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https://www.readbyqxmd.com/read/29164151/naturally-occurring-resistance-associated-variants-to-hepatitis-c-virus-direct-acting-antiviral-agents-in-treatment-naive-hcv-genotype-6a-infected-patients
#1
Zhanyi Li, Ying Liu, Ying Zhang, Xiaoqiong Shao, Qiumin Luo, Xiaoyan Guo, Guoli Lin, Qingxian Cai, Zhixin Zhao, Yutian Chong
Background and Objective: The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods: Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29151275/rav-transcription-factors-are-essential-for-disease-resistance-against-cassava-bacterial-blight-via-activation-of-melatonin-biosynthesis-genes
#2
Yunxie Wei, Yanli Chang, Hongqiu Zeng, Guoyin Liu, Chaozu He, Haitao Shi
With one AP2 domain and one B3 domain, 7 MeRAVs in apetala2/ethylene response factor (AP2/ERF) gene family have been identified in cassava. However, the in vivo roles of these remain unknown. Gene expression assays showed that the transcripts of MeRAVs were commonly regulated after Xanthomonas axonopodis pv manihotis (Xam) and MeRAVs were specifically located in plant cell nuclei. Through virus-induced gene silencing (VIGS) in cassava, we found that MeRAV1 and MeRAV2 are essential for plant disease resistance against cassava bacterial blight, as shown by the bacterial propagation of Xam in plant leaves...
November 19, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29143142/prevalence-of-ns5b-resistance-associated-variants-in-treatment-na%C3%A3-ve-asian-patients-with-chronic-hepatitis-c
#3
Song Yang, Huichun Xing, Shenghu Feng, Wei Ju, Shunai Liu, Xiaomei Wang, Weini Ou, Jun Cheng, Calvin Q Pan
There is little information on the association between baseline non-structural protein (NS) 5b resistance-associated variants (RAVs) and treatment failure in hepatitis C patients. This study examined the frequencies of natural hepatitis C virus (HCV) NS5B resistance-associated variants (RAVs) in an Asian cohort. Samples from Asian HCV patients enrolled between October 2009 and September 2014 were analyzed for NS5B RAVs within the region from amino acid 230 to 371. Serum samples were tested by PCR genotyping, with sequence alignment performed using the neighbor-joining method...
November 15, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29103467/visualization-of-right-adrenal-vein-comparison-with-three-phase-dynamic-contrast-enhanced-ct
#4
Yoshifumi Noda, Satoshi Goshima, Shoma Nagata, Hiroshi Kawada, Nobuyuki Kawai, Hiromi Koyasu, Masayuki Matsuo
PURPOSE: To evaluate the visualization of the right adrenal vein (RAV) on dynamic contrast-enhanced computed tomography (CT) images in patients with primary aldosteronism. MATERIALS AND METHODS: We evaluated 27 consecutive patients with primary aldosteronism who underwent contrast-enhanced dynamic CT and subsequent adrenal venous sampling. Scan delays were 10-, 20- and 60-s after a bolus-tracking program detected that the threshold of a 100 Hounsfield units (HU) increase in the abdominal aorta had been achieved...
November 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/29082495/high-content-positional-biosensor-assay-to-screen-for-compounds-that-prevent-or-disrupt-androgen-receptor-and-transcription-intermediary-factor-2-protein-protein-interactions
#5
Yun Hua, Daniel P Camarco, Christopher J Strock, Paul A Johnston
Transcriptional Intermediary Factor 2 (TIF2) is a key Androgen receptor (AR) coactivator that has been implicated in the development and progression of castration resistant prostate cancer (CRPC). This chapter describes the implementation of an AR-TIF2 protein-protein interaction (PPI) biosensor assay to screen for small molecules that can induce AR-TIF2 PPIs, inhibit the DHT-induced formation of AR-TIF2 PPIs, or disrupt pre-existing AR-TIF2 PPIs. The biosensor assay employs high content imaging and analysis to quantify AR-TIF2 PPIs and integrates physiologically relevant cell-based assays with the specificity of binding assays by incorporating structural information from AR and TIF2 functional domains along with intracellular targeting sequences using fluorescent protein reporters...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29080280/usefulness-of-semiquantitative-pcr-invader-assay-for-selecting-candidates-for-daclatasvir-plus-asunaprevir-combination-therapy-among-patients-with-hepatitis-c-virus-genotype-1b
#6
Koichi Honda, Masataka Seike, Junya Oribe, Mizuki Endo, Mie Arakawa, Masanori Tokoro, Masao Iwao, Tetsu Mori, Junko Nishimura, Yukou Takahashi, Kaoru Omori, Tsutomu Yamashita, Toyokichi Muro, Kazunari Murakami
BACKGROUND & AIMS: PCR-Invader is a highly sensitive assay for detecting nonstructural protein 5A (NS5A) resistance-associated variants (RAVs) of hepatitis C virus (HCV). Here, we validated the accuracy of the semiquantitative PCR-Invader (SQ-PI) assay compared to direct sequencing (DS) for identifying NS5A RAVs, and we evaluated the treatment efficacy of daclatasvir plus asunaprevir (DCV+ASV) for patients judged to be nonpositive for NS5A RAVs by SQ-PI. METHODS: Detection rates of NS5A RAVs by SQ-PI and DS were compared for 204 patients with HCV genotype 1b...
