bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traditional Chinese Medicine Based On Tongjiang Methodology Combined With Proton Pump Inhibitors (PPIs) De-Escalation In Treating Non-Erosive Reflux Disease: A Study Protocol For A Multicentred, Randomized Controlled Clinical Trial
Authors: Li Xia , Wu Haomeng , Chen Ting , Zhang Beihua , Shi Xiaoshuang , Ma Jinxin , Zhang Jiaqi , Tang Xudong , Wang Fengyun 
Published: September 2021

Abstract
Background: Non-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation, but an absence of oesophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPIs de-escalation therapy for NERD patients who did not respond to PPIs alone. Method: This multicentred, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPIs de-escalation group (n=87) and the TCM granules placebo combined with PPIs de-escalation group (n=87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status and quality of life at each visit. The primary outcome measurements include Visual Analogue Scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD–HRQL and TCM syndromes scales.Discussion: Previous research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients’ physical and psychological burdens, and achieve good social benefits.Trial registration number: Clinicaltrials.gov: NCT04340297
Future Challenges in Medical Education System in COVID-19 Pandemic: Scenario Planning
Authors: Rezaee Rita , Pourmohammadi Kimia , Bordbar Najmeh , Ghorbanian Azimeh , Kojouri Javad , Shieh Hajar , Salehi Nasim , Mohammadpour Mohammadtaghi 
Published: September 2021

Abstract
Background: With the outbreak of the COVID-19 pandemic, all the aspects of educational institutions such as universities have been affected. Trainings have changed from face-to-face and physical to online and digital. Therefor an educational reform has been recognized as a priority toward adaptation of universities with the current situation and transition to third-generation universities in order to synchronize with global trends. This study evaluated the preparedness of universities to manage the outbreak and moving toward a new generation, using the scenario planning approach. Methods: A mixed method design was used including three phases: 1) Identifying the variables affecting the future of medical education, 2) Prediction and building scenarios (future estimates), 3) Building the future (scenario-making).Results: The COVID-19 pandemic represents an enduring transformation in education with the advancement of smart universities, telehealth, adaptive research protocols, personalized and self-controlled learning and flexible approaches to achieve solutions. Conclusions: It is Inevitable that in this situation, the future of this path, must be clarified and a joint vision (scenarios) must be created. It is suggested that educational and environmental key factors should be constantly monitored to keep up with the process of managing the situation, globalization and the expansion of entrepreneurial universities.
Combined Recession–Resection of The Superior Rectus Muscle in the Treatment of Dissociated Vertical Deviation.
Authors: Mattout Hala Kamal , Fouda Sameh Mosaad 
Published: September 2021

Abstract
Purpose

This is retrospective study that evaluates the use of combined recession-resection of the superior rectus muscle in the treatment of dissociated vertical deviation (DVD)
Methods

The medical records of 21 patients with bilateral DVD were retrospectively reviewed. Preoperative data were extracted for age, gender, BCVA (logMAR), amblyopia, angle of stereopsis, previous strabismus surgeries and angle of deviation. All included patients received resection of 2.5 mm of the superior rectus muscle prior to its recession in an amount determined by the maximum DVD angle. The main outcome measure was postoperative angle of DVD at the end of six postoperative months and success was identified as absence of manifest DVD .
Results

The mean angle of preoperative DVD was 18.09 PD in the right eye and 16.76 PD in the left ‎eye‎. The mean amount of SR recession was 8.9 ‎±1.4 ‎mm in the right e‎‎ye and 8.7 ‎±1.5 in the left ‎eye with symmetrical surgery performed in only 7 patients. Mean postoperative angle of DVD was ‎5.96‎ in the right eye and ‎5.86 ‎in the left eye. Surgical success was achieved in 15 patients (71%).
Conclusions

