bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoter Hypermethylation Identifies Progression Risk in Bladder Cancer
Authors: Yates David R. , Rehman Ishtiaq , Abbod Maysam F. , Meuth Mark , Cross Simon S. , Linkens Derek A. , Hamdy Freddie C. , Catto James W.F. 
Published: April 2007

AbstractPurpose: New methods to accurately predict an individual tumor behavior are urgently required to improve the treatment of cancer. We previously found that promoter hypermethylation can be an accurate predictor of bladder cancer progression, but it is not cancer specific. Here, we investigate a panel of methylated loci in a prospectively collected cohort of bladder tumors to determine whether hypermethylation has a useful role in the management of patients with bladder cancer.Experimental Design: Quantitative methylation-specific PCR was done at 17 gene promoters, suspected to be associated with tumor progression, in 96 malignant and 30 normal urothelial samples. Statistical analysis and artificial intelligence techniques were used to interrogate the results.Results: Using log-rank analysis, five loci were associated with progression to more advanced disease (RASSF1a, E-cadherin, TNFSR25, EDNRB, and APC; P &lt; 0.05). Multivariate analysis revealed that the overall degree of methylation was more significantly associated with subsequent progression and death (Cox, P = 0.002) than tumor stage (Cox, P = 0.008). Neuro-fuzzy modeling confirmed that these five loci were those most associated with tumor progression. Epigenetic predictive models developed using artificial intelligence techniques identified the presence and timing of tumor progression with 97% specificity and 75% sensitivity.Conclusion: Promoter hypermethylation seems a reliable predictor of tumor progression in bladder cancer. It is associated with aggressive tumors and could be used to identify patients with either superficial disease requiring radical treatment or a low progression risk suitable for less intensive surveillance. Multicenter studies are warranted to validate this marker.
Angiopoietin 2 Is a Potential Mediator of High-Dose Interleukin 2–Induced Vascular Leak
Authors: Gallagher Diana C. , Bhatt Rupal S. , Parikh Samir M. , Patel Parin , Seery Virginia , McDermott David F. , Atkins Michael B. , Sukhatme Vikas P. 
Published: April 2007

AbstractPurpose: High-dose interleukin 2 (HDIL2) produces durable tumor regressions in 10% of patients with metastatic renal cell carcinoma and melanoma. However, a major toxicity is vascular leak syndrome (VLS). We previously reported elevated serum angiopoietin 2 (Ang2) in septic patients with vascular leak and hypothesized that Ang2 might also contribute to HDIL2 VLS.Experimental Design: Blood was collected from 14 patients receiving HDIL2 and from 4 patients receiving HDIL2 and bevacizumab, an antibody against vascular endothelial growth factor (VEGF). The effect of Ang2 was studied in vitro by incubating high Ang2 patient serum with cultured endothelial cells.Results: Pretreatment Ang2 levels were in the reference range (median, 3.3 ng/mL) and rose with each day of IL-2 therapy (median peak, 29.7 ng/mL). No trend was seen in free VEGF levels during therapy. Patients treated with HDIL2 and bevacizumab all developed VLS and elevated Ang2. High Ang2 patient sera induced propermeability structural changes in endothelial cells, an effect reversed by blockade with the competitive ligand angiopoietin 1 (Ang1).Conclusions: Ang2 may be a mediator of HDIL2 VLS as evidenced by (a) an increase in Ang2 in all patients on HDIL2; (b) the effect of high Ang2 patient serum on cultured endothelial cells; (c) rescue of those structural changes by Ang1. The lack of correlation between VLS and serum VEGF levels in patients treated with HDIL2 alone or in combination with bevacizumab suggests that VEGF is not a major contributor to VLS or Ang2 release. These data suggest that the inhibition of Ang2 may mitigate VLS in patients receiving HDIL2.
Identification of Molecular Predictors of Response in a Study of Tipifarnib Treatment in Relapsed and Refractory Acute Myelogenous Leukemia
Authors: Raponi Mitch , Harousseau Jean-Luc , Lancet Jeffrey E. , Löwenberg Bob , Stone Richard , Zhang Yi , Rackoff Wayne , Wang Yixin , Atkins David 
Published: April 2007

