bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carrier diagnostics and prevention of hemoglobinopathies in early pregnancy in The Netherlands: a pilot study
Authors: Giordano P. C. , Plancke A. , Van Meir C. A. , Janssen C. A. H. , Kok P. J. M. J. , Van Rooijen‐Nijdam I. H. , Tanis B. C. , van Huisseling J. C. M. , Versteegh F. G. A. 
Published: June 2006

AbstractBackgroundWe have offered, for the first time in The Netherlands, carrier diagnostics for hemoglobinopathies (HbP) to early pregnant women. The aim of this study was to establish whether carrier analysis would be welcome by the public and feasible at the outpatient level.MethodOne hundred and thirty‐nine randomly selected women were informed and offered basic carrier diagnostics at the first pregnancy control.ResultsCarrier diagnostics was accepted by 136 women (97.8%). The population consisted of 31% of recent immigrants and 69% of native Dutch. One carrier of HbS and one of β‐thalassemia were found, both among the group of the recent immigrants. In both cases, partners were tested excluding a couple at risk. In addition, five carriers of α+‐thalassemia were diagnosed at the molecular level, one of them in the native Dutch population. Basic carrier analysis was done both at the Hospital Laboratory and at the Reference Laboratory. No discrepancies were found.ConclusionsThis pilot study shows that (1) as predicted the prevalence of risk‐related HbP and of α+‐thalassemia is high in the immigrant population. (2) The compliance with carrier analysis in both native Dutch and immigrants is virtually total and (3) carrier diagnosis in early pregnancy and partner analysis in Hospital Laboratories is possible and is an effective tool for primary prevention of HbP in The Netherlands. Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis and characterization of polypeptide containing liver‐targeting group
Authors: Cha Rui‐tao , Du Tian , Li Ji‐hong , Yuan Zhi 
Published: June 2006

AbstractGlycyrrhetinic acid, glycyrrhizic acid and bile acid were reported to be accumulated in liver. A series of novel liver‐specific targeting polypeptides, poly(γ‐benzyl‐L‐glutamate), were synthesized by ring‐opening polymerization (ROP) of N‐carboxyanhydride of γ‐benzyl‐L‐glutamate (BLG‐NCA) with amine‐terminated compounds containing the above‐mentioned liver‐targeting group as an initiator. The molecular weights of the polypeptides were measured by gel permeation chromatography. The structures of these polypeptides and their initiators were confirmed by FTIR and 1H‐NMR spectroscopy. The results demonstrate that it is an efficient strategy to introduce a liver‐targeting group into polymers via amine‐terminated compounds containing glycyrrhetinic acid, glycyrrhizic acid and bile acid. The novel polymers have potential medical applications in targeted drug delivery. Copyright © 2006 Society of Chemical Industry
Kinetics and mechanism of the reactions of S‐4‐nitrophenyl 4‐methylthiobenzoate with secondary alicyclic amines and pyridines
Authors: Castro Enrique A. , Aguayo Raul , Bessolo Jorge , Santos José G. 
Published: June 2006

AbstractThe reactions of the title substrate with a series of six secondary alicyclic amines and a series of eight pyridines are subjected to a kinetic investigation in 44 wt% ethanol‐water, at 25.0°C, and an ionic strength of 0.2 mol · dm−3. Under amine excess pseudo first‐order rate coefficients (kobs) are obtained. Plots of kobs against free amine concentration at constant pH are linear, with the slope (kN) independent of pH. The Brønsted‐type plots (log kN against pKa of the conjugate acids of the amines) are non‐linear, with the curvature center located at pKa (pK) 9.7 and 9.4, for the reactions of secondary alicyclic amines and pyridines, respectively. The plots are consistent with a zwitterionic tetrahedral intermediate (T±) on the reaction path and a change in rate‐determining step. The greater pK value for secondary alicyclic amines than pyridines is explained by the greater nucleofugality from T± of secondary alicyclic amines compared to isobasic pyridines. These pK values are lower than those found for the reactions of S‐4‐nitrophenyl 4‐Y‐substituted thiolbenzoates (Y = H, Cl, NO2) with the corresponding amine series. These results indicate that electron donation from the non‐leaving group in T± favors leaving group expulsion from T± relative to amine expulsion. Copyright © 2006 John Wiley & Sons, Ltd.
A missing data approach to semi‐competing risks problems
Authors: Dignam James J. , Wieand Kelly , Rathouz Paul J. 
Published: June 2006

