bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of ribavirin in direct acting antiviral drug regimens for chronic hepatitis C
Authors: Clark Virginia , Nelson David R. 
Published: December 2011

AbstractDespite years of clinical use and extensive research efforts, the mechanism of action of ribavirin (RBV) is not well understood. Although it has only a mild, transient antiviral effect on HCV replication when administered as monotherapy, when combined with interferon, RBV improves sustained virological response (SVR) rates by approximately 25–30%. Proposed mechanisms of action for RBV against HCV include (1) a direct effect against the HCV RNA dependent RNA polymerase; (2) induction of misincorporation of nucleotides leading to lethal mutagenesis; (3) depletion of intracellular pools via inhibition of inosine monophosphate dehydrogenase; (4) alteration in the cytokine balance between a Th2 profile (anti‐inflammatory) to a Th1 profile (pro‐inflammatory); and (5) potentiating the effect of interferon via up‐regulation of genes involved in interferon signalling. Given the lack of a clear understanding of RBV mechanism of action, it has been challenging to confidently position this drug with new direct antiviral agents (DAA). However, early clinical studies provide strong evidence for a benefit of RBV in combination with DAAs for both IFN containing and sparing regimens. The addition of RBV reduces viral breakthroughs and/or relapses, at least when drugs with low to moderate genetic barriers to resistance are paired together. This is particularly true in patients harbouring HCV subtype 1a. Ongoing studies are now addressing the utility of RBV in nucleoside containing DAA regimens, which offer both potent antiviral activity as well as a high genetic barrier to resistance. It is remarkable that the age‐old question of the role of RBV in the future of HCV therapy remains as real today as it was two decades ago.
Triple therapy for HCV genotype 1 infection: telaprevir or boceprevir?
Authors: Shiffman Mitchell L. , Esteban Rafael 
Published: December 2011

AbstractBoceprevir and telaprevir are the first two protease inhibitors available for the treatment of patients infected with hepatitis C virus (HCV) genotype 1. A sustained virological response (SVR) of 70–80% is observed when either of these protease inhibitors is utilized with pegylated interferon (PEG‐IFN) and ribavirin (RBV) in treatment naïve patients. Both agents are also highly effective in patients who failed to achieve a SVR during previous treatment with PEG‐IFN/RBV. A rapid virological response (RVR) is observed in 56–60% of treatment naïve patients. Patients who achieve a RVR can be treated with a shorter course of therapy (24–28 weeks) and still achieve a SVR rate of 90% or higher. Patients who do not achieve a RVR, those with cirrhosis and certain prior non‐responders should be treated for 48 weeks. Although the SVR rates observed with boceprevir and telaprevir are quite similar both globally and within sub‐populations, the treatment algorithms for the two agents are unique. The decision of which protease inhibitor to use should assess several factors including the treatment scheme, duration of therapy, adverse event profile, cost and the likelihood of achieving a RVR. The latter is highly dependent upon IFN sensitivity and the IL28B genotype.
Contribution of ribavirin transporter gene polymorphism to treatment response in peginterferon plus ribavirin therapy for HCV genotype 1b patients
Authors: Tsubota Akihito , Shimada Noritomo , Yoshizawa Kai , Furihata Tomomi , Agata Rie , Yumoto Yoko , Abe Hiroshi , Ika Makiko , Namiki Yoshihisa , Chiba Kan , Fujise Kiyotaka , Tada Norio , Aizawa Yoshio 
Published: December 2011

