bluuebunny/crossref_metadata_2025 huggingface dataset:
Iliac vein thrombectomy in a metastatic ovarian cancer patient: a case report and literature review
Authors: Yang Fanchun , Liu Jie , Luo Ning , Jiang Hui ci , Guo Jing , Cheng Zhongping
Published: November 2020

BackgroundCirculating tumor cells (CTCs) is a major prognostic factor in both primary and metastatic tumor and associated with thrombosis,which may resulted in the formation of Venous thromboembolism (VTE) and the incidence of some adverse events. For the VTE, we can use anticoagulant treatment and Inferior vena cava filter (IVCF) to reduce the risk of pulmonary embolism (PE). However, For large vessels thrombus, These methods can’t solve the problem. So, innovative therapies can quickly and effectively alleviate symptoms and remove tumor thrombus, reducing the possibility of tumor hematogenous dissemination. External iliac venous thrombosis from metastatic ovarian cancer has rarely been reported, especially involving the mechanism that CTCs may lead to the formation of VTE. And little has been reported about the therapy of iliac vein thrombectomy to remove embolus. Here, we present a case of external iliac venous thrombosis and review relevant literature to provide a better recognition of this disease and relevant mechanism.Case presentationThe present case report describes a 60-year-old woman with the external iliac vein thrombosis. She received anticoagulant treatment and we inserted an IVCF to reduce the risk of PE. But it can’t alleviate symptoms and remove tumor thrombus. Finally, we incised external iliac vein to remove the embolus by open operation with the help of multiple disciplinary teamwork(MDT). The IVCF was retrieved on postoperative day nine. And the patient was discharged home on postoperative day twelve. She has good recovery after operation and has no recurrence. ConclusionsThe current report demonstrated that Preoperative IVCF insertion and iliac vein thrombectomy combined with MDT in the treatment of this metastatic cancer patient with deep venous thrombosis(DVT) is effective. And CTCs may involve in the formation of DVT of cancer patients, Exploring the mechanism of VTE that is associated with CTCs is vital important. In addition, Using innovative therapies such as iliac vein thrombectomy to remove embolus is also significant.
Clinical features and outcomes of new daily persistent headache in patients in China and comparison with medication-overuse headache: A double-center retrospective study
Authors: Liu Huanxian , Ran Ye , Dang Liang , Yang Ruirui , Sun Shuping , Zhang Meichen , Li Ke , Chen Chunfu , Dong Zhao , Yu Shengyuan
Published: November 2020

Background: This study examined the clinical features and outcomes of NDPH patients and comparison with medication-overuse headache (MOH) in mainland China.Methods: This retrospective study observed patients with NDPH and medication-overuse headache (MOH) visiting two outpatient clinics between November 2011 and December 2019. Clinical information was collected and all patients were followed by telephone.Results: The study recruited 73 NDPH and 638 MOH patients. The NDPH patients included 39 males (53.4%) and 34 females (46.6%), with an average age of 37.4 years and average headache duration of 10.6 years. Headache-precipitating factors included infection (15.1%) and stress (30.1%). Compared to MOH patients, NDPH patients had a male predominance (53.4% vs. 22.6%, p<0.001), younger age of CDH onset (26.7±12.3 vs. 41.4±11.3 years, p<0.001), and longer duration of CDH (10.6±11.8 vs. 6.1±6.2 years, p=0.023). Of the 62 NDPH patients followed up for 31 months, on average, therapeutic responses were more effective in NDPH patients with trigger factors than in those without trigger factors (71.4% vs. 32.4%; p = 0.002); the odds ratio (OR) of an effective outcome was 5.25 (1.73-17.84, p = 0.005).Conclusions: NDPH is significantly different from MOH, with a male predominance, younger age of CDH onset, and longer duration of CDH. The presence of trigger factors is an independent predictor of better treatment effect in NDPH patients.
Functional proximity mapping of RNA binding proteins uncovers a mitochondrial mRNA anchor that promotes stress recovery
Authors: Qin Wei , Myers Samuel , Carey Dominique , Carr Steven , Ting Alice
Published: November 2020

