bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation abnormalities of imprinted genes in congenital heart disease: A pilot study
Authors: Chang Shaoyan , Wang Yubo , Xin Yu , Wang Shuangxing , Luo Yi , Wang Li , Zhang Hui , Li Jia 
Published: November 2020

Abstract
Background: Congenital heart disease (CHD) is resulted from the interaction of genetic aberration and environmental factors. Imprinted genes, which are regulated by epigenetic modifications, are essential for the normal embryonic development. However, the role of imprinted genes in the etiology of CHD remains unclear. Results: We investigated the alterations of imprinted gene germline differential methylation regions (gDMRs) methylation in patients with CHD. Eighteen imprinted genes that are known to affect early embryonic development were selected and the methylation modification genes were detected by massarray in 27 CHD children and 28 healthy children. Altered gDMR methylation level of 8 imprinted genes was found, including 2 imprinted genes with hypermethylation of GRB10 and MEST and 6 genes with hypomethylation of PEG10, NAP1L5, INPP5F, PLAGL1, NESP and MEG3. Stratified analysis showed that the methylation degree of imprinted genes was different in different types of CHD. Risk analysis showed that 6 imprinted genes, except MEST and NAP1L5, within a specific methylation level range were the risk factors for CHDConclusion: Altered methylation of imprinted genes is associated with CHD and varies in different types of CHD. Further experiments are warranted to identify the methylation characteristics of imprinted genes in different types of CHD and clarify the etiologies of imprinted genes in CHD.
A Digital Twin Framework For Analysing Students’ Behaviours Using Educational Process Mining
Authors: Azeta Ambrose , Agono Frank , Falade Adesola , Azeta ea , Nwaocha Vivian 
Published: November 2020

Abstract
Learning management systems (LMS) logs all actions taken on the system. These logs provide additional data about the activities and behaviour of users. Educational process mining techniques can use these data to unveil useful information to help instructors, educators and administrators accurately monitor, analyze and improve the online learning patterns of students. This research work presents a framework that uses process mining approach to analyse event log data generated within educational information systems, such as LMSs. In this framework, digital twin concept is employed to present a virtual representation of the students’ activities on the LMS. This framework also used inductive and fuzzy miner algorithms to produce a process model which was represented using virtual model of student’s learning patterns. This model was then evaluated for conformance with the activities observed in the log. The analysis conducted during this study showed the disparity between the behaviours of students that passed a particular course and students that failed the course. Findings also showed that the using the inductive and the fuzzy miner algorithms produced better fitness levels for the process model when compared with other previously used algorithms such as the heuristic miner and alpha miner algorithms. This paper concluded by recommending that the development of educational process mining specific tools can help domain experts better understand students’ learning patterns.
Prediction of enhancer-promoter interactions using the cross-cell information and domain adversarial neural network
Authors: Jing Fang , Zhang Shao-Wu , Zhang Shihua 
Published: November 2020

Abstract
Background: Enhancer-promoter interactions (EPIs) play key roles in transcriptional regulation and disease progression. Although several computational methods have been developed to predict such interactions, their performances are not satisfactory when training and testing data from different cell lines. Currently, it is still unclear what extent EPI prediction across cell lines can be made based on sequence-level information. Results: In this work, we present a novel Sequence-based method (called SEPT) to predict the Enhancer-Promoter interactions in the new cell line by using the cross-cell information and Transfer learning. SEPT first learns the features of enhancer and promoter from DNA sequences with convolutional neural network (CNN), then designing the gradient reversal layer of transfer learning to reduce the cell line specific features meanwhile retaining the features associated with EPIs. When the locations of enhancers and promoters are provided in new cell line, SEPT can successfully recognize EPIs in this new cell line based on labeled data of other cell lines. The experiment results show that SEPT can effectively learn the latent import EPIs-related features between cell lines and achieves the best prediction performance in terms of AUC. Conclusion: SEPT is an effective method for predicting EPIs in the new cell line. Domain adversarial architecture of transfer learning used in SEPT can learn the latent EPI features shared among cell lines from all other existing labeled data. It can be expected that SEPT will be of interest to researchers concerned with biological interaction prediction.
CircSOD2 induced epigenetic alteration drives hepatocellular carcinoma progression through activating JAK2/STAT3 signaling pathway
Authors: Zhao Zhongwei , Song Jingjing , Tang Bufu , Fang Shiji , Zhang Dengke , Zheng Liyun , Wu Fazong , Gao Yang , Chen Chunmiao , Hu Xianghua , Weng Qiaoyou , Yang Yang , Tu Jianfei , Ji Jiansong 
Published: November 2020

