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Performance of the Enhanced Liver Fibrosis Score,Comparison with Vibration-controlled Transient Elastography Data,and Development of a Simple Algorithm to Predict Significant Liver Fibrosis in a Community-based Liver Service:A Retrospective Evaluation

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 800-808页

作者： Tina Reinson Janisha Patel Mead Mathews Derek Fountain Ryan M.Buchanan christopher DByrne nutrition and Metabolism Faculty of MedicineUniversity of SouthamptonSouthamptonUK national Institute for Health and Care Research Southampton Biomedical Research CenterUniversity Hospital SouthamptonSouthamptonUK Hepatology Department University Hospital SouthamptonSouthamptonUK St Mary’s Surgery SouthamptonUK Core Minutes Ltd RingwoodUK Clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthamptonUK

Background and Aims:Liver fibrosis is a key risk factor for cirrhosis,hepatocellular carcinoma and end stage liver *** national Institute for Health and Care Excellence guidelines for assessment for advanced(≥F3)liver fibrosis in people with nonalcoholic fatty liver disease recommend the use of enhanced liver fibrosis(ELF)test,followed by vibration-controlled transient elastography(VCTE).Performance of ELF at predicting significant(≥F2)fibrosis in real-world practice is *** assess the accuracy of ELF using VCTE;investigate the optimum ELF cutoff value to identify≥F2and≥F3;and develop a simple algorithm,with and without ELF score,for detecting≥***:Retrospective evaluation of patients referred to a Community Liver Service for VCTE,Jan-Dec *** included:body mass index(BMI),diabetes status,alanine aminotransferase(ALT)levels,ELF score and biopsy-validated fibrosis stages according to ***:Data from 273 patients were available.n=110 patients had *** showed fair performance for≥F2 and≥F3,area under the curve(AUC)=0.70,95%confidence interval(CI)0.64-0.76 and AUC=0.72,95%CI:0.65-0.79 ***≥F2 Youden's index for ELF=9.85 and for≥F3,ELF=*** ALT,BMI,and HbA1c(ALBA algorithm)to predict≥F2 showed good performance(AUC=0.80,95%CI:0.69-0.92),adding ALBA to ELF improved performance(AUC=0.82,95%CI:0.77-0.88).Results were independently ***:Optimal ELF cutoff for≥F2 is 9.85 and 9.95 for≥***,BMI,and HbA1c(ALBA algorithm)can stratify patients at risk of≥*** is improved by adding ALBA.

关键词： Primary health care Retrospective evaluation Liver disease Diabetes nonalcoholic fatty liver disease

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Development process for a higher capacity Propsetter~ system

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International Journal of Mining Science and Technology 2018年第1期28卷 121-126页

作者： christopher J.Brown Product Development-Strata Worldwide LLC

As longwall tailgate support technologies continue to be developed and improved, strata worldwide has worked to design and manufacture a revised Propsetter to provide additional support capacity and enable applications at greater mine *** support is targeted for tailgate applications, however, it can also be utilized for roof support in various types of mining *** paper describes the design changes for enhancing the support capacity of the Propsetter to more closely align its performance with other support technologies currently being employed in longwall *** changes to each design aspect of the Propsetter was key to successfully improving the roof support's load capacity while maintaining controlled *** the load capacity would allow a mine to improve support efficiency with a smaller, less intrusive support compared to support alternatives and reduce the cost per foot of supported *** target support capacity was 711–890 k n at 50 mm of deformation to more closely match the performance of competing tailgate supports such as the 610 mm-diameter CAn~.To achieve this goal, changes were made to all design aspects of the Propsetter: diameter, wedge cut depth and angle, pod size, and confinement *** results from the nIOSH Mine Roof Simulator verified that these design changes were successful in increasing the capacity of the Propsetter to the 711–890 k n range at fifty mms of deformation.

