bluuebunny/crossref_metadata_2025 huggingface dataset:
Foot-and-mouth Disease Virus type (O) Overhangs Livestock Industry of both Young and Adult Cattle and Buffalo in Egypt
Authors: Abd-Ellatieff Hoda A. , Hegazy Asmaa A. , Hassan Aziza M. , El-Shehawi Ahmed M. , Bazh Eman K. , AbouRawash Abdel-Rahman A. , Shukry Mustafa , Tohamy Hossam G.
Published: September 2021

Egyptian farms is still attacked by several outbreaks of FMDV, a highly contagious viral disease that threatens the livestock industry worldwide. Many of these outbreaks are unreported. Hence, the epidemiological situation and molecular characterization of the currently responsible strains of recent FMD outbreaks are missed. To identify FMDV strains currently circulating in cattle herds and catch the recent update in the morphophonological changes due to that virus, we carried out this study on the FMD outbreak from 2016–2017 in Egypt. Clinical samples (post mortem tissues samples, oral swabs, epithelial suspensions from ruptured vesicles, and blood) were collected from clinically examined animals suspected to be of being FMD virus = 229 cattle and 138 buffalo. Of 175, 96 (54.8%) samples and 85 (44.3%) from 192 samples were positive in 2016 and 2017, respectively. Pathological examination revealed the classical lesions of FMDV as vesicular and erosive lesions on cornified epithelial tissues. Multi-focal areas of lympho-plasmocytic myocarditis were seen in the heart of all calves. Similar lesions were also observed in the heart of adult cattle that died in that outbreaks. Detailed pathological alterations in adult and young animals were described. Polymerase chain reaction (PCR) screening of tissue specimens using specific primers for FMDV was done. Serotype O was the only serotype that was detected in our study and submitted in the Genebank. The four field isolates of serotype O that have been submitted in the Genebank had been found to belong to the EA-3 topotype. Nucleotide sequencing of the VP1 region and phylogenetic analysis has been used to determine the relationships between our field isolates, other recently isolated Egyptian isolates, and other isolates from some African countries and vaccinal strain used for serotype O in Egypt. The presence of strains of increased virulence among cattle and buffalo in Egypt could be attributed to the introduction of new viral strains through uncontrolled transboundary movements of animals during the last public revolution in Egypt in 2011.
Oleanolic Acid Inhibits the Proliferation and Invasion of U251Glioma Cells and Promotes their Apoptosis through the IKK-β, MAPK3, and MAPK4 Signaling Pathway
Authors: Huang Jinxiang , Lin Shengnan , Zhu Feng , Chen Dengsheng , Huang Fang , xu luning
Published: September 2021

Object: To investigate the effects of Oleanolic acid (OA) on proliferation, apoptosis, migration, and invasion of human glioma cell U251, as well as IKK-β and MAPK signaling pathways.Methods: The binding of OA to IKK-β and MAPK signaling pathway essential proteins IKK-β, MAPK3, and MAPK4 was analyzed by molecular docking technique. U251 cells were treated with different concentrations of OA. The proliferation and apoptosis rates of U251 cells were detected by CCK-8 assay, MTT assay, cell cloning assay, and AnnexinⅤ FITC/PI double staining assay. Transwell chamber assay was used to detect migration and invasion of U251 cells. Western blot was used to detect and analyze the expression levels of CYP17A1, IKK-β, PTGS2 and MAPK3/4 protein in U251 cells after OA treatment. Finally, the transcriptome sequencing method was used to detect the differentially expressed genes in the two groups, and the GO and KEGG enrichment analysis were performed.Results: The results of molecular docking showed that OA could stably bind to IKK-β, MAPK3, and MAPK4 proteins. OA could not only effectively inhibit the proliferation and induce apoptosis of U251 cells (P < 0.05), but also significantly inhibit the invasion of U251 cells (P < 0.005). Western blot assay confirmed that OA could dramatically inhibit the protein expression levels of CYP17A1, IKK-β, PTGS2, MAPK3, and MAPK4 in U251 cells (P < 0.01). A total of 446 significantly differentially expressed genes were detected in transcriptome sequencing, of which 96 were up-regulated genes and 350 were down-regulated genes. These genes are mainly involved in processes such as inflammation, metabolism, immunity, and regulation of cell growth.Conclusions: OA may inhibit the proliferation, migration, and invasion of glioma U251 cells by binding key molecules of the IKK-β signaling pathway and essential target proteins of MAPK3 and MAPK4 in the MAPK signaling pathway.
Neurological Assessment Skill Competency of Registered Nurses in Traumatic Brain Injury Patients: A One Group Pre-Post Design
Authors: Yousef Nazia , Hussain Muhammad , Perveen Kousar , Afzal Muhammad , Gilani Syed Amir
Published: September 2021