October 28, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28961511/identification-and-functional-prediction-of-stress-responsive-ap2-erf-transcription-factors-in-brassica-napus-by-genome-wide-analysis
#7
Hajar Owji, Ali Hajiebrahimi, Hassan Seradj, Shiva Hemmati
Using homology and domain authentication, 321 putative AP2/ERF transcription factors were identified in Brassica napus, called BnAP2/ERF TFs. BnAP2/ERF TFs were classified into five major subfamilies, including DREB, ERF, AP2, RAV, and BnSoloist. This classification is based on phylogenetic analysis, motif identification, gene structure analysis, and physiochemical characterization. These TFs were annotated based on phylogenetic relationship with Brassica rapa. BnAP2/ERF TFs were located on 19 chromosomes of B...
September 14, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28881052/asunaprevir-and-daclatasvir-for-recurrent-hepatitis-c-after-liver-transplantation-a-japanese-multicenter-experience
#8
Toru Ikegami, Yoshihide Ueda, Nobuhisa Akamatsu, Kohei Ishiyama, Ryoichi Goto, Akihiko Soyama, Kaori Kuramitsu, Masaki Honda, Masahiro Shinoda, Tomoharu Yoshizumi, Hideaki Okajima, Yuko Kitagawa, Yukihiro Inomata, Yonson Ku, Susumu Eguchi, Akinobu Taketomi, Hideki Ohdan, Norihiro Kokudo, Mitsuo Shimada, Katsuhiko Yanaga, Hiroyuki Furukawa, Shinji Uemoto, Yoshihiko Maehara
The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients...
September 7, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28874040/direct-acting-antiviral-agents-in-korean-patients-with-chronic-hepatitis-c-and-hemophilia-who-are-treatment-na%C3%A3-ve-or-treatment-experienced
#9
Hyun Woong Lee, Ki Young Yoo, Joung Won Won, Hyung Joon Kim
Background/Aims: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. Methods: Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety...
September 15, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28851606/clinical-evaluation-of-a-newly-developed-automated-massively-parallel-sequencing-assay-for-hepatitis-c-virus-genotyping-and-detection-of-resistance-association-variants-comparison-with-a-line-probe-assay
#10
Narathon Manee, Nipa Thongbaiphet, Ekawat Pasomsub, Wasun Chantratita
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. Recently, HCV was classified into 6 major genotypes (GTs) and 67 subtypes (STs). Efficient genotyping has become an essential tool for prognosis and indicating suitable treatment, prior to starting therapy in all HCV-infected individuals. The widely used genotyping assays have limitation with regard to genotype accuracy. This study was a comparative evaluation of exact HCV genotyping in a newly developed automated-massively parallel sequencing (MPS) system, versus the established Line probe assay 2...
August 26, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28836992/real-life-prevalence-of-resistance-associated-variants-against-non-structural-protein-5a-inhibitors-and-efficiency-of-daclatasvir%C3%A2-%C3%A2-asunaprevir-therapy-in-korean-patients-with-genotype-1b-hepatitis-c
#11
Jung Hwan Yu, Jung Il Lee, Kwan Sik Lee, Ja Kyung Kim
BACKGROUND: Direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) treatment are tolerable and highly effective in a shorter period of time than before. However, resistance-associated variants (RAVs) can affect the efficacy of DAAs. The aim of this study was to investigate the real-life prevalence of RAVs against non-structural protein 5A (NS5A) inhibitors in Korean patients with genotype 1b chronic hepatitis C. METHODS: All consecutive patients with CHC genotype 1b who underwent a RAV test at a single referral hospital were enrolled...