AbstractBackgroundStandard‐dose ribavirin is crucial for the standard‐of‐care treatment of chronic hepatitis C virus (HCV) infection. Equilibrative nucleoside transporter 1 (ENT1), encoded by SLC29A1 gene, is the main transporter that imports ribavirin into human hepatocytes. Aims:To determine whether single nucleotide polymorphisms (SNPs) at the SLC29A1 gene could influence the probability of treatment response compared with other baseline and host genetic factors.MethodsA total of 526 East Asian patients monoinfected with HCV genotype 1b who had received pegylated interferon alpha plus ribavirin therapy were enrolled in this study. They were assigned randomly to the derivation and confirmatory groups. SNPs related to the IL28B, ITPA and SLC29A1 genes were genotyped using real‐time detection polymerase chain reaction. Factors associated with sustained virological response (SVR) were analysed using multiple logistic regression analysis.ResultsMultivariate analysis for the derivation group identified six baseline variables significantly and independently associated with SVR: age [P = 0.023, odds ratio (OR) = 0.97], gender (P = 0.0047, OR = 2.25), platelet count (P = 0.00017, OR = 1.11), viral load (P = 0.00026, OR = 0.54), IL28B SNP rs12979860 (P = 1.09 × 10−7, OR = 8.68) and SLC29A1 SNP rs6932345 (P = 0.030, OR = 1.85). Using the model constructed by these independent variables, positive and negative predictive values and predictive accuracy were 73.3, 70.1 and 71.9% respectively. For the confirmatory group, they were 71.4, 84.6 and 75.3% respectively. The SLC29A1 and IL28B SNPs were also significantly associated with rapid virological response.ConclusionsThe SNP at the major ribavirin transporter ENT1 gene SLC29A1 was one of significantly independent factors influencing treatment response, although the impact on the prediction was small.
A rest period before agitation may improve some in vitro apheresis platelet parameters during storage
Authors: Skripchenko Andrey , Myrup Andrew , Awatefe Helen , Thompson‐Montgomery Dedeene , Wagner Stephen J. 
Published: December 2011

BACKGROUND: Whole blood‐derived platelets (PLTs) prepared by the PLT‐rich plasma method are subjected to a recommended 1‐hour rest period after the second centrifugation to avoid excessive PLT activation. Different apheresis PLT preparation methods demonstrate different levels of PLT activation and ability to form macroscopic aggregates immediately after collection. PLT collections are lost on Day 1 of storage if aggregates are not dispersed. It is possible that a rest period may help to disperse PLT aggregates. It is not established whether apheresis PLTs require a rest period before agitation and what the length of this period should be.STUDY DESIGN AND METHODS: Apheresis PLTs (Amicus, Fenwal, Inc.) were divided into five identical aliquots. One aliquot was placed on the flatbed agitator immediately after division. The other aliquots were subjected to agitation after 1, 2, 4, and 6 hours of rest. Samples were taken on Days 1, 5, and 7 for standard PLT assays.RESULTS: No differences during 7‐day storage were observed in PLT content, mean PLT volume, pH levels, bicarbonate, glucose, lactate, oxygen and carbon dioxide levels, hypotonic shock response, aggregation, and activation markers in PLT aliquots subjected to different rest periods or without a rest period. In contrast, values of extent of shape change, percentage of discoid PLTs, and expression of GP1b‐α were greater in aliquots subjected to different periods of rest compared to those of PLTs without a rest period.CONCLUSION: A rest period from 1 to 6 hours may improve some but not all in vitro PLT storage parameters.
Factors affecting microbial contamination rate of cord blood collected for transplantation
Authors: Clark Pamela , Trickett Annnette , Stark Damien , Vowels Marcus 
Published: December 2011

BACKGROUND: Collection and processing of cord blood (CB) is associated with significant risk of microbial contamination and hence relevant standards mandate microbial screening of the final product. This study aimed to determine the contamination rate and associated risk factors during 14 years of banking at the Sydney Cord Blood Bank.STUDY DESIGN AND METHODS: CB was collected and processed using a closed system and tested for contamination using blood culture bottles (BacT/ALERT, bioMérieux) incubated for a minimum of 5 days. Four microbial screening methods were used with different combinations of inoculated bottles (adult or pediatric) and associated sample volumes (10 or 1 mL).RESULTS: Of 13,344 CB units screened, 537 (4.0%) tested positive for contamination, with Bacteroides spp. (20.9%), Staphylococcus spp. (18.6%), and Propionibacterium spp. (13.7%) being the most common isolates. The contamination rate reduced from 10% in 1997 to 1.1% in 2009. Multivariate analysis demonstrated the following variables were independently associated with higher contamination rates: vaginal delivery, collection by obstetric staff, and use of an anaerobic bottle in addition to an aerobic bottle (which facilitated a larger sample inoculation volume than pediatric bottles).CONCLUSIONS: This study demonstrates that contamination rates of CB collected for transplantation can be substantially reduced by collection after cesarean delivery and utilizing trained CB collection staff. These data also indicate that the common practice of testing using a pediatric (aerobic) bottle with its attendant small volume of the final CB product may be suboptimal for sensitive detection of contaminating anaerobic microbes.
Spark Plasma Sintering of Diamond Binderless WC Composites
Authors: Grasso Salvatore , Hu Chunfeng , Maizza Giovanni , Sakka Yoshio 
Published: December 2011

