bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substituent electronic descriptors for fast QSAR/QSPR
Authors: Hemmateenejad Bahram , Sanchooli Mahmood 
Published: May 2007

AbstractSubstituent electronic descriptors (SED), calculated by ab initio quantum chemical methods for radical substituents, were proposed as an efficient and simple to use descriptors for use in Quantitative structure‐activity/property relationships (QSPR/QSAR) studies. Twenty five SED parameters were calculated for a set of simple substituents using orbital energies, local charges, and dipole moments. Calculation of these parameters for a substituent takes much lower time comparing with that for parent molecule. Different chemical and biological data were analyzed by the SED parameters and it was found that in addition to the simplicity and speed of calculations, models obtained by SED parameters have better or comparable efficiency in relative to existing models. Copyright © 2007 John Wiley & Sons, Ltd.
Quantum‐chemical calculations on the electronic circular dichroism of (−)‐dibromophakellin and (−)‐dibromophakell‐statin
Authors: Atodiresei Iuliana , Zöllinger Michael , Lindel Thomas , Fleischhauer Jörg , Raabe Gerhard 
Published: May 2007

AbstractThe CD spectra of the pyrrole‐imidazole alkaloids, (−)‐dibromophakellin and (−)‐dibromophakellstatin, have been calculated employing the quantum‐chemical time‐dependent density functional theory. Comparison of calculated and measured spectra showed that this well‐established method is also a useful tool to elucidate the absolute stereochemistry of this class of compounds. The computational results have further been used to analyze the spectra measured in methanol and to explain the remarkable red shift of one CD band when trifluoroethanol is used as a solvent instead of methanol. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Stereoselective hexobarbital 3′‐hydroxylation by CYP2C19 expressed in yeast cells and the roles of amino acid residues at positions 300 and 476
Authors: Saito Keita , Dan Hikari , Masuda Kazufumi , Katsu Takashi , Hanioka Nobumitsu , Yamamoto Shigeo , Miyano Kazuko , Yamano Shigeru , Narimatsu Shizuo 
Published: May 2007

AbstractWe examined the enzymatic function of recombinant CYP2C19 in enantiomeric hexobarbital (HB) 3′‐hydroxylation, and searched the roles of amino acid residues, such as Phe‐100, Phe‐114, Asp‐293, Glu‐300, and Phe‐476 of CYP2C19 in the stereoselective HB 3′‐hydroxylation, using a yeast cell expression system and site‐directed mutagenesis method. CYP2C19 wild‐type exerted substrate enantioselectivity of (R)‐HB ≫ (S)‐HB and metabolite diastereoselectivity of 3′(R) < 3′(S) in 3′‐hydroxylation of HB enantiomers. The substitution of Asp‐293 by alanine failed to yield an observable peak at 450 nm in its reduced carbon monoxide‐difference spectrum. CYP2C19‐E300A and CYP2C19‐E300V with alanine and valine, respectively, in place of Glu‐300 exerted total HB 3′‐hydroxylation activities of 45 and 108%, respectively, that of the wild‐type. Interestingly, these two mutants showed substrate enantioselectivity of (R)‐HB < (S)‐HB, which is opposite to that of the wild‐type, while metabolite diasteroselectivity remained unchanged. The replacement of Phe‐476 by alanine increased total HB 3′‐hydroxylation activity to approximately 3‐fold that of the wild‐type. Particularly, 3′(S)‐OH‐(S)‐HB‐forming activity elevated to 7‐fold that of the wild‐type, resulting in the reversal of the substrate enantioselectivity. In contrast, the substitution of phenylalanine at positions 100 and 114 by alanine did not produce a remarkable change in the total activity or the substrate enantioselectivity. These results indicate that Glu‐300 and Phe‐476 are important in stereoselective oxidation of HB enantiomers by CYP2C19. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C‐related cirrhosis
Authors: Pekow Joel R. , Bhan Atul K. , Zheng Hui , Chung Raymond T. 
Published: May 2007

