bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Significance of Plasma Osteopontin in Patients with Locoregionally Advanced Head and Neck Squamous Cell Carcinoma Treated on TROG 02.02 Phase III Trial
Authors: Lim Annette M. , Rischin Danny , Fisher Richard , Cao Hongbin , Kwok Kathleen , Truong Daniel , McArthur Grant A. , Young Richard J. , Giaccia Amato , Peters Lester , Le Quynh-Thu 
Published: November 2011

Abstract
Purpose: High plasma osteopontin (OPN) levels have been reported to be an adverse prognostic factor in head and neck squamous cell carcinomas (HNSCC), correlate with tumor hypoxia, and be predictive of benefit from hypoxia-targeted therapy. We sought to confirm the prognostic and predictive significance of OPN in patients treated on a large international trial.
Experimental Design: Patients with stage III/IV HNSCC were randomized to receive definitive radiotherapy concurrently with cisplatin or cisplatin plus the hypoxic cell cytotoxin, tirapazamine (TPZ). Eligibility criteria for this prospective substudy included plasma sample availability for OPN assay by ELISA and absence of major radiation therapy deviations (N = 578). OPN concentrations were analyzed for overall survival (OS) and time to locoregional failure (TTLRF), adjusting for known prognostic factors. Additional analysis was carried out in patients with available tumor p16INK4A staining status.
Results: The median OPN level was 544 ng/mL (range: 7–2,640). High OPN levels were not associated with worse OS (relative HR, 1.03 for highest tertile) or TTLRF (relative HR 0.91 for highest tertile). There was no interaction between OPN and treatment arm for OS or TTLRF (P = 0.93 for OS; P = 0.87 for TTLRF). For the highest tertile the 2-year OS was 66% on control arm and 67% on TPZ arm (HR = 1.11, P = 0.67). Similarly for p16INK4A negative patients in the highest tertile, the 2-year OS was 61% on control arm and 63% on TPZ arm (HR = 1.05, P = 0.86).
Conclusions: We found no evidence that high plasma OPN levels were associated with an adverse prognosis in HNSCC, or were predictive of benefit with hypoxia targeting therapy. Clin Cancer Res; 18(1); 301–7. ©2011 AACR.
Apigenin Induces Apoptosis in Human Leukemia Cells and Exhibits Anti-Leukemic Activity In Vivo
Authors: Budhraja Amit , Gao Ning , Zhang Zhuo , Son Young-Ok , Cheng Senping , Wang Xin , Ding Songze , Hitron Andrew , Chen Gang , Luo Jia , Shi Xianglin 
Published: November 2011

Abstract
In this study, we investigated the functional role of Akt and c-jun-NH2-kinase (JNK) signaling cascades in apigenin-induced apoptosis in U937 human leukemia cells and anti-leukemic activity of apigenin in vivo. Apigenin induced apoptosis by inactivation of Akt with a concomitant activation of JNK, Mcl-1 and Bcl-2 downregulation, cytochrome c release from mitochondria, and activation of caspases. Constitutively active myristolated Akt prevented apigenin-induced JNK, caspase activation, and apoptosis. Conversely, LY294002 and a dominant-negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. Interruption of the JNK pathway showed marked reduction in apigenin-induced caspase activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin resulted in attenuation of tumor growth in U937 xenografts accompanied by inactivation of Akt and activation of JNK. Attenuation of tumor growth in U937 xenografts by apigenin raises the possibility that apigenin may have clinical implications and can be further tested for incorporating in leukemia treatment regimens. Mol Cancer Ther; 11(1); 132–42. ©2011 AACR.
Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy
Authors: Yang Liying , Horibe Tomohisa , Kohno Masayuki , Haramoto Mari , Ohara Koji , Puri Raj K. , Kawakami Koji 
Published: November 2011

