bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to optimize HCV therapy in genotype 1 patients: predictors of response
Authors: Petta Salvatore , Craxì Antonio 
Published: January 2013

AbstractThe advent of triple therapy (TT) with first‐generation protease inhibitors boceprevir (BOC) and telaprevir (TVR) in addition to pegylated interferon and ribavirin (PEG‐IFN/RBV) has resulted in a significant improvement in the sustained virological response (SVR) rate and potentially in life years gained compared to dual therapy (DT), when treating naïve or treatment‐experienced patients with genotype 1 (G1) chronic hepatitis C (CHC). This benefit is partly offset by the increased complexity of treatment, and the increased costs and risks of therapy, making it necessary to optimize the indications for TT. Naïve patients with mild fibrosis and the IL28B CC polymorphism and/or with a rapid virological response (RVR) to DT can still benefit from DT, while TT is preferable in all others. Phase 3 trials have clearly shown that a 1 log10 decrease in HCVRNA after 4 weeks of DT associated with a favourable IL28B genotype and a low stage of fibrosis, and a pattern of previous response to DT in treatment‐experienced patients are the strongest predictors of an SVR to TT. Moreover, an extended rapid virological response (eRVR) is associated with an SVR rate >90%, so that the overall duration of treatment can be shortened in a high proportion of patients. Further efforts to optimize the current TT regimens both by increasing efficacy and improving tolerance are still needed. Most important, in the future, treatment can probably be personalized based on data from post‐marketing surveillance of TT providing information about patient groups that were underrepresented in phase 3 studies such as those with cirrhosis.
How to optimize HCV therapy in genotype 2 patients
Authors: Grassi Eleonora , Aghemo Alessio 
Published: January 2013

AbstractHepatitis C Virus (HCV) Genotype 2 accounts for 10% of the patients with chronic HCV worldwide. The current standard of care (SOC) in these patients is 24 weeks of Pegylated Interferon (PEG‐IFN) plus Ribavirin (RBV), with sustained virological response rates (SVR) of 80–90%. However, there are subgroups of patients with HCV‐2, such as those with advanced fibrosis/cirrhosis, in whom SVR rates are still suboptimal, and highly responsive groups in whom SVR rates reach 95%. Treatment optimization is necessary to maximize efficacy in the former group and reduce treatment‐related side effects in the latter. Unfortunately, any attempt to modify the duration or dosing of the SOC according to baseline factors has been disappointing and should not be continued at present. On the other hand on‐treatment HCV RNA kinetics are fundamental for individualized treatment regimens because achieving negative HCV RNA at week 4 (rapid virological response, RVR) is the key factor when the duration of PEG‐IFN/RBV is tailored in HCV‐2 patients. Several studies have shown that treatment can be shortened to 16 weeks in HCV‐2 patients with a RVR, without increasing the risk of post‐treatment relapse, thus increasing tolerance to treatment while reducing healthcare costs. On the other hand, patients who do not achieve a RVR correspond to a population of difficult‐to‐cure HCV‐2 patients who need alternative treatment strategies which are not yet available.
Impact of therapy on the outcome of chronic hepatitis B
Authors: Liaw Yun‐Fan 
Published: January 2013

AbstractChronic hepatitis B virus (HBV) infection is a dynamic state in which HBV replication is the key driving force of disease progression, resulting in the development of hepatic decompensation, cirrhosis and hepatocellular carcinoma (HCC). The primary aim of therapy is to eliminate or suppress HBV to reduce the activity of hepatitis thus reducing the risk of or slowing the progression of liver disease. Treatment with nucleos(t)ide analogues (Nuc) may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function thus increasing survival in patients with hepatic decompensation. The long‐term benefits of a finite course of interferon α (IFN) therapy include a sustained and cumulative response, as well as a reduction in the progression of fibrosis and in the development of cirrhosis and/or HCC. Long‐term Nuc therapy may also result in histological improvement or reversal of advanced fibrosis and reduction in disease progression including the development of HCC. Hepatitis B surface antigen (HBsAg) seroclearance, a status close to a “cure”, may also occur in patients with a sustained or maintained viral response, especially in those with IFN‐based therapy. Pegylated IFN (PEG‐IFN) and newer Nucs may have even better long‐term outcomes because of improved efficacy and/or a low risk of drug resistance. However, treatment outcomes are still far from satisfactory. The development of more effective and safe but affordable anti‐HBV agents/strategies is needed to further improve outcomes.
New therapeutic strategies in HCV: second‐generation protease inhibitors
Authors: Clark Virginia C. , Peter Joy A. , Nelson David R. 
Published: January 2013

