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Targeted agents for second-line treatment of advanced hepatocellular carcinoma

World Journal of Gastrointestinal Oncology 2019年第10期11卷 788-803页

作者： nicola Personeni Tiziana Pressiani Silvia Bozzarelli Lorenza Rimassa Medical Oncology and Hematology Unit Humanitas Cancer CenterHumanitas Clinical and Research CenterIRCCSRozzano 20089MilanItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090MilanItaly

Over the past ten years,sorafenib,a multikinase inhibitor,has been the standard of care for patients with unresectable hepatocellular carcinoma(HCC)and wellpreserved liver ***,lenvatinib,a different multikinase inhibitor,was shown to be non-inferior to sorafenib,in terms of survival,while all other agents previously tested failed to prove non-inferiority(or superiority)when compared to ***,in the second-line setting,most investigational drugs failed to provide better survival outcomes than ***,in the last 2 years three positive phase III trials have been published in this *** RESORCE trial,a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib,showed better outcomes with regorafenib compared to *** recently,the phase III CELESTIAL trial demonstrated the superiority of cabozantinib,a multikinase inhibitor targeting vascular endothelial growth factor receptor,MET,and AXL,vs placebo in the second-and third-line setting in patients progressing on or intolerant to *** survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein ***,the adverse events reported in these trials were in line with the known safety profiles of the tested *** nearly a decade of a certain degree of stagnation,we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.

关键词： Hepatocellular carcinoma Advanced-metastatic Second-line Third-line Regorafenib Cabozantinib Ramucirumab Angiogenesis Multikinase inhibitor MET AXL Vascular endothelial growth factor receptor 2

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Transport coefficients of a massive pion gas

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Chinese Physics C 2010年第9期34卷 1453-1455页

作者： D.Fernández-Fraile A.Gómez nicola Institut für Theoretische Physik Johann Wolfgang Goethe-Universitt Departamento de Física Teórica II Universidad Complutense

We review our main results concerning the transport coefficients of a light meson gas,in particular we focus on the case of a massive pion *** order results according to the chiral power-counting are presented for the DC electrical conductivity,thermal conductivity,shear viscosity,and bulk *** also comment on the possible correlation between the bulk viscosity and the trace anomaly in QCD,as well as the relation between unitarity and a minimum of the quotient η/s near the phase transition.

关键词： transport coefficients heavy-ion collisions Chiral Perturbation Theory

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Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst's exponent

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World Journal of Gastroenterology 2006年第14期12卷 2187-2194页

作者： nicola Dioguardi Fabio Grizzi Barbara Franceschini Paola Bossi Carlo Russo Laboratori di Medicina Quantitativa Istituto Clinico Humanitas IRCCS RozzanoMilanand "Michele Rodriguez" FoundationInstitute for Quantitative Methods in MedicineMilanItaly Department of Pathology Istituto Clinico Humanitas IRCCS RozzanoMilanItaly

AIM： To provide the accurate alternative metrical means of monitoring the effects of new antiviral drugs on the reversal of newly formed collagen. METHODS： Digitized histological biopsy sections taken from 209 patients with chronic C virus hepatitis with different grade of fibrosis or cirrhosis, were measured by means of a new, rapid, user-friendly, fully computeraided method based on the international system meter rectified using fractal principles. RESULTS： The following were described： geometric perimeter, area and wrinkledness of fibrosis; the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal-rectified metric measurements; the meaning of the physical composition of fibrosis in relation to the magnitude of collagen islets; the intra- and inter-biopsy sample variability of these parameters; the ＂staging＂ of biopsy sections indicating the pathway covered by fibrosis formation towards its maximum known value; the quantitative liver tissue architectural changes with the Hurst exponent. CONCLUSION： Our model provides the first metrical evaluations of the geometric properties of fibrosis and the quantitative architectural changes of the liver tissue. The representativeness of histological sections of the whole liver is also discussed in the light of the results obtained with the Hurst coefficient.

关键词： Liver Fibrosis Cirrhosis Staging Image analysis Fractals

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Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

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World Journal of Gastroenterology 2014年第22期20卷 6707-6715页

作者： Evangelista Sagnelli Caterina Sagnelli Mariantonietta Pisaturo nicola Coppola Section of Infectious Diseases Department of Mental Health and Public MedicineSecond University of Naples80131 NaplesItaly Mariantonietta Pisaturo Division of Infectious DiseasesAORN Sant’Anna e San Sebastiano di Caserta81100 CasertaItaly Department of Clinical and Experimental Medicine and Surgery "F Magrassi e A Lanzara" Second University of Naples80131 NaplesItaly

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of *** remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the *** a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular *** indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity *** etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

关键词： Chronic hepatitis C virus infection Hepatic flares Hepatic flares in immunocompromised patients Immunocompromised patients Hepatitis A virus superinfection

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Pediatric fatty liver disease:Role of ethnicity and genetics

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World Journal of Gastroenterology 2014年第23期20卷 7347-7355页

作者： Pierluigi Marzuillo Emanuele Miraglia del Giudice nicola Santoro Department of Women and Children and General and Specialized Surgery Seconda Università degli Studi di Napoli80138 NaplesItaly Department of Pediatrics Yale University School of MedicineNew HavenCT 06520United States

Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.

