bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease‐Specific Differentiation Between Drugs and Non‐Drugs Using Principal Component Analysis of Their Molecular Descriptor Space
Authors: García‐Sosa Alfonso T. , Oja Mare , Hetényi Csaba , Maran Uko 
Published: May 2012

AbstractThe physicochemical descriptor space has been extensively mapped and described in the literature for orally administered drugs and lead compounds. However, consideration of negative examples (non‐drugs) or disease pathophysiology is not common in many studies. In the present work, a principal component analysis was carried out using drugs and non‐drugs taking into account disease‐ and organ‐specific categories, as well as different administration routes in addition to oral. The study involves 1386 relevant small‐molecules including natural and synthetic products. Drug‐specific as well as disease‐category‐specific or organ‐specific regions and their respective threshold sets (ranges of descriptors) relative to non‐drugs were elucidated on the scores plot and validated with external, independent sets of drugs and non‐drugs. The respective loadings plot of molecular descriptors was rationalized in terms of physicochemically relevant groups related to the components of solvation free energy. The results of this analysis can contribute to the improved profiling of drug candidates and libraries making use of disease‐ and organ‐specificity coded by physicochemical descriptors and ligand binding efficiency.
An optimized velocity selective arterial spin labeling module with reduced eddy current sensitivity for improved perfusion quantification
Authors: Meakin James A. , Jezzard Peter 
Published: May 2012

AbstractVelocity‐selective (VS) arterial spin labeling is a promising method for measuring perfusion in areas of slow or collateral flow by eliminating the bolus arrival delay associated with other spin labeling techniques. However, B0 and B1 inhomogeneities and eddy currents during the VS preparation hinder accurate quantification of perfusion with VS arterial spin labeling. In this study, it is demonstrated through simulations and experiments in healthy volunteers that eddy currents cause erroneous tagging of static tissue. Consequently, mean gray matter perfusion is overestimated by up to a factor of 2, depending on the VS preparation used. A novel eight‐segment B1 insensitive rotation VS preparation is proposed to reduce eddy current effects while maintaining the B0 and B1 insensitivity of previous preparations. Compared to two previous VS preparations, the eight‐segment B1 insensitive rotation is the most robust to eddy currents and should improve the quality and reliability of VS arterial spin labeling measurements in future studies. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Natalist Policies in the United States
Authors: Lopoo Leonard M. , Raissian Kerri M. 
Published: May 2012

AbstractThis retrospective reviews the policies that affect the fertility of American women, both policies designed to alter fertility intentionally as well as those that change childbearing unintentionally. Becker's seminal work on the economics of fertility serves as the theoretical foundation for this literature. After describing Becker's economic model, we review the empirical literature on fertility responses to social welfare policies, tax policies, the mandated health care coverage of infertility treatments, abortion policies, and government‐sponsored family planning services. We also address several Supreme Court cases that have played an important role in the interpretation of these policies. Where relevant, this retrospective describes the distributional effects of these natalist policies. We also discuss the limitations of this literature and identify important gaps. Unlike most developed countries that have created strategies to increase fertility to support their ageing population, the United States spends considerably less time and thought on this issue. Our reading of the literature suggests that we have many public policies that have affected and continue to influence the fertility choices made by families in the United States and that this is a topical area that deserves more attention in policy debates.
Advanced glycation end product Nε‐carboxymethyllysine induces endothelial cell injury: the involvement of SHP‐1‐regulated VEGFR‐2 dephosphorylation
Authors: Liu Shing Hwa , Sheu Wayne Huey Herng , Lee Maw Rong , Lee Wen Jane , Yi Yu Chiao , Yang Tzung Jie , Jen Jen Fon , Pan Hung Chuan , Shen Chin Chang , Chen Wen Bao , Tien Hsing Ru , Sheu Meei Ling 
Published: May 2012

