bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stopping smoking advice given by practice assistants after routine cervical screening in general practice: a qualitative exploration of potential barriers and enablers.
Authors: Mansour Marthe B.L. , Crone Matty R. , Weert Henk C. van , Chavannes Niels H. , Asselt Kristel M. van 
Published: April 2020

Abstract
The authors have withdrawn this preprint due to author disagreement.
Multivariate joint modeling to identify markers of growth and lung function decline that predict cystic fibrosis pulmonary exacerbation onset
Authors: Andrinopoulou Eleni-Rosalina , Clancy John Paul , Szczesniak Rhonda 
Published: April 2020

Abstract
Background: Attenuated decreases in lung function can signal the onset of acute respiratory events known as pulmonary exacerbations (PEs) in children and adolescents with cystic fibrosis (CF). Univariate joint modeling facilitates dynamic risk prediction of PE onset and accounts for measurement error of the lung function marker. However, CF is a multi-system disease and the extent to which simultaneously modeling growth and nutrition markers improves PE predictive accuracy is unknown. Furthermore, it is unclear which routinely collected clinical indicators of growth and nutrition in early life predict PE onset in CF. Methods: Using a longitudinal cohort of 17,100 patients aged 6-20 years (US Cystic Fibrosis Foundation Patient Registry; 2003-2015), we fit a univariate joint model of lung-function decline and PE onset and contrasted its predictive performance with a class of multivariate joint models that included combinations of growth markers as additional submodels. Outcomes were longitudinal lung function (forced expiratory volume in 1 s of % predicted), percentiles of body mass index, weight-for-age and height-for-age and PE onset. Relevant demographic/clinical covariates were included in submodels. We implemented a univariate joint model of lung function and time-to-PE and four multivariate joint models including growth outcomes. Results: All five joint models showed that declining lung function corresponded to slightly increased risk of PE onset (hazard ratio from univariate joint model: 0.97, P < 0.0001), and all had reasonable predictive accuracy (cross-validated area under the receiver-operator characteristic curve > 0.70). None of the growth markers alongside lung function as outcomes in multivariate joint modeling appeared to have an association with hazard of PE. Jointly modeling only lung function and PE onset yielded the most accurate (area under the receiver-operator characteristic curve = 0.75) and precise (narrowest interquartile range) predictions. Dynamic predictions were accurate across forecast horizons (0.5, 1 and 2 years) and precision improved with age. Conclusions: Including growth markers via multivariate joint models did not yield gains in prediction performance, compared to a univariate joint model with lung function. Individualized dynamic predictions from joint modeling could enhance physician monitoring of CF disease progression by providing PE risk assessment over a patient’s clinical course.
Exploration of Anti-inflammatory Mechanism of Forsythiaside A and Forsythiaside B in CuSO4-Induced Inflammation in Zebrafish by Metabolomic and Proteomic Analyses
Authors: Gong Lihong , Yu Linyuan , Gong Xiaohong , Wang Cheng , Hu Naihua , Dai Xuyang , Li Yunxia 
Published: April 2020

