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Hepatitis c virus cure with direct acting antivirals: clinical,economic, societal and patient value for china

World Journal of Hepatology 2019年第5期11卷 421-441页

作者： Qing Xie Jian-Wei Xuan Hong Tang Xiao-Guang Ye Peng Xu I-Heng Lee Shan-Lian Hu Department of Infectious Diseases Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Health Economic Research Institute School of PharmacySun Yat-Sen UniversityGuangzhou 510006Guangdong ProvinceChina Center of Infectious Diseases West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260Guangdong ProvinceChina Gilead Sciences Inc Shanghai 200122China Gilead Sciences Inc Foster CityCA 94404United States School of Public Health Fudan UniversityShanghai 200032China Shanghai Health Development Research Center Shanghai 200032China

About 10 million people in china are infected with hepatitis c virus(HcV),with the seroprevalence of anti-HcV in the general population estimated at 0.6%.Delaying effective treatment of chronic hepatitis c(cHc)is associated with liver disease progression,cirrhosis,hepatocellular carcinoma,and liver-related *** extrahepatic manifestations of cHc further add to the disease burden of *** cHc-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and *** of work productivity due to reduced well-being and quality of life in cHc patients further compounds the economic burden of the ***,pegylatedinterferon plus ribavirin(PR)was the standard of ***,a substantial number of patients are ineligible for PR treatment,and only 40%–75%achieved sustained virologic ***,PR is associated with impairment of patient-reported outcomes(PROs),high rates of adverse events,and poor *** the advent of direct acting antivirals(DAAs),the treatment of cHc patients has been *** have broader eligible patient populations,higher efficacy,better PRO profiles,fewer adverse events,and better adherence rates,thereby making it possible to cure a large proportion of all cHc *** article aims to provide a comprehensive evaluation on the value of effective,curative hepatitis c treatment from the clinical,economic,societal,and patient experience perspectives,with a focus on recent data from china,supplemented with other Asian and international experiences where china data are not available.

关键词： Hepatitis c Value of cure Sustained virologic response End stage liver disease Prevention of transmission cost-effectiveness Productivity Societal value Patient-reported outcomes

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Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel c. elegans single-copy transgenic model

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MOLEcULAR NEURODEGENERATION 2020年第1期15卷 65-65页

作者： Guha, Sanjib Fischer, Sarah Johnson, Gail V. W. Nehrke, Keith Univ Rochester Dept Anesthesiol & Perioperat Med Med Ctr Box 604601 Elmwood Ave Rochester NY 14642 USA Univ Rochester Dept Med Nephrol Div Med Ctr Box 675601 Elmwood Ave Rochester NY 14642 USA

Background A defining pathological hallmark of the progressive neurodegenerative disorder Alzheimer's disease (AD) is the accumulation of misfolded tau with abnormal post-translational modifications (PTMs). These include phosphorylation at Threonine 231 (T231) and acetylation at Lysine 274 (K274) and at Lysine 281 (K281). Although tau is recognized to play a central role in pathogenesis of AD, the precise mechanisms by which these abnormal PTMs contribute to the neural toxicity of tau is unclear. Methods Human 0N4R tau (wild type) was expressed in touch receptor neurons of the genetic model organism c. elegans through single-copy gene insertion. Defined mutations were then introduced into the single-copy tau transgene through cRISPR-cas9 genome editing. These mutations included T231E, to mimic phosphorylation of a commonly observed pathological epitope, and K274/281Q, to mimic disease-associated lysine acetylation - collectively referred as "PTM-mimetics" - as well as a T231A phosphoablation mutant. Stereotypical touch response assays were used to assess behavioral defects in the transgenic strains as a function of age. Genetically-encoded fluorescent biosensors were expressed in touch neurons and used to measure neuronal morphology, mitochondrial morphology, mitophagy, and macro autophagy. Results Unlike existing tau overexpression models, c. elegans single-copy expression of tau did not elicit overt pathological phenotypes at baseline. However, strains expressing disease associated PTM-mimetics (T231E and K274/281Q) exhibited reduced touch sensation and neuronal morphological abnormalities that increased with age. In addition, the PTM-mimetic mutants lacked the ability to engage neuronal mitophagy in response to mitochondrial stress. conclusions Limiting the expression of tau results in a genetic model where modifications that mimic pathologic tauopathy-associated PTMs contribute to cryptic, stress-inducible phenotypes that evolve with age. These findings and thei

关键词： Alzheimer’ s disease c elegans Tau Neurodegeneration Post-translational modifications

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Microstructure and mechanical behaviour of Al/B 4 c metal matrix composite

