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Response rates to direct antiviral agents among hepatitis C virus infected patients who develop hepatocellular carcinoma following direct antiviral agents treatment

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Hepatoma Research 2020年第2期6卷 1-10页

作者： Michela Emma Burlone Stefano Fangazio Alessandro Croce Elisa Ceriani Rachele Rapetti Cristina Rigamonti Carlo Smirne Stelvio Tonello Paolo Ravanini rosalba minisini Mario Pirisi Internal Medicine Azienda Ospedaliero-Universitaria Maggiore della CaritàNovara 28100Italy Department of Translational Medicine Universitàdel Piemonte OrientaleNovara 28100Italy Laboratory of Virology Azienda Ospedaliero-Universitaria Maggiore della CaritàNovara 28100Italy

Aim:Patients with chronic hepatitis C virus(HCV)infection who develop hepatocellular carcinoma(HCC)soon after treatment with direct antiviral agents(DAA)may have been harboring hitherto hidden *** this were true,they should have a lower sustained viral response(SVR)rate,since active HCC hampers DAA *** aimed to verify this ***:We included all patients who attended an HCV clinic,provided that they:(1)had no previous history of HCC;(2)had received at least one DAA dose;and(3)had been followed-up clinically and ultrasonographically for at least six months after concluding ***:The study population included n=789 patients(55%males,median age 62 years).A median of 9.3 months(8.8-11.9)after concluding DAA,n=19(2.4%)patients were discovered to harbor *** comparison to all others,patients with HCC were more commonly male(84%vs.54%,P=0.009),obese(47%vs.17%,P=0.002),and cirrhotic(95%vs.35%,P<0.001)and had less commonly achieved an SVR(68%vs.98%,P<0.001).Moreover,they had a trend for being less commonly treatment na?ve(58%vs.67%,P=0.051).Based on multivariate analysis, ;the independent predictors of HCC were male sex(P=0.031),cirrhosis(P=0.004),obesity(P=0.006),and failure to achieve an SVR(P<0.001).Conclusion:Lack of achieving SVR is a strong independent predictor of development of HCC early after treatment of hepatitis C with *** failure should further alert clinicians to the possibility of this dreadful complication.

关键词： Chronic hepatitis C direct antiviral agent sustained viral response hepatocellular carcinoma obesity cirrhosis

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Excess body weight, liver steatosis, and early fibrosis progression due to hepatitis C recurrence after liver transplantation

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World Journal of Gastroenterology 2005年第38期11卷 5944-5950页

作者： Pierluigi Toniutto Carlo Fabris Claudio Avellini rosalba minisini Davide Bitetto Elisabetta Rossi Carlo Smirne Mario Pirisi Liver Transplantation Unit Pathology Department of Medical Sciences

AIM: To investigate how weight gain after OLT affects the speed of fibrosis progression (SFP) during recurrent hepatitis C virus (HCV) infection of the ***: Ninety consecutive patients (63 males,median age 53 years; 55 with HCV-related liver disease),transplanted at a single institution, were studied. All were followed for at least 2 years after OLT and had at least one follow-up graft biopsy, performed not earlier than 1 year after the transplant operation. For each biopsy, a single,experienced pathologist gave an estimate of both the staging according to Ishak and the degree of hepatic *** SFP was quantified in fibrosis units/month (FU/mo).The lipid metabolism status of patients was summarized by the plasma triglycerides/cholesterol (T/C) ratio. Body mass index (BMI) was measured before OLT, and 1 and 2 years after ***: In the HCV positive group, the highest SFP was observed in the first post-OLT year. At that time point,a SFP ≤0.100 FU/mo was observed more frequently among recipients who had received their graft from a young donor and had a pre-transplant BMI value ＞26.0 kg/m2. At completion of the first post-transplant year, a BMI value ＞26.5 kg/m2 was associated with a T/C ratio ≤1. The proportion of patients with SFP ＞0.100 FU/mo descended in the following order: female recipients with a high T/C ratio, male recipients with high T/C ratio, and recipients of either gender with low T/C ratio. Hepatic steatosis was observed more frequently in recipients who, in the first post-transplant year, had increased their BMI ≥1.5 kg/m2 in comparison to the pre-transplant value. Hepatic steatosis was inversely associated with the staging ***: Among HCV positive recipients, excessweight gain post-OLT does not represent a factor favoring early liver fibrosis development and might even be protective against it.

