bluuebunny/crossref_metadata_2025 huggingface dataset:
New Stage of Rodless Artificial Lift Operation: the First Field Application of Submersible Motor Cable Plug with Electric Submersible Progressing Cavity Pump in CNPC
Authors: Zhu Shijia , Hao Zhongxian , Zhang Lixin , Ming Eryang , Wang Quanbin
Published: November 2020

After years of testing and development, the rodless artificial lift technology for low production wells including submersible plunger pump and ESPCP is going into scale applications stage in CNPC. About 150 ESPCP field applications have been used, the performance of system showed longer running time, great energy saving and less workload of maintenance compared to the previous rod pumping unit. But from the statistic of field applications, the cable failure is one of the most common failures. So, we proposed a new cable installation equipment and method with submersible cable plug with ESPCP in this paper.

Compared to the traditional method that the cable is fixed outside the tubing, we located the cable in the tubing. There is a cable socket above the pump. In this way, the cable plug was lowered down into the tubing with the cable after putting the tool string downhole. The plug was put into the socket by the gravity force. Therefore, there was a heavy-weight part above the cable plug to guarantee the high successful rate of lowing and plug-in process. Up to now, we have used this submersible motor cable plug technology in seven wells in Xinjiang oil field.

The results show that the cable can connect to the socket successfully in ESPCP field applications. There are lots of advantages compared to the traditional operation technology. First, the operation time was shortened from 3 days to 1.5 days by eliminating the installation of cable clips and insulation test when each 10 tubings were lowed in. It can enhance the operation efficiency and reducing the operation time. Second, there was less cable clip using in this technology. It can decrease the operation cost of cable clip. At last, it avoided the cable abrasion from the tubing when lowed the string into the well, which is one the most likely failure reasons. In this way, it enhances the safety factor of operation and the cable can be reused in another well.

This technology makes the operation safer and more efficient. It can be used with not only ESPCP technology, but also other submersible artificial lift technologies.
Signal Loss Recovery System for Downhole Electric Submersible Pump Sensors
Authors: Fontana Marcio , Reges Galdir Damasceno , dos Reis Ricardo André , de Jesus Raimundo Jorge , Morais Carlos Stênio , Ribeiro Marcos Pellegrini , Lima Antonio Cezar , Schnitman Leizer
Published: November 2020

An Electric Submersible Pump (ESP) artificial lifting downhole sensor data transmission may fail due to a reduced ESP electric cable isolation. An electronic recovering system prototype is proposed to re-establish the lost sensor signal due to the electrical current leakage that flows from the conductors to the ground. An innovative electronic system prototype has been developed to monitor an ESP downhole sensor operation and recover its lost signal due to the current leakage is proposed. Experimental tests are discussed, simulating high current leakage, and the transmission data recovered by the prototype are compared with data from a conventional oil industry downhole sensor.
Neighborhood's locality, road types, and residents' multimorbidity: evidence from China's middle-aged and older adults
Authors: Yu Xuexin , Zhang Wei
Published: November 2020

Background Neighborhood factors have gained increasing attention, while the association between the neighborhood's characteristics and multimorbidity has not been clarified. In this study, we aim to depict variations in the number of non-communicable chronic diseases (NCDs) as a function of urban vs. rural settings and road types.Methods The present cross-sectional study derived data from the China Health and Retirement Longitudinal Study 2011 National Baseline Survey. Negative binomial regression with clustered robust standard errors was performed to analyze variations in the number of NCDs among 13,414 Chinese middle-aged and older adults. Logistic regression models were employed to investigate the association between neighborhood-level characteristics and each NCD, respectively. Results First, over 65% of subjects had at least one NCDs, and over 35% had multimorbidity. Arthritis (33.08%), hypertension (24.54%), and digestive disease (21.98%) were the most prevalent NCDs. Urban vs. rural differences in multimorbidity were fully explained by neighborhood clustering variations (IRR = 1.02, 95% CI, 0.95 - 1.10). Living with paved roads was associated with a smaller number of NCDs relative to living with unpaved roads (IRR = 0.86, 95% CI, 0.78 - 0.95). Results from subgroup analyses suggested that in comparison with those living with unpaved roads, individuals living with paved roads respectively had lower odds of chronic lung disease (OR = 0.76, 95% CI, 0.63 - 0.93), chronic liver disease (OR = 0.74, 95% CI, 0.55 - 0.99), chronic kidney disease (OR = 0.68, 95% CI, 0.51 - 0.89), digestive disease (OR = 0.82, 95% CI, 0.69 - 0.97), arthritis or rheumatism (OR = 0.69, 95% CI, 0.55 - 0.87), and asthma (OR = 0.67, 95% CI, 0.51 - 0.88). Conclusions Urban vs. rural disparities in multimorbidity appeared to result from within-neighborhoods characteristics. The improvement in neighborhood-level characteristics, such as road pavement, holds promise to alleviate the increasing disease burden of chronic diseases.
Increased Association of Deamidated αA-N101D with Lens Membrane of Transgenic αAN101D vs. Wild Type αA Mice: Potential Effects on Intracellular Ionic Imbalance and Membrane Disorganization
Authors: Srivast Om , Srivast Kiran , Joseph Roy , Wilson Landon
Published: November 2020

