bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and Validation of an Immune-related Gene Pairs Prognostic Model for Breast Cancer
Authors: Zhong Ying , Wang Zhe , Zhou Yidong , Mao Feng , Lin Yan , Guan Jinghong , Shen Songjie , Xu Yali , Huang Xin , Wang Xuefei , Sun Qiang 
Published: January 2021

Abstract
Background: Immunotherapy plays an increasingly important role in the treatment of advanced female breast cancer, which has the highest mortality rate among malignant tumors. The purpose of this study was to identify immune-related genes associated with breast cancer prognosis as possible targets of immunotherapy, and their related biological processes and signaling pathways.Methods: Clinical data and gene expression profiles of patients with breast cancer were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and divided into training (n = 1053) and verification (n = 508) groups. CIBERSORT was used to predict differences in immune cell infiltration in patient subsets stratified according to risk. Gene Ontology (GO) enrichment analysis was used to identify pathways associated with immune-related genes in patient subsets stratified according to risk.Results: The prognostic model composed of 27 immune-related gene pairs significantly distinguished between high- and low-risk patients. Univariate and multivariate analyses indicated that the model was an independent prognostic factor for breast cancer. Among the identified genes, APOBEC3G, PLXNB1, and C3AR1 had not been previously studied in breast cancer and warrant further exploration. CCR chemokine receptor binding, regulation of leukocyte-mediated cytotoxicity, T cell migration, T cell receptor complex, and other pathways were significantly enriched in low-risk patients. M2 and M0 macrophages were more highly expressed in high-risk than in low-risk patients. CD8+ T cells and naïve B cells were more abundant in low-risk than in high-risk patients.Conclusion: The immune-related gene pairs prognostic model developed in the current study can help assess breast cancer prognosis and provides a potential target and research direction for breast cancer immunotherapy in the future.
Behavioural Support and Nicotine Replacement Therapy for Smokeless Tobacco Cessation: Protocol for a Pilot Randomised-controlled Multi-country Trial
Authors: Siddiqui Faraz , Bauld Linda , Croucher Ray , Jackson Cath , Kellar Ian , Kanaan Mona , Pokhrel Subhash , Huque Rumana , Iqbal Romaina , Khan Javaid Ahmed , Mehrotra Ravi , Siddiqi Kamran 
Published: January 2021

Abstract
Background: Smokeless Tobacco (ST) is consumed globally by more than 350 million people, with approximately 85% of all users based in South and Southeast Asia. In this region, ST products are cheap and easily accessible. Evidence-based interventions to people quit ST use are lacking. This study aims to test the feasibility of conducting a future definitive trial of ST cessation, using a culturally adapted behavioural intervention, and/or nicotine replacement therapy (NRT) in three South Asian countries. Methods: We will conduct a randomised, factorial design pilot trial in Bangladesh, India and Pakistan. Daily ST users will be recruited from primary health care settings in Dhaka, Noida and Karachi. Participants will be individually randomised to receive Intervention A (4 or 6 mg NRT chewing gum for 8-weeks), Intervention B (BISCA: face-to-face behavioural support for ST cessation), combination of Interventions A and B, or Usual Care (Very Brief Advice - VBA). Participants will provide demographic and ST use related data at baseline, and at 6, 12 and 26 weeks follow-up. The primary trial outcome will be validated abstinence to all forms of tobacco at 26 weeks, using a carbon monoxide breath test and salivary cotinine level. Secondary outcomes will be self-reported point prevalence of tobacco use at 6, 12 and 26 weeks. An embedded process evaluation (at 6 weeks) and data collection on health resource use and quality of life (at baseline and 26 weeks) will also be conducted. We will report on the feasibility of intervention delivery, recruitment, randomisation and retention. Discussion: The widespread and continued use of ST products in South Asia is consistent with a high rate of associated diseases and negative impact on the quality of life. The identification of feasible, effective and cost-effective interventions for ST is necessary to inform national and regional efforts to reduce ST use at the population level. Findings of this pilot trial will inform the development of larger trials for ST cessation among South Asian users, with relevance to wider regions and populations having high rates of ST use. Trial registration: ISRCTN identifier 65109397Trial funding: NIHR (programme reference 17/63/76/ Global Health Research Groups)
Overexpression of a novel oncogene Cadherin 6 correlates with tumor progression and poor prognosis in gastric cancer
Authors: Zhao Zongxian , Li Shuliang , Li Shilong , Wang Jun , Lin Hai , Fu Weihua 
Published: January 2021

Abstract
BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.
Matrix stiffness mediates glioma cells stemness through an integrin/JAK/STAT3 signaling pathway
Authors: Yao Wu , Bei Tao , Tangming Peng , Xiaobo Yang , Lilei Peng , Xiangguo Xia , Ligang Chen , Zhong Chuanhong 
Published: January 2021

