bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated External Defibrillator Program Does Not Impair Cardiopulmonary Resuscitation Initiation in the Public Access Defibrillation Trial
Authors: Hedges Jerris R. , Sehra Ruchir , Van Zile Jonathan W. , Anton Andrew R. , Bosken Lois A. , O'Connor Robert E. , Moore Richard , Powell Judy L. , McBurnie Mary Ann 
Published: April 2006

Abstract
Objectives:
To evaluate whether automated external defibrillator (AED) training and AED availability affected the response of volunteer rescuers and performance of cardiopulmonary resuscitation (CPR) in presumed out‐of‐hospital cardiac arrest (OOH‐CA) during the multicenter Public Access Defibrillation Trial.
Methods:
The Public Access Defibrillation Trial recruited 1,260 facilities in 24 North American regional sites to participate in a trial addressing survival from OOH‐CA when AED training and availability were added to a volunteer‐based emergency response team. Volunteers at each facility were trained to perform either CPR alone (CPR) or CPR in conjunction with AED use (CPR+AED) according to randomized assignments. This study reports the frequency of response and initiation of CPR actions (chest compressions and/or ventilations) by volunteers in the CPR and CPR+AED study groups.
Results:
A total of 314 presumed OOH‐CA episodes occurred in CPR facilities, and 308 occurred in CPR+AED facilities. The volunteers were matched well for age, gender, and other features. Overall, ventilations (23.1% vs. 13.1%), chest compressions (24.4% vs. 12.1%), and both actions (19.8% vs. 10.5%; all p < 0.05) were more commonly performed in OOH‐CA cases in the CPR+AED group. However, when only OOH‐CA cases with volunteers responding were analyzed, the rates of CPR actions were similar. In the subgroup of CPR+AED cases with a responding volunteer, the AED was turned on for only 47% of cases. Volunteers initiated a CPR action more commonly when the AED was turned on (60.7% vs. 39.3%; p = 0.003).
Conclusions:
In the Public Access Defibrillation Trial, rates of CPR actions for presumed OOH‐CA victims were low but similar for CPR and CPR+AED responding volunteer rescuers. Factors associated with volunteer response, CPR action initiation, and AED activation warrant further investigation.
Reliability of a Core Competency Checklist Assessment in the Emergency Department: The Standardized Direct Observation Assessment Tool
Authors: Shayne Philip , Gallahue Fiona , Rinnert Stephan , Anderson Craig L. , Hern Gene , Katz Eric 
Published: April 2006

Objectives:
A Council of Emergency Medicine Residency Directors task force developed the Standardized Direct Observation Assessment Tool (SDOT), a 26‐item checklist assessment tool to evaluate Accreditation Council for Graduate Medical Education resident core competencies by direct observation. Each of the checklist items is assigned to one or more of five core competencies. The objective of this study was to test the interrater measurement properties of the SDOT instrument.
Methods:
Two videos of simulated patient–resident–attending physician encounters were produced. Academic emergency medicine faculty members not involved in the development of the form viewed the two encounters and completed the SDOT for each. Faculty demographic data were collected. Data were collected from 82 faculty members at 16 emergency medicine residency programs. The checklist items were used to generate a composite score for each core competency of patient care, medical knowledge, interpersonal and communication skills, professionalism, and systems‐based practice.
Results:
Univariate analysis demonstrated a high degree of agreement between evaluators in evaluating residents for both videos. Multivariate analysis found no differences in rating by faculty when examined by experience, academic title, site, or previous use of the SDOT.
Conclusions:
Faculty from 16 emergency medicine residency programs had a high interrater agreement when using the SDOT to evaluate resident core competency performance. This study did not test the validity of the tool. This data analysis is mainly descriptive, and scripted video scenarios may not approximate direct observation in the emergency department.
Comprehensive Analysis ofUGT1APolymorphisms Predictive for Pharmacokinetics and Treatment Outcome in Patients With Non–Small-Cell Lung Cancer Treated With Irinotecan and Cisplatin
Authors: Han Ji-Youn , Lim Hyeong-Seok , Shin Eun Soon , Yoo Yeon-Kyeong , Park Yong Hoon , Lee Jong-Eun , Jang In-Jin , Ho Lee Dae , Soo Lee Jin 
Published: April 2006