Proximity labeling (PL) with genetically-targeted promiscuous enzymes has emerged as a powerful tool for unbiased proteome discovery. By combining the spatiotemporal specificity of PL with methods for functional protein enrichment, it should be possible to map specific protein subclasses within distinct compartments of living cells. Here we demonstrate this capability for RNA binding proteins (RBPs), by combining peroxidase-based PL with organic-aqueous phase separation of crosslinked protein-RNA complexes (“APEX-PS”). We validated APEX-PS by mapping nuclear RBPs, then applied it to uncover the RBPomes of two unpurifiable subcompartments - the nucleolus and the outer mitochondrial membrane (OMM). At the OMM, we discovered the RBP SYNJ2BP, which retains specific nuclear-encoded mitochondrial mRNAs during translation stress, to promote their local translation and import of protein products into the mitochondrion during stress recovery. APEX-PS is a versatile tool for compartment-specific RBP discovery and expands the scope of PL to functional protein mapping.
Real Time Viral Sub-Strains Discovery in Emerging Infectious Disease Situation – The African Perspective
Authors: Ekpenyong Moses Effiong , Edoho Mercy , Inyang Udoinyang G. , Uzoka Faith-Michael , Udo Ifiok J , Uto Nseobong P. , Ekaidem Itemobong S. , Moses Anietie E. , Anwana Enoabasi D. , Tatfeng Youchou M. , Joseph Geoffrey , Dan Emmanuel A.
Published: November 2020

BackgroundThe increased number of accessible genomes has prompted large-scale comparative studies for decerning evolutionary knowledge of infectious diseases, but challenges such as non-availability of close reference sequence(s), incompletely assembled or large number of genomes, preclude real time multiple sequence alignment and sub-strain(s) discovery. This paper introduces a cooperatively inspired open-source framework, for intelligent mining of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes. We situate this study within the African context, to drive advancement on state-of-the-art, towards intelligent infectious disease characterization and prediction. The outcome is an enriched Knowledge Base, sufficient to provide deep understanding of the viral sub-strains’ identification problem. We also open investigation by gender, which to the best of our knowledge has been ignored in related research. Data for the study came from the Global Initiative on Sharing All Influenza Data database (https://gisaid.org) and processed for precise discovery of viral sub-strains transmission between and within African countries. To localize the transmission route(s) of each isolate excavated and provide appropriate links to similar isolate strain(s), a cognitive solution was imposed on the genome expression patterns discovered by unsupervised self-organizing map (SOM) component planes visualization. The Freidman-Nemenyi’s test was finally performed to validate our claim.ResultsEvidence of inter- and intra-genome diversity was noticed. While some isolates (or genomes) clustered differently, implying different evolutionary source (or high-diversity), others clustered closely together, indicating similar evolutionary source (or less-diversity). SOM component planes analysis revealed multiple sub-strains patterns, strongly suggesting local or intra-community and country to country transmissions. Cognitive maps of both male and female isolates revealed multiple transmission routes. Statistical results indicate significant difference between the various isolate groups at the 0.05 level of significance.ConclusionThe proposed framework offers explanations to SARS-CoV-2 diversity and provides real time identification to disease transmission routes, as well as rapid decision support for facilitating inter- and intra-country contact tracing of infected case(s). Intermediate data produced in this paper are helpful to enrich the genome datasets for intelligent characterization and prediction of COVID-19 and related pandemics, as well as the construction of intelligent device for accurate infectious disease monitoring.
Non Linearity Coefficient Evaluation of Zinc Oxide Doped Modulated Red Sea Egyptian Clay as a Varistor
Authors: Elkhatib Mohamed Ibrahim Elsaeed , Dawoud Maher , Ramah Yasser , Hammad Fawzy
Published: November 2020

Doping ZnO with different ratios of clays can increase the value of nonlinear parameters. The natural clay has been precipitated in water column, as a result of the difference in the physical properties of the different phases, the clay will precipitate in layers lighter by lighter from the bottom of the water column, So SiO2 concentrates in lower layers and decreases to the upper layers, whereas Albite, montomorillonite, and dolomite behaves in opposite.ZnO has been doped with different layers up to 20 % clay and sintered at 1200 C for one hour. The obtained samples have been prepared for the different measurements XRD, J-E characteristics, and SEM. XRD showed different phases with different percentages along the whole divided layers of the precipitated column. The maximum value of SiO2 concentrates at layer 3 while the other phases have their lowest values. The electrical measurements (J-E) declared that the maximum value of α obtained by dope ZnO with layer 7 or layer no.11. The peak in α obtained at doping levels 10% or 18% for all the studied layers, this indicates the proper concentration of Si and Al that stabilize the interface potential barrier.
Proteomic Analysis for Identification of Novel Urinary Biomarkers in Juvenile Systemic Lupus Erythematosus
Authors: Zhang Song , CAI Zhe , Zhi Cheng , Lin Yanhao , Wu Ping , Ren Qi , Wei Ping , Chen Rui , Li Feng , Xie Ying , Wong Chun Kwok , Tang Hong , Zeng Huasong
Published: November 2020