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Materials Today: Proceedings 2020年 25卷 751-754页

作者： Shashi Prakash Dwivedi G. L. Bajaj Institute of Technology & Management Greater Noida Gautam Buddha Nagar U.P. 201310 India

In the present investigation, an attempt was made to develop an aluminium base metal matrix composite with lightweight and good mechanical properties. In this study, AA2014 aluminium alloy was taken as matrix material which density is 2.80 g/cm 3 . Reinforcement material was taken as B 4 c which density is 2.52 g/cm 3 . Uniform distribution of boron carbide was observed inside the AA2014 matrix material. Maximum hardness and tensile strength were found for 10 wt% reinforced boron carbide composite. Toughness, ductility and density reduced by increasing the boron carbide percentage in the matrix material.

关键词： composite Density B 4 c Ductility Porosity

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Identification of transcription factors MYc and c/EBPβ mediated regulatory networks in heart failure based on gene expression omnibus datasets

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BMc cARDIOVAScULAR DISORDERS 2020年第1期20卷 250-250页

作者： Wang, Haiwei Wang, Xinrui Xu, Liangpu cao, Hua Fujian Med Univ Fujian Matern & Child Hlth Hosp Affiliated Hosp Fuzhou 350001 Fujian Peoples R China

BackgroundHeart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure *** transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by *** with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYc and c/EBP beta were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYc and c/EBP beta were down regulated in failing heart tissues. Furthermore, MYc and c/EBP beta mediated downstream target genes were also decreased in failing heart tissues. MYc and c/EBP beta were positively correlated with each other. At last, we constructed MYc and c/EBP beta mediated regulatory networks in failing heart tissues, and identified the MYc and c/EBP beta target genes which had been reported involving the heart failure developmental *** results suggested that metabolism pathways a

关键词： Heart failure c EBP beta MYc Networks Metabolism signaling pathway Insulin signaling pathway

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Hepatitis c virus antigens enzyme immunoassay for one-step diagnosis of hepatitis c virus coinfection in human immunodeficiency virus infected individuals

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World Journal of Hepatology 2019年第5期11卷 442-449页

作者： Ke-Qin Hu Wei cui Susan D Rouster Kenneth E Sherman Division of GI/Hepatology University of CaliforniaIrvineSchool of MedicineOrangeCA 92868United States Division of Digestive Diseases University of Cincinnati College of MedicineCincinnatiOH 45267United States

BAcKGROUND current diagnosis of hepatitis c virus(HcV)infection requires two sequential steps:testing for anti-HcV followed by HcV RNA PcR to confirm *** have developed a highly sensitive and specific HcV-antigens enzyme immunoassay(HcV-Ags EIA)for one-step diagnosis of viremic HcV *** To assess the clinical application of the HcV-Ags EIA in one-step diagnosis of viremic HcV infection in human immunodeficiency virus(HIV)-coinfected *** The study blindly tested HcV-Ags EIA for its performance in one-step diagnosing viremic HcV infection in 147 sera:10 without HcV or HIV infection;54 with viremic HcV monoinfection;38 with viremic HcV/HIV coinfection;and 45 with viremic HcV and non-viremic HIV *** Upon decoding,it was 100%accordance of HcV-Ags EIA to HcV infection status by HcV RNA PcR *** five sera with HcV infection,HcV RNA was as low as 50-59 IU/mL,and four out of five tested positive for HcV-Ags ***,it was also 100%accordance of HcV-Ags EIA to HcV infection status by HcV RNA PcR in 83 sera with HcV and HIV coinfection,regardless if HIV infection was active or *** The modified HcV-Ags EIA has a lower detection limit equivalent to serum HcV RNA levels of approximately 100 IU/*** is highly sensitive and specific in the setting of HIV coinfection,regardless of HIV infection status and cD4 *** data support the clinical application of the HcV-Ags EIA in one-step diagnosis of HcV infection in HIV-infected individuals.

关键词： Hepatitis c virus Hepatitis c virus antigens Hepatitis c virus core antigen Hepatitis c virus diagnostic test Diagnostic assay Enzyme immunoassay

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coupling Remote Sensing With a Process Model for the Simulation of Rangeland carbon Dynamics

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JOURNAL OF ADVANcES IN MODELING EARTH SYSTEMS 2025年第3期17卷