AbstractFor event time data involving multiple mutually exclusive competing causes of failure, classic competing risks results show that marginal survival distributions are not identifiable. In a related instance, one or more failure modes may be observed provided that the failure events occur in a specific order. In such situations, sometimes referred to as semi‐competing risks problems, the observations may under realistic assumptions lend information about parameters of interest that would be nonidentifiable in the strict competing risks case. Here, we present an approach that makes use of partially observable multiple modes of failures to obtain an estimate of the marginal distribution of one event type that may occur prior to the occurrence of another event type or be precluded by it. We apply the proposed method to the problem of estimating the distribution of time to tumour recurrence at specific sites among breast cancer patients participating in randomized clinical trials. Copyright © 2006 John Wiley & Sons, Ltd.
Application of the promotion time cure model with time‐changing exposure to the study of HIV/AIDS and other infectious diseases
Authors: Tournoud M. , Ecochard R. 
Published: June 2006

AbstractInfectious diseases are caused by single or successive contacts with pathogens. Nevertheless, contacts with pathogens do not implicate infection. In 1993, Yakovlevet al.proposed a model to study a population of cancer patients with a cured fraction, a well adapted model to describe an infectious disease with a unique infection occasion. Extensions of this model have been proposed in the recent years. We present a mechanistic formulation in the context of infectious diseases with multiple infection occasions. It is a mixture model that enables to study risk factors associated with infection intensity at each infection occasion and factors shortening the delay from exposure to clinical event. Simulations are performed to evaluate the model fitting and two examples are presented for illustration: an analysis of an HIV‐1 mother‐to‐child transmission data set and an analysis of nosocomial urinary tract infections data set. Copyright © 2006 John Wiley & Sons, Ltd.
Repeated measures analyses of dose timing of antiretroviral medication and its relationship to HIV virologic outcomes
Authors: Liu Honghu , Miller Loren G. , Golin Carol E. , Hays Ron D. , Wu Tongtong , Wenger Neil S. , Kaplan Andrew H. 
Published: June 2006

AbstractMedication adherence is a critical predictor of the effectiveness of antiretroviral medications in the treatment of HIV/AIDS. Studies of adherence, however, have focused primarily on the per cent of prescribed doses taken (per cent adherence). In the Adherence and Efficacy of Protease Inhibitor Therapy study, we collected detailed adherence data including dose timing information as well as data regarding patients' virologic responses. For 48 weeks, adherence data and virologic outcomes were collected every 4 weeks, and demographics and other measures were collected at baseline and at weeks 8, 24, and 48. We constructed eight different dose timing error (DTE) measures and evaluated their associations with virologic outcomes using longitudinal analyses. Repeated measures mixed effect models were fitted to evaluate the predicting power of each of the DTE measures. Among 52 036 electronically measured doses obtained from 122 patients, DTE measures significantly predicted virologic outcomes. Of the eight different DTE measures, the six DTE measures were significantly predictive of virologic outcomes even after controlling for per cent adherence. In conclusion, we identified several measures of DTE that explain HIV virologic outcomes not captured by traditional adherence measures. Investigations of adherence to antiretrovirals would benefit from measuring not only per cent adherence but dose timing adherence. Copyright © 2006 John Wiley & Sons, Ltd.
Incorporating missingness for estimation of marginal regression models with multiple source predictors
Authors: Litman Heather J. , Horton Nicholas J. , Hernández Bernardo , Laird Nan M. 
Published: June 2006

AbstractMultiple informant data refers to information obtained from different individuals or sources used to measure the same construct; for example, researchers might collect information regarding child psychopathology from the child's teacher and the child's parent. Frequently, studies with multiple informants have incomplete observations; in some cases the missingness of informants is substantial. We introduce aMaximum Likelihood(ML) technique to fit models with multiple informants as predictors that permits missingness in the predictors as well as the response. We provide closed form solutions when possible and analytically compare the ML technique to the existingGeneralized Estimating Equations(GEE) approach. We demonstrate that the ML approach can be used to compare the effect of the informants on response without standardizing the data. Simulations incorporating missingness show that ML is more efficient than the existing GEE method. In the presence of MCAR missing data, we find through a simulation study that the ML approach is robust to a relatively extreme departure from the normality assumption. We implement both methods in a study investigating the association between physical activity and obesity with activity measured using multiple informants (children and their mothers). Copyright © 2006 John Wiley & Sons, Ltd.
HIV‐1 viral fitness estimation using exchangeable on subsets priors and prior model selection
Authors: Kitchen Christina M. R. , Weiss Robert E. , Liu Gang , Wrin Terri 
Published: June 2006

AbstractThe phenotype–genotype problem is a fundamental problem of biology where an organism's genotype (genetic information) predicts its phenotype (observable characteristic). Viral fitness, defined as the reproductive capacity of a virus compared to a standard, is a continuous phenotype. We construct models to predict viral fitness as a function of mutation away from the standardwildtypevirus. Data of this nature are difficult to analyse because there are potentially many more parameters than observations. We treat this issue as a regression problem using a prior with both a shrinkage component and a variable selection component. The key to practical implementation of the model is the prior specification for the regression coefficients. We use results from the scientific literature to construct several informative exchangeable within subsets priors (ESP). We use prior model selection (PMS) to select among our priors. Two novel graphics present results from five models each with 71 predictors. Copyright © 2006 John Wiley & Sons, Ltd.
Appropriateness of some resampling‐based inference procedures for assessing performance of prognostic classifiers derived from microarray data
Authors: Lusa Lara , McShane Lisa M. , Radmacher Michael D. , Shih Joanna H. , Wright George W. , Simon Richard 
Published: June 2006

