bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Metabolomic Profiling Detects Novel Markers of Myocardial Infarction among Cardiac-chest Pain Cases
Authors: Aa Nan , Lu Ying , Yu Mengjie , Tang Heng , Lu Zhenyao , Sun Runbin , Wang Liansheng , Li Chunjian , Yang Zhijian , Aa Jiye , Kong Xiangqing , Wang Guangji 
Published: December 2020

Abstract
Background: A unique human plasma metabolic pattern of myocardial infarction (MI) has been recognized for over a decade. The discriminant metabolites are potential diagnosis and warning markers, and have connections with traditional cardiovascular risk factors and circulating transcriptomics. Methods: A total of 146 chest pain (85 MIs and 61 non-MI chest pain cases) and 84 control individuals were recruited. GC/MS and LC/MS were applied to identify and quantify the plasma metabolites. The metabolites were analyzed by multivariate statistical analysis to describe different patterns of CADs with chest pain. Receiver operating characteristic （ROC） and odds ratio (OR) were calculated to identify potential markers of MI cases, and the markers were further evaluated based on human circulating transcriptomics from the GEO database. The correlation of metabolites to clinical indices was assessed. Results: MI can be clearly distinguished from non-MI chest pain cases by the metabolites we identified, better than by medical history combined with routine biochemical parameters. Pathway analysis highlighted an upregulated methionine metabolism and downregulated arginine biosynthesis that were deeply involved in MI cases. Among all the metabolites, deoxyuridine (dU) and methionine scored highly in ROC (>0.91) and are related to LDH and AST (p<0.05). OR values (logOR>2) suggested, with or without adjusting by lipid levels, age, smoking, diabetes and hypertension, that dU and methionine are risk factors for alerting about MI occurrence. Transcriptomics data showed elevations of plasma CDA and UPP1, and a decrease of cardiac MARS, which are consistent with the increased levels of plasma dU and methionine, respectively. Conclusions: For the first time, dU and methionine were suggested as markers for MI diagnosis and as high-risk markers to alert about an onset of MI. Plasma metabolite changes are not only directly related to cardiac damage but also could be related to circulating cells.
Based on the Effect of Huazhengsanji Prescription and Cisplatin on Hypoxia-Induced HepG2 Hepatoma Cells HIF-1α and VEGF
Authors: Wang Shanshan , Yangyang Liu , Xiaohao Xu , Tiejun Liu , Zunhua Shu , Xiong Zhuang 
Published: December 2020

Abstract
BackgroundHepatoma is one of the most common malignant tumors in my country, and its occurrence and development play an important role in the molecular mechanism of hypoxia microenvironment and angiogenesis. Huazhengsanji prescription(HZSJ) is an empirical prescription for the treatment of liver cancer, but its specific anti-tumor molecular mechanism is still unclear, and whether it has a synergistic effect with cisplatin(DDP), a chemotherapy drug for liver cancer, has not been reported yet. This article discusses the inhibition of the proliferation and migration of HepG2 hepatocarcinoma cells and the difference in the expression of HIF-1α and VEGF when the HZSJ, DDP and the two are used in combination, and compares and analyzes the mechanism of the HZSJ in enhancing the anticancer sensitivity of chemotherapeutics.MethodsHepG2 Hepatoma cells were divided into blank control group, hypoxia model group, DDP group, HZSJ group, HZSJ+DDP group, and the hypoxia environment was induced by the CoCl2 method. MTT method detects cell proliferation ability, scratch test detects cell migration ability, immunofluorescence method and western blot detect HIF-1α and VEGF protein expression.ResultsHZSJ has the effect of inhibiting the proliferation and migration of HepG2 cells, and has obvious concentration-dependent; The combined application of HZSJ and DDP has significantly stronger inhibitory effect on cell proliferation than the HZSJ group (P<0.01) and the DDP group (P<0.01, P<0.001). High-dose HZSJ can inhibit the migration ability of HepG2 cells (P<0.01); the combination of HZSJ and DDP can significantly reduce the migration rate of HepG2 cells after induction (P<0.01, P<0.01, P <0.01). The results of immunofluorescence and western blot showed that: compared with the blank control group, the expression levels of HIF-1α and VEGF protein in the model group were significantly increased (P<0.05, P<0.01, P<0.001); compared with the model group and DDP The expression of HIF-1α protein in the high-dose HZSJ group (200μg/mL) and the combination group decreased (P<0.05, P<0.01, P<0.001), but there was no difference between the groups. Compared with the model group, the high-dose HZSJ group (200μg/mL) can reduce the expression of VEGF (P<0.05); compared with the model group and the DDP group, the combination group can reduce the expression of VEGF (P< 0.01, P<0.001), and has obvious concentration dependence.ConclusionsHZSJ can inhibit the proliferation and migration of HepG2 hepatoma cells under hypoxia, which may be related to the reduction of HIF-1α and VEGF expression, and its increase in the anticancer sensitivity of the chemotherapy drug DDP may be related to both The synergistic inhibition of VEGF expression is related.
Tumorigenicity of Ascites-Derived Tumor Cells: Insights Into the Molecular Mechanisms of Ovarian Cancer Progression and Therapy Resistance
Authors: Ding Yi , Labitzky Vera , Legler Karen , Qi Minyue , Schumacher Udo , Schmalfeldt Barbara , Stürken Christine , Oliveira-Ferrer Leticia 
Published: December 2020