ObjectivesTo assess the effect of educational pedagogy on the skill of nurses in neurological assessment of traumatic brain injury patientsMethodsThis one group pre-post-test study investigated the effect an educational pedagogy on 36 registered nurses of trauma center, general surgery and neuro surgery department of a tertiary care hospital. A 20 items validated competency checklist was used to assess the skill of nurses before and after educational training regarding Neurological (Glasgow Coma Scale) assessment of TBI patients.ResultsFrequency and percentages of demographic and professional variables were checked. 36 (100%) of the nurses showed incompetent skills practice and having scores from 0 to 13. post test results of the study illustrated that 7 (19.4 %) nurses having score 0 to 13 and had incompetent skill practices. 29 (80.6 %) nurses having score from 14 to 20 and had competent skills practice. mean ( of the posttest skills score was significantly higher than the mean ( of the pre test skills score. ConclusionBefore and after educational training there is significant paired mean difference in skill competency of nurses. Hence the educational intervention was effective in improving skills competency of registered nurses in neurological assessment.
Mechanisms of Sex Differences in Ankylosing Spondylitis: Interleukin 2 Receptor Subunit Beta and CD3d Molecule Play an Important Role
Authors: Yu Chaojie , Liu Chong , Liang Tuo , Liao Shian , Chen Liyi , Huang Risheng , Sun Xunhua , Ye Zhen , Guo Hao , Yao Yuanlin , Zhan Xinli , Zhao Jinmin
Published: September 2021

Introduction:ankylosing spondylitis (AS) is characterized by sexual dimorphism in clinical manifestations. Our aim is to reveal the reason for gender difference in AS. Material and Methods: we used bioinformatics to analyze gene expression data of GSE73754. And verified by PCR and ELISA. Results: the pathogenic pathways leading to AS are Th1 and Th2 cell differentiation. The key gene involved in this pathway in male is interleukin 2 receptor subunit beta (IL2RB). The key genes involved in female are IL2RB and CD3d molecule (CD3D) . Both genes are immune-related genes.Conclusion: differences in key genes contribute to gender differences in AS. Male AS may require only one gene, while female AS requires two genes.
Validation of Chinese Version of SKT (Syndrom Kurztest): A Short Cognitive Performance Test for the Assessment of Memory and Attention.
Authors: Lu Yao , Hu Jingchao , Stemmler Mark , Guo Qihao
Published: September 2021

Aim: The SKT (Syndrom Kurztest) is a short cognitive performance test that consists of nine subtests and assesses deficits of memory and attention. It was aimed at exploring the SKT target population in China and to evalute the reliability and validity of the Chinese version of SKT.Method: A total of 1624 patients (599 cognitively normal controls, 359 subjectively cognitively impairment, 666 individuals with mild cognitive impairment) aged over 60 years old were recruited in the Sixth People’s Hospital in Shanghai. Cognitive screening tests (Chinese version of SKT, MMSE, MoCA-BC, ACE-III, AVLT, BVMT-R) and global functional tests (ECOG, ADL) were carried out. The SKT raw scores were recorded. Cronbach’s alpha coefficient was determined to assess the internal consistency reliability of the SKT. Principal factor analysis was performed to evaluate the factor structure of the SKT subtests. Correlation analyses were carried out to confirm the relationship between the modified SKT and standardized neuropsychological tests. The influence of age and educational years on SKT raw scores were detected using multiple regression analyses. Validations of the SKT subtests for detecting MCI from NC were determined by Receiver operating characteristic (ROC) curves.Result: The internal consistency among the subtests’ scores was high: Cronbach’s α=0.827. The dimension reduction analysis showed the good factor structure of SKT subtests. Correlation analysis indicated the SKT raw scores of each subtest was negatively correlated with the corresponding MMSE and MoCA-B score. Correlation analysis revealed that age and education years were correlated to SKT raw scores (all p <0.001). We separated the participants into four subgroups according to educational years and age. Among the four groups, The old-old with higher educational level (group 4) had the largest area under the ROC curve (AUC) for SKT memory test, 0.821(95%CI: 0.747,0.876), with sensitivity 84.3% and specificity 62.1%. SKT memory test provided a high predictive validity in detecting aMCI with sensitivity 90.1% and specificity 79.3%.Conclusion: Based on our experience with 1624 old patients in Shanghai, the Chinese version of SKT has good stability which might be a reliable and valid screening tool for detecting MCI. However, test results must be interpreted with caution considered individuals’ age and educational level.
Network And Meta-Omics Reveal The Key Degrader And Cooperation Patterns In An Efficient 1,4-Dioxane-Degrading Microbial Community
Authors: Dai Chuhan , Wu Hao , Wang Xuejun , Zhao Kankan , Lv Zhenmei
Published: September 2021