AbstractTelaprevir and boceprevir are the first direct‐acting antiviral agents approved for use in HCV treatment and represent a significant advance in HCV therapy. However, these first‐generation drugs also have significant limitations related to thrice‐daily dosing, clinically challenging side‐effect profiles, low barriers to resistance and a lack of pan‐genotype activity. A second wave of protease inhibitors are in phase II and III trials and promise to provide a drug regimen with a better dosing schedule and improved tolerance. These second‐wave protease inhibitors will probably be approved in combination with PEG‐IFN and Ribavirin (RBV), as well as future all‐oral regimens. The true second‐generation protease inhibitors are in earlier stages of development and efficacy data are anxiously awaited as they may provide pan‐genotypic antiviral activity and a high genetic barrier to resistance.
Best strategies for global HCV eradication
Authors: Hagan Liesl M. , Schinazi Raymond F. 
Published: January 2013

AbstractWorldwide eradication of hepatitis C virus (HCV) is possible through a combination of prevention education, universal clinical and targeted community screening, effective linkage to care and treatment with promising new direct‐acting antiviral drug regimens. Universal screening should be offered in all healthcare visits, and parallel community screening efforts should prioritize high‐prevalence, high‐transmission populations including injection drug users, prison inmates and those with HIV/HCV co‐infection. Increasing awareness of HCV infection through screening, improving treatment uptake and cure rates by providing linkage to care and more effective treatment, and ultimately combining education efforts with vaccination campaigns to prevent transmission and reinfection can slow and eventually stop the ‘silent epidemic’.
Optimal management of chronic hepatitis B patients with treatment failure and antiviral drug resistance
Authors: Zoulim Fabien , Locarnini Stephen 
Published: January 2013

AbstractThe management of treatment failure in patients with chronic hepatitis B, remains a clinical concern. Incomplete viral suppression and the emergence of drug resistance are key determinants of treatment failure. The correct choice of a potent first‐line therapy to achieve sustained long‐term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance have significantly lower rates of resistance compared with those with a low barrier to resistance. Management of treatment failure requires precise clinical and virological monitoring as well as early treatment intervention with appropriate noncross‐resistant antivirals. Long‐term surveillance of treatment efficacy and possible emergence of drug resistance is necessary in patients who have been sequentially treated with multiple antivirals. The identification of novel treatment targets remains a major research goal to improve the efficacy of current antiviral therapy through combination therapy regimens.
Treatment of HBV related cirrhosis
Authors: van Bömmel Florian , Berg Thomas 
Published: January 2013

AbstractUntil very recently, hepatitis B virus (HBV)‐associated cirrhosis was often regarded as an irreversible condition. It is associated with strongly increased mortality and a high risk of the development of hepatocellular carcinoma (HCC). Indeed, the incidence of HCC per 100 person years was shown to be 2–3.7 in patients with cirrhosis compared with only 0.3–0.6 in patients with active hepatitis B without cirrhosis and 0.02–0.2 in asymptomatic carriers. Liver transplantation was considered to be the only medical intervention, which could resolve this condition and which could improve the general condition of these patients. However, it is now becoming increasingly evident that long‐term suppression of viral replication allows the regenerative potential of the liver to reverse even high grade liver fibrosis. For the management of HBV‐related cirrhosis, it is therefore important to provide effective treatment and to identify and avoid risk factors for the development of cirrhosis and hepatic decompensation.
Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues
Authors: Dusheiko Geoffrey 
Published: January 2013

