bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amlexanox enhances temozolomide-induced anti-tumor effects in human glioblastoma cells by inhibiting IKBKE and the Akt-mTOR signaling pathway
Authors: Xiong Jinbiao , Guo Gaochao , Guo Lianmei , Wang Zengguang , Chen Zhijuan , Nan Yang , Cao Yiyao , Li Ruilong , Yang Xuejun , Dong Jun , Jin Xun , Yang Weidong , Huang Qiang 
Published: August 2020

Abstract
Background: Temozolomide (TMZ), as the first-line chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM), often fails to improve the prognosis of GBM patients due to the quick development of resistance. The need for more effective management of GBM is urgent. The aim of this study is to evaluate the efficacy of combined therapy with TMZ and amlexanox, a selective inhibitor of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), for GBM. Methods: in vitro, cell viability assay, apoptosis analysis, western blot, migration and invasion assay were used. In vivo, intracranial tumor models were constructed and the immunohistochemistry were used. Results: We found that combined treatment resulted in significant induction of cellular apoptosis and the inhibition of cell viability, migration and invasion in primary glioma cell and in the human glioma cell line, U87 MG. TMZ enhanced expression of phosphoration of adenosine 5‘-monophosphate-activated protein kinase (p-AMPK) and amlexanox led to reduction of IKBKE, with no impact on p-AMPK. Furthermore, we demonstrated that, compared to other groups treated with each component alone, TMZ combined with amlexanox effectively inhibited phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR). In addition, the combination treatment also clearly reduced in vivo tumor volume and prolonged median survival time in the xenograft mouse model. Conclusion: These results suggest that amlexanox sensitized primary glioma cell and U87 MG cell to TMZ at least partially though the suppression of IKBKE activation and the attenuation of AKT activation. Overall, combined treatment with TMZ and amlexanox may provide a promising possibility for improving the prognosis of glioblastoma patients in clinical practice.
Classifying information-sharing methods: a citation-mining systematic review
Authors: Nikolaidis Georgios Filippos , Woods Beth , Palmer Stephen , Soares Marta O 
Published: August 2020

Abstract
BackgroundSparse relative eectiveness evidence is a frequent problem in Health Technology Assessment(HTA). Where evidence directly pertaining to the decision problem is sparse, it may be feasible to expand theevidence-base to include studies that relate to the decision problem only indirectly: for instance, when there isno evidence on a comparator, evidence on other treatments of the same molecular class could be used;similarly, a decision on children may borrow-strength from evidence on adults. Usually, in HTA, such indirectevidence is either included by ignoring any dierences (`lumping`) or not included at all (`splitting`). However,a range of more sophisticated methods exists, primarily in the biostatistics literature. The objective of thisstudy is identify and classify the breadth of the available information-sharing methods.MethodsForwards and backwards citation-mining techniques were used on a set of seminal papers on thetopic of information-sharing. Papers were included if they specied (network) meta-analytic methods forcombining information from distinct populations, interventions, outcomes or study-designs.Results: Overall, 89 papers were included. A plethora of evidence synthesis methods have been used forinformation-sharing. Most papers (n = 78) described methods that shared information on relative treatmenteects. Amongst these, there was a strong emphasis on methods for information-sharing across multipleoutcomes (n = 39) and treatments (n = 23), with fewer papers focusing on study-designs (n = 10) orpopulations (n = 6). We categorise and discuss the methods under four 'core' relationships ofinformation-sharing: functional, exchangeability-based, prior-based and multivariate relationships, and explainthe assumptions made within each of these core approaches.ConclusionsThis study highlights the range of information-sharing methods available. These methods oftenimpose more moderate assumptions than lumping or splitting. Hence, the degree of information-sharing thatthey impose could potentially be considered more appropriate. Our identication of four `core` methods ofinformation-sharing allows for an improved understanding of the assumptions underpinning the dierentmethods. Further research is required to understand how the methods dier in terms of the strength of sharingthey impose and the implications of this for health care decisions.
Ang II Enhances Atrial Fibroblast Autophagy and Promotes Atrial Remodeling Through the AT1-ERK-mTOR Signaling Pathway
Authors: Xu Xudong , Chen Mengmeng , Qiu Hangyuan , Zhou Kuangshi , Zhu Jun , Cheng Hui , Wang Yunhe , Fu Guosheng , Jiang Ruhong , Jiang Chenyang 
Published: August 2020