AbstractNε‐carboxymethyllysine (CML), a major advanced glycation end product, plays a crucial role in diabetes‐induced vascular injury. The roles of protein tyrosine phosphatases and vascular endothelial growth factor (VEGF) receptors in CML‐related endothelial cell injury are still unclear. Human umbilical vein endothelial cells (HUVECs) are a commonly used human EC type. Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)‐mediated SH2 domain‐containing tyrosine phosphatase‐1 (SHP‐1) activation by CML inhibits the VEGF receptor‐2 (VEGFR‐2, KDR/Flk‐1) activation, resulting in HUVEC injury. CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR‐2 activation in parallel with the increased SHP‐1 protein expression and activity in HUVECs. Adding recombinant VEGF increased forward biological effects, which were attenuated by CML. The effects of CML on HUVECs were abolished by SHP‐1 siRNA transfection. Exposure of HUVECs to CML also remarkably escalated the integration of SHP‐1 with VEGFR‐2. Consistently, SHP‐1 siRNA transfection and pharmacological inhibitors could block this interaction and elevating [3H]thymidine incorporation. CML also markedly activated the NADPH oxidase and ROS production. The CML‐increased SHP‐1 activity in HUVECs was effectively attenuated by antioxidants. Moreover, the immunohistochemical staining of SHP‐1 and CML was increased, but phospho‐VEGFR‐2 staining was decreased in the aortic endothelium of streptozotocin‐induced and high‐fat diet‐induced diabetic mice. We conclude that a pathway of tyrosine phosphatase SHP‐1‐regulated VEGFR‐2 dephosphorylation through NADPH oxidase‐derived ROS is involved in the CML‐triggered endothelial cell dysfunction/injury. These findings suggest new insights into the development of therapeutic approaches to reduce diabetic vascular complications. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Improvement of interfacial interaction, dispersion, and properties of chlorosulfonated polyethylene/sio2 nanocomposites using CSPE‐g‐Sio2 nanoparticles synthesized under ultrasonics
Authors: Bai Xuefeng , He Xuelian , Zhang Jun , Zhu Xiao , Zhang Haiyang , Cheng Ruihua , Liu Boping 
Published: May 2012

AbstractChlorosulfonated polyethylene (CSPE) is a widely used elastomer because of the resistance to gases and aggressive chemicals, fire‐retarding, and electric insulating properties. Silica nanoparticles were usually introduced into the elastomer to improve its critical properties. However, there were some problems of strong aggregation and poor dispersion of nanoparticles in the nanocomposites. In this work, an efficient approach of grafting matrix CSPE onto silica surface was proposed to solve the problems. CPSE‐g‐SiO2 nanoparticles were prepared via an in situ radical reaction between Cl in CSPE and SiOH on silica surface under ultrasonics. The successful chemical graft reaction was confirmed using Fourier transform infrared, ultraviolet–visible spectroscopy, 1H‐NMR, and X‐ray photoelectron spectroscopy. Thermogravimetric analysis indicated that the grafting amount of CSPE was 4.68 wt%. Grafting CSPE onto silica surface significantly improved the dispersion of CSPE‐g‐SiO2 nanoparticles in CSPE matrix and the interfacial interaction. Therefore, the mechanical, thermal stability, damping capacity, and rheology properties of CSPE/CSPE‐g‐SiO2 nanocomposites were improved. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Carbon nanotubes grafting PBO fiber: A study on the interfacial properties of epoxy composites
Authors: Zhang Chunhua , Xu Huifang , Jiang Zaixing , Zhu Fenglei , Huang Yudong 
Published: May 2012