We have generated two mouse models, in one by inserting the human lens αAN101D transgene in CRYαAN101D mice, and in the other by inserting human wild-type αA-transgene in CRYαAWT mice. The CRYαAN101D mice developed cortical cataract at about 7-months of age relative to CRYαAWT mice. The objective of the study was to determine the following relative changes in the lenses of CRYαAN101D- vs. CRYαAWT mice: age-related changes with specific emphasis on protein insolubilization, relative membrane-association of αAN101D vs. WTαA proteins, and changes in intracellular ionic imbalance and membrane organization. Methods: Lenses of varying ages from CRYαAWT and CRYαAN101D mice were compared for an age-related protein insolubilization. The relative lens membrane-association of the αAN101D- and WTαA proteins in the two types of mice was determined by immunohistochemical-, immunogold-labeling-, and western blot analyses. The relative levels of membrane-binding of recombinant αAN101D- and WTαA proteins was determined by an in vitro assay, and the levels of intracellular Ca2+ uptake and Na, K-ATPase mRNA were determined in the cultured epithelial cells from lenses of the two types of mice.Results: Compared to the lenses of CRYαAWT, the lenses of CRYαAN101D mice exhibited: (A) An increase in age-related protein insolubilization beginning at about 4-months of age. (B) A greater lens membrane-association of αAN101D- relative to WTαA protein during immunogold-labeling- and western blot analyses, including relatively a greater membrane swelling in the CRYαAN101D lenses. (C) During in vitro assay, the greater levels of binding αAN101D- relative to WTαA protein to membranes was observed. (D) The 75% lower level of Na, K-ATPase mRNA but 1.5X greater Ca2+ uptake were observed in cultured lens epithelial cells of CRYαAN101D- than those of CRYαAWT mice. Conclusions: The results show that an increased lens membrane association of αAN101D--relative WTαA protein in CRYαAN101D mice than CRYαAWT mice occurs, which causes intracellular ionic imbalance, and in turn, membrane swelling that potentially leads to cortical opacity.
Etiology, clinical characteristics and coinfection status of bronchiolitis in Suzhou
Authors: Tan Jiahong , Wu Jinfeng , Jiang Wujun , Huang Li , Ji Wei , Yan Yongdong , Wang Meiuan , Shao Xuejun
Published: November 2020

Background: Bronchiolitis is a clinical syndrome commonly encountered in practice, particularly among infants and young children. To investigate the prevalence of pathogens in hospitalized children with bronchiolitis and study the clinical characteristics of bronchiolitis with or without coinfections. Methods: We investigated the respiratory specimens and clinical data of 1012 children with bronchiolitis who were treated at the Children’s Hospital of Soochow University between November 2011 and December 2018. The nasopharyngeal aspirates were examined to detect viruses by direct immunofluorescence assay or polymerase chain reaction (PCR). Mycoplasma pneumoniae (MP) was tested by PCR and enzyme-linked immunosorbent assay.Results: Of the 1012 children less than 2 years with bronchiolitis, causative pathogen was detected in 83.4% (842 of 1012). The majority of these (614 [72.9%] of 842) were single virus infection. The most common pathogens detected were respiratory syncytial virus (RSV) (44.4%), MP (15.6%), and human rhinovirus (HRV) (14.4%). Coinfection was identified in 13.5% (137 of 1012) of the patients. Coinfection includes virus mixed virus infection and virus mixed MP infection. Children with single virus infection had a higher rate of oxygen therapy compared with single MP infection. Conclusions: The most common pathogen detected in children with bronchiolitis is RSV, followed by MP and HRV. The high mix infection burden in bronchiolitis underscores a need for the sensitive and rapid diagnostics to accurately identify pathogens.
Understanding Implicit and Explicit Learning in Adolescents With and Without Anorexia Nervosa
Authors: Sternheim Lot , Wickham Miriam , Danner Unna , Maddox Todd , Filoteo Vincent , Shott Megan , Frank Guido
Published: November 2020

Backgroundcognitive disturbances such as impairments in learning are thought to play a role in adult Anorexia Nervosa (AN). It is remains unclear to what extend these disturbances result from starvation of the brain, or relate to an abnormal premorbid cognitive profile. This study investigates learning processes in adolescents with AN, hypothesizing that implicit learning is intact, as found previously in explicit learning tasks. Secondly, we hypothesized that anxiety and depression symptoms, inherent to AN, are associated to learning processes in AN, and thirdly we aimed to explore any cultural learning differences in individuals from the Netherlands or the USA. Methods: in total 46 adolescents diagnosed with AN and 44 control participants were administered an implicit category learning task in which they were asked to categorize simple perceptual stimuli (Gabor patches) based on a linear integration (i.e., an implicit task) of orientation and spatial frequency of the stimulus. A subgroup of adolescents also completed a task assessing explicit learning. Resultsmodel-based analyses indicated that adolescents with AN performed significantly more accurately compared to their healthy peers regardless whether they used the optimal strategy or not. Depression and anxiety did not relate to learning performance in the AN group, no cultural differences in learning were found. Conclusionsoverall, our findings of augmented implicit and explicit learning in adolescents with AN corroborate recent studies that suggested higher stimulus-response learning during prediction error paradigms. Learning disturbances in adult AN may then be due to malnourishment, highlighting the importance of early recognition and refeeding in treatments for AN.
Emergency Medicine Physicians’ Knowledge and Perceptions of Training, Education, and Resources in Eating Disorders
Authors: Ma Connie , Gonzales-Pacheco Diana , Cerami Jean , Coakley Kathryn E
Published: November 2020

