bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Different Transcranial Doppler-derived Indices of Cerebrovascular Dynamics With Delayed Cerebral Ischemia in Patients Suffering From Subarachnoid Hemorrhage: A Retrospective Study
Authors: Papaioannou Vasilios , Budohoski Karol , Placek Michal , Czosnyka Zofia , Smielewski Peter , Czosnyka Marek 
Published: November 2020

Abstract
Background Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial doppler-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia.MethodsA retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in 2 groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) and arterial blood pressure was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Results In the whole population (N=32), magnitude of SWs of ipsilateral CBFV was increased during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/sec, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (p < 0.001) and were strongly predictive of DCI, with area under the curve = 0.745, p = 0.009. VS caused shortening of tau (ipsilateral to spasm: 0.17 ± 0.08 vs before: 0.25 ± 0.17 sec, p = 0.04) and interhemispheric asymmetry with lower values on ipsilateral side (p < 0.01). In patients with DCI (N=19), Mxa was increased during VS (ipsilateral to spasm: 0.36 ± 0.18 vs before: 0.26 ± 0.23, p = 0.04). ConclusionsIn the whole group of patients, VS was associated with increased CBFV SWs in both temporal and spatial assessments. Greater SWs before VS in DCI group, were strongly predictive of DCI.
AGLR is a Novel Index for the Prognosis of Hepatocellular Carcinoma Patients: A Retrospective Study
Authors: Liao Yan , Wei Rongyu , Yao Renzhi , Qin Liling , Li Jun , Yu Junxiong , Liao Weijia 
Published: November 2020

Abstract
Background: Most hepatocellular carcinoma (HCC) patients’ liver function indexes are abnormal. We aimed to investigate the relationship between (alkaline phosphatase + gamma-glutamyl transpeptidase) / lymphocyte ratio (AGLR) and the progression as well as the prognosis of HCC. Methods: A total of 495 HCC patients undergoing radical hepatectomy were retrospectively analyzed. We randomly divided these patients into the training cohort (n = 248) and the validation cohort (n = 247). In the training cohort, receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of AGLR for predicting postoperative survival of HCC patients, and the predictive value of AGLR was evaluated by concordance index (C-index). Further analysis of clinical and biochemical data of patients and the correlation analysis between AGLR and other clinicopathological factors were finished. Univariate and multivariate analyses were performed to identify prognostic factors for HCC patients. Survival curves were analyzed using the Kaplan-Meier method.Results: According to the ROC curve analysis, the optimal predictive cut-off value of AGLR was 90. The C-index of AGLR was 0.637 in the training cohort and 0.654 in the validation cohort, respectively. Based on this value, the HCC patients were divided into the low-AGLR group (AGLR ≤ 90) and the high-AGLR group (AGLR > 90). Preoperative AGLR level was positively correlated with α-fetoprotein (AFP), tumor size, tumor-node-metastasis (TNM) stage, and microvascular invasion (MVI) (all p < 0.05). In the training and validation cohorts, patients with AGLR > 90 had significantly shorter OS than patients with AGLR ≤ 90 (p < 0.001). Univariate and multivariate analyses of the training cohort (HR, 1.79; 95% CI, 1.21-2.69; p < 0.001) and validation cohort (HR, 1.82; 95% CI, 1.35-2.57; p < 0.001) had identified AGLR as an independent prognostic factor. A new prognostic scoring model was established based on the independent predictors determined in multivariate analysis.Conclusions: The elevated preoperative AGLR level indicated poor prognosis for patients with HCC; the novel prognostic scoring model had favorable predictive capability for postoperative prognosis of HCC patients, which may bring convenience for clinical management.
What Are the Results of Limb Salvage Surgery for Primary Malignant Bone Tumor in the Forearm?
Authors: Liu Weifeng , Yang Yongkun , Jin Tao , Sun Yang , Li Yuan , Hao Lin , Zhang Qing , Niu Xiaohui 
Published: November 2020