Abstract
Background: Atrial remodeling is a common pathological change in atrial fibrillation (AF), while the mechanism of atrial remodeling remains unclear. In the present study, we investigated the autophagy and collagen secretion in atrial fibroblasts in response to renin-angiotensin system (RAS) activation and elucidated the relationship between atrial fibroblast autophagy and atrial remodeling. Methods: Right atrial tissues was obtained from patients that underwent cardiac valve replacement after signed the informed consent form. In vivo, subcutaneous perfusion of angiotensin II (Ang II) was used to mimic activation of the RAS and induce atrial remodeling. Electrical remodeling and AF induction were assessed by electrophysiology and programmed stimulation. In vitro, atrial fibroblasts were isolated and cultured. Autophagic flux changes were assessed by mCherry‑GFP‑LC3 adenovirus transfection. All samples were collected, collagen expression, autophagy changes and atrial remodeling were evaluated by western blot, masson’s trichrome staining, immunohistochemistry and immunoﬂuorescence mainly.Results: Atrial tissue samples from patients with atrial fibrillation showed more collagen deposition and enhanced autophagy than those with sinus rhythm. Chronic subcutaneous Ang II perfusion in mice promoted atrial remodeling and susceptible to AF induction. In cultured atrial fibroblasts, the expression of collagen I (COL-I) and collagen III (COL-III) and autophagy both increased when cells were treated with Ang II, and the autophagic flux was enhanced by Ang II. However, blocking autophagy reduced the expression of COL-I and COL-III. Besides, Ang II induced the phosphorylation of ERK and suppressed the phosphorylation of mTOR. In contrast, inhibition of the angiotensin II type 1 receptor (AT1) or ERK signaling pathway not only suppressed the autophagy induced by Ang II but also reduced COL-I and COL-III expression. Conclusions: In summary, these results suggest that Ang II promotes autophagy in atrial fibroblasts, which aggravates atrial remodeling and increases the susceptibility to AF induction. Autophagy may be a potential target for relieving atrial remodeling and AF after RAS activation.
Efficiency of Online Course of Medical Statistics in Nanjing Medical University During the COVID-19 Epidemic
Authors: Ni Senmiao , Chen Wensong , Yi Honggang , Zhao Yang , Tong Na , Chen Ran , Yu Hao , Liu Jiyong , Bai Jianling , Chen Feng 
Published: August 2020

Abstract
Background: To analyze the online course efficiency of a combined mode of Massive Open Online Course (MOOC) micro-video and E-learning platform in Nanjing Medical University during the COVID-19 epidemic. Methods: We developed a new questionnaire to assess the efficiency of online teaching of medical statistics in Nanjing Medical University. This investigation enrolled students participating in the online course of medical statistics from January 2020 to June 2020. The “Questionnaire Star” electronic questionnaire collection system was used to collect data. Results: In total, 1050 of the 1210 (86.78%) students completed the questionnaire, including 971 (92.48%) juniors. To be specific, 57.33% of the students majored in clinical medicine, 15.14% in pharmacy, 10.38% in pediatrics, 8.00% in medical imageology, and 6.29% in basic medicine. As to the question "Are you satisfied with the current online teaching method?", 354 (32.77%) students responded with "Agree" and "Strongly Agree", and 1012 (96.47%) thought they needed to consolidate what they had learned after returning to school. Most students reported their "Difficulties in the learning process" by "Learning motivation" and "Personal inertia" (59.90% and 58.29%, respectively).Conclusions: The online course of medical statistics was favored by most students, suggesting its efficiency an efficient alternative to classroom study during the COVID-19 pandemic. Yet there were still some problems, such as inconvenient communication between teachers and students, poor mastery of key knowledge, which should be resolved in classroom teaching at school.
Pan-cancer analysis of RNA expression of ANGIOTENSIN-CONVERTING ENZYME II (ACE2) and cellular proteases reveals high variability and possible impact on COVID-19 clinical outcomes
Authors: Elliott Andrew , Saul Michelle , Zeng Jia , Marshall John , Kim Edward , Nagasaka Misako , Lenz Heinz-Josef , Schwartzberg Lee , Spetzler David , Abraham Jim , Xiu Joanne , Stafford Phillip , Korn Wolgang 
Published: August 2020

Abstract
Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with heightened susceptibility to SARS-CoV-2 infection in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.
Antibiotic prescription in primary care from the perspective of family physicians: a qualitative study
Authors: Hosoglu Salih , Claßen Annika Yanina 
Published: August 2020