AbstractBACKGROUND.Chronic hepatitis C can result in fatty changes in the liver. Previous studies have suggested that hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus (HCV) infection. The authors sought to determine whether hepatic steatosis is associated with hepatocellular carcinoma (HCC) in a cohort of patients with hepatitis C‐related cirrhosis.METHODS.The authors retrospectively identified 94 consecutive patients with hepatitis C cirrhosis who underwent liver transplantation from 1992 to 2005 and had pathology available for review. Of these, 32 had evidence of HCC, and 62 had no HCC on explant histology. All explant specimens were graded again for steatosis by a single, blinded pathologist. Steatosis, age, sex, body mass index, HCV RNA, HCV genotype, Model for End‐Stage Liver Disease (MELD) score, chronic alcohol use, and diabetes were examined in univariate and multivariate analyses for association with HCC.RESULTS.In total, 69% of patients in the HCC group and 50% of patients in the control group had evidence of steatosis (1+) on histology. Odds ratios for the development of HCC for each grade of steatosis compared with grade 0 were as follows: grade 1 (1.61 [0.6–4.3]), grade 2 (3.68 [1.1–12.8]), and grade 3 or 4 (8.02 [0.6–108.3]) (P = .03 for the trend). In univariate analysis, there was a significant association between increasing steatosis grade (P = .03), older age (56 years vs 49 years; P < .02), higher aspartate aminotransferase (122.5 U/L vs 91.5 U/L; P = .005), higher alanine aminotransferase (95.8 U/L vs 57.2 U/L; P = .002), higher alpha‐fetoprotein (113.5 ng/mL vs 17.8 ng/mL; P < .001), lower median HCV RNA (239,000 IU/mL vs 496,500 IU/mL; P = .02), higher biologic MELD score (21.8 vs 20.3; P = .03), and risk of HCC. In multivariate analysis, age (P = .02), AFP (P = .007), and steatosis (P = .045) were significantly associated with HCC.CONCLUSIONS.In patients with HCV‐related cirrhosis, the presence of hepatic steatosis is independently associated with the development of hepatocellular carcinoma. These findings suggest that steatosis poses an additional risk for HCC and that increased vigilance should be practiced in surveillance of persons with both HCV and steatosis. Cancer 2007. © 2007 American Cancer Society.
Redefining pT3 renal cell carcinoma in the modern era
Authors: Margulis Vitaly , Tamboli Pheroze , Matin Surena F. , Meisner Matthew , Swanson David A. , Wood Christopher G. 
Published: May 2007

AbstractBACKGROUND.The 2002 American Joint Committee on Cancer (AJCC) tumor classification for renal cell carcinoma (RCC) does not take into account concomitant venous invasion and extrarenal tumor extension (ERE). In the current study, the authors evaluated the prognostic significance of venous tumor thrombus (VTT) and its extent, the presence and location of ERE, and a combination of both features on survival after the surgical management of patients with pathologic T3 (pT3) RCC.METHODS.With Institutional Review Board approval, the institutional nephrectomy database of 3470 patients treated at the University of Texas M. D. Anderson Cancer Center from 1990 to 2006 was searched for pT3 RCC patients who were treated with partial or radical nephrectomy. Patients with nonmetastatic, lymph node‐negative RCC and a minimum follow‐up of 6 months were included in the analysis.RESULTS.A total of 419 patients with pT3N0/NxM0 RCC and a mean follow‐up of 40.8 months met the study inclusion criteria. In multivariate Cox regression analyses, the 2002 AJCC primary tumor classification was not found to be an independent predictor of cancer‐specific mortality. A total of 211 patients with ERE only (50.4%) and 72 patients with VTT only (17.2%) were found to have a similar risk of death from RCC (hazards ratio [HR] of 1.018; P = .957), whereas 136 patients harboring both features (32.5%) were found to be significantly more likely to die from RCC (HR of 2.660; P < .001). The authors proposed a new primary tumor classification in which they grouped patients with both ERE and VTT (which was found to be an independent predictor of cancer‐specific survival) into a separate staging category, and demonstrated improved prognostic ability when compared with the 2002 AJCC classification (c indexes of 0.625 vs 0.580, respectively).CONCLUSIONS.The prognostic accuracy of the 2002 AJCC pT3 tumor classification can be improved by subclassifying patients with ERE only and those with VTT only into a prognostic category that is separate from patients with both ERE and VTT. Cancer 2007. © 2007 American Cancer Society.
Overexpression of vitamin D receptor indicates a good prognosis for cholangiocarcinoma
Authors: Seubwai Wunchana , Wongkham Chaisiri , Puapairoj Anucha , Khuntikeo Narong , Wongkham Sopit 
Published: May 2007