Abstract
Background The forearm primary malignant bone tumor is rare and limb salvage is difficult. The purpose of this study was to analyze epidemiological characteristics of forearm primary malignant bone tumors and to explore oncological and functional results of limb salvage surgery in forearm.Methods 369 patients with primary forearm malignant bone tumors were retrospectively analyzed from 2000 to 2017. There were 266 patients with radius tumor and 46 (17.3%) of them were malignancy, while 103 patients with ulna lesion and 22 (21.4%) of them were malignant tumor. The oncological results, prognostic factors and functional results after limb salvage surgery of forearm malignancy were analyzed.Results A total of 60 patients received limb salvage surgery. Fifty-six patients followed more than 12 months or progressions within 12 months were included in final evaluation. Radius resection was performed in 38 patients and distal radius (25 patients) was most frequent. Ulna resection was performed in 18 patients and proximal ulna (13 patients) was most frequent. The surgical margin contained intracapsular resection in 3 patients, marginal resection in 8 patients and wide resection in 45 patients. The follow-up averaged 72.1 (7-192, median 62.5) months. Local recurrence occurred in 11 patients (19.6%) and distant metastasis occurred in 14 patients (25%). The 5-year recurrence free survival rates was 79.8%. Univariate analysis showed history of unplanned resection, tumor located in ulna, tumor located in proximal forearm and inadequate surgical margin were associated with recurrence. The overall 5-year and 10-year survival rates were 83.5% and 71.7%, respectively. Univariate analysis showed inadequate surgical margin, local recurrence and distant metastasis were associated with death. Forty-two patients were evaluated by MSTS score with an average of (93.0 ± 5.1) %.Conclusions The incidence of radius malignant tumor is higher than that of ulna. The distal radius and proximal ulna are most frequency involved sites. Unplanned resection, tumor located in ulna, tumor located in proximal forearm and inadequate surgical margin are risk factors for local recurrence; local recurrence and distant metastasis are independent prognostic factors of death. The oncology control and function result of limb salvage surgery was satisfactory.
Impact of Educational Self-Efficacy Enhancement Program on Quality of Life, Pain Management, Self-Efficiency Behaviors, and Its Impact of Satisfaction among Adult Diabetic Patients with Peripheral Neuropathy Pain
Authors: Abu-Shennar Jawad Ahmad , Bayraktar Nurhan 
Published: November 2020

Abstract
Aims:This study aims to investigate the impact of the educational self-efficacy enhancement program on quality of life, pain management, self-efficiency behaviors, and its impact satisfaction among adult diabetic patients with peripheral neuropathy pain.Materials and methods:This randomized controlled study was conducted at the Jordanian Ministry of Health. during the period from October - March 2020 with 72 adult diabetic patients with peripheral neuropathy pain, after the ethical approval. Study group participants have implemented an educational self-efficacy enhancement program. Demographic data from, Diabetes Self-Efficacy Scale, Quality of Life Questionnaire (EQ-5D), Pain Intensity Scale, and Patient Satisfaction Questionnaire were used in data collection. Results: This study found that the self-efficacy enhancement program had a significantly positive impact on diabetic peripheral neuropathy pain patients’ QoL, pain levels, self-efficiency behaviors, and satisfaction. Conclusion: It is crucial to improve their self-efficacy behaviors and modification of lifestyle and behavioral changes such as appropriate diet, exercise, reduce weight and encouragement stop smoking, and regularly visit treating physicians.
Fbw7 Inhibits the Progression of Activated B-cell Like Diffuse Large B-cell Lymphoma by Targeting the Positive Feedback Loop of the LDHA/lactate/miR-223 Axis
Authors: Yao Su , Guo Tairan , Zhang Fen , Chen Yu , Xu Fangping , Luo Donglan , Luo Xinlan , Lin Danyi , Chen Wendan , Li Zhi , Liu Yanhui 
Published: November 2020