Abstract
Background：Emerging evidence suggests that circular RNAs play critical roles in disease development especially in cancers. Previous genome-wide RNA-seq studies found that a circular RNA derived from SOD2 gene was highly upregulated in hepatocellular carcinoma (HCC), however, the role of circSOD2 in HCC remains largely unknown. Methods: The expression profiling of circSOD2 and microRNA in HCC patients were assessed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). SiRNA or CRISPR-CAS9 were used to silence gene expression. The biological function of circSOD2 in HCC was investigated using in vitro and in vivo studies including, trans-well cell migration, cell apoptosis, cell cycle, CCK8, siRNA interference, western blots, and xenograft mouse model. The underlying molecular mechanism was determined by Chromatin Immunoprecipitation quantitative real time PCR (ChIP-qPCR), bioinformatic analysis, biotin-pull down, RNA immunoprecipitation, 5-mc DNA pulldown and luciferase assays. Results: In accordance with previous sequencing results, here, we demonstrated that circSOD2 was highly expressed in HCC tumor tissues compared with normal liver tissues. Mechanically, we showed that histone writer EP300 and WDR5 bind to circSOD2 promoter and trigger its promoter H3K27ac and H3K4me3 modification, respectively, which further activates circSOD2 expression. SiRNA mediated circSOD2 suppression impaired liver cancer cell growth, cell migration, prohibited cell cycle progression and in vivo tumor growth. By acting as a sponge, circSOD2 inhibits miR-502-5p expression and rescues miR-502-5p target gene DNMT3a expression. As a DNA methyltransferase, upregulated DNMA3a suppresses SOCS3 expression by increasing SOCS3 promoter DNA methylation. This event further accelerates SOCS3 downstream JAK2/STAT3 signaling pathway activation. In addition, we also found that activated STAT3 regulates circSOD2 expression in a feedback way. Conclusion: The novel signaling axis circSOD2/miR-502-5p/DNMT3a/JAK2/STAT3/circSOD2 provides a better understanding of HCC tumorigenesis. The molecular mechanism underlying this signaling axis offers new prevention and treatment of HCC.
4-week eicosapentaenoic acid-rich fish oil supplementation partially protects muscular damage following eccentric contractions
Authors: Tsuchiya Yosuke , Ueda Hisashi , Yanagimoto Kenichi , Kato Ayaka , Ochi Eisuke 
Published: November 2020

Abstract
Background: We previously showed 8-weeks of fish oil supplementation attenuated muscle damage. However, the effect of a shorter period of fish oil supplementation is unclear. The present study investigated the effect of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for 4 weeks on muscular damage caused by eccentric contractions (ECCs) of the elbow flexors.Methods: Twenty-two untrained men were recruited in this double-blind, placebo-controlled, parallel design study and the subjects were randomly assigned to the EPA and DHA group (EPA and DHA, n = 11) and placebo group (PL, n = 11). They consumed either EPA 600 mg and DHA 260 mg per day or placebo supplement for 4 weeks prior to exercise. Subjects performed 60 ECCs at 100% maximal voluntary contraction (MVC) using a dumbbell. Changes in MVC torque, range of motion (ROM), upper arm circumference, muscle soreness, echo intensity, muscle thickness, serum creatine kinase (CK), and interleukin-6 (IL-6) were assessed before exercise; immediately after exercise; and 1, 2, 3, and 5 days after exercise.Results: ROM was significantly higher in the EPA and DHA group than in the PL group immediately after performing ECCs (p < 0.05). No differences between groups were observed in terms of MVC torque, upper arm circumference, muscle soreness, echo intensity, and thickness. A significant difference was observed in serum CK 3 days after ECCs (p < 0.05).Conclusion: We concluded that shorter period EPA and DHA supplementation benefits joint flexibility and protection of muscle fiber following ECCs.
Knowledge, Attitude, And Perception of Oral and Maxillofacial Surgery Specialty Amongst Healthcare Professionals, and the General Public from a Gulf Cooperation Council (GCC) Country
Authors: Kamal Mohammad , Abdulwahab Mohammad , Al-Zaid Ahmed 
Published: November 2020