Abstract
Interleukin-4 receptor α (IL-4Rα) chain is highly expressed on the surface of various human solid tumors. We designed a novel hybrid peptide termed IL-4Rα–lytic peptide that targets the IL-4Rα chain. The IL-4Rα–lytic peptide contains a target moiety to bind to IL-4Rα and a cellular toxic lytic peptide that selectively kills cancer cells. The anticancer activity of the IL-4Rα–lytic peptide was evaluated in vitro and in vivo. It was found that the IL-4Rα–lytic peptide has cytotoxic activity in cancer cell lines expressing IL-4Rα, determined by quantitative real-time PCR. The IC50 ratios of the lytic peptide to the IL-4Rα–lytic peptide correlated well with the expression levels of IL-4Rα on cancer cells (r = 0.80). In addition, IL-4Rα–lytic peptide administered either intratumoraly or intravenously significantly inhibited tumor growth in xenograft model of human pancreatic cancer (BXPC-3) in mice. These results indicate that the IL-4Rα–lytic peptide generated in this study has a potent and selective anticancer potential against IL-4Rα–positive solid cancers. Mol Cancer Ther; 11(1); 235–43. ©2011 AACR.
A Critical Role for the Protein Apoptosis Repressor With Caspase Recruitment Domain in Hypoxia-Induced Pulmonary Hypertension
Authors: Zaiman Ari L. , Damico Rachel , Thoms-Chesley Alan , Files D. Clark , Kesari Priya , Johnston Laura , Swaim Mara , Mozammel Shehzin , Myers Alan C. , Halushka Marc , El-Haddad Hazim , Shimoda Larissa A. , Peng Chang-Fu , Hassoun Paul M. , Champion Hunter C. , Kitsis Richard N. , Crow Michael T. 
Published: November 2011

Background—
Pulmonary hypertension (PH) is a lethal syndrome associated with the pathogenic remodeling of the pulmonary vasculature and the emergence of apoptosis-resistant cells. Apoptosis repressor with caspase recruitment domain (ARC) is an inhibitor of multiple forms of cell death known to be abundantly expressed in striated muscle. We show for the first time that ARC is expressed in arterial smooth muscle cells of the pulmonary vasculature and is markedly upregulated in several experimental models of PH. In this study, we test the hypothesis that ARC expression is essential for the development of chronic hypoxia-induced PH.

Methods and Results—
Experiments in which cells or mice were rendered ARC-deficient revealed that ARC not only protected pulmonary arterial smooth muscle cells from hypoxia-induced death, but also facilitated growth factor-induced proliferation and hypertrophy and hypoxia-induced downregulation of selective voltage-gated potassium channels, the latter a hallmark of the syndrome in humans. Moreover, ARC-deficient mice exhibited diminished vascular remodeling, increased apoptosis, and decreased proliferation in response to chronic hypoxia, resulting in marked protection from PH in vivo. Patients with PH have significantly increased ARC expression not only in remodeled vessels but also in the lumen-occluding lesions associated with severe disease.

Conclusions—
These data show that ARC, previously unlinked to pulmonary hypertension, is a critical determinant of vascular remodeling in this syndrome.
Status of Cardiovascular Health in US Adults
Authors: Shay Christina M. , Ning Hongyan , Allen Norrina B. , Carnethon Mercedes R. , Chiuve Stephanie E. , Greenlund Kurt J. , Daviglus Martha L. , Lloyd-Jones Donald M. 
Published: November 2011

Background—
The American Heart Association's 2020 Strategic Impact Goals define a new concept, cardiovascular (CV) health; however, current prevalence estimates of the status of CV health in US adults according to age, sex, and race/ethnicity have not been published.

Methods and Results—
We included 14 515 adults (≥20 years of age) from the 2003 to 2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20–39 years), middle (40–64 years), and older (≥65 years) ages. CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Fewer than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, nonsmoking was most prevalent (range, 60.2%–90.4%), whereas ideal Healthy Diet Score was least prevalent (range, 0.2%–2.6%) across groups. Prevalences of ideal body mass index (range, 36.5%–45.3%) and ideal physical activity levels (range, 50.2%–58.8%) were higher in young adults compared with middle or older ages. Ideal total cholesterol (range, 23.7%–36.2%), blood pressure (range, 11.9%–16.3%), and fasting blood glucose (range, 31.2%–42.9%) were lower in older adults compared with young and middle-aged adults. Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups.

Conclusions—
These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in US adult populations.
Heparin Elevates Circulating Soluble fms-Like Tyrosine Kinase-1 Immunoreactivity in Pregnant Women Receiving Anticoagulation Therapy
Authors: Rosenberg Victor A. , Buhimschi Irina A. , Lockwood Charles J. , Paidas Michael J. , Dulay Antonette T. , Ramma Wenda , Abdel-Razeq Sonya S. , Zhao Guomao , Ahmad Shakil , Ahmed Asif , Buhimschi Catalin S. 
Published: November 2011

Background—
Alterations in circulating levels of pro- and antiangiogenic factors have been associated with adverse pregnancy outcomes. Heparin is routinely administered to pregnant women, but without clear knowledge of its impact on these factors.

