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Old-fashioned and newly discovered biomarkers:the future of NAFLD-related HCC screening and monitoring

Hepatoma Research 2022年第1期8卷 415-434页

作者： Roberto Piciotti Miriam Longo Adele Agresta erika Paolini Annalisa Cespiati Marica Meroni Paola Dongiovanni General Medicine and Metabolic Diseases Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilan 20122Italy Department of Pathophysiology and Transplantation Universitàdegli Studi di MilanoMilano 20122Italy Department of Clinical Sciences and Community Health Universitàdegli Studi di MilanoMilano 20122Italy Department of Pharmacological and Biomolecular Sciences Universitàdegli Studi di MilanoMilano 20133Italy

Nonalcoholic fatty liver disease(NAFLD)is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis(NASH),which may progress into cirrhosis and hepatocellular carcinoma(HCC).HCC represents the most common liver cancer,and it is a leading cause of death worldwide with an increasing trend for the *** to late diagnosis,non-responsiveness to systemic therapy,and high cancer heterogeneity,the treatment of this malignancy is *** date,liver biopsy and ultrasound(US)are the gold standard procedures for HCC diagnosis and surveillance,although they are not suitable for mass ***,it is impelling to find new,less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and *** and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor ***,epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic *** severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs(ctDNAs),microRNAs(miRNAs),and noncoding RNAs(ncRNAs),which are involved in several pathological processes that feature cancer,including cell growth,survival,and differentiation,thus representing appealing biomarkers for ***,this review discusses the current options for HCC surveillance,focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management.

关键词： NAFLD-HCC screening genetic biomarkers ncRNAs epigenetics early HCC detection

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Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment:A case report and review of the literature

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World Journal of Gastroenterology 2008年第39期14卷 6087-6092页

作者： Tatsuhiro Tsujimoto erika Shioyama Kei Moriya Hideto Kawaratani Yasuyo Shirai Masahisa Toyohara Akira Mitoro Jun-ichi Yamao Hisao Fujii Hiroshi Fukui Third Department of Internal Medicine Nara Medical UniversityKashiharaNara 634-8522Japan Department of Endoscopy and Ultrasound Nara Medical UniversityKashiharaNara 634-8522Japan

A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004,and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus,and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (αGI) was added in March 2006,resulting in good glycemic control. He experienced symptoms of abdominal distention,increased flatus,and constipation in October 2007,and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the αGI voglibose was suspected as the cause of this patient's PCI,treatment was conservative,ceasing voglibose,with fasting and fluid supplementation. The patient progressed well,and was discharged 2 wk later. Recently,several reports of PCI associated with αGI therapy have been published,predominantly in Japan where αGIs are commonly used. If the use of αGIs becomes more widespread,we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms,and the gastrointestinal tract should be thoroughly investigated in these patients.

关键词： Alpha-glucosidase inhibitor Colonoscopy Diabetes mellitus Pneumatosis cystoides intestinalis Voglibose

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Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第29期25卷 3870-3896页

作者： Elena De Mattia erika Cecchin Michela Guardascione Luisa Foltran Tania Di raimo Francesco Angelini Mario D’Andrea Giuseppe Toffoli Clinical and Experimental Pharmacology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano (PN) 33081 Italy Department of Medical Oncology Centro di Riferimento Oncologico di Aviano (CRO) IRCCS Aviano (PN) 33081 Italy Medical Oncology and Anatomic Pathology Unit “San Filippo Neri Hospital” Rome 00135 Italy Department of Oncology “San Filippo Neri Hospital” Rome 00135 Italy

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and

关键词： Hepatocellular carcinoma Pharmacogenetics Genetic markers Sorafenib Regorafenib Immune checkpoint inhibitors Cytochromes UDP glucuronosyltransferase 1A

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Contrasting soil fungal communities in Mediterranean pine forests subjected to different wildfire frequencies

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Fungal Diversity 2015年第1期70卷 85-99页