关键词： Liver transplantation Hepatitis C infection Liver fibrosis Liver steatosis Body mass index

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Finding the seed of recurrence:Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment

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World Journal of Gastrointestinal Surgery 2021年第9期13卷 967-978页

作者： Francesca Carissimi Matteo Nazzareno Barbaglia Livia Salmi Cristina Ciulli Linda Roccamatisi Giuseppe Cordaro Venkata Ramana Mallela rosalba minisini Biagio Eugenio Leone Matteo Donadon Guido Torzilli Mario Pirisi Fabrizio Romano Simone Famularo School of Medicine and Surgery University of Milano-BicoccaMonza 20900Italy Department of Translational Medicine Universitàdel Piemonte OrientaleNovara 28100Italy Unit of Pathology San Gerardo HospitalMonza 20900Italy Department of Hepatobiliary and General Surgery IRCCS Humanitas Clinical and Research Hospital-Department of Biomedical ScienceHumanitas UniversityPieve Emanuele 20090Italy Department of Medicine and Surgery University of Milan-BicoccaMonza 20900Italy

The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 *** pre-operative tools are currently available to assess the recurrence risk tailored to every single *** liquid biopsy has shown interesting results in diagnosis,prognosis and treatment allocation strategies in other types of cancers,since its ability to identify circulating tumor cells(CTCs)derived from the primary *** cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for *** fact,after being modified by the epithelial-mesenchymal transition,CTCs circulate as“seeds”in peripheral blood,then reach the target organ as dormant cells which could be subsequently“awakened”and activated,and then initiate *** presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections,particularly in the case of microvascular invasion,which has been recently pointed as a histological sign of the spread of those ***,their presence,also in the early stages,may justify the recurrence event also in the contest of liver *** the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based ***,it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies,and in perspective,it could also become a new method to allocate organs for transplantation,according to the risk of relapse after liver *** present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC,highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.

关键词： Hepatocellular carcinoma Liquid biopsy Circulating tumor cells Liver surgery Microvascular invasion Hepatocellular carcinoma recurrence

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Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis

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World Journal of Gastroenterology 2010年第24期16卷 3016-3024页

作者： Edmondo Falleti Davide Bitetto Carlo Fabris Annarosa Cussigh Elisabetta Fontanini Ezio Fornasiere Elisa Fumolo Sara Bignulin Sara Cmet rosalba minisini Mario Pirisi Pierluigi Toniutto Laboratory Medicine University of Udine Department of Medical Sciences Clinical and Experimental Medical Liver Transplant UnitUniversity of Udine Department of Clinical and Ex-perimental Medicine University of Eastern Piedmont "A. Avoga-dro"

AIM: To assess the relationship between vitamin D re-ceptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucle-otide gene polymorphisms of the VDR were investigatedby polymerase chain reaction and restriction fragment length polymorphism: FokI C>T (F/f), BsmI A>G (B/b), ApaI T>G (A/a) and TaqI T>C (T/t) (BAT). RESULTS: The frequencies of genotypes in patients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for ApaI A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotype of BsmI and the T/T genotype of TaqI was signif icantly associated with HCC (45/160 vs 33/80, P < 0.05 and 44/160 vs 32/80, P < 0.05, respectively). The absence of the A-T-C protective allele of BAT was signif i-cantly associated with the presence of HCC (46/80 vs 68/160, P < 0.05). A strong association was observed between carriage of the BAT A-T-C and G-T-T haplotypes and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, P < 0.002, respectively).CONCLUSION: VDR genetic polymorphisms are sig-nificantly associated with the occurrence of HCC in patients with liver cirrhosis. This relationship is more specific for patients with an alcoholic etiology.

关键词： Alcohol Hepatocellular carcinoma Liver cirrhosis Vitamin D receptor polymorphisms

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Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese Department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly Department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly Department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

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News about non-secretory exocytosis: mechanisms, properties, and functions

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Journal of Molecular Cell Biology 2019年第9期11卷 736-746页

作者： rosalba D'Alessandro Jacopo Meldolesi Scientific Institute S.De Beilis Via Turi 277013Castellana GrotteItaly Scientific Institute San Raffaele and Vita Salute San Raffaele University Via Olgettina 5820132MilanItaly

The fusion by exocytosis of many vesicles to the plasma membrane induces the discharge to the extracellular space of their abundant luminal *** exocytic vesicles,however,do not contain cargoes,and thus,their fusion is not followed by ***,two distinct processes of exocytosis exist,one secretory and the other *** present review deals with the knowledge of non-secretory exocytosis developed during recent *** such developments are the dual generation of the exocytic vesicles,initially released either from the trans-Golgi network or by endocytosis;their traffic with activation of receptors,channels,pumps,and transporters;the identification of their tethering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor complexes that govern membrane fusions;the growth of axons and the membrane *** of potential relevance of these processes for pathology and medicine are also *** developments presented here offer interesting chances for future progress in the field.