AbstractThe goal of many gene‐expression microarray profiling clinical studies is to develop a multivariate classifier to predict patient disease outcome from a gene‐expression profile measured on some biological specimen from the patient. Often some preliminary validation of the predictive power of a profile‐based classifier is carried out using the same data set that was used to derive the classifier. Techniques such as cross‐validation or bootstrapping can be used in this setting to assess predictive power, and if applied correctly, can result in a less biased estimate of predictive accuracy of a classifier. However, some investigators have attempted to apply standard statistical inference procedures to assess the statistical significance of associations between true and cross‐validated predicted outcomes. We demonstrate in this paper that naïve application of standard statistical inference procedures to these measures of association under null situations can result in greatly inflated testing type I error rates. Under alternatives of small to moderate associations, confidence interval coverage probabilities may be too low, although for very large associations coverage probabilities approach their intended values. Our results suggest that caution should be exercised in interpreting some of the claims of exceptional prognostic classifier performance that have been reported in prominent biomedical journals in the past few years. Copyright © 2006 John Wiley & Sons, Ltd.
Misspecified regression model for the subdistribution hazard of a competing risk
Authors: Latouche A. , Boisson V. , Chevret S. , Porcher R. 
Published: June 2006

AbstractWe consider a competing risks setting, when evaluating the prognostic influence of an exposure on a specific cause of failure. Two main regression models are used in such analyses, the Cox cause‐specific proportional hazards model and the subdistribution proportional hazards model. They are exemplified in a real data example focusing on relapse‐free interval in acute leukaemia patients. We examine the properties of the estimator based on the latter model when the true model is the former. An explicit relationship between subdistribution hazards ratio and cause‐specific hazards ratio is derived, assuming a flexible parametric distribution for latent failure times. Copyright © 2006 John Wiley & Sons, Ltd.
Re‐examining the precepts of the blade element momentum theory for coning rotors
Authors: Crawford Curran 
Published: June 2006

AbstractBlade element momentum (BEM) theory remains the core analytic approach behind most wind turbine analysis codes. The development of the theory extends over 100 years and thus bears re‐examination for applications involving coned rotors, for which it was never designed. This article reviews the underlying assumptions of BEM with a view to properly formulating a modified BEM theory for coned rotors. The postulate is that the critical limitation of BEM is the usual assumed relation between disc and far wake induction. Proper consideration of the relative placement of the wake and radially induced velocity, using potential flow theory, yields corrections to the BEM method. Using the modified BEM method, results are presented and compared with computational fluid dynamics (CFD) studies for ideal and real rotors to validate the new approach. It is found that the main limitation of BEM in application to coned rotors is in the assumed wake position, not the planar disc or the independence of stream‐tube assumptions. The latter is found only to have a strong effect at high induction factors and thrust coefficients, which are manifest in deficient local thrust coefficient models that seek to model transient recirculating flow conditions within the confines of a steady stream‐tube method. Copyright © 2006 John Wiley &Sons, Ltd.
The PPARα/γ dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats
Authors: Li Ping‐Ping , Shan Song , Chen Yue‐Teng , Ning Zhi‐Qiang , Sun Su‐Juan , Liu Quan , Lu Xian‐Ping , Xie Ming‐Zhi , Shen Zhu‐Fang 
Published: June 2006

The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L‐glutamate (MSG) obese rats and to determine whether its lipid‐lowering effect is mediated through its activation of PPARα.
Chiglitazar is a PPARα/γ dual agonist.
The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats.
Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets.
Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein‐cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARα, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats.
These data suggest that PPARα/γ coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARγ agonists.

British Journal of Pharmacology (2006) 148, 610–618. doi:10.1038/sj.bjp.0706745
Group I mGlu receptor stimulation inhibits activation‐induced cell death of human T lymphocytes
Authors: Chiocchetti Annalisa , Miglio Gianluca , Mesturini Riccardo , Varsaldi Federica , Mocellin Marco , Orilieri Elisabetta , Dianzani Chiara , Fantozzi Roberto , Dianzani Umberto , Lombardi Grazia 
Published: June 2006

