bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic RGD Peptidomimetics Containing Bifunctional Diketopiperazine Scaffolds as New Potent Integrin Ligands
Authors: Marchini Mattia , Mingozzi Michele , Colombo Raffaele , Guzzetti Ileana , Belvisi Laura , Vasile Francesca , Potenza Donatella , Piarulli Umberto , Arosio Daniela , Gennari Cesare 
Published: April 2012

AbstractThe synthesis of eight bifunctional diketopiperazine (DKP) scaffolds is described; these were formally derived from 2,3‐diaminopropionic acid and aspartic acid (DKP‐1–DKP‐7) or glutamic acid (DKP‐8) and feature an amine and a carboxylic acid functional group. The scaffolds differ in the configuration at the two stereocenters and the substitution at the diketopiperazinic nitrogen atoms. The bifunctional diketopiperazines were introduced into eight cyclic peptidomimetics containing the Arg‐Gly‐Asp (RGD) sequence. The resulting RGD peptidomimetics were screened for their ability to inhibit biotinylated vitronectin binding to the purified integrins αvβ3 and αvβ5, which are involved in tumor angiogenesis. Nanomolar IC50 values were obtained for the RGD peptidomimetics derived from trans DKP scaffolds (DKP‐2–DKP‐8). Conformational studies of the cyclic RGD peptidomimetics by 1H NMR spectroscopy experiments (VT‐NMR and NOESY spectroscopy) in aqueous solution and Monte Carlo/Stochastic Dynamics (MC/SD) simulations revealed that the highest affinity ligands display well‐defined preferred conformations featuring intramolecular hydrogen‐bonded turn motifs and an extended arrangement of the RGD sequence [Cβ(Arg)Cβ(Asp) average distance ≥8.8 Å]. Docking studies were performed, starting from the representative conformations obtained from the MC/SD simulations and taking as a reference model the crystal structure of the extracellular segment of integrin αvβ3 complexed with the cyclic pentapeptide, Cilengitide. The highest affinity ligands produced top‐ranked poses conserving all the important interactions of the X‐ray complex.
Stereoselective metabolism of tetrahydropalmatine enantiomers in rat liver microsomes
Authors: Zhao Ming , Li Li‐Ping , Sun Dong‐Li , Sun Si‐Yuan , Huang Shan‐Ding , Zeng Su , Jiang Hui‐Di 
Published: April 2012

AbstractTetrahydropalmatine (THP), with one chiral center, is an active alkaloid ingredient in Rhizoma Corydalis. The aim of the present paper is to study whether THP enantiomers are metabolized stereoselectively in rat, mouse, dog, and monkey liver microsomes, and then, to elucidate which Cytochrome P450 (CYP) isoforms are predominately responsible for the stereoselective metabolism of THP enantiomers in rat liver microsomes (RLM). The results demonstrated that (+)‐THP was preferentially metabolized by liver microsomes from rats, mice, dogs, and monkeys, and the intrinsic clearance (Clint) ratios of (+)‐THP to (−)‐THP were 2.66, 2.85, 4.24, and 1.67, respectively. Compared with the metabolism in untreated RLM, the metabolism of (−)‐THP and (+)‐THP was significantly increased in dexamethasone (Dex)‐induced and β‐naphthoflavone (β‐NF)‐induced RLM; meanwhile, theClintratios of (+)‐THP to (−)‐THP in Dex‐induced and β‐NF‐induced RLM were 5.74 and 0.81, respectively. Ketoconazole had stronger inhibitory effect on (+)‐THP than (−)‐THP, whereas fluvoxamine had stronger effect on (−)‐THP in untreated and Dex‐induced or β‐NF‐induced RLM. The results suggested that THP enantiomers were predominately metabolized by CYP3A1/2 and CYP1A2 in RLM, and CYP3A1/2 preferred to metabolize (+)‐THP, whereas CYP1A2 preferred (−)‐THP.Chirality 24:368–373, 2012. © 2012 Wiley Periodicals, Inc.
A fluorescent chiral chemosensor for the recognition of the two enantiomers of chiral carboxylates
Authors: Li Yinan , Tamilavan Vellaiappillai , Hyun Myung Ho 
Published: April 2012

