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Boceprevir early-access for advanced-fibrosis/cirrhosis in Asia-pacific hepatitis c virus genotype 1 non-responders/relapsers

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World Journal of Gastroenterology 2015年第28期21卷 8660-8669页

作者： Wattana Sukeepaisarnjaroen Tri Pham Tewesak Tanwandee Saroja Nazareth Sam Galhenage Lindsay Mollison Leanne Totten Alan Wigg Rosalie Altus Anton colman Brenda Morales Sue Mason Tracey Jones Nadine Leembruggen Vince Fragomelli cheryl Sendall Richard Guan Dede Sutedja Soek Siam Tan Yock Young Dan Yin Mei Lee Widjaja Luman Eng Kiong Teo Yin Min Than Teerha Piratvisuth Seng Gee Lim Srinagarind Hospital Cabramatta Practice Siriraj Hospital Bangkok Royal Perth Hospital Fremantle Hospital Flinders Medical Centre Royal Adelaide Hospital Austin Hospital Royal Prince Alfred Hospital John Hunter Hospital Nepean Hospital Cairns Base Hospital Mount Elizabeth Medical Centre Gleneagles Hospital Selayang Hospital National University Health System Yong Loo Lin School of Medicine National University of Singapore Changi General Hospital NKC Institute of Gastroenterology and Hepatology Prince of Songkla University

AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis c virus genotype 1(HcVGT1) PR treatmentfailures in ***:The Boceprevir Named-Patient Program provided boceprevir to HcVGT1 PR *** physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and *** analysis was performed to determine predictors of ***:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HcVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HcVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%*** patients were similar to caucasian patients with regards to on-treatment *** with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment *** with the IL28 B cc genotype(80%) had higher SVRs than those with the cT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of *** adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping ***:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.

关键词： chronic hepatitis c Treatment failure Rapid virological response Lead-in Null response Partial response Relapse cirrhosis Response guidedtherapy

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Micro RNA expression in hepatitis c virus-related malignancies: A brief review

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World Journal of Gastroenterology 2015年第28期21卷 8562-8568页

作者： Laura Gragnani Alessia Piluso Elisa Fognani Anna Linda Zignego Center for Systemic Manifestations of Hepatitis Viruses Department of Experimental and Clinical Medicine University of Florence

Not only is chronic hepatitis c virus(HcV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's *** characteristics mean that HcV is the only virus infecting humans that is able to cause two different *** fine pathogenetic and molecular mechanisms by which HcV induces these two malignancies are not completely *** the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising ***,we briefly describe the current knowledge about microRNAs' involvement in HcV-related molecular *** decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HcV *** of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of *** is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.

关键词： MicroRNA Hepatitis c virus Hepatocellularcarcinoma Lymphoma

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Hepatitis c treatment in the elderly:New possibilities and controversies towards interferon-free regimens

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World Journal of Gastroenterology 2015年第24期21卷 7412-7426页

作者： Umberto Vespasiani-Gentilucci Giovanni Galati Paolo Gallo Antonio De Vincentis Elisabetta Riva Antonio Picardi Internal Medicine and Hepatology Unit University Campus Bio-Medico Virology Unit University Campus Bio-Medico

Due to the progressive aging of the hepatitis c virus(HcV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HcV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HcV-related liver disease gets faster with aging, and that even extrahepatic manifestations of HcV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the wellknown contraindications and side effects of interferon(IFN). The arrival of several new anti-HcV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HcV as an infection of the elderly, the evidences that HcV harms the health of the aged patient more than that of the young one, and the available experiences of HcV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFNfree regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues g

关键词： Hepatitis c virus Elderly Interferon Ribavirin Telaprevir Boceprevir Sofosbuvir Simeprevir Daclatasvir Side effects Drug-drug interactions

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Hepatitis c:New challenges in liver transplantation

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World Journal of Gastroenterology 2015年第19期21卷 5768-5777页

作者： Tajana Filipec Kanizaj Nino Kunac Department of Gastroenterology University Hospital Merkur School of Medicine University of Zagreb University Hospital Merkur

In an era of great achievements in liver transplantation, hepatitis c viral infection(HcV) remains an unsolved problem. As a leading indication for liver transplantation in Western countries, HcV poses a significant burden both before and after transplantation. Post-transplant disease recurrence occurs in nearly all patients with detectable pretransplant viremia, compromising the lifesaving significance of transplantation. Many factors involving the donor, recipient and virus have beenevaluated throughout the literature, although few have been fully elucidated and implemented in actual clinical practice. Antiviral therapy has been recognized as a cornerstone of HcV infection control; however, experience and success are diminished following transplantation in a challenging cohort of patients with liver cirrhosis. current therapeutic protocols surpass those used previously, both in sustained viral response and side-effect profile. In this article we review the most relevant and contemporary scientific evidence regarding hepatitis c infection and liver transplantation, with special attention dedicated to novel, more efficient and safer antiviral regimens.