关键词： Non alcoholic fatty liver disease Ethnicity Patatin like phospholipase containing domain 3 gene Obesity Insulin resistance Glucokinase regulatory protein Apolipoprotein C3 gene Farnesyl-diphosphate farnesyltransferase 1

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What Drives Private Equity Minority Acquisitions? A Multiple-Case Analysis on the Influences and Determinants within the Investment Decision Process

What Drives Private Equity Minority Acquisitions? A Multiple...

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作者： nicola HONORATI 复旦大学

学位级别：硕士

鉴于最近几年国际金融市场一直处在不断的动荡变化中,私募股权融资的运营商们为了支持企业发展,通过对少数股权投资企业的投资,在企业急需资金,而投资者需要投资回报这两者之间起到了积极有力的促进融资的作用。尽管此类交易的潜力尚未... 详细信息

鉴于最近几年国际金融市场一直处在不断的动荡变化中,私募股权融资的运营商们为了支持企业发展,通过对少数股权投资企业的投资,在企业急需资金,而投资者需要投资回报这两者之间起到了积极有力的促进融资的作用。尽管此类交易的潜力尚未被完全开发出来,目前有25%左右的私募股权融资企业在市场上占有一席之地,但从学术方面来看,其仍然是一个未热起来的话题。本论文的目的是通过回答“是什么因素促使私募股权融资公司对少数股本交易机构进行收购呢?”这一问题,对少数股本交易企业的投资决策程序进一步拓展研究,旨在通过从学术观点去分析识别私募股本融资企业对少数股本交易的决定性因素。通过对一些在意大利少数股本交易市场的主要运营商的专访,重点针对十个应用中的案例内分析及交叉案例的研究。每项资金涉及的投资程序均以他们所进行的少数股本交易为参考,该专访主要集中对每项资金的特点及危机程度的分析。通过编码方案的方式对已经建立的案例进行分析而得出结论,并采取对案例的对比分析来帮助理解这些资金的特点是怎样对投资决策过程产生影响的。出于三个基本原因对意大利国内市场进行重点分析。首先,从事该行业的业内人士坚信私募股权融资的实力,特别是对少数股本交易充满了信心,这一信心给意大利工业企业的振兴创造了良好的环境—支持企业发展、推动经济增长、恢复社会民众的信心。在过去的几年里,通过公私合作的模式和强有力的企业支持,这种信念被进一步的坚定下去;其次,这个市场在国家支柱产业和少数股本交易的典型目标企业之间创造了特别的机会;最后,由于意大利工业企业的典型特征,包括中小型规模的家庭式企业,有限的金融信用,这些特征都能在其他一些地域市场找到(比如：欧洲国家和中国),所以这种研究在新的地域环境中就具有某种可复制性和适用性。从广泛的学术观点来看,投资决策过程被推断出的八项假设和十五项新的理论命题以及理论框架都从分析中取得了进展。这项研究的主要结论是投资决策对于投资目标来说确实受到其内部特征的积极影响。需要特别指出的是,基于行为决策理论及其相关的一系列派生理论,由本文得出的结论：内部特性的影响产生于三个连续的步骤：首先是内部人力资本,组织学习与股权所有制结构影响了少数股本交易策略的决定;其次,为了实现战略目标,投资策略会影响金融投资行为、人力资本、组织学习以及运营商自己提供的投资方式;最后,金融投资行为对投资策略的影响,研究发现金融投资并不是构成其正面影响的主要因素,而人力资本、组织学习与投资方式才是私募资本投资运营商对少数资本投资的最主要的决定性因素。最后的结论是：在特殊形式的交易中,对于所有以此策略为目标或已采用该策略的私募股本融资运营商：以上所提及的决定性特征一旦从理论观点上得到证实,那么就能有助于私募股本融资运营商成功地执行特定的交易,也就是说,就能在市场上证明其是最佳的策略。

关键词：私募股权融资投资决策过程少数股本交易

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A framework for the extended evaluation of ABAC policies

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Cybersecurity 2019年第1期2卷 117-137页

作者： Charles Morisset Tim A.C.Willemse nicola Zannone Newcastle University NewcastleTyneUK Eindhoven University of Technology P.O.Box 5135600 MBEindhovenNetherlands

A main challenge of attribute-based access control(ABAC)is the handling of missing *** studies have shown that the way standard ABAC mechanisms,*** on XACML,handle missing information is flawed,making ABAC policies vulnerable to attribute-hiding *** work has addressed the problem of missing information in ABAC by introducing the notion of extended evaluation,where the evaluation of a query considers all queries that can be obtained by extending the initial *** method counters attribute-hiding attacks,but a na飗e implementation is intractable,as it requires an evaluation of the whole query *** this paper,we present a framework for the extended evaluation of ABAC *** framework relies on Binary Decision Diagram(BDDs)data structures for the efficient computation of the extended evaluation of ABAC *** also introduce the notion of query constraints and attribute value power to avoid evaluating queries that do not represent a valid state of the system and to identify which attribute values should be considered in the computation of the extended evaluation,*** illustrate our framework using three real-world policies,which would be intractable with the original method but which are analyzed in seconds using our framework.