Combined recession-resection of the superior rectus muscle seems to be an effective technique in the management of DVD and could represent a good alternative to other surgical procedures.
Polymorphism Analysis and Expression Profile of the Estrogen Receptor 2 Gene in Leizhou Black Duck
Authors: Asiamah Collins Amponsah , Liu Yuanbo , Ye Rungen , Pan Yiting , Lu Li-li , Zhao Zhihui , Su Ying 
Published: September 2021

Abstract
BackgroundOur previous study on the ovarian transcriptomic analysis in Leizhou black duck revealed that the ESR2 gene was involved in hormone regulation in reproduction and the estrogen signaling pathway related to reproductive performance was enriched. This suggested that ESR2 may have a functional role in the reproductive performance of the Leizhou black duck. Thus, this study aimed at evaluating the polymorphism of the ESR2 gene and its association with egg-laying traits and the distribution pattern of ESR2 mRNA in laying and non-laying Leizhou black ducks. MethodIn this study, genomic DNA was extracted from blood samples of 101 Leizhou black ducks to identify single nucleotide polymorphisms (SNPs) of the ESR2 gene to elucidate molecular markers highly associated with egg-laying traits. Four (4) each of laying and non-laying Leizhou black ducks were selected to collect different tissues to analyze the ESR2 gene expression. ResultsA total of 23 SNPs were identified and association analysis of the single SNP sites showed that SNPs g.56805646 T>C and exon 3-20G>A were significantly (P < 0.05) associated with egg weight. Ducks with CT and AG genotypes had significantly higher (P < 0.05) egg weights than their respective other genotypes. Haplotype association analysis of g.56805646 T>C and exon 320G>A showed that the haplotypes were significantly associated with egg weight where higher egg weight was seen in individuals with H3H4 haplotypes. In the hypothalamus-pituitary-gonadal (HPG) axis, the results of qRT/PCR showed that ESR2 mRNA was significantly (P < 0.05) expressed in the ovaries of both duck groups than in the hypothalamus and pituitary. In the oviduct, ESR2 was significantly (P < 0.05) higher in the infundibulum and magnum of laying and nonlaying ducks respectively. ConclusionThis study provides molecular marker for selecting Leizhou black ducks for egg production and provides theoretical knowledge for the study of the related biological functions of the ESR2 gene at the cellular level.
Immunohistochemistry and Expression Profile of Estrogen Receptor 2 Gene in Different Grade Size Ovarian Follicles of Leizhou Black Ducks
Authors: Asiamah Collins Amponsah , Liu Yuanbo , Ye Rungen , Pan Yiting , Lu Li-li , Zhao Zhihui , Su Ying 
Published: September 2021

Abstract
BackgroundEstrogen receptor 2 (ESR2) plays significant biological roles in the reproductive system and ovarian follicle development. This study, therefore, aimed to reveal the expression pattern and cell-specific localization of ESR2 in the ovarian follicles of Leizhou black ducks. MethodFour laying Leizhou black ducks at 43 weeks old were annihilated and different grade-sized follicles were collected for immunohistochemistry and expression profile study. The follicles were grouped into seven (7) as small white follicles (SWF), large white follicles (LWF), small yellow follicles (SYF), large yellow follicles (LYF), follicle 5 (F5), follicle 2 (F2), and follicle 1 (F1). ResultsThe qRT/PCR results displayed that ESR2 mRNA was expressed in all follicles with the highest (P < 0.05) level of expression found in F1 compared to other follicles. Immunohistochemistry analysis of the cell-specific localization of ESR2 protein revealed that ESR2 was distributed in both granulosa and theca cells region in all the follicles examined. There was a significantly higher localization of ESR2 protein in the granulosa cells than the theca cells of SWF, SYF, LYF, F2, and F1. Comparatively, ESR2 was highly expressed in the granulosa cells of LYF than in all the other follicles. ConclusionThese results provide theoretical knowledge for the in-depth study of the related biological functions of the ESR2 gene and its application at the cellular level.
Camrelizumab In Patients With Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Cost-Effective Analysis In China
Authors: Xie Qian , Zheng Hanrui , Su Na , Li Qiu 
Published: September 2021