Abstract
Background: Inflammation is a general pathological phenomenon during severe disturbance of homeostasis. Forsythiaside A (FA) and Forsythiaside B (FB) are phenylethanoid components isolated from dried fruits of Forsythia suspensa (Thunb.) Vahl., which show a significant effect against inflammation. However, the anti-inflammatory properties and therapeutic mechanisms of FA and FB have not yet been systematically clarified. Methods: In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced inflammation in zebrafish. Intracellular ROS and NO generation in zebrafish were investigated using fluorescent probes. Metabolomics and proteomics analyses using liquid chromatography mass spectrometry were carried out to identify the expressions of metabolites and proteins associated with the treatment of FA and FB in CuSO4-induced inflammation in zebrafish larvae. Quantitative polymerase chain reaction (PCR) was performed to detect the progressive changes in genes. Results: FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish. Metabolomic analysis indicated that Nicotinate and nicotinamide metabolism, Energy metabolism, Pyrimidine metabolism and Purine metabolism were mainly involved. Proteomic analysis identified 146 differentially expressed proteins between control and model group. The changed expressions of Collagen (collagen type II alpha 1b precursor (col2a1b), collagen alpha-2(IX) chain precursor (col9a2), collagen type IX alpha I precursor (col9a1b)), nucleoside diphosphate kinase 3 isoform X1 (Nme3), WD repeat-containing protein 3 (Wdr3), 28S ribosomal protein S7 mitochondrial precursor (Mrps7) in model group were all reversed after being treated by FA or FB. FA and FB could reverse the abnormal expressions of potential metabolite and protein biomarkers to alleviate CuSO4 damage to the neuromasts in the lateral line of zebrafish. Conclusions: Our results indicated that FA and FB possessed remarkable anti-inflammatory activities against CuSO4-induced neuromasts damage in zebrafish larvae, and suggested a multi-component and multi-regulatory therapeutic mechanism of FA and FB.
Cytokine profile in the sputum of subjects with post-tuberculosis airflow obstruction and in those with tobacco related chronic obstructive pulmonary disease
Authors: Guiedem Elise , Pefura-Yone Eric Walter , Ikomey George Mondinde , Nkenfou Céline , Mesembe Martha , Mbanyamsig Yivala Mispa , Bih Chende Hycenta , Greame Jacobs Brendon , Chegou Novel Njweipi , Okomo Marie Claire Assoumou 
Published: April 2020

Abstract
Background: Previous studies have shown that tuberculosis (TB) is a risk factor for chronic airflow limitation. Chronic obstructive pulmonary disease (COPD) is recognized as the result of chronic inflammation, usually related to noxious particles. Post-TB airflow obstruction and tobacco-related COPD have the same functional pathway characterized by persistent airflow limitation. We sought to compare the profile of 29 cytokines in the sputum of subjects with post-TB airflow obstruction and those with COPD related to tobacco.Results: The forced expiratory volume in the first second (FEV1) and forced expiratory volume/forced vital capacity (FEV/FVC) ratio were lower in the COPD patients with the history of smoking compared to the post-TB airflow obstruction subgroup. The stages of the disease were more advanced in COPD / tobacco patients. Among the cytokines, IL-1α, IL-1β, MIP-1β, sCD40L and VEGF levels were higher in COPD patients, compared to the controls with p values ​​of 0.003, 0.0001, 0.03, 0.0001 and 0.02 respectively. When the two COPD subgroups were compared, IL-1α, IL-6, TNF-α and IL-8 levels were higher in the COPD patients with the history of tobacco compared to the COPD patients with the history of TB with p-values ​​of 0.031, 0.05, 0.021 and 0.016, respectively. Conclusion: COPD related to tobacco is more severe than post-TB airflow obstruction. The pathogenesis of post-TB airflow obstruction appears to involve the cytokines IL-1RA, IL-1α, IL-1β, IL-17, GRO and sCD40L, while COPD related to tobacco involves more cytokines.
The Role of NMDA receptors in rat propofol self-administration
Authors: Chen Bei ping , Huang Xi-xi , Dong Dong-mei , Wu Hui , Zhu Tian-qi , WANG Ben-fu 
Published: April 2020

Abstract
Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.
The Relationship between Clinical Dishonesty and Perceived Clinical Stress among Nursing Students in Southeast of Iran
Authors: Rafati Foozieh , Bagherian Behnaz , Mangolian Parvin , Imani-Goghary Zahra 
Published: April 2020