AbstractA new 7‐nitrobenz‐2‐oxa‐1,3‐diazole (NBD)‐based fluorescent chiral chemosensor (NBD‐1) was prepared and applied to the recognition of the two enantiomers of the tetrabutylammonium salts of N‐t‐Boc‐α‐amino acids and chiral carboxylic acids including naproxen. In particular, the chiral recognition by the new fluorescent chiral chemosensor for the two enantiomers of N‐t‐Boc‐threonine (tetrabutylammonium salt) was quite excellent, the Stern‐Volmer constant ratio (KD/KL) for the two enantiomers being as high as 4.89. Chirality 24:406–411, 2012. © 2012 Wiley Periodicals, Inc.
Development of Selective Estrogen Receptor Modulator (SERM)‐Like Activity Through an Indirect Mechanism of Estrogen Receptor Antagonism: Defining the Binding Mode of 7‐Oxabicyclo[2.2.1]hept‐5‐ene Scaffold Core Ligands
Authors: Zheng Yangfan , Zhu Manghong , Srinivasan Sathish , Nwachukwu Jerome C. , Cavett Valerie , Min Jian , Carlson Kathryn E. , Wang Pengcheng , Dong Chune , Katzenellenbogen John A. , Nettles Kendall W. , Zhou Hai‐Bing 
Published: April 2012

AbstractPreviously, we discovered estrogen receptor (ER) ligands with a novel three‐dimensional oxabicyclo[2.2.1]heptene core scaffold and good ER binding affinity act as partial agonists via small alkyl ester substitutions on the bicyclic core that indirectly modulate the critical switch helix in the ER ligand binding domain, helix 12, by interactions with helix 11. This contrasts with the mechanism of action of tamoxifen, which directly pushes helix 12 out of the conformation required for gene activation. We now report that a much larger substitution can be tolerated at this position of the bicyclic core scaffold, namely a phenyl sulfonate group, which defines a novel binding epitope for the estrogen receptor. We prepared an array of 14 oxabicycloheptene sulfonates, varying the phenyl sulfonate group. As with the parent compound, 5,6‐bis‐(4‐hydroxyphenyl)‐7‐oxabicyclo[2.2.1]hept‐5‐ene‐2‐sulfonic acid phenyl ester (OBHS), these compounds showed preferential affinity for ERα, and the disposition and size of the phenyl substituents were important determinants of the binding affinity and selectivity of these compounds, with those having ortho substituents giving the highest, and para substituents the lowest affinities for ERα. A few analogues exhibit ERα binding affinities that are comparable to or, in the case of the ortho‐chloro analogue, higher than that of OBHS itself. In cell‐based studies, we found several compounds with activity profiles comparable to tamoxifen, but acting entirely as indirect antagonists, allosterically interfering with recruitment of coactivator proteins to the receptor. Thus, the OBHS binding epitope represents a novel approach to the development of estrogen receptor antagonists via an indirect mechanism of antagonism.
Serum autoantibodies to pancreatic cancer antigens as biomarkers of pancreatic cancer in a San Francisco Bay Area case–control study
Authors: Bracci Paige M. , Zhou Mi , Young Scott , Wiemels Joseph 
Published: April 2012

AbstractBACKGROUND:Screening and early diagnosis tools are lacking for pancreatic adenocarcinoma; most patients are diagnosed with metastatic disease. Autoantibodies to tumor‐associated antigens (TAAs) can be present months to years before diagnosis and hold promise as biomarkers for early detection.METHODS:TAAs to pancreatic cancer autoantibodies CTDSP1 (carboxy‐terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1), MAPK9 (mitogen‐activated protein kinase 9), and NR2E3 (nuclear receptor subfamily 2, group E, member 3), which were identified as potentially promising biomarkers in exploratory studies, were evaluated in serum from participants (300 cases, 300 controls) in a population‐based case–control pancreatic cancer study in the San Francisco Bay Area. Patients were identified through cancer registry rapid case ascertainment, newly diagnosed from 1995 to 1999 and followed up through 2008. Autoantibody levels were analyzed as continuous and grouped (quartiles) variables. Multivariable unconditional logistic regression was used to compute odds ratios (ORs) as estimates of autoantibody levels associated with disease status. Kaplan‐Meier product limit estimates and multivariable Cox proportional hazards regression were used to assess autoantibody levels associated with case survival duration.RESULTS:Cases had higher levels of CTDSP1 (P = .004), MAPK9 (P = .0002), and NR2E3 (P ≤ .0001) autoantibodies than controls (fourth vs first quartile: CTDSP1 OR = 1.7, MAPK9 OR = 2.5, NR2E3 OR = 4.0). High body mass index and tobacco use were associated with levels in controls but were not statistical confounders. High CTDSP1 levels were somewhat associated with better survival (hazard ratio = 0.77, P = .07).CONCLUSIONS:Combined with previous results, this study contributes evidence that cancer‐related host immune‐response factors may be useful diagnostic screening tools and prognostic indicators for pancreatic cancer. Further studies are needed to critically assess the value of autoantibody panels to TAAs in diagnostic screening, prognosis, and immunotherapy of pancreatic and other cancers. Cancer 2012. © 2012 American Cancer Society.
Measuring psychosocial distress and parenting concerns among adults with cancer
Authors: Muriel Anna C. , Moore Cynthia W. , Baer Lee , Park Elyse R. , Kornblith Alice B. , Pirl William , Prigerson Holly , Ing Jennifer , Rauch Paula K. 
Published: April 2012