作者： erika Buscardo Susana Rodríguez-Echeverría Helena Freitas Paolo De Angelis João Santos Pereira Ludo A.H.Muller Centro de Ecologia Funcional(CEF) Departamento de Ciências da VidaUniversidade de CoimbraCalçada Martim de Freitas3000-456 CoimbraPortugal Department for Innovation in Biological Agro-Food and Forest Systems(DIBAF)University of TusciaVia S.Camillo de Lellis snc01100 ViterboItaly Escritório Central do LBA Instituto Nacional de Pesquisa da Amazônia(INPA)Av.AndréAraújo2936Campus IIAleixo69060-001 ManausAmazonasBrazil Departamento de Engenharia Florestal Instituto Superior de AgronomiaUniversidade Técnica de LisboaTapada da Ajuda1349-018 LisbonPortugal Institut für Biologie—Botanik Freie Universität BerlinAltensteinstrasse 614195 BerlinGermany

Mediterranean forest ecosystems are characterized by various vascular plant groups with their associated mycor-rhizae and free living soil fungi with various ecological *** plays a major role in Mediterranean ecosystem dynamics and impacts both above-and below-ground community structure and ***,studies on the effects induced by altered disturbance regimes(associated with recent land use and climate extremes)on fire ecology and especially on its below-ground impacts are *** objectives of this study were to evaluate the effects of different wildfire regimes on soil fungal community structure using two different molecular *** investigated the long-term effects of wildfire on soil fungal communities associated with Pinus pinaster forests in central Portugal,by comparing the results of denaturing gradient gel electrophoresis(DGGE)-based profiling with those obtained with 454 *** forest stands with differing fire history and fire return interval,and vegetation cover(mature forest,early successional stage of pine regeneration,and forest converted to scrubland)were sampled 6 years after the last fire *** pyrosequencing-based approach indicated ***-fold higher numbers of taxa than ***,fungal community fingerprinting data obtained for the different study stands with DGGE were congruent with those obtained with *** short(7.6 years)and long(24 years)fire return intervals(indicated by the presence of ericaceous shrubs in the understorey)induced a decrease in the abun-dance ratio between basidiomycetes and ascomycetes and appeared to reduce the frequency of ectomycorrhizal fungal species and *** significantly reduced the frequency of late stage successional taxa(*** and Cantharellales)and known or putative saprophytes belonging to the Clavulinaceae and the ***,early successional fungal species belonging to the Thelephoraceae were fav

关键词： 454 Pyrosequencing DGGE Wildfire frequency Soil fungal community Maritime pine

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Synthesis and cytotoxicity of 28-carboxymethoxy lupane *** of 28-O-acylation over 28-O-alkylation of betulm by ethyl bromoacetate

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Chinese Chemical Letters 2009年第10期20卷 1141-1144页

作者： Aye Aye Mar Ali Koohang Nathan D.Majewski erika L.Szotek David A.Eiznhamer Michael T.Flavin Advanced Life Sciences Inc.1440 Davey RoadWoodridgeIL 60517 USA

28-Carboxymethoxy lupane tritepenoids 3 and 4 were synthesized by alkylation of betulin with the THP protected 2- hydroxyethyl iodide followed by oxidation and reduction. Direct reaction of betulin （5） or betulone （10） with ethyl bromoacetate led to 28-O-acylation, instead of 28-O-alkylation. The targeted compounds 3 and 4 were not cytotoxic at the highest concentration tested （75 μmol/L）, suggesting that elongation of the chain length at the 28-position in both betulinic acid （1） and betulonic acid （2） was detrimental to the cytotoxicity. The acylation products 28-O-bromoacetates （Sa, 8b and 11） and 28-O-methoxyacetate 13 exhibited cytotoxicity against several cancer cell lines tested.