Background: To identify new markers of juvenile systemic lupus erythematosus (JSLE) that facilitate patient stratification and prognosis is quite important. Therefore, our aim of the present study is to analyze alteration of protein expression and potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE) urine. Methods: Based on this aim, proteomics assay analyzed the changes of urinary proteins in study groups consisting of 9 healthy controls, 9 inactive JSLE and 10 active JSLE patients. And the correlationship between clinical characteristics of JSLE patients and new biomarkers discovered from proteomics assay was qualified.Results: We have identified a group of 105 differentially expressed proteins with ≥1.3 fold up-regulation or ≤0.77 fold down-regulation in JSLE patients. In gene ontology and functional enrichment analysis, we discovered these proteins were involved in several important biological processes such as acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation. Interestingly, we found that Ephrin type-A receptor 4 (EPHA4) and Vitronectin (VTN) were significantly reduced in the urine of both inactive and active JSLE patients. Especially, the urinary VTN was also linear correlated with clinical characteristics of JSLE. Conclusion: In summary, this study provided a reliable proteomic reference profile for JSLE. Patients with active and inactive JSLE have differentially obvious metabolic proteins in the urine. VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. These identified proteins as new biomarkers in this study can warrant some further exploiting in a larger prospective validation study.
Juvenile Idiopathic Arthritis in Jordan: Single-Center Experience
Authors: Alzyoud Raed , Alsuweiti Motasem O. , Almaaitah Heba Q. , Aladaileh Bushra N. , Alnoubani Mohammad K. , Alwahadneh Adel M.
Published: November 2020

Background: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders, including all forms of arthritis, begin in children who are less than 16 years old. This study aims to evaluate the clinical and laboratory features of JIA in Jordanian children in a single center.Methods: A retrospective analysis of the medical records of pediatric patients who were diagnosed as JIA based on the International League of Associations for Rheumatology (ILAR) criteria from 2015 through 2019 at a pediatric Rheumatology clinic in Queen Rania Children Hospital. All patients were below the age of 14 at the time of diagnosis. Collected data included age, gender, age at initial presentation and diagnosis, JIA subtypes, and laboratory data.Results: A total of 210 patients were included in this cohort (94 males and 116 females) with a mean age at diagnosis 5.33 ± 3.4 years and the mean age at onset of the disease was 5.08 ± 3.4 years (range 7 months – 14 years). Oligoarticular JIA was the commonest subtype (54.7%), followed by systemic arthritis (17.1%), polyarticular (12.3%). ANA was positive in 70 patients (33.6%). Uveitis occurred in thirty (14.2%) patientsConclusion: To the best of our knowledge, this cohort is the first report on JIA in Jordan, in comparison with other regional and international published reports, Oligoarticular JIA found to be the most common Subtype in our experience. To have more details about JIA characteristics, a population-based rather than a single-center study needs to be conducted in Jordan
Are the Effects in Temperature and Current Flow Dependent on the Areas of Electrode Application of Capacitive-resistive Electric Transfer on the Shoulder? A Cadaveric Study
Authors: Rodríguez-Sanz Jacobo , López-de-Celis Carlos , Hidalgo-García César , Canet-Vintró Max , Fanlo-Mazas Pablo , Pérez-Bellmunt Albert
Published: November 2020

Background

Impingement syndrome is currently estimated to represent 60% of all shoulder pain disorders. Capacitive-Resistive electric transfer therapy is aimed to provoke temperature and current flow changes in superficial and deep tissues. This in vitro study has evaluated the variation of temperature and current flow in the shoulder tissues during two different areas of application of the movable capacitive-resistive electric transfer electrode.
Methods

A cross-sectional study designed, five fresh cryopreserved cadavers (10 shoulders) were included in this study. Four interventions (capacitive and resistive modes; low- and high-power) were performed for 5 minutes each by a diathermy “T-Plus” device in two shoulder regions: postero-superior and antero-lateral. Supraspinatus tendon, glenohumeral capsule and superficial temperatures were recorded at 1-min intervals and 5 min after treatment.
Results