Abstract
Background: Ovarian cancer (OvCa) cells disseminate primarily intraperitoneally. Here, detached tumor cell aggregates (spheroids) from the primary tumor are generally regarded as “metastatic units”, which exhibit a survival benefit, probably due to the protective microenvironment and their unique molecular characteristics. Hence, current therapeutic concepts such as classical chemotherapy are not sufficient preventing growth and spread of OvCa spheroids. Methods: In the current study we analyzed the cellular composition of ascites from ovarian cancer patients using flow cytometry and the tumorigenic potential of the different subpopulations in an intraperitoneal mouse model. Comparative transcriptome analyses (RNAseq) from ascites-derived tumor cells spheroids (n=10) vs. tumor samples from different metastatic sites (n=30) were further performed in order to identify key molecular players responsible for the special cellular characteristics of OvCa spheroids. Results: In vitro culture of ascites-derived cells gave rise to two different subpopulations: an adherent cell population (ADs) including mainly CD90+ cells with highly proliferative rates in vitro but no tumorigenic potential in vivo, and a non-adherent cell population (NADs) containing principally EpCAM+/CD24+ cells with low proliferative potential in vitro. NADs included cell aggregates and single cells, the first showing a high content (> 80%) of tumor cells (EpCAM+/CD24+). Enriched tumor cell spheroids from the ascites using cell strainers showed higher tumorigenic potential in vivo in comparison to the original ascites-derived cell population. Interestingly, the different metastatic spread patterns observed in the mice resembled the tumor dissemination pattern found in the corresponding patients. RNAseq analyses from tumor-spheroids revealed up-regulation of genes involved in chemoresistance (TGM1, HSPAs, MT1s), cell-adhesion and cell barrier (PKP3, CLDNs, PPL) and the oxidative phosphorylation (OXPHOS) process compared to the solid tumor tissue samples. Additionally, down-regulation of extracellular matrix components and angiogenesis-related genes could be observed. Targeting OXPHOS by metformin treatment led to reduced viability of ascites-derived spheroids from OvCa patients, showing to some extent a synergistic effect with cisplatin treatment. Conclusions: the actual study contributes to a better understanding of the biology of ovarian cancer spheroids and to the identification of new treatment opportunities in advanced ovarian cancer.
Identification of a Metabolism-Related Risk Signature to Predict the Outcome and Immune Infiltration of Esophageal Squamous Cell Carcinoma
Authors: Liu Yu , Wang Liyu , Liu Hengchang , Tian He , Fan Tao , Xue Liyan , Zheng Bo , Tan Fengwei , Xue Qi , Gao Shugeng , li chunxiang , He Jie 
Published: December 2020