作者： Xia, Yushu Sanderman, Jonathan Watts, Jennifer D. Machmuller, Megan B. Mullen, Andrew L. Rivard, charlotte Endsley, Arthur Hernandez, Haydee Kimball, John Ewing, Stephanie A. Litvak, Marcy Duman, Tomer Krishnan, Praveena Meyers, Tilden Brunsell, Nathaniel A. Mohanty, Binayak Liu, Heping Gao, Zhongming chen, Jiquan Abraha, Michael Scott, Russell L. Flerchinger, Gerald N. clark, Patrick E. Stoy, Paul c. Khan, Anam M. Brookshire, E. N. Jack Zhang, Quan cook, David R. Thienelt, Thomas Mitra, Bhaskar Mauritz-Tozer, Marguerite Tweedie, craig E. Torn, Margaret S. Billesbach, Dave Woodwell Climate Res Ctr Falmouth MA USA Columbia Univ Lamont Doherty Earth Observ Palisades NY USA Montana State Univ Dept Land Resources & Environm Sci Bozeman MT USA Colorado State Univ Nat Resources Ecol Lab Ft Collins CO 80523 USA Brookings Inst Ctr Sustainable Dev Washington DC USA Univ Montana WA Franke Coll Forestry & Conservat Missoula MT USA Colorado Field Off Nat Conservancy Boulder CO USA Univ New Mexico Albuquerque NM USA NOAA Atmospher Turbulence & Diffus Div Oak Ridge TN USA Univ Kansas Dept Geog & Atmospher Sci Lawrence KS USA Texas A&M Univ Biol & Agr Engn Dept College Stn TX USA Washington State Univ Dept Civil & Environm Engn Pullman WA 99164 USA Sun Yat Sen Univ Sch Atmospher Sci Zhuhai Peoples R China Michigan State Univ Dept Geog Environm & Spatial Sci E Lansing MI USA USDA ARS Southwest Watershed Res Ctr Tucson AZ USA USDA ARS Northwest Watershed Res Ctr Boise ID USA Univ Wisconsin Madison Dept Biol Syst Engn Madison WI USA Univ Wisconsin Madison Dept Forest & Wildlife Ecol Madison WI USA Indiana Univ Sch Publ & Environm Affairs Indianapolis IN USA Wuhan Univ Renmin Hosp Wuhan Peoples R China Argonne Natl Lab Div Environm Sci Lemont IL USA Martin Luther Univ Halle Wittenberg Dept Geoecol Wittenberg Germany James Hutton Inst Informat & Computat Sci Aberdeen Scotland Univ Texas El Paso Dept Biol Sci El Paso TX 79968 USA Lawrence Berkeley Natl Lab Climate & Ecosyst Sci Div Berkeley CA USA Univ Nebraska Lincoln Dept Biol Syst Engn Lincoln NE USA

Rangelands provide significant environmental benefits through many ecosystem services, which may include soil organic carbon (SOc) sequestration. However, quantifying SOc stocks and monitoring carbon (c) fluxes in rangelands are challenging due to the considerable spatial and temporal variability tied to rangeland c dynamics as well as limited data availability. We developed the Rangeland carbon Tracking and Management (RcTM) system to track long-term changes in SOc and ecosystem c fluxes by leveraging remote sensing inputs and environmental variable data sets with algorithms representing terrestrial c-cycle processes. Bayesian calibration was conducted using quality-controlled c flux data sets obtained from 61 Ameriflux and NEON flux tower sites from Western and Midwestern US rangelands to parameterize the model according to dominant vegetation classes (perennial and/or annual grass, grass-shrub mixture, and grass-tree mixture). The resulting RcTM system produced higher model accuracy for estimating annual cumulative gross primary productivity (GPP) (R-2 > 0.6, RMSE <390 g c m(-2)) relative to net ecosystem exchange of cO2 (NEE) (R-2 > 0.4, RMSE <180 g c m(-2)). Model performance in estimating rangeland c fluxes varied by season and vegetation type. The RcTM captured the spatial variability of SOc stocks with R-2 = 0.6 when validated against SOc measurements across 13 NEON sites. Model simulations indicated slightly enhanced SOc stocks for the flux tower sites during the past decade, which is mainly driven by an increase in precipitation. Future efforts to refine the RcTM system will benefit from long-term network-based monitoring of vegetation biomass, c fluxes, and SOc stocks.

