50 kg/m2 Prior to Bariatric Surgery
Authors: Sari Cetin , Seip Richard L. , Umashanker Devika
Published: February 2021

FDA approved anti-obesity medications may not be cost effective for patients struggling with pre-operative weight loss prior to bariatric surgery. Metformin, a biguanide, and Topiramate, a carbonic anhydrase inhibitor, both cost effective medications, have demonstrated weight loss when used for the treatment of type 2 diabetes or seizures, respectively. The aim of the three cases is to demonstrate the clinical utility of topiramate and metformin for preoperative weight loss in patients with a body mass index (BMI) ≥ 50 kg/m2 prior to bariatric surgery who are unable to follow the bariatric nutritional prescription due to a dysregulated appetite system Each patient was prescribed metformin and/or topiramate in an off-label manner in conjunction with lifestyle modifications and achieved >8% total body weight loss during the preoperative period.
Investigation on Transient Characteristics of High Pressure Vessel Water Level Measurement
Authors: Wang Meng , Chen Wenzhen , Fan Guangming
Published: February 2021

An experimental study was conducted on the characteristics of high pressure vessel water level systems at both fast and slow depressurization states. The swollen and collapsed water levels were observed experimentally. The test results show that the swollen water level has a relatively fixed difference compared to the collapsed one for the transient of both high and low depressurization rates. Under the conditions of steady and heat up, the differences between the swollen and collapsed water levels are acceptable. For the transients of depressurization, the outputs from the three channels of the inside vessel double-reference-tube water level system have a great deal of differences between each other because of the thermal inertia of the two reference tubes and the water levels in the cistern. In view of nuclear power plant safety and operation, the outside vessel single-reference-tube water level system used in the current pressurizer is adequate and the inside vessel double-reference-tube water level system is suggested as an additional reference to monitor the water level in the steam generator.
A Comprehensive Analysis and Splicing Characterization of Naturally Occurring Synonymous Variants in the ATP7B Gene
Authors: Zhou Xiaoying , Zhou Wei , Wang Chunli , Wang Lan , Jin Yu , Jia Zhanjun , Liu Zhifeng , Zheng Bixia
Published: February 2021

Next-generation sequencing is effective for the molecular diagnosis of genetic diseases. However, the identification of the clinical significance of synonymous variants remains a challenge. Our previous study showed that some synonymous variants in ATP7B gene produced splicing disruptions, leading to Wilson disease (WD). To test the hypothesis that synonymous variants of ATP7B cause abnormal splicing by disrupting authentic splice sites or splicing regulatory elements, we used computational tools and minigene assays to characterize 253 naturally occurring ATP7B gene synonymous variants in this study. Human Splicing Finder (HSF) and ESE Finder 3.0 were used to predict the impact of these rare synonymous variants on pre-mRNA splicing. Then, we cloned 14 different wild-type Minigene_ATP7B_ex constructs for in vitro minigene assay, including 16 exons of ATP7B gene. After computational prediction, 85 candidate variants were selected to be introduced into the corresponding Minigene_ATP7B_ex constructs for splicing assays. Using this two-step procedure, we demonstrated that 11 synonymous variants in ExAc database (c.1620C>T, c.3888C>T, c.1554C>T, c.1677C>T, c.1830G>A, c.1875T>A, c.2826C>A, c.4098G>A, c.2994C>T, c.3243G>A, and c.3747G>A) disrupted RNA splicing in vitro, and two (c.1620C>T and c.3243G>A) of these caused a complete exon skipping. The results not only provided a reliable experimental basis for the genetic diagnosis of WD patients but also offered some new insights into the pathogenicity of synonymous variants in genetic diseases.
Polluted Air Exposure Compromises Corneal Immunity and Exacerbates Inflammation in Acute Herpes Simplex Keratitis
Authors: Sendra Victor G. , Tau Julia , Zapata Gustavo , Lasagni Vitar Romina M. , Illian Eduardo , Chiaradía Pablo , Berra Alejandro
Published: February 2021

Air pollution is a serious environmental issue worldwide in developing countries’ megacities, affecting the population’s health, including the ocular surface, by predisposing or exacerbating other ocular diseases. Herpes simplex keratitis (HSK) is caused by the herpes simplex virus type 1 (HSV-1). The primary or recurring infection in the ocular site causes progressive corneal scarring that may result in visual impairment. The present study was designed to study the immunopathological changes of acute HSK under urban polluted air, using the acute HSK model combined with an experimental urban polluted air exposure from Buenos Aires City. We evaluated the corneal clinical outcomes, viral DNA and pro-inflammatory cytokines by RT-PCR and ELISA assays, respectively. Then, we determined the innate and adaptive immune responses in both cornea and local lymph nodes after HSV-1 corneal by immunofluorescence staining and flow cytometry. Our results showed that mice exposed to polluted air develop a severe form of HSK with increased corneal opacity, neovascularization, HSV-1 DNA and production of TNF-α, IL-1β, IFN-γ, and CCL2. A high number of corneal resident immune cells, including activated dendritic cells, was observed in mice exposed to polluted air; with a further significant influx of bone marrow-derived cells including GR1+ cells (neutrophils and inflammatory monocytes), CD11c+ cells (dendritic cells), and CD3+ (T cells) during acute corneal HSK. Moreover, mice exposed to polluted air showed a predominant Th1 type T cell response over Tregs in local lymph nodes during acute HSK with decreased corneal Tregs. These findings provide strong evidence that urban polluted air might trigger a local imbalance of innate and adaptive immune responses that exacerbate HSK severity. Taking this study into account, urban air pollution should be considered a key factor in developing ocular inflammatory diseases.
Circulating Neutrophil Dysfunction in HBV-Related Acute-on-Chronic Liver Failure
Authors: Wu Wei , Sun Shanshan , Wang Yijie , Zhao Ruihong , Ren Haotang , Li Zhiwei , Zhao Hong , Zhang Yi , Sheng Jifang , Chen Zhi , Shi Yu
Published: February 2021