Abstract
Background: Clinical dishonesty is a complex problem that threatens the health and safety of patients. This study aimed to investigate the relationship between clinical dishonesty and perceived clinical stress in nursing students. Method: This cross-sectional correlational study was conducted among 395 nursing students from 4 nursing colleges. Data were collected using a demographic information questionnaire, Nursing Student ' s Perception of Clinical Stressors, and a 12-item researcher-made questionnaire to evaluate the frequency of clinical dishonesty in the previous semester, the frequency of witnessing dishonest behavior among peers, and the perceived severity of behavior as unethical behavior. Results: In this study, 89.1% of the students had at least one dishonest clinical behavior in the previous semester. The frequency of clinical dishonesty was significantly correlated with the frequency of observing dishonesty among peers(r=0.053, p˂0.01), perceived severity of behaviors as unethical behavior(r=-0.4, p˂0.01), and perceived stress of students in the clinical setting(r=0.28, p˂0.01). Also, there was significant differences in the frequency of clinical dishonesty by gender (p=0.006), interest in the field of study (p=0.004) and academic year (p=0.002). Conclusion: The frequency of clinical dishonesty among nursing students is high and needs attention. Also, considering the positive relationship between dishonesty and perceived clinical stress, it is essential to teach effective strategies to nursing students to empower them to cope with clinical stress.
Building a Model for Predicting Target Gene Expression in Rice T-DNA Insertional Mutants by Machine Learning Approaches
Authors: Liao Chi-Chou , Chen Liang-Jwu , Lo Shuen-Fang , Chen Chi-Wei , Chen Jia-Jyun , Chu Yen-Wei 
Published: April 2020

Abstract
Background

T-DNA activation-tagging technology is widely used to enhance flanking gene expression near the site of insertion for functional genomics research in rice. However, whether the expression of a gene of interest is enhanced must be validated experimentally.
Results

In this study, we built a model to predict gene expression in T-DNA mutants by machine learning approaches, thereby improving the efficiency of screening for activated genes. We gathered experimental consisting of gene expression data in T-DNA mutants and captured the PROMOTER and MIDDLE sequences for encoding. In first-layer models, SVM models were constructed with nine features consisting of information about biological function and local and global sequences. Feature-encoding based on the PROMOTER sequence was weighted by logistic regression. The second-layer models integrated 16 first-layer models with feature selection and the algorithm, which were selected from nine feature selection methods and 65 classified methods, respectively. The accuracy of the final two-layer machine learning model, referred to as was 99.3% based on five-fold cross-validation, and 85.6% based on independent-testing.
Conclusion

We discovered that the information within the local sequence had a greater contribution than the global sequence with respect to classification had a good predictive ability for target genes within 20 from the 35S enhancer. Based on the analysis of significant sequences, the G-box regulatory sequence may also play an important role in the mechanism of activation of the 35S enhancer.
Roles of HDAC3-Orchestrated Circadian Clock Gene Oscillations in Diabetic Rats Following Myocardial Ischemia/Reperfusion Injury
Authors: Qiu Zhen , Ming Hao , Lei Shaoqing , Zhou Bin , Zhao Bo , Yu Yanli , Xue Rui , Xia Zhong-yuan 
Published: April 2020