Abstract
Background: F-box and WD repeat domain-containing 7 (Fbw7) is an ubiquitin ligase and tumor suppressor which targets a variety of oncogenic proteins for proteolysis. We previously reported that Fbw7 regulates apoptosis in diffuse large B-cell lymphoma (DLBCL) through Fbw7-mediated ubiquitination of Stat3. However, the mechanism by Fbw7-mediated tumor metabolism remains undefined. We examined the function of Fbw7 for tumor metabolism and progression in DLBCL.Methods: The effect of Fbw7 overexpression on Lactate Dehydrogenase A (LDHA)-related tumor metabolism was explored in activated B-cell (ABC) like DLBCL. And Fbw7-mediated expression of LDHA in DLBCL was detected by immunoprecipitation for protein interaction, ubiquitination assay, western blotting and mRNA qualitative analyses. In vitro and in vivo studies were done to measure the function of the Fbw7-mediated LDHA/lactate/miR-223 axis in DLBCL progression.Results: We demonstrated that the ubiquitin-ligase Fbw7 played a key role in LDHA-related metabolism. As LDHA and its catalytic lactate were critical for tumor growth and progression in ABC-DLBCL, our results demonstrated that Fbw7 could interact with LDHA to trigger its ubiquitination and degradation, and lactate negatively regulated Fbw7 via inducing the expression of miR-223, which targeted Fbw7 3’-UTR to inhibit its expression. In vivo and in vitro studies revealed that miR-223 promoted tumor growth and that the effects of miR-223 on tumor growth were primarily related to the inhibition of Fbw7-mediated LDHA’s ubiquitination. Conclusions: Our study uncovers a positive functional loop consisting of a Fbw7-mediated LDHA/lactate/miR-223 axis, which may support the future ABC-DLBCL therapy by targeting LDHA-related inhibition.
ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer
Authors: cui hanwei , Yi Qian , Tian Min , Liang Yuteng , Huang Jie , Zeng Qi , Sun Weichao , Han Jian , Guo Jianxin , Yu Zhiying , Liu Wenlan , Ye Xiufeng 
Published: November 2020

Abstract
BackgroundAdenosine (A)-to-inosine (I) RNA editing is the most prevalent RNA editing mechanism, in which adenosine deaminases acting on RNA 1 (ADAR1) is a major adenosine deaminase. Increasing evidence suggests that editing dysregulation of ADAR1 plays an important role in human tumorigenesis, while the underlying mechanism remains elusive. MethodsThe clinical relevance of ADAR1 was analyzed by real-time PCR, western blotting and immunohistochemistry of ovarian cancer tissues. ADAR1 function on ovarian cancer cells in vitro were explored by colony formation assay, transwell assay and Brdu-based cell cycle assay in vitro and xenograft models in vivo. Western blotting, immunostaining and DNA/RNA immunoprecipitation-qPCR were conducted to confirm DNA damage and R-loop accumulation in ovarian cancer cells. Co-immunoprecipitation and DNA/RNA immunoprecipitation were performed to detect interaction of DHX9, ADAR1 and R-loop complex in ovarian cancer cells.ResultsWe demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients. Importantly, silence of ADAR1 repressed ovarian cancer cell growth and colony formation in vitro and inhibited ovarian cancer cell tumorigenesis in vivo. Further cell cycle and transcriptome profile analysis revealed that silence of ADAR1 in ovarian cancer cells induced cell cycle arrest at G1/G0 stage. Mechanically, loss of ADAR1 caused R-loop abnormal accumulation, thereby contributing to single stand DNA break and ATR pathway activation. Additionally, ADAR1 interacted with DHX9 to regulate R-loop complex formation, and A-to-I editing of nascent RNA repressed R-loop formation during co-transcriptional process. ConclusionsOur results identify a novel ADAR1/R-loop/ATR axis critical for ovarian cancer progression and a potential target for ovarian cancer therapy.
Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling
Authors: Gao Zicong , Han Xingxing , Zhu Yuying , Zhang He , Tian Ran , Wang Zhiyong , Cui Yanfen , Wang Zhaosong , Niu Ruifang , Zhang Fei 
Published: November 2020

