bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of Ligand‐ and Target‐Based Virtual Screening for the Discovery of Cruzain Inhibitors
Authors: Wiggers H. J. , Rocha J. R. , Cheleski J. , Montanari C. A. 
Published: June 2011

AbstractA myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand‐Based Virtual Screening (LBVS) and Target‐Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled‐rank‐by‐number, rank‐by‐rank and rank‐by‐vote, with the most thriving the scaled‐rank‐by‐number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand‐based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.
MPO Inhibitors Selected by Virtual Screening
Authors: Malvezzi Alberto , Queiroz Raphael F , de Rezende Leandro , Augusto Ohara , Amaral Antonia T.‐do 
Published: June 2011

AbstractThe hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure‐based drug design (SBDD) and ligand‐based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical‐chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC50 values ranging from 1.0 to 2.8 µM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.
Trans‐resveratrol simultaneously increases cytoplasmic Ca2+ levels and nitric oxide release in human endothelial cells
Authors: Elíes Jacobo , Cuíñas Andrea , García‐Morales Verónica , Orallo Francisco , Campos‐Toimil Manuel 
Published: June 2011

AbstractScope: The aim of this study was to investigate whether the dietary polyphenol trans‐resveratrol (t‐Resv) increases [Ca2+]c in endothelial cells, leading to a simultaneous augmentation of nitric oxide (NO) biosynthesis.Methods and results: We have separately and simultaneously measured [Ca2+]c and NO in human endothelial cells using the Ca2+ indicator fura‐2 and the NO‐sensitive fluorescent probe 4,5‐diaminofluorescein. In ∼30% of cells, t‐Resv (30 μM) induced an increase in [Ca2+]c with a transient as well as sustained component and a simultaneous increase in NO biosynthesis. This effect was reduced by non‐selective Ca2+ channel blockers, inhibition of intracellular Ca2+ release, inhibition of endothelial nitric oxide synthase (eNOS) and, to a lesser extent, inhibition of extracellular signal‐regulated kinase 1/2 (ERK 1/2) or 5′ adenosine monophosphate‐activated protein kinase (AMPK). t‐Resv did not modify in vitro eNOS activity, suggesting that the observed stimulation of NO generation proceeds via mobilisation of Ca2+ and not through direct effects on eNOS.Conclusion: We therefore show, for the first time, that t‐Resv induces a concentration‐dependent, simultaneous increase in [Ca2+]c and NO biosynthesis that could be linked to its endothelium‐dependent vasorelaxant effect. Under the assumption that t‐Resv exhibits similar behaviour in human blood vessels in vivo, the pharmacological properties described here may contribute to the beneficial cardiovascular effects of this polyphenol by improving endothelial function.
Ultrashort echo time imaging using pointwise encoding time reduction with radial acquisition (PETRA)
Authors: Grodzki David M. , Jakob Peter M. , Heismann Bjoern 
Published: June 2011

AbstractSequences with ultrashort echo times enable new applications of MRI, including bone, tendon, ligament, and dental imaging. In this article, a sequence is presented that achieves the shortest possible encoding time for each k‐space point, limited by pulse length, hardware switching times, and gradient performance of the scanner. In pointwise encoding time reduction with radial acquisition (PETRA), outer k‐space is filled with radial half‐projections, whereas the centre is measured single pointwise on a Cartesian trajectory. This hybrid sequence combines the features of single point imaging with radial projection imaging. No hardware changes are required. Using this method, 3D images with an isotropic resolution of 1 mm can be obtained in less than 3 minutes. The differences between PETRA and the ultrashort echo time (UTE) sequence are evaluated by simulation and phantom measurements. Advantages of pointwise encoding time reduction with radial acquisition are shown for tissue with a T2 below 1 ms. The signal to noise ratio and Contrast‐to‐noise ratio (CNR) performance, as well as possible limitations of the approach, are investigated. In‐vivo head, knee, ankle, and wrist examples are presented to prove the feasibility of the sequence. In summary, fast imaging with ultrashort echo time is enabled by PETRA and may help to establish new routine clinical applications of ultrashort echo time sequences. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Accelerated water–fat imaging using restricted subspace field map estimation and compressed sensing
Authors: Sharma Samir D. , Hu Houchun H. , Nayak Krishna S. 
Published: June 2011

