bluuebunny/crossref_metadata_2025_split huggingface dataset:
Undetectable HCV‐RNA at treatment‐week 8 results in high‐sustained virological response in HCV G1 treatment‐experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program
Authors: Bruno S. , Bollani S. , Zignego A. L. , Pascasio J. M. , Magni C. , Ciancio A. , Caremani M. , Mangia A. , Marenco S. , Piovesan S. , Chemello L. , Babudieri S. , Moretti A. , Gea F. , Colletta C. , Perez‐Alvarez R. , Forns X. , Larrubia J. R. , Arenas J. , Crespo J. , Calvaruso V. , Ceccherini Silberstein F. , Maisonneuve P. , Craxì A. , Calleja J. L. ,   Italian and Spanish (IAS)‐BoC Study Group
Published: October 2014

SummaryIn many countries, first‐generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV‐infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under‐represented in clinical trials. All treatment‐experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian–Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on‐treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25–78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child–Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV‐RNA at treatment‐week (TW)8. Among patients with TW8 HCV‐RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV‐RNA ≥ 1log10‐decline from baseline, undetectable TW8 HCV‐RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/μL. Metavir F4, Child‐Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment‐experienced patients with advanced liver disease eligible for IFN‐based therapy, TW8 HCV‐RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV‐RNA as a futility rule, BOC/P/R appears to have a favourable benefit–risk profile.
Pattern and process in the afterlife: legacy effects of canopy tree distribution on post‐disturbance regeneration
Authors: Canham Charles D. 
Published: October 2014

AbstractWild et al. (2014, Journal of Vegetation Science 25: 1327–1340) document persistent effects of the spatial distribution of canopy trees on the distribution of regeneration following stand‐replacing disturbance in montane Norway spruce forests. The authors suggest a simple physical process for these legacy effects – the accumulation of winter‐dispersed seeds in ‘tree‐wells’ with lower snow depth around the trunks of living and recently dead trees.
The serum IL‐23 level predicts the response to pegylated interferon therapy in patients with chronic hepatitis B
Authors: Yu Chengbo , Gong Xianli , Yang Qian , Lian Jiangshan , Xu Kaijin , Ruan Bin , Li Lanjuan 
Published: October 2014

AbstractBackground & AimsThis study investigated the possible use of interleukin (IL)‐23 and IL‐17 serum levels as indicators for anti‐hepatitis B virus (HBV) therapy.MethodsA total of 127 patients with chronic hepatitis B (CHB) who received pegylated interferon (PegIFN) therapy, 20 chronic asymptomatic HBV carriers (AsCs) and 32 healthy controls were recruited. The serum levels of IL‐23 and IL‐17 were detected by ELISA. The predictive value of baseline and early on‐treatment changes in the levels of IL‐23 and IL‐17 for therapeutic response were evaluated by receiver operating characteristic analysis. Multivariate logistic regression models were generated to identify independent factors that affect the clearance of hepatitis B e antigen (HBeAg) and the decline in hepatitis B surface antigen (HBsAg).ResultsThe baseline serum levels of IL‐23 and IL‐17 were higher in patients with CHB than in normal controls and in AsCs. High levels of pre‐treatment IL‐23 and IL‐17 and more significant on‐treatment reductions in IL‐23 and IL‐17 levels were observed in patients with CHB who achieved HBeAg clearance or a decline in HBsAg >1 log10 IU/ml compared with patients who were persistently HBeAg‐positive or who experienced a decline in HBsAg <1 log10 IU/ml. The predictive cut‐off value of IL‐23 for HBeAg clearance was 135 pg/ml, and the specificity and sensitivity were 71.4% and 70% respectively. A high pre‐treatment level of IL‐23 was an independent factor for the prediction of the therapeutic response in patients with HBeAg‐positive CHB. Early on‐treatment changes of IL‐23 and IL‐17 showed no predictive value.ConclusionsA high pre‐treatment serum IL‐23 level predicts the therapeutic response in HBeAg‐positive CHB patients during PegIFN therapy.
Novel mutation in the methyltransferase domain of DNMT1 in a hereditary sensory and autonomic neuropathy patient with hearing loss, cataract, and dementia
Authors: Nishihara Hideaki , Yuan Junhui , Omoto Masatoshi , Ogasawara Jun‐ichi , Koga Michiaki , Kawai Motoharu , Higuchi Yujiro , Hashiguchi Akihiro , Takashima Hiroshi , Kanda Takashi 
Published: October 2014

