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Hepatitis C virus NS5A inhibitors and drug resistance mutations

World Journal of Gastroenterology 2014年第11期20卷 2902-2912页

作者： Shingo Nakamoto Tatsuo Kanda Shuang Wu hiroshi shirasawa Osamu Yokosuka Department of Molecular Virology Graduate School of MedicineChiba UniversityChiba 260-8677Japan Department of Gastroenterology and Nephrology Graduate School of MedicineChiba UniversityChiba 260-8677Japan

Some direct-acting antiviral agents for hepatitis C virus (HCV), such as telaprevir and boceprevir have been available since 2011. It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis. HCV NS5A inhibitors efficiently inhibited HCV replication in vitro. Human studies showed that dual, triple and quad regimens with HCV NS5A inhibitors, such as daclatasvir and ledipasvir, in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin, could efficiently inhibit HCV replication according to HCV genotypes. These combinations might be a powerful tool for “difficult-to-treat” HCV-infected patients. “First generation” HCV NS5A inhibitors such as daclatasvir, ledipasvir and ABT-267, which are now in phase III clinical trials, could result in resistance mutations. “Second generation” NS5A inhibitors such as GS-5816, ACH-3102, and MK-8742, have displayed improvements in the genetic barrier while maintaining potency. HCV NS5A inhibitors are safe at low concentrations, which make them attractive for use despite low genetic barriers, although, in fact, HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors, HCV NS5B inhibitors or peginterferon plus ribavirin. This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.

关键词： ACH-3102 Direct-acting antiviral agents Daclatasvir Hepatitis C virus Ledipasvir

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Hepatitis C virus genotypes in Myanmar

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World Journal of Gastroenterology 2016年第27期22卷 6095-6099页

作者： Nan Nwe Win Tatsuo Kanda Shingo Nakamoto Osamu Yokosuka hiroshi shirasawa Department of Molecular Virology Chiba University Chuo-ku Chiba 260-8670 Japan Department of Gastroenterology and Nephrology Chiba University Chuo-ku Chiba 260-8670 Japan

Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus(HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response(SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates(90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined.

关键词： Direct-acting antivirals Genotypes Hepatitis C virus Interferon-free Myanmar

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Antiviral therapies for chronic hepatitis C virus infection with cirrhosis

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World Journal of Hepatology 2015年第8期7卷 1133-1141页

作者： Shingo Nakamoto Tatsuo Kanda hiroshi shirasawa Osamu Yokosuka Depart-ment of Gastroenterology and Nephrology Chiba UniversityGraduate School of Medicine Department of Molecular Virology Chiba University Graduate School of Medicine

Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or mo

关键词： Hepatitis C virus Hepatocellular carcinoma Interferon-free regimen Liver cirrhosis Direct-actingantiviral agent

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Estimating the effective reproduction number of COVID-19 from population-wide wastewater data:An application in Kagawa,Japan

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Infectious Disease Modelling 2024年第3期9卷 645-656页

作者： Yuta Okada hiroshi Nishiura Kyoto University School of Public Health Yoshida-KonoeSakyoKyoto606-8601Japan

Although epidemiological surveillance of COVID-19 has been gradually downgraded globally,the transmission of COVID-19 *** is critical to quantify the transmission dynamics of COVID-19 using multiple datasets including wastewater virus concentration ***,we propose a comprehensive method for estimating the effective reproduction number using wastewater *** wastewater virus concentration data,which were collected twice a week,were analyzed using daily COVID-19 incidence data obtained from Takamatsu,Japan between January 2022 and September *** estimated the shedding load distribution(SLD)as a function of time since the date of infection,using a model employing the delay distribution,which is assumed to follow a gamma distribution,multiplied by a scaling *** also examined models that accounted for the temporal smoothness of viral load measurement *** model that smoothed temporal patterns of viral load was the best fit model(WAIC=2795.8),which yielded a mean estimated distribution of SLD of 3.46 days(95%CrI:3.01–3.95 days).Using this SLD,we reconstructed the daily incidence,which enabled computation of the effective reproduction *** the best fit posterior draws of parameters directly,or as a prior distribution for subsequent analyses,we first used a model that assumed temporal smoothness of viral load concentrations in wastewater,as well as infection counts by date of *** the subsequent approach,we examined models that also incorporated weekly reported case counts as a proxy for weekly incidence *** approaches enabled estimations of the epidemic curve as well as the effective reproduction number from twice-weekly wastewater viral load *** weekly case count data reduced the uncertainty of the effective reproduction *** conclude that wastewater data are still a valuable source of information for inferring the transmission dynamics of COVID-19,and that inferential performance is enhanced when tho

关键词： Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Wastewater-based epidemiology Shedding load distribution'Mathematical model

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The design and engineering strategies of metal tellurides for advanced metal-ion batteries

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Journal of Energy Chemistry 2024年第2期89卷 579-598,I0013页