关键词： gross primary productivity net ecosystem exchange soil organic carbon rangeland flux towers modeling c carbon DNDc Denitrification-Decomposition DSM digital soil mapping fPAR fraction of absorbed photosynthetically active radiation GEE Google Earth Engine GPP Gross Primary Productivity HOc humus organic carbon L4c Level 4 carbon LOOcV leave-one-out cross-validation LUE light use efficiency MBE mean bias error NDVI Normalized Difference Vegetation Index NEE net ecosystem exchange of carbon dioxide NEON National Ecological Observatory Network NIR near infrared band NLcD National Land cover Database NLDAS North American Land Data Assimilation System NPP net primary productivity nRMSE normalized Root Mean Square Error PI principal investigator POc particulate organic carbon Qc quality control RAP Rangeland Analysis Platform RB relative bias RcTM Rangeland carbon Tracking and Management REcO ecosystem respiration RMSE Root Mean Square Error ROc resistant organic carbon Rothc Rothamsted carbon RS remote sensing SMAP Soil Moisture Active-Passive SMLR stepwise multiple linear regression SOc SOM soil organic matter STARFM Spatial and Temporal Adaptive Reflectance Fusion Model VPD vapor pressure deficit

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Sensitive detection methods are key to identify secondary EGFR c.2369c>T p.(Thr790Met) in non-small cell lung cancer tissue samples

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BMc cANcER 2020年第1期20卷 366-366页

作者： Keppens, cleo Dequeker, Elisabeth M. c. Rouleau, Etienne 't Hart, Nils Bubendorf, Lukas Dufraing, Kelly Garrec, celine Gueguen, Paul Lamy, Aude Marchetti, Antonio Pauwels, Patrick Ryska, Ales Tack, Veronique Tornillo, Luigi Van casteren, Kaat von der Thusen, Jan H. Zwaenepoel, Karen Lissenberg-Witte, Birgit Thunnissen, Erik Schuuring, Ed Univ Leuven Dept Publ Hlth & Primary Care Biomed Qual Assurance Res Unit Leuven Belgium Gustave Roussy Serv Genet Tumeurs Villejuif France Univ Groningen Univ Med Ctr Groningen UMCG Dept Pathol Hanzepl 1POB 30001 NL-9700 RB Groningen Netherlands Isala Dept Pathol Zwolle Netherlands Univ Hosp Basel Inst Pathol Basel Switzerland CHU Hotel Dieu Inst Biol Lab Genet Mol Nantes 1 France CHRU Brest Hop Morvan Lab Genet Mol & Histocompatibilite Brest France CHU Rouen Hop Charles Nicolle Lab Genet Somat Tumeurs Rouen France Univ G dAnnunzio Ctr Adv Studies & Technol Lab Mol Diagnost I-66100 Chieti Italy Univ Hosp Antwerp Dept Pathol Edegem Belgium Univ Antwerp Ctr Oncol Res CORE Edegem Belgium Charles Univ Prague Dept Pathol Med Fac Hosp Hradec Kralove Czech Republic GILAB Allschwil AG Switzerland Erasmus MC Dept Pathol Rotterdam Netherlands Vrije Univ Amsterdam Dept Epidemiol & Biostat Amsterdam UMC Amsterdam Netherlands VU Univ Med Ctr VUMC Amsterdam Dept Pathol Amsterdam Netherlands

Background correct identification of the EGFR c.2369c>T p.(Thr790Met) variant is key to decide on a targeted therapeutic strategy for patients with acquired EGFR TKI resistance in non-small cell lung cancer. The aim of this study was to evaluate the correct detection of this variant in 12 tumor tissue specimens tested by 324 laboratories participating in External Quality Assessment (EQA) schemes. Methods Data from EQA schemes were evaluated between 2013 and 2018 from cell lines (6) and resections (6) containing the EGFR c.2369c>T p.(Thr790Met) mutation. Adequate performance was defined as the percentage of tests for which an outcome was available and correct. Additional data on the used test method were collected from the participants. chi-squared tests on contingency tables and a biserial rank correlation were applied by IBM SPSS Statistics version 25 (IBM, Armonk, NY, USA). Results In 26 of the 1190 tests (2.2%) a technical failure occurred. For the remaining 1164 results, 1008 (86.6%) were correct, 151 (12.9%) were false-negative and 5 (0.4%) included incorrect mutations. correct p.(Thr790Met) detection improved over time and for repeated scheme participations. In-house non-next-generation sequencing (NGS) techniques performed worse (81.1%, n = 293) compared to non-NGS commercial kits (85.2%, n = 656) and NGS (97.0%, n = 239). Over time there was an increase in the users of NGS. Resection specimens performed worse (82.6%, n = 610 tests) compared to cell line material (90.9%, n = 578 tests), except for NGS (96.3%, n = 344 for resections and 98.6%, n = 312 for cell lines). Samples with multiple mutations were more difficult compared to samples with the single p.(Thr790Met) variant. A change of the test method was shown beneficial to reduce errors but introduced additional analysis failures. conclusions A significant number of laboratories that offer p.(Thr790Met) testing did not detect this relevant mutation compared to the other EQA participants. However, correct