A new method was developed to fully consolidate binderless tungsten carbide and diamond powders by means of spark plasma sintering (SPS) in current‐control mode (CCm). Below 900°C, the 2 cm diameter sample was slowly heated by a dc current of 1000 A. Above 900°C the imposed current was suddenly raised to 4000 A. The combination of the relatively high heating rate of 2000°C/min and the relatively short holding time of 1.5 min (above 1300°C) was successful to fabricate fully dense binderless WC/diamond composite. No graphitization of diamond was detected after ultrafast sintering as confirmed by optical and SEM microstructure observations, XRD and Raman analysis. The sample showed very high wear resistance in comparison to fully dense monolithic binderless WC compacts. The developed method, unlike previously published works, did not require any diamond coating to prevent diamond graphitization.
Intracranial Abscess as a Complication of Allergic Fungal Sinusitis
Authors: Holbrook John F. , Eastwood James D. , Kilani Ramsey K. 
Published: December 2011

ABSTRACTBACKGROUND AND PURPOSEThis case involves a common disease, allergic fungal sinusitis (AFS), with the uncommon complication of intracranial abscess. Although AFS is known to result in bone erosion, invasive complications are rare.METHODSThe clinical and pathologic information were reviewed. A literature review was performed to clarify the clinical, radiologic, and pathologic features of AFS.RESULTSThe clinical and radiographic presentations were typical for AFS, including the relatively common complication of sinus wall erosion. Follow‐up imaging demonstrated spread of fungal disease into the adjacent masticator space and intracranial spread by foramen ovale.CONCLUSIONThis case illustrates the importance of identifying AFS and describing findings such as sinus erosion that may alter management. In this example, knowledge of the altered anatomy and potential for mucosal injury may facilitate surgical planning and decrease the likelihood of future complications.
The influence of enamel matrix derivative on the angiogenic activity of primary endothelial cells
Authors: Kasaj A. , Meister J. , Lehmann K. , Stratul S. I. , Schlee M. , Stein J. M. , Willershausen B. , Schmidt M. 
Published: December 2011

Kasaj A, Meister J, Lehmann K, Stratul SI, Schlee M, Stein JM, Willershausen B, Schmidt M. The influence of enamel matrix derivative on the angiogenic activity of primary endothelial cells. J Periodont Res 2012; 47: 479–487. © 2011 John Wiley & Sons A/SBackground and Objective:  Angiogenesis plays a crucial role in early wound healing and tissue regeneration. Although enamel matrix derivative (EMD) has demonstrated the potential to stimulate periodontal regeneration, the biological effects of EMD on angiogenesis and underlying mechanisms have not been fully elucidated. The aim of the present study was to examine the angiogenic effects of EMD in vitro.Material and Methods:  Human umbilical vein endothelial cells (HUVECs) were used to assess the effect of EMD on proliferation, survival, adhesion and migration. The effect of EMD on HUVEC angiogenesis was assessed by a three‐dimensional sprouting assay. In order to understand the signalling mechanism of altered cell proliferation of HUVECs caused by EMD, the phosphorylation status of ERK1/2 and of the serine/threonine protein kinase Akt was analysed by western blot using phospho‐specific antibodies.Results:  The proliferation of HUVECs was stimulated by 50 μg/mL EMD, whereas higher concentrations (≥ 100 μg/mL) resulted in an increased apoptotic rate. The mitogenic response to EMD was associated with the activation of ERK1/2. Enamel matrix derivative did not affect cell adhesion, but all concentrations of EMD tested (0.1–250 μg/mL) promoted migration of HUVECs. Furthermore, EMD induced capillary‐like sprout formation from HUVEC spheroids in a dose‐dependent manner.Conclusion:  Our data indicate that EMD acts as a proangiogenic factor in vitro and, as such, might contribute to periodontal tissue regeneration by stimulation of vessel formation during wound healing.
Protective effects of β‐carotene and melanin against protoporphyrine IX‐induced phototoxicity in the photo hen's egg test
Authors: Bafteh Pascal R. , Siegesmund Marko , Hanneken Sandra , Neumann Norbert J. 
Published: December 2011