AbstractTo improve the interfacial performance of poly[p‐phenylene benzobisoxazole] (PBO) fiber and epoxy resin, a modified multiwalled carbon nanotubes (MWCNTs‐Ecp) were used to achieve this purpose through grafting onto PBO fiber surface using a gamma ray radiation method. Experimental results indicated that the equilibrium wetting rate and equilibrium adsorption amount of the modified PBO fiber for epoxy resin and acetone were all higher than that of as received PBO fiber. The interfacial shear strength (IFSS) of single fiber composite increased from 31.4 to 77.5 MPa after modification. The fracture models of composites are changed from pure interfacial failure to combination failure of interface and resin interlayer. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Synthesize of polymer–silicate nanocomposites by in situ metal‐catalyzed living radical polymerization
Authors: Abbasian Mojtaba , Mahi Robab 
Published: May 2012

AbstractPolymer–silicate nanocomposites were synthesized with atom transfer radical polymerization (ATRP). An ATRP initiator, consisting of a quaternary ammonium salt moiety and an α‐phenyl chloroacetyl chloride moiety, were intercalated into the interlayer spacings of the layered silicate. Subsequent ATRP of styrene with CuCl/2,2′‐bipyridine (bipy) as the catalyst with the initiator‐modified silicate afforded homopolymers with predictable molecular weights and low polydispersities, both characteristics of living radical polymerization. The polystyrene nanocomposites contained both intercalated and exfoliated silicate structures. The prepared materials were characterized by XRD, SEM, TEM, FTIR, and 1H NMR techniques. Effect of silicate on thermal properties and glass transition temperature of polystyrene was investigated using thermogravimetric analysis and differential scanning calorimetric techniques. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Polyamide 6‐wheat straw composites: Degradation kinetics
Authors: Amintowlieh Yasaman , Sardashti Amirpouyan , Simon Leonardo C. 
Published: May 2012

AbstractDegradation kinetics of ground wheat straw (WS), polyamide 6, and a WS‐polyamide 6 composites obtained from extrusion were investigated. 15 wt% of ground WS was melt blended with other additives naming; lithium chloride salt (LiCl) and N‐butylbenzenesulfonamide plasticizer (N‐BBSA) as matrix treatments. The additives were added to reduce the melting point of polyamide 6 and ease of composite processing (reduction in processing temperature and time). Two commonly used non‐isothermal kinetic models were used to investigate the degradation kinetics of WS and the composite. Thermal gravimetric analysis was utilized to measure the thermal stability and degradation kinetics of different composite formulation. The activation energy of WS was identified by iso‐conversional Friedman kinetic method. Through this method, WS activation energy was found to be around 141.4 kJ/mol. Composite kinetic studies were based on the Coats and Redfern procedure. It was concluded that the composite activation energy was correlated to the residual weight percentage of the composite at the maximum thermal degradation temperature. The onset of degradation of WS was dictated by the thermal stability of its lignin content and was found to be around 188°C. WS, however, did not go through a major degradation up to 245°C at which drastic decomposition starts. This temperature range overlaps with processing temperature of Polyamide 6 and required matrix/WS treatments. Addition of salt and plasticizer individually or with each other at any level decreased the onset of degradation temperature. Addition of plasticizer at 4 wt% level, however, shifted the degradation peak to higher temperature representing a more thermally stable composite. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers
Prior event rate ratio adjustment: numerical studies of a statistical method to address unrecognized confounding in observational studies
Authors: Yu Menggang , Xie Dawei , Wang Xingmei , Weiner Mark G. , Tannen Richard L. 
Published: May 2012

