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| 1 | From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis显示文摘After that the era of chemotherapy in the treatment of solid tumors have been overcome by the 'translational era', with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new 'immunotherapy era' with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade. | Melissa Bersanelli Sebastiano Buti | 2017 | World Journal of Clinical Oncology2017，8，1： | 15 |
| 2 | Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study显示文摘 | Patrick Marcellin Edward Gane Maria Buti Nezam Afdhal William Sievert Ira M Jacobson Mary Kay Washington George Germanidis John F Flaherty Raul Aguilar Schall Jeffrey D Bornstein Kathryn M Kitrinos G Mani Subramanian John G McHutchison E Jenny Heathcote | 2012 | The Lancet2012，，： | 14 |
| 3 | Quasispecies structure,cornerstone of hepatitis B virus infection: Mass sequencing approach显示文摘Hepatitis B virus(HBV)is a DNA virus with complex replication,and high replication and mutation rates,leading to a heterogeneous viral population.The population is comprised of genomes that are closely related,but not identical;hence,HBV is considered a viral quasispecies.Quasispecies variability may be somewhat limited by the high degree of overlapping between the HBV coding regions,which is especially important in the P and S gene overlapping regions,but is less significant in the X and preCore/Core genes.Despite this restriction,several clinically and pathologically relevant variants have been characterized along the viral genome.Next-generation sequencing(NGS)approaches enable high-throughput analysis of thousands of clonally amplified regions and are powerful tools for characterizing genetic diversity in viral strains.In the present review,we update the information regarding HBV variability and present a summary of the various NGS approaches available for research in this virus.In addition,we provide an analysis of the clinical implications of HBV variants and their study by NGS. | Francisco Rodriguez-Frias Maria Buti David Tabernero Maria Homs | 2013 | World Journal of Gastroenterology2013，19，41： | 11 |
| 4 | Molecular genetics and genomics of the Rosoideae: state of theart and future perspectives显示文摘The Rosoideae is a subfamily of the Rosaceae that contains a number of species of economic importance,including the soft fruit species strawberry(Fragaria 3ananassa),red(Rubus idaeus)and black(Rubus occidentalis)raspberries,blackberries(Rubus spp.)and one of the most economically important cut flower genera,the roses(Rosa spp.).Molecular genetics and genomics resources for the Rosoideae have developed rapidly over the past two decades,beginning with the development and application of a number of molecular marker types including restriction fragment length polymorphisms,amplified fragment length polymorphisms and microsatellites,and culminating in the recent publication of the genome sequence of the woodland strawberry,Fragaria vesca,and the development of high throughput single nucleotide polymorphism(SNP)-genotyping resources for Fragaria,Rosa and Rubus.These tools have been used to identify genes and other functional elements that control traits of economic importance,to study the evolution of plant genome structure within the subfamily,and are beginning to facilitate genomic-assisted breeding through the development and deployment of markers linked to traits such as aspects of fruit quality,disease resistance and the timing of flowering.In this review,we report on the developments that have been made over the last 20 years in the field of molecular genetics and structural genomics within the Rosoideae,comment on how the knowledge gained will improve the efficiency of cultivar development and discuss how these advances will enhance our understanding of the biological processes determining agronomically important traits in all Rosoideae species. | Sara Longhi Lara Giongo Matteo Buti Nada Surbanovski Roberto Viola Riccardo Velasco Judson AWard Daniel J Sargent | 2014 | Horticulture Research2014，1，1： | 7 |
| 5 | Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection显示文摘 | Nezam Afdhal Stefan Zeuzem Paul Kwo Mario Chojkier Norman Gitlin Massimo Puoti Manuel Romero-Gomez Jean-Pierre Zarski Kosh Agarwal Peter Buggisch Graham R. Foster Norbert Br?u Maria Buti Ira M. Jacobson G. Mani Subramanian Xiao Ding Hongmei Mo Jenny C. Ya | 2014 | The New England Journal of Medicine2014，，： | 6 |
| 6 | Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection显示文摘Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels.The HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity.RESULTS CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation. | Cristina Godoy David Tabernero Sara Sopena Josep Gregori Maria Francesca Cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela Maria Buti Francisco Rodríguez-Frías | 2019 | World Journal of Gastroenterology2019，25，13： | 6 |
| 7 | Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy显示文摘AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also analyzed.RESULTS NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSION Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype. | Carolina González David Tabernero Maria Francesca Cortese Josep Gregori Rosario Casillas Mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando Marcal Yll Rosa Lopez-Martinez Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，19： | 6 |
