bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordance between HCV RNA Assays for Week 24 HCV RNA Determination during Pegylated Interferon-α/Ribavirin Treatment for Chronic Hepatitis C
Authors: Roomer Robert , van Vuuren Anneke J , Schutten Martin , Heijens Angela , Janssen Harry LA , de Knegt Robert J 
Published: April 2011

Background The development of more sensitive HCV RNA assays might necessitate re-evaluation of the rules for stopping treatment (for example, HCV RNA negativity at week 24 during treatment with pegylated interferon-α and ribavirin for chronic hepatitis C). The aim of this study was to assess discordance between the week 24 HCV RNA test results of two PCR-based assays (Amplicor and Taq-Man) and the transcription-mediated amplification (TMA) HCV RNA qualitative assay. Methods A total of 89 week 24 samples that were negative using PCR-based assays during treatment were retested with the TMA qualitative assay to investigate discordance between tests results. All week 24 samples were HCV RNA negative by Amplicor or by TaqMan. Results Of the 89 patients, 46 (52%) achieved sustained virological response (SVR). Viral breakthrough or relapse occurred in 43 patients (48%). All 89 HCV RNA negative week 24 samples were retested with the qualitative TMA assay. Eleven out of 89 samples had detectable HCV RNA (12%). All patients with detectable HCV RNA experienced breakthrough or relapse (negative predictive value 100%). Of the 78 patients with undetectable HCV RNA at week 24 using the TMA assay, 46 achieved SVR. This resulted in a positive predictive value (PPV) of 59% for the TMA assay compared with a PPV of 52% for the PCR-based assays. Conclusions All patients with detectable HCV RNA at week 24 using the TMA assay eventually relapsed. On the basis of these results, the use of this more sensitive HCV RNA assay could lead to the prevention of unnecessary treatment.
Efavirenz and Rifampicin in the South African Context: Is There a Need to Dose-Increase Efavirenz with Concurrent Rifampicin Therapy?
Authors: Orrell Catherine , Cohen Karen , Conradie Francesca , Zeinecker Jennifer , Ive Prudence , Sanne Ian , Wood Robin 
Published: April 2011

Background Increasing efavirenz (EFV) dose from 600 mg to 800 mg daily has been suggested with concomitant rifampicin (RFN), as induction of cytochrome P450 isoenzymes may reduce EFV plasma concentrations Methods Individuals from the CIPRA-South Africa cohort taking EFV-based antiretroviral therapy with concomitant tuberculosis (TB) were dosed with either increased (800 mg) or standard (600 mg) dose EFV during TB treatment. After TB therapy, all individuals took 600 mg EFV. Two mid-dosing interval EFV concentrations were determined from each individual: after 4 weeks of concomitant EFV and RFN therapy, and ≥4 weeks after TB therapy completion. Mid-dosing interval EFV concentrations were compared within individuals using the Wilcoxon signed– rank test. Results Paired samples were collected from 72 individuals. Overall, 45 (63%) were women and median weight was 59 kg (IQR 52–67). At antiretroviral therapy start, median CD4+ T-cell count was 114 cells/mm3 (IQR 37–165), median viral load was 5.5 log (IQR 5.1–5.9). A total of 38 (53%) individuals took 800 mg EFV during TB treatment and 34 (47%) took 600 mg. EFV concentrations in the 800 mg group were higher with RFN (2.9 mg/l [IQR 1.8–5.6]) than without (2.1 mg/l [IQR 1.4–3.0]; P=0.0003). There was no significant difference in EFV concentrations with RFN (2.4 mg/l [IQR 1.2–5.1]) or without (2.2 mg/l [IQR 1.4–3.7]) in the 600 mg group. There was no increase in EFV-linked adverse effects in either group. The proportion of virologically suppressed individuals at 48 weeks was similar in both groups. Conclusions EFV concentrations were significantly increased in the EFV 800 mg group on RFN. There was no significant decrease in EFV concentrations when on RFN in the 600 mg group. Dose escalation of EFV 600 mg to 800 mg is not required during concomitant TB therapy in South Africa.
Staphylococcus aureus Metalloprotease Aureolysin Cleaves Complement C3 To Mediate Immune Evasion
Authors: Laarman Alexander J. , Ruyken Maartje , Malone Cheryl L. , van Strijp Jos A. G. , Horswill Alexander R. , Rooijakkers Suzan H. M. 
Published: April 2011