Abstract
Background: Metabolic reprogramming is associated with tumor heterogeneity and progression. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) might help us to uncover new biomarkers for patient outcomes and targets for therapies.Methods: In this study, metabolism-related genes were screened from mRNA microarray data (GSE53624, GSE53622). Consensus clustering analysis was used to divide tumors into subgroups. Survival analysis and univariate Cox analysis were performed to select prognostic genes. A metabolism-related gene signature was established with multivariate Cox proportional hazards regression (PHR) analysis in the training group (GSE53624). Gene set enrichment analysis (GSEA) and CIBERSORT were used to analyze functional enrichment and immune cell infiltration.The gene signature and immune infiltration were verified in two public databases (GSE53622, TCGA-ESCC) and in two independent cohorts, 95 and 119 ESCC patients, by immunohistochemistry (IHC) analysis. Results: Based on prognosis-related metabolic gene expression, three cluster subgroups (k = 3) were identified with significantly different immune cell infiltration patterns, clinical features and overall survival (OS) times. Then, we developed a multigene (INPP5E, CD38 and POLR3G) prognostic signature that showed better predictive ability and was found to be an independent prognostic risk factor in ESCC database and two public database analyses. This result could also be verified by multicenter IHC experiment and indicated the clinical application potential. In addition, GSEA showed that several tumor-related pathways were associated with the prognostic signature. Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells displayed an obvious correlation with prognostic signature and IHC experiment in 119 cohort also support this result.Conclusions: Our study indicated that the metabolism-related prognostic gene could stratify patients into subgroups and was associated with immune infiltration, clinical features and outcomes. The three-gene prognostic signature from metabolic-related gene displays a good ability to predict OS and the infiltration of immunosuppressive Tregs and plasma cells.
WBP2 Negatively Regulates Hippo Pathway By Competitively Binding To WWC3 With LATS1 To Promote The Malignant Phenotype Of Non-Small Cell Lung Cancer
Authors: Han Qiang , Rong Xuezhu , Lin Xu-Yong , Zhang Xiupeng , Fan Chuifeng , Zhao Huanyu , Wang Enhua 
Published: December 2020

Abstract
Background: WW domain binding protein-2 (WBP2) can function as a YAP/TAZ co-activator and play a vital role in promoting breast cancer progression. However, the expression and potential molecular mechanism of WBP2 in the context of lung cancer are not fully understood. Methods: Expression and subcellular localization of WBP2 in clinical samples and in lung cancer cell lines were analyzed with respect to various clinical pathological parameters using Chi-square tests. We used a series of cell function experiments and tumor formation experiments in nude mice to verify the effect of WBP2 on tumor cell proliferation and invasion. Dual-directional regulation of WBP2 expression, immunoprecipitation, luciferase reporter assays, and quantitative PCR analyses were used to explore the regulatory mechanisms and identify associated molecular markers.Results: We determined that WBP2 was highly expressed in lung cancer specimens and cell lines and that this expression was closely related to the pTNM stage, lymph node metastasis, and poor prognosis of patients. Additionally, gain and loss of function experiments revealed that WBP2 could significantly promote the proliferation and invasion of lung cancer cells both in vivo and in vitro. To elucidate the underlying molecular mechanism, we determined that wild-type WBP2 could competitively bind to the WW domain of WWC3 with LATS1 through its PPxY motifs to inhibit the formation of the WWC3-LATS1 complex, reduce the phosphorylation level of LATS1, and ultimately promote YAP nuclear translocation to suppress the activity of the Hippo pathway. Conclusions: From the aspect of upstream molecules of Hippo signaling, WBP2 promotes the malignant phenotype of lung cancer cells in a unique manner that is not directly dependent upon YAP, thus providing a corresponding experimental basis for the development of targeted therapeutic drugs for lung cancer.
Machine Learning Algorithm Guiding Local&nbsp;Treatment Decisions For Lung Cancer Patients With Bone Metastases
Authors: Wang Zhiyu , Sun Jing , Sun Yi , Gu Yifeng , Xu Yongming , Zhao Bizeng , Yang Mengdi , Yao Guangyu , Zhou Yiyi , li Yuehua , Du Dongping , Zhao Hui 
Published: December 2020