Background: 1,4-dioxane is an emerging wastewater contaminant with probable human carcinogenicity. Our current understanding of microbial interactions during 1,4-dioxane biodegradation process in mix cultures is limited. Here, we applied metagenomic, metatranscriptomic and co-occurrence network analyses to unraveling the microbial cooperation between degrader and non-degraders in an efficient 1,4-dioxane-degrading microbial community CH1.Results: The 1,4-dioxane degrading bacterium, Ancylobacter polymorphus ZM13, was isolated from CH1 and proved to be the key degrader because of the high relative abundance, highly expressed toluene monooxygenase genes tmoABCDEF and high betweenness centrality of networks. The strain ZM13 cooperated obviously with 6 bacterial genera in the network, among which Xanthobacter and Mesorhizobium were proved to be involved in the intermediate metabolism with responsible genes encoding alcohol dehydrogenase (adh), aldehyde dehydrogenase (aldh), glycolate oxidase (glcDEF), glyoxylate carboligase (gcl), malate synthase (glcB) and 2-isopropylmalate synthase (leuA) upregulated. Also, 1,4-dioxane facilitated the shift of biodiversity and function of CH1, and those cooperators of CH1 cooperated with ZM13 in the way of providing amino acids or fatty acids and relieving environmental stresses to promote biodegradation.Conclusions: This study revealed the biodiversity, community structure, microbial functions and interactions in a microbial community CH1 during the efficient 1,4-dioxane degradation and proved the degrader Ancylobacter polymorphus ZM13 that isolated from CH1 was the key degrading bacterium. These results provide new insights into our understanding of how the key degrading bacterium interacted with cooperators in a 1,4-dioxane-degrading community, and has important implications for predicting microbial cooperation and constructing highly efficient synthetic 1,4-dioxane-degrading communities.
Bioinformatic Analysis of Transcriptome Changes Underlying Metformin-induced Reversal of Drug Resistance in Head and Neck Squamous Cell Carcinoma Cells
Authors: hou shanchun , Li Qi , Jin Wulong , Peng You , Niu Sujuan , Zhang Xuebing , Bai Yijie , Xu Xiaohui , Hou Jianming , Na La , Bi Zhehui , Geng Shuo , Xu Peng , Jun Feng
Published: September 2021

Background: Metformin is the first-line drug for type II diabetes, and recent studies indicate that metformin plays an inhibitory role in multiple cancers. Metformin can also enhance the effect of chemotherapy. Although head and neck squamous cell carcinoma cells are sensitive to metformin, the mechanisms related to the metformin response and the chemosensitization effect have not been fully studied. Results: In this study, we aimed to elucidate the molecular mechanisms of metformin in HNSCC by transcriptome analysis and to reveal the underlying mechanisms of the sensitizing effects of metformin by combined online dataset analysis. mRNA sequencing and functional analysis of HNSCC samples after metformin treatment and functional analysis of mRNAs with opposite metformin-induced effects in chemosensitive versus chemoresistant cells revealed the molecular pathways, mainly the base excision repair pathway, by which this small molecule drug sensitizes HNSCC cells to treatment. Conclusions: These findings indicate that metformin exerts a hypersensitization effect by regulating the BER pathway in tumour cells, reducing their self-repair capacity after chemotherapy-induced DNA damage. In addition, the genes identified by transcriptome analysis are candidates for further investigation into the effector targets of metformin in the inhibition of HNSCC and could be applied to improve the treatment in HNSCC patients who develop resistance after advanced chemotherapy.
Application of The QFD-fuzzy-SERVQUAL Methodology as a Quality Planning Tool at the Surgical Centre of a Public Teaching Hospital
Authors: Junior Jurandir Barreto Galdino , Hékis Hélio Roberto , Costa José Alfredo Ferreira , de Andrade Íon Garcia Mascarenhas , Cabral Eric Lucas dos Santos , Castro Wilkson Ricardo Silva , Florentino Davidson Rogério de Medeiros , Barreto Tiago de Oliveira , Junior João Florêncio da Costa
Published: September 2021

Background: In Brazil, many public hospitals face constant problems related to high demand vis-à-vis an overall scarcity of resources, which hinders the operations of different sectors such as the surgical centre, as it is considered one of the most relevant pillars for the proper hospital functioning, due to its complexity, criticality as well as economic and social importance. Proper asset management based on well-founded decisions is, therefore, a sine-qua-non condition for addressing such demands. However, subjectivity and other difficulties present in decisions make the management of hospital resources a constant challenge.Methods: Thus, the present work proposes the application of a hybrid approach, formed by the QFD tools, fuzzy logic and SERVQUAL as a decision support tool for the quality planning of the surgical centre of the Onofre Lopes Teaching Hospital (Hospital Universitário Onofre Lopes - HUOL). To accomplish such objective, it was necessary to discover and analyse the main needs of the medical team working in the operating room, through the application of the SERVQUAL questionnaire, associated with fuzzy logic. Results: Then, the most relevant deficiencies were transformed into entries for the QFD-fuzzy, where they were translated into project requirements. Soon after, the analysis of the existing relationships between the inputs and these requirements was carried out, generating the ranking of actions with the greatest impact on the improvement of the surgical centre overall quality. Conclusions: As a result, it was found that the proposed methodology can optimize the decision process to which hospital managers are submitted, improving the surgical centre operation efficiency.
Spatial Heterogeneity and Socio-economic Correlates of Unmet Need for Spacing Contraception in India: Evidences from National Family Health Survey, 2015-16
Authors: Rahaman Margubur , Rana Md Juel , Roy Avijit , Chouhan Pradip
Published: September 2021