August 24, 2017: Virology Journal
https://www.readbyqxmd.com/read/28815329/efficacy-and-safety-of-ledipasvir-sofosbuvir-with-ribavirin-in-chronic-hepatitis-c-patients-who-failed-daclatasvir-asunaprevir-therapy-pilot-study
#12
Yoshiiku Kawakami, Hidenori Ochi, Clair Nelson Hayes, Michio Imamura, Masataka Tsuge, Takashi Nakahara, Yoshio Katamura, Hiroshi Kohno, Hirotaka Kohno, Keiji Tsuji, Shintaro Takaki, Nami Mori, Yohji Honda, Keiko Arataki, Shoichi Takahashi, Shinsuke Kira, Toru Tamura, Kazunari Masuda, Toshio Nakamura, Masaya Kikkawa, Kazuaki Chayama
BACKGROUND: In Japan, daclatasvir (DCV) and asunaprevir (ASV) therapy was the first IFN-free treatment to be approved, and thousands of patients have since been successfully treated, with an SVR rate of around 90%. The converse, however, is that around 10% of patients fail to achieve viral eradication and must be retreated using a different approach. This study is to evaluate treatment efficacy of ledipasvir/sofosbuvir and ribavirin in patients who failed to respond to DCV and ASV therapy...
August 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28679980/selection-of-regimens-for-patients-with-hepatitis-c-virus-genotype-serotype-discrepancy
#13
Shinji Katsushima, Tatsuro Kobata, Toshiki Komeda, Seiko Hamada, Kouki Chikugo, Shigeharu Nakano, Tsubasa Shimogama, Ken Kumagai, Yoshiyuki Ohta, Bunji Endoh, Naoki Esaka, Satoru Iwamoto, Katsuhiro Kasahara, Nobuko Shima, Yoshinori Mizumoto
In the present study, the usefulness of the resistance-associated variant (RAV) analysis to select direct acting antiviral (DAA) drugs for patients with hepatitis C virus (HCV) genotype/serotype discrepancy was evaluated. The core-genotype and serotype were determined in the 559 patients recruited in the study. The RAV analysis and NS5B-genotype determination were performed in the eight patients who exhibited a genotype/serotype discrepancy. One of these patients exhibited a core-genotype 1b/serotype 2, and detection by RAV analysis was possible in this patient...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28667225/using-patient-reported-outcome-measures-proms-to-promote-quality-of-care-and-safety-in-the-management-of-patients-with-advanced-chronic-kidney-disease-pro-track-project-a-mixed-methods-project-protocol
#14
Olalekan Lee Aiyegbusi, Derek Kyte, Paul Cockwell, Tom Marshall, Mary Dutton, Anita Slade, Neil Marklew, Gary Price, Rav Verdi, Judi Waters, Keeley Sharpe, Melanie Calvert
INTRODUCTION: Advanced chronic kidney disease (CKD) has a major effect on the quality of life and health status of patients and requires accurate and responsive management. The use of electronic patient-reported outcome measures (ePROMs) could assist patients with advanced pre-dialysis CKD, and the clinicians responsible for their care, by identifying important changes in symptom burden in real time. We report the protocol for 'Using Patient-Reported Outcome measures (PROMs) to promote quality of care and safety in the management of patients with Advanced Chronic Kidney Disease' (PRO-trACK) project, which will explore the feasibility and validity of an ePROM system for use in patients with advanced CKD...
June 30, 2017: BMJ Open
https://www.readbyqxmd.com/read/28657143/emergence-of-drug-resistance-associated-variants-and-changes-in-serum-lipid-profiles-in-sofosbuvir-plus-ledipasvir-treated-chronic-hepatitis-c-patients
#15
Hiromi Kan, Michio Imamura, Yoshiiku Kawakami, Kana Daijo, Yuji Teraoka, Fumi Honda, Yuki Nakamura, Kei Morio, Tomoki Kobayashi, Takashi Nakahara, Yuko Nagaoki, Tomokazu Kawaoka, Masataka Tsuge, Hiroshi Aikata, Clair Nelson Hayes, Daiki Miki, Hidenori Ochi, Yoji Honda, Nami Mori, Shintaro Takaki, Keiji Tsuji, Kazuaki Chayama
Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing...