AbstractInterferon alpha has restricted efficacy in as much as only a proportion of patients show a response. However, in appropriately selected HBeAg‐positive and HBeAg‐negative patients, sustained suppression of viral replication can be achieved, and HBeAg or even HBsAg seroconversion can be attained. Thus, finite course of interferon alpha can be successful, and offer an advantage to patient. Interferon (IFN) remains a benchmark therapy for chronic hepatitis B. The main advantages of IFN‐α over nucleoside analogues are the absence of resistance and the possibility of immune‐mediated clearance of hepatitis B. Unfortunately, side effects preclude the use of interferon alpha in substantial proportions of patients, and prolonged maintenance therapy to suppress hepatitis B virus (HBV) is not feasible. Nucleoside analogues are given by mouth, once per day, and the safety, potency and efficacy have improved and facilitated treatment. However, maintenance of long‐term suppression is required for the majority of patients. In general, treatment of chronic hepatitis B should target patients with active disease and viral replication, preferably before the signs and symptoms of cirrhosis or significant injury has occurred. Current EASL guidelines suggest that treatment be based on the evaluation of three criteria: Serum aminotransferase levels, serum HBV DNA levels and histological grade and stage. Many questions remain unanswered on the optimal treatment of patients with chronic hepatitis B with a nucleoside vs interferon alpha. Both forms of treatment have benefits and the choice should be selected and tailored. Stopping or futility rules can be implemented in patients who fail interferon. Recent data suggest the safety and efficacy of nucleoside analogues in the third trimester of pregnancy to reduce the risk of transmission from mothers to their children.
Phylogeography of the widespread African puff adder (Bitis arietans) reveals multiple Pleistocene refugia in southern Africa
Authors: Barlow Axel , Baker Karis , Hendry Catriona R. , Peppin Lindsay , Phelps Tony , Tolley Krystal A. , Wüster Catharine E. , Wüster Wolfgang 
Published: January 2013

AbstractEvidence from numerous Pan‐African savannah mammals indicates that open‐habitat refugia existed in Africa during the Pleistocene, isolated by expanding tropical forests during warm and humid interglacial periods. However, comparative data from other taxonomic groups are currently lacking. We present a phylogeographic investigation of the African puff adder (Bitis arietans), a snake that occurs in open‐habitat formations throughout sub‐Saharan Africa. Multiple parapatric mitochondrial clades occur across the current distribution of B. arietans, including a widespread southern African clade that is subdivided into four separate clades. We investigated the historical processes responsible for generating these phylogeographic patterns in southern Africa using species distribution modelling and genetic approaches. Our results show that interior regions of South Africa became largely inhospitable for B. arietans during glacial maxima, whereas coastal and more northerly areas remained habitable. This corresponds well with the locations of refugia inferred from mitochondrial data using a continuous phylogeographic diffusion model. Analysis of data from five anonymous nuclear loci revealed broadly similar patterns to mtDNA. Secondary admixture was detected between previously isolated refugial populations. In some cases, this is limited to individuals occurring near mitochondrial clade contact zones, but in other cases, more extensive admixture is evident. Overall, our study reveals a complex history of refugial isolation and secondary expansion for puff adders and a mosaic of isolated refugia in southern Africa. We also identify key differences between the processes that drove isolation in B. arietans and those hypothesized for sympatric savannah mammals.
Comparison of the 308‐nm excimer laser with the 308‐nm excimer lamp in the treatment of vitiligo – a randomized bilateral comparison study
Authors: Shi Qiong , Li Kai , Fu Jun , Wang Yanchun , Ma Cuiling , Li Qiang , Li Chunying , Gao Tianwen 
Published: January 2013