AbstractBACKGROUND:A 2‐phase, mixed methods study was conducted to develop a Parenting Concerns Questionnaire (PCQ) for adults with cancer. Limited information about this area of psychosocial distress highlights the need for a measurement tool that can identify adult oncology patients with heightened parenting concerns who could benefit from additional intervention.METHODS:Telephone focus groups were conducted with 16 oncology patients who had children 18 years old and younger. Group interview transcripts were analyzed to generate qualitative themes and candidate items for the PCQ. A 38‐item version of the questionnaire was completed by 173 oncology outpatients who had children 18 years old and under. Participants also completed the Distress Thermometer, HADS (Hospital Anxiety and Depression Scale), and FACT‐G (Functional Assessment of Cancer Therapy–General). Exploratory factor analyses revealed the emergence of 3 subscales of 5 items each, yielding a 15‐item questionnaire. Associations between total PCQ scores, standardized measures of distress, depression, anxiety, quality of life, and demographic and illness characteristics were examined.RESULTS:The 15‐item PCQ demonstrates good internal consistency (Cronbach's α = .83). PCQ scores were significantly associated (P < .01) with standardized measures of psychosocial distress (Distress Thermometer, HADS, and FACT‐G) in the expected directions. Higher PCQ scores were associated with female sex, single parenthood, metastatic or recurrent cancer, subjective understanding of incurable disease, comorbid chronic health condition, and current mental health treatment.CONCLUSIONS:The PCQ proved a reliable and valid measure of parenting distress among cancer patients, and thus merits further study. Cancer 2012. © 2012 American Cancer Society.
Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer
Authors: Xu Zhi , Zhu Haixia , Luk John M. , Wu Dongmei , Gu Dongying , Gong Weida , Tan Yongfei , Zhou Jianwei , Tang Jinhai , Zhang Zhengdong , Wang Meilin , Chen Jinfei 
Published: April 2012

AbstractBACKGROUND:Excessive reactive oxygen species (ROS) accumulation is a common phenomenon in carcinogenesis. However, the rationale behind ROS involvement in gastric cancer is unclear. In this study, the authors investigated the clinical significance of the single nucleotide polymorphisms (SNPs) of 2 ROS metabolic process‐related genes: superoxide dismutase 2 (SOD2) and glutathione S‐transferase π (GSTP1).METHODS:In total of 929 patients with gastric cancer who had definitive clinicopathologic and follow‐up data were collected. SOD2 reference SNP 4880 (rs4880) and GSTP1 rs1695 genotyping were examined in DNA samples extracted from paraffin‐embedded tumor tissue. Association of the 2 SNPs with each clinicopathologic feature was analyzed using the Pearson chi‐square test and the independent Student t test. Gastric cancer‐specific overall survival was analyzed using Kaplan‐Meier curves and log‐rank tests. Multivariate Cox regression analyses of these SNPs also were performed.RESULTS:The SOD2 rs4880 CT + CC genotypes were significantly associated with a high level of lymph node metastasis (P = .023), whereas the GSTP1 rs1695 GA + GG genotypes were significantly associated with larger tumor size (>5 cm long; P = .048). Kaplan‐Meier and Cox regression data indicated that the SOD2 rs4880 CT + CC genotypes alone (hazard ratio, 1.299; 95% confidence interval, 1.053‐1.603; P = .015) and the GSTP1 rs1695 GA + GG combined genotypes (hazard ratio, 1.496; 95% CI, 1.078‐2.074; P = .016) were independent predictors for overall survival.CONCLUSIONS:The current data, based on a large cohort (n = 929) of Chinese patients with gastric cancer, suggested that the presence of SOD2 rs4880 and GSTP1 rs1695 genotypes may contribute to cancer progression as well as tumor aggressiveness. The components of ROS metabolism pathways may be potential therapeutic targets for this aggressive malignancy. Cancer 2012. © 2012 American Cancer Society.
Clear cell adenocarcinoma of the lower urinary tract: Cytopathologic characteristics and differential diagnoses
Authors: Whitworth Scott A. , Subhawong Andrea P. , Rosenthal Dorothy L. , Ali Syed Z. 
Published: April 2012