Background:The high unmet need for contraception among women who wants to delay their subsequent births for two or more years (UNS) is a challenging issue in India. Therefore, the present study aims to display spatial heterogeneity and determine the associated factors underlying the UNS among the currently married women aged 15-49 years with a demand for spacing births in India.Methods:The present study used data from the National Family and Health Survey, 2015-16. Unmet need for spacing (UNS) used as outcomes and socio-cultural and demographic factors as explanatory variables. Among the comprehensive family planning, 16.7% (56742 women) of currently married women had demand for spacing births were used for analysis. Univariate, bivariate with chi-square significance test, spatial natural break technique, and multivariate logistic regression were used to accomplish the study objectives. Results:Almost 17% of women had demand spacing out of total demand for family planning in India. High unmet need for contraception found among them except the women with higher-level education and wealth status. District level spatial heterogeneity of UNS shows 248 districts had remarkably high unmet for spacing (68% and above). Results from multivariate logistic regression show that UNS's likelihood was noticeably high among the women with parity three or more (AOR: 1.42 [1.3-1.55]) compared to their counterparts. Similarly, 44% (AOR: 1.44[1.38-1.51]) more likely found among the OBC than General caste. Rural (AOR: 1.24[1.19-1.30]) women compared to urban, women living in South (AOR: 6.19 [5.76-6.65]), Central (AOR: 1.52 [1.43-1.61]), and West (AOR: 1.80 [1.68-1.92]) region compared to those from North had higher odds of UNS. Conclusion:Deal with the UNS in India requires scaling up women education, client choice-based services, campaign on benefits of spacing births and available contraception, and socio-economically backward group centric policies.
Cognitive Composites for Genetic Frontotemporal Dementia: GENFI-Cog
Authors: Poos Jackie M. , Moore Katrina M. , Nicholas Jennifer , Russell Lucy L. , Peakman Georgia , Convery Rhian S. , Jiskoot Lize C. , Ende Emma L. van der , Berg Esther van den , Papma Janne M. , Seelaar Harro , Pijnenburg Yolande A.L. , Moreno Fermin , Sanchez-Valle Raquel , Borroni Barbara , Laforce Robert , Masellis Mario , Tartaglia Carmela , Graff Caroline , Galimberti Daniela , Rowe James , Finger Elizabeth , Synofzik Matthis , Vandenberghe Rik , Mendonça Alexandre , Tiraboschi Pietro , Santana Isabel , Ducharme Simon , Butler Chris , Gerhard Alexander , Levin Johannes , Danek Adrian , Otto Markus , Ber Isabel Le , Pasquier Florence , Swieten John C. van , Rohrer Jonathan D.
Published: September 2021

Background: Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) and recommend on recruitment and duration in clinical trial design.Methods: A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR® plus NACC-FTLD≥0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier groups and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR® plus NACC-FTLD ≥1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC-FTLD=0.5 to ≥1 (and therefore how long a trial would need to be). Results: Results from the logistic regression analyses resulted in different composite scores for each mutation carrier group. The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after three years ~50% of individuals had converted from CDR® plus NACC-FTLD 0.5 to ≥1.DISCUSSION: We created gene-specific cognitive composite scores for C9orf72, GRN and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.
Nanoparticles Delivering Antagomir-483-5p to Bone Marrow Mesenchymal Stem Cells Prevent Osteoporosis by Increasing Bone Formation
Authors: Zhou Yue , Jia Hao , Hu Aihua , Liu Rangru , Zeng Xiangzhou , Wang Hua
Published: September 2021

Background: Promoting bone marrow mesenchymal stem cell (BMSC) osteoblastic diﬀerentiation is a promising therapeutic strategy for osteoporosis (OP). The present study demonstrates that miR-483-5p inhibits the osteogenic differentiation of BMSCs. Therefore, selectively delivering the nanoparticles carrying antagomir-483-5p (miR-483-5p inhibitor) to BMSCs is expected to become an effective treatment drug for OP.Methods: Real-time PCR assays were used to analyse miR-483-5p, ALP and Bglap levels in BMSCs of ovariectomized and aged osteoporotic mice. To selectively and efficiently deliver antagomir-483-5p to BMSCs in vivo, immunoglobulin G and poloxamer-188 were used to encapsulate the functional small molecules, and BMSC-targeting aptamer was employed to confirm the direction of the nanoparticles. Luciferase assays were used to determine the target genes of miR-483-5p. Western blot assays and immunohistochemistry staining were used to detect the targets in vitro and vivo.Results: miR-483-5p levels were increased in BMSCs of ovariectomized and aged osteoporotic mice. Inhibition of miR-483-5p levels in BMSCs by antagomir-483-5p in vitro promoted the expression of bone formation markers, such as ALP and Bglap. The FAM-BMSC-aptamer-nanoparticles carrying antagomir-483-5p were taken up by BMSCs, resulting in stimulation of BMSC osteoblastic diﬀerentiation in vitro and osteoporosis prevention in vivo. Furthermore, our research demonstrated that mitogen-activated protein kinase 1 (MAPK1) and SMAD family member 5 (Smad5) were direct targets of miR-483-5p in regulating BMSC osteoblastic diﬀerentiation and osteoporosis pathological processes. Conclusions: The important therapeutic role of FAM-BMSC-aptamer-nanoparticles carrying antagomir-483-5p in osteoporosis was established in our study. These nanoparticles are novel candidate for the clinical prevention and treatment of osteoporosis. The optimized targeted drug delivery platform for small molecules will provide new ideas for the treatment of clinical diseases.
Synergistic Effect of Nickel on Tungsten Oxide Hydrate (WO3.H2O) as Photoanode for Dye-Sensitized Solar cell
Authors: A Manimekalai , R Parimaladevi , M Umadevi
Published: September 2021