SummaryPurposeThe aim of our study was to evaluate the photoprotective potential of melanin and β‐carotene against protoporphyrine IX‐induced phototoxicity via photo hen's egg test.MethodsIn three independent test groups, the yolk sac blood vessel system of hen's eggs was exposed to protoporphyrine IX and irradiated with ultraviolet A (UVA). One of the test groups also received melanin to investigate its photoprotective capacity; another test group received β‐carotene for the same purpose. Morphological changes and embryo lethality were recorded in these three test groups for a period of 24 h. The same parameters were obtained in five different control groups.ResultsThe control groups exhibited only minimal morphological changes and no fatalities. In contrast, severe phototoxic damage and a high lethality rate (75%) were observed in the test group exposed to protoporphyrine IX and UVA. Lethality was somewhat lower in the β‐carotene test group (58%) and was considerably lower in the melanin test group (17%).ConclusionsThe photoprotective potential against protoporphyrine IX‐induced phototoxic damage was moderate for β‐carotene and was remarkable for melanin. Given that synthetic melanocyte stimulating hormone (MSH) analogues induce a de novo synthesis of melanin without any previous ultraviolet irradiation in human skin, the application of MSH analogues might be conceived of as ‘light hardening’ without light. Synthetic MSH analogues thus may represent a new promising therapeutic option for photodermatoses especially for erythropoietic protoporphyria.
Incomplete efficacy of 5‐aminolevulinic acid (5 ALA) photodynamic therapy in the treatment of widespread extramammary Paget's disease
Authors: Al Yousef Abdullah , Boccara Olivia , Moyal‐Barracco Micheline , Zimmermann Ute , Saiag Philippe 
Published: December 2011

SummaryPhotodynamic therapy (PDT) using 5‐aminolevulinic acid (5‐ALA) is an effective treatment for several conditions such as Bowen's disease, subsets of basal cell carcinomas and actinic keratosis. Surgical resection is the first‐choice therapy for extramammary Paget's disease (EMPD), but extensive resection is highly invasive and recurrences are frequent. We report two cases of genital EMPD treated by PDT with partial efficacy. The first patient, a 78‐year‐old male, suffered from pubic and scrotal Paget's disease for 6 years despite numerous treatments. The second patient, a 78‐year‐old female, had vulvar involvement for 2 years that was resistant to multiple treatments. The disease was recurrent and chronic with important pruritus and significant impact on the quality of life. Methyl 5‐aminolevulinate was applied for 3 h, and irradiation was applied with red light (630 nm) using a total light dose of 37 J/cm2 for a period of 10 min. The patients were treated every 2 to 4 weeks for a total of at least three treatments. Both patients experienced a partial transient reduction in their symptoms. One patient had a partial transient remission (< 50% reduction of the involved surface), whereas in the other patient, PDT failed to reduce the surface area of the lesions.
Primary cutaneous B‐cell lymphomas
Authors: Kempf Werner , Denisjuk Natalja , Kerl Katrin , Cozzio Antonio , Sander Christian 
Published: December 2011

SummaryCutaneous B‐cell lymphomas (CBCL) are the second most common form of primary cutaneous lymphomas. The cutaneous follicle center lymphoma and the cutaneous marginal zone lymphoma (extranodal MALT type lymphoma) account for the vast majority of CBCL and manifest with nodules. These two lymphoma entities have an indolent, slowly progressive course and an excellent prognosis despite a high rate of recurrences. In contrast, cutaneous diffuse large B‐cell lymphoma, leg type, and other rare forms of CBCL display an impaired prognosis and therefore require to be treated with multiagent chemotherapy and anti‐CD20 monoclonal antibodies in most cases. Clinico‐pathologic correlation, histology with immunohistochemical profile and genotyping as well as staging examinations are crucial diagnostic elements in the work‐up of CBCL.
Should children dive with self‐contained underwater breathing apparatus (SCUBA)?
Authors: Winkler Bernd E , Muth Claus‐Martin , Tetzlaff Kay 
Published: December 2011