关键词： Betulinic acid Betulin Betulonic acid 28-O-Alkylation 28-O-Acylation Cytotoxicity

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A randomized trial comparing the Tennant Biomodulator to transcutaneous electrical nerve stimulation and traditional Chinese acupuncture for the treatment of chronic pain in military service members

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Military Medical Research 2020年第2期7卷 140-150页

作者： Kimberly S.Peacock erika Stoerkel Salvatore Libretto Weimin Zhang Alice Inman Michael Schlicher John D.Cowsar Jr David Eddie Joan Walter University of Texas Health San Antonio 7703 Floyd Curl DriveSan AntonioTX78229USA TLI Foundation 1750 Tysons BoulevardMcLeanVirginia22102USA Henry M.Jackson Foundation 6720A Rockledge DriveBethesdaMD20817USA BD Life Sciences 1 Becton DriveFranklin LakesNJ07417USA Brooke Army Medical Center 3551 Roger Brooke DriveFort Sam HoustonTX78234USA Madigan Army Medical Center 9040A Jackson AveJoint Base Lewis-McChordWA98431USA MedPost Urgent Care Center 513 Cibolo Valley DriveCiboloTX78108USA Massachusetts General Hospital Harvard Medical School151 Merrimac St.6th FloorBostonMA02114USA H&S Ventures Samueli Integrative Health Program1800 Diagonal RoadSuite 617AlexandriaVA22314USA

Background:The present investigation tested the efficacy of the Tennant Biomodulator,a novel pain management intervention that uses biofeedback-modulated electrical stimulation,to reduce chronic pain and its psychosocial sequelae in a sample of current and former military service *** Tennant Biomodulator used on its most basic setting was compared to two commonly used,non-pharmacological pain treatments—traditional Chinese acupuncture and transcutaneous electrical nerve stimulation(TENS)—in a comparative efficacy,randomized,open-label ***:Participants included 100 active duty and retired service men and women with chronic pain undergoing treatment at the Brooke Army Medical Center in Texas,USA,randomly assigned to receive six,weekly sessions of either Tennant Biomodulator treatment,traditional Chinese acupuncture,or TENS,in addition to usual *** was conducted between May 2010 to September *** measures were collected at intake,before and after each treatment session,and at a 1-month ***-to-treat analyses were used throughout,with mixed models used to investigate main effects of group,time,and group×time interactions with consideration given to quadratic *** measured included ratings of chronic pain,pain-related functional disability,and symptoms of post-traumatic stress disorder(PTSD)and ***:On average,regardless of their treatment group,participants exhibited a 16%reduction in pain measured by the Brooke Army Medical Center’s Clinic Pain Log[F(1,335)=55.7,P<0.0001]and an 11%reduction in pain-related disability measured by the Million Visual Analog Scale[MVAS:F(1,84)=28.3,P<0.0001]from baseline to the end of treatment,but no one treatment performed better than the other,and the reductions in pain and pain-related disability were largely lost by 1-month *** of PTSD and depression did not change significantly as a function of time or ***:Findings build on previ

关键词： Tennant biomodulator Acupuncture Transcutaneous electrical nerve stimulation Chronic pain Military service members

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The use of pharmacogenetics to increase the safety of colorectal cancer patients treated with fluoropyrimidines

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Cancer Drug Resistance 2019年第1期2卷 116-130页

作者： Elena De Mattia Rossana Roncato Chiara Dalle Fratte Fabrizio Ecca Giuseppe Toffoli erika Cecchin Experimental and Clinical Pharmacology Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano 33081Italy

Fluoropyrimidines(FP)are given in the combination treatment of the advanced disease or as monotherapy in the neo-adjuvant and adjuvant treatment of colorectal cancerand other solid tumors including breast,head and neck and gastric *** present a narrow therapeutic index with 10 to 26% of patients experiencing acute severe or life-threatening *** the high number of patients receiving FP-based therapies,and the significant effects of toxicities on their quality of life,the prevention of FP-related adverse events is of major clinical *** genetic variants in the rate limiting enzyme dihydropyrimidine dehydrogenase(DPYD)gene are related to the occurrence of extremely severe,early onset toxicity in FP treated *** pre-treatment diagnostic test of 4 DPYD genetic polymorphisms is suggested by the currently available pharmacogenetic *** prospective implementation projects are ongoing to support the introduction of up-front genotyping of the patients in clinical *** pharmacogenetic studies tried to assess the predictive role of other polymorphisms in genes involved in the FP pharmacokinetics/pharmacodynamic pathways,TYMS and MTHFR,but no additional clinically validated genetic markers of toxicity are available to *** development of next-generation sequencing platforms opens new possibilities to highlight previously unreported genetic ***,the investigation of the genetic variation in the patients immunological system,a pivotal target in cancer treatment,could bring notable advances in the *** review will describe the most recent literature on the use of pharmacogenetics to increase the safety of a treatment based on FP administration in colorectal cancer patients.