AbstractWater–fat separation techniques play an important role in a variety of clinical and research applications. In particular, multiecho separation methods remain a topic of great interest due to their ability to resolve water and fat images in the presence of B0‐field inhomogeneity. However, these methods are inherently slow as they require multiple measurements. An accelerated technique with reduced k‐space sampling is desirable to decrease the scan time. This work presents a new method for water–fat separation from accelerated multiecho acquisitions. The proposed approach does not require the region‐growing or region‐merging schemes that are typically used for field map estimation. Instead, the water, fat, and field map signals are estimated directly from the undersampled k‐space measurements. In this work, up to 2.5×‐acceleration is demonstrated in a water–fat phantom, ankle, knee, and liver. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Komplexität ohne Kompliziertheit
Authors: Jung Udo 
Published: July 2011

AbstractSind globale Megatrends ein Erfolgsfaktor oder eine Worthülse? Beeinflussen sie die Wachstums‐ und Wertschaffungschancen chemischer Unternehmen unterschiedlich, oder sind sie wenig differenzierend, da ja fast alle davon profitieren? Europäische Chemieunternehmen sollten den Trends folgen, ihre Gravitätszentren verschieben und die Fähigkeit nutzen, komplexe Geschäfte unkompliziert zu steuern.
Transient partial response to sorafenib treatment in an adolescent patient with MEN2B Syndrome and end‐stage medullary thyroid carcinoma
Authors: Aller Steven , Popescu Andrada , Rao Sudha , Morgan Elaine , Gosiengfiao Yasmin 
Published: June 2011

AbstractMetastatic medullary thyroid carcinoma (MTC) is an aggressive malignancy with an extremely poor prognosis. Currently no effective conventional systemic therapies exist to treat pediatric MTC. We describe an adolescent female with newly diagnosed MEN2B syndrome who presented with advanced stage metastatic MTC and demonstrated a partial transient response to sorafenib monotherapy. This clinical result supports further research into the use of sorafenib in the treatment of pediatric MTC. Pediatr Blood Cancer 2012; 58: 98–100. © 2011 Wiley Periodicals, Inc.
Neuropsychological outcomes of standard risk and high risk patients treated for acute lymphoblastic leukemia on Dana‐Farber ALL consortium protocol 95‐01 at 5 years post‐diagnosis
Authors: Waber Deborah P. , Queally Jennifer Turek , Catania Lori , Robaey Philippe , Romero Ivonne , Adams Heather , Alyman Cheryl , Jandet‐Brunet Christine , Sallan Stephen E. , Silverman Lewis B. 
Published: June 2011

AbstractBackgroundChildren treated for acute lymphoblastic leukemia (ALL) as High Risk (HR) patients may be more vulnerable to neurocognitive late effects because of the greater intensity of their therapy. We compared neuropsychological outcomes in children treated for Standard Risk (SR) or HR ALL on Dana‐Farber Cancer Institute (DFCI) Consortium ALL Protocol 95‐01. We also evaluated their performance relative to normative expectations.ProcedureBetween 1996 and 2000, 498 children with newly diagnosed ALL were treated on Protocol 95‐01, 298 of whom were eligible for neuropsychological follow‐up. A feature of this protocol was modification of risk group criteria to treat more children as SR rather than HR patients, intended to minimize toxicities. Testing was completed at a median of 5.3 years post‐diagnosis for 211 patients (70.8%; ages 6–25 years; 45.5% male; 40% HR), all of whom were in continuous complete remission.ResultsTest scores for both groups were generally at or above normative expectation, with the exception of verbal working memory, processing complex visual information, and parent ratings of metacognitive skills. After adjusting for covariates, the SR group performed better on measures of IQ and academic achievement, working memory and visual learning. Effect sizes, however, were only in the small to moderate range.ConclusionsHR patients exhibited neuropsychological deficits relative to SR patients, though the differences were modest in degree. Modification of the risk group criteria to treat more children on the SR protocol therefore likely afforded some benefit in terms of neurocognitive late effects. Pediatr Blood Cancer 2012; 58: 758–765. © 2011 Wiley Periodicals, Inc.
Genetic screening in a university clinic: impact of primary language
Authors: Hawk Angela F. , Pastore Lisa , Saller Devereux N. 
Published: June 2011