作者： Wenmiao Zhao Xiaoyuan Shi Bo Liu hiroshi Ueno Ting Deng Weitao Zheng Key Laboratory of Automobile Materials of MOE School of Materials Science and EngineeringJilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy MaterialsJilin UniversityChangchun 130012JilinChina Key Laboratory of Polyoxometalate Science of Ministry of Education Northeast Normal UniversityChangchun 130024JilinChina Key Laboratory of Preparation and Application of Environmental Friendly Materials(Jilin Normal University) Ministry of EducationChangchun 130103JilinChina Creative Interdisciplinary Research Division The Frontier Research Institute for Interdisciplinary Sciences(FRIS)Department of ChemistryGraduate School of ScienceTohoku UniversitySendai 980-8578Japan

Owning various crystal structures and high theoretical capacity,metal tellurides are emerging as promising electrode materials for high-performance metal-ion batteries(MBs).Since metal telluride-based MBs are quite new,fundamental issues raise regarding the energy storage mechanism and other aspects affecting electrochemical *** volume expansion,low intrinsic conductivity and slow ion diffusion kinetics jeopardize the performance of metal tellurides,so that rational design and engineering are crucial to circumvent these ***,this review provides an in-depth discussion of recent investigations and progresses of metal tellurides,beginning with a critical discussion on the energy storage mechanisms of metal tellurides in various *** the following,recent design and engineering strategies of metal tellurides,including morphology engineering,compositing,defect engineering and heterostructure construction,for high-performance MBs are *** primary focus is to present a comprehensive understanding of the structural evolution based on the mechanism and corresponding effects of dimension control,composition,electron configuration and structural complexity on the electrochemical *** closing,outlooks and prospects for future development of metal tellurides are *** work also highlights the promising directions of design and engineering strategies of metal tellurides with high performance and low cost.

关键词： Metal tellurides Metal-ion battery Energy storage mechanism Material design and engineering

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Epidemiological impact of revoking mask-wearing recommendation on COVID-19 transmission in Tokyo,Japan

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Infectious Disease Modelling 2024年第4期9卷 1289-1300页

作者： Mayu Nagata Yuta Okada hiroshi Nishiura Kyoto University School of Public Health Yoshida-KonoeSakyoKyoto606-8601Japan

Despite the global implementation of COVID-19 mitigation measures,the disease continues to maintain *** mask wearing became one of the key measures for preventing the transmission of COVID-19 early in the pandemic period,many countries have relaxed the mandatory or recommended wearing of *** objective of the present study was to estimate the epidemiological impact of removing the mask-wearing recommendation in *** developed a model to assess the consequences of declining mask-wearing coverage after the government revoked its recommendation in February *** declining mask-wearing coverage was estimated using serial cross-sectional data,and a mathematical model was devised to determine the age-specific incidence of COVID-19 using the observed case count in Tokyo from week of October 3,2022 to October 30,*** explored model-based counterfactual scenarios to measure hypothetical situations in which the mask-wearing coverage decreases or increases relative to the observed *** results show that mask-wearing coverage declined from 97%to 69%by the week of October 30,2023,and that if the mask-wearing recommendation had continued,427 lives could have been saved in *** the mask-wearing coverage had declined to 25%of the observed level,the model suggests there might have been 1587 additional ***,revoking the mask-wearing recommendation had a substantial epidemiological *** future pandemics,our proposed approach could provide a realtime quantification of the effects of relaxing countermeasures.

关键词： COVID-19 Mask wearing recommendation Health policy Counterfactual Mathematical model

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Caspase-11 mediated inflammasome activation in macrophages by systemic infection of *** exacerbates arthritis

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International Journal of Oral Science 2024年第3期16卷 499-514页

作者： Tokuju Okano hiroshi Ashida Noriko Komatsu Masayuki Tsukasaki Tamako Iida Marie Iwasawa Yuto Takahashi Yasuo Takeuchi Takanori Iwata Miwa Sasai Masahiro Yamamoto hiroshi Takayanagi Toshihiko Suzuki Department of Bacterial Pathogenesis Infection and Host ResponseGraduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Lifetime Oral Health Care Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Periodontology Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunoparasitology Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan

Clinical studies have shown that Aggregatibacter actinomycetemcomitans(***)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly ***,we show that systemic infection with *** triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in *** administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in *** data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with *** work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with ***.