Abstract
Background Camrelizumab is a selective, humanized, high-affinity IgG4 kappa monoclonal antibody against programmed cell death 1 (PD-1) that shows effective antitumor activity with acceptable toxicity in multiple tumor types. The CameL trial demonstrated that camrelizumab plus chemotherapy significantly prolonged the median progression-free survival (PFS) and median overall survival (OS) versus chemotherapy alone in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Because of a rapid cancer burden increase in China, our study was conducted to investigate the cost-effectiveness of the two strategies in chemotherapy-naive patients with advanced non-squamous NSCLC.Methods A Markov simulation model was generated based on the CameL trial. The two simulated treatments included camrelizumab plus chemotherapy (CC) and chemotherapy alone (CA). Utility was derived from published literature, and costs were calculated based on those at our hospital in Chengdu, China. Incremental cost-effectiveness ratios (ICERs) were calculated to compare the cost-effectiveness of the two treatment arms.Results The total costs were $64,874.51 and $13,531.38 for CC and CA treatment, respectively. The CC treatment produced 1.19 quality-adjusted life years (QALYs), and the CA treatment produced 0.96 QALYs. Hence, patients who were in the CC group spent an additional $51,343.44 and generated an increase of 0.23 QALYs, resulting in an ICER of $223,232.35 per QALY. Currently, in China, CC treatment is not cost-effective when considering a willingness-to-pay (WTP) threshold of $28,130 per QALY gained.Conclusions For chemotherapy-naive patients with advanced non-squamous NSCLC, camrelizumab plus chemotherapy is not considered a cost-effective therapy versus chemotherapy alone in China.
Associations of Bisphenol Exposure With The Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study In Guangxi, China
Authors: Tang Peng , Liang Jun , Liao Qian , Huang Huishen , Guo Xiaojing , Lin Mengrui , Liu Bihu , Wei Bincai , Zeng Xiaoyun , Liu Shun , Huang Dongping , Qiu Xiaoqiang 
Published: September 2021

Abstract
A growing number of epidemiologic studies have estimated the associations between endocrine-disrupting chemicals and gestational diabetes mellitus (GDM). However, reports on the association between bisphenol A (BPA) substitutes and GDM are limited. This investigation aimed to explore the associations of maternal serum BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) with the risk of GDM. A nested case-control study was performed among 500 pregnant women. Associations between the serum bisphenol levels and the risk of GDM were assessed by conditional logistic regression analysis and two-mixture modeling approaches (Bayesian kernel machine regression [BKMR] and quantile g-computation). BPA and TBBPA were negatively associated with the risk of GDM in the adjusted models, respectively. Intermediate BPS levels were associated with increased odds (OR: 1.84; 95% CI: 1.04, 3.27) of GDM compared with the low concentration groups only based on the single-bisphenol models. Associations between BPA, BPS, and TBBPA with the risk of GDM were also found in the BKMR analysis. The quantile g-computation (OR: 0.55; 95% CI: 0.43, 0.69) and BKMR models revealed a statistically significant and negative joint effect of the five bisphenols on the risk of GDM. This study demonstrates the association between exposure to BPS with the increased risk of GDM. In addition, exposure to BPA and TBBPA were associated with the reduced risk of GDM. Moreover, exposure to the mixture of the five bisphenols was negatively associated with the risk of GDM.
Berberine Inhibits FoxM1 Dependent Transcriptional Regulation of POLE2 and Interferes with the Survival of Lung Adenocarcinoma
Authors: Ni Lulu , Sun Ping , Fan Xiaochun , Li Zhongjie , Ren Hongli , Li Jiangan 
Published: September 2021