关键词： Hepatitis c Liver transplantation Treatmentprotocols Pegylated interferon Ribavirin Direct actingantivirals

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Effect of Magnetic Field on Natural convection in a c -shaped cavity Filled with Ferrofluid

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Procedia Engineering 2015年 105卷 96-104页

作者： Satyajit Mojumder Sourav Saha Sumon Saha M.A.H. Mamun Department of Mechanical Engineering Bangladesh University of Engineering and Technology Dhaka 1000

In this paper, natural convection heat transfer has been analyzed for a c -shaped cavity filled with ferrofluid. cobalt-kerosene ferrofluid is selected here for different solid volume fractions ( φ = 0 ∼ 0.15). Galerkin weighted residual method is applied to obtain the numerical solution. Simulations are carried out for a wide range of Rayleigh ( Ra = 10 3 ∼ 10 7 ) and Hartmann ( Ha = 0 ∼ 100) numbers for both the ferrofluid and the plain fluid. From this work, it is found that higher Rayleigh number enhances the heat transfer rate significantly, whereas presence of magnetic field tries to retard convection. Moreover, addition of 15% solid volume fraction of nanoparticle can augment the heat transfer rate up to 52.65% at moderate Rayleigh number compared to the base fluid. By an optimization of these parameters, effective heat transfer control equipment can be developed. Results are interpreted on the basis of streamline and isotherm patterns, and average Nusselt number of the heated wall and average fluid temperature of the cavity.

关键词： Ferrofluid c -shaped cavity Magnetic field Natural convection

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MPSoc可调度性分析的价格时间自动机模型

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西北工业大学学报 2017年第2期35卷 292-297页

作者：汪群博赵政文张涛程胜朱海涛李坤西北工业大学软件与微电子学院北京神州航天软件技术有限公司

多处理器片上系统(MPSoc)是在单一芯片上集成多个处理器的复杂Soc,是多核时代Soc的最新发展方向,保证MPSoc可调度是其设计的重点。针对MPSoc的特性,使用价格时间自动机,对其构建一种可调度性分析模型,并使用模型检测工具UPPAAL中的统计... 详细信息

多处理器片上系统(MPSoc)是在单一芯片上集成多个处理器的复杂Soc,是多核时代Soc的最新发展方向,保证MPSoc可调度是其设计的重点。针对MPSoc的特性,使用价格时间自动机,对其构建一种可调度性分析模型,并使用模型检测工具UPPAAL中的统计模型检测引擎自动模拟系统,并估算不可调度概率。实例验证结果表明,该模型检测方法降低了分析成本,可以分析传统模型检测方法所不能判定的复杂系统。

关键词： MPSo c 价格时间自动机 UPPAAL 可调度性模型检测

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多因素联合对肥胖伴卵巢囊肿的诊断价值分析

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中国科技期刊数据库医药 2022年第1期 018-023页

作者：阮强陈皖京程云生汪泳安徽医科大学第二附属医院安徽合肥230000

筛选肥胖合并卵巢囊肿患者的诊断指标,并评估这些指标在肥胖合并卵巢囊肿患者中的筛查价值。方法:回顾性分析 2020年1月-2021年3月入住安徽医科大学第二附属医院减重代谢中心的单纯性肥胖及肥胖合并卵巢囊肿患者共 146 例,完善一般资料... 详细信息

筛选肥胖合并卵巢囊肿患者的诊断指标,并评估这些指标在肥胖合并卵巢囊肿患者中的筛查价值。方法:回顾性分析 2020年1月-2021年3月入住安徽医科大学第二附属医院减重代谢中心的单纯性肥胖及肥胖合并卵巢囊肿患者共 146 例,完善一般资料测量,并在住院当天行妇科彩超(经阴道)及腹盆腔 cT,且所有患者均于次日清晨行 TSH、c 肽、性激素六项及糖化血红蛋白等,分析肥胖合并卵巢囊肿的临床特点及影响因素。结果:共纳入146例肥胖患者,其中单纯性肥胖患者70人,肥胖合并卵巢囊肿患者76人。采用多因素Logistic回归分析显示卵巢囊肿的独立影响因素主要包括 c 肽、TSH 和腰臀比(p<0.05),受试者工作特征曲线(ROc)分析显示 c 肽、TSH 和腰臀比的曲线下面积(AUc)分别为:0.851、0.832、0.726,联合使用c肽、TSH和腰臀比可提高 AUc(0.916),在肥胖合并卵巢囊肿患者的诊断中灵敏度为 92.0%,特异度为 85.8%。结论:1.对于肥胖患者,c肽、TSH 和腰臀比联合检测具有很好的灵敏度及良好特异度,可用于肥胖合并卵巢囊肿患者的筛查;2.c 肽与TSH可能与卵巢囊肿直径的大小密切相关。

关键词：肥胖卵巢囊肿 TSH c 肽筛查

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Fuzzing High-Level Synthesis Tools 21