Abstract
Background: As life expectancy increases for lung cancer patients who develop bone metastases, the need for personalized local treatment for bone metastases is expanding.Methods: Lung cancer patients with bone metastases were treated by a multidisciplinary team via surgery, percutaneous osteoplasty, or radiation. The pre- and post-treatment visual analog scale (VAS) and Quality of Life (QoL) scores were analyzed. QoL at 12 weeks was the main outcome. Treatment-related costs and overall survival time (OS) were collected. We used machine learning to develop and test models to predict which patients should receive local treatment. Models discrimination were evaluated by the area under curve (AUC), and the best one was used for validation in clinical use. Results: Under the direction of a multidisciplinary team, 161 patients in the training set, and 32 patients in the test set underwent local treatment. A decision tree model included VAS scale, bone metastases character, Frankel classification, Mirels score, age, driver gene, aldehyde dehydrogenase 2, and enolase 1 expression had a best AUC of 0.92 (95%CI 0.89 to 0.94), and 36 patients in a validation set underwent local treatment guided by the model. Improved QoL and VAS scores were observed at 12 weeks after local treatment in training, test, and validation sets (p < 0.05), with no significant differences among the three datasets. There were no significant differences in mean costs among the three datasets in the four treatment groups. OS was 18.03±0.45 months and did not significantly differ among treatment groups or the three datasets. Conclusions: Local treatment not only had no negative influence on OS but also provided significant pain relief and improved QoL. QoL, OS or costs did not significantly differ between patients whose treatment was guided by a multidisciplinary team or machine learning model. Our machine learning model using clinical data can help guide clinicians to make local treatment decisions to improve patients’ QoL.Trial registration: No. ChiCRT-ROC-16009501
Cancer Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma By Affecting Autophagy-Associated Chemoresponse
Authors: Thongchot Suyanee , Vidoni Chiara , Ferraresi Alessandra , Loilome Watcharin Loilome , Khuntikeo Narong , Sa-Ngiamwibool Prakasit , Titapun Attapol , Isidoro Ciro , Namwat Nisana 
Published: December 2020

Abstract

Background: Interleukin-6 (IL-6) massively released by cancer-associated fibroblast (CAFs) has been shown to associate with the malignant behavior of cholangiocarcinoma (CCA). In vitro studies demonstrated the ability of CAFs-derived IL-6 to inhibit autophagy in CCA cells thus promoting their proliferation and invasiveness potential. Here, we aimed to validate with clinical and molecular data the hypothesis that CAFs infiltration and release of IL-6 predict poor prognosis in CCA patients following dysregulation of autophagy in cancer cells.Methods: Stromal IL-6 and cancer cell-associated autophagy proteins LC3 and p62 were assayed by Tissue MicroArray immunohistochemistry and their expression correlated with overall survival (OS) in a cohort of 70 CCA patients. Additionally, copy number and mRNA expression data of BECN1, MAP1-LC3B, p62/SQSTM1 and IL6 were extracted from a CCA database in TCGA and correlated with OS. 5-FU Cytotoxicity in CCA cells was assessed by cell counting, clonogenic assay, cytofluorometry and western blotting and immunofluorescence of apoptotic-related proteins. Results: We show that patients bearing a CCA with low production of stromal IL-6 and active autophagy flux in the cancer cells have the best prognosis and this correlates with a more effective response to post-operative chemotherapy. Similar trend was observed in CCA patients from TCGA database. In vitro experiments with primary CAFs isolated from human CCA and epigenetic manipulations showed that IL-6 plays a pivotal role in determining the autophagy-associated apoptotic response to chemotherapeutic drug in cultured human CCA cells. Conclusions: Our data support a therapeutic strategy that includes autophagy-enhancing drugs along with adjuvants limiting the stromal inflammation (i.e., the secretion of IL-6) to improve the survival of CCA patients.
NK Cells Adjuvant Therapy Reveals Obvious Survival Benefits in a Gastric Mixed Signet Ring Cell Carcinoma Patient: A Case Report
Authors: Jin Yuan-yuan , Yang Wen-zhuo , Sun Zheng-yang , Wang Zhong-bo , Chen Jian , Wu Chun-tao , Yang Zhao-yong 
Published: December 2020