Abstract
Background: The failure of chemotherapy is accompanied by the emergence of drug resistance and tumor relapse. Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying the pro-invasive and metastatic ability of drug resistance remain elusive. Exosome-mediated intercellular communications between cancer cells and stromal cells in tumor microenvironment are required for cancer initiation and progression. Recent reports have shown that communications between cancer cells also promote tumor aggression. However, little attention has been regarded on this aspect. In this study, we aimed to investigate the mechanisms of exosomes derived from drug-resistant cells in regulating the invasion and metastasis of sensitive breast cancer cells.Methods: Exosomes isolated from drug-resistant breast cancer cells and their parental cells were used to treat breast cancer cells, and then the migration and invasion abilities were examined. The tandem mass tag (TMT)-based quantitative proteomic method was carried out to identify key molecules that regulate cancer aggressiveness. Lentivirus-mediated shRNAs, overexpression, point mutation, truncation mutation, Western blotting, tumor xenograft mice models, and in vivo breast cancer metastatic models were used to investigate the functional role of EphA2 on the invasion and metastatic potential of breast cancer cells.Results: We demonstrated that drug-resistant cell-derived exosomes promoted the migration and invasion of sensitive breast cancer cells. Quantitative proteomic analysis showed that EphA2 was rich in exosomes from drug-resistant cells. Exosomal EphA2 conferred the invasive/metastatic phenotype transfer from drug-resistant cells to sensitive cells. In addition, we provided considerable evidence that exosomal EphA2 activated ERK1/2 signaling through the ligand Ephrin A1-dependent reverse pathway rather than the forward pathway, thereby promoting breast cancer progression. Conclusions: Our findings indicate the key functional role of exosomal EphA2 in the transmission of aggressive phenotype between cancer cells that do not rely on direct cell–cell contact. Our study also suggests that the increase of EphA2 in drug-resistant cell-derived exosomes may be an important mechanism of chemotherapy/drug resistance-induced breast cancer progression.
Exosomes from Gastric Cancer Suppressed Adipo-differentiation of Adipose Mesenchymal Stem Cells to Promote Cancer-associated Cachexia via miR-155/ C/EPBβ pathway
Authors: Liu Ying , Lin Dan , Wang Huiya , Zhang Haiyang , Deng Ting , Liu Rui , Ning Tao , Bai Ming , Ying Guoguang , Ba Yi 
Published: November 2020

Abstract
BACKGROUND: Cancer-associated cachexia (CAC) is defined as a multifactorial syndrome including depletion of adipose tissue and skeletal muscle. Adipose tissue wasting, as a key characteristic of CAC, occurs early and is related with poor survival. However, the influence of exosomes on adipo-differentiation in CAC remained be mysterious.METHODS: Oil-red staining, western blotting, and real-time polymerase chain reaction (RT-PCR) were used to investigate the adipo-differentiation capacity of A-MSCs from GC patients and healthy donors. Adipo-differentiation capacity of A-MSCs treated with exosomes from GES-1 or GC cell lines was also detected. To further explore the effects of exosomal miR-155 on adipo-differentiation in vitro, we carried out luciferase reporter assay. Finally, to evaluate the function of exosomal miR-155 in vivo, BALB/c mice were subcutaneously transplanted with SGC7901 cells transfected with lentivirus containing a miR-155 overexpressing (miR-155 OE) sequence or miR-155 shRNA (miR-155 KO) or control lentivirus(NC) to observe the change of adipo-differentiation of A-MSCs.RESULTS: We showed that miR-155 was high expressed in adipose mesenchymal stem cells (A-MSCs) isolated from GC patients, which exhibited significantly suppressed adipo-differentiation. Mechanistically, targeting C/EPBβ and suppressing C/EPBα and PPARγ by GC exosomal miR-155 was demonstrated to be involved in impairing the differentiation of A-MSCs into adipocytes. The expression of C/EPBβ C/EPBα and PPARγ were rescued through downregulating miR-155 in GC exosomes. Moreover, overexpression of miR-155 improved cancer cachexia in tumor-implanted mice, charactered by weight loss, tumor progression and low expression of C/EPBβ, C/EPBα, and PPARγ in A-MSCs as well as FABP4 in tumor-related adipose tissue. Decreasing level of miR-155 in implanted tumor blocked the anti-adipogenic effects of GC. CONCLUSION: GC exosomsal miR-155 suppressed adipo-differentiation of A-MSCs via targeting C/EPBβ of A-MSCs plays a crucial role in CAC.
H3K4me3 and H3K27ac Activated lncRPL34-AS1 Acts as a Suppressor of Esophageal Squamous Cell Carcinoma via Targeting miR-575/ACAA2 Axis and Binding to ALOX12B and CAT
Authors: Zhang Hu , Pan Enchun , Zhang Ying , Zhao Chao , Liu Qiwei , Lu Qiang , Zhou Jingjing , Liu Ran , Wang Shizhi , Pu Yuepu , Yin Lihong 
Published: November 2020