Background: Eating disorders, specifically anorexia nervosa, have one of the highest mortality rates of all mental illnesses.(1) Knowledge and perceptions of patients with eating disorders (ED) in the Emergency Medicine (EM) specialty is not explored. EM physicians may be the first or only provider a patient interacts with. The purpose of this study is to explore previous training/education, perceptions of available resources, and educational needs in treating eating disorders in practicing Emergency Medicine (EM) physicians. Methods: A 36-question investigator-developed survey was used in this cross-sectional study. Data were extracted from Opinio for statistical analyses. SAS 9.4 was used to analyze data. The survey assessed EM physicians’ previous training, education, and confidence in treating and diagnosing eating disorders in adults and adolescents. The primary outcomes assessed were participants’ previous training/education in eating disorders, knowledge of resources for patients, and educational needs.Results: Of the 162 participants, just 1.9% completed a rotation on eating disorders during residency. Ninety-three percent were unfamiliar with the American Psychiatric Association’s Practice Guideline for the Treatment of Patients with Eating Disorders; 95% were unfamiliar with the publication, “ED [Emergency Department] management of patients with eating disorders”. At least 50% were unaware of seven of the ten resources for patients with eating disorders examined. At least 50% agreed additional education on 15 of the 19 topics examined would be useful; 85% agreed to education on assessment of patients with eating disorders in the ED.Conclusions: Providing EM physicians with comprehensive education and training and increasing awareness of eating disorder resources could result in identifying more patients with eating disorders to increase treatment post-discharge.
Coastal Microbiomes Reveal Associations between Pathogenic Vibrio Species, Environmental Factors, and Planktonic Communities
Authors: Diner Rachel E. , Kaul Drishti , Rabines Ariel , Zheng Hong , Steele Joshua A , Griffith John F , Allen Andrew Ellis
Published: November 2020

Background Many species of coastal Vibrio spp. bacteria can infect humans, representing an emerging health threat linked to increasing seawater temperatures. Vibrio interactions with the planktonic community impact coastal ecology and human infection potential. In particular, interactions with eukaryotic and photosynthetic organism may provide attachment substrate and critical nutrients (e.g. chitin, phytoplankton exudates) that facilitate the persistence, diversification, and spread of pathogenic Vibrio spp.. Vibrio interactions with these organisms in an environmental context are, however, poorly understood. Results After quantifying pathogenic Vibrio species, including V. cholerae , V. parahaemolyticus , and V. vulnificus, over one year at 5 sites, we found that all three species reached high abundances, particularly during Summer months, and exhibited species-specific temperature and salinity distributions. Using metabarcoding we established a detailed profile of the both prokaryotic and eukaryotic coastal microbial communities, finding that pathogenic species were frequently associated with specific ASVs of chitin-producing eukaryotes such as diatoms and copepods. Furthermore, environmental variables had a significant effect not only on pathogenic Vibrio species but entire microbial communities, suggesting in some cases shared environmental preferences. Several significant ASV-level associations were revealed, indicating that commonly used broad taxonomic classifications (e.g. based on microbial class or Vibrio as a genus) likely mask ecologically important interactions. Shotgun metagenomic analyses revealed diverse vibrio communities that harbored additional potential vibrio pathogens, antibiotic resistance genes, and genes associated with virulence. Conclusions Taken together, this data shows that abundant pathogenic Vibrio species likely containing both antibiotic resistance and virulence-associated genes are associated with chitin producing organisms which could act as an attachment substrate, facilitating environmental persistence and horizontal gene transfer. Shared environmental conditions such as high temperatures were associated with both high levels of pathogenic vibrios and potential environmental reservoirs, which should be taken into consideration when modelling vibrio infection risk in the face of climate change and identifying biomarkers of pathogen species. Furthermore, ASV-level associations may be critical to understanding vibrio microbial ecology and should be taken into consideration while developing environmentally relevant laboratory model systems.
High-Risk Behaviors Among Iranian University Students: A Web-Based Survey
Authors: Shekari Farhad , Habibi Peyman , Nadrian Haidar , Mohammadpoorasl Asghar
Published: November 2020

Background :High-risk behaviors is one of the most serious factors threatening the physical and mental health of adolescents and young adults. The aims of this study were to investigate thesubgroups of students based on risky behaviors and to identify the prevalence rate of these subgroups. Methods: This cross-sectional web-based survey was conducted from July to August 2019 in Tabriz, Iran. Sampling of all universities in the city was performed proportionally according to the number of students in each university. . Applying an online survey questionnaire, the data were collected from 3649 students and included into Latent Class Analysis. Results: For both genders, standardized prevalence rates of cigarrette smoking, hookah use, alcohol consumption, substance abuse and unsafe sex were 18.5 (CI 95%: 17.3-19.8), 9.1 (CI 95%: 8.2-10.1), 9.2 (CI 95%: 8.3-10.2), 8.3 (CI 95%: 7.4-9.3) and 14.5 (CI 95%: 13.3-15.7), respectively. Three latent classes of risky behaviors were determined among students: 1) low risk 2) smoking and 3) high risk. About 18% of boys and 1.5% of girls were in the high risk class. Cigarrette smoking (18.5%, CI 95%: 17.3-19.8) and substance abuse (8.3%, CI 95%: 7.4-9.3) were the most and the least common risky behaviors among the students. Conclusion: In this we-based survey, a considerable percentage of students, particularly boys, were at high-risk class, stressing the need for preventive interventions for this group of youth. Our findings are beneficial for planning and development of risky-behavior preventive measures to prevent high-risk behaviors among college students.
The Moderating Effect of Emotional Competence on Job Satisfaction and Organisational Commitment of Healthcare Professionals
Authors: Stamouli Elena , Gerbeth Sebastian
Published: November 2020