AbstractBackgroundVitiligo is an acquired pigment disorder characterized by areas of depigmented skin resulting from the loss of epidermal melanocytes. Recently, several investigations have documented the benefits of excimer phototherapy (e.g., using the 308‐nm excimer laser or the 308‐nm excimer lamp) for the treatment of vitiligo.AimTo compare the effectiveness of the 308‐nm excimer laser with the 308‐nm excimer lamp in the treatment of vitiligo patients.MethodsThis intervention study was designed as a randomized self‐control trial. Fourteen subjects with 48 symmetrical vitiligo lesions were enrolled in this study. One lesion was treated with the 308‐nm excimer laser, and its counterpart was treated with the 308‐nm excimer lamp. Lesions were treated three times a week with the same dose on both sides for a total of 20 sessions.ResultsAll of the patients completed the study, and 48 lesions were treated. The two treatments exhibited similar results in terms of repigmentation.ConclusionsThe 308‐nm excimer lamp and the 308‐nm excimer laser exhibited similar efficacies in treating vitiligo.
Cryopreservation of Zona‐Free Cloned Buffalo (Bubalus Bubalis) Embryos: Slow Freezing vs Open‐Pulled Straw Vitrification
Authors: Sirisha K , Selokar NL , Saini M , Palta P , Manik RS , Chauhan MS , Singla SK 
Published: January 2013

ContentsThis study was carried out to compare the post‐thaw cryosurvival rate and the level of apoptosis in vitro produced zona‐free cloned buffalo blastocysts subjected to slow freezing or vitrification in open‐pulled straws (OPS). Zona‐free cloned embryos produced by handmade cloning were divided into two groups and were cryopreserved either by slow freezing or by vitrification in OPS. Cryosurvival of blastocysts was determined by their re‐expansion rate following post‐thaw culture for 22–24 h. The post‐thaw re‐expansion rate was significantly (p < 0.05) higher following vitrification in OPS (71.2 ± 2.3%) compared with that after slow freezing (41.6 ± 4.8%). For examining embryo quality, the level of apoptosis in day 8 frozen‐thawed blastocysts was determined by TUNEL staining. The total cell number was not significantly different among the control non‐cryopreserved cloned embryos (422.6 ± 67.8) and those cryopreserved by slow freezing (376.4 ± 29.3) or vitrification in OPS (422.8 ± 36.2). However, the apoptotic index, which was similar for embryos subjected to slow freezing (14.8 ± 2.0) or OPS vitrification (13.3 ± 1.8), was significantly (p < 0.05) higher than that for the control non‐cryopreserved cloned embryos (3.4 ± 0.6). In conclusion, the results of this study demonstrate that vitrification in OPS is better than slow freezing for the cryopreservation of zona‐free cloned buffalo blastocysts because it offers a much higher cryosurvival rate.
Occupational Change and Mobility Among Employed and Unemployed Job Seekers
Authors: Longhi Simonetta , Taylor Mark 
Published: January 2013

AbstractWe use data from the Labour Force Survey to show that employed and unemployed job seekers in Great Britain originate from different occupations and find jobs in different occupations. We find substantial differences in occupational mobility between job seekers: employed job seekers are most likely to move to occupations paying higher average wages relative to their previous occupation, while unemployed job seekers are most likely to move to lower paying occupations. Employed and unemployed job seekers exhibit different patterns of occupational mobility and, therefore, do not accept the same types of jobs.
English for Bible and Theology: Understanding and Communicating Theology Across Cultural and Linguistic Barriers
Authors: Pierson Cheri , Bankston Will 
Published: January 2013

AbstractThis article introducesEnglish forBible and Theology (EBT), an inherently interdisciplinary field that mergesEnglish language learning with the content of biblical and theological studies in a context that is, by nature, cross‐cultural. Within this collaboration there exists the possibility not only to enable theological study, but also to enhance it through a focus on personal meaning and its communication, both of which are foundational to the communicative language classroom. That is,EBTseeks both to aid students worldwide in attaining the specialized language and cultural proficiency necessary to accessEnglish theological resources and to provide a community in which students can connect theological content to their lives. It is this second aim that providesEBTits relevance across a range of theological contexts, as nativeEnglish‐speaking students likewise stand to benefit from the application ofEBT's principles.
From Classroom to Controversy: Conflict in the Teaching of Religion
Authors: Neal Lynn S. 
Published: January 2013