AbstractDNMT1 encodes DNA methyltransferase 1, which is a critical enzyme responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 mutations have been reported, including hereditary sensory and autonomic neuropathy type IE, and autosomal dominant cerebellar ataxia, deafness and narcolepsy. We report a sporadic Japanese patient with dysautonomia, hearing loss, cataract, sensory disturbance and mild dementia. A novel missense mutation, c.4001C>T, was identified in exon 35, which encodes the methyltransferase domain of DNMT1. Until now, all reported mutations of DNMT1 were within the replication focus targeting sequence domain of DNA methyltransferase 1. This is the first report of a mutation in the methyltransferase domain of DNA methyltransferase 1. Our patient showed remarkable autonomic dysfunction along with cataract, a possible new phenotype of DNMT1 mutations.
Spatially Weighted Functional Clustering of River Network Data
Authors: Haggarty R. A. , Miller C. A. , Scott E. M. 
Published: October 2014

SummaryIncorporating spatial covariance into clustering has previously been considered for functional data to identify groups of functions which are similar across space. However, in the majority of situations that have been considered until now the most appropriate metric has been Euclidean distance. Directed networks present additional challenges in terms of estimating spatial covariance due to their complex structure. Although suitable river network covariance models have been proposed for use with stream distance, where distance is computed along the stream network, these models have not been extended for contexts where the data are functional, as is often the case with environmental data. The paper develops a method of calculating spatial covariance between functions from sites along a river network and applies the measure as a weight within functional hierarchical clustering. Levels of nitrate pollution on the River Tweed in Scotland are considered with the aim of identifying groups of monitoring stations which display similar spatiotemporal characteristics.
Optimal Experimental Design for Systems with Bivariate Failures Under a Bivariate Weibull Function
Authors: Kim Sungwook , Flournoy Nancy 
Published: October 2014

SummaryIn manufacturing industry, it may be important to study the relationship between machine component failures under stress. Examples include the failures of integrated circuits and memory chips in electronic merchandise given various levels of electronic shock. Such studies are important for the development of new products and for the improvement of existing products. We assume two-component systems for simplicity and we assume that the joint probability of failures increases with stress as a cumulative bivariate Weibull function. Optimal designs have been developed for two correlated binary responses by using the Gumbel model, the bivariate binary Cox model and the bivariate probit model. In all these models, the amount of damage ranges from −∞ to ∞. In the Weibull model, the amount of damage is positive, which is natural for experimental factors such as voltage, tension or pressure. We describe locally optimal designs under bivariate Weibull assumptions. Since locally optimal designs with non-linear models depend on predetermined parameter values, misspecified parameter values may lead to inefficient designs. However, we find that optimal designs under the Weibull model are surprisingly efficient over a wide range of misspecified parameter values. To improve the efficiency, we recommend a multistage procedure. We show how using a two-stage procedure can provide a substantial improvement over a design that was optimal for misspecified parameters.
How have Labour Market Developments Affected Labour Costs in China?
Authors: Han Gaofeng , Zhang Wenlang 
Published: October 2014

AbstractIn this paper, we study how labour market developments have affected labour costs in China. We find labour market tightness, and hence labour migration, have some impact on the labour costs of HMT firms and private enterprises, but the overall impact is limited. It appears there is no absolute shortage of labour, but there is skill and education mismatch in labour market. As such, it is necessary to remove the barriers to labour migration, and upgrade production chains to reduce labour market distortion.
Colistin Pharmacokinetics in Burn Patients during Continuous Venovenous Hemofiltration
Authors: Akers Kevin S. , Rowan Matthew P. , Niece Krista L. , Stewart Ian J. , Mende Katrin , Cota Jason M. , Murray Clinton K. , Chung Kevin K. 
Published: October 2014

ABSTRACTWhile colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for patients who require renal replacement remains a challenge. Here, we present pharmacokinetic data for colistin from two burn patients (37 and 68 years old) infected with colistin-susceptible isoclonalAcinetobacter baumanniiand receiving continuous venovenous hemofiltration (CVVH). To our knowledge, we are the first to examine data from before and during CVVH (for one patient), allowing analysis of the effect of CVVH on colistin pharmacokinetics. Pharmacokinetic/pharmacodynamic analysis indicated that a dose increase from 1.5 to 2.2 mg/kg of body weight colistin base activity on CVVH was insufficient to satisfy the target parameter of an AUC24/MIC (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of ≥60 at an MIC of ≥1 μg/ml in one patient with residual endogenous renal function. Plasma concentrations of colistin ranged from 0 to 15 μg/ml, with free colistin levels ranging from 0.4 to 2.2 μg/ml. While both patients resolved their clinical infections and survived to discharge, colistin-resistant colonizing isolates resulted from therapy in one patient. The variabilities observed in colistin concentrations and pharmacokinetic characteristics highlight the importance of pharmacokinetic monitoring of antibiotics in patients undergoing renal replacement therapy.
Continuous versus Short-Term Infusion of Cefuroxime: Assessment of Concept Based on Plasma, Subcutaneous Tissue, and Bone Pharmacokinetics in an Animal Model
Authors: Tøttrup Mikkel , Bibby Bo M. , Hardlei Tore F. , Bue Mats , Kerrn-Jespersen Sigrid , Fuursted Kurt , Søballe Kjeld , Birke-Sørensen Hanne 
Published: October 2014