Background: Medical organisations such hospitals are largely being seen as task-based wherein different individuals are expected to work in interdependent teams. The present study seeks to demonstrate the relevance of individual factors (job satisfaction) and individual competences (emotional competence) for organisational commitment in a sample of healthcare professionals. Methods: Using multi-source data, the empirical study examined the interaction effect by analysing data collected from 96 healthcare professionals of five hospitals in Germany. To investigate the relationship between emotional competence, job satisfaction and organisational commitment moderated regression analysis, as well as simple slope analysis, were performed. Results: Hierarchical multiple regression analysis shows that emotional competence moderated the relationship between satisfaction with the job and commitment to the job. Our findings confirm that healthcare professionals with high emotional competence are able to deal more effectively with dissatisfaction in the workplace so that organisational commitment remains unaffected.Conclusion: Based on the results of this study emotional competence of healthcare professionals is important for increasing job satisfaction and commitment to the job. Especially for healthcare professionals whose job satisfaction is low, a high level of emotional competence enables them to maintain a high level of organisational commitment. The findings of the study are discussed at the theoretical level for researchers and practical level for hospital managers.
Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials
Authors: Zhang Ying-Ying , Zhou Rong , Gu Wan-Jie
Published: November 2020

Background: Opioid-induced constipation (OIC) is a distressing side effect during opioid analgesia and is mainly mediated by gastrointestinal μ opioid receptors. Methylnaltrexone, a peripheral μ opioid receptor antagonist with restricted ability to cross the blood-brain barrier, may alleviate OIC without reversing analgesia. We performed a meta-analysis to assess the efficacy and safety of methylnaltrexone for the treatment of OIC.Methods: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials that compared methylnaltrexone with placebo for the treatment of OIC. The primary efficacy outcome was rescue-free bowel movement (RFBM) within 4 hours after the first dose. Secondary efficacy outcomes included RFBM within 24 hours after the first dose, RFBM ≥3 times per week, and need take rescue laxatives. The primary safety outcome was any adverse events. Secondary safety outcomes included abdominal pain, diarrhea, nausea, vomiting, and flatulence. Relative risks (RR) and 95% confidence interval (CI) were pooled using random-effects model with the intention-to-treat principle. We used the GRADE approach to assess the certainty of the evidence.Results: Eight trials with 2,034 participants were included. Compared with placebo, methylnaltrexone significantly increased RFBM within 4 hours after the first dose (8 trials; 1,833 participants; RR 3.74, 95% CI 3.02-4.62; I2 = 0%; high-certainty evidence), RFBM within 24 hours after the first dose (2 trials; 614 participants; RR 1.98, 95% CI 1.52-2.58; I2 = 9%; moderate-certainty evidence), and RFBM ≥3 times per week (3 trials; 1,396 participants; RR 1.33, 95% CI 1.17-1.52; I2 = 0%; moderate-certainty evidence) and decreased need to take rescue laxatives (3 trials; 807 participants; RR 0.73, 95% CI 0.63-0.85; I2 = 0%; moderate-certainty evidence). For safety outcomes, there was no difference in any adverse events between the two groups (8 trials; 2,034 participants; RR 1.11, 95% CI 0.99-1.23; I2 = 34%; moderate-certainty evidence), including diarrhea, nausea, vomiting, and flatulence; but for the most commonly reported adverse events, the abdominal pain was higher in methylnaltrexone group than that in placebo group (6 trials; 1,813 participants; RR 2.30, 95% CI 1.29-4.08; I2 = 62%; moderate-certainty evidence).Conclusions: Methylnaltrexone is an effective and safe drug for treating OIC. But the safety of abdominal pain should be considered.Trial registration: PROSPERO (CRD42020187290).
TMT-based Quantitative Proteomic Analysis Reveals Defense Mechanism of Wheat Against the Crown Rot Pathogen Fusarium Pseudograminearum
Authors: Qiao Fangfang , Yang Xiwen , Xu Fengdan , Huang Yuan , Zhang Jiemei , Song Miao , Zhou Sumei , He Dexian , Zhang Meng
Published: November 2020

Background: Fusarium crown rot a major disease in wheat. However, wheat defense mechanisms remain poorly understood.Results: In this study, we employed tandem mass tag (TMT) quantitative proteomics technology for one disease-susceptible (UC1110 (S1)) and one disease-tolerant wheat cultivar (PI610750 (S2)) inoculated with Fusarium pseudograminearum WZ-8A. Analysis of morphology and physiology showed that average seedling root diameter was significantly decreased 3 days post-inoculation (dpi) in both cultivars. Malondialdehyde content decreased in PI610750 and catalase activity increased in UC1110, indicating that morphology, physiology, and biochemistry differed in both cultivars in response to disease. TMT analysis identified 366 differentially expressed proteins (DEPs) by Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes in the two comparison groups, S1-3dpi/S1-0dpi (163) and S2-3dpi/S2-0dpi (203). We concluded that phenylpropanoid biosynthesis (8), secondary metabolite biosynthesis (12), linolenic acid metabolites (5), glutathione metabolism (8), plant hormone signal transduction (3), MAPK signaling pathway-plant (4), and photosynthesis (12) contributed to wheat defense mechanisms. Protein-protein interaction network analysis showed that DEPs interacted in sugar metabolism and photosynthesis pathways. We validated 16 genes by real-time quantitative polymerase chain reaction.Conclusion: The results were consistent with proteomics data. Our results provided insight into molecular mechanisms of interaction between wheat and F. pseudograminearum.
Investigating Psychometric Properties of the Arm Activity Measure – Thai Version (ArmA-TH) Sub-scales Using the Rasch Model
Authors: Buntragulpoontawee Montana , Khunachiva Jeeranan , Euawongyarti Patreeya , Wongpakaran Nahathai , Wongpakaran Tinakon , Kaewma Atcharee , Ashford Stephen
Published: November 2020