PurposeTo determine whether uridine diphosphate-glucuronosyltransferase 1A1, UGT1A7, and UGT1A9 polymorphisms affect the pharmacokinetics (PK) of irinotecan and treatment outcome of Korean patients with advanced non–small-cell lung cancer (NSCLC).MethodsEighty-one patients with advanced NSCLC were treated with irinotecan (80 mg/m2) on day 1 and 8 and cisplatin (60 mg/m2) on day 1 intravenously of each 3-week cycle. Genomic DNA was extracted from peripheral blood and genotyped using direct sequencing. We analyzed the association of UGT1A genotypes with irinotecan PK and clinical outcomes. All statistical tests were two-sided.ResultsIn genotype-PK association analysis, UGT1A1*6/*6 (n = 6), UGT1A7*3/*3 (n = 6), and UGT1A9-118(dT)9/9(n = 11) were associated with significantly lower area under the time-concentration curve (AUC) SN-38G to SN-38 (AUCSN-38G/AUCSN-38) ratio (P = .002, P = .009, and P = .001, respectively). In linkage disequilibrium analysis, the UGT1A7 variants were highly linked with the UGT1A1*6 (D′ = 0.85, r2= 0.63) and UGT1A9*22 (D′ = 0.95, r2= 0.88), which was substantiated in haplotype analysis. Patients with UGT1A1*6/*6 had lower tumor response and higher incidence of severe neutropenia. UGT1A9-118(dT)9/9also showed a trend for high incidence of severe diarrhea, but not tumor response. In survival analysis, patients with UGT1A1*6/*6 had significantly shorter progression-free survival (P = .001) and overall survival (P = .017).ConclusionThese findings suggest that UGT1A1*6 and UGT1A9*22 genotypes may be important for SN-38 glucuronidation and associate with irinotecan-related severe toxicity. Specifically, UGT1A1*6 might be useful for predicting tumor response and survival outcome of Korean patients with NSCLC treated with irinotecan-based chemotherapy.
Epigenetic Modification of the X Chromosome Influences Susceptibility to Polycystic Ovary Syndrome
Authors: Hickey T. E. , Legro R. S. , Norman R. J. 
Published: April 2006

Abstract
Context: The cause of polycystic ovary syndrome (PCOS) is unknown, although genetic and environmental influences are clearly implicated. Some genetic studies have suggested the involvement of X-linked genes in PCOS, but the influence of X chromosome inactivation (XCI) on manifestation of this disorder has not previously been examined.
Objective: The objective of the study was to test the null hypothesis that XCI has no influence on clinical presentation of PCOS.
Design: We examined patterns of XCI between sister pairs with the same genotype at a polymorphic locus on the X chromosome in families with PCOS.
Setting: The study was conducted at a private practice.
Participants: PCOS was defined as hyperandrogenemia with chronic anovulation. Forty families were studied in which DNA was obtained from at least one parent, the proband, and one sister that could be accurately diagnosed as being affected or unaffected.
Main Outcome Measure(s): Relative expression of two X-linked alleles was determined, and the ratio of one to the other represented the pattern of XCI.
Results: The statistical odds on a different clinical presentation between sisters was approximately 29 times higher in sister pairs with different patterns of XCI, compared with sister pairs with the same pattern of XCI (odds ratio 28.9; 95% confidence interval 4.0–206; P = 0.0008).
Conclusions: This study provides evidence to refute the null hypothesis and propose a closer inspection of X-linked genes in PCOS, one in which both genotype and epigenotype are considered. Environmental determinants of PCOS may alter clinical presentation via epigenetic modifications, which currently remain undetected in traditional genetic analyses.
Surgical Remission of Pituitary Adenomas Confined to the Neurohypophysis in Cushing’s Disease
Authors: Weil Robert J. , Vortmeyer Alexander O. , Nieman Lynnette K. , DeVroom Hetty L. , Wanebo John , Oldfield Edward H. 
Published: April 2006