Abstract
Complement is one of the first host defense barriers against bacteria. Activated complement attracts neutrophils to the site of infection and opsonizes bacteria to facilitate phagocytosis. The human pathogen Staphylococcus aureus has successfully developed ways to evade the complement system, for example by secretion of specific complement inhibitors. However, the influence of S. aureus proteases on the host complement system is still poorly understood. In this study, we identify the metalloprotease aureolysin as a potent complement inhibitor. Aureolysin effectively inhibits phagocytosis and killing of bacteria by neutrophils. Furthermore, we show that aureolysin inhibits the deposition of C3b on bacterial surfaces and the release of the chemoattractant C5a. Cleavage analyses show that aureolysin cleaves the central complement protein C3. Strikingly, there was a clear difference between the cleavages of C3 in serum versus purified conditions. Aureolysin cleaves purified C3 specifically in the α-chain, close to the C3 convertase cleavage site, yielding active C3a and C3b. However, in serum we observe that the aureolysin-generated C3b is further degraded by host factors. We pinpointed these factors to be factor H and factor I. Using an aureolysin mutant in S. aureus USA300, we show that aureolysin is essential and sufficient for C3 cleavage by bacterial supernatant. In short, aureolysin acts in synergy with host regulators to inactivate C3 thereby effectively dampening the host immune response.
Strength of TCR–Peptide/MHC Interactions and In Vivo T Cell Responses
Authors: Corse Emily , Gottschalk Rachel A. , Allison James P. 
Published: April 2011

AbstractThe TCR can detect subtle differences in the strength of interaction with peptide/MHC ligand and transmit this information to influence downstream events in T cell responses. Manipulation of the factor commonly referred to as TCR signal strength can be achieved by changing the amount or quality of peptide/MHC ligand. Recent work has enhanced our understanding of the many variables that contribute to the apparent cumulative strength of TCR stimulation during immunogenic and tolerogenic T cell responses. In this review, we consider data from in vitro studies in the context of in vivo immune responses and discuss in vivo consequences of manipulation of strength of TCR stimulation, including influences on T cell–APC interactions, the magnitude and quality of the T cell response, and the types of fate decisions made by peripheral T cells.
Female X-Chromosome Mosaicism for NOX2 Deficiency Presents Unique Inflammatory Phenotype and Improves Outcome in Polymicrobial Sepsis
Authors: Chandra Rachna , Federici Stephanie , Németh Zoltán H. , Horváth Béla , Pacher Pál , Haskó György , Deitch Edwin A. , Spolarics Zoltán 
Published: April 2011

Abstract
Cellular X-chromosome mosaicism, which is unique to females, may be advantageous during pathophysiological challenges compared with the single X-chromosome machinery of males, and it may contribute to gender dimorphism in the inflammatory response. We tested the hypothesis of whether cellular mosaicism for the X-linked gp91phox (NOX2) deficiency, the catalytic component of the superoxide anion-generating NADPH oxidase complex, is advantageous during polymicrobial sepsis. Deficient, wild-type (WT), and heterozygous/mosaic mice were compared following polymicrobial sepsis initiated by cecal ligation and puncture. Compared with WT littermates, sepsis-induced mortality was improved in deficient mice, as well as in mosaic animals carrying both deficient and WT phagocyte subpopulations. In contrast, blood bacterial counts were greatest in deficient mice. Consistent with poor survival, WT mice also showed the most severe organ damage following sepsis. In mosaic animals, the deficient neutrophil subpopulations displayed increased organ recruitment and elevated CD11b membrane expression compared with WT neutrophil subpopulations within the same animal. The dynamics of sepsis-induced blood and organ cytokine content and WBC composition changes, including lymphocyte subsets in blood and bone marrow, showed differences among WT, deficient, and mosaic subjects, indicating that mosaic mice are not simply the average of the deficient and WT responses. Upon oxidative burst, interchange of oxidants between WT and deficient neutrophil subpopulations occurred in mosaic mice. This study suggests that mice mosaic for gp91phox expression have multiple advantages compared with WT and deficient mice during the septic course.
Rapid Increase of the Serum PSA Level in Response to High-Intensity Focused Ultrasound Therapy may be a Potential Indicator of Biochemical Recurrence of Low- and Intermediate-Risk Prostate Cancer
Authors: Inamoto Teruo , Komura Kazumasa , Watsuji Toshikazu , Azuma Haruhito 
Published: April 2011