| 8 | Three-Year Efficacy and Safety of Tenofovir Disoproxil Fumarate Treatment for Chronic Hepatitis B显示文摘 | E. Jenny Heathcote Patrick Marcellin Maria Buti Edward Gane Robert A. De Man Zahary Krastev George Germanidis Samuel S. Lee Robert Flisiak Kelly Kaita Michael Manns Iskren Kotzev Konstantin Tchernev Peter Buggisch Frank Weilert Oya Ovunc Kurdas Mitchell L | 2011 | Gastroenterology2011，，1： | 5 |
| 9 | Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep-pyrosequencing显示文摘AIM:To investigate the variability of the main immunodominant motifs of hepatitis B virus(HBV) core gene by ultra-deep-pyrosequencing(UDPS).METHODS:Four samples(2 genotype A and 2 genotype D) from 4 treatment-na ve patients were assessed for baseline variability.Two additional samples from one patient(patient 4,genotype D) were selected for analysis:one sample corresponded to a 36-mo treatment-free period from baseline and the other to the time of viral breakthrough after 18 mo of lamivudine treatment.The HBV region analyzed covered amino acids 40 to 95 of the core gene,and included the two main epitopic regions,Th50-69 and B74-84.UDPS was carried out in the Genome Sequencer FLX system(454 Life Sciences,Roche).After computer filtering of UDPS data based on a Poisson statistical model,122 813 sequences were analyzed.The most conserved position detected by UDPS was analyzed by site-directed mutagenesis and evaluated in cell culture.RESULTS:Positions with highest variability rates were mainly located in the main core epitopes,confirming their role as immune-stimulating regions.In addition,the distribution of variability showed a relationship with HBV genotype.Patient 1(genotype A) presented the lowest variability rates and patient 2(genotype A) had 3 codons with variability higher than 1%.Patient 3 and 4(both genotype D) presented 5 and 8 codons with variability higher than 1%,respectively.The median baseline frequencies showed that genotype A samples had higher variability in epitopic positions than in the other positions analyzed,approaching significance(P = 0.07,sample 1 and P = 0.05,sample 2).In contrast,there were no significant differences in variability between the epitopic and other positions in genotype D cases.Interestingly,patient 1 presented a completely mutated motif from amino acid 64 to 67(E 64 LMT 67),which is commonly recognized by T helper cells.Additionally,the variability observed in all 4 patients was particularly associated with the E 64 LMT 67 motif.Codons 78 and 79 were highly conserved in all samples,in keeping with their involvement in the interaction between the HBV virion capsid and the surface antigens(HBsAg).Of note,codon 76 was even more conserved than codons 78 and 79,suggesting a possible role in HBsAg interactions or even in hepatitis B e antigen conformation.Sequential analysis of samples from patient 4(genotype D) illustrated the dynamism of the HBV quasispecies,with strong selection of one minor baseline variant coinciding with a decrease in core variability during the treatment-free and lamivudinetreated period.The drop in variability seemed to result from a 'steady state' situation of the HBV quasispecies after selection of the variant with greatest fitness.CONCLUSION:Host immune pressure seems to be the main cause of HBV core evolution.UDPS analysis is a useful technique for studying viral quasispecies. | Maria Homs Maria Buti David Tabernero Josep Quer Alex Sanchez Noelia Corral Rafael Esteban Francisco Rodriguez-Frias | 2012 | World Journal of Gastroenterology2012，18，42： | 5 |
| 10 | Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population显示文摘AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null. | Rosario Casillas David Tabernero Josep Gregori Irene Belmonte Maria Francesca Cortese Carolina González Mar Riveiro-Barciela Rosa Maria López Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，6： | 5 |
| 11 | Particulate matter pollution in Kunshan High-Tech zone: Source apportionment with trace elements, plume evolution and its monitoring显示文摘Particulate matter(PM) in the Kunshan High-Tech zone is studied during a three-month campaign. PM and trace elements are measured by the online pollution monitoring, forecastwarning and source term retrieval system AS3. Hourly measured concentrations of PM_(10), PM_(2.5) and 16 trace elements in the PM_(2.5) section(Ca, Pb, Cu, Cl, V, Cr, Fe, Ti, Mn, Ni, Zn, Ga, As, Se, Sr, Ba)are focused. Source apportionment of trace elements by Positive Matrix Factorization modeling indicates that there are five major sources, including dust, industrial processing, traffic,combustion, and sea salt with contribution rate of 23.68%, 21.66%, 14.30%, 22.03%, and 6.89%,respectively. Prediction of plume dispersion from concrete plant and traffic emissions shows that PM_(10) pollution of concrete plant is three orders of magnitude more than that of the traffic. The influence range can extend to more than 3 km in 1 hr. Because the footprint of the industrial plumes is constantly moving according to the local meteorological conditions, the fixed monitoring sites scattered in a few hundred meters haven't captured the heaviest pollution plume at the local scale of a few km^2. As a more intensive monitoring network is not operationally possible, the use of online modeling gives accurate and quantitative information of plume location, which increases the spatial pollution monitoring capacity and improves the understanding of measurement data. These results indicate that the development of the AS3 system, which combines monitoring equipment and air pollution modeling systems, is beneficial to the real-time pollution monitoring in the industrial zone. | Suwei Zhang Qijie Zhang Armand Albergel Didier Buty Liangmin Yu Haiting Wang Wuxia Bi Peng Cheng Fu Chen Jun Fang Ruirui Hou Xudong Luan Changgan Shu Jingjing Su | 2018 | Journal of Environmental Sciences2018，30，9： | 3 |