关键词： Propsetter Can Longwall mining Tailgate roof support Controlled deformation

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MTBSTFA derivatization-LC-MS/MS approach for the quantitative analysis of endogenous nucleotides in human colorectal carcinoma cells

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Journal of Pharmaceutical Analysis 2022年第1期12卷 77-86页

作者： Huixia Zhang Yan Li Zheng Li christopher Wai-Kei Lam Peng Zhu Caiyun Wang Hua Zhou Wei Zhang State Key Laboratory of Quality Research in Chinese Medicines Macao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyTaipaMacaoChina

Endogenous ribonucleotides(Rns)and deoxyribonucleotides(dRns)are important metabolites related to the pathogenesis of many *** light of their physiological and pathological significances,a novel and sensitive pre-column derivatization method with n-(t-butyldimethylsilyl)-n-methyltrifluoroacetamide(MTBSTFA)was developed to determine Rns and dRns in human cells using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A one-step extraction of cells with 85%methanol followed by a simple derivatization reaction within 5 min at room temperature contributed to shortened analysis *** derivatives of 22 nucleoside mono-,di-and tri-phosphates were retained on the typical C;column and eluted by ammonium acetate and acetonitrile in 9 *** these optimal conditions,good linearity was achieved in the tested calibration *** lower limit of quantitation(LLOQ)was determined to be 0.1-0.4μM for the tested Rns and 0.001-0.1μM for *** addition,the precision(CV)wasnd the RSD of stability was lower than 10.4%.Furthermore,this method was applied to quantify the endogenous nucleotides in human colorectal carcinoma cell lines HCT 116 exposed to *** conclusion,our method has proven to be simple,rapid,sensitive,and *** may be used for specific expanded studies on intracellular pharmacology in vitro.

关键词： Ribonucleotides Deoxyribonucleotides Derivatization n-(t-butyldimethylsilyl)-n-methyltrifluoroacetamide High-performance liquid chromatography tandem mass spectrometry

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Patterns of cancer recurrence in localized resected hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2015年第3期14卷 269-275页

作者： Aryavarta MS Kumar Elisha T Fredman christopher Coppa Galal El-Gazzaz Federico n Aucejo May Abdel-Wahab Department of Radiation Oncology 9500 Euclid AveT28 Cleveland ClinicCleveland OH 44195 USA Department of Radiology 9500 Euclid Ave Hb6 Cleveland ClinicCleveland OH 44195 USA Department of Hepato-pancreato-biliary & Transplant Surgery 9500 Euclid Ave A100Cleveland OH 44195 USA

BACKGROUnD： Tumor resection in non-metastatic hepato- cellular carcinoma （HCC） patients with adequate liver reserve offers a potential cure, but has a high 5-year recurrence rate. We analyzed the patterns of cancer... 详细信息

关键词： hepatocellular carcinoma patterns of failure partial hepatectomy

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Vitamin B_(12)-auxotrophy in dinoflagellates caused by incomplete or absent cobalamin-independent methionine synthase genes(metE)

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Fundamental Research 2022年第5期2卷 727-737页

作者： Siheng Lin Zhangxi Hu Xiaoying Song christopher JGobler Ying Zhong Tang CAS Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdao 266071China Laboratory for Marine Ecology and Environmental Science Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China University of Chinese Academy of Sciences Beijing 100049China School of Marine and Atmospheric Sciences Stony Brook UniversityNY11790USA Department of Biological Sciences and Biotechnology Minnan Normal UniversityZhangzhou 363000China

Dinoflagellates are responsible for most marine harmful algal blooms (HABs) and play vital roles in many ocean *** than 90% of dinoflagellates are vitamin B_(12) auxotrophs and that B_(12) availability can control dinoflagellate HABs,yet the genetic basis of B_(12) auxotrophy in dinoflagellates in the framework of the ecology of dinoflagellates and particularly HABs,which was the objective of this ***,we investigated the presence,phylogeny,and transcription of two methionine synthase genes(B_(12)-dependent metH and B_(12)-independent metE)via searching and assembling transcripts and genes from transcriptomic and genomic databases,cloning 38 cDnA isoforms of the two genes from 14 strains of dinoflagellates,measuring the expression at different scenarios of B_(12),and comprehensive phylogenetic analyses of more than 100 *** found that 1)metH was present in all 58 dinoflagellates accessible and metE was present in 40 of 58 species,2)all metE genes lacked n-terminal domains,3)metE of dinoflagellates were phylogenetically distinct from other known metE genes,and 4)expression of metH in dinoflagellates was responsive to exogenous B_(12) levels while expression of metE was not responding as that of genuine metE *** conclude that most,hypothetically all,dinoflagellates have either non-functional metE genes lacking n-terminal domain for most species,or do not possess metE for other species,which provides the genetic basis for the widespread nature of B_(12) auxotrophy in *** work elucidated a fundamental aspect of the nutritional ecology of dinoflagellates.