Objectives To determine the incidence and magnitude of the rapid increase in the serum PSA (riPSA) level after high-intensity focused ultrasound (HIFU) therapy for prostate cancer, and its correlation with clinical factors. Methods A total of 176 patients with localized prostate cancer underwent HIFU therapy. Serum riPSA was determined on the basis of the same criteria as those for “PSA bounce”, ie, an increase of ≥0.2 ng/ml with a spontaneous return to the prebounce level or lower. Patients were stratified according to neoadjuvant PSA level, T stage, risk group, age, Gleason score, pretreatment PSA level, post-treatment PSA nadir, and number of HIFU sessions. Results riPSA was seen in 53% of patients during a median follow-up period of 43 months. A PSA nadir was achieved within 3 months for 85.1% of the treatments. In all cases, onset of riPSA was seen two days after HIFU therapy, and the median magnitude was 23.69 ng/ml. A magnitude of >2 ng/ml was seen in 89.4% of cases. Univariate analysis revealed that patients with riPSA were associated with usage of hormonal therapy and the post-treatment PSA nadir level. Multivariate Cox regression analysis revealed that riPSA and the number of HIFU sessions were predictors of biochemical recurrence. A significant statistical association was found between the presence of riPSA and the risk of biochemical failure only in the low- and intermediate-risk group. Conclusion Patients treated with HIFU who experience post-treatment riPSA may have an increased risk of biochemical recurrence, especially in non-high-risk patients.
Social and environmental factors affecting fecal glucocorticoids in wild, female white‐faced capuchins (Cebus capucinus)
Authors: Carnegie Sarah D. , Fedigan Linda M. , Ziegler Toni E. 
Published: April 2011

AbstractAssessing glucocorticoid levels in free‐ranging nonhuman primates provides a means to determine the social and environmental stress load for individuals. We investigated the effect of four proximate variables—reproductive state, season, male rank stability, and dominance rank—on the level of fecal glucocorticoids (cortisol metabolites) in eight adult female white‐faced capuchin monkeys in Costa Rica. Reproductive state, season, and male rank stability significantly affected fecal glucocorticoids while female dominance rank did not. Cortisol levels were significantly higher in pregnant females as compared with lactating or other reproductive states. Cortisol levels were higher among females during the dry season compared with the wet season, suggesting a metabolic adaptation to maintain homeostasis in drier, hotter conditions. Although unfamiliar males present a greater infanticidal threat than do familiar ones, we found that females experienced higher glucocorticoid levels during male rank instability events, regardless of whether the alpha male role was taken over by a familiar or an unfamiliar male. Our findings provide important benchmark and comparative data for future studies on the variables that affect glucocorticoid levels in this species and other mammals. Am. J. Primatol. 73:861–869, 2011. © 2011 Wiley‐Liss, Inc.
Dearomatization Strategies in the Synthesis of Complex Natural Products
Authors: Roche Stéphane P. , Porco John A. 
Published: April 2011

AbstractEvolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemoselective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three‐dimensional molecular architectures.
The Price of a Piece of Cheese: Value from Fit Between Epistemic Needs and a Learning Versus an Outcome Focus
Authors: McNeill Ilona M. , Higgins E. Tory , De Dreu Carsten K. W. , Nijstad Bernard A. 
Published: April 2011

ABSTRACTIn decision making, people can focus on decisional outcomes (outcome focus), but they can also focus on gaining knowledge about the decisional domain (learning focus). Furthermore, people differ in the strength of their epistemic needs—their preference for developing a rich and accurate understanding of the world. We invoke the regulatory fit theory to predict that higher epistemic needs better fit a learning focus than lower epistemic needs, resulting in a greater increase in valuation of the chosen option when a learning rather than an outcome focus is induced. This general hypothesis was tested and supported in three studies, each focusing on a different proxy to epistemic needs. Thus, individuals experienced greater value when they had lower expertise (Study 1), higher need for assessment (Study 2), and higher need for cognition (Study 3) when a learning rather than an outcome focus was induced. Implications for work on epistemic needs, regulatory fit theory, and decision‐making practice are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Determination of dipyridamole using TCPO–H2O2 chemiluminescence in the presence of silver nanoparticles
Authors: Wang Lijuan , Tang Yuhai 
Published: April 2011

ABSTRACTThe method is based on the fact that dipyridamole can enhance the chemiluminescence (CL) emission from the redox reaction of bis (2,4,6‐tricholorophenyl) oxalate (TCPO) with H2O2 in the presence of silver nanoparticles (AgNPs). The CL reaction mechanism was discussed. The effect of concentrations of TCPO, H2O2, AgNPs and pH value on the CL reaction were investigated. Under the optimum conditions, the linear dynamic range was 1.0–1000 × 10−9 g/mL and the detection limit (3σ) was 9 × 10−10 g/mL. The relative standard deviation (RSD) was 4.8% for 1.0 × 10−9 g/mL dipyridamole (n = 7). The proposed method has been successfully applied to the determination of dipyridamole tablets and the recovery was 99–103%. Copyright © 2011 John Wiley & Sons, Ltd.
Insight into the Role of the Counteranion of an Imidazolium Salt in Organocatalysis: A Combined Experimental and Computational Study
Authors: Wei Siping , Wei Xi‐Guang , Su Xiaoyu , You Jingsong , Ren Yi 
Published: April 2011