Abstract
Background: Circadian clock has been closely related to the development of diabetes mellitus and cardiovascular disease; the disruption of circadian clock exacerbates myocardial ischemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop by recruitmenting the expression pattern of circadian nuclear receptor Rev-erbα, then to maintain the stability of circadian gene such as BMAL1. In this research, we explored the mechanism of HDAC3-orchestrated Rev-erbα/BMAL1 pathway in increasing MI/RI vulnerability of diabetes, and its relationship with mitophagy.Methods and results: Streptozocin (STZ) was used to establish type 1 diabetes by intraperitoneal injection. After 8 weeks, the diabetic and non-diabetic rats were exposed to MI/RI by ligating the left anterior descending coronary artery (LDA) for 30 minutes and reperfusion for 120 minutes at four time points of zeitgeber (ZT) 0, 6, 12 and 18. Circadian clock gene oscillations were rapidly attenuated in diabetic I/RI hearts, versus sham and/or the non-diabetic I/RI hearts, in accord with circadian mitophagy. By utilizing AAV-HDAC3 to knockdown HDAC3 expression, HDAC3 deficiency significantly attenuated diabetic MI/RI associated with increased autophagy activation. In vitro experiments, primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA exposed to hypoxia/reoxygenation (H/R). The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high glucose condition with decreased BMAL1 expression and autophagy level. After H/R stimulation, the cell injury was obviously increased with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 level. Moreover, high glucose aggravated H/R injury compared with low glucose by reducing autophagy level, increasing the levels of HDAC3 and Rev-erbα and down-regulating BMAL1 expression. HDAC3 and Rev-erbα siRNA can alleviate high glucose and H/R-induced injury by up-regulating BMAL1 expression and mitophagy levels.Conclusion: These findings suggest that in diabetic rat MI/RI , the circadian clocks were rapidly impaired then to inhibit mitophagy; cardiac-targeted manipulation of HDAC3-orchestrated Rev-erbα/BMAL1 pathway may be the mechanism of the decreased toleration to ischemia with a circadian dependent variability.
Sex Differences in Stress Reactivity to the Trier Social Stress Test in Virtual Reality
Authors: Liu Qing , Zhang Wenjuan 
Published: April 2020

Abstract
Background: The aim of the present study is to investigate the sex differences in stress reactivity to the Trier Social Stress Test (TSST) in a virtual reality(TSST-VR). Methods: Healthy young male (n = 30) and female (n = 30) undergraduates were randomly assigned to a psychosocial stress protocol (TSST) condition or to a non-stressful control condition (Placebo-TSST) under VR. Electrodermal activity (EDA), heart rate (HR) and heart rate variability (HRV) were measured throughout the study. The subjective scales of stress and emotion were also conducted. Results: The results showed that after VR, the stress group reported higher stress perceptions than the non-stress group. Compared with females, the males stronger EDA and higher HRV before the VR, and lower HR during VR as well as higher HRV after VR. The correlation between subjective and objective reactivity demonstrated that HRV during VR was negatively correlated to depression and negative affect. The HRV after VR was negatively correlated to the positive coping but was positively correlated to the depression. Conclusions: These findings suggest that the TSST-VR could be used as an available tool for testing gender differences to social stress induction in experimental settings. Compared with females, males were more sensitive to stress.
Estimated treatment effects of tight glycaemic targets in mild gestational diabetes mellitus: a multiple cut-off regression discontinuity study design.
Authors: Song David , Hurley James C , Lia Maryanne 
Published: April 2020

Abstract
Background
We investigated the treatment effects of tight glycaemic targets in a population universally screened according to the International Association of Diabetes and Pregnant Study Groups/World Health Organisation gestational diabetes mellitus (GDM) guidelines.
Methods
A multiple cut-off regression discontinuity study design in a retrospective observational cohort undergoing oral glucose tolerance tests (n = 1178). Treatment of GDM women with the targets: fasting glucose of ≤ 5.0 mmol/L and the 2-hour post-prandial glucose of ≤ 6.7 mmol/L.
Results
Treated GDM women had lower rates of large for gestational age 4.6% versus those just below diagnostic thresholds 12.6%, relative risk 0.37 (95% CI, 0.16–0.85); reduced caesarean section rates, 32.2% versus 43.0%, relative risk 0.75 (95% CI, 0.56–1.01). The subgroup analysis suggested that treatment of GDM women with BMI ≥ 30 kg/m2 drove the reduction in caesarean section rates: 32.9% versus 55.9%, relative risk 0.59 (95%CI, 0.4–0.87). Linear regression interaction term effects between non-GDM and treated GDM were significant for LGA (p = 0.001) and caesarean sections (p = 0.015).
Conclusions
Tight glycaemic targets reduced rates of large for gestational age and caesarean sections compared to a counterfactual group just below the diagnostic thresholds albeit at the expense of increased rates of neonatal hypoglycaemia, induced deliveries, and insulin usage.
School trajectory disruption among adolescents living with perinatal HIV receiving antiretroviral treatments: a case-control study in Thailand
Authors: Merville Ophélie , Puangmala Patcharee , Suksawas Pranee , Kliangpiboon Woranut , Keawvilai Waraporn , Tunkam Chorkanikar , Yama Suvimon , Sukhaphan Usa , Sathan Somporn , Marasri Siriporn , Rolland-guillard Louise , Sirirungsi Wasna , Coeur Sophie Le 
Published: April 2020