| 12 | Telbivudine Improves Renal Function in Patients With Chronic Hepatitis B显示文摘 | Edward J. Gane Gilbert Deray Yun-Fan Liaw Seng Gee Lim Ching-Lung Lai Jens Rasenack Yuming Wang George Papatheodoridis Adrian Di Bisceglie Maria Buti Didier Samuel Alkaz Uddin Sophie Bosset Aldo Trylesinski | 2014 | Gastroenterology2014，，1： | 2 |
| 13 | Predicted Effects of Treatment for HCV Infection Vary Among European Countries显示文摘 | Sylvie Deuffic–Burban Pierre Deltenre Maria Buti Tommaso Stroffolini Julie Parkes Nikolai Mühlberger Uwe Siebert Christophe Moreno Angelos Hatzakis William Rosenberg Stefan Zeuzem Philippe Mathurin | 2012 | Gastroenterology2012，，4： | 2 |
| 14 | Major-effect candidate genes identified in cultivated strawberry(Fragaria×ananassa Duch.)for ellagic acid deoxyhexoside and pelargonidin-3-O-malonylglucoside biosynthesis,key polyphenolic compounds显示文摘Strawberries are rich in polyphenols which impart health benefits when metabolized by the gut microbiome,including anti-inflammatory,neuroprotective,and antiproliferative effects.In addition,polyphenolic anthocyanins contribute to the attractive color of strawberry fruits.However,the genetic basis of polyphenol biosynthesis has not been extensively studied in strawberry.In this investigation,ripe fruits from three cultivated strawberry populations were characterized for polyphenol content using HPLC-DAD-MSn and genotyped using the iStraw35k array.GWAS and QTL analyses identified genetic loci controlling polyphenol biosynthesis.QTL were identified on four chromosomes for pelargonidin-3-O-malonylglucoside,pelargonidin-3-O-acetylglucoside,cinnamoyl glucose,and ellagic acid deoxyhexoside biosynthesis.Presence/absence of ellagic acid deoxyhexoside and pelargonidin-3-O-malonylglucoside was found to be under the control of major gene loci on LG1X2 and LG6b,respectively,on the F.×ananassa linkage maps.Interrogation of gene predictions in the F.vesca reference genome sequence identified a single candidate gene for ellagic acid deoxyhexoside biosynthesis,while seven malonyltransferase genes were identified as candidates for pelargonidin-3-O-malonylglucoside biosynthesis.Homologous malonyltransferase genes were identified in the F.×ananassa‘Camarosa’genome sequence but the candidate for ellagic acid deoxyhexoside biosynthesis was absent from the‘Camarosa’sequence.This study demonstrated that polyphenol biosynthesis in strawberry is,in some cases,under simple genetic control,supporting previous observations of the presence or absence of these compounds in strawberry fruits.It has also shed light on the mechanisms controlling polyphenol biosynthesis and enhanced the knowledge of these biosynthesis pathways in strawberry.The above findings will facilitate breeding for strawberries enriched in compounds with beneficial health effects. | Jahn Davik Kjersti Aaby Matteo Buti Muath Alsheikh NadaŠurbanovski Stefan Martens Dag Røen Daniel James Sargent | 2020 | Horticulture Research2020，7，1： | 2 |
| 15 | Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: An international multicenter cohort study显示文摘 | Jorg Petersen Vlad Ratziu Maria Buti Harry L.A. Janssen Ashley Brown Pietro Lampertico Jan Schollmeyer Fabien Zoulim Heiner Wedemeyer Martina Sterneck Thomas Berg Christoph Sarrazin Marc Lutgehetmann Peter Buggisch | 2011 | Journal of Hepatology2011，，3： | 2 |
| 16 | 1413 SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN FOR TREATMENT OF CHRONIC HCV GENOTYPE-1 INFECTION IN TREATMENT-NA?VE PATIENTS: RESULTS FROM QUEST-2, A PHASE III TRIAL显示文摘 | M. Manns P. Marcellin F.P. Fred Poordad E. Stanislau Affonso de Araujo M. Buti Y. Horsmans E.J. Ewa Janczewska F. Villamil M. Peeters O. Lenz S. Ouwerkerk-Mahadevan R. Kalmeijer M. Beumont-Mauviel | 2013 | Journal of Hepatology2013，，： | 2 |
| 17 | Adherence to Lamivudine after an early withdrawal of hepatitis B immune globulin plays an important role in the long-term prevention of hepatitis B virus recurrence 显示文摘 | Buti M Mas A Prieto M | 2007 | Transplantation2007，84，5： | 1 |
| 18 | Genetic alterations in the S gene of hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis and after liver transplantation 显示文摘 | Buti M Jardi R | 1999 | Liver1999，19，3： | 1 |
| 19 | Hepatitis B virus genome variability and disease progression:the impact of pre-core mutants and HBV genotypes显示文摘 | BUTI M RODRIGUEZ-FRIAS F JARDI R | 2005 | J Clin Virol2005，34，1： | 1 |
| 20 | Genetic analysis of hepatitis A virus strains recovered from the environment and from patients with acute hepatitis 显示文摘 | Pina S Buti M Jardf R | 2001 | J Gen Virol2001，82，12： | 1 |
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