Tungsten oxide hydrate (PW) and Nickel tungsten oxide nanocomposites (NW NCs) namely NW1, NW2, NW3 and NW4 were successfully synthesized by the hydrothermal method. The synthesized NCs were characterized using advanced techniques such as X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), UV–visible spectroscopy and Photoluminescence (PL). XRD pattern shows the formation of face-centered cubic phase for PW and monoclinic/orthorhombic phase for NW respectively. The nanoflakes like morphology for NW NCs were confirmed by SEM. The MB dye was successfully degraded using NW4 NCs with a rate constant of 0.02266 /minute. The photovoltaic performance of the photoanodes with various weight percentages (wt%) of Ni was measured by recording the photocurrent-photovoltaic curves. The result indicated that NW4 NCs exhibited the best power conversion efficiency (PCE) with high short circuit current density (Jsc) and open-circuit voltage (Voc). This enhanced photocatalytic and photovoltaic performance of NWNCs may be due to the visible light-harvesting, increased dye loading capacity and reduced photoelectron recombination.
A comprehensive survey of bat sarbecoviruses across China for the origin tracing of SARS-CoV and SARS-CoV-2
Authors: Wu Zhiqiang , Han Yelin , Wang Yuyang , Liu Bo , Zhao Lamei , Zhang Junpeng , Su Hao-Xiang , Zhao Wenliang , Liu Liguo , Bai Shibin , Dong Jie , Sun Lilian , Zhu Yafang , Zhou Siyu , Song Yiping , Sui Hongtao , Yang Jian , Wang Jianwei , Zhang Shuyi , Qian Zhaohui , Jin Qi
Published: September 2021

Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 have been thought to originate from bat, but whether the cross-species transmission occurred directly from bat to human or through an intermediate host remains elusive. In this study, we performed CoV screening of 102 samples collected from animal-selling stalls of Wuhan Huanan Market (WHM) and pharyngeal and anal swabs from13,064 bats collected at 703 locations across China, covering almost all known southern hotspots for sarbecovirus, between 2016 and 2021. This is the first systematic survey of bat CoV in China during the outbreak of Corona Virus Disease 2019. We found four non-sarbeco CoVs in samples of WHM, and 142 SARS-CoV related CoVs (SARSr-CoV) and 4 recombinant CoVs in bats, of which YN2020B-G share the highest sequence identity with SARS-CoV among all known bat CoVs, suggesting endemic SARSr-CoVs in bats in China. However, we did not find any SARS-CoV-2 related CoVs (SC2r-CoV) in any samples, including specimens collected from the only two domestic places where RaTG13 and RmYN02 were previously reported (the Tongguan caves and the karst caves around the Xishuangbanna Tropical Botanical Garden), indicating that SC2r-CoVs might not actively circulate among bats in China. Phylogenetic analysis showed that there are three different lineages of sarbecoviruses, L1 (SARSr-CoV), L2 (SC2r-CoV), and L-R (a novel CoV lineage from L1 and L2 recombination), in China. Of note, L-R CoVs are only found in R. pusillus. Further macroscopical analysis of the genetic diversity, host specificity for colonization and accidental infection, and geographical characteristics of available CoVs in database revealed the presence of a general geographical distribution pattern for bat sarbecoviruses, with the highest genetic diversity and sequence homology to SARS-CoV or SARS-CoV-2 along the southwest border of China, the least in the northwest of China. Considering the receptor binding motifs for spike gene of sarbecoviruses in Indochina Peninsula show the greatest diversity, our data provide the rationale that extensive surveys in further south and southwest to or of China might be needed for finding closer ancestors of SARS-CoV and SARS-CoV-2.
Factors Influencing COVID-19 Testing: A Qualitative Study in Bhutan
Authors: Yangchen Sonam , Ha Solip , Assan Abraham , Tobgay Tashi
Published: September 2021