Abstract
Background: Advanced signet ring cell (SRC) carcinoma has a worse prognosis. Therefore, early diagnosis and prevention is particularly important; SRC tumours have lower R0 resection rate and are thought to be less chemosensitive than non-SRCC. Consequently, a novel postoperative adjuvant treatment is urgently needed to improve clinical outcomes.Case presentation: A 41-year-old female with paroxysmal vomiting for more than one year come to hospital for gastroscopy examination in 2015. The gastroscopy revealed signet ring cell carcinoma of gastric antrum and poorly differentiated adenocarcinoma in some areas. The patient was treated with radical gastrectomy for gastric cancer and oxaliplatin-based regimen for 6 cycles after surgery. Natural killer (NK) cells immunotherapy was started after November 2016, three times a year, up to now, no suspicious lesions were evident, and the levels of serum tumor markers were normal.Conclusions: Intravenous injections of NK cells combination with surgical treatment and chemotherapy showed therapeutic effects in this patient with possible relapse.
Early Prediction Model for Preterm Birth Combining Demographic Characteristics and Clinical Characteristics
Authors: Chen Mengfan , Xie Ni , Liang Zhaoxia , Qian Tingting , Chen Danqing 
Published: December 2020

Abstract
Objective. To create early prediction models for preterm birth (PTB) based on the Chinese population, combining demographic characteristics and clinical characteristics.Methods. A retrospective study on 15197 pregnant women who were recruited in Obstetrics and Gynecology Hospital of Zhejiang University from January1, 2017 to December 31, 2017. Demographic characteristics and clinical characteristics were collected and were randomly divided into the observation group (80%) and the validation group (20%). Multivariable Logistics regression analysis was performed to develop a risk prediction model in the observation group and the validation group. It was evaluated by the value of area under the curve (AUC) of receiver operating characteristic (ROC). Finally, we got a simple scoring system to present the preterm birth risk. Results. There were 1082 pregnant women (8.9%) developed PTB in the observation group and 316 pregnant women (10.3%) in the validation group. Gravidity, educational level, residence, previous history of PTB, twin pregnancy, pre-gestational diabetes mellitus (type I or II), chronic hypertension, placenta previa, gestational hypertension were significant predictors of future PTB. These factors were all included in the model, the AUC was 0.746 with sensitivity of 61.4% (95%CI: 61.4-66.7%) and specificity of 86.6% (95%CI: 85.2-87.9%) at the threshold score of 8.Conclusion. PTB can be predicted by demographic characteristics and clinical characteristics pre-pregnancy or during pregnancy, thus predicting and preventing PTB as early as possible.
Identification of the Wheat VQ Protein Family and Expression Analysis of Candidate Genes Associated with Seed Dormancy and Germination
Authors: Cheng Xinran , Gao Chang , Liu Xue , Xu Dongmei , Pan Xu , Gao Wei , Yan Shengnan , Yao Hui , Cao Jiajia , Min Xiaoyu , Lu Jie , Chang Cheng , Zhang Haiping , Ma Chuanxi 
Published: December 2020

Abstract
Background: Seed dormancy and germination determine wheat pre-harvest sprouting resistance and thereby affect grain yield and quality. Arabidopsis VQ genes have been shown to influence seed germination; however, the functions of wheat VQ genes have not been characterized. Results: In this study, we identified 65 TaVQ genes in common wheat and named them TaVQ1–65. We identified 48 paralogous pairs, 37 of which had Ka/Ks values lager than 1, suggesting that most TaVQ genes have suffer positive selection. Chromosome location, gene structure, promoter element and gene ontology annotation showed that the structure of the genes determined their function and that structural change reflected functional diversity. The transcriptome expression analysis of 62 TaVQ genes and microarray analysis of 11 TaVQ genes indicated that they played important roles in diverse biological processes. We compared TaVQ gene expression and corresponding seed germination index values among wheat varieties with contrasting seed dormancy and germination phenotypes and found that 21 TaVQ genes may be related to seed dormancy and germination. Conclusions: Sixty-five TaVQ proteins were identified for the first time in common wheat, and bioinformatics analysis was performed to investigate their phylogenetic relationships and evolutionary divergence. The qRT-PCR data showed that 21 TaVQ candidate genes were potentially involved in seed dormancy and germination. These findings provide effective information for further cloning and functional analysis of TaVQ genes, as well as useful candidate genes for improvement of PHS resistance in wheat.