Abstract
Background Antibiotic consumption rates increase worldwide steadily. Turkey is now top on the list of global consumption and a prototype of excessive use of antibiotics. In the last two-decades, family physicians (FPs) have become key figures in the healthcare system. The aim of this study is to understand the reasons for inappropriate prescription and to elicit suggestions for ways of improving antibiotic use in primary care from doctors themselves.Methods This is a qualitative study using semi-structured interviews with key individuals. Fourteen FPs from different parts of Turkey participated in these interviews. They were questioned on major indications for antibiotic prescription, reasons for inappropriate antibiotic prescription, obstacles to decision making in antibiotic use and their suggestions for improving antibiotic use. The interviews were recorded, transcribed, and analyzed for common themes. Thematic coding was used in the formulation of themes.Results Interviewees emphasized the coercive factors that lead to inappropriate antibiotic prescription: patient expectations, defensive medical decision making, constraints due to workload and limited access to laboratories. The most powerful suggestions for improving the quality of antibiotic prescription were public campaigns, improvements in the diagnostic infrastructures of primary care centers and enhancing the social status of FPs. The FPs expressed strong concerns related to the complaints that patients make to administrative bodies. Conclusions Physicians in primary care work under immense pressure stemming mainly from workload, patient expectations and obstacles to diagnostic processes. Improving the social status of physicians, increasing public awareness and the facilitation of diagnostic procedures were the methods suggested for increasing antibiotic prescription accuracy.
A Novel Risk Scoring Tool to Predict Saphenous Vein Graft Occlusion in Patients with Type 2 Diabetes Mellitus After Cardiac Artery Bypass Graft Surgery
Authors: Cheng Yujing , Ma Xiaoteng , Liu Xiaoli , Zhao Yingxin , Sun Yan , Zhang Dai , Zhao Qi , Xu Yingkai , Zhou Yujie 
Published: August 2020

Abstract
Background: Coronary artery bypass grafting (CABG) success is reduced by graft occlusion. Patients with type 2 diabetes mellitus(T2DM) are more likely to develop graft occlusion. Understanding factors associated with graft occlusion may improve T2DM patient outcomes. The aim of this study was to develop a predictive risk score for saphenous vein graft (SVG) occlusion in T2DM patients after CABG.Methods: This retrospective cohort study enrolled 3716 CABG patients with T2DM from January 2012 to March 2013. The development cohort included 2477 patients and the validation cohort included 1239 patients. The baseline clinical data at index CABG was analyzed for their independent impact on graft occlusion in our study using Cox proportional hazards regression. The predictive risk scoring tool was weighted by beta coefficients from the final model. Concordance (c)-statistics and comparison of the predicted and observed probabilities of predicted risk were used for discrimination and calibration.Results: A total of 959 (25.8%) out of 3716 patients developed at least one SVG occlusion. Significant risk factors for occlusion were male sex, estimated glomerular filtration rate<90, smoking (currently), hyperuricemia, dyslipidemia, prior percutaneous coronary intervention (PCI), a rising number of lesion vessels, and SVG. On-pump surgery, and the use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) were protective factors. The risk scoring tool with 11 variables was developed from the derivation cohort, which delineated each patient into risk quartiles. The c-statistic for this model was 0.71 in the validation cohort.Conclusions: An easy-to-use risk scoring tool that used common clinical variables was developed and validated. The scoring tool accurately estimated the risk of late SVG occlusion in T2DM patients after CABG.
Dynamic immunity gene and lncRNA regulatory cooperative pairs revealed prognostic signatures in the development of colon cancer
Authors: Wang Chun Jing , You Liu Ping , Wang Fujing , Cui Hao , Hu Yu Zhou , Li Sheng Long 
Published: August 2020

Abstract
Background: The pathological development of colon cancer is a complex progression that depends on multiple alterations of coding and non-coding genes. Colon cancer are challenged by the immune system and acquire features to evade its surveillance during the whole process of occurrence and development. Therefore, it is important to capture the immune regulatory events during the progression of colon cancer development and to identify reliable markers for predicting clinical outcomes in patients. Methods: Here, a standardized computational procedures was developed to evaluate immune cell populations-associated gene (immuneCPa gene)-lncRNA relationships in diverse stages (I, II, III and IV) of colon cancer based on genes and lncRNAs expression. Stage-specific immuneCPa genes and lncRNAs were identified in each colon cancer stage. Results: Dynamic stage-specific immuneCPa gene-lncRNA regulatory networks were constructed and characterized in colon cancer development. A immuneCPa gene-lncRNA activity profile across different stages revealed that lncRNAs were highly stage-selective in regulating immuneCPa genes in colon cancer. Specify scores of immune indicated that diverse kinds of immune cells were temporally-specific in colon cancer. NK CD56bright cell showed strongest stage common features in colon cancer. Further survival analysis indicated that some stage specific immuneCPa gene-lncRNA relationships may have the potential for predicting colon cancer prognosis. Conclusions: Collectively, our study leads to a novel starting point for future functional explorations, the identification of immune-related biomarkers, and lncRNA-based targeted therapy for colon cancer.
Diagnostic and Prognostic implications of AAGAB expression in human breast cancer
Authors: Zhang Cheng , Gong Chen , Liu Yang , Wang Changcai , Zeng Cheng , Yang Kai , Yin Dan 
Published: August 2020