ABSTRACT
The relatively short half-lives of most β-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 μg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach.
Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for the Cryptococcus neoformans-Cryptococcus gattii Species Complex Using the CLSI M27-A3 Broth Microdilution Method
Authors: Espinel-Ingroff A. , Chowdhary A. , Gonzalez G. M. , Guinea J. , Hagen F. , Meis J. F. , Thompson G. R. , Turnidge J. 
Published: October 2014

ABSTRACT

Epidemiological cutoff values (ECVs) of isavuconazole are not available for
Cryptococcus
spp. The isavuconazole ECVs based on wild-type (WT) MIC distributions for 438
Cryptococcus neoformans
nongenotyped isolates, 870 isolates of genotype VNI, and 406
Cryptococcus gattii
isolates from six laboratories and different geographical areas were 0.06, 0.12, and 0.25 μg/ml, respectively. These ECVs may aid in detecting non-WT isolates with reduced susceptibilities to isavuconazole.
Antimalarial Activity of Granzyme B and Its Targeted Delivery by a Granzyme B–Single-Chain Fv Fusion Protein
Authors: Kapelski Stephanie , de Almeida Melanie , Fischer Rainer , Barth Stefan , Fendel Rolf 
Published: October 2014

ABSTRACT

We present here the first evidence that granzyme B acts against
Plasmodium falciparum
(50% inhibitory concentration [IC
50
], 1,590 nM; 95% confidence interval [95% CI], 1,197 to 2,112 nM). We created a novel antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8-fold reduction in the IC
50
(176 nM; 95% CI, 154 to 202 nM). This study confirms the therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B.
Susceptibility to Plasmodium yoelii Preerythrocytic Infection in BALB/c Substrains Is Determined at the Point of Hepatocyte Invasion
Authors: Kaushansky Alexis , Austin Laura S. , Mikolajczak Sebastian A. , Lo Fang Y. , Miller Jessica L. , Douglass Alyse N. , Arang Nadia , Vaughan Ashley M. , Gardner Malcolm J. , Kappe Stefan H. I. 
Published: October 2014

ABSTRACTAfter transmission byAnophelesmosquitoes,Plasmodiumsporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. This has been mainly attributed to differences in innate immune responses and parasite infectivity. Here, we report that BALB/cByJ mice are more susceptible toPlasmodium yoeliipreerythrocytic infection than BALB/cJ mice. This difference occurs at the level of early hepatocyte infection, but expression levels of reported host factors that are involved in infection do not correlate with susceptibility. Interestingly, BALB/cByJ hepatocytes are more frequently polyploid; thus, their susceptibility converges on the previously observed preference of sporozoites to infect polyploid hepatocytes. Gene expression analysis demonstrates hepatocyte-specific differences in mRNA abundance for numerous genes between BALB/cByJ and BALB/cJ mice, some of which encode hepatocyte surface molecules. These data suggest that a yet-unknown receptor for sporozoite infection, present at elevated levels on BALB/cByJ hepatocytes and also polyploid hepatocytes, might facilitatePlasmodiumliver infection.
Mucosal Immunization with the Live Attenuated Vaccine SPY1 Induces Humoral and Th2-Th17-Regulatory T Cell Cellular Immunity and Protects against Pneumococcal Infection
Authors: Xu Xiuyu , Wang Hong , Liu Yusi , Wang Yiping , Zeng Lingbing , Wu Kaifeng , Wang Jianmin , Ma Feng , Xu Wenchun , Yin Yibing , Zhang Xuemei 
Published: October 2014

ABSTRACT
Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the mechanism was unknown. Our study found that mucosal delivery with the live attenuated SPY1 vaccine strain can confer T cell- and B cell-dependent protection against pneumococcal colonization and invasive infection; yet it is still unclear which cell subsets contribute to the protection, and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naive μMT mice, and immune T cells were indispensable to protection examined in nude mice. A critical role of interleukin 17A (IL-17A) in colonization was demonstrated in mice lacking IL-17A, and a vaccine-specific Th2 immune subset was necessary for systemic protection. Of note, we found that SPY1 could stimulate an immunoregulatory response and that SPY1-elicited regulatory T cells participated in protection against colonization and lethal infection. The data presented here aid our understanding of how live attenuated strains are able to function as effective vaccines and may contribute to a more comprehensive evaluation of live vaccines and other mucosal vaccines.
Characterization of a Novel Plasmid-Borne Thiopeptide Gene Cluster in Staphylococcus epidermidis Strain 115
Authors: Bennallack Philip R. , Burt Scott R. , Heder Michael J. , Robison Richard A. , Griffitts Joel S. 
Published: October 2014