AbstractObjectiveTo contrast Spanish‐speaking (S) with English‐speaking (E) obstetric patients regarding utilization of genetic screening, motivation for undergoing/declining screening, pregnancy‐related anxiety, knowledge about genetic conditions, and printed information as an adjunct to counseling.MethodPaper surveys were given to patients (n = 121) in an academic OB/GYN clinic or placed in charts (n = 271) over a 4‐week period. Comparisons were evaluated with Chi‐square and Fisher's exact tests.ResultsCompleted surveys were returned from 245 gravidas (response rate 63%, S 48%, and E 67%). Uptake of genetic screening was similar between the groups (S 69% vs E 57%, p = 0.13). No significant differences were noted in patients' motivation regarding screening, source of screening information, or self‐assessed pregnancy‐related anxiety. Familiarity of genetic disorders other than Down syndrome differed between the S and E groups (p < 0.003). Perceived positive utility of printed information differed significantly when groups were analyzed by language (S 85% vs E 47%, p < 0.001) and by uptake of screening(screened 62% vs not screened 44%, p = 0.006).ConclusionA majority of study participants (n = 147, 60%) chose genetic screening; uptake and motivation were similar across language groups. Familiarity with genetic conditions was deficient and screening terminology confusing regardless of primary language. The perceived positive utility of printed information (S > E) highlights the importance of clear and early counseling. Copyright © 2011 John Wiley & Sons, Ltd.
Prenatal brain imaging in congenital toxoplasmosis
Authors: Malinger G. , Werner H. , Rodriguez Leonel J. C. , Rebolledo M. , Duque M. , Mizyrycki S. , Lerman‐Sagie T. , Herrera M. 
Published: June 2011

AbstractObjectiveTo describe brain imaging findings and outcomes in fetuses with confirmed congenital toxoplasmosis (CTX).MethodsPhysicians from Prenatal Diagnosis Units in ten Latin American countries were contacted and asked to provide data on fetuses with ultrasound findings suggestive of intrauterine infection and a positive diagnosis of CTX. The imaging studies were reviewed, and findings were described and tabulated.ResultsIntracranial findings suggestive of CTX were identified in eight patients at a median gestational age of 31.5 weeks (range, 24.4–34 weeks). Ventriculomegaly was found in seven patients [severe (3), mild (4)]. Multiple echogenic nodular foci consistent with calcifications were found in seven patients [brain parenchyma (7), periventricular zone (3) and caudothalamic zone (3)]. Diffuse periventricular echogenicity or cysts were seen in three and callosal dysgenesis in one. All six survivors have choroidoretinitis and intracranial calcifications, four suffer from developmental delay and three of these four children also suffer from seizures and blindness. Postnatal hydrocephaly was found in five children.ConclusionsVentriculomegaly associated with multiple echo‐dense nodules is characteristic of severe fetal toxoplasmosis and carries a poor prognosis. When the ventricles have normal size or are only mildly dilated, the nodules restricted to the parenchyma development may be normal. Copyright © 2011 John Wiley & Sons, Ltd.
Confounding adjustment via a semi‐automated high‐dimensional propensity score algorithm: an application to electronic medical records
Authors: Toh Sengwee , García Rodríguez Luis A. , Hernán Miguel A. 
Published: June 2011