Abstract
Purpose: Microarray technology was used to identify gene expression markers that predict response to the orally available farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777) in acute myelogenous leukemia (AML).
Experimental Design: Gene expression profiles from 58 bone marrow samples from a cohort of relapsed and refractory AML patients were analyzed on the Affymetrix U133A gene chip that contains ∼22,000 genes.
Results: Supervised statistical analysis identified eight gene expression markers that could predict patient response to tipifarnib. The most robust gene was the lymphoid blast crisis oncogene (AKAP13), which predicted response with an overall accuracy of 63%. This gene provided a negative predictive value of 93% and a positive predictive value of 31% (increased from 18%). AKAP13 was overexpressed in patients who were resistant to tipifarnib. When overexpressed in the HL60 and THP1 cell lines, AKAP13 increased the resistance to tipifarnib by approximately 5- to 7-fold.
Conclusion: Diagnostic gene expression signatures may be used to select a group of AML patients that might respond to tipifarnib.
The African Union's Capacity in Promoting Good Governance
Authors: Kingah Sevidzem Stephen 
Published: April 2007

AbstractIn the spirit of the Constitutive Act of the African Union we must work for a continent characterized by democratic principles and institutions which guarantee popular participation and provide for good governance. Through our actions, let us proclaim to the world that this is a continent of democracy, a continent of democratic institutions and culture. Indeed, a continent of good governance, where the people participate and the rule of law is upheld.
The Analgesic Effect of Tribulus terrestris Extract and Comparison of Gastric Ulcerogenicity of the Extract with Indomethacine in Animal Experiments
Authors: HEIDARI M.R. , MEHRABANI M. , PARDAKHTY A. , KHAZAELI P. , ZAHEDI M.J. , YAKHCHALI M. , VAHEDIAN M. 
Published: April 2007

Abstract:
Tribulus terrestris has been used in traditional medicine for relieving rheumatic pain and as an analgesic plant for a long time. In this investigation the analgesic effect of methanolic extract of this plant on male albino mice was evaluated by formalin and tail flick test. Extraction of the fruits of the plant was done by two different methods (suxheletion and percolation) with methanol 80%. The percolated extract was injected intraperitoneally in mice at 50, 100, 200, 400, and 800 mg/kg. The results showed that a dose of 100 mg/kg of percolated extract had the highest significant analgesic effect compared to the control group (P < 0.01) in formalin and tail flick test. There is no significant difference in the analgesic effect of suxheleted and percolated extract. The analgesic effect of the extract was lower than morphine, 2.5 mg/kg in both tests, and higher than ASA 300 mg/kg in chronic phase of pain in formalin test (P < 0.05). Pretreatment of animal with naloxone did not change the analgesia induced by the plant extract in both tests, therefore the involvement of opioid receptor in the analgesic effect of this plant was excluded. The results of ulcerogenic studies indicate that the gastric ulcerogenecity of plant extract is lower than the indomethacin in the rat's stomach. It can therefore be concluded that T. terrestris extract has a suitable analgesic effect and further studies are required to produce a more effective product of this plant to substitute for conventional analgesic drugs.
Cross-coupling Reaction of Allylic and Benzylic Carbonates with Organo[2-(hydroxymethyl)phenyl]dimethylsilanes
Authors: Nakao Yoshiaki , Ebata Shiro , Chen Jinshui , Imanaka Hidekazu , Hiyama Tamejiro 
Published: April 2007

Abstract
The title reaction is found to proceed in the presence of a palladium catalyst and in the absence of any activator. Various functional groups are tolerated to give a diverse range of 1,4-diene and diarylmethane products, which are ubiquitous units of natural products and pharmaceuticals.
Controlled Organization of Silver Nanoparticles into Network Assemblies by Tuning pH Values
Authors: Sun Lanlan , Wei Gang , Song Yonghai , Wang Li , Guo Cunlan , Sun Yujing , Li Zhuang 
Published: April 2007

Abstract
We demonstrate the pH-induced assembly of 2-mercaptosuccinic acid-functionalized silver nanoparticles (MSA–Ag NPs) in the absence of hard or soft template. Two-dimensional (2D) and three-dimensional (3D) networks of silver NPs were achieved by tuning pH of the medium. The assembly process was monitored using atomic forces microscopy. The key factor affects the formation of network of silver NPs may be intermolecular hydrogen bonding between two carboxylic acid groups of MSA on two adjacent silver NPs.
Induction of DC-STAMP by Alternative Activation and Downstream Signaling Mechanisms
Authors: Yagi Mitsuru , Ninomiya Ken , Fujita Nobuyuki , Suzuki Toru , Iwasaki Ryotaro , Morita Kozo , Hosogane Naobumi , Matsuo Koichi , Toyama Yoshiaki , Suda Toshio , Miyamoto Takeshi 
Published: April 2007