关键词： Attribute-based access control Policy evaluation Missing attributes Attribute power Attribute-hiding attacks

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Bromelain and Cardiovascular Risk Factors in Diabetes:An Exploratory Randomized,Placebo Controlled,Double Blind Clinical Trial

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Chinese Journal of Integrative Medicine 2016年第10期22卷 728-737页

作者：黎七妹倪青廖星高怀林 nicola Robinson School of Health and Social Care London South Bank University Department of Endocrinology Guang'anmen Hospital China Academy of Chinese Medical Sciences Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Department of Endocrinology Yiling Hospital Affiliated to Hebei Medical University

Objective： To assess whether the dietary supplement （bromelain） has the potential to reduce plasma fibrinogen and other cardiovascular disease （CVD） risk factors in patients with diabetes. Methods： This randomized placebo controlled, double blind, parallel design, efficacy study was carried out in China and investigated the effect of 12 weeks of bromelain （1,050 mg/day） on plasma fibrinogen, This randomized controlled trial （RCT） recruited 68 Chinese diabetic patients [32 males and 36 females; Han origin, mean age of 61.26 years （standard deviation （SD）, 12.62 years）] with at least one CVD risk factor. Patients were randomized into either bromelain or placebo group. While bromelain group received bromelain capsule, the placebo group received placebo capsule which consisted inert ingredient and has no treatment effect. Subjects were required to take 1,050 mg （3× 350 mg） of either bromelain or starch-tiffed placebo capsules, two to be taken （2 × 350 mg） after breakfast and another （350 mg） after dinner, daily for 12 weeks. Plasma fibrinogen, CVD risk factors and anthropometric indicators were determined at baseline and at 12 weeks. Results： The change in the flbrinogen level in the bromelain group at the end of the study showed a mean reduction of 0.13 g/L （standard deviation （SD） 0.86g/L） compared with the mean reduction of 0.36 g/L （SD 0.96 g/L） for the placebo group. However, there was no significant difference in the mean change in fibrinogen between the placebo and bromelain groups （mean difference=0.23g/L （SD 0.22 g/L）, P=0.291）. Similady, the difference in mean change in other CVD risk factors （blood lipids, blood pressure）, blood glucose, C-reactive protein and anthropometric measures between the bromelain and placebo groups was also not statistically significant. Statistical differences in fibrinogen between bromelain and placebo groups before the trial despite randomization may have influenced the results of this study. Conclusion： This RCT failed to show a

关键词： cardiovascular disease fibrinogen diabetes bromelain randomized control trial

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Image Deblurring of Video Surveillance System in Rainy Environment

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Computers, Materials & Continua 2020年第10期65卷 807-816页

作者： Jinxing Niu Yajie Jiang Yayun Fu Tao Zhang nicola Masini North China University of Water Resources and Electric Power Zhengzhou450045China Institute of Science of Cultural Heritage National Research CouncilC.da Santa LojaTito Scalo(PZ)85050Italy

Video surveillance system is used in various fields such as transportation and social *** bad weather can lead to the degradation of the video surveillance image *** rainy environment,the raindrops and the background are mixed,which lead to make the image degradation,so the removal of the raindrops has great significance for image *** this article,after analyzing the inter-frame difference method in detecting and removing raindrops,a background difference method is proposed based on Gaussian *** this method,the raindrop is regarded as a moving object relative to the *** principle and procedure of the method are given to detect and remove *** parameters of the single Gaussian background model are studied in this *** important parameter of the learning rate of Gaussian model is explored in order to better detection and removal of *** shows that the results of removal of raindrops by using the proposed algorithm are better than that by using the inter-frame difference *** image processing effect is the best when the learning rate is *** research results can provide technical reference for similar research on eliminating the influence of rainy weather.

关键词： Inter-frame difference method Gaussian model raindrop background difference

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To Establish A Body of Evidence on Safety for Postmarketing Chinese Medicine：A New Research Paradigm

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Chinese Journal of Integrative Medicine 2017年第3期23卷 226-232页

作者： LIAO Xing XIE Yan-ming nicola Robinson WANG Yong-yan Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Beijing 100700 China

The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in China’s mainland recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for efficacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this field both in China and abroad are urgently needed.

关键词： postmarketing Chinese medicine safety research Kudiezi Injection body of evidence

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