ABSTRACTPurposeA semi‐automated high‐dimensional propensity score (hd‐PS) algorithm has been proposed to adjust for confounding in claims databases. The feasibility of using this algorithm in other types of healthcare databases is unknown.MethodsWe estimated the comparative safety of traditional non‐steroidal anti‐inflammatory drugs (NSAIDs) and selective COX‐2 inhibitors regarding the risk of upper gastrointestinal bleeding (UGIB) in The Health Improvement Network, an electronic medical record (EMR) database in the UK. We compared the adjusted effect estimates when the confounders were identified using expert knowledge or the semi‐automated hd‐PS algorithm.ResultsCompared with the 411,616 traditional NSAID initiators, the crude odds ratio (OR) of UGIB was 1.50 (95%CI: 0.98, 2.28) for the 43,569 selective COX‐2 inhibitor initiators. The OR dropped to 0.81 (0.52, 1.27) upon adjustment for known risk factors for UGIB that are typically available in both claims and EMR databases. The OR remained similar when further adjusting for covariates—smoking, alcohol consumption, and body mass index—that are not typically recorded in claims databases (OR 0.81; 0.51, 1.26) or adding 500 empirically identified covariates using the hd‐PS algorithm (OR 0.78; 0.49, 1.22). Adjusting for age and sex plus 500 empirically identified covariates produced an OR of 0.87 (0.56, 1.34).ConclusionsThe hd‐PS algorithm can be implemented in pharmacoepidemiologic studies that use primary care EMR databases such as The Health Improvement Network. For the NSAID–UGIB association for which major confounders are well known, further adjustment for covariates selected by the algorithm had little impact on the effect estimate. Copyright © 2011 John Wiley & Sons, Ltd.
Proteomic analysis of the hepatic tissue of Long–Evans Cinnamon (LEC) rats according to the natural course of Wilson disease
Authors: Lee Beom H. , Kim Jae‐Min , Heo Sun H. , Mun Joo H. , Kim Jihun , Kim Joo H. , Jin Hye Y. , Kim Gu‐Hwan , Choi Jin‐Ho , Yoo Han‐Wook 
Published: July 2011

AbstractCopper‐induced toxicity is important in the pathogenic process of Wilson's disease (WD). Using Long–Evans Cinnamon (LEC) rats, an animal model of WD, the study was undertaken to identify proteins involved in the process of WD and to investigate their functional roles in copper‐induced hepatotoxicity. In early stages, expression levels of mitochondrial matrix proteins including agmatinase, isovaleryl coenzyme A dehydrogenase, and cytochrome b5 were downregulated. As mitochondrial injuries progressed, along with subsequent apoptotic processes, expressions of malate dehydrogenase 1, annexin A5, transferrin, S‐adenosylhomocysteine hydrolase, and sulfite oxidase 1 were differentially regulated. Notably, the expression of malate dehydrogenase 1 was downregulated while the annexin A5 was overexpressed in an age‐dependent manner, indicating that these proteins may be involved in the WD process. In addition, pronounced under‐expression of S‐adenosylhomocysteine hydrolase in elderly LEC rats, also involved in monoamine neurotransmitter metabolism, indicates that this protein might be related to the development of neurological manifestations in WD. The results of our study help to understand the pathogenic process of WD in hepatic tissues, identifying the important proteins associated with the disease process of WD, and to investigate the molecular pathogenic process underlying the development of neurological manifestations in WD.
Retracted: Isocratic Method for Affinity Enrichment of Covalently‐linked Peptides in Cyanogen Bromide Cleavage of Proteins
Authors: Shi Tujin , Liu Jing , Yan Chen , Wang Xiaocong 
Published: July 2011

AbstractThe following article from Proteomics, “Isocratic method for affinity enrichment of covalently‐linked peptides in cyanogen bromide cleavage of proteins” by T. Shi, J. Liu, C. Yan and X. Wang, published online as “Accepted Article” on 4 July 2011 (DOI: 10.1002/pmic.201100126) in the Wiley Online Library (http://www.onlinelibrary.wiley.com), has been retracted by agreement between the authors, the Editor‐in‐Chief and Wiley‐VCH Verlag GmbH & Co. KGaA. The retraction has been agreed due to partial overlap between this article and the following article published in Analytical Chemistry, “Method for the affinity purification of covalently linked peptides following cyanogens bromide cleavage of proteins” by T. Shi et al. (Anal. Chemistry 2009, 81, 9885–9895). In addition, the author T. Shi was wrongly affiliated with the Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Acrylic copolymers with pendant 1,2,4‐triazole moieties as colorimetric sensory materials and solid phases for the removal and sensing of cations from aqueous media
Authors: Gómez‐Valdemoro Ana , Trigo Miriam , Ibeas Saturnino , García Félix Clemente , Serna Felipe , García José Miguel 
Published: June 2011