ABSTRACT

Thiopeptides are small (12- to 17-amino-acid), heavily modified peptides of bacterial origin. This antibiotic family, with more than 100 known members, is characterized by the presence of sulfur-containing heterocyclic rings and dehydrated residues within a macrocyclic peptide structure. Thiopeptides, including micrococcin P1, have garnered significant attention in recent years for their potent antimicrobial activity against bacteria, fungi, and even protozoa. Micrococcin P1 is known to target the ribosome; however, like those of other thiopeptides, its biosynthesis and mechanisms of self-immunity are poorly characterized. We have discovered an isolate of
Staphylococcus epidermidis
harboring the genes for thiopeptide production and self-protection on a 24-kb plasmid. Here we report the characterization of this plasmid, identify the antimicrobial peptide that it encodes, and provide evidence of a target replacement-mediated mechanism of self-immunity.
Action Schools! BC implementation: from efficacy to effectiveness to scale-up
Authors: McKay Heather A , Macdonald Heather M , Nettlefold Lindsay , Masse Louise C , Day Meghan , Naylor Patti-Jean 
Published: October 2014

ObjectivesTo describe Action Schools! BC (AS! BC) from efficacy to scale-up.Participants/settingEducation and health system stakeholders and children in grades 4–6 from elementary schools in British Columbia, Canada.InterventionAt the provincial level, the AS! BC model reflected socioecological theory and a partnership approach to social change. Knowledge translation and exchange were embedded as a foundational element. At the school level, AS! BC is a comprehensive school health-based model providing teachers and schools with training and resources to integrate physical activity (PA) and healthy eating (HE) into the school environment. Our research team partnered with key community and government stakeholders to deliver and evaluate AS! BC over efficacy, effectiveness and implementation trials.ResultsOn the basis of significant increases in PA, cardiovascular fitness, bone and HE in AS! BC schools during efficacy trials, the BC government supported a provincial scale-up. Since its inception, the AS! BC Support Team and >225 trained regional trainers have delivered 4677 teacher-focused workshops (training approximately 81 000 teachers), reaching approximately 500 000 students. After scale-up, PA delivery was replicated but the magnitude of change appeared less. One (HE) and 4 (PA) years after scale-up, trained AS! BC teachers provided more PA and HE opportunities for students even in the context of supportive provincial policies.ConclusionsWhole school models like AS! BC can enhance children's PA and health when implemented in partnership with key stakeholders. At the school level, adequately trained and resourced teachers and supportive school policies promoted successful scale-up and sustained implementation. At the provincial level, multisectoral partnerships and embedded knowledge exchange mechanisms influenced the context for action at the provincial and school level, and were core elements of successful implementation.Trial registration numberClinical Trials RegistryNCT01412203.
The inverse equity hypothesis: Does it apply to coverage of cancer screening in middle-income countries?
Authors: Lee John Tayu , Huang Zhilian , Basu Sanjay , Millett Christopher 
Published: October 2014

BackgroundIt is uncertain whether the inverse equity hypothesis—the idea that new health interventions are initially primarily accessed by the rich, but that inequalities narrow with diffusion to the poor—holds true for cancer screening in low and middle income countries (LMICs).This study examines the relationship between overall coverage and economic inequalities in coverage of cancer screening in four middle-income countries.MethodsSecondary analyses of cross-sectional data from the WHO study on Global Ageing and Adult Health in China, Mexico, Russia and South Africa (2007–2010). Three regression-based methods were used to measure economic inequalities: (1) Adjusted OR; (2) Relative Index of Inequality (RII); and (3) Slope Index of Inequality.ResultsCoverage for breast cancer screening was 10.5% in South Africa, 19.3% in China, 33.8% in Russia and 43% in Mexico, and coverage for cervical cancer screening was 24% in South Africa, 27.2% in China, 63.7% in Mexico and 81.5% in Russia. Economic inequalities in screening participation were substantially lower or non-existent in countries with higher aggregate coverage, for both breast cancer screening (RII: 14.57 in South Africa, 4.90 in China, 2.01 in Mexico, 1.04 in Russia) and cervical cancer screening (RII: 3.60 in China, 2.47 in South Africa, 1.39 in Mexico, 1.12 in Russia).ConclusionsEconomic inequalities in breast and cervical cancer screening are low in LMICs with high screening coverage. These findings are consistent with the inverse equity hypothesis and indicate that high levels of equity in cancer screening are feasible even in countries with high income inequality.