Abstract
Context: Partial or total removal of the pituitary cures 60–80% of patients with Cushing’s disease (CD) in whom an adenoma cannot be identified at surgery. Many patients who fail complete or partial hypophysectomy are cured by sellar and parasellar irradiation.
Design/Patients: As part of a series of prospective studies of CD, we identified 12 patients (34.5 ± 19.9 yr; 11 females; four children) with tumors located completely within the neurohypophysis among 730 patients undergoing surgery for CD.
Setting: The study was conducted at a tertiary referral center at a clinical research hospital.
Results: All 12 patients had clinical and biochemically defined CD. Tumor was visible at surgery in 11 patients; all 12 tumors were positive for ACTH by immunohistochemistry. Two tumors were excised at repeat surgery because of persistent hypercortisolism within 14 d of negative exploration of the adenohypophysis. There were no long-term complications. At follow-up of 71.9 ± 34.2 months (range, 30–138 months), all patients are in remission of CD. Adult patients have had significant improvement in weight and body mass indices, with restoration of normal menses in all women. In the four pediatric patients, height, weight, and body mass indices have been restored toward normal by surgical remission of CD. Hypopituitarism or long-term neurohypophysial dysfunction has not occurred.
Conclusion: We report a new subset of patients with CD, ACTH-secreting adenomas that arise wholly within the posterior lobe of the pituitary gland. In cases of CD in which an adenoma is not identified in the adenohypophysis and in patients with persistent hypercortisolism after complete or partial excision of the anterior lobe, tumor within the neurohypophysis should be considered; selective adenomectomy of a neurohypophyseal, ACTH-secreting tumor can produce long-term remission.
Poly(N-isopropylacrylamide) Microparticle Formation in Water by Infrared Laser-Induced Photo-Thermal Phase Transition
Authors: Ishikawa Masazumi , Misawa Hiroaki , Kitamura Noboru , Masuhara Hiroshi 
Published: April 2006

Abstract
Irradiation of a focused 1064 nm laser beam to an aqueous poly(N-isopropylacrylamide) solution resulted in the reversible microparticle (diameter ≈ 7 μm) formation through local heating of water by the laser beam and subsequent phase transition of the polymer solution. The microparticle produced was simultaneously manipulated in three-dimensional space by the incident 1064 nm laser beam.
Giant Metal-Insulator-Metal Transition Induced by Selective Deuteration of the Molecular Conductor, (DMe-DCNQI)2Cu (DMe-DCNQI = 2,5-dimethyl-N,N′-dicyanoquinonediimine)
Authors: Aonuma Shuji , Sawa Hiroshi , Kato Reizo , Kobayashi Hayao 
Published: April 2006

Abstract
The Cu salts of selectively deuterated DMe-DCNQI’s were prepared, and the electrical conductivities were examined. By deuteration of two hydrogens of the methyl groups, a drastic metal-insulator-metal transition was induced for the first time in a non-alloy system at ambient pressure. On the other hand, deuteration of two ring hydrogens or one methyl hydrogen did not affect the stability of a metallic state down to 4.2 K. These phenomena are discussed in terms of the “chemical pressure” effect.
Effect of Substituents on the Equilibrium between Trans and Perpendicular Conformers in the Triplet Excited State of Substituted Styrylpyrenes
Authors: Kikuchi Yoshihiko , Okamoto Hiroaki , Arai Tatsuo , Tokumaru Katsumi 
Published: April 2006

Abstract
In the equilibrium between trans (3t*) and perpendicular (3p*) conformers in the triplet excited state of 1-styrylpyrenes, substitution by electron-accepting groups at the para-position of styryl group more effectively stabilizes 3t* than 3p*, therefore affording very high composition of their trans isomers at the photostationary state.
Efficient Electrochemical Reduction of N2 to NH3 Catalyzed by Lithium
Authors: Tsuneto Akira , Kudo Akihiko , Sakata Tadayoshi 
Published: April 2006

Abstract
A novel electrochemical N2 reduction system is reported. Ammonia was formed with a significant current efficiency (up to 8%) by a simple electrolysis, which was conducted under N2 now (1 atm) in a solution of LiClO4 (0.2 M) in tetrahydrofuran/ethanol (99:1 v/v) on some metal electrodes. Higher current efficiency (48.7%) for NH3 formation was achieved when the electrolysis was conducted under high pressure of N2 (50 atm). Lithium seemed to act as a catalyst (mediator) in this electrochemical system.
The Strange Attractor of Chaotic Voltage Oscillation in Water-Oil-Water Liquid Membrane Containing Cationic Surfactant
Authors: Takahashi Koichi , Yasukawa Hideaki , Sugimura Takaaki 
Published: April 2006

Abstract
A strange attractor of chaotic voltage oscillation caused by micelle formation of cationic surfactant in the water-oil-water liquid membrane was found. The topology of the strange attractor is the mirror image of the Rössler’s attractor. The correlation dimension of the attractor is 2.4.
Precursor of Carthamin, A Constituent of Safflower
Authors: Kumazawa Toshihiro , Sato Shingo , Kanenari Daisuke , Kunimatsu Akira , Hirose Ryoji , Matsuba Shigeru , Obara Heitaro , Suzuki Masanobu , Sato Masaya , Onodera Jun-ichi 
Published: April 2006