June 28, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28642765/genome-wide-identification-of-ap2-erf-transcription-factors-in-cauliflower-and-expression-profiling-of-the-erf-family-under-salt-and-drought-stresses
#16
Hui Li, Yu Wang, Mei Wu, Lihong Li, Cong Li, Zhanpin Han, Jiye Yuan, Chengbin Chen, Wenqin Song, Chunguo Wang
The AP2/ERF transcription factors (TFs) comprise one of the largest gene superfamilies in plants. These TFs perform vital roles in plant growth, development, and responses to biotic and abiotic stresses. In this study, 171 AP2/ERF TFs were identified in cauliflower (Brassica oleracea L. var. botrytis), one of the most important horticultural crops in Brassica. Among these TFs, 15, 9, and 1 TFs were classified into the AP2, RAV, and Soloist family, respectively. The other 146 TFs belong to ERF family, which were further divided into the ERF and DREB subfamilies...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28634481/genome-wide-analysis-of-the-rav-family-in-soybean-and-functional-identification-of-gmrav-03-involvement-in-salt-and-drought-stresses-and-exogenous-aba-treatment
#17
Shu-Ping Zhao, Zhao-Shi Xu, Wei-Jun Zheng, Wan Zhao, Yan-Xia Wang, Tai-Fei Yu, Ming Chen, Yong-Bin Zhou, Dong-Hong Min, You-Zhi Ma, Shou-Cheng Chai, Xiao-Hong Zhang
Transcription factors play vital roles in plant growth and in plant responses to abiotic stresses. The RAV transcription factors contain a B3 DNA binding domain and/or an APETALA2 (AP2) DNA binding domain. Although genome-wide analyses of RAV family genes have been performed in several species, little is known about the family in soybean (Glycine max L.). In this study, a total of 13 RAV genes, named as GmRAVs, were identified in the soybean genome. We predicted and analyzed the amino acid compositions, phylogenetic relationships, and folding states of conserved domain sequences of soybean RAV transcription factors...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28614668/cryptic-microheteroresistance-explains-mycobacterium-tuberculosis-phenotypic-resistance
#18
John Z Metcalfe, Elizabeth Streicher, Grant Theron, Rebecca E Colman, Christopher Allender, Darrin Lemmer, Rob Warren, David M Engelthaler
RATIONALE: Minority drug-resistant Mycobacterium tuberculosis subpopulations can be associated with phenotypic resistance but are poorly detected by Sanger sequencing or commercial molecular diagnostic assays. OBJECTIVES: To determine the role of targeted next-generation sequencing in resolving these minor variant subpopulations. METHODS: We used single molecule overlapping reads (SMOR), a targeted next-generation sequencing approach that dramatically reduces sequencing error, to analyze primary cultured isolates phenotypically resistant to rifampin, fluoroquinolones, or aminoglycosides, but for which Sanger sequencing found no resistance-associated variants (RAVs) within respective resistance-determining regions (study group)...
November 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28569206/virology-analysis-in-hcv-genotype-1-infected-patients-treated-with-the-combination-of-simeprevir-and-tmc647055-ritonavir-with-and-without-ribavirin-and-jnj-56914845
#19
Leen Vijgen, Kim Thys, An Vandebosch, Pieter Van Remoortere, René Verloes, Sandra De Meyer
BACKGROUND: In study TMC647055HPC2001, a 3-direct-acting-antiviral (DAA) regimen combining NS3/4A protease inhibitor simeprevir (SMV), non-nucleoside NS5B inhibitor TMC647055/ritonavir (RTV) and NS5A inhibitor JNJ-56914845 resulted in high sustained virologic response 12 weeks after actual end of treatment (SVR12) in chronic hepatitis C virus (HCV) genotype 1-infected patients. SVR12 rates were generally lower in the 2-DAA regimen SMV + TMC647055/RTV with or without ribavirin. The objective of this study was to identify and characterise pre-existing and emerging resistance-associated variants (RAVs) in patients enrolled in study TMC647055HPC2001...
May 31, 2017: Virology Journal
https://www.readbyqxmd.com/read/28560477/daclatasvir-and-asunaprevir-in-hemodialysis-patients-with-hepatitis-c-virus-infection-a-nationwide-retrospective-study-in-japan
#20
Goki Suda, Norihiro Furusyo, Hidenori Toyoda, Yoshiiku Kawakami, Hiroki Ikeda, Michihiro Suzuki, Keiko Arataki, Nami Mori, Keiji Tsuji, Yoshio Katamura, Koichi Takaguchi, Toru Ishikawa, Kunihiko Tsuji, Noritomo Shimada, Atsushi Hiraoka, Sho Yamsaki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Kanji Kato, Yoshiyuki Ueno, Etsuko Iio, Yasuhito Tanaka, Masayuki Kurosaki, Takashi Kumada, Kazuaki Chayama, Naoya Sakamoto
BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV)...
May 30, 2017: Journal of Gastroenterology
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