Abstract
DC-STAMP is essential for fusion of osteoclasts and foreign body giant cells; however, it is not known whether dc-stamp expression in these two cell types is differentially regulated. Here, we show that dc-stamp expression and cell–cell fusion are regulated in a cell type–specific manner.
Introduction: The transcription factors c-Fos and NFATc1 cooperate to regulate osteoclast differentiation, whereas PU.1 and NF-κB are activated in macrophages and osteoclasts or in both cell types. Thus, we asked what role c-Fos, NFATc1, PU.1, and NF-κB played in regulating dendritic cell–specific transmembrane protein (dc-stamp) expression and fusion of osteoclasts and macrophage giant cells.
Materials and Methods: Transcriptional activation by c-Fos and NFATc1 was examined by dc-stamp promoter analysis. Multinuclear cell formation was analyzed in cells from c-Fos–deficient mice or in wildtype cells treated with the NFAT inhibitor FK506. The role of DC-STAMP in cell fusion was examined in vitro in a macrophage giant cell formation assay using DC-STAMP–deficient cells. Recruitment of c-Fos, NFATc1, PU.1, and NF-κB to the dc-stamp promoter in osteoclasts and macrophage giant cells was analyzed by chromatin-immunoprecipitation analysis.
Results: Both activator protein-1 (AP-1) and NFAT binding sites in the dc-stamp promoter were needed for dc-stamp expression after RANKL stimulation of osteoclasts. dc-stamp expression was induced in osteoclasts and macrophage giant cells, and cells from DC-STAMP–deficient mice failed to form either multinuclear osteoclasts or macrophage giant cells. In contrast, c-Fos is indispensable for dc-stamp expression and cell–cell fusion under conditions favoring in vitro and in vivo induction of osteoclasts but not macrophage giant cells. Consistently, an NFAT inhibitor suppressed multinuclear osteoclast formation but not macrophage giant cell formation. In addition, PU.1 and NF-κB binding sites were detected in the dc-stamp promoter, and both PU.1 and NF-κB were recruited to the dc-stamp promoter after granulocyte-macrophage colony stimulating factor (GM-CSF) + interleukin (IL)-4 stimulation.
Conclusions: dc-stamp expression is regulated differently in osteoclasts and macrophage giant cells. c-Fos and NFATc1, both of which are essential for osteoclast differentiation, are needed for dc-stamp expression and cell–cell fusion in osteoclasts, but both factors are dispensable for giant cell formation by macrophages. Because PU.1 and NF-κB are recruited to the dc-stamp promoter after stimulation with GM-CSF + IL-4, dc-stamp transcription is regulated in a cell type–specific manner.
Accretion of Bone Quantity and Quality in the Developing Mouse Skeleton
Authors: Miller Lisa M , Little William , Schirmer Anne , Sheik Farhan , Busa Bhavin , Judex Stefan 
Published: April 2007

Abstract
In this work, we found that bone mineral formation proceeded very rapidly in mice by 1 day of age, where the degree of mineralization, the tissue mineral density, and the mineral crystallinity reached 36%, 51%, and 87% of the adult values, respectively. However, even though significant mineralization had occurred, the elastic modulus of 1-day-old bone was only 14% of its adult value, indicating that the intrinsic stiffening of the bone lags considerably behind the initial mineral formation.
Introduction: To meet the mechanical challenges during early development, the skeleton requires the rapid accretion of bone quality and bone quantity. Here, we describe early bone development in the mouse skeleton and test the hypothesis that specific compositional properties determine the stiffness of the tissue.
Materials and Methods: Tibias of female BALB mice were harvested at eight time-points (n = 4 each) distributed between 1 and 40 days of age and subjected to morphometric (μCT), chemical (Fourier transform infrared microspectroscopy), and mechanical (nanoindentation) analyses. Tibias of 450-day-old mice served as fully mineralized control specimens.
Results: Bone growth proceeded very rapidly; at 1 day of age, the degree of mineralization (phosphate/protein ratio), the density of mineralized bone (TMD), and mineral crystallinity had reached 36%, 51%, and 87% of the adult (450 days) values, respectively. Spatially, the variability in mineralization across the mid-diaphysis was very high for the early time-points and declined over time. In contrast to the notable changes in mineralization, carbonate substitution into the mineral lattice (carbonate/phosphate ratio) and collagen cross-linking did not show any significant changes over this time period. Even though significant mineralization had occurred, the elastic modulus of 1-day-old bone was only 14% of the adult value and increased to 89% (of its adult value) after 40 days. Between samples of different time-points, significant positive correlations were observed between the elastic modulus and TMD (r2 = 0.84), phosphate/protein ratio (r2 = 0.59), and crystallinity (r2 = 0.23), whereas collagen cross-linking showed a small but significant negative correlation (r2 = 0.15).
Conclusions: These data indicate that specific chemical and morphometric properties modulate bone's stiffness during early growth. The intrinsic stiffening of the bone, however, lags considerably behind the initial mineral formation, emphasizing the importance of bone mineral quality for optimizing matrix integrity.
Persistent Socioeconomic Disparities in Infant, Neonatal, and Postneonatal Mortality Rates in the United States, 1969–2001
Authors: Singh Gopal K. , Kogan Michael D. 
Published: April 2007