Abstract
Precursor of Carthamin was isolated from the flowers of Carthamin tinctorius L. (Safflower) and its structure was characterized as 1 on the basis of spectroscopic analysis and by comparing its properties with those of synthetic model compound.
Dehydroepiandrosterone sulphate interferes with the Abbott Architect direct immunoassay for testosterone
Authors: Warner M H , Kane J W , Atkin S L , Kilpatrick E S 
Published: April 2006

Background: There are known difficulties in measuring testosterone in women using 'direct' (non-extraction) immunoassays. The positive bias encountered in many of these assays has been attributed to an unidentified interfering substance. We have evaluated the potential for dehydroepiandrosterone sulphate (DHEA-S) to cross-react in the Abbott Architect testosterone assay. Methods: Samples ( n = 81) from female patients who had DHEA-S, direct and extracted testosterone measured were examined retrospectively. Possible cross-reactivity was evaluated by spiking both testosterone free assay diluent and serum from a woman with exogenous DHEA-S. Results: The retrospective patient analysis of the data demonstrated a relationship between interference and DHEA-S ( r = 0.78, P - 0.0001). Spiking studies revealed a linear relationship between added DHEA-S and the measured testosterone concentration. Consistent with the retrospective study, for every 1 μmol/L increase in DHEA-S, 0.23 nmol/L of testosterone was measured in the diluent. Spiking DHEA-S into serum gave only a 0.12 nmol/L increase in measured testosterone for every 1 μmol/L rise in DHEA-S. Conclusion: DHEA-S cross-reacts in the Abbott Architect direct immunoassay for testosterone to a clinically significant effect. This cross-reactivity is likely to be responsible for much of the interference observed when measuring testosterone in women by this method.
Effect of plantain on therapeutic drug monitoring of digoxin and thirteen other common drugs
Authors: Dasgupta Amitava , Davis Bonnette , Wells Alice 
Published: April 2006

Introduction: Plantain, a herbal remedy, has been reported to interfere with therapeutic drug monitoring of digoxin. We evaluated three commercially available plantain products for potential interference with therapeutic drug monitoring of digoxin and 13 other common drugs. Method: Dry content of plantain capsule or plantain leaf was extracted with either methanol or ethanol:water (60:40 by volume), added to drug-free serum and apparent digoxin was measured by both fluorescence polarization immunoassay and microparticle enzyme immunoassay. Using immunoassays, we also measured apparent concentrations of 13 other drugs (tobramycin, procainamide, tricyclic antidepressants, quinidine, carbamazepine, phenytoin, theophylline, valproic acid, amikacin, gentamycin, phenobarbital, salicylate and acetaminophen [paracetamol]) due to the presence of plantain. In separate experiments, a serum pool prepared from patients receiving digoxin was further supplemented with plantain and observed digoxin values were compared with original digoxin concentration. The presence of any cardiac glycoside in plantain was also investigated using thin layer chromatography (TLC). Results: We observed no apparent digoxin in the presence of plantain in serum. Moreover, when aliquots of digoxin serum pool were supplemented with various amounts of plantain, the observed digoxin concentrations in the presence of plantain compared well with original digoxin concentration. TLC analysis did not show the presence of either digoxin or digitoxin in plantain products studied. Moreover, plantain did not affect immunoassay results of the 13 other drugs studied. Conclusions: The plantain products studied did not interfere with therapeutic drug monitoring of digoxin as well as 13 other commonly monitored drugs.
Residues Determining the Binding Specificity of Uncompetitive Inhibitors to Tissue-Nonspecific Alkaline Phosphatase
Authors: Kozlenkov Alexey , Le Du Marie Helene , Cuniasse Philippe , Ny Tor , Hoylaerts Marc F , Millán José Luis 
Published: April 2006