AbstractClear cell adenocarcinomas (CCAs) of the lower urinary tract are uncommon neoplasms that may present in routinely processed urinary cytology specimens. There is only limited discussion of the features of CCA of the lower urinary tract in the cytology literature. The authors report a series of 3 cases of this unusual tumor, and correlate cytomorphology with histologic specimens. Two of the cases were diagnosed accurately as adenocarcinoma, and 1 case was diagnosed as atypical cells of undetermined significance. Cytomorphologic features included variably cellular samples with 3‐dimensional fragments of malignant cells that had enlarged nuclei, prominent nucleoli, and occasional hobnail configurations. Some fragments showed luminal formation with collections of neutrophils. CCA must be included in the differential diagnosis of malignant cells in a urinary specimen, particularly if the features are not typical of urothelial carcinoma. Other diagnostic considerations include metastatic adenocarcinomas, nephrogenic adenomas, and benign glandular lesions involving the bladder and urinary tract such as mullerianosis. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.
The Role of Effective Mass of Carrier in the Photocatalytic Behavior of Silver Halide‐Based Ag@AgX (X=Cl, Br, I): A Theoretical Study
Authors: Ma Xiangchao , Dai Ying , Guo Meng , Huang Baibiao 
Published: April 2012

AbstractThe recent discovery of Ag@AgX (X=Cl, Br, I) plasmonic photocatalysts motivates us to elucidate the origin of the higher photocatalytic performance compared to commonly used TiO2‐based materials. Herein, the electronic structure and effective masses of electrons at the conduction band minimum (CBM) and holes at the valence band maximum (VBM) are studied along different directions in the silver halide for the first time by means of first‐principles calculations. It is revealed that the smaller effective mass of electrons at the CBM in silver halides contributes to the higher photocatalytic performance. The remarkable dependence of the effective mass of holes on the direction and the anion of the silver halide explains well the experimental observed morphology and anion dependence of photocatalytic activities of Ag@AgX. The crystal field splitting of the Ag 4d bands in the valance band of silver halides is found to be a main factor leading to the large effective mass of the photogenerated holes and consequently to a weaker transfer ability. A new crystal design and exerting strain along the coordinate axis are proposed as solutions to decrease the effective mass of holes. The present work may be helpful in exploring this novel class of silver halide‐based photocatalysts.
Defects in MOFs: A Thorough Characterization
Authors: St. Petkov Petko , Vayssilov Georgi N. , Liu Jinxuan , Shekhah Osama , Wang Yuemin , Wöll Christof , Heine Thomas 
Published: April 2012

AbstractAs indicated by nearly perfect XRD data, but challenged by a two‐signal IR spectrum of CO guest molecules, it is confirmed by computer simulations and XPS experiments that the most defect‐free SURMOFs contain about 4 % defective Cu sites.
Novel APP/Aβ mutation K16N produces highly toxic heteromeric Aβ oligomers
Authors: Kaden Daniela , Harmeier Anja , Weise Christoph , Munter Lisa M. , Althoff Veit , Rost Benjamin R. , Hildebrand Peter W. , Schmitz Dietmar , Schaefer Michael , Lurz Rudi , Skodda Sabine , Yamamoto Raina , Arlt Sönke , Finckh Ulrich , Multhaup Gerd 
Published: April 2012

AbstractHere, we describe a novel missense mutation in the amyloid precursor protein (APP) causing a lysine‐to‐asparagine substitution at position 687 (APP770; herein, referred to as K16N according to amyloid‐β (Aβ) numbering) resulting in an early onset dementia with an autosomal dominant inheritance pattern. The K16N mutation is located exactly at the α‐secretase cleavage site and influences both APP and Aβ. First, due to the K16N mutation APP secretion is affected and a higher amount of Aβ peptides is being produced. Second, Aβ peptides carrying the K16N mutation are unique in that the peptide itself is not harmful to neuronal cells. Severe toxicity, however, is evident upon equimolar mixture of wt and mutant peptides, mimicking the heterozygous state of the subject. Furthermore, Aβ42 K16N inhibits fibril formation of Aβ42 wild‐type. Even more, Aβ42 K16N peptides are protected against clearance activity by the major Aβ‐degrading enzyme neprilysin. Thus the mutation characterized here harbours a combination of risk factors that synergistically may contribute to the development of early onset Alzheimer disease.
NERC matters: Vexatious PRC‐005
Authors: Carpentier Deborah 
Published: April 2012