Background: This study investigated the ArmA-TH measurement properties based on item response theory, using the Rasch model. Methods: Patients with upper limb hemiplegia resulting from cerebrovascular and other brain disorders were asked to completed the ArmA-TH questionnaire. Rasch analysis was performed to test how well the ArmA-TH passive and active function sub-scales fit the Rasch model by investigating unidimensionality, response category functioning, reliability of the person and item, and differential item functioning (DIF) for age, sex and education. Results: Participants had stroke or other acquired brain injury (n=185) and the majority were men 126(68.1%), with a mean age of 55(SD 22). Most patients 91(49.2%) graduated elementary/primary school. For the ArmA-TH passive function scale, all items had acceptable fit statistics. The scale’s unidimensionality, and local independence were supported. The reliability was acceptable. Disordered threshold was found in five items, none was DIF. For the ArmA-TH active function scale, one item was misfitting and three were locally dependent. The reliability was good. DIF was not found. All items had disordered thresholds, and data fitted the Rasch model better after rescoring.Conclusions: Both sub-scales of ArmA-TH fitted the Rasch model, and are valid and reliable. The disordered thresholds should be further investigated.
Immunotherapy Against Acetylated Tau at K280 Ameliorates Behavioral Impairments and Pathologies of Tau Transgenic Mouse
Authors: Kim Na-Young , Song Ha-Lim , Cho Kwangmin , Shim Young-Lim , Lee Kyounghye , Mun Yeon-Seon , Lee Seung-Eun , Kim Min-Seok , Kim Hyun-Ju , Kim Dong-Hou , Yoon Seung-Yong
Published: November 2020

Background : Tau is gaining attention as a target of therapeutic antibodies for Alzheimer's disease (AD) and other tauopathies but it was recently of debate which epitope on tau has therapeutic potency. While the hexapeptide 275VQIINK280 is a critical region for tau aggregation and K280 is acetylated in various tauopathies including AD, there has been no immunotherapy targeting acetylated K280. Methods : Acetylated K280 was first chosen as therapeutic target from small pilot studies comparing in vivo behavioral efficacy of tau transgenic mice by immunizing with several putatively pathogenic epitopes such as acetylated or phosphorylated or cleaved tau. Results : Therapeutic efficacy in tau transgenic mice was further evaluated with behavior, pathology and biochemical experiments after either active immunization with tau peptide acetylated at K280 or passive immunization with anti-tau antibody targeting K280 acetylation. Vaccination with tau peptide acetylated at K280 or antibody (Y01) targeting it ameliorated memory impairments and pathology in tau transgenic mice via intracerebroventricular or intraperitoneal route. Conclusions : This study showed that acetylated K280 tau is a good therapeutic target and Y01 could be a novel therapeutic antibody for AD and other tauopathies.
Could the Perioperative Use of Opioids Influence Cancer Outcomes After Surgery? A Scoping Review Protocol
Authors: Cascella Marco , Cuomo Arturo , Bifulco Francesca , Caprio Barbara Di , Accardo Rosanna , Forte Cira Antonietta , Esposito Gennaro , Fiore Marco
Published: November 2020

BackgroundOpioids are commonly used for the treatment of cancer and non-cancer pain, and during and after general anesthesia. Because preclinical studies underlined a potential opioid-mediated immunosuppression, it was postulated that the perioperative administration of opioids could influence cancer outcomes after surgery. Nevertheless, clinical data have been extrapolated mainly from retrospective analyses. Thus, the precise link between perioperative opioids use and cancer recurrence/metastasis or cancer-related mortality/morbidity remains unresolved.Methods/designThis scoping review is planned following the Joanna Briggs Institute recommendations. The authors will conduct a literature review through the PRISMA statement using PubMed and EMBASE databases; the Grey literature will be explored using Google Scholar, Conference Proceedings Citation Index (via Web of Science) and Open Grey. The search strategy will be limited to articles published in the English language and to human studies. The database searches are planned from the inception to November 2020. Two reviewers will independently screen titles and abstracts, followed by a full-text screening of potentially relevant articles with standardized data extraction. Any disagreement for the inclusion between the two reviewers will be discussed with a third reviewer.DiscussionThe review aim to map the available literature focusing on a possible association between the perioperative opioids use and cancer outcomes in patients undergoing surgery. The proposed approach will allow to identify and analyze the knowledge gap in the field and, serving as a prerequisite for future research including systematic reviews and clinical studies.Scoping review registrationOpen Science Framework https://osf.io/ng57c/ DOI 10.17605/OSF.IO/NG57C
rAAV-Delivered PTEN Therapeutics for Prostate Cancer
Authors: Ai Jianzhong , Li Jia , Su Qin , Ma Hong , He Ran , Wei Qiang , Li Hong , Gao Guangping
Published: November 2020