Abstract
Background：Berberine is one of the most interesting and promising natural anticancer drugs. POLE2 is involved in many cellular functions such as DNA replication and is highly expressed in a variety of cancers. However, the specific molecular mechanism of berberine interfering with POLE2 expression in lung adenocarcinoma (LUAD) is still unknown to a great extent.Method:The KEGG database (Release 91.0) and Gene Ontology (GO) category database were used for functional annotation of differentially expressed genes after berberine treatment. Reproducibility assessment using TCGA dataset. The biological functions of berberine in LUAD were investigated by a series of in vitro and in vivo experiments: MTT, colony formation, mouse xenograft and plasmid transfection. The molecular mechanisms of berberine were demonstrated by plasmid transfection, quantitative RT-PCR and Western blotting.Result:The elevated expression of FoxM1 and the high enrichment of DNA replication pathway were confirmed in LUAD by microarray and TCGA analysis, and were positively correlated with poor prognosis. Functionally, berberine inhibited the proliferation and survival of LUAD cell lines in vitro and in vivo. Mechanistically, berberine treatment down regulated the expression of FoxM1which closely related to survival, survival related genes in cell cycle and DNA replication pathway, and significantly down regulated the expression of survival related POLE2. Interestingly, we found that the transcription factor FoxM1 could act as a bridge between berberine and POLE2.Conclusion: Berberine significantly inhibited LUAD progression via the FoxM1/POLE2, and FoxM1/POLE2 may act as a clinical prognostic factor and a therapeutic target for LUAD. Berberine may be used as a promising therapeutic candidate for LUAD patients.
Prescribed Fire Limits Wildfire Severity Without Altering Ecological Importance for Birds
Authors: Latif Quresh , Saab Victoria , Dudley Jonathan 
Published: September 2021

Abstract
Background: Fire suppression and anthropogenic land use have increased severity of wildfire in dry conifer forests. Mangers use fuels reduction (e.g., prescribed fire) to limit high-severity wildfire and restore ecological function to fire-adapted dry conifer forests. Many species that evolved in these forests, however, are adapted to high-severity wildfire. To fully understand the ecological implications of fuels reduction treatments, we need to understand direct treatment effects and how treatments modulate subsequent wildfire effects on natural communities. We studied bird population and community patterns over 9 years, including unburned (2002–2003), after prescribed fire (2004–2007), and after wildfire (2008–2010). We used a before-after, control-impact (BACI) approach to analyze shifts in species occupancy and richness with respect to treated units following prescribed fire and burn severity following wildfire.Results: We found both positive and negative wildfire and prescribed fire effects on birds largely consistent with species life history traits; several woodpecker species, secondary cavity-nesting species, aerial insectivores, and understory species exhibited positive effects, whereas open cup canopy-nesting species and foliage- or bark-gleaning insectivores exhibited negative effects. Also as expected, wildfire affected more species more consistently through time than did prescribed fire. Wildfire burned units initially treated with prescribed fire less severely than untreated units, but wildfire effects on birds were similar regardless of treatment.Conclusions: Our results suggest managers can employ prescribed fire to reduce wildfire severity without necessarily altering the ecological importance of wildfire to birds. Additional study of the ecological implications of various fuels reduction practices, representing a range of intensities and fire regimes, would further inform forest management that includes biodiversity objectives.
The Effect of Governance On Entrepreneurship: From All Income Economies Perspective
Authors: Abegaz Mekonnen Bogale , Debela Kenenisa Lemi , Hundie Reta Megersa 
Published: September 2021

Abstract
The purpose of this study is to analyze the effect of governance indicators on Entrepreneurship. Explanatory research design with Pearson correlation and multiple linear regression models were applied. Five-year World Bank data (2014–2018) of 126 countries from all economic development levels were used. Worldwide governance indicators considered are voice and accountability, political stability, government effectiveness, regulatory quality, rule of law, and corruption control. Gross net income was taken as a control variable. To measure entrepreneurship, the number of formally registered limited liability businesses as a percentage of the working-age population, was used. To make highly skewed time series data of dependent variable (entrepreneurship) closer to normal, logarithmic transformation was made and heteroscedasticity of residuals was checked. The finding of Pearson correlation shows that there are strong and significant correlations(r > 0.466, p < 0.01) between predictors and the outcome variable and among predictor variables. Regression analysis was computed after two highly collinear variables were dropped from the model using the VIF test. The study found that the remaining four independent variables and the control variable predict 71.5% of the variance in the outcome variable. Except for voice and accountability, all predictors have their own statistically significant influence on entrepreneurship. Thus, working on each predictor up to the standard application can bring incremental changes in new business formation and entry. The researchers believe that this study is of significant interest to policymakers, program developers, entrepreneurs, analysis, and supporters since it provides useful insight on how governance indicators influence entrepreneurship.
Machine Learning based Self-sensing the Stiffness of Shape Memory Coil Actuator
Authors: Sul Bhagoji B. , Dhanalakshmi K. 
Published: September 2021