Abstract
Recent data have pointed to TNALP as a therapeutic target for soft-tissue ossification abnormalities. Here, we used mutagenesis, kinetic analysis, and computer modeling to identify the residues important for the binding of known ALP inhibitors to the TNALP active site. These data will enable drug design efforts aimed at developing improved specific TNALP inhibitors for therapeutic use.
Introduction: We have shown previously that the genetic ablation of tissue-nonspecific alkaline phosphatase (TNALP) function leads to amelioration of soft-tissue ossification in mouse models of osteoarthritis and ankylosis (i.e., Enpp1−/− and ank/ank mutant mice). We surmise that the pharmacologic inhibition of TNALP activity represents a viable therapeutic approach for these diseases. As a first step toward developing suitable TNALP therapeutics, we have now clarified the residues involved in binding well-known uncompetitive inhibitors to the TNALP active site.
Materials and Methods: We compared the modeled 3D structure of TNALP with the 3D structure of human placental alkaline phosphatase (PLALP) and identified the residues that differ between these isozymes within a 12 Å radius of the active site, because these isozymes differ significantly in inhibitor specificity. We then used site-directed mutagenesis to substitute TNALP residues to their respective homolog in PLALP. In addition, we mutagenized most of these residues in TNALP to Ala and the corresponding residues in PLALP to their TNALP homolog. All mutants were characterized for their sensitivity toward the uncompetitive inhibitors l-homoarginine (L-hArg), levamisole, theophylline, and L-phenylalanine.
Results and Conclusions: We found that the identity of residue 108 in TNALP largely determines the specificity of inhibition by L-hArg. The conserved Tyr-371 is also necessary for binding of L-hArg. In contrast, the binding of levamisole to TNALP is mostly dependent on His-434 and Tyr-371, but not on residues 108 or 109. The main determinant of sensitivity to theophylline is His-434. Thus, we have clarified the location of the binding sites for all three TNALP inhibitors, and we have also been able to exchange inhibitor specificities between TNALP and PLALP. These data will enable drug design efforts aimed at developing improved, selective, and drug-like TNALP inhibitors for therapeutic use.
Secreted Frizzled-Related Protein-1 Inhibits RANKL-Dependent Osteoclast Formation
Authors: Häusler Karl D , Horwood Nicole J , Chuman Yoshiro , Fisher Jane L , Ellis Jennifer , Martin T John , Rubin Jeffrey S , Gillespie Matthew T 
Published: April 2006

Abstract
We determined that sFRP-1 mRNA was differentially expressed by osteoblast/stromal cell lines and that sFRP-1 neutralizing antibodies and siRNA complementary to sFRP-1 coding sequence enhanced, while recombinant sFRP-1 inhibited, osteoclast formation. In studying the mechanism of action for sFRP-1, we found that sFRP-1 could bind recombinant RANKL. These results suggest potential cross-talk between Wnt and RANKL pathways.
Introduction: Osteoclast formation in normal bone remodeling requires the presence of osteoblast lineage cells that express RANKL and macrophage-colony-stimulating factor (M-CSF), which interact with their cognate receptors on the osteoclast precursor. We identified secreted Frizzled-related protein-1 (sFRP-1), which is known to bind to Wnt and inhibit the Wnt signaling pathway, as an osteoblast-derived factor that impinges on osteoclast formation and activity.
Materials and Methods: Differential display of mRNA from osteoblast lineage cell lines established sFRP-1 to be highly expressed in an osteoclast supporting cell line. sFRP-1 expression in bone was determined by in situ hybridization, and the effects of sFRP-1 on osteoclast formation were determined using a neutralizing antibody, siRNA, for sFRP-1 and recombinant protein.
Results: In situ hybridization revealed sFRP-1 mRNA expression in osteoblasts and chondrocytes in murine bone. sFRP-1 mRNA expression could be elevated in calvarial primary osteoblasts in response to prostaglandin E2 (PGE2) or interleukin (IL)-11, whereas many other osteotropic agents (e.g., IL-1, IL-6, calcitrol, parathyroid hormone) were without any effect. In vitro assays of osteoclast formation established sFRP-1 to be an inhibitor of osteoclast formation. Neutralizing antibodies against sFRP-1 enhanced TRACP+ mononuclear and multinuclear osteoclast formation (3- and 2-fold, respectively) in co-cultures of murine osteoblasts with spleen cells, whereas siRNA complementary to sFRP-1 coding sequence significantly enhanced osteoclast formation in co-cultures of KUSA O (osteoblast/stromal cell line) and bone marrow cells, cultured in the presence of PGE2 and 1,25(OH)2 vitamin D3. Recombinant sFRP-1 dose-dependently inhibited osteoclast formation in osteoblast/spleen co-cultures, RANKL + M-CSF-treated splenic cultures, and RANKL-treated RAW264.7 cell cultures, indicating a direct action of sFRP-1 on hematopoietic cells. Consistent with this, sFRP-1 was found to bind to RANKL in ELISAs.
Conclusion: sFRP-1 is expressed by osteoblasts and inhibits osteoclast formation. While sFRP-1 activity might involve the blocking of endogenous Wnt signaling, our results suggest that, alternatively, it could be because of direct binding to RANKL. This study describes a new mechanism whereby osteoblasts regulate osteoclastogenesis through the expression and release of sFRP-1.