A statistically significant difference was found only for the superficial area and time interaction, with high power-resistive application at the postero-superior shoulder area (P < 0.035). All the applications showed a final temperature increase compared with the basal data, in all the application points. Superficial temperature in the high power-resistive application showed the greatest percent increase (42.93% ± 22.58), followed by the temperature in the tendon area with the same high power-resistive application (22.97% ± 14.70). The high power-resistive application showed the greatest percent of temperature increase in the applications, reaching 65.9% ± 22.96 at 5-min at the superficial level, and 32% ± 24.25 at 4-min at the level of the supraspinatus tendon. At the capsule level, high power-resistive was also the application that showed the greatest percent of increase, with 21.52% ± 16.16. The application with the lowest percent of temperature increase was the low power-capacitive, with a mean value of 4.86% at supraspinatus tendon level and 7.47% at capsular level.
Conclusion

The shoulder postero-superior or antero-lateral areas of application of capacitive-resistive electric transfer did not cause statistically significant differences in the temperature changes in either supraspinatus tendon or glenohumeral capsule tissues in cadaveric samples. The high power-resistive application in the postero-superior area significantly increased superficial temperature compared with the same application in the antero-lateral position area.
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

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

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

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

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

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

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

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

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

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

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.
Samba II PCR testing for COVID-19 in an unselected cohort of pregnant women in the UK
Authors: Xu Ruiling , Pauley Tara Alicia , Missfelder-Lobos Hannah , Haddon Richard John , Gupta Ravindra Kumar , Chong Hsu Phern
Published: November 2020

OBJECTIVE: Asymptomatic carriage of COVID-19 in pregnant women has been reported and could lead to outbreaks in maternity units. We sought to ascertain the impact of rapid isothernal nucleic acid based testing for COVID-19 in an unselected cohort of pregnant women attending our maternity unit. We also assessed the correlation between community prevalence and asymptomatic carriage.DESIGN: Retrospective cohort analysis and literature reviewSETTING: Tertiary hospital in Cambridge, UKPOPULATION: Pregnant women (with gestation age between 12-42 weeks) admitted to a single maternity unit over a 4-week period (07/05/2020-06/06/2020) METHODS: Data were collected using computerised hospital records. Literature searches were performed across multiple repositories. COVID-19 prevalence was extracted from online repositories.RESULTS: NP and OP swabs were obtained from 457/465 women during the study period (98%). The median turnaround time for results was 5.3 hours (interquartile range (IQR) 2.6-8.9 hours). 92% of results were returned within 24 hours. In our cohort, only one woman tested positive, giving a screen positive rate of 0.22% (1/457; 95% confidence interval: 0.04-1.23%). One woman who tested negative developed a fever postnatally following discharge but was lost to follow-up. From our literature review, we did not find any correlation between asymptomatic carriage in pregnant women and the reported regional prevalence of COVID-19. CONCLUSIONS: Testing using the SAMBA-II machine was acceptable to the vast majority of pregnant women requiring admission and had a low turnaround time. Asymptomatic carriage is low, but not correlated to community prevalence rates. Screening pregnant women on admission will remain an important component in order to minimise nosocomial infection.
Characterizing Environmental Inequalities Using Integrated Exposure Assessment and Spatial Approach
Authors: Caudeville Julien , REGRAIN Corentin , TOGNET Frederic , BONNARD Roseline , GUEDDA Mohammed , BROCHOT Celine , BEAUCHAMP Maxime , LETINOIS Laurent , MALHERBE Laure , MARLIERE Fabrice , LESTREMAU Francois , CHARDON Karen , BACH Veronique , ZEMAN Florence Anna
Published: November 2020