AbstractN‐Heterocyclic carbenes (NHCs) can serve as very reactive nucleophilic catalysts and exhibit strong basicity. Herein, we initiate a combined experimental and computational investigation of the NHC‐catalyzed ring‐closing reactions of 4‐(2‐formylphenoxy)but‐2‐enoate derivatives 1 to uncover the relationship between the counteranion of an azolium salt, the nucleophilicity and basicity of the carbene species, and the catalytic performance of the carbene species by taking imidazolium salts IPr⋅HX (X=counteranion, IPr=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) as the representative precatalysts. The plausible mechanisms of IPr‐mediated ring‐closing reactions have been investigated by using DFT calculations. The hydrogen‐accepting ability, assigned as the basicity of the counteranion of IPr⋅HX and evaluated by DFT calculations, is correlated with the rate of deprotonation of C2 in IPr⋅HX, which could be monitored by the capture of the free carbene formed in situ with elemental sulfur. The deprotonation of C2 in IPr⋅HX with a more basic anion gives rise to a higher concentration of the free carbene and vice versa. At a relatively low concentration, IPr prefers to show a nucleophilic character to induce the intramolecular Stetter reaction. At a relatively high concentration, IPr primarily acts as a base to afford benzofuran derivatives. These data comprehensively disclose, for the first time, that the counteranions of azolium salts significantly influence not only the catalytic activity, but also possibly the reaction mechanism.
An Easy and Versatile Approach for the Regioselective De‐O‐benzylation of Protected Sugars Based on the I2/Et3SiH Combined System
Authors: Pastore Antonello , Valerio Silvia , Adinolfi Matteo , Iadonisi Alfonso 
Published: April 2011

AbstractThe use of cheap and easy to handle reagents, such as I2 and Et3SiH, at low temperature allows the regioselective removal of benzyl protecting groups from highly O‐benzylated carbohydrates. The observed regioselectivity is dependent on the nature of the precursor, the least accessible carbinol often being liberated. A mechanistic investigation reveals that in situ generated HI is the promoter of the process, whereas the regioselectivity appears to be mainly controlled by steric effects. However, the presence of an electron withdrawing acyl protecting group can switch the regioselectivity to favour deprotection of the carbinol position farthest from the ester group. The protocol is experimentally simple and provides straightforward access in useful yields to a wide range of partially protected mono‐ and disaccharide building blocks that are valuable for the synthesis of either biologically useful oligosaccharides or highly functionalised chiral compounds. Partially protected sugars thus obtained can also be coupled in situ with a glycosyl donor, as illustrated by the one‐pot synthesis of a Lewis X mimic from fully protected precursors.
Ferrocene‐Based Trimethylsilyl Chalcogenide Reagents for the Assembly of Functionalized Metal–Chalcogen Architectures
Authors: MacDonald Daniel G. , Eichhöfer Andreas , Campana Charles F. , Corrigan John F. 
Published: April 2011

AbstractThe ferrocene‐based trimethylsilyl chalcogenide reagents [FcC(O)OCH2CH2ESiMe3] (2, E=S, 3 E=Se, Fc=[Fe(η5‐C5H5)(η5‐C5H4)]) and [FcC(O)NHCH2CH2SSiMe3] (8b) have been synthesized. The reagents were reacted with solubilized transition‐metal acetates to yield functionalized complexes and clusters, including the spherical nanocluster [Ag14S{SCH2CH2O(O)CFc)}12(PPh3)6] (11, PPh3=triphenylphosphine). The complexes were characterized by NMR spectroscopy and X‐ray crystallography. The electrochemical behavior of the complexes was explored by cyclic voltammetry and each displayed a single quasi‐reversible redox wave with some adsorption to the electrode surface.
Heterogeneous Organocatalysis at Work: Functionalization of Hollow Periodic Mesoporous Organosilica Spheres with MacMillan Catalyst
Authors: Shi Jiao Yi , Wang Chang An , Li Zhi Jun , Wang Qiong , Zhang Yuan , Wang Wei 
Published: April 2011