Fuzzing High-Level Synthesis Tools

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The 2021 AcM/SIGDA International Symposium on Field-Programmable Gate Arrays

作者： Zewei Du Yann Herklotz Nadesh Ramanathan John Wickerson Imperial College London London United Kingdom

ISBN: (纸本)9781450382182

High-level synthesis (HLS) is becoming an increasingly important part of the computing landscape, even in safety-critical domains where correctness is key. As such, HLS tools are increasingly relied upon. But are they trustworthy?We have subjected three widely used HLS tools - LegUp, Xilinx Vivado HLS, and the Intel HLS compiler - to a rigorous fuzzing campaign using thousands of random, valid c programs that we generated using a modified version of the csmith tool. For each c program, we compiled it to a hardware design using the HLS tool under test and checked whether that hardware design generates the same output as an executable generated by the Gcc compiler. When discrepancies arose between Gcc and the HLS tool under test, we reduced the c program to a minimal example in order to zero in on the potential bug. Our testing campaign has revealed that all three HLS tools can be made either to crash or to generate wrong code when given valid c programs, and thereby underlines the need for these increasingly trusted tools to be more rigorously engineered. Out of 6700 test cases, we found 272 programs that failed in at least one tool, out of which we were able to discern at least 6 unique bugs.

关键词： high-level synthesis c c++ fuzzing

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Fuzzy Logic Strategy for Solving an Optimal control Problem of Therapeutic Hepatitis c Virus Dynamics

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Open Journal of Applied Sciences 2015年第9期5卷 527-541页

作者： Jean Marie Ntaganda Mahamat Saleh Daoussa Haggar Benjamin Mampassi College of Science and Technology School of Sciences Department of Mathematics University of Rwanda Butare Rwanda Department of Mathematics Faculty of Exact and Applied Sciences N’Djamena University N’Djamena Chad Department of Mathematics Faculty of Sciences and Technology Dakar University Dakar Senegal

This paper aims at the development of an approach integrating the fuzzy logic strategy for a therapeutic hepatitis c virus dynamics optimal control problem. To test the efficiency of this strategy, the authors propose a numerical comparison with the direct method by taking the values of determinant parameters of this disease for people administrating the drugs. The results are in good agreement with experimental data.

关键词： Fuzzy Logic Optimal control Membership Function Membership Degree Hepatitis c Virus Uninfected Hepatocytes Infected Hepatocytes Numerical Simulation

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c 14 -Polyacetylene glucosides from codonopsis pilosula

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Journal of Asian Natural Products Research 2015年第6期17卷 601-614页

作者： Yue-Ping Jiang Yu-Feng Liu Qing-Lan Guo Zhi-Bo Jiang cheng-Bo Xu cheng-Gen Zhu Yong-chun Yang Sheng Lin Jian-Gong Shi State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China

Seven new c 14 -polyacetylene glucosides codonopilodiynosides A–G ( 1 – 7 ) were isolated from an aqueous extract of the codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods as (–)-(5 S ,6 E ,12 E )-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5- O -β- d -glucopyranoside ( 1 ), (–)-(5 S ,6 E ,12 E )-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5- O -β- d -glucopyranosyl-(1″ → 2′)-β- d -glucopyranoside ( 2 ), (–)-(5 S ,6 E ,12 E )-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5,14-di- O -β- d -glucopyranoside ( 3 ), (–)-(5 S ,6 E )-tetradeca-6-en-8,10-diyn-1,5,14-triol 5- O -β- d -glucopyranoside ( 4 ), (–)-(5 S ,6 E ,12 E )-tetradeca-6,12-dien-8,10-diyn-1,5-diol 5- O -β- d -glucopyranosyl-(1″ → 2′)-β- d -glucopyranoside ( 5 ), (–)-(6 S ,4 E ,12 E )-tetradeca-4,12-dien-8,10-diyn-1,6-diol 6- O -β- d -glucopyranosyl-(1″ → 2′)-β- d -glucopyranoside ( 6 ), and (–)-(5 S ,6 E )-tetradeca-6-en-1,5-epoxy-8,10-diyn-14-ol 14- O -β- d -glucopyranosyl-(1″ → 2′)-β- d -glucopyranoside ( 7 ), respectively. The absolute configurations of 1 – 7 were assigned by enzymatic hydrolysis followed by isolation of glucose and aglycones ( 1a and 4a – 7a ), and subsequent comparison of specific rotation, TLc, and 1 H NMR data of the glucose with an authentic sugar sample and application of modified Mosher's method based on the MPA determination rule of Δδ RS values for 1a and 4a, and Δδ S values for 6a . The configuration of 7 was assigned by electronic circular dichroism calculations based on the quantum-mechanical time-dependent density functional theory.

关键词： campanulaceae codonopsis pilosula codonopilodiynosides A–G c 14 -polyacetylene glucosides absolute configuration

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