Abstract
Background：Matrix stiffness in tumor microenvironment is tightly correlated with the tumor progression in solid cancer. However, the potential role of matrix stiffness in glioma progression remains controversial. Our study aimed to explore the underlying mechanism of glioma progression induced by matrix stiffness. Methods: Atomic force microscopy analysis was performed to examine the stiffness of tumor tissues. tunable polyacrylamide (PA) hydrogels were used for cells culture with different matrix stiffness. CCK-8 analysis was used to examine the cells proliferation. Colony formation analysis and subcutaneous tumor-bearing mice model were used to detect the capability of tumorigenesis. Western blotting and immunofluorescent staining were performed to examine the signals activation in glioma cells. Results: In our study, we observed a higher matrix stiffness in high degree glioma tissues from patients. We demonstrated that a higher stiffness culture system could mediate the upregulation of stemness in glioma cells, resulting in the strengthen capability of tumor growth and relapse in glioma. In mechanism, we observed activation of integrin α5β1/JAK1/STAT3/c-Myc signaling pathway in glioma cells under the simulation of a higher matrix stiffness. Combination of STAT3 inhibitor STAT3-IN-1 and chemotherapeutic temozolomide (TMZ) obviously suppressed the xenogenous glioma mice model, which revealed strengthen anticancer effects and improved outcome.Conclusion: We demonstrated that a higher matrix stiffness could promote glioma progression through an integrin α5β1/JAK1/STAT3/c-Myc signaling pathway. Blockade of STAT3 signals improved the anticancer effects of chemotherapy, providing new insights for glioma therapy in clinic.
Protection of Coenzyme Q-10 Against Contrast-induced Acute Kidney Injury in Diabetic Rats
Authors: Couto Sheila Marques Fernandes , Fonseca Cassiane Dezoti da , Watanabe Mirian , Vattimo Maria de Fátima Fernandes 
Published: January 2021

Abstract
Background: Diabetes Mellitus (DM) is a important risk factor for Contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI share oxidative damage and inflammation mechanisms that induction of protective and cellular adaptation enzymes as coenzyme Q-10 (COQ-10). The aim of this study was to investigate the therapeutic potential of COQ-10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats submitted to the CI-AKI model. Methods: Wistar rats, male, randomized into four groups: Citrate- control animals, received citrate buffer (streptozotocin vehicle, 0.4 ml); DM- animals that received streptozotocin (60 mg/kg); DM+IC: DM animals, treated with iodinated contrast (IC, 6 ml/kg); DM+IC+COQ-10: DM animals treated with COQ-10 (10 mg/kg) and that received with IC (6 ml/kg). The protocols lasted 4 weeks. Were evaluated the renal function by inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis.Results: DM animals showed reduced renal function which was reflected with an increase of serum creatinine and significant reduced of inulin clearance, as well as a reduction on RBF, increased RVR and redox imbalance with a higher urinary peroxides, nitrate lipid peroxidation levels and depletion of thiols in renal tissue. IC treatment exacerbated theses changes in DM + IC. COQ-10 administration ameliorates renal function, prevented hemodynamic changes, neutralize oxidative damage and progression of the histologic damage in the DM+IC+COQ-10 group. Conclusion: This study is the first that demonstrated a renoprotection of COQ-10 in experimental model of risk factor of DM for CI-AKI. COQ-10 presented an antioxidant effect on the CI-AKI in diabetic rats, by improving function and renal hemodynamics, preserving morphology and reducing oxidative stress.
Molecular Mechanisms of TanshinoneIIA in Hepatocellular carcinomatherapy via WGCNA-based Network Pharmacology Analysis
Authors: Zhao Han , Guo Jing , Chi Qingjia , Fang Meng 
Published: January 2021