Abstract
Background: Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRPL34-AS1 in the development and progression of ESCC. Methods: The expression level of lncRPL34-AS1 in ESCC tissues and different cell lines was determined by quantitative real-time PCR (RT-qPCR). Chromatin immunoprecipitation (ChIP) assay was used to evaluate the regulatory effect of histone modification on lncRPL34-AS1. Then, functional experiments in vitro and in vivo were employed to explore the effects of lncRPL34-AS1 on tumor growth and metastasis in ESCC. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between lncRPL34-AS1, miR-575 and ACAA2. In addition, comprehensive identification of RNA binding proteins (ChIRP), mass spectrometry, and RIP assay were used to identify lncRPL34-AS1-interacting proteins.Results: LncRPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. The chromatin immunoprecipitation (ChIP) assays indicated that gain of H3K4me3 and H3K27 acetylation-activated lncRPL34-AS1 was down-regulated in ESCC. Functionally, upregulation of lncRPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, cell cycle progression and induced apoptosis in vitro, whereas knockdown of lncRPL34-AS1 elicited the opposite function. Consistently, overexpression of lncRPL34-AS1 inhibited tumor growth and metastasis in vivo. Mechanistically, lncRPL34-AS1 acted as competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. In addition, protein ALOX12B and CAT resulted direct binding targets of lncRPL34‐AS1 and affected biological process in ESCC. Conclusions: Together, our results reveal a role for lncRPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using lncRPL34-AS1 as a potential biomarker and a therapeutic target for patients with ESCC.
Genome Instability and Pressure on Non-Homologous end Joining drives Chemotherapy Resistance via a DNA Repair Crisis Switch in Triple Negative Breast Cancer.
Authors: Wiegmans Adrian , Ward Ambber , Ivanova Ekaterina , Duijf Pascal H G , VanOosterhout Romy , Sadowski Martin C , Kelly Greg , Morrical Scott , Lee Jason S , Richard Derek J 
Published: November 2020

Abstract
Background: Chemotherapy intensifies pressure on the DNA repair pathways that can lead to deregulation. There is an urgent clinical need to be able to track the emergence of chemotherapy resistance and tailor patient staging appropriately. This is especially evident in the triple negative breast cancer (TNBC) subtype, of which standard of care is chemotherapy with tumours displaying high levels of inherent genome instability. TNBC has an overall poor prognosis for survival. There have been numerous studies into single agent chemoresistance but to date no study has elucidated in detail the roles of the key DNA repair components in resistance associated with the frontline clinical combination of anthracyclines and taxanes together. Methods: In this study, we hypothesized that the emergence of chemotherapy resistance is driven by changes in functional signaling in the DNA repair pathways. We identified the importance of the DNA repair pathways in chemoresistant clinical samples and characterized the emergence of chemoresistance in TNBC cell lines. We utilized classical DNA repair assays and specific targeting of key DNA repair proteins to elucidate a new mechanism for adaptation to the combination of doxorubicin and docetaxel. Results: We identified that consistent pressure on the non-homologous end joining pathway in the presence of genome instability causes failure of the key kinase DNA-PK, loss of p53 and compensation by p73. In-turn a switch to reliance on the homologous recombination pathway and RAD51 recombinase occurs to repair residual double strand DNA breaks. Conclusions: We demonstrate that RAD51 is an actionable target for resensitization to chemotherapy in resistant cells with a matched gene expression profile of resistance highlighted by homologous recombination.