Background: Prostate cancer (PCa) is the second most popular diagnosed cancer and the fifth leading cause of cancer-related mortality for males globally. At present, effective treatments for PCa need to be further developed. To further understand the molecular mechanism and develop novel therapeutics for PCa, the role of phosphatase and tensin homolog (PTEN) signaling in PCa progression was investigated. Previous studies have reported that PTEN and its downstream target cyclin-dependent kinase inhibitor 1B (CDKN1B) are significantly downregulated in PCa cells compared to normal controls; therefore, modulation of PTEN and CDKN1B expression might be a promising therapeutic approach for PCa treatment. Methods: The expression of PTEN and CDKN1B was first verified in specimens from PCa patients or transgenic adenocarcinoma mouse prostate (TRAMP) mice. The effect of PTEN on PCa cell migration, apoptosis and cell cycle was analyzed by wound healing assay and flow cytometry in vitro. Next, we tested the concept of intraprostatic and intratumoral injection of recombinant adeno-associated virus (rAAV) 9 expressing Pten or Cdkn1b (4x1011 genome copies (GCs)/prostate) into 8-week-old TRAMP mice and a subcutaneous tumor xenograft mouse model (5x1011 GCs/tumor), respectively, to inhibit PCa progression. Results: PTEN and CDKN1B were significantly downregulated in human and mouse PCa samples, and CDKN1B expression was positively correlated with PTEN expression. Further, PTEN overexpression significantly inhibited the cell migration and cell cycle progression and promoted the apoptosis of PCa cells by decreasing Ccnd1 expression and increasing Cdkn1b expression. Importantly, rAAV9.Pten or rAAV9.Cdkn1b treatment significantly extended the lifespan of TRAMP mice and inhibited the growth rate of tumor xenografts by regulating downstream gene expression. Moreover, we confirmed that neoplasia in the treated prostates was significantly diminished compared to that in the control prostates and that apoptosis was markedly observed in xenografts treated with Pten or Cdkn1b, highlighting changes in two crucial factors for PCa progression. Conclusions: Taken together, these data indicate that rAAV-based PTEN/CDKN1B delivery holds promise for the development of novel therapeutics for PCa.
Sulforaphane Activates Brain-Derived Neurotrophic Factor (BDNF) Transcription by NF-E2-Related factor-2 (Nrf2), Showing Prevention Effects on the Microglial of Stressed Mice
Authors: Tang Rui , Cao Qianqian , He Lujuan , Du Pengfei , Chen Gang , Fu Rao , Xiao Fei , Sun Yirong , Zhang Ji-chun
Published: November 2020

Background: Accumulating evidence suggested that sulforaphane (SFN) showed prevention effects in stressed mice by activating the NF-E2-related factor-2 (Nrf2). However, the mechanism remains poorly understood. The present study aimed to investigate whether the prevention effects of SFN in stressed mice by activating brain-derived neurotrophic factor (BDNF) transcription on the microglial and revising abnormal dendritic spine morphology. Methods: In vitro study, we performed the Luciferase assay, Chromatin immunoprecipitation assay, Immunofluorescence, and Western blot to investigate whether SFN could activate Nrf2, resulting in BDNF transcription on the BV2 cell. In vivo study, we employed the Social defeat stress mice model, Behavior test, Western blots, Immunofluorescence, and Enzyme-linked immunosorbent assay to further explore whether the prevention effects of SFN in stressed mice by activating BDNF transcription on the microglial and revising abnormal dendritic spine morphology.Results: First, we found that SFN could activate Nrf2, resulting in Nrf2 binding to the BDNF exon I promoter, leading to BDNF protein expression on the BV2 cell. Second, SFN attenuated the decreased levels of Nrf2, and increased levels of MeCP2 expression, revising abnormal BDNF expression in the stressed mice. Third, we further found that the SFN could attenuate the decreased levels of Nrf2 and increased levels of MeCP2 expression on the microglial and revising microglial dysfunction in the stressed mice. Fourth, SFN could attenuate the increased levels of pro-inflammatory cytokine and the decreased levels of anti-inflammatory cytokine release in the stressed mice. Finally, SFN showed prevention effects and revised abnormal dendritic spine morphology in the stressed mice. Conclusions: Therefore, the prophylactic effects of SFN in the stressed mice by activating BDNF transcription on the microglial and revising abnormal dendritic spine morphology.
Betulinic Acid Inhibits ROS-Mediated Pyroptosis in Spinal Cord Injury by Augmenting Autophagy via the AMPK-mTOR-TFEB Signaling Pathway
Authors: Wu Chenyu , Chen Huanwen , Zhuang Rong , Wang Yongli , Hu Xinli , Zhang Haojie , Xu Yu , Li Jiafeng , Li Yao , Xu Huazi , Xu Hui , Ni Wenfei , zhou kailiang
Published: November 2020

Background：Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. Methods：Using a mouse model of SCI, survival and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, and pyroptosis; ROS- and AMPK-related signaling pathways were also examined. Results：Our results showed that BA significantly improves functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS-activity and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induces mitophagy to eliminate the accumulation of ROS and subsequently inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Conclusion: BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.
Cytochrome P450-Epoxygenated Fatty Acids Inhibit Müller Glial Inflammation
Authors: Ontko Cayla D. , Capozzi Megan E. , Kim Minjae J. , McCollum Gary W. , Penn John S.
Published: November 2020