The effects ofL‐glutamate on activation‐induced cell death (AICD) of human activated (1 μg ml−1phytohemagglutinin plus 2 U ml−1interleukin‐2; 8 days) T lymphocytes were studied by measuring anti‐CD3 monoclonal antibody (10 μg ml−1; 18 h)‐induced cell apoptosis (Annexin V and propidium iodide staining).L‐Glutamate (1 × 10−8–1 × 10−4 M) significantly (P0.01) inhibited AICD in a concentration‐dependent manner (EC50=6.3 × 10−8 M; maximum inhibition 54.8±6.3% at 1 × 10−6 M).TheL‐glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC50values were: 3.2 × 10−7 Mfor (1S,3R)‐ACPD; 4.5 × 10−8 Mfor quisqualate; 1.0 × 10−6 Mfor (S)‐3,5‐DHPG; 2.0 × 10−5 Mfor CHPG.Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10−6 M. The IC50values calculated were: 8.7 × 10−5, 4.3 × 10−6and 6.3 × 10−7 Mfor AIDA, LY 367385 and MPEP, respectively.L‐Glutamate (1 × 10−6M; 18 h) significantly (P0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling.Expression of both mGlu1and mGlu5receptor mRNA by T lymphocytes and T‐cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests thatL‐glutamate‐mediated inhibition of AICD was exerted on T cells.These data depict a novel role forL‐glutamate in the regulation of the immune response through group I mGlu receptor‐mediated mechanisms.British Journal of Pharmacology(2006)148, 760–768. doi:10.1038/sj.bjp.0706746
Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder
Authors: Abrams Paul , Andersson Karl‐Erik , Buccafusco Jerry J , Chapple Christopher , de Groat William Chet , Fryer Alison D , Kay Gary , Laties Alan , Nathanson Neil M , Pasricha Pankaj Jay , Wein Alan J 
Published: June 2006

The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth muscle cells, as well as on nondetrusor structures.Muscarinic M3receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M2receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents.Although the role of muscarinic receptors in the bladder, other than M3receptors, remains unclear, their role in other body systems is becoming increasingly well established, with emerging evidence supporting a wide range of diverse functions. Blockade of these functions by muscarinic receptor antagonists can lead to similarly diverse adverse effects associated with antimuscarinic treatment, with the range of effects observed varying according to the different receptor subtypes affected.This review explores the evolving understanding of muscarinic receptor functions throughout the body, with particular focus on the bladder, gastrointestinal tract, eye, heart, brain and salivary glands, and the implications for drugs used to treat OAB. The key factors that might determine the ideal antimuscarinic drug for treatment of OAB are also discussed. Further research is needed to show whether the M3selective receptor antagonists have any advantage over less selective drugs, in leading to fewer adverse events.British Journal of Pharmacology(2006)148, 565–578. doi:10.1038/sj.bjp.0706780
Citrobacter rodentium‐induced NF‐κB activation in hyperproliferating colonic epithelia: role of p65 (Ser536) phosphorylation
Authors: Wang Yu , Xiang Guang‐Sheng , Kourouma Famourou , Umar Shahid 
Published: June 2006

The transcription factors of the NF‐κB/Rel family form dimeric complexes that control expression of various genes involved in inflammation and proliferation.
During transmissible murine colonic hyperplasia (TMCH) induced by Citrobacter rodentium, nuclear translocation of NF‐κB in isolated colonic crypts increased 3 day's post‐infection and continued over 12 days paralleling peak hyperplasia. Antibody supershifts for both p65/p50 hetero‐ and p50/p50 homodimers occurred. Expression levels of both p50 and p65 subunits increased in cytosolic/nuclear extracts and correlated with NF‐κB activation kinetics. IκBα levels decreased during this time.
Phosphorylation of IKKα (at Ser176/180) and ‐β (at Ser177/181) increased significantly during TMCH suggesting activation in vivo.
p65‐Ser536 (p65536) exhibited increased phosphorylation on immunoblotting and immunohistochemistry (IHC) both at day 6 and 12 TMCH. p65536 translocated to nucleus and interacted with transcriptional coactivator CREB binding protein (CBP).
Proteasomal inhibitor bortezomib (Velcade®) caused accumulation of Ser32/36‐phosphorylated IκBα and significant inhibition of NF‐κB activity in vivo. Velcade® also blocked nuclear translocation of activated p65: both immunoblotting and IHC failed to detect p65536 nuclear immunoreactivity. Velcade®, however, did not abrogate TMCH.
p65 interacted strongly with ribosomal S6 kinase 1 (RSK‐1) during coimmunoprecipitation but not with IKKα or ‐β.
Thus, NF‐κB activation during TMCH involves both IκBα degradation and p65‐Ser536 phosphorylation. p65/RSK‐1 interaction and concomitant increase in p65536 complexed with CBP may be important in modulating NF‐κB activity in vivo. Activated NF‐κB, besides modulating proliferation, may aid in providing protective immunity against C. rodentium infection in vivo.

British Journal of Pharmacology (2006) 148, 814–824. doi:10.1038/sj.bjp.0706784