Abstract
Self-sensing actuation (SSA) assists in sensing the vital property of the shape memory coil which can be used to monitor and control the actuation. The stiffness characteristic of the shape memory coil is sensed during actuation which plays a significant role in development of Intelligent Robotics in defense systems. The electrical property of shape memory coil such as electrical resistance changes due to martensitic phase transformation which is further used to sense the mechanical properties such as strain, stress, temperature, length, and force. Nowadays electrical properties are used to sense the stiffness of the shape memory coil. As of now, there is no well-established analytical model to predict the stiffness of sensing during actuation accurately. Therefore, Machine Learning (ML) based data-driven intelligent model is proposed in this paper for auto-sensing of the stiffness. The experimental facility has been developed for the collection of data with respect to diverse Joule heating currents. To determine the experimental data values of stiffness and electrical resistance of shape memory coil is a cumbersome task. Hence we have proposed an automated method to predict the stiffness of the shape memory coil using ML methods. The Classical Polynomial and Feedforward Neural Network (FFNN) models are developed for analyzing the stiffness of the shape memory coil. It is found that FFNN model outperforms the other ML based model by attaining 95.2650 % accuracy. The FFNN model is also able to explain almost all the predicted stiffness values which are experimentally recorded. The FVU (Fraction Variance Unexplained) statistical parameter explains the prediction of FFNN with the value of 0.0842. The great advantage of the ML model is to replace two sensors (Force and displacement sensors) with one soft sensor (ML model). It will be useful in the controlling robotics and other devices which require high precision in data generated by the sensors.
Concurrent Metformin Use and Survival Among Finnish Non-Small Cell Lung Cancer Patients Treated With EGFR TKIs
Authors: Tiainen Satu , Iivanainen Sanna , Alanen Virve , Arffman Martti , Koivunen Jussi P. 
Published: September 2021

Abstract
Purpose

Many studies have shown correlation between metformin use and lower incidence and improved outcomes of lung cancer. We investigated the potential association between metformin use and survival among Finnish non-small cell lung cancer (NSCLC) patients treated with EGFR TKIs.
Methods

Nationwide registries were utilized to identify all the patients with use of EGFR TKIs in NSCLC between 2011–2016, and 1242 patients were included in further analyses. Data related to cancer, survival, and drug purchases were combined with personal identity codes. Concurrent use of diabetes medications was defined as their purchase +/-120 days from the first purchase of EGFR TKI. The impact of diabetes medication use was investigated separately in the whole and in the EGFR mutant type cohort (n = 481).
Results

Concurrent metformin use was found in 10 % (n = 124) and use of other diabetes medication in 5 % (n = 60) of the patients. In the whole patient cohort, metformin use did not associate with survival but in the EGFR mutant type cohort a non-significant trend for higher mortality was found (HR 1.42, 95% CI 0.99–2.02). Metformin use associated also with a shorter EGFR TKI treatment duration (HR 1.26, 95 % CI 1.04–1.52). The use of other diabetes medication than metformin did not associate with survival or EGFR TKI treatment duration.
Conclusion

Concomitant metformin use associated with a shorter EGFR TKI treatment duration, however, no statistically significant correlation with survival was found. Ethnicity, comorbidities, and metformin dosage may influence on the associations found between metformin use and EGFR TKI treatment responses.