AbstractWe report a new method for the synthesis of hollow‐structured phenylene‐bridged periodic mesoporous organosilica (PMO) spheres with a uniform particle size of 100–200 nm using α‐Fe2O3 as a hard template. Based on this method, the hollow‐structured phenylene PMO could be easily functionalized with MacMillan catalyst (H‐PhPMO‐Mac) by a co‐condensation process and a “click chemistry” post‐modification. The synthesized H‐PhPMO‐Mac catalyst has been found to exhibit high catalytic activity (98 % yield, 81 % enantiomeric excess (ee) for endo and 81 % ee for exo) in asymmetric Diels–Alder reactions with water as solvent. The catalyst could be reused for at least seven runs without a significant loss of catalytic activity. Our results have also indicated that hollow‐structured PMO spheres exhibit higher catalytic efficiency than solid (non‐hollow) PMO spheres, and that catalysts prepared by the co‐condensation process and “click chemistry” post‐modification exhibit higher catalytic efficiency than those prepared by a grafting method.
Viability of 4,5‐Dihydro‐1,2,3,4‐oxatriazoles Reinvestigated
Authors: Firdous Samia , Banert Klaus , Auer Alexander A. 
Published: April 2011

AbstractThe first procedures to prepare 4‐bromo‐4‐methylpentanal and 4‐azido‐4‐methylpentanal are reported. The latter compound and also the parent 4‐azidobutanal do not lead to 4,5‐dihydro‐1,2,3,4‐oxatriazoles by intramolecular 1,3‐dipolar cycloaddition, although it was claimed to be so in the literature. The NMR spectroscopic data of such heterocycles reported previously do not agree with those of similar substances and are incompatible with 13C NMR spectroscopic chemical shifts calculated by quantum chemical methods in the presented work. These calculations show furthermore that the intramolecular cycloaddition of 4‐azidobutanals to give the title compounds is strongly endothermic and thus most probably not possible.
Synthesis of (+)‐Dumetorine and Congeners by Using Flow Chemistry Technologies
Authors: Riva Elena , Rencurosi Anna , Gagliardi Stefania , Passarella Daniele , Martinelli Marisa 
Published: April 2011

AbstractAn efficient total synthesis of the natural alkaloid (+)‐dumetorine by using flow technology is described. The process entailed five separate steps starting from the enantiopure (S)‐2‐ (piperidin‐2‐yl)ethanol 4 with 29 % overall yield. Most of the reactions were carried out by exploiting solvent superheating and by using packed columns of immobilized reagents or scavengers to minimize handling. New protocols for performing classical reactions under continuous flow are disclosed: the ring‐closing metathesis reaction with a novel polyethylene glycol‐supported Hoveyda catalyst and the unprecedented flow deprotection/Eschweiler–Clarke methylation sequence. The new protocols developed for the synthesis of (+)‐dumetorine were applied to the synthesis of its simplified natural congeners (−)‐sedamine and (+)‐sedridine.
Evidence for a One‐Electron Mechanistic Regime in Dirhodium‐Catalyzed Intermolecular CH Amination
Authors: Kornecki Katherine P. , Berry John F. 
Published: April 2011

AbstractSwift and energy efficient conversion of chemical feedstocks to pharmaceuticals and agrochemicals requires the development of new methods to add nitrogen functionality to unfunctionalized organic substrates. Dirhodium‐catalyzed insertion of nitrene species into CH bonds is a promising new method, the main drawback of which is the currently limited understanding of the catalytic mechanism. Herein, cyclic voltammetry and controlled potential electrolysis measurements have enabled us to solve many of the mechanistic mysteries of intermolecular CH amination catalyzed by [Rh2(esp)2] (esp=α,α,α′,α′‐tetramethyl‐1,3‐benzenedipropanoate). The primary result is that, in addition to a simple nitrene‐transfer mechanism that dominates the early stages of the reaction, another mechanism is available that relies on sequential proton‐coupled electron transfer steps. Whereas the nitrene‐transfer mechanism requires the use of expensive, atom‐inefficient oxidants, we show that simple one‐electron oxidants such as Ce4+ may be used to achieve catalytic CH amination via the one‐electron mechanistic regime.
Organocatalytic enantioselective Michael addition of malononitrile to nitroolefins catalyzed by bifunctional thiourea
Authors: Guo Hai‐Ming , Li Jian‐Guo , Qu Gui‐Rong , Zhang Xiao‐Mei , Yuan Wei‐Cheng 
Published: April 2011

AbstractA novel enantioselective Michael addition of malononitrile to trans‐β‐nitroolefins in the presence of bifunctional amine thiourea organocatalyst is developed. The Michael reaction catalyzed by amine thioureas containing both central and axial chiral elements proceeded smoothly and provided the desired adducts with high yields (up to 96% yield) and moderate enantioselectivities (up to 83% enantiomeric excess). Chirality, 2011. © 2011 Wiley‐Liss, Inc.