Methods and Results—

We conducted a longitudinal study of 42 pregnant women. Twenty-one women received prophylactic heparin anticoagulation, and 21 healthy pregnant women served as controls. Compared with gestational age-matched controls, heparin treatment was associated with increased circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in the third trimester (
P
<0.05), in the absence of preeclampsia, placental abruption, or fetal growth restriction. Heparin had no effect on circulating levels of vascular endothelial growth factor, placenta growth factor, or soluble endoglin as assessed by ELISA. In vitro, low-molecular weight and unfractionated heparins stimulated sFlt-1 release from placental villous explants, in a dose- and time-dependent manner. This effect was not due to placental apoptosis, necrosis, alteration in protein secretion, or increased transcription. Western blot analysis demonstrated that heparin induced shedding of the N-terminus of Flt-1 both in vivo and in vitro as indicated by a predominant band of 100–112 kDa. By using an in vitro angiogenesis assay, we demonstrated that serum of heparin-treated cases inhibited both basal and vascular endothelial growth factor-induced capillary-like tube formation.

Conclusions—
Heparin likely increases the maternal sFlt-1 through shedding of the extracellular domain of Flt-1 receptor. Our results imply that upregulation of circulating sFlt-1 immunoreactivity in pregnancy is not always associated with adverse outcomes, and that heparin's protective effects, if any, cannot be explained by promotion of angiogenesis.
Pathogenic Cycle Between the Endogenous Nitric Oxide Synthase Inhibitor Asymmetrical Dimethylarginine and the Leukocyte-Derived Hemoprotein Myeloperoxidase
Authors: von Leitner Eike-Christin , Klinke Anna , Atzler Dorothee , Slocum Jessica L. , Lund Natalie , Kielstein Jan T. , Maas Renke , Schmidt-Haupt Robin , Pekarova Michaela , Hellwinkel Olaf , Tsikas Dimitrios , D'Alecy Louis G. , Lau Denise , Willems Stephan , Kubala Lukas , Ehmke Heimo , Meinertz Thomas , Blankenberg Stefan , Schwedhelm Edzard , Gadegbeku Crystal A. , Böger Rainer H. , Baldus Stephan , Sydow Karsten 
Published: November 2011

Background—
The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leukocyte-derived hemoprotein myeloperoxidase (MPO) are associated with cardiovascular diseases. Activation of monocytes and polymorphonuclear neutrophils (PMNs) with concomitant release of MPO is regulated in a nitric oxide–dependent fashion. The aim of the study was to investigate a potential 2-way interaction between ADMA and MPO.

Methods and Results—

Ex vivo, ADMA uptake by isolated human PMNs, the principal source of MPO in humans, significantly impaired nitric oxide synthase activity determined by gas chromatography–mass spectrometry. In humans, short-term ADMA infusion (0.0125 mg · kg
−1
· min
−1
) significantly increased MPO plasma concentrations. Functionally, PMN exposure to ADMA enhanced leukocyte adhesion to endothelial cells, augmented NADPH oxidase activity, and stimulated PMN degranulation, resulting in release of MPO. In vivo, a 28-day ADMA infusion (250 μmol · kg
−1
· d
−1
) in C57Bl/6 mice significantly increased plasma MPO concentrations, whereas this ADMA effect on MPO was attenuated by human dimethylarginine dimethylaminohydrolase1 (hDDAH1) overexpression. Moreover, the MPO-derived reactive molecule hypochlorous acid impaired recombinant hDDAH1 activity in vitro. In MPO
−/−
mice, the lipopolysaccharide-induced increase in systemic ADMA concentrations was abrogated.