ABSTRACTPurposeThe purpose of this study was to evaluate a statistical method, prior event rate ratio (PERR) adjustment, and an alternative, PERR‐ALT, both of which have the potential to overcome “unmeasured confounding,” both analytically and via simulation.MethodsFormulae were derived for the target estimates of both PERR methods, which were compared with results from simulations to ensure their validity. In addition to the theoretical insights gained, relative biases of both PERR methods for estimating exposure effects were also investigated via simulation studies and compared empirically with electronic medical record database study results.ResultsTheoretical derivations closely matched simulated results. In simulation studies, both PERR methods significantly reduce bias from unmeasured confounding compared with the standard Cox model. When there is no interaction between unmeasured confounders and time intervals, the estimate from PERR‐ALT is unbiased, whereas the estimate from PERR has well‐controlled relative bias. When interactions exist, relative biases tend to increase but not greatly, especially when the exposure effect is relatively large in comparison with the interaction effects. When the event rate is low and the sample size is limited, PERR is more computationally stable than PERR‐ALT. In empiric study comparisons with randomized controlled trials, both PERR methods show potential to reduce bias from the standard Cox model similarly when unmeasured confounding is present.ConclusionsExtensive simulation studies and theoretical derivation show that PERR‐based methods may reduce bias from unmeasured confounders when the exposure effect is relatively large in comparison with confounder–exposure interaction. The rare study event situation warrants further investigation. Copyright © 2012 John Wiley & Sons, Ltd.
Merging of the National Cancer Institute–funded cooperative oncology group data with an administrative data source to develop a more effective platform for clinical trial analysis and comparative effectiveness research: a report from the Children's Oncology Group
Authors: Aplenc R. , Fisher B. T. , Huang Y. S. , Li Y. , Alonzo T. A. , Gerbing R. B. , Hall M. , Bertoch D. , Keren R. , Seif A. E. , Sung L. , Adamson P. C. , Gamis A. 
Published: May 2012

ABSTRACTPurposeThe National Cancer Institute–funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment‐associated resource utilization and costs, and to address important clinical epidemiology questions.MethodsCOG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data.ResultsOf 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti‐infective exposures were tabulated and standardized costs were described.ConclusionsThese data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Comparative effectiveness research using matching‐adjusted indirect comparison: an application to treatment with guanfacine extended release or atomoxetine in children with attention‐deficit/hyperactivity disorder and comorbid oppositional defiant disorder
Authors: Signorovitch James , Erder M. Haim , Xie Jipan , Sikirica Vanja , Lu Mei , Hodgkins Paul S. , Wu Eric Q. 
Published: May 2012

ABSTRACTObjectivesTo illustrate a matching‐adjusted indirect comparison by comparing the efficacy of guanfacine extended release (GXR) and atomoxetine (ATX) in reducing oppositional symptoms in children with attention‐deficit/hyperactivity disorder and comorbid oppositional defiant disorder.MethodsIndividual patient data were used from a GXR trial; only published summary data were used from ATX trials. In a matching‐adjusted indirect comparison, individual patients from the GXR trial were weighted such that their mean baseline characteristics matched those published for ATX trials. Placebo‐arm outcomes were then compared to further assess balance between the matched populations. Changes in the Conners' Parent Rating Scale‐Revised Short Form Oppositional Subscale from baseline to endpoint among GXR‐treated and ATX‐treated patients were then compared.ResultsBefore matching, the GXR (n = 143) and ATX (n = 98) trial populations had significant differences in baseline characteristics and placebo‐arm outcomes. After matching, baseline characteristics were well balanced across trials, and placebo‐arm outcomes became nearly identical. Comparing active treatment arms across the matched populations, GXR was associated with a significantly greater reduction in mean Conners' Parent Rating Scale‐Revised Short form oppositional subscale compared with ATX {−5.0 [95% confidence interval (CI): −6.6 to −3.4] vs. −2.4 [CI: −3.7 to −1.1], p = 0.01, effect size = 0.58}.ConclusionsIn the absence of head‐to‐head randomized trials, matching‐adjusted indirect comparisons can provide timely and reliable comparative evidence for decision makers and can be applied even when very few trials are available for the treatments of interest. Copyright © 2012 John Wiley & Sons, Ltd.
Confronting “confounding by health system use” in Medicare Part D: comparative effectiveness of propensity score approaches to confounding adjustment
Authors: Polinski Jennifer M. , Schneeweiss Sebastian , Glynn Robert J. , Lii Joyce , Rassen Jeremy A. 
Published: May 2012