Abstract
Background: Oral and maxillofacial surgery specialty has grown rapidly in Kuwait in recent years. However, the general public and healthcare professionals remain unaware of its expanding scope of practice. The aim of the study is to assess public and professional (dental and medical) perception of the oral and maxillofacial surgical specialty in Kuwait.Methods: This is a cross-sectional study evaluating responses of dental professionals, medical professionals, and general public in Kuwait toward the oral and maxillofacial surgical specialty using a previously validated survey instrument with 100 participants in each group. Participants were asked to choose the most appropriate specialist to treat certain procedures across 4 disciplines: reconstruction, trauma, pathology, and cosmetic. Statistical comparison was conducted between dentists and medical doctors using Fisher’s exact test with a p-value of < 0.05. Results: Disparities were noted each group’s responses. Oral and maxillofacial surgery was preferred overall for most clinical scenarios in trauma (p < 0.001), pathology (p < 0.001), and reconstructive surgery (p < 0.001). Plastic surgery was preferred for cosmetic surgeries (p < 0.001). Conclusions: This study indicates the need to increase awareness and conduct health campaigns regarding oral and maxillofacial surgery among healthcare professionals, especially medical doctors, and the general public.
A Microfluidic Platform for in situ Investigation of Biofilm Formation and its Treatment under Controlled Conditions
Authors: Straub Hervé , Eberl Leo , Zinn Manfred , Rossi René M , Maniura-Weber Katharina , Ren Qun 
Published: November 2020

Abstract
Background Studying bacterial adhesion and early biofilm development is crucial for understanding the physiology of sessile bacteria and forms the basis for the development of novel antimicrobial biomaterials. Microfluidics technologies can be applied in such studies since they permit dynamic real-time analysis and a more precise control of relevant parameters compared to traditional static and flow chamber assays. In this work, we aimed to establish a microfluidic platform that permits real-time observation of bacterial adhesion and biofilm formation under precisely controlled homogeneous laminar flow conditions. Results Using Escherichia coli as the model bacterial strain, a microfluidic platform was developed to overcome several limitations of conventional microfluidics such as the lack of spatial control over bacterial colonization and allow label-free observation of bacterial proliferation at single-cell resolution. This platform was applied to demonstrate the influence of culture media on bacterial colonization and the consequent eradication of sessile bacteria by antibiotic. As expected, the nutrient-poor medium (modified M9 medium containing 1 g/l of organic nitrogen) was found to promote bacterial adhesion and to enable a higher adhesion rate compared to the nutrient-rich medium (tryptic soy broth containing 20 g/l of organic nitrogen). However, in rich medium the adhered cells colonized the glass surface faster than those in poor medium under otherwise identical conditions. For the first time, this effect was demonstrated to be caused by a higher retention of newly generated bacteria in the rich medium, rather than faster growth especially during the initial adhesion phase. These results also indicate that higher adhesion rate does not necessarily lead to faster biofilm formation. Antibiotic treatment of sessile bacteria with colistin was further monitored by fluorescence microscopy at single-cell resolution, allowing in situ analysis of killing efficacy of antimicrobials.Conclusion The platform established here represents a powerful and versatile tool for studying environmental effects such as medium composition on bacterial adhesion and biofilm formation. Our microfluidic setup shows great potential for the in vitro assessment of new antimicrobials and antifouling agents under flow conditions.
Autistic traits are associated with the functional connectivity of between—but not within—attention systems in the general population
Authors: Yoshimura Sayaka , Kobayashi Kei , Ueno Tsukasa , Miyagi Takashi , Oishi Naoya , Murai Toshiya , Fujiwara Hironobu 
Published: November 2020

Abstract
Background: Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) exhibit dysfunction in the three attention systems (i.e., alerting, orienting, and executive control) as well as atypical relationships among these systems. Additionally, other studies have reported that individuals with subclinical but high levels of autistic traits show similar attentional tendencies to those observed in ASD. Based on these findings, it was hypothesized that autistic traits would affect the functions and relationships of the three attention systems in a general population. Resting-state functional magnetic resonance imaging (fMRI) was performed in 119 healthy adults to investigate relationships between autistic traits and within- and between-system functional connectivity (FC) among the three attention systems. Twenty-six regions of interest that were defined as components of the three attention systems by a previous task-based fMRI study were examined in terms of within- and between-system FC. We assessed autistic traits using the Autism-Spectrum Quotient.Results: Correlational analyses revealed that autistic traits were significantly correlated with between-system FC, but not with within-system FC.Conclusions: Our results imply that a high autistic trait level, even when subclinical, is associated with the way the three attention systems interact.
Association of serum Cyr61 levels with peripheral arterial disease in subjects with type 2 diabetes
Authors: Bin Feng , Xu Guidong , Sun Kangyun , Duan Kaipeng , Shi Bimin , Zhang Nannan 
Published: November 2020