关键词： Harmful algal blooms(HABs)Dinoflagellates Vitamin B_(12) (cobalamin) Auxotrophy Methionine synthase genes Phytoplankton ecology

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Mycorrhizal Symbioses of Cotton Grown on Sodic Soils:A Review from an Australian Perspective

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Pedosphere 2017年第6期27卷 1015-1026页

作者： Samieh ESKAnDARI christopher n.GUPPY Oliver G.G.KnOX David BACKHOUSE Rebecca E.HALInG School of Environmental and Rural Science University of New EnglandArmidale NSW 2351(Australia) CSIRO Agriculture Canberra ACT 2601(Australia)

The majority of terrestrial plants form some type of mycorrhizal *** established symbiosis therefore exists in most commercially important crops, which includes *** mycorrhizal fungus(AMF) can colonise 50%–90% of cotton root length under field and controlled *** improves growth and nutrient uptake(especially phosphorus) of cotton,particularly at the early growth *** symbioses help plants to counter the stresses imposed by physical and chemical soil constraints; however, adverse environmental conditions may restrict the mycorrhizal associations and consequently may reduce nutrient uptake and impair plant *** Australia, cotton is mainly grown on sodic soils that contain more than 6% of the total cations as exchangeable *** levels of sodium in the soil create adverse physical and chemical soil conditions that may negatively affect mycorrhizal symbioses of *** review discusses the cotton mycorrhizal colonisation, plant growth, and disease protection effects, potential negative effects of physical and chemical properties of sodic soils, and influences of some agronomic management *** addition, the research gaps were identified and some practical applications of the research outcomes were suggested.

关键词： agronomic management arbuscular mycorrhizal fungus(AMF) disease protection exchangeable sodium pathogen plant growth soil property

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Aneuploidy in pluripotent stem cells and implications for cancerous transformation

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Protein & Cell 2014年第8期5卷 569-579页

作者： Jie na Duncan Baker Jing Zhang Peter W. andrews Ivana Barbaric School of Medicine Tsinghua University Beijing 100084 China Sheffield Diagnostic Genetic Services Sheffield Children's Hospital Sheffield S10 2TH UK Centre for Stem Cell Biology Department of Biomedical Science The University of Sheffield Sheffield S10 2TN UK

Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure （particularly of chromosomes 1, 12, 17 and 20）, remi- niscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving for- ces behind the genome evolution that may eventually lead to cancerous transformation.

关键词： human pluripotent stem cells (hPSCs),culture adaptation aneuploidy cancer genetic changes

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Liver transplantation in patients with incidental hepatocellular carcinoma/cholangiocarcinoma and intrahepatic cholangiocarcinoma： a single-center experience

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 264-270页

作者： Mohammed Elshamy naftali Presser Abdulrahman Y Hammad Daniel J Firl christopher Coppa John Fung Federico n Aucejo Hepatobiliary and Transplant Surgery Digestive Disease and Surgery Institute Cleveland Clinic Cleveland OH USA Imaging Institute Cleveland Clinic Cleveland OH USA

BACKGROUnD： Reports of fiver transplantation （LT） in patients with mixed hepatocellular carcinoma/cholangiocarcinoma （HCC/CC） and intrahepatic cholangiocarcinoma （ICC） are modest and have been mostly retrospective after pathological categorization in the setting of presumed HCC. Some studies suggest that patients undergoing LT with small and unifocal ICC or mixed HCC/CC can achieve about 40%-60% 5-year post-transplant survival. The study aimed to report our experience in patients undergoing LT with explant pathology revealing HCC/CC and ICC. METHODS： From a prospectively maintained database, we performed cohort analysis. We identified 13 patients who underwent LT with explant pathology revealing HCC/CC or ICC. RESULTS： The observed recurrence rate post-LT was 31% （4/13） and overall survival was 85%, 51%, and 51% at 1, 3 and 5 years, respectively. Disease-free survival was 68%, 51%, and 41% at 1, 3 and 5 years, respectively. In our cohort, four patients would have qualified for exception points based on updated HCC Organ Procurement and Transplantation network imaging guidelines. COnCLUSIOnS： Lesions which lack complete imaging characteristics of HCC may warrant pre-LT biopsy to fully elucidate their pathology. Identified patients with early HCC/CC or ICC may benefit from LT if unresectable. Additionally, incorporating adjunctive perioperative therapies such as in the case of patients undergoing LT with hilar cholangiocarcinoma may improve outcomes but this warrants further investigation.