AbstractBACKGROUND.Up‐regulation of vitamin D receptor (VDR) expression has been shown in several tumors and is thought to represent an important endogenous response to tumor progression. The authors aimed to verify the expression of VDR and its clinical significance in histologically proven cholangiocarcinoma (CCA).METHODS.The antiproliferative activity of vitamin D3 on CCA cell lines was explored. The immunohistochemistry of 111 paraffin‐embedded CCA tissues showed that VDR expression gradually increased during CCA development. Normal bile duct epithelium rarely expresses VDR, whereas more than 74% of CCA tissues showed positive VDR staining, of which 40% were high. Approximately 80%–90%of CCA patients with papillary and well differentiated adenocarcinomas had positive VDR expression in tumor tissues, whereas 39% positive VDR expression was found in those with poorly differentiated CCAs (P < .001).RESULTS.Expression of VDR was shown to be compatible with an overall favorable prognosis for CCA. Treatment with 1,25(OH)2D3, an active metabolite of vitamin D3, in the CCA cell lines with high expression of VDR significantly reduced cell proliferation in a dose‐dependent manner. The effect was not demonstrated in the CCA cell lines that had lower VDR expression.CONCLUSIONS.These data indicated an active role for VDR in mediating the antiproliferative effects of 1,25(OH)2D3 in CCA cell lines. VDR expression may constitute an important prerequisite for using vitamin D and/or its analogs in the treatment of CCA. Investigation of a mechanism by which VDR and its ligand mediate these processes is needed to provide the basis for the potential use of this hormone and its derivatives in the prevention and treatment of CCA. Cancer 2007. © 2007 American Cancer Society.
Need for closure and competition in intergroup conflicts: experimental evidence for the mitigating effect of accessible conflict‐schemas
Authors: de Zavala Agnieszka Golec , Federico Christopher M. , Cisłak Aleksandra , Sigger Jonathan 
Published: May 2007

AbstractThree experimental studies demonstrate that momentarily accessible conflict‐schemas moderate the relationship between need for closure and conflict‐strategy preferences, with the relationship between a high need for closure and increased competitiveness reduced to non‐significance when a cooperative conflict‐schema is made salient but strengthened when a hostile one is activated. Study 1 manipulated the accessibility of competitive versus cooperative conflict‐schemas using different descriptions of a contemporary political conflict, while Studies 2 and 3 manipulated conflict‐schema accessibility using primes embedded in an ostensibly unrelated lexical decision task. Together, the present studies provide a strong pattern of experimental support for the moderating effect of conflict‐schema accessibility suggested by earlier correlational studies. The implications for conflict reduction are discussed. Copyright © 2007 John Wiley & Sons, Ltd.
Optimization of a pressurized liquid junction nanoelectrospray interface between CE and MS for reliable proteomic analysis
Authors: Kusý Petr , Klepárník Karel , Aturki Zeineb , Fanali Salvatore , Foret František 
Published: May 2007

AbstractA pressurized liquid junction nanoelectrospray interface was designed and optimized for reliable on‐line CE‐MS coupling. The system was constructed as an integrated device for highly sensitive and selective analyses of proteins and peptides with the separation and spray capillaries fixed in a pressurized spray liquid reservoir equipped with the electrode for connection of the electrospray potential. The electrode chamber on the injection side of the separation capillary and the spray liquid reservoir were pneumatically connected by a Teflon tube filled with pressurized nitrogen. This arrangement provided precisely counterbalanced pressures at the inlet and outlet of the separation capillary. The pressure control system was driven by an electrically operated valve and maintained the optimum flow rate for the electrospray stability. All parts of the interface being in contact with the CEBGE, spray liquid and/or sample were made of glass or Teflon. The use of these materials minimized the electrospray chemical noise often caused by plastic softeners or material degradation. During optimization, the transfer of the separated zones between the separation and electrospray capillaries was monitored by UV absorbance and contactless conductivity detectors placed at the outlet of the separation capillary and inlet of the electrospray tip, respectively. This arrangement allowed independent monitoring of the effects of pressure, CE voltage and geometry of the liquid junction on the spreading and dilution of the separated zones after passage through the interface.
An evaluation of parsimony for microbial risk assessment models
Authors: Soller Jeffrey A. , Eisenberg Joseph N. S. 
Published: May 2007