AbstractNorth American Electric Reliability Corporation (NERC) reliability standard PRC‐005, which pertains to maintenance and testing of generation and transmission Protection Systems, is the “most violated standard of all time.”1 And notwithstanding NERC's efforts at providing guidance to improve compliance, the standard remains vexatious. Moreover, recent changes to PRC‐005 intended to provide clarity might increase the uncertainty as to how best to comply. At a minimum, registered entities will need to commit additional resources to revise their programs to satisfy these new requirements.
Cognitive impairment in primary ambulatory health care: pharmacotherapy and the use of potentially inappropriate medicine
Authors: Fiss Thomas , Thyrian Jochen René , Fendrich Konstanze , van den Berg Neeltje , Hoffmann Wolfgang 
Published: April 2012

ObjectiveDrug intake is associated with a risk of drug‐related problems, for example, the intake of potentially inappropriate medication (PIM), especially for cognitively impaired individuals. The proportion of PIM taken by immobile individuals, especially patients with suspicion of dementia in the AGnES studies (German: Arzt‐entlastende Gemeinde‐nahe E‐Health‐gestützte Systemische Intervention), and possible determinants were analyzed.MethodsIn a community‐based, prospective cohort study in the ambulatory healthcare sector, a sample of 342 patients aged ≥65 years were screened for dementia and received a home medication review. The screening for dementia was positive in 111 cases (32.5%). Data assessment included sociodemographic variables and medical diagnoses. The German PRISCUS list was used to detect PIM and drug–condition interactions.ResultsPotentially inappropriate medication in dementia was identified in 22 (19.8%) patients with suspicion of dementia. A multivariate binary logistic regression revealed that the number of drugs taken (one to four drugs: OR = 0.059; 95% CI 0.006–0.55, p = 0.0133; Ref.: >9 drugs) and female gender (OR = 10.362; 95% CI: 1.28–83.87) were risk factors for PIM intake in patient with suspicion of dementia.ConclusionsInappropriate medication use in a community‐based sample positively screened for dementia appears to be determined by sex and the number of drugs taken. The intake of fewer than five drugs and receiving support with regard to drug intake protects from the intake of PIM. Patients could benefit from medication management in a collaborative network of healthcare professionals. The implementation of systematic medication review and drug documentation should be extended and standardized in both research studies and routine primary health care. Copyright © 2012 John Wiley & Sons, Ltd.
Canadian breast implant cohort: Extended follow‐up of cancer incidence
Authors: Pan Sai Yi , Lavigne Eric , Holowaty Eric J. , Villeneuve Paul J. , Xie Lin , Morrison Howard , Brisson Jacques 
Published: April 2012

AbstractCosmetic breast implants are not associated with increased breast cancer incidence, but variations of risk according to implant characteristics are still poorly understood. As well, the assessment of cancer risk for sites other than breast needs to be clarified. The purpose of this study was to fill these research gaps. This study presents an extended analysis of 10 more years of follow‐up of a large Canadian cohort of women who received either cosmetic breast implants (n = 24,558) or other cosmetic surgery (15,893). Over 70% of the implant cohort was followed for over 20 years. Cancer incidence among implant women was compared to those of controls using multivariate Poisson models and the general female population using the standardized incidence ratios (SIRs). Women with breast implants had reduced rates of breast and endometrial cancers compared to other surgery women. Subglandular implants were associated to a reduced rate of breast cancer compared to submuscular implants [incidence rate ratio (IRR) = 0.78, 95% confidence interval (CI) = 0.63–0.96] and this reduction persisted over time. We observed a sevenfold increased rate (IRR = 7.36, 95% CI = 1.86–29.12) of breast cancer in the first 5 years after the date of surgery for polyurethane‐coated subglandular implant women but this IRR decreased progressively over time (p value for trend = 0.02). We also observed no increased risk of rarer forms of cancer among augmented women. A reduction in breast cancer incidence was observed for women with subglandular implants relative to women with submuscular implants. Possible increase of breast cancer incidence shortly after breast augmentation with polyurethane implants needs to be verified.