Background: The COVID-19 pandemic has reaffirmed an all-knowing truth – that health is central in the 2030 Sustainable Development Agenda. To fully meet its associated challenges, global campaigns edge countries to implement strategies addressing COVID-19, including measures to scale-up testing. This study explored factors that influenced COVID-19 testing in Bhutan. It is envisioned findings could serve as a roadmap to effectively respond to COVID-19 and future outbreaks, particularly in low- and middle-income countries.Methods: The study employed an exploratory qualitative design. Data collection methods included interviews with key informants with a purposively selected sample of 20 participants and documentary review. A hybrid approach of inductive and deductive coding and theme development was conducted to analyze findings. A tailored version of the WHO Health System Framework incorporating the Essential Public Health Function was used to guide data interpretation.Results: Improved political will through the influence and leadership of the Royal King of Bhutan played a crucial role in raising attention to the problem, and provision of adequate financial and technical relief to ensure that all people irrespective of their socioeconomic status do not pay to get tested of COVID-19. Further, a combination of multifaceted factors such as: the whole of society approach to health; Bhutan’s pragmatic tactic in delivering on the promise of universal health coverage through primary health care strategy; the use of information technology for awareness creation and improving surveillance system; all fast-tracked COVID-19 testing service delivery. Conclusion: Bhutan’s success relied greatly on multi-sectoral and systems approach during policy design, implementation and monitoring, and active collaborative efforts involving consultation and engagements with a broad range of local (community members), national and global actors accelerated COVID-19 testing. These efforts were made possible through improved health governance and leadership at the highest level in the country.
Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer
Authors: Gao Shenshuo , Zhang Zhikai , Wang Xubin , Ma Yan , Li Chensheng , Liu Hongjun , Jing Changqing , Li Leping , Guo Xiaobo
Published: September 2021

Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.
An Economic-environmental-energy Efficiency Analysis for Optimizing Organic Waste Treatment of a Livestock-orchard System: A Case in the Mekong Delta, Vietnam
Authors: Thao Nguyen Thi Thu , Hieu Tran Thi , Thao Nguyen Thi Phuong , Vi Le Quoc , Schnitzer Hans , Thanh Son Le , Braunegg Gerhart , Braunegg Sibylle , Le Hai Thanh
Published: September 2021

BackgroundEconomic benefit has been analyzed for the yield of farming products when designing a farming system, while waste treatment also generates profitable energy products for this system. The economic factor is decisive in decision-making for applying waste treatment solutions for a small-scale farming system. A household farming system in ​​the Mekong Delta generates many kinds of organic wastes, but most of the agricultural waste resources are disposed of into the environment. MethodsThis study approaches an analysis of economic-environmental-energy (EEE) efficiency for waste treatment of an integrated livestock-orchard (LO) system on a household scale in the Mekong Delta. This novel analysis method is based on the energy content of biomass and its cost. The EEE efficiency is optimized to gain objective functions regarding energy yield efficiency, system profit, and CO2 sequestration for the treatment model. The algorithms are built for optimizing these objective functions. ResultsThe optimization results show the treatment model of pyrolysis and pelleting gain all the objective functions with high efficiency. The model is efficiently applied for the LO system that generates more than 100 kilograms of orchard residues and 3,000 kilograms of pig manure. The system with a charcoal oven and pellet machine is capable to gain energy efficiency due to its potential biofuel products, such as biochars and pellet products. A treatment model of composting, pyrolysis, and pelleting gives the best performance of overall EEE efficiency. ConclusionsThis work has proven economic benefits from integrating biogas tank, charcoal oven, and pellet machine in an integrated LO system. The system contributes not only for reducing CO2 emissions but also for supplementing secondary renewable bioenergy, as well as for increasing incomes and thus supporting livelihoods for the local farming households.
Biocidal Activity of Low Temperature Plasma to Xylella Fastidiosa
Authors: Ambrico Paolo F. , Zicca Stefania , Ambrico Marianna , Rotondo Palma R. , Stradis Angelo , Saponari Maria , Boscia Donato , Saldarelli Pasquale
Published: September 2021

The quarantine bacterium Xylella fastidiosa was first detected in Salento (Apulia, Italy) in 2013 and caused severe symptoms in olives, leading to plant death. The disease, named Olive Quick Decline Syndrome (OQDS), is caused by the strain "De Donno" ST53 of the subspecies pauca of this bacterium (XfDD), which is spread by Philaenus spumarius. The epidemic poses a serious threat to the agricultural economy and the landscape, as X. fastidiosa infects several plant species and there is yet no recognized solution. Research on OQDS is focused on finding strategies to control its spread or mitigate its symptoms. In this context, we investigated the feasibility of using low-temperature plasma and plasma-activated water to kill bacterial cells. Experiments were conducted in vitro to test the biocidal effect of a Surface Dielectric Barrier Discharge plasma on bacteria. The results showed a high decontamination rate even for cells of XfDD embedded in biofilms grown on solid media. Application to trees requires protocols and tools that can reach the bacterium in the xylem vessels. Plasma Activated Water was tested as a biocidal agent that can move freely in the xylem network. Results in the liquid culture medium showed complete inactivation of XfDD cells and paved the way to test the strategy on infected plants.
Targeting the Nervous System of the Parasitic Worm, Haemonchus Contortus, With Quercetin.
Authors: Goel Vanshita , Chakroborty Neloy , Sharma Sunidhi , Singla Lachhman , Choudhury Diptiman
Published: September 2021

Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary drugs lead to a pressing need to develop new anthelmintic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of the H. contortus. Further, histological analysis demonstrated damage of various body parts, including isthmus, brut, pseudocoele, and other organs due to quercetin treatment. Mechanistic studies revealed the generation of oxidative stress and alterations in activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of ROS-generation disclosed neuropils as the primary targets of quercetin in the adult worms, which eventually lead to the paralysis and death of the worms. Thus, altogether, this work demonstrates that the nervous system of the parasitic helminth, H. contortus, is a novel target of the drug quercetin.
Genomic Characteristics and Evolutionary Analysis of a Rare GI.1 Norovirus Isolate From Beijing, China
Authors: Zhang Weishan , Zhang Wei , Hu Xinling , Zhou Xintong , Tian Guobao , Xu Yinghua , Mi Kaixia
Published: September 2021

Noroviruses are one of the main pathogens of acute gastroenteritis, causing frequent outbreaks worldwide every year that seriously affect human health. The GII.4 genotype causes most norovirus (NoV) infections and large-scale outbreaks. By contrast, the GI genotype is relatively rare. In this study, the whole genome sequence of a newly isolated ZD strain from a patient in Beijing, China, was sequenced and analyzed. The ZD strain genome consisted of 7,597 nucleotides and contained three open reading frames. Whole-genomic analysis indicated the strain was a GI.1 genotype, and no recombination site was detected in the genome. The histo-blood group antigen (HBGA)binding site associated with invasion of the GI genotype did not change, implying relatively conservative evolution. Phylogenetic analysis indicated the VP1 sequence of GI.1 strains could be divided into three clusters according to time of appearance: older (1968-2011), earlier (2011-2015), and new (2017-2018). Each cluster showed distinctive amino acid substitution characteristics, and the number of substitutions increased with time. The isolated ZD strain was in the new cluster. This study is the first to conduct a phylogenetic analysis of a GI genotype NoV isolated from Beijing. The results improve understanding of NoV diversity in China and can be a reference for further study of nondominant epidemic strains of NoVs as well as epidemic prevention and control.
TGF-β activates NLRP3 Inflammasome by an Autocrine Production of TGF-β in LX-2 Human Hepatic Stellate Cells
Authors: Oh Yoon Sin , Kang Hwansu , Seo Eunhui , Jun Hee-Sook
Published: September 2021

Inflammation contributes to the pathogenesis of liver disease, and inflammasome activation has been identified as a major contributor to the amplification of liver inflammation. Transforming growth factor-beta (TGF-β) is a key regulator of liver physiology, contributing to all stages of liver disease. We investigated whether TGF-β is involved in inflammasome-mediated fibrosis in hepatic stellate cells. Treatment with TGF-β increased priming of NLRP3 inflammasome signaling by increasing NLRP3 levels and activating TAK1-NF-kB signaling. Moreover, TGF-β increased the expression of p-Smad2/3-NOX4 in LX-2 cells and consequently increased ROS content, which is a trigger for NLRP3 inflammasome activation. Elevated expression of NEK7 and active caspase-1 was also shown in TGF-β-induced LX-2 cells, and this level was reduced by (5Z)-oxozeaenol, a TAK inhibitor. Finally, TGF-β-treated cells significantly increased TGF-β secretion levels, and their production was inhibited by IL-1β receptor antagonist treatment. In conclusion, TGF-β may represent an endogenous danger signal to the active NLRP3 inflammasome, by which IL-1β mediates TGF-β expression in an autocrine manner. Therefore, targeting the NLRP3 inflammasome may be a promising approach for the development of therapies for TGF-β-induced liver fibrosis.
Preoperative and Postoperative Nomograms in Predicting Early Recurrence of Hepatocellular Carcinoma Without Macrovascular Invasion After Curative Resection
Authors: Zhang Yanfang , Xu Liangliang , Xu Mingqing , Tang Hong
Published: September 2021

This study aimed to establish pre- and postoperative nomograms in predicting postoperative early recurrence (ER) for hepatocellular carcinoma (HCC) without macrovascular invasion. The patients who underwent curative LR for HCC from January 2012 to December 2016 in our center were divided into training and internal prospective validation cohorts. Nomograms were constructed based on the independent risk factors derived from multivariate logistic regression analyses in training cohort. The predictive performance of nomograms was validated by internal prospective validation cohort. A total of 698 patients fulfilled with eligible criteria. Among them, 265 out of 482 patients (55.0%) in training cohort and 120 out 216 (55.6%) patients in validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha fetoprotein (AFP), tumor diameter, tumor number; the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvasular invasion (MVI) and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy with C-indices of 0.712 and 0.850 in training cohort, and 0.754 and 0.857 in validation cohort, respectively. The calibration curves showed optimal agreement between the prediction by the nomograms and actual observation. The area under the receiver operating characteristic curves of pre- and postoperative nomograms were 0.721 and 0.848 in training cohort, and 0.754 and 0.844 in validation cohort, respectively. Present nomograms showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery, which were helpful for doctors in designation of treatments and selection of patients for regularly surveillance or administration of neoadjuvant therapies.
MDO: A Computational Protocol for Accurate Prediction of Full Flexibility Receptor-Ligand Binding Mode Structures
Authors: Al-Ansi Amar Y. , Lin Zijing
Published: September 2021