Background and Aims

Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation accompanied by defective anti-bacterial immunity. The role of neutrophils in immune derangement of ACLF has not been fully elucidated. This study is aimed to characterize the role of circulating neutrophils in HBV-related ACLF patients.

Methods

Quantitative, phenotypic, transcriptomic, and functional alterations of circulating neutrophils were compared in ACLF and non-ACLF subjects and analyzed for associations with short-term outcomes. Interventional experiments were performed to test the impact on ACLF-patient neutrophil function in vitro.

Results

Circulating absolute neutrophil count was significantly increased in patients with ACLF and was an independent risk factor for 28-day mortality. ACLF-patient neutrophils differentially expressed a panel of surface markers (include TLR-1, TLR-2, TLR-4, CEACAM-1 and FPR1), as well as a distinct transcriptomic signature. ACLF-neutrophils displayed significantly impaired phagocytosis but an increased capacity to form neutrophil extracellular traps (NETs), which was more pronounced in patients with poor outcome. Healthy neutrophils mimicked functional characteristics of ACLF counterpart after co-cultured with plasma from ACLF patients. The oxidative burst and cytokine production capacities remained unchanged. Plasma GM-CSF, IL-6, IL-8, IL-10, and IP-10 levels, as well as lipopolysaccharide (LPS) concentration, were markedly elevated in ACLF patients but not DAMP molecules HMGB-1 and HSP70. Finally, a glycolysis inhibitor, 2-deoxy-glucose, reduced NET formation of ACLF patients’ neutrophils.

Conclusions

Circulating ACLF-patient neutrophils exhibit alterations in number, phenotype, gene expression and function, which was associated with poor outcome and shaped by the ACLF circulatory environment. Inhibiting glycolysis can reverse neutrophil dysfunction in ACLF patients.
Celiac Disease Causes Epithelial Disruption and Regulatory T Cell Recruitment in the Oral Mucosa
Authors: Sanchez-Solares Javier , Sanchez Luis , Pablo-Torres Carmela , Diaz-Fernandez Celso , Sørensen Poul , Barber Domingo , Gomez-Casado Cristina
Published: February 2021

Celiac disease (CD) is a chronic autoimmune disease characterized by an immune-triggered enteropathy upon gluten intake. The only current treatment available is lifelong Gluten Free Diet (GFD). Several extraintestinal manifestations have been described in CD, some affecting the oral mucosa. Thus, we hypothesized that oral mucosa could potentially be a target for novel biomarkers and an administration route for CD treatment. Six de novo diagnosed and seven CD patients under GFD for at least 1 year were recruited. Non-celiac subjects (n = 8) were recruited as control group. Two biopsies of the cheek lining were taken from each subject for mRNA analysis and immunohistochemical characterization. We observed a significant decrease in the expression of epithelial junction proteins in all CD patients, indicating that oral mucosa barrier integrity is compromised. FoxP3+ population was greatly increased in CD patients, suggesting that Tregs are recruited to the damaged mucosa, even after avoidance of gluten. Amphiregulin mRNA levels from Peripheral Blood Mononuclear Cells (PBMCs) and epithelial damage in the oral mucosa correlated with Treg infiltration in all the experimental groups, suggesting that recruited Tregs might display a “repair” phenotype. Based on these results, we propose that oral mucosa is altered in CD and, as such, might have diagnostic potential. Furthermore, due to its tolerogenic nature, it could be an important target for oral immunotherapy.
Multilayer Maraging/CoCrNi Composites With Synergistic Strengthening-Toughening Behavior
Authors: Chen C. X. , Ge Y. F. , Fang W. , Zhang X. , Liu B. X. , Feng J. H. , Yin F. X.
Published: February 2021

A novel multilayer maraging/CoCrNi composite with good mechanical properties was successfully fabricated by a vacuum hot-rolling and aging treatment. The yield strength, tensile strength, uniform elongation, and fracture elongation reached 1,151, 1,380 MPa, 15.7, and 24% respectively, realizing the aim of synergistic strengthening–toughening by effectively improving the yield strength of the CoCrNi alloy and strain-hardening capacity of the maraging steel. The vacuum state, high rolling reduction ratio, and alloy element diffusion are beneficial in strengthening the clad interface. The good work-hardening capacity of the CoCrNi alloy compensates for the poor strain-softening behavior of the maraging steel, effectively delaying the premature localized necking of the multilayer composites. The strengthening–toughening mechanism of the multilayer maraging/CoCrNi composites is mainly attributed to the strong interface, nanoscale precipitation, and strain-induced twinning.