Conclusions—
ADMA profoundly impairs nitric oxide synthesis of PMNs, resulting in increased PMN adhesion to endothelial cells, superoxide generation, and release of MPO. In addition, MPO impairs DDAH1 activity. Our data reveal an ADMA-induced cycle of PMN activation, enhanced MPO release, and subsequent impairment of DDAH1 activity. These findings not only highlight so far unrecognized cytokine-like properties of ADMA but also identify MPO as a regulatory switch for ADMA bioavailability under inflammatory conditions.
Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment (FAST)
Authors: Boersma Lucas V.A. , Castella Manuel , van Boven WimJan , Berruezo Antonio , Yilmaz Alaaddin , Nadal Mercedes , Sandoval Elena , Calvo Naiara , Brugada Josep , Kelder Johannes , Wijffels Maurits , Mont Lluís 
Published: November 2011

Background—
Catheter ablation (CA) and minimally invasive surgical ablation (SA) have become accepted therapy for antiarrhythmic drug–refractory atrial fibrillation. This study describes the first randomized clinical trial comparing their efficacy and safety during a 12-month follow-up.

Methods and Results—

One hundred twenty-four patients with antiarrhythmic drug–refractory atrial fibrillation with left atrial dilatation and hypertension (42 patients, 33%) or failed prior CA (82 patients, 67%) were randomized to CA (63 patients) or SA (61 patients). CA consisted of linear antral pulmonary vein isolation and optional additional lines. SA consisted of bipolar radiofrequency isolation of the bilateral pulmonary vein, ganglionated plexi ablation, and left atrial appendage excision with optional additional lines. Follow-up at 6 and 12 months was performed by ECG and 7-day Holter recording. The primary end point, freedom from left atrial arrhythmia >30 seconds without antiarrhythmic drugs after 12 months, was 36.5% for CA and 65.6% for SA (
P
=0.0022). There was no difference in effect for subgroups, which was consistent at both sites. The primary safety end point of significant adverse events during the 12-month follow-up was significantly higher for SA than for CA (n=21 [34.4%] versus n=10 [15.9%];
P
=0.027), driven mainly by procedural complications such as pneumothorax, major bleeding, and the need for pacemaker. In the CA group, 1 patient died at 1 month of subarachnoid hemorrhage.

Conclusion—
In atrial fibrillation patients with dilated left atrium and hypertension or failed prior atrial fibrillation CA, SA is superior to CA in achieving freedom from left atrial arrhythmias after 12 months of follow-up, although the procedural adverse event rate is significantly higher for SA than for CA.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00662701.
Intercomparison of Four Commercial Analyzers for Water Vapor Isotope Measurement
Authors: Wen Xue-Fa , Lee Xuhui , Sun Xiao-Min , Wang Jian-Lin , Tang Ya-Kun , Li Sheng-Gong , Yu Gui-Rui 
Published: November 2011

Abstract
The δ18O and δD of atmospheric water vapor are important tracers in hydrological and ecological studies. Isotope ratio infrared spectroscopy (IRIS) provides an in situ technology for measuring δ18O and δD in ambient conditions. An intercomparison experiment was carried out with four commercial IRIS analyzers to characterize their performance and transferability of calibration methods. Over a 15-day atmospheric measurement, during which the water vapor concentration ranged from 14 to 27 mol mol−1 and the isotopic ratios spanned about 90‰ and 13‰ for δD and δ18O, respectively, these analyzers tracked the natural variability in ambient conditions very well and achieved an average difference between one another within 2‰ for δD and within 0.1‰ for δ18O after calibration at appropriate frequencies. Two of the calibration methods (discrete liquid water injection and continuous dripping) agreed with each other within the tolerance thresholds of 2‰ for δD and 0.1‰ for δ18O. The Rayleigh distillation technique appeared to be acceptable as a calibration standard for δD but not for δ18O. The δD measurements were less prone to concentration dependence errors than the δ18O measurements. The concentration dependence underscores the importance of using a calibration procedure at multiple mixing ratios to bracket the range of natural variability.
Assessing Stability of CERES-FM3 Daytime Longwave Unfiltered Radiance with AIRS Radiances
Authors: Huang Xianglei , Loeb Norman G. , Chuang Huiwen 
Published: November 2011