Abstract
Background: The prevalence of peripheral artery disease (PAD) is obviously increased in patients with diabetes. Existing evidence shows that cysteine-rich angiogenic inducer 61 (Cyr61), a 40-kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 and atherosclerosis. However, the relationship between Cyr61 levels and PAD in patients with type 2 diabetes (T2DM) remains obscure.Methods:. Data from a total of 306 subjects with T2DM were cross-sectionally analysed. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We measured serum Cyr61 concentrations by ELISA in subjects with and without PAD at Fontaine’s stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD.Results: Out of the 306 subjects enrolled, 150 were free from PAD, while 156 had clinically significant PAD. In subjects with PAD, the prevalences of Fontaine classification stages II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend < 0.001). The prevalence of PAD on the basis of severity increased with increasing Cyr61 quartiles (all P values for trends < 0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r = 0.227, P = 0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis.Conclusions: Our results demonstrated that Cyr61 was significantly increased in PAD patients with T2DM and that Cyr61 levels were positively associated with disease severity. Cyr61 could be a promising biomarker and further studies are needed to assess its clinical utility.
Large-scale, enzyme-based xenobiotic identification for exposomics
Authors: Liu Ken , Lee Choon , Singer Grant , Woodworth Michael , Ziegler Thomas , Kraft Colleen , Miller Gary , Li Shuzhao , Go Young-Mi , Morgan Edward , Jones Dean 
Published: November 2020

Abstract
Advances in genomics have revealed many of the genetic underpinnings of human disease, but exposomics methods are currently inadequate to obtain a similar level of understanding of environmental contributions to human disease. Exposomics methods are limited by low abundance of xenobiotic metabolites and lack of authentic standards, which precludes identification using solely mass spectrometry-based criteria. Here, we develop and validate a method for enzymatic generation of xenobiotic metabolites for use with high-resolution mass spectrometry (HRMS) for chemical identification. Generated xenobiotic metabolites were used to confirm identities of respective metabolites in mice and human samples based upon accurate mass, retention time and co-occurrence with related xenobiotic metabolites. The results establish a generally applicable enzyme-based identification (EBI) for mass spectrometry identification of xenobiotic metabolites.
Accuracy of Whole-Body Diffusion-Weighted MRI (WB-DWI/MRI) in Diagnosis, Staging and Follow-Up of Gastric Cancer, in Comparison to CT: A Pilot Study.&nbsp;
Authors: De Vuysere Sofie , Vandecaveye Vincent , De Bruecker Yves , Carton Saskia , Vermeiren Koen , Tollens Tim , De Keyzer Frederik , Dresen Raphaëla Carmen 
Published: November 2020

Abstract
Background: Accurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed Tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high spatial and contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer.Methods: This retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 Tesla, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard.Results: For overall tumor detection (n=32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n=18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/ PPV/ NPV of 50%/ 100%/ 100%/ 71.4%, and 15.4%/ 100%/ 100%/ 31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumor infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%.Conclusions: WB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer. These results need to be confirmed in larger studies.
Structural basis for repurposing a 100-years-old drug suramin for treating COVID-19
Authors: Xu H. Eric , Yin Wanchao , Luan Xiaodong , Li Zhihai , Zhang Leike , Zhou Ziwei , Gao Minqi , Wang Xiaoxi , Fulai Zhou , Shi Jingjing , You Erli , Liu Mingliang , Wang Qingxia , Wang Qingxing , Jiang Yi , Jiang Hualiang , Xiao Gengfu , Yu Xuekui , Zhang Shuyang 
Published: November 2020

Abstract
The COVID-19 pandemic by non-stop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report the discovery of suramin, a 100-year-old drug, as a potent inhibitor of the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) through blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for COVID-19. The 2.6 Å cryo-EM structure of the viral RdRp bound to suramin reveals two binding sites of suramin, with one site directly blocking the binding of the RNA template strand and the other site clash with the RNA primer strand near the RdRp catalytic active site. Furthermore, suramin potently inhibits SARS-CoV-2 duplication in Vero E6 cells. These results provide a structural mechanism for the first non-nucleotide inhibitor of the SARS-CoV-2 RdRp and a rationale for repurposing suramin for treating COVID-19.