AbstractWhat happens when a class assignment becomes a source of controversy? How do we respond? What do we learn? By describing the controversy surrounding an assignment on religion and representation, this article examines conflict's productive role in teaching about New Religious Movements (NRMs) and religion. It suggests that we consider how our personal and institutional dispositions toward conflict influence our pedagogies. Moreover, it urges us to consider how teaching conflicts within and/or between disciplines can enhance our learning objectives and stimulate students' ability to think critically.
Financial Integration in East Asia: An Empirical Investigation
Authors: Lee Hyun‐Hoon , Huh Hyeon‐Seung , Park Donghyun 
Published: January 2013

AbstractThe central objective of this paper is to empirically evaluate the degree of linkages among East Asian equity and bond markets. Using data from the IMF’s Coordinated Portfolio Investment Survey (CPIS), we find that intra‐East Asian financial asset holdings of four East Asian countries – Japan, Korea, Hong Kong and Singapore – are larger than the levels predicted by the financial gravity model. However, our analysis suggests that this result is likely to be driven by intra‐regional trade linkages and reflect those linkages. Therefore, the salient implication for regional policymakers is that they should continue to promote intra‐regional financial integration. This paper also aims to analyse the impact of three different types of country‐specific risks – political, economic and financial risks – on investment from the four countries. This analysis yields a clear positive relationship between destination‐country risk, in particular political risk, and capital inflows.
Restrictive orbital myofibroblastic sarcoma in a cat – Cross‐sectional imaging (MRI&CT) appearance, treatment, and outcome
Authors: Thomasy Sara M. , Cissell Derek D. , Arzi Boaz , Vilches‐Moure Jose G. , Lo Winnie Y. , Wisner Erik R. , Dubielzig Richard R. , Maggs David J. 
Published: January 2013

AbstractA 16‐year‐old spayed female cat was evaluated for lagophthalmos and chronic exposure keratitis in both eyes. Ophthalmic examination revealed upper and lower eyelid entropion of the left eye (OS) and markedly decreased retropulsion, restricted eye movement, marked episcleral congestion, and severe keratitis of both eyes (OU). Magnetic resonance imaging of both orbits revealed extensive, irregular, contrast‐enhancing tissue without evidence of osteolysis considered compatible with diffuse inflammatory tissue. Feline herpesvirusDNAwas not detected in conjunctival samples. Partial temporary tarsorrhaphies were placedOU, and the cat was treated with topically administered erythromycin ointmentOU, orally administered famciclovir and prednisolone, and sublingually administered buprenorphine. Little improvement was noted after 2 weeks. Six weeks after initial presentation, a left exenteration was performed and histopathology was consistent with idiopathic sclerosing orbital pseudotumor (ISOP). Ten weeks after initial presentation, the patient represented for weight loss and jaw pain. Computed tomography demonstrated disease progression in the right orbit and the patient was euthanized. Histopathology of the decalcified skull revealed an aggressive and highly infiltrative mass involving the right orbit with extension to the maxilla, hard palate, nasal cavity and gingiva most consistent with feline restrictive orbital myofibroblastic sarcoma (FROMS). Clinical data from this patient support the reclassification ofISOPasFROMS.MRIandCTmay provide supportive evidence forFROMS, but histopathology is necessary for definitive diagnosis. Aggressive and early surgical treatment, including bilateral exenteration, with adjunctive radiotherapy and/or chemotherapy should be considered for patients withFROMS.
Metastatic uveal schwannoma of blue‐eyed dogs
Authors: Duke Felicia D. , Brudenall Denise K. , Scott Erin M. , Teixeira Leandro B. C. , Dubielzig Richard R. 
Published: January 2013

AbstractA formalin‐fixed left, blue eye, from a 9‐year‐old, spayed female beagle dog was submitted to theComparativeOcularPathologyLaboratory ofWisconsin (COPLOW) for light microscopic evaluation. The history included glaucoma and an abnormal appearance for 6 months and then the development of a uveal mass. The histologic diagnosis was a spindle cell tumor of blue‐eyed dogs (SCTBED). InJune of 2012, the dog was euthanized due to ailing health, and there was radiographic andpostmortemexamination evidence of neoplastic metastasis. This is the first reported case of this primary ocular neoplasm metastasizing, and we propose to renameSCTBEDas a uveal schwannoma of blue‐eyed dogs.