Abstract
Background: Alpha and gamma adaptin binding protein p34 (AAGAB) was previously reported as a novel on-treatment biomarker can improve prediction of response to neoadjuvant chemotherapy in breast cancer. However, the expression and prognostic value of AAGAB in breast cancer is unknown, the function of AAGAB in breast cancer remains to be elucidated. Methods: Herein we investigated the role of AAGAB in human breast cancer from the TCGA database, immunohistochemistry, Gene set enrichment analysis (GSEA) and immune infiltration analysis. Results: Increased AABAB expression in breast cancer was significantly associated with age, gender, race, ER status, PR status, N-stage, PAM50 classification and histological type (all p-values<0.05). Kaplan-Meier survival analysis showed that breast cancer patients with AAGAB-high had a worse prognosis than that with AAGAB-low (p=0.005). Univariate analysis using logistic regression revealed that age, pathological stage, and number of lymph nodes were significantly associated with poor overall survival (OS) (all p <0.05). AAGAB expression level was significantly correlated with cell purity, CD8 T cells, macrophages, CD4 T cells and dendritic cells. Functional annotations indicated that AAGAB is involved in the most significant signaling pathways including intra Golgi traffic and peroxisomal lipid metabolism pathways. Conclusions: Our study revealed that elevated AAGAB expression was significantly correlated with aggressive progression, poor survival in breast cancer patients. AAGAB may serve as a new biomarker and potential treatment target in breast cancer.
Effect of Insulin Resistance on Cardiac Mass in Elderly Normotensive People: A Cross-sectional Study
Authors: Kamal Amr , Mahmoud Dina , Hemida Kamel , Abdelaaty Talaat 
Published: August 2020

Abstract
Background

The increased left ventricular mass (LVM) is a well-known risk indicator for occurrences concerning cardiovascular disease. The risk of these changes in cardiac morphology is intensified for subjects with type 2 diabetes. While insulin resistance has been embroiled in the pathogenesis of ventricular (LV) hypertrophy, earlier research studies have produced contradictory findings which are constrained by comparison bias. The present study focuses on the independent effect of insulin resistance on LVM in the elderly normotensive population.
Methods

The study included 50 subjects excluding patients with myocardial infarction, heart failure, systemic hypertension and aortic stenosis. Group I included 30 patients with glucose intolerance, insulin resistance, or type 2 DM while Group II included 20 control subjects of matched age and sex. Participants involved in the study underwent clinical examination, laboratory investigation (including 75-g oral glucose tolerance test, HbA1c, Plasma insulin level, calculated HOMA-IR, Fasting Lipid profile, Serum albumin/ creatinine ratio) and echocardiography.
Results

LV mass index was significantly different between the 2 group being higher (142.07 ± 53.34) in the study group compared to (92.05 ± 9.42) in the control group, (P = 0.000). Waist circumference, HOMA-IR, FBS, HbA1c and systolic BP have significant positive correlations with LV mass index. However, only HOMA-IR has a significant independent positive correlation with LV mass index.
Conclusions

It is inferred from the present study that insulin resistance is associated with increased cardiac mass in normotensive elderly people.
Correlation Between Facet Tropism and Lumbar Disc Herniation
Authors: Ye Han , Xiaodong Wang , zepei Zhang , shrestha Deepak , Kepeng Li , Yang Song , Jun Miao 
Published: August 2020

Abstract
Purpose The relationship between facet tropism (FT) and lumbar disc herniation (LDH) is not clear. In the present study, MRI was used to assess the relationship between lumbar facet joint tropism and disc herniation. This paper is the first to assess the relationship between facet joint tropism and LDH from the sagittal view.
Methods 122 patients (154 segments) with lumbar disc herniation and 102 normal subjects (306 segments) who visited our hospital from 01-Jan-2020 to 01-Apr-2020 were included in this study. The axial and sagittal angles of facet joints were measured using an MRI scan. The difference of 10° in facet angles between left and right was defined as lumbar facet tropism. The relationship between the two was analyzed.
Results In the axial, 95/154 segments with lumbar disc herniation had FT whereas, 48/258 segments had FT in the normal segments(p<0.01). In the sagittal, 61/154 segments with lumbar disc herniation had FT and 48/306 had FT in the control(p<0.01).
Conclusion The proportion of FT is better in patients with lumbar disc herniation, and there is a significant correlation between FT and lumbar disc herniation.