AbstractDiving with self‐contained underwater breathing apparatus (SCUBA) has become a popular recreational activity in children and adolescents. This article provides an extensive review of the current literature.Conclusions:  Medical contraindications to SCUBA diving for adults apply to children and adolescents, too, but must be adapted. Additional restrictions to the fitness to dive must apply to both, children and adolescents. Children should always be accompanied by a trained adult when diving.
Oral microcirculation in post‐menopause: a possible correlation with periodontitis
Authors: Scardina Giuseppe A. , Messina Pietro 
Published: December 2011

doi: 10.1111/j.1741‐2358.2011.00608.xOral microcirculation in post‐menopause: a possible correlation with periodontitisObjectives:  The reduction in the level of oestrogen, typical in menopause, has some effect on the health of the oral cavity. In fact, post‐menopausal women present more severe periodontal disease than pre‐menopausal women. Numerous factors can be held to be responsible for this increase, among which are the effects of oestrogens on the oral epithelium, on the salivary glands, on bone tissue and on the endothelium. Our double blind study aims to evaluate the possible variations in oral microcirculation in post‐menopausal women.Methods:  Twenty‐seven women in post‐menopause (age: Mean ± SD: 57.3 ± 8.73) and 27 women in pre‐menopause (age: Mean ± SD: 27.77 ± 3.56) were examined. Oral microcirculation was investigated using oral videocapillaroscopy.Results:  The study showed significant differences between cases and controls for the following parameters: decrease in diameter of loops (mean ± SD: 0.038 ± 0.008; 0.045 ± 0.005), increase in tortuosity (mean ± SD: 3.83 ± 1.13; 1.83 ± 1.06) in labial mucosa and decrease in density in periodontal mucosa (Mean ± SD: 28.86 ± 10.92; 89.62 ± 17.83).Conclusion:  The decrease in periodontal density may compromise the epithelium tropism, making it prone to inflammation. The tortuosity may indicate a greater permanence of inflammatory factors, increased in post‐menopausal women.
Testing cosmology with extreme galaxy clusters
Authors: Harrison Ian , Coles Peter 
Published: December 2011

ABSTRACT
Motivated by recent suggestions that a number of observed galaxy clusters have masses which are too high for their given redshift to occur naturally in a standard model cosmology, we use extreme value statistics to construct confidence regions in the mass–redshift plane for the most extreme objects expected in the universe. We show how such a diagram not only provides a way of potentially ruling out the concordance cosmology, but also allows us to differentiate between alternative models of enhanced structure formation. We compare our theoretical prediction with observations, placing currently observed high- and low-redshift clusters on a mass–redshift diagram, and find – provided we consider the full sky to avoid a posteriori selection effects – that none is in significant tension with concordance cosmology.
On the efficiency of the Blandford–Znajek mechanism for low angular momentum relativistic accretion
Authors: Das Tapas K. , Czerny B. 
Published: December 2011

ABSTRACT
The Blandford–Znajek (BZ) mechanism has usually been studied in the literature for accretion with considerably high angular momentum leading to the formation of either a cold Keplerian disc or a hot and geometrically thick sub-Keplerian flow as described within the framework of advection-dominated accretion flow/radiatively inefficient accretion flow. However, in nearby elliptical galaxies, as well as for our own Galactic Centre, accretion with very low angular momentum is prevalent. Such quasi-spherical strongly sub-Keplerian accretion has complex dynamical features and can accommodate stationary shocks. In this Letter, we present our calculation for the maximum efficiency obtainable through the BZ mechanism for complete general relativistic weakly rotating axisymmetric flow in the Kerr metric. Both shocked and shock-free flows have been studied in detail for rotating and counter-rotating accretion. Such a study has never been done in the literature before. We find that the energy extraction efficiency is low, about 0.1 per cent, and increases by a factor of 15 if the ram pressure is included. Such an efficiency is still much higher than the radiative efficiency of such optically thin flows. For the BZ mechanism, shocked flow produces a higher efficiency than the shock-free solutions and retrograde flow provides a slightly larger value of the efficiency than that for the prograde flow.
Evolutionary Perspectives on Rural Australia
Authors: TONTS MATTHEW , ARGENT NEIL , PLUMMER PAUL 
Published: December 2011

AbstractAn enduring concern within Australian rural geography has been to understand the nature and implications of change. Much of the intellectual effort has been focused on interpreting how rural economies, populations, social institutions, cultures, and land uses have been transformed through processes operating across a range of spatial and temporal scales. This paper offers a critical appraisal of recent rural research in Australia and how this body of work has attempted to make sense of change. It argues that despite an ongoing focus on the nature of change, it is often reduced to a relatively simple historical narrative. We suggest that some of the emerging ideas in ‘evolutionary economic geography’ might offer an alternative means of conceptualising the trajectories of rural economies, institutions, and communities. The paper outlines the contours of evolutionary economic geography and the ways in which some of its key conceptual foundations might offer a means of understanding not only rural change, but also continuity.