Abstract
Clouds and the Earth’s Radiant Energy System (CERES) daytime longwave (LW) radiances are determined from the difference between a total (TOT) channel (0.3–200 μm) measurement and a shortwave (SW) channel (0.3–5 μm) measurement, while nighttime LW radiances are obtained directly from the TOT channel. This means that a drift in the SW channel or the SW portion of the TOT channel could impact the daytime longwave radiances, but not the nighttime ones. This study evaluates daytime and nighttime CERES LW radiances for a possible secular drift in CERES LW observations using spectral radiances observed by Atmospheric Infrared Sounder (AIRS). By examining the coincidental AIRS and CERES Flight Model 3 (FM3) measurements over the tropical clear-sky oceans for all of January and July months since 2005, a secular drift of about −0.11% yr−1 in the daytime CERES-FM3 longwave unfiltered radiance can be identified in the CERES Single Scanner Footprint (SSF) Edition 2 product. This provides an upper-bound estimation for the drift in daytime outgoing longwave radiation, which is approximately −0.323 W m−2 yr−1. This estimation is consistent with the independent assessment concluded by the CERES calibration team. Such secular drift has been greatly reduced in the latest CERES SSF Edition 3 product. Comparisons are conducted for the CERES window channel as well, and it shows essentially no drift. This study serves as a practical example illustrating how the measurements of spectrally resolved radiances can be used to help evaluate data products from other narrowband or broadband measurements.
Incidence and causes for syringe driver site reactions in palliative care: A prospective hospice-based study
Authors: Mitchell Kath , Pickard Jennie , Herbert Annie , Lightfoot Jenny , Roberts Dai 
Published: November 2011

Background Syringe drivers are routinely used in palliative care for the subcutaneous infusion of drugs for pain and symptom control. Local site reactions occurring at the site of infusion can lead to patient discomfort and the potential for sub-optimal symptom control. Aim The aim of this study was to investigate whether there was a correlation between drugs administered subcutaneously via a syringe driver and the incidence of syringe driver site reactions, further linking this to time to syringe driver site reaction. Design: Prospective quantitative data collection of syringe driver use for 170 hospice inpatients. Setting/participants: Specialist palliative care inpatient facility in the UK. Syringe driver recording forms were retrieved from case notes of consecutive patients who received medication via a syringe driver. Results: An association between the presence of cyclizine and levomepromazine and the incidence of syringe driver site reactions was identified. A marked difference in incidence of syringe driver site reaction was observed between the two study centres (26.5% vs. 7.7%). Although baseline patient characteristics were comparable, a difference in practice between the centres was identified, i.e. use of parenteral cannulae. An association between the time a syringe driver was in situ and the occurrence of a syringe driver site reaction was also demonstrated. Conclusions: Recommendations can be made for the frequency of syringe driver site changes based on which drugs are in use. Incidental findings from the study have been used to change practice at the hospice study site, with regard to choice of parenteral cannulae.
Thermal gravimetric/Fourier transform infrared spectroscopy analyses of oil palm fibre reinforced polypropylene composites
Authors: Ramli R , Yunus RM , Beg MDH 
Published: November 2011

In this study, the effects of fibre loading and coupling agent on the performance of empty fruit bunch (EFB) fibre composites of oil palm biomass were investigated. The dried EFB were ground into random sizes for composite production. Ground fibre was compounded with polypropylene (PP) by means of a twin-screw compounder for preparing EFB/PP composites. Maleic anhydride-grafted polypropylene was used as a coupling agent. The incorporated fibre contents for EFB composites were 10 wt% to 40 wt% (by weight). The test specimens were prepared by injection moulding. The composites were characterized by melt flow index, mechanical tests such as tensile strength, tensile modulus, flexural strength, flexural modulus and impact strength. Surface morphology was also studied by scanning electron microscope. Bonding/interaction mechanism was studied by Fourier transform infrared spectroscopy and thermal stability was studied by thermal gravimetric analysis form where the activation energy was calculated for different composites. It was found that both coupling agent and fibre content play an important role in composites properties.
Preparation and properties of agave fiber-reinforced polystyrene composites
Authors: Singha AS , Rana Raj K 
Published: November 2011

In the present work, Agave americana fibers have been used as a reinforcement in the preparation of polystyrene matrix-based biocomposites using compression molding technique. The composites thus prepared were subjected to the evaluation of different mechanical properties such as tensile, compressive and flexural strength. The results obtained suggest that composites reinforced with agave fibers exhibited better mechanical properties than neat polystyrene. The morphological and thermal properties of matrix, fibers and composites have also been investigated by scanning electron microscopy and thermogravimetric analysis, respectively. Further composites were subjected to the evaluation of physicochemical properties such as swelling behavior in different solvents and resistance to acid, alkali and salt of 1 N strength for different time intervals.