关键词： Fluoropyrimidines pharmacogenetics colorectal cancer toxicity DPYD TYMS MTHFR

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Hepatitis B virus infection in Latin America:A genomic medicine approach

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World Journal of Gastroenterology 2014年第23期20卷 7181-7196页

作者： Sonia Roman Alexis Jose-Abrego Nora Alma Fierro Griselda Escobedo-Melendez Claudia Ojeda-Granados erika Martinez-Lopez Arturo Puro Department of Molecular Biology in Medicine Civil Hospital of Guadalajara "Fray Antonio Alcalde" and University of GuadalajaraGuadalajaraJalisco 44280Mexico Immunovirology Unit Department of Molecular Biology in MedicineCivil Hospital of Guadalajara "Fray Antonio Alcalde" and University of GuadalajaraGuadalajaraJalisco 44280Mexico Viral Hepatitis Clinic Pediatric Infectious Disease UnitDepartment of Pediatric Hematology and OncologyCivil Hospital of Guadalajara "Juan I.Menchaca" and University of GuadalajaraGuadalajaraJalisco 44280Mexico

Hepatitis B virus(HBV)infection is the leading cause of severe chronic liver *** article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin *** levels of evolutionary adaptation may correlate with the clinical outcomes of HBV *** in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America;these strains have historically circulated among the indigenous *** genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South *** contrast,genotypes F,A and D are common in acute and chronic infections among mestizos with Caucasian *** carcinoma is rare in Mexicans,but it has been associated with genotype F1b among *** observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America,which contrast with those reported in other regions of the world.

关键词： Genomic medicine Hepatitis B virus Hepatitis B virus genotypes Latin America Mexico Central America South America

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Talking with Children about Cancer: A Content Analysis of Text in Children’s Picture Books

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Health 2020年第7期12卷 750-763页

作者： Noyuri Yamaji Megumi Sawaguchi erika Ota Department of Global Health Nursing Graduate School of Nursing Science St. Luke’s International University Tokyo Japan Department of Child Health Nursing School of Nursing Tokyo Women’s Medical University Tokyo Japan

Introduction: To tell children that they are diagnosed with cancer is challenging for any healthcare professional and family. Pictures books are one of the communication tools for talking with children about severe diseases. However, little research is available about the contents of picture books about cancer for children. Therefore, this study aimed to examine the contents of children’s picture books about cancer and explore the advantages and disadvantages of using picture books to communicate with children about cancer. Methods: We searched the picture books about cancer written for children aged under ten years old on the *** Web site on 5 July 2019 and hand-searched on the cancer-related institutes’ Web site. We extracted the texts of relevant picture books and conducted a content analysis of them. Results: We identified 2555 picture books and included 30 of them. We identified three main contents, 1) cancer-related knowledge, 2) impacts of cancer, and 3) dealing with cancer. These contents were written with simple words and illustrations. Some of them included the essential contents, which might be misunderstood by children. Conclusions: Picture books might be helpful for children to understand about cancer. However, as these books do not include all contents, it is necessary to select and use multiple books depending on the content which is wanted to tell the child. Further research should evaluate the impacts of these books as a communication tool when talking with children diagnosed with cancer.

关键词： Cancer Oncology Pediatrics Communication Picture Books Contents Analysis

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Hepatitis C virus/human T lymphotropic virus 1/2 coinfection:Regional burden and virological outcomes in people who inject drugs

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World Journal of Virology 2016年第2期5卷 68-72页

作者： erika Castro Elena Roger Addiction Medicine Centre Service of Community PsychiatryDepartment of PsychiatryCentre Hospitalier Universitaire Vaudois

This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.

关键词： Hepatitis C virus Human T lymphotropic virus Hepatitis C virus/human T lymphotropic virus-1/2 co-infection People who inject drugs Human T lymphotropic virus-1/2 screening among people who inject drugs Co-infection treatment

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