Abstract
Background: Hepatocellular carcinoma (HCC) is a worldwide malignant tumor that caused irreversible consequences. The studies of Tanshinone IIA showed that Tanshinone IIA has played a notable role in HCC treatment. However, it is still to be investigated to discover the potential targets and associating mechanism of Tanshinone IIA against HCC. Methods: To analyze the correlation between genes and specific clinical features, we applied weighted gene co-expression network analysis (WGCNA), which can help us identify the targets of Tanshinone IIA related to the clinical features of Hepatocellular carcinoma. Results: We screened out 105 overlapping genes by integrating the predicted targets of Tanshinone IIA and the gene expression profile of HCC from the Cancer Genome Atlas (TCGA) database. For WGCNA, we used the RNA-seq profile of the overlapping genes and the related clinical information of HCC from TCGA. And 23 genes related to clinical tumor grade in the important module (R2 = 0.37) were imported for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) analysis. Compared to the key genes in the significant module from WGCNA with the high connectivity nodes from the PPI network, we can analyze three hub genes, AURKB, KIF11, and PLK1, for further verification. We tested the binding of Tanshinone IIA to the targets of Hepatocellular carcinoma using Autodock Vina. The survival curve validated that the three hub genes represented a poor prognosis. Receiver operating characteristic (ROC) curves demonstrated that the three hub genes were effective in diagnosis. The mRNA expression of the three hub genes was upregulated in the HCC than the normal. AURKB, KIF11 and PLK1 were further upregulated in advanced tumor stage and grade. Moreover, AURKB, KIF11 and PLK1 also had higher protein expression in HCC tissues. Conclusions: In the study, WGCNA revealed grade-specific gene modules, indicating that Tanshinone IIA probably plays its therapeutical effect in the differentiation process of HCC. And the study partly interpreted the pharmacological mechanism of Tanshinone IIA against HCC.
T-cell Non-Hodgkin Lymphoma&nbsp;of the&nbsp;Ileum&nbsp;Presenting as Perforation&nbsp;and Peritonitis: A Case Report
Authors: Yong Tian , Xiang Zhang Zheng , Li Chuan Fang , Ming Tian Qing , Gang Ye , Song Qiao 
Published: January 2021

Abstract
Background Non-Hodgkin Lymphoma (NHL) of the ileum presenting as perforation and peritonitis is a rare disease, derived from intestinal intraepithelial T lymphocytes.The degree of malignancy is extremely high. The pathogenic factors of ileal perforation caused by NHL are not clear yet, Chromosome and immune system abnormalities, which may be related to the NHL, are indistinguishable from other benign and malignant conditions and clinically nonspecific. Case presentation Here,We described an 84 year old male with abdominal pain for four days and aggravating for three hours. The pain was initially considered as gastrointestinal perforation, and was initially located at the upper abdomen area.The persistent insidious pain,and was accompanied by nausea, vomiting and fever. According to the abdominal physical examination, the patient had pain all over his abdomen, rebound pain and muscle tension, and bowel sounds were reduced on auscultation. The abdominal CT scan showed abdominal cavity free gas.We diagnosed the patient with peritonitis due to the perforation of the hollow viscus. We promptly performed exploratory laparotomy.Intraoperative findings,showed perforations in the ileum that were approximately 40 cm from the ileocecal region and had a size of 3～8 mm. Segmental distribution was observed, and the intestinal contents overflowed with purulent moss around the perforation surface. Resection and ileostomy were performed as intervention, and the clinical histopathological examination showed the T-cell lymphoma. Conclusion:Timely emergency surgery is the key to the treatment of the ileal perforation caused by T-cell lymphoma.Resection and ileostomy were performed as intervention, and the subsequent histopathological examination showed T-cell lymphoma. Clinical follow-up was performed, and the patient was advised to go to the oncology department for further chemotherapy.
Conditions and Barriers for Quality Improvement Work. A Qualitative Study of How Professionals and Health Centre Managers Experience Audit and Feedback Practices in Swedish Primary Care
Authors: Arvidsson Eva , Dahlin Sofia , Anell Anders 
Published: January 2021

Abstract
BackgroundHigh quality primary care is expected to be the basis of many health care systems. Expectations on primary care are rising as societies age and the burden of chronic disease grows. To stimulate adherence to guidelines and quality improvement, audit and feedback to professionals is often used, but the effects vary. Even with carefully designed audit and feedback practices, barriers related to contextual conditions may prevent quality improvement efforts. The purpose of this study was to explore how professionals and health centre managers in Swedish primary care experience existing forms of audit and feedback, and conditions and barriers for quality improvement, and to explore views on the future use of clinical performance data for quality improvement. MethodsWe used an explorative qualitative design. Focus groups were conducted with health centre managers, physicians and other health professionals at seven health centres. The interviews were audio recorded, transcribed and analysed using qualitative content analysis.ResultsFour different types of audit and feedback that regularly occurred at the health centres were identified. The main part of the audit and feedback was “external”, from the regional purchasers and funders, and from the owners of the health centres. This audit and feedback focused on non-clinical measures such as revenues, utilisation of resources, and the volume of production. The participants in our study did not perceive that existing audit and feedback practices contributed to improved quality in general. This, along with lack of time for quality improvement, lack of autonomy and lack of quality improvement initiatives at the system (macro) level, were considered barriers to quality improvement at the health centres.ConclusionsProfessionals and health centre managers did not experience audit and feedback practices and existing conditions in Swedish primary care as supportive of quality improvement work. From a professional perspective, audit and feedback with a focus on clinical measures, as well as autonomy for professionals, are necessary to create motivation and space for quality improvement work. Such initiatives also need to be supported by quality improvement efforts at the system (macro) level, which would favour transformation to a primary care based system.
Triage Category and Factors Influencing Priority of Acute Myocardial Infarction Patients at Tikur Anbessa Specialized Hospital
Authors: Tola Firaol Birhanu 
Published: January 2021