关键词： exocytosis Golgi complex vesicles endocytosis

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Space-Time Decomposition of Kalman Filter

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Numerical Mathematics(Theory,Methods and Applications) 2023年第4期16卷 847-882页

作者： Luisa D’Amore rosalba Cacciapuoti University of Naples Federico II NaplesItaly

We present an innovative interpretation of Kalman filter(KF)combining the ideas of Schwarz domain decomposition(DD)and parallel in time(PinT)*** we call it *** contrast to standard DD approaches which are already incorporated in KF and other state estimation models,implementing a straightforward data parallelism inside the loop over time,DD-KF ab-initio partitions the whole model,including filter equations and dynamic model along both space and time directions/*** a consequence,we get local KFs reproducing the original filter at smaller dimensions on local ***,sub problems could be solved in *** order to enforce the matching of local solutions on overlapping regions,and then to achieve the same global solution of KF,local KFs are slightly modified by adding a correction term keeping track of contributions of adjacent subdomains to overlapping *** a correction term balances localization errors along overlapping regions,acting as a regularization constraint on local ***,such a localization excludes remote observations from each analyzed location improving the conditioning of the error covariance *** dynamic model we consider shallow water equations which can be regarded a consistent tool to get a proof of concept of the reliability assessment of DD-KF in monitoring and forecasting of weather systems and ocean currents.

关键词： Data assimilation Kalman filter domain decomposition filter localization model reduction numerical algorithm

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Can foods influence the onset and progress of neurodegenerative diseases?

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Neural Regeneration Research 2022年第11期17卷 2443-2444页

作者： Luca Piemontese Leonardo Brunetti rosalba Leuci Department of Pharmacy and Pharmaceutical Sciences University of Bari Aldo Moro

Over the course of the last few years,the advertisement and marketing of commercial food products in the European market has seen an increasing focus on the beneficial effects of such products for consumer health(Regulation,2006).These so-called"health claims", which can be found on the label of some food products,have become a very important medium,aiming to reach the maximum amount of potential consumers possible,and the delivery of these promises has become a crucial objective for food companies or ***,in most cases,the evidence backing up such claims(and their coveted acknowledgment on the product label) has often been cited as insufficient by institutions such as the European Food and Safety Authority (EFSA,Parma,Italy).

关键词： companies Authority claims

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Topographic effects observed at Amatrice hill during the 2016-2017 Central Italy seismic sequence

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Earthquake Engineering and Engineering Vibration 2021年第1期20卷 63-78页

作者： Gerardo Grelle Laura Bonito Maresca rosalba Silvia Iacurto Claudia Madiai Paola Revellino Giuseppe Sappa Department of Civil Building and Environmental EngineeringSapienza University of RomeItaly Department of Sciences and Technologies University of SannioItaly Department of Civil and Environmental Engineering University of FlorenceItaly

The estimate of seismic site effects by experimental approaches is based on different assumptions aimed at simplifying the complex actual site conditions and related ***,the reliability of the results can increase if the experimental data is focused on quite strong seismic sequences and the on-site acquisition of a large number of signals is deemed strategic for the assessment of the expected *** on these considerations,the ground motion at the Red Zone sector of Amatrice hill,violently struck by the 2016-2017 Central Italy seismic sequence,was analyzed via an observational approach.A large set of weak motions(moment magnitude Mw 2.5-3.9)was analyzed in this study by means of standard(SSR)and horizontal to vertical(HVSR)spectral ratio *** results from the experimental analysis of the site effects by using weak motion and noise signals show a significant amplification at the top of Amatrice hill with a remarkable polarization of the motion and changes in spectral shapes according to the topographic setting of the relief.

关键词： topographic effects standard spectra ratio(SSR) horizontal and vertical spectral ratio(HVSR) directional effects

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Adjuvant chemotherapy for gastric cancer:Current evidence and future challenges

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World Journal of Gastroenterology 2014年第16期20卷 4516-4525页

作者： rosalba Miceli Gianluca Tomasello Giacomo Bregni Maria Di Bartolomeo Filippo Pietrantonio Unit of Medical Statistics Biometry and BioinformaticsFondazione IRCCS Istituto Nazionale Tumori20133 MilanItaly Medical Oncology Division Azienda Istituti Ospitalieri di Cremona26100 CremonaItaly Medical Oncology Department Fondazione IRCCS Istituto Nazionale Tumori20133 MilanItaly

Gastric cancer still represents one of the major causes of cancer mortality *** survival is mainly related to stage,with a high proportion of patients with metastatic disease at ***,the cure rate largely depend upon surgical *** the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment ***,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual *** choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United *** the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and *** most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall *** finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.

关键词： Gastric cancer Adjuvant chemotherapy Radiotherapy Randomized trial

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