关键词： mixed hepatocellular carcinoma/ cholangiocarcinoma liver transplantation survival outcomes

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neuromyelitis optica spectrum disorders and anti-myelin oligodendrocyte glycoprotein positive optic neuropathies

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International Journal of Ophthalmology(English edition) 2022年第7期15卷 1095-1107页

作者： Patrick Murtagh Amy Coman Kirk Stephenson Maria Gaughan David Ryan Graeme Mcneill christopher McGuigan Lorraine Cassidy Royal Victoria Eye and Ear Hospital Adelaide RoadDublin 2D02 XK51Republic of Ireland St Vincent’s University Hospital Elm ParkDublin 4D04 N2E0Republic of Ireland

AIM: To describe the clinical characteristics and treatments associated with antibody positive optic neuropathies including anti-myelin oligodendrocyte glycoprotein(MOG) and anti-aquaporin 4(AQP4), alongside diagnostic modalities, investigations, and outcomes. METHODS: A cross-sectional single-centre retrospective case series consisting of 16 patients including 12 antiMOG positive patients and 4 anti-AQP4 positive patients. Each of these patients had clinical signs and symptoms of optic neuritis and consisted of all patients who had a positive blood antibody result in our centre. Clinical findings including presence of a relative afferent pupillary defect, colour vision and disc assessment were recorded. Structured clinical exam and multimodal imaging was undertaken sequentially on each. Optical coherence tomography(OCT) scanning was preformed to examine the correlation between ganglion cell layer(GCL) thickness and visual acuity(VA) at presentation and as a determinant of final visual outcome in both groups. Initial and long-term treatment is also summarised. RESULTS: A total of 16 patients were included in the study consisting of 12 anti-MOG and 4 anti-AQP4 positive patients. nine of the 16 patients were female and the average age of onset was 29.2 y in the MOG group and 42 y in the AQP4 group. There was no statistically significant correlation(Pearson correlation) between GCL thickness and presenting and final VA [r(10)=0.081, P=0.08 and r(10)=0.089, P=0.34 respectively]. The same statistical analysis was performed for the correlation between retinal nerve fibre layer(RnFL) and VA and similar outcomes wereobserved [r(10)=0.04, P=0.22 and r(10)=0.09, P=0.04]. no correlation was seen for initial RnFL thickness and final visual outcome in this group either [r(2)=0.19, P=0.38]. Visual field testing and radiological findings for each group are described. COnCLUSIOn: no correlation between initial VA or RnFL and final visual outcome is identified. A broad range of visu

关键词： neuromyelitis anti-myelin oligodendrocyte glycoprotein antibody anti-aquaporin 4

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Inhibition of retroviral Gag assembly by non-silencing miRnAs promotes autophagic viral degradation

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Protein & Cell 2018年第7期9卷 640-651页

作者： na Qu Zhao Ma Mengrao Zhang Muaz n. Rushdi christopher J. Krueger Antony K. Chen Department of Biomedical Engineering College of Engineering Peking University Beijing 100871 China Wallace H Coulter Department of Biomedical-Engineering Georgia Institute of Technology Atlanta GA 30332 USA

We recently reported an unconventional mechanism by which miRnAs inhibit HIV-1 viral production. This occurs when miRnAs bind nonspecifically to the viral structural protein Gag, interfering with viral RnA-medi- ated Gag assembly at the plasma membrane. Conse- quently, misassembled viral complexes are redirected into the endocytic pathway where they are delivered to lysosomes for degradation. In this study, we demon- strate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific. Misassembled viral complexes were found to colocalize extensively with LC3 and p62 in late endo- somesllysosomes, demonstrating a convergence of autophagy with functional degradative compartments. Knocking down autophagosome formation machineries reduced this convergence, while treatment with autop- hagy-inducer rapamycin enhanced the convergence. Furthermore, similar autophagy-dependent nonspecific miRnA inhibition of murine leukemia virus （MLV） assembly was shown. Overall, these results reveal autophagy as a crucial regulator of the retroviral degradation pathway in host cells initiated by non- specific miRnA-Gag interactions. These findings could have significant implications for understanding how cells may regulate retroviral complex assembly by miRnA expression and autophagy, and raise the possi- bility that similar regulations can occur in other biolog- ical contexts.

关键词： microRnA Gag protein autophagy

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