关键词： Non-small cell lung cancer External quality assessment Predictive biomarker EGFR c 2369c>T p (Thr790Met) Resistance Osimertinib

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Evolution of Physical and Mechanical Properties of Al5083/B 4 c composites fabricated through Stir casting

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Materials Today: Proceedings 2020年 21卷 1229-1233页

作者： Gurpreet Singh Neeraj Sharma Amity University Uttar Pradesh 201313 India Department of Mechanical Engineering Maharishi Markandeshwar (Deemed to be University) Mullana Ambala Haryana 133207 India

In the present work, Aluminium composites were fabricated through conventional stir casting process. The composites were fabricated at 800°c inside the electric furnace in the presence of inert gas. AA5083 and B 4 c particulates with varying weight % of 5, 10, 15 and 20 were used as the starting materials. The microstructure of the composites was examined using scanning electron microscopy (SEM). The physical and mechanical properties of the composites were investigated and the results show that the increase in B 4 c content in the aluminium matrix increases the tensile strength and hardness of the composites to a significant level. The decrease in density accompanied by increase in porosity was also observed with the increase in B 4 c.

关键词： AA5083/B 4 c Tensile strength Hardness Density Porosity

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Hypomethylation of nerve growth factor (NGF) promotes binding of c/EBPα and contributes to inflammatory hyperalgesia in rats

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JOURNAL OF NEUROINFLAMMATION 2020年第1期17卷 34-34页

作者： Yuan, Hongjie Du, Shibin chen, Liping Xu, Xiaoqing Wang, Yufeng Ji, Fuhai Soochow Univ Affiliated Hosp 1 Suzhou 215006 Jiangsu Peoples R China Nantong Hosp Tradit Chinese Med Dept Pain Med Nantong 226001 Jiangsu Peoples R China Shenzhen Univ Gen Hosp Clin Med Acad Dept Anesthesiol Shenzhen 518055 Guangdong Peoples R China Nantong Hosp Tradit Chinese Med Dept Radiol Nantong 226001 Jiangsu Peoples R China

Background chronic pain usually accompanied by tissue damage and inflammation. However, the pathogenesis of chronic pain remains unclear. Methods We investigated the role of nerve growth factor (NGF) in chronic inflammatory pain induced by complete Freund's adjuvant (cFA), explored the methylation status of cpG islands in the promoter region of the NGF gene, and clarified the function and mechanism of c/EBP alpha-NGF signaling pathway from epigenetic perspective in the chronic inflammatory pain model. Results cFA induced significant hyperalgesia and continuous upregulation of NGF mRNA and protein levels in the L4-6 dorsal root ganglions (DRGs) in rats. Hypomethylation of cpG islands occurred in the NGF gene promoter region after cFA treatment. At the same time, the miR-29b expression level was significantly increased, while the DNA methyltransferase 3b (DNMT3b) level reduced significantly. Moreover, cFA treatment promoted binding of c/EBP alpha to the NGF gene promoter region and c/EBP alpha siRNA treatment obviously decreased expression of NGF levels and also alleviate inflammatory hyperalgesia significantly in rats. conclusion collectively, the results indicated that cFA leads to the upregulation of miR-29b level, which represses the expression of DNMT3b, enhances the demethylation of the NGF gene promoter region, and promotes the binding of c/EBP alpha with the NGF gene promoter, thus results in the upregulation of NGF gene expression and maintenance of chronic inflammatory pain.

关键词： NGF c EBP alpha Inflammatory pain DNA methylation Epigenetics

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Necrolytic acral erythema in a human immunodeficiency virus/hepatitis c virus coinfected patient:A case report

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World Journal of Hepatology 2019年第2期11卷 226-233页

作者： Katerina G Oikonomou Dost Sarpel Alexandra Abrams-Downey Adnan Mubasher Douglas T Dieterich Division of Infectious Diseases Icahn School of Medicine at Mount Sinai Department of Pathology Icahn School of Medicine at Mount Sinai Division of Liver Diseases Icahn School of Medicine at Mount Sinai

BAcKGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis c virus(HcV) infection or zinc *** is characterized by erythematous or violaceous lesions occurring primarily in the lower *** treatment includes systemic steroids and oral zinc *** report a case of NAE in a 66-year-old human immunodeficiency virus(HIV)/HcV co-infected woman with *** is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still *** SUMMARY A 66-year-old HIV/HcV co-infected female patient presented with painless,nonpruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and *** skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with *** was started on prednisone and zinc supplementation with resolution of the lesions and improvement of *** clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HcV.

关键词： Necrolytic acral erythema Human immunodeficiency virus Hepatitis c virus Zinc deficiency case report

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