Abstract
Background: - Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. AMI should be treated within a “golden time”, which is < 90 minutes from the onset of the symptom to balloon insertion. Late recognition of diagnosis has increase mortality and long term outcome of the patients in AMI patients. Patients in high priority triage categories were under triage which leads to long waiting time. Determine the associated factors for high priority triage category scale of AMI patients.Result: Among the total of 131 study participants, 91(69.5%) of them were males. The mean age of the study participants were 54 year with the standard deviation of 12.75. Patients who were categorized under high priority triage category accounts 47.3% of the total study participants with 95% CI (38.9-56.5). Among the total study participants 78(59.5%) of them were ST elevation myocardial infarction. Having more than 5 years of triage experience (OR: 13.63, 95% CI (2.32-79.86)) and having Triage early warning score of 5-10 during admission (OR: 65.28, 95% CI (5.39-790.52)) has a significant association on categorizing AMI patients in High priority triage category.Conclusion & Recommendation: Nearly half of the patients at emergency room were categorized under high priority. Triage early warning score and triage nurse experience were the factors which had a significant effect on categorizing AMI patients as high priority triage. Assigning of senior nurses at emergency triage room could improve triage category and early diagnosis and treatment for AMI patients at Tikur Anbessa Specialized Hospital.
Multiplex Immunoassay of Cytokines for The Short-Term Prognosis Predictive Value of Patients With Acute-on-Chronic Liver Failure
Authors: Zheng Yongyuan , Zhang Genglin , Wu Lina , Xiong Jing , Wang Lu , Li Xuejun , Li Jianguo , Xie Chan , Peng Liang 
Published: January 2021

Abstract
Background: Since the systemic inflammation has been found to be associated with disease progression and mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF), the objective of this study was to detect inflammatory factors in ACLF patients by a Luminex-based multiplex immunoassay system for high throughput screening of the cytokine with the most prognostic value.Methods: Luminex-based multiplex immunoassay technology was used to determine the concentrations of 48 cytokines in total at once in serum samples from 40 patients with HBV-ACLF, 30 patients with chronic hepatitis B (CHB) and 25 healthy volunteers as normal controls (NC). Then, the receiver operating characteristic (ROC) curve analysis was applied to evaluate the prognostic prediction accuracy. Besides, Kaplan–Meier curves was used to analyze survival, while the Cox regression analysis to determine the mortality predictors.Results: The level of IL-6, IL-10, IL-15, IL-18, M-CSF, IP-10 and CXCL9 were significantly higher in patients with HBV-ACLF than in either patients with CHB or NC subjects, while the level of EGF, PDGF-AA, PDGF-AB/BB, MDC and sCD40L were significantly lower. The concentrations of IL-6, CXCL9, and IL-15 was higher in non-surviving patients with HBV-ACLF than in surviving patients while MDC was lower. Increased serum IL-6 was positively correlated with disease severity. The ROC curve analysis showed that IL-6 and CXCL-9 accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na. Kaplan–Meier analysis showed an association between the increase in serum concentration of IL-6 as well as CXCL9 and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that only serum IL-6 was an independent predictor of overall survival in patients with HBV-ACLF.Conclusion: Although HBV-related ACLF patients have significantly increased serum levels of multiple cytokines, only serum IL-6 levels could be an independent prognostic biomarker in patients with HBV-ACLF.
Identification of Novel Potential Biomarkers in Hepatocarcinoma Cancer; A Transcriptome Analysis
Authors: kakar Mohib , Mehboob Muhammad , Akram Muhammad , Iqbal Imran , Ijaz Hafza , Aziz Ubair , Lodhi Adil , Rasheed Madiha , Deng Yulin , Dai Rongji 
Published: January 2021

Abstract
The goal of this study was to understand possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Gene Expression Omnibus (GEO) contains datasets of gene expression, miRNA and methylation patterns of diseased and healthy/control patients. GSE62232 Dataset was selected by employing the server GEO. A total of 91 samples were collected, including 81 HCC samples and 10 healthy samples as control. GSE62232 was analyzed through GEO2R, and functional enrichment analysis was performed to extract rational information from a set of DEGs. The protein-protein relationship networking search method was used for extracting interacting genes. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analyzed using GEPIA to estimate the effect of their differential expression on cancer progression. We identified the top 10 hub genes through Cytohubba plugin. These genes include cell cycle regulatory cyclins and cyclin-dependent proteins CCNA2, CCNB1 and CDK1. The pathogenesis and prognosis of HCC may be directly linked with the aforementioned genes. In this analysis, we found critical genes for HCC that showed recommendations for more diagnostic and predictive biomarker studies that could promote selective molecular therapy for HCC.