关键词： CD11b inflam infection

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Dynamic ultrasonography for optimizing treatment position in superior mesenteric artery syndrome:Two case reports and review of literature

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World Journal of Gastroenterology 2024年第5期30卷 499-508页

作者： Nobuaki Hasegawa Akihiko Oka Muyiwa Awoniyi Yuri Yoshida hiroshi Tobita Norihisa Ishimura Shunji Ishihara Department of Internal Medicine II Shimane University Faculty of MedicineIzumo 693-8501ShimaneJapan Department of Gastroenterology Hepatology and NutritionDigestive Disease and Surgery InstituteHepatology SectionCleveland ClinicClevelandOH 44195United States Clinical Laboratory Division Shimane University HospitalIzumo 693-8501ShimaneJapan Division of Hepatology Shimane University HospitalIzumo 693-8501Japan

BACKGROUND Superior mesenteric artery(SMA)syndrome is a rare cause of duodenal obstruction by extrinsic compression between the SMA and the aorta(SMA-Ao).Although the left lateral recumbent position is considered effective in the treatment of SMA syndrome,individual variations in the optimal patient position have been *** this report,we present two elderly cases of SMA syndrome that exhibited rapid recovery due to ultrasonographic dynamic evaluation of the optimal position for each *** SUMMARY Case 1:A 90-year-old man with nausea and *** diagnosis of SMA syndrome by computed tomography(CT),ultrasonography(US)revealed the SMA-Ao distance in the supine position(4 mm),which slightly improved in the lateral position(5.7–7.0 mm)without the passage of duodenal ***,in the sitting position,the SMA-Ao distance was increased to 15 mm accompanied by improved content ***,US indicated enhanced passage upon abdominal massage on the right *** day 2,the patient could eat comfortably with the optimal position and *** 2:An 87-year-old woman with *** the diagnosis of SMA syndrome and aspiration pneumonia by CT,dynamic US confirmed the optimal position(SMA-Ao distance was improved to 7 mm in forward-bent position,whereas it remained at 5 mm in the supine position).By day 7 when her pneumonia recovered,she could eat with the optimal *** The optimal position for SMA syndrome varies among *** US appears to be a valuable tool in improving patient outcomes.

关键词： Superior mesenteric artery syndrome Wilkie’s syndrome Cast syndrome Aorto-mesenteric compass syndrome Ultrasonography Case report

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Diverse genotypes of norovirus genogroup I and II contamination in environmental water in Thailand during the COVID-19 outbreak from 2020 to 2022

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Virologica Sinica 2024年第4期39卷 556-564页

作者： Kattareeya Kumthip Pattara Khamrin Aksara Thongprachum Rungnapa Malasao Arpaporn Yodmeeklin hiroshi Ushijima Niwat Maneekarn Department of Microbiology Faculty of MedicineChiang Mai UniversityChiang MaiThailand Center of Excellence(Emerging and Re-emerging Diarrheal Viruses) Chiang Mai UniversityChiang MaiThailand Faculty of Public Health Chiang Mai UniversityChiang MaiThailand Department of Community Medicine Faculty of MedicineChiang Mai UniversityChiang MaiThailand Department of Pathology and Microbiology Nihon University School of MedicineTokyoJapan

Noroviruses(NoVs)are the most significant viral pathogens associated with waterborne and foodborne outbreaks of nonbacterial acute gastroenteritis in humans *** study aimed to investigate the prevalence and diversity of NoVs contaminated in the environmental water in Chiang Mai,Thailand.A total of 600 environmental water samples were collected from ten sampling sites in Chiang Mai from July 2020 to December *** presence of NoV genogroups I(GI),GII,and GIV were examined using real-time RT-PCR *** genotype of the virus was determined by nucleotide sequencing and phylogenetic *** results showed that NoV GI and GII were detected at 8.5%(51/600)and 11.7%(70/600)of the samples tested,***,NoV GIV was not detected in this *** circulated throughout the year,with a higher detection rate during the winter *** NoV GI genotypes(GI.1-GI.6)and eight NoV GII genotypes(GII.2,GII.3,GII.7,GII.8,GII.10,GII.13,GII.17,and GII.21)were *** 121 NoV strains detected,GII.17 was the most predominant genotype(24.8%,30 strains),followed by GII.2(21.5%,26 strains),GI.3(17.4%,21 strains),and GI.4(16.5%,20 strains).Notably,NoV GII.3,GII.7,GII.8,and GII.10 were detected for the first time in water samples in this *** study provides insight into the occurrence and seasonal pattern of NoV along with novel findings of NoV strains in environmental water in Thailand during the COVID-19 *** findings emphasize the importance of further surveillance studies to monitor viral contamination in environmental water.

关键词： Detection Environmental water Norovirus(NoVs) Wastewater Thailand

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Correction: MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

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Oncology Research 2024年第8期32卷 1369-1370页

作者： HUI SUN MASANORI KAWANO TATSUYA IWASAKI ICHIRO ITONAGA YUTA KUBOTA hiroshi TSUMURA KAZUHIRO TANAKA Department of Orthopaedic Surgery Faculty of MedicineOita UniversityOita879-5503Japan

In the article‘MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1’(Oncology Research,2024,Vol.32,No.3,pp.463−***:10.32604/or.2023.044085),there was an error in the compilation of *** have revised Fig.8D to correct this error.A corrected version of Fig.8 is *** correction does not change any results or conclusions of the *** apologize for any inconvenience caused.

关键词： osteosarcoma correction revised

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