BackgroundMüller cell (MC) inflammation is an early pathogenic step in the vision-threatening disease diabetic retinopathy (DR). Recent evidence indicates that diabetes-induced free fatty acid (FFA) dysregulation can elicit the release of inflammatory cytokines from MC, promoting DR progression. Palmitic acid (PA) is elevated in the sera of diabetics and stimulates the production of the DR-relevant cytokines by MC, including interleukin-1β (IL-1β), IL-6, IL-8 and tumor necrosis factor-α (TNFα). IL-1β is elevated in DR and is purported to be a “master regulator” of cytokine-induced inflammation. IL-1β activates MC to produce itself (IL-1β auto-amplification) and other inflammatory cytokines in the retina. Consequently, a modality that blocks both FFA- and IL-1β-induced MC inflammation has therapeutic potential in DR. The CYP-derived epoxygenated fatty acids, epoxyeicosatrienoic acid (EET) and epoxydocosapentaenoic acid (EDP), offer one such therapeutic strategy. In this study we propose that experimental elevation of EET and EDP will reduce PA- and IL-1β-induced MC inflammation.MethodsHuman MC (hMC) were treated with vehicle, broad-spectrum CYP inhibitor SFK-525a, or PA or IL-1β in the presence or absence of 11,12-EET, 19,20-EDP or GSK2256294, a soluble epoxide hydrolase (sEH) inhibitor. Relative expression of TNFα, IL-1β, IL-6, and IL-8 was assayed via qRT-PCR and NFκB-dependent transcription was tested using a luciferase assay. Data were analyzed using ANOVA with Tukey’s multiple comparisons post-hoc test. ResultsCYP inhibition by SKF-525a increased hMC expression of inflammatory cytokines. Exogenous 11,12-EET and 19,20-EDP both significantly decreased PA- and IL-1β-induced hMC expression of IL-1β and IL-6. Both epoxygenated fatty acids significantly decreased IL-8 expression in IL-1β-induced hMC and TNFα in PA-induced hMC. Interestingly, 11,12-EET and 19,20-EDP significantly increased TNFα in IL-1β-treated hMC. GSK2256294 significantly reduced PA- and IL-1β-stimulated hMC cytokine expression, demonstrating efficacy over a range of concentrations. 11,12-EET and 19,20-EDP were also found to decrease PA- and IL-1β-induced NFκB-dependent transcriptional activity.ConclusionsIn summary, these data suggest that experimental elevation of 11,12-EET and 19,20-EDP decreases MC inflammation occurring under diabetes-relevant conditions and may represent a viable therapeutic strategy for inhibition of early retinal inflammation in DR. Our data suggest that these epoxygenated fatty acids exert their anti-inflammatory activities, at least in part, by blocking NFκB-dependent transcription.
Upregulation of ICAM-1 and HLA-G Genes Expression in Cumulus Cells of Infertile Women with Poor Response to Ovarian Stimulation with a Healthy Lifestyle
Authors: Aftabsavad Somayeh , Noormohammadi Zahra , Moini Ashraf , Karimipoor Morteza
Published: November 2020

Purpose: Diagnosis of women with poor ovarian response (POR) to exogenous gonadotropin stimulation is a challenge for reproductive specialists. This study aimed to investigate the expression profile for ICAM-1 and HLA-G genes in the cumulus cells of infertile women with POR based on their healthy lifestyle. Methods: Eighty women under the age of 35 were enrolled and divided into two groups: 1- POR without a healthy lifestyle (n=40) and POR with a healthy lifestyle (n=40). The ICAM-1 and HLA-G genes expression was compared by the quantitative PCR between the groups. The ICAM-1 and HLA-G protein levels were analyzed by the western blotting technique, and the methylation pattern was investigated by the methylation-specific PCR.Results: The qRT-PCR assay showed that ICAM-1 and HLA-G genes were differentially expressed between the two groups studied. ICAM-1,HLA-G genes,and proteins expressions in POR with healthy lifestyle were upregulated compared to the second group (P<0.05). ICAM-1 and HLA-G DNA methylation status in the POR with a healthy lifestyle were decreased compared to the other group (P<0.05). The oocyte quality and clinical pregnancy ratio were significantly higher in the POR with a healthy lifestyle women than in the other ones (P<0.05). Conclusion: Theupregulation of ICAM-1 and HLA-G in POR women is probably related to lifestyle. Lifestyle may affect the methylation pattern, protein levels and alteration of gene expression profiles in the cumulus cells of POR women. Additionally, lifestyle may be considered a marker for ovulation, oocyte maturation, preimplantation and clinical pregnancy process.
CircRNA circFADS2 is Under-expressed in Sepsis and Protects Lung Cell From LPS-induced Apoptosis by Downregulating miR-133a
Authors: Niu Fang , Liang Xiaofeng , Ni Jindi , Xia Zhuye , Jiang Lijing , Wang Hong , Liu Hongjie , Shen Guofeng , Li Xiang
Published: November 2020

Background: It has been reported that circFADS2 and miR-133a play opposite roles in LPS-induced cell apoptosis, which contributes to the development of sepsis. This study was carried out to explore the interaction between circFADS2 and miR-133a in sepsis. Methods: Expression of circFADS2 and miR-133a in plasma from both sepsis patients (n=62) and healthy controls (n=62) was studied by RT-qPCR. The effects of LPS on the expression of circFADS2 and miR-133a were also analyzed by RT-qPCR. The crosstalk between circFADS2 and miR-133a was analyzed by overexpression, followed by RT-qPCR. The role of circFADS2 and miR-133a in regulating the apoptosis of lung cells induced by LPS was analyzed by cell apoptosis assay.Results: We found that circFADS2 was under-expressed in sepsis and miR-133a was overexpressed in sepsis. An inverse correlation between circFADS2 and miR-133a was observed across sepsis samples. In lung cells, LPS treatment decreased the expression of circFADS2 and increased the expression of miR-133a. In lung cells, circFADS2 overexpression decreased the expression of miR-133a. Moreover, circFADS2 overexpression reduced the enhancing effects of miR-133a overexpression on cell apoptosis induced by LPS. Conclusion: Therefore, circFADS2 is under-expressed in sepsis and may protect lung cell from LPS-induced apoptosis by downregulating miR-133a.
Treatment of Venous Thromboembolism in Cancer Patients: A Systemic Review and Meta-analysis on the Efficacy and Safety of Different DOACs
Authors: Song Xiaojun , Liu Zhili , Zeng Rong , Shao Jiang , Liu Bao , Zheng Yuehong , Liu Changwei , Ye Wei
Published: November 2020