AbstractMicrobial risk assessment (MRA) is a process that evaluates the likelihood of adverse human health effects following exposure to a medium in which pathogens are present. Several different classes of models are available to quantitatively characterize risks to human health from exposure to pathogens. Herein, we consider the question of parsimony for specific realizations of representative static and dynamic MRA models and identify conditions under which the more complex dynamic model provides sufficient additional insight to justify the added modeling complexity. To address this question, a standard static individual‐level risk model is compared to a deterministic dynamic population‐level model that explicitly includes secondary transmission and immunity processes. Exposure parameters are based on a scenario defined by human exposure to pathogens in reclaimed water. A sensitivity analysis is implemented to identify conditions under which static and dynamic models yield substantially different results. Under low risk conditions, defined by a combination of exposure levels and infectivity of the pathogen, the simpler static model provides satisfactory risk estimates. The approach presented here provides a basis for model selection for a broad range of MRA applications. Copyright © 2007 John Wiley & Sons, Ltd.
Sequential haplotype scan methods for association analysis
Authors: Yu Zhaoxia , Schaid Daniel J. 
Published: May 2007

AbstractMulti‐locus association analyses, including haplotype‐based analyses, can sometimes provide greater power than single‐locus analyses for detecting disease susceptibility loci. This potential gain, however, can be compromised by the large number of degrees of freedom caused by irrelevant markers. Exhaustive search for the optimal set of markers might be possible for a small number of markers, yet it is computationally inefficient. In this paper, we present a sequential haplotype scan method to search for combinations of adjacent markers that are jointly associated with disease status. When evaluating each marker, we add markers close to it in a sequential manner: a marker is added if its contribution to the haplotype association with disease is warranted, conditional on current haplotypes. This conditional evaluation is based on the well‐known Mantel‐Haenszel statistic. We propose two permutation based methods to evaluate the growing haplotypes: a haplotype method for the combined markers, and a summary method that sums conditional statistics. We compared our proposed methods, the single‐locus method, and a sliding window method using simulated data. We also applied our sequential haplotype scan algorithm to experimental data for CYP2D6. The results indicate that the sequential scan procedure can identify a set of adjacent markers whose haplotypes might have strong genetic effects or be in linkage disequilibrium with disease predisposing variants. As a result, our methods can achieve greater power than the single‐locus method, yet is much more computationally efficient than sliding window methods.Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
A dictionary model for haplotyping, genotype calling, and association testing
Authors: Ayers Kristin L. , Sabatti Chiara , Lange Kenneth 
Published: May 2007

AbstractWe propose a new method for haplotyping, genotype calling, and association testing based on a dictionary model for haplotypes. In this framework, a haplotype arises as a concatenation of conserved haplotype segments, drawn from a predefined dictionary according to segment specific probabilities. The observed data consist of unphased multimarker genotypes gathered on a random sample of unrelated individuals. These genotypes are subject to mutation, genotyping errors, and missing data. The true pair of haplotypes corresponding to a person's multimarker genotype is reconstructed using a Markov chain that visits haplotype pairs according to their posterior probabilities. Our implementation of the chain alternates Gibbs steps, which rearrange the phase of a single marker, and Metropolis steps, which swap maternal and paternal haplotypes from a given maker onward. Output of the chain include the most likely haplotype pairs, the most likely genotypes at each marker, and the expected number of occurrences of each haplotype segment. Reconstruction accuracy is comparable to that achieved by the best existing algorithms. More importantly, the dictionary model yields expected counts of conserved haplotype segments. These imputed counts can serve as genetic predictors in association studies, as we illustrate by examples on cystic fibrosis, Friedreich's ataxia, and angiotensin‐I converting enzyme levels. Genet. Epidemiol. © 2007 Wiley‐Liss, Inc.
Caspase‐3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation
Authors: Acarin Laia , Villapol Sonia , Faiz Maryam , Rohn Troy T. , Castellano Bernardo , González Berta 
Published: May 2007