OBJECTIVES. This study examines changing patterns of inequalities in US infant, neonatal, and postneonatal mortality rates between 1969 and 2001 by area deprivation and maternal education.
METHODS. A deprivation index was linked to county vital records data to derive annual infant mortality rates by deprivation quintiles from 1969 to 2000. Rates by maternal education were computed for 1986, 1991, 1996, and 2001 using national linked birth/infant death files. Log-binomial regression was used to estimate relative risks of infant mortality by deprivation and time period. Cox regression was used to model overall and birth weight–specific infant mortality risks by maternal education after adjusting for covariates. Temporal disparities were summarized by log-linear regression and inequality indices.
RESULTS. Although absolute disparities have narrowed over time, relative socioeconomic disparities in infant mortality have increased since 1985. In 1985–1989, infants in the most deprived group had, respectively, 36% and 57% higher risks of neonatal and postneonatal mortality than infants in the least deprived group. The corresponding relative risks increased to 43% and 96% in 1995–2000. The adjusted risk of infant mortality was 22% higher in 1986 for mothers with &lt;12 years of education than for those with ≥16 years of education, with the relative risk increasing to 41% in 2001. Disparities were greatest among normal birth weight infants, with education-specific relative risks of neonatal and postneonatal mortality increasing significantly between 1986 and 2001.
CONCLUSIONS. Dramatic declines in infant mortality among all of the socioeconomic groups during 1969–2001 represent a major public health success. However, substantial socioeconomic disparities persisted in both neonatal and postneonatal mortality. Relatively larger declines in infant and postneonatal mortality among higher socioeconomic groups have contributed to the widening gap in mortality since 1985. Persistent disparities in infant mortality may reflect increasing polarization among socioeconomic groups in material and social conditions, smoking during pregnancy, and health care services.
Multidrug-Resistant Bacteria in Hospitalized Children: A 5-Year Multicenter Study
Authors: Raymond Josette , Nordmann Patrice , Doit Catherine , Vu Thien Hoang , Guibert Michèle , Ferroni Agnès , Aujard Yannick 
Published: April 2007

OBJECTIVE. The objective of this study was to determine the incidence of multidrug-resistant bacteria in hospitalized children
METHODS. This multicenter study was conducted in 5 hospitals in the Paris area from 1999 to 2003. We recorded all isolations of multidrug-resistant bacteria from clinical samples that were obtained from hospitalized children. Strains that were isolated during systematic screening for carriers were excluded.
RESULTS. The mean incidences were 0.9 per 1000 hospitalization-days for methicillin-resistant Staphylococcus aureus, 0.45 for extended-spectrum β-lactamase–producing Klebsiella pneumoniae, 0.32 for extended-spectrum β-lactamase–producing Enterobacteriaceae other than Klebsiella pneumoniae, 0.40 for Enterobacter species with derepressed cephalosporinase, and 0.01 for vancomycin-resistant Enterococcus. The incidences per 1000 hospitalization-days of methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase–producing Klebsiella pneumoniae, extended-spectrum β-lactamase–producing Enterobacteriaceae other than Klebsiella pneumoniae, and Enterobacter species with derepressed cephalosporinase decreased significantly from 1999 to 2003, whereas the incidence of vancomycin-resistant Enterococcus remained very low. The proportion of resistant strains within the species did not vary significantly for methicillin-resistant Staphylococcus aureus (11% to 9.6%), extended-spectrum β-lactamase–producing Enterobacteriaceae other than Klebsiella pneumoniae (1.1%), and vancomycin-resistant Enterococcus (0.03% to 0.023%). In contrast, the frequency of extended-spectrum β-lactamase–producing Klebsiella pneumoniae decreased from 31.6% to 7.4%, and that of Enterobacter species with derepressed cephalosporinase decreased from 38.8% to 18.5%.
CONCLUSIONS. We report significant decreases in the incidence of methicillin-resistant Staphylococcus aureus, extended-spectrum β-lactamase–producing Klebsiella pneumoniae, extended-spectrum β-lactamase–producing Enterobacteriaceae other than Klebsiella pneumoniae, and Enterobacter species with derepressed cephalosporinase in hospitalized children during a 5-year period.
Injury-Prevention Counseling and Behavior Among US Children: Results From the Second Injury Control and Risk Survey
Authors: Chen Jieru , Kresnow Marcie-jo , Simon Thomas R. , Dellinger Ann 
Published: April 2007