ABSTRACTPurposeUnder Medicare Part D, patient characteristics influence plan choice, which in turn influences Part D coverage gap entry. We compared predefined propensity score (PS) and high‐dimensional propensity score (hdPS) approaches to address such “confounding by health system use” in assessing whether coverage gap entry is associated with cardiovascular events or death.MethodsWe followed 243,079 Medicare patients aged 65+ years with linked prescription, medical, and plan‐specific data in 2005–2007. Patients reached the coverage gap and were followed until an event or year's end. Exposed patients were responsible for drug costs in the gap; unexposed patients (patients with non‐Part D drug insurance and Part D patients receiving a low‐income subsidy) received financial assistance. Exposed patients were 1:1 PS‐matched or hdPS‐matched to unexposed patients. The PS model included 52 predefined covariates; the hdPS model added 400 empirically identified covariates. Hazard ratios for death and any of five cardiovascular outcomes were compared. In sensitivity analyses, we explored residual confounding using only low‐income subsidy patients in the unexposed group.ResultsIn unadjusted analyses, exposed patients had no greater hazard of death (HR = 1.00; 95%CI, 0.84–1.20) or other outcomes. PS‐matched (HR = 1.29; 0.99–1.66) and hdPS‐matched (HR = 1.11; 0.86–1.42) analyses showed elevated but non‐significant hazards of death. In sensitivity analyses, the PS analysis showed a protective effect (HR = 0.78; 0.61–0.98), whereas the hdPS analysis (HR = 1.06; 0.82–1.37) confirmed the main hdPS findings.ConclusionAlthough the PS‐matched analysis suggested elevated but non‐significant hazards of death among patients with no financial assistance during the gap, the hdPS analysis produced lower estimates that were stable across sensitivity analyses. Copyright © 2012 John Wiley & Sons, Ltd.
Changes in antipsychotic use among patients with severe mental illness after a Food and Drug Administration advisory
Authors: Dusetzina Stacie B. , Busch Alisa B. , Conti Rena M. , Donohue Julie M. , Caleb Alexander G. , Huskamp Haiden A. 
Published: May 2012

ABSTRACTPurposeA 2003 Food and Drug Administration advisory warned of increased hyperlipidemia and diabetes risk for patients taking second‐generation antipsychotics (SGAs). After the advisory, a professional society consensus statement provided treatment recommendations and stratified SGAs into high, intermediate, and low metabolic risk. We examine subsequent changes in incident and prevalent SGA use among individuals with severe mental illness.MethodsWe created a retrospective cohort using Florida Medicaid's claims from 2001 to 2006. We included non‐Medicare eligible adults with bipolar disorder or schizophrenia who filled an SGA prescription. We assessed changes in overall and agent‐specific use, discontinuations, interruptions, and therapeutic alternative use among prevalent users and agent‐specific use among incident users. Pre‐advisory utilization was compared with utilization initially after the advisory and two subsequent periods.ResultsAmong prevalent users, overall SGA use decreased slightly, and no increases in treatment interruptions or discontinuations were observed after the advisory and consensus statement publication. Compared with the pre‐advisory period, in the months immediately after the advisory, the use of the highest metabolic‐risk agent, olanzapine, decreased by 34% among prevalent users with bipolar disorder (adjusted risk ratio [aRR] = 0.66, 95%CI = 0.59–0.74) and 26% among prevalent users with schizophrenia (aRR = 0.74, 95%CI = 0.72–0.76). A greater decrease was estimated among incident users with bipolar disorder (aRR = 0.37, 95%CI = 0.29–0.47) and schizophrenia (aRR = 0.42, 95%CI = 0.35–0.51) during this period. During each subsequent post‐advisory period, olanzapine use continued to decrease whereas quetiapine, ziprasidone, and aripiprazole use increased.ConclusionsThe metabolic risk advisory and the published consensus statement were associated with a selective reduction in olanzapine use without evidence of treatment disruptions among this population. Copyright © 2012 John Wiley & Sons, Ltd.