AbstractCaspase‐3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non‐apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase‐3 was analyzed following excitotoxic damage in postnatal rats to determine if its presence is associated with apoptotic cell death, cell proliferation, or cytoskeletal remodeling. A well‐characterized in vivo model of excitotoxicity was studied, where damage was induced by intracortical injection of N‐methyl‐D‐asparate (NMDA) in postnatal day 9 rats. Our results demonstrate that cleaved caspase‐3 was mainly observed in the nucleus of activated astrocytes in the lesioned hemisphere as early as 4 h postlesion and persisted until the glial scar was formed at 7–14 days, and it was not associated with TUNEL labeling. Caspase‐3 enzymatic activity was detected at 10 h and 1 day postlesion in astrocytes, and co‐localized with caspase‐cleaved fragments of glial fibrillary acidic protein (CCP‐GFAP). However, at longer survival times, when astroglial hypertrophy was observed, astroglial caspase‐3 did not generally correlate with GFAP cleavage, but instead was associated with de novo expression of vimentin. Moreover, astroglial caspase‐3 cleavage was not associated with BrdU incorporation. These results provide further evidence for a nontraditional role of caspases in cellular function that is independent of cell death and suggest that caspase activation is important for astroglial cytoskeleton remodeling following cellular injury. © 2007 Wiley‐Liss, Inc.
Predicting 6‐week treatment response to escitalopram pharmacotherapy in late‐life major depressive disorder
Authors: Saghafi Ramin , Brown Charlotte , Butters Meryl A. , Cyranowski Jill , Dew Mary Amanda , Frank Ellen , Gildengers Ariel , Karp Jordan F. , Lenze Eric J. , Lotrich Francis , Martire Lynn , Mazumdar Sati , Miller Mark D. , Mulsant Benoit H. , Weber Elizabeth , Whyte Ellen , Morse Jennifer , Stack Jacqueline , Houck Patricia R. , Bensasi Salem , Reynolds Charles F. 
Published: May 2007

AbstractObjectiveApproximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first‐line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non‐response to escitalopram monotherapy of unipolar MDD in later life.MethodsOne hundred and seventy‐five patients aged 60 and older were assessed at baseline on demographic variables, depression severity, hopelessness, anxiety, cognitive functioning, co‐existing medical illness burden, social support, and quality of life (disability). Subjects received 10 mg/d of open‐label escitalopram and were divided into full (n = 55; 31%), partial (n = 75; 42.9%), and non‐responder (n = 45; 25.7%) groups based on Hamilton depression scores at week 6. Univariate followed by multivariate analyses tested for differences between the three groups.ResultsNon‐responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders, more disabled, and with lower self‐esteem than full responders. In general partial responders resembled full responders more than they resembled non‐responders. In multivariate models, more severe anxiety symptoms (both psychological and somatic) and lower self‐esteem predicted worse response status at 6 weeks.ConclusionAmong treatment‐seeking elderly persons with MDD, higher anxiety symptoms and lower self‐esteem predict poorer response after six weeks of escitalopram treatment. Copyright © 2007 John Wiley & Sons, Ltd.
Public attitudes to life‐sustaining treatments and euthanasia in dementia
Authors: Williams Nia , Dunford Charlotte , Knowles Alice , Warner James 
Published: May 2007

AbstractBackgroundIssues surrounding end of life care, such as how aggressively to treat life threatening medical conditions in patients with dementia and when, if ever, to withhold or withdraw treatment require further scrutiny and debate.MethodsWe conducted a cross‐sectional survey to elicit the views of the general public on euthanasia and life‐sustaining treatments in the face of dementia.ResultsSeven hundred and twenty‐five members of the general public completed this questionnaire throughout London and the South East. In the face of severe dementia, less than 40% of respondents would wish to be resuscitated after a heart attack, nearly three‐quarters wanted to be allowed to die passively and almost 60% agreed with physician assisted suicide. Respondents were more likely to be in favour of life‐sustaining treatments for their partner than for themselves and the opposite was true regarding euthanasia. White respondents were significantly more likely to refuse life‐sustaining treatment and to agree to euthanasia compared with black and Asian respondents.ConclusionOur survey suggests that a large proportion of the UK general public do not wish for life‐sustaining treatments if they were to become demented and the majority agreed with various forms of euthanasia. Copyright © 2007 John Wiley & Sons, Ltd.