Predicting the binding structure of bio-complex is essential for understanding its properties, functions, and mechanisms, but is rather difficult due to the huge sampling space involved. A new computational protocol, MDO, for finding the ligand binding structure is proposed. MDO consists of global sampling via MD simulation and clustering of the receptor configurations, local sampling via molecular docking and clustering of the ligand conformations, and binding structure optimization by the ONIOM (QM/QM) method. MDO is tested on 15 protein-ligand complexes with known accurate structures. The success rate of MDO predictions, with RMSD < 2 Å, is found to be 67%, substantially higher than the 40% success rate of conventional methods. The MDO success rate can be increased to 83% if the ONIOM calculations are applied only for the starting poses with ligands inside the binding cavities. The MDO protocol is a promising tool for the structure based drug design.
Fatigue of full crown monolithic CAD/CAM restorations for posterior teeth
Authors: Bataineh khaled , Alkarasneh assem Al
Published: September 2021

Objective

The purpose of this study is to estimate the fatigue life of five polycrystalline zirconia CAD/CAM ceramic materials used for posterior restoration. This study presents the first time methodology to translate raw data obtained from laboratory test into useful data to predict the clinical life of dental restoration.
Methods

A typical model for the first molar restored crown is built and transferred into finite element software ANSYS 18.1 flor execution FEA. The materials are: two Y-TZP zirconia (LAVA (LVs), and EVEREST (KVs); IPS e.max CAD; Suprinity PC; and Celtra Duo. Two types of loads are applied, axial load and axial load followed by the sliding motion of lower jaw. The fatigue resistance of various restorative materials is determined.
Results

Experimental findings show that all the samples have fractured between cusps at the same location, which is slightly off the symmetry fissure plane. For crowns made of LAVA and EVEREST, the life is longer than 10 years under an axial load of 1000 N, while the lives for IPS e.max CAD; Suprinity PC; and Celtra Duo were longer than 10 years under an axial load of 185 N. The life of all-ceramic crown materials was predicted by FEA and found to conform to previous experimental and clinical observations.
Conclusion

Crowns made of Y-TZP zirconia has superior fatigue resistance compared to other ceramic CAD/CAM materials.
Regional Living Conditions and the Prevalence, Awareness, Treatment, Control of Hypertension at the Individual Level in Russia
Authors: Maksimov Sergey Alekseevich , Balanova Yulia A. , Shalnova Svetlana A. , Muromtseva Galina A. , Kapustina Anna V. , Drapkina Oksana M.
Published: September 2021

Background. The objective of this study was to analyze the influence of the living characteristics of large regions on the possible presence, awareness, management and control of hypertension at the individual level in the Russian population.Methods. Regional characteristics were obtained from the official website of the Federal State Statistics Service of Russia. Principal component analysis was used to reduce the dimensionality of data; it allowed defining 5 integral regional indices: Socio-Geographical, Demographic, Industrial, Mixed, Economic. Presence, awareness, management and control of hypertension were assessed according to the data of the cross-sectional stage of ESSE-RF study that was conducted in 2013-2014. The final sample included 19,791 patients from 12 regions of Russia. Generalized estimation equations were used to determine associations between regional indices and presence, awareness, management and control of hypertension at the individual level taking into consideration nested data structures (individuals in regions).Results. The Socio-Geographic Index demonstrated the positive impact on hypertension among male (OR = 1.18; 95% CI: 1.05-1.32), undereducated individuals (OR = 1.14; 95% CI: 1.02-1.27) and elderly people (OR = 1.16; 95% CI: 1.02-1.32). Awareness of hypertension is positively associated with Demographic (OR = 1.13; 95% CI: 1.02-1.25) and Industrial Indices (OR = 1.15; 95% CI: 1.01-1.33). Worsening of social environment (Socio-Geographic Index) reduces adherence to management (OR = 0.76; 95% CI: 0.64-0.90) and control of hypertension (OR = 0.79; 95% CI: 0.69-0.90). Impact of regional living conditions on the prevalence of hypertension is not high, compared to the individual predictors, but for the awareness, treatment and control of hypertension, this influence is important.Conclusions: The study performed allowed assessing the influence of living characteristics of the population in the large regions of Russia on the prevalence of hypertension and on the awareness, management and control of this disease. The data obtained provide new knowledge not only in terms of epidemiology of cardiovascular diseases in Russia but also in general, that is, in the context of studying the influence of living conditions on the health of population.