Abstract
Background: In the HIV/AIDS pandemic, the perinatally HIV-infected children, who are surviving to adolescence, constitute a particular group, with specific needs to manage HIV disease and to prepare their future. Adolescents living with perinatal HIV (ALPHIV) often experience difficult living circumstances that can impact educational achievement and thus, insertion in the adult life. We explore the school trajectories of ALPHIV and determine the relative contribution of HIV-infection and the contextual environment to their schooling situations.Methods: We used data from the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional case-control study, conducted from 2011 to 2014 in Thailand. We analysed data for 707 ALPHIV (cases) aged 12–19 years, receiving antiretroviral therapy in 20 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected in the general population and individually matched for sex, age and residence. Schooling disruption was defined as ≥1 year academic delay or early school dropout. Logistic regression was used to assess factors independently associated with schooling disruption and to estimate the attributable fraction of school disruption related to HIV-infection. We used multivariate imputations by chained equations to manage missing data and we performed two sensitivity analyses to evaluate the reliability of our main model.Results: ALPHIV were 5 times more likely to experience schooling disruption than controls after adjustment on sociodemographic factors ( ORA=5.2 [3.7-7.2]). About 50% of schooling disruption could be attributed to HIV-infection. Boys and adolescents living in institutions were more likely to experience schooling disruption (ORA =1.8 [1.3-2.4] and ORA =11.0 [7.7-15.8], respectively). Among ALPHIV, mental and growth delays were significantly associated with schooling disruption (ORA =3.3 [2.1-5.2] and =1.8 [1.3-2.6], respectively). For ALPHIV living in family, schooling disruption was also associated with stigmatization experiences (ORA =1.9 [1.2-3.1]) and caregiver’s low education (ORA =2.1 [1.1-3.9]). Conclusions: HIV and contextual factors combine to aggravate ALPHIV educational disadvantage. Further research is needed to clarify the pathways leading to a disrupted school trajectory among ALPHIV. The impact of this educational disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be explored in future research.
Loss of p53 expression in the gastric epithelial cells of Helicobacter pylori infected Jordanian patients
Authors: Abu-Lubad Mohammad A. , Helaly Ghada F. Helaly , Haddadin Weliam J. , Jarajreh Dua’a AK. , Aqel Amin A. , Al-Zeer Munir A. 
Published: April 2020

Abstract
Background: Helicobacter pylori infection is one of the most common chronic infections worldwide. Around half of the global population is chronically infected with this stomach bacterium. H. pylori infection is a strong risk factor for gastric cancer development. It is well-established that infection of the gastric epithelium with H. pylori induces the production of reactive oxygen species, DNA damage and accelerates the degradation of the tumor suppressor protein p53. This p53 dysregulation induced by H. pylori infection contributes to gastric carcinogenesis through complex processes including but not limited to cell proliferation and apoptosis. Methods: In the current study, we examined whether the epithelium of the gastric glands express p53 in subjects infected, chronically, with H. pylori. Seventy-five samples from Jordanian patients were analyzed for the presence of H. pylori as well as the p53 expression levels in the mucosa and submucosa by immunohistochemical analyses. Results: In H. pylori positive-specimens, p53-positive cells in the gastric mucosa were found significantly lower than in H. pylori negative-specimens. Conclusion: We demonstrated that p53 expression level is downregulated in gastric mucosa of patients from Jordan infected with H. pylori and this alteration may predispose individuals for possible tumor initiation in individuals chronically infected with H. pylori.