BackgroundAt a regional or continental scale, the characterization of environmental health inequalities (EHI) expresses the idea that populations are not equal in the face of pollution. It implies the analysis in order to identifying and managing areas at risk of overexposure where increasing risk to human health is suspected. The development of methods is a prerequisite for the implementation of public health actions aimed at the protection of populations.MethodsThis paper presents the methodological framework developed by INERIS (French national institute for industrial environment and risks) to identify a common framework for conceptualizing and operationalizing environmental exposures as an important step towards articulating a science of EHI. We develop an integrated exposure assessment approach capable to integrate the multiplicity of exposure pathways from various sources, through a series of models up to the internal exposure.ResultsMeasured data from environmental networks reflecting the actual contamination of the environment are reused to characterize the population's exposure. Sophisticated methods of spatial analysis are applied to include additional information and take benefit from spatial and inter-variable correlation to improve data representativeness and characterize associated uncertainty. Integrated approaches bring together all information necessary for assessing the source-to-human-dose continuum using Geographic Information System, multimedia exposure and toxicokinetic model. ConclusionThis framework could be used for many purposes, such as mapping EHI, identifying vulnerable populations and determinants of exposure to manage and plan remedial actions and assessing spatial relationships between health and environmental to identify factors that influence the variability of disease patterns.
Removal of Cu (II) ion from Ezana (Meli) Gold Mining Wastewater Using Eucalyptus Bark as Adsorbent
Authors: Hagos Mebrahtom , Yimam Abubeker , Gebru Kibrom Alebel
Published: November 2020

This study investigated the potential use of Eucalyptus Bark (EB) powder as an adsorbent in batch mode experiments for removal of Cu2+ from Ezana (Meli) wastewater. The discharge of untreated gold mining wastewater contaminated by Cu (II), which is threatening ecosystems and carcinogenic to the human. Since the removal by using adsorption method is cost effective and environmentally friendly, it has been widely studied by many researchers. Characterizations of Eucalyptus Bark were analyzed using proximate analysis, Fourier transform infrared (FTIR) and X-ray diffractometer (XRD). Various characterization techniques showed that the effluent discharged from the factory contains: total suspended solid (TSS), turbidity, Electrical conductivity (EC), Total dissolved solid (TDS), COD, Temperature, pH, cyanide WAD with <11°C (ppm). Atomic absorption spectroscopy study indicated that heavy metals found in the wastewater were in the order Fe2+> Cu (II) >Pb (II) >Mn> Cr (VI) >Zn > Co > Ni > Cd in ppm. The selected parameters were pH, adsorbent dosage and contacting time. The highest percentage of Cu (II) removal achieved was 92%. In this study, the adsorption data were well-fitted to the Langmuir isotherm model.
Genetic Diversity, Population Structure Analysis Using Ultra-High Throughput Diversity array Technology (DArTseq) in Different Origin Sesame (Sesamum	indicum L)
Authors: NEGASH TEWODROS TESFAYE , TESFAYE KASSAHUN , WAKEYO GEMECHU KENENI , ZIYOMO CATHRINE
Published: November 2020

BackgroundSesame is an important oil crop widely cultivated in Africa and Asia continent. Characterization of genetic diversity and population structure of sesame genotypes in these continents can be used to designing breeding methods. In the present study, 300 sesame genotypes comprising 209 local, and 75 exotic collection, and 16 released varieties provided from the Ethiopian Biodiversity Institute and research centers were used in the present study.ResultsThe panel was genotyped using two ultra-high-throughput diversity array technology (DArT) markers (silicoDArT and SNP). Both markers were used to identify the genetic diversity and population structure of sesame germplasm. A total of 6115 silicoDArT and 6474 SNP markers were reported, of which 5002 silicoDArT and 4638 SNP markers were screening with quality control parameters. The average polymorphic information content values of silicoDArT and SNP markers were 0.07 and 0.08, respectively. For further analysis, the allele frequency for each SNP site was calculated and purified with MAF < 0.01 and left 2997 high-quality SNPs evenly distributed across the whole genome that could be used for subsequent analysis. All genotypes used in this study were descended from eight 8 geographical origins. The genetic diversity analysis showed that the average nucleotide diversity of the panel was 0.14. Considering the genotypes based on their geographical origin, Africa collections (0.21) as a whole without Ethiopian collection was more diverse than Asia and when further portioned Africa, North Africa (0.23) collection was more diverse than others, but at the continent level, Asia (0.17) was more diverse than Africa (0.14). The genetic distance among the sesame populations was ranged from 0.015 to 0.394, with an average of 0.165. The sesame populations was clustered into four groups. The structure analysis divided the panel into four subgroups and 21 genotypes were clustered as an admixture. These indicates genotypes from the same origin didn’t classify properly on the premise of the country of origin. ConclusionsThe genetic diversity and population structure revealed in this study should guide the future research work to design association studies and the systematic utilization of the genetic variation characterizing the sesame panel.