OBJECTIVES. The purpose of this work was to provide recent national prevalence estimates of pediatric injury-prevention counseling by health care providers, to compare these latest findings with those from a similar survey conducted in 1994, and to ascertain the association between counseling and safety behaviors.METHODS. We conducted a cross-sectional, list-assisted random-digit-dial telephone survey of randomly selected children in English- or Spanish-speaking households in all 50 US states and the District of Columbia. The main outcome measures were respondents' reports that they or their children received injury-prevention counseling from their child's health care provider in the 12 months preceding the interview, children's practices of safety behaviors, and the association of injury-prevention counseling and such behaviors.RESULTS. The overall proportion of US children receiving any injury-prevention counseling (42.4%) remained relatively unchanged, whereas counseling on selected injury-prevention topics increased significantly compared with reports based on the 1994 survey. Topic-specific injury-prevention counseling was positively associated with the posting of the poison control center telephone number in homes with children &lt;6 years of age and with bicycle-helmet use among children 5 to 14 years of age.CONCLUSIONS. Although the prevalence of pediatric injury-prevention counseling remains low, such counseling was associated with safer behaviors. This suggests the importance of pediatric injury-prevention counseling and indicates the need for health care providers to increase pediatric injury-prevention counseling in clinical practices.
Long-term Outcome and Clinical Spectrum of 73 Pediatric Patients With Mitochondrial Diseases
Authors: Debray François-Guillaume , Lambert Marie , Chevalier Isabelle , Robitaille Yves , Decarie Jean-Claude , Shoubridge Eric A. , Robinson Brian H. , Mitchell Grant A. 
Published: April 2007

OBJECTIVES. We sought to determine the clinical spectrum, survival, and long-term functional outcome of a cohort of pediatric patients with mitochondrial diseases and to identify prognostic factors.
METHODS. Medical charts were reviewed for 73 children diagnosed between 1985 and 2005. The functional status of living patients was assessed prospectively by using the standardized Functional Independence Measure scales.
RESULTS. Patients fell into 7 phenotypic categories: neonatal-onset lactic acidosis (10%), Leigh syndrome (18%), nonspecific encephalopathy (32%), mitochondrial (encephalo)myopathy (19%), intermittent neurologic (5%), visceral (11%), and Leber hereditary optic neuropathy (5%). Age at first symptoms ranged from prenatal to 16 years (median: 7 months). Neurologic symptoms were the most common (90%). Visceral involvement was observed in 29% of the patients. A biochemical or molecular diagnosis was identified for 81% of the patients as follows: deficiency of complex IV (27%), of pyruvate dehydrogenase or complex I (25% each), of multiple complexes (13%), and of pyruvate carboxylase (5%) or complexes II+III (5%). A mitochondrial DNA mutation was found in 20% of patients. At present, 46% of patients have died (median age: 13 months), 80% of whom were &lt;3 years of age. Multivariate analysis showed that age at first symptoms was a major independent predictor of mortality: patients with first symptoms before 6 months had a highly increased risk of mortality. Cardiac or visceral involvement and neurologic crises were not independent prognostic factors. Living patients showed a wide range of independence levels that correlated positively with age at first symptoms. Among patients aged &gt;5 years (n = 32), 62% had Functional Independence Measure quotients of &gt;0.75.
CONCLUSIONS. Mitochondrial diseases in children span a wide range of symptoms and severities. Age at first symptoms is the strongest predictor mortality. Despite a high mortality rate in the cohort, 62% of patients aged &gt;5 years have only mild impairment or normal functional outcome.