In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Input: Consider Input: Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an in vitro system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection.

Output: Counteraction of HCV-Induced Oxidative Stress Concurs to Establish Chronic Infection in Liver Cell Cultures


Input: Consider Input: Ubiquitination, a post-translational modification, mediates diverse cellular functions including endocytic transport of molecules. Kaposi's sarcoma-associated herpesvirus (KSHV), an enveloped herpesvirus, enters endothelial cells primarily through clathrin-mediated endocytosis. Whether ubiquitination and proteasome activity regulates KSHV entry and endocytosis remains unknown. We showed that inhibition of proteasome activity reduced KSHV entry into endothelial cells and intracellular trafficking to nuclei, thus preventing KSHV infection of the cells. Three-dimensional (3-D) analyses revealed accumulation of KSHV particles in a cytoplasmic compartment identified as EEA1+ endosomal vesicles upon proteasome inhibition. KSHV particles are colocalized with ubiquitin-binding proteins epsin and eps15. Furthermore, ubiquitination mediates internalization of both KSHV and one of its receptors integrin b1. KSHV particles are colocalized with activated forms of the E3 ligase c-Cbl. Knock-down of c-Cbl or inhibition of its phosphorylation reduced viral entry and intracellular trafficking, resulting in decreased KSHV infectivity. These results demonstrate that ubiquitination mediates internalization of both KSHV and one of its cognate receptors integrin b1, and identify c-Cbl as a potential E3 ligase that facilitates this process.

Output: Associated Herpesvirus in Endothelial Cells


Input: Consider Input: Background: Although the mini-clinical evaluation (mini-CEX) exercise has been adapted to a broad range of clinical situations, limited studies of the mini-CEX for postgraduate residency training in emergency medicine (EM) have been documented. Aim: The purpose of this study is to analyze the results of implementing the mini-CEX into the one-month postgraduate residency training in EM. Materials and methods: This study is a retrospective review of mini-CEXs completed by ED faculty members from August 2009 to December 2010. All PGY-1 residents enrolled in this study rotated through the one-month EM training. Each PGY-1 resident received one week of trauma training and three weeks of non-trauma training. The clinical competencies of each PGY-1 resident were evaluated with mini-CEXs, rated by a trauma surgeon and three emergency physicians (EPs). We analyzed the validity of weekly mini-CEX and the impact of seniority and specialty training of ED faculties on observation time, feedback time and rating scores. Results: Fifty-seven ED faculty members (42 EPs and 15 trauma surgeons) evaluated 183 PGY-1 residents during the 17 months of EM training. ED faculties with different specialty training provided similar assessment processes. Most competencies were rated significantly higher by trauma surgeons than by EPs. On the computerized mini-CEX rating, no data was missed and junior EPs rated all competencies significantly higher. The evaluators and PGY-1 residents were generally satisfied with the computerized format. As compared to the first assessment, only some competencies of PGY-1 residents were rated significantly higher in subsequent evaluations. Conclusion: The seniority and specialty training of ED faculty affected the mini-CEX ratings. The computer-based mini-CEX facilitated complete data gathering but showed differences for ED faculty with different levels of seniority. Further studies of the reliability and validity of the mini-CEX for PGY-1 EM training are needed.


Output: Implementation of the mini-clinical evaluation exercise in postgraduate Year 1 residency training in emergency medicine: Clinical experience at Chang Gung Memorial Hospital ScienceDirect