AbstractLinear water‐soluble polymers and nets with gel‐like behavior were prepared for use as colorimetric sensors and selective extracting agents for naked eye detection and solid–liquid removal of heavy‐metal cations from aqueous environments. Triazole is a well‐known, heavy‐metal cation host. A water‐insoluble methacrylamide containing a 1,2,4‐triazole receptor derivative was copolymerized with highly hydrophilic and water‐soluble methacrylamides to yield a water‐soluble polymer or a cross‐linked network as a powder or a dense membrane. In powder form, the material selectively removed Hg2+, Pb2+, and Ag+ from aqueous media. In the form of swelled dense membranes or films, the material acted as colorimetric sensor for Fe3+. When the membrane was soaked in a yellow aqueous solution of Fe3+, the former colorless, transparent membrane became reddish (but retained its transparency), and the solution became colorless. Aqueous conductivity studies confirmed that both the extraction and the sensing phenomena arose from the interaction of the cations with the triazole moieties. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Compatibility studies of polystyrene and poly(vinyl acetate) blends using electrostatic force microscopy
Authors: Kummali Mohammed M. , Schwartz Gustavo A. , Alegría Angel , Arinero Richard , Colmenero Juan 
Published: June 2011

AbstractThe effect of thermal treatment on the phase separation process of the components of a polymer blend was investigated using electrostatic force microscopy (EFM). EFM technique is an advance on conventional atomic force microscopy, which enables us to measure locally the dielectric properties of the samples under investigation providing compositional information. In this work, we studied the phase separation process of the polymer blend thin films made of polystyrene and poly(vinyl acetate) (PS/PVAc) (75/25 weight fraction). The samples were subjected to different thermal treatments. It was found that at low annealing temperature, PVAc forms many small islands within PS matrix. As the annealing temperature increases, the number of PVAc islands decreases with an increase in the size of the islands. These islands take spherical‐like shape when annealed at a temperature well above the glass transition temperatures of both the component polymers. Despite these morphological/topographical changes, EFM images evidence that there is no interdiffusion which was further confirmed by quantitatively measuring the value of the dielectric permittivity across the interphase. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1332–1338, 2011
Surface Modification of Nanoclays by Plasma Polymerization of Ethylene
Authors: Neira‐Velázquez María Guadalupe , Ramos‐deValle Luis Francisco , Hernández‐Hernández Ernesto , Ponce‐Pedraza Arturo , Solís‐Rosales Silvia Guadalupe , Sánchez‐Valdez Saúl , Bartolo‐Pérez Pascual , González‐González Virgilio A. 
Published: June 2011

AbstractSodium nanoclay was modified by plasma polymerization using ethylene gas. Due to the complexity of its lamellar morphology that prevents ethylene from entering into the clay galleries, a new two‐step strategy was employed. This method proved to be effective in overcoming the limited accessibility by first exposing the nanoclay to ethylene under a pressure of 0.14 MPa (1.4 kg · cm−2), followed by the ethylene plasma polymerization while within the clay galleries. Fourier transform infrared (FTIR)spectroscopy, dispersion tests in water, Raman spectroscopy, X‐ray photoelectronic spectroscopy (XPS), thermogravimetric analysis (TGA), X‐ray diffraction (XRD), high‐resolution transmission electron microscopy (HRTEM), and high‐annular angle dark field (HAADF) were used to characterize the modified nanoclay. XRD analysis indicated that the nanoclays layers were intercalated with polyethylene. Dispersion tests in water confirmed the nanoclays change from hydrophilic to organophilic. New chemical bondings (C–Si, C–O–Al, C–O, and C=O) were found by XPS. The presence of plasma polymer on the surface and inside the nanoclays galleries was corroborated by HRTEM. magnified image