Background: To evaluate the efficacy and safety of different direct oral anticoagulants (DOACs) compared with low molecular weight heparin (LMWHs) in the treatment of venous thromboembolism (VTE) in cancer patients.Methods: Literature was searched in databases including Cochrane Library, EMBASE (Ovid) and MEDLINE (Pubmed). Eligible studies were included and data were collected independently by two reviewers. We conducted a systemic review of the efficacy and safety of DOACs in the treatment of VTE in cancer patients. The odds ratios of different DOACs compared with LMWHs for VTE, DVT, PE recurrences, major bleeding and clinically relevant non-major bleeding (CRNMB) were calculated in meta-analyses and subgroup analyses.Results: A total of 18 articles were eligible for analyses, including 4 randomized controlled trials (RCTs) and 14 retrospective studies. Both RCTs and retrospective studies confirmed that DOACs decreased the risk of VTE recurrence (RCTs: OR, 0.60; 95%CI, 0.45-0.80; retrospective studies: OR, 0.73; 95%CI, 0.59-0.90) and DVT recurrence (RCTs: OR, 0.54; 95%CI, 0.36-0.80; retrospective studies: OR, 0.20; 95%CI, 0.06-0.63), but not PE recurrence or fatal PE in cancer patients. Subgroup analyses revealed an important role of rivaroxaban in decreasing recurrent VTE. Meanwhile, major bleeding events were not increased in the DOAC group, but the risk of CRNMBs were significantly elevated. Subgroup analyses confirmed the role of rivaroxaban in increasing the risk of major bleeding events and CRNMBs. Conclusions: Compared with LMWHs, DOACs, especially rivaroxaban, significantly reduced the risk of VTE and DVT, rather than PE, recurrence in patients with cancer. Although DOACs did not increase the major bleeding events in pooled analysis, rivaroxaban was showed an elevated risk of this adverse effect in subgroup analysis. In addition, the risk of CRNMB events was increased after the application of DOACs including rivaroxaban.
Warfarin Versus Direct Oral Anticoagulants for Treating Left Ventricular Thrombus: A Systematic Review and Meta-Analysis
Authors: Dalia Tarun , Lahan Shubham , Ranka Sagar , Goyal Amandeep , Zoubek Sara , Gupta Kamal , Shah Zubair
Published: November 2020

Background: Left ventricular thrombus (LVT) is not uncommon and pose a risk of systemic embolism, which can be mitigated by adequate anticoagulation. Direct oral anticoagulants (DOACs) are increasingly being used as alternatives to warfarin for anticoagulation, but their efficacy and safety profile has been debated. We aim to compare the therapeutic efficacy and safety of DOACs versus warfarin for the treatment of LVT.Methodology: We systematically searched PubMed/Medline, Google Scholar, Cochrane library, and LILCAS databases from inception to 14th August 2020 to identify relevant studies comparing warfarin and DOACs for LVT treatment and used the pooled data extracted from retrieved studies to perform a meta-analysis.Results: We report pooled data on 1955 patients from 8 studies, with a mean age of 61 years and 59.7 years in warfarin and DOACs group, respectively. The pooled odds ratio for thrombus resolution was 1.11 (95% CI 0.51–2.39) on comparing warfarin to DOAC, but it did not reach a statistical significance (p = 0.76). The pooled risk ratio (RR) of stroke or systemic embolization and bleeding in patients treated with warfarin vs DOACs was 1.04 (95% CI 0.64–1.68; p = 0.85), and 1.15 (95% CI 0.62–2.13; p = 0.57), respectively; with an overall RR of 1.09 (95% CI 0.70–1.70; p =0.48) for mortality.Conclusions: DOACs appears to be non-inferior or at least as effective as warfarin in the treatment of left ventricular thrombus without any statistical difference in stroke or bleeding complications.
Evaluation on the Diagnostic Efficiency of Different Methods in Detecting COVID-19.
Authors: Yang Haitao , Lan Yuzhu , Yao Xiujuan , Lin Sheng , Xie Baosong
Published: November 2020

Objective: To evaluate the diagnostic efficiency of different methods in detecting COVID-19.Methods: PubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC. Results: 18 articles (3648 cases) were included. EPlex: pooled sensitivity was 0.94; specificity 1.0; PLR 90.91; NLR 0.07; DOR 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity 0.98; PLR 42.46; NLR 0.02; DOR 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity 0.97; PLR 26.67; NLR 0.01; DOR 3100.93; AUC=0.9970, Q*=0.9800. Cobas®: pooled sensitivity was 0.99; specificity 0.96; PLR 37.82; NLR 0.02; DOR 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity 0.99; PLR 36.22; NLR 0.04; DOR 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity 0.97; PLR 27.44; NLR 0.01; DOR 3488.15; AUC=0.9977, Q*=0.9829.Conclusions: These methods (ePlex, Panther Fusion, Simplexa, Cobas®, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.