bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin αvβ3-Targeted IRDye 800CW Near-Infrared Imaging of Glioblastoma
Authors: Huang Ruimin , Vider Jelena , Kovar Joy L. , Olive D. Michael , Mellinghoff Ingo K. , Mayer-Kuckuk Philipp , Kircher Moritz F. , Blasberg Ronald G. 
Published: August 2012

Abstract
Purpose: Integrin αvβ3 plays an important role in tumor angiogenesis, growth, and metastasis. We have tested a targeted probe to visualize integrin receptor expression in glioblastomas using near-infrared fluorescent (NIRF) imaging.
Experimental design: A transgenic glioblastoma mouse model (RCAS-PDGF-driven/tv-a glioblastoma, which mimics the infiltrative growth pattern of human glioblastomas) and two human orthotopic glioblastoma models (U-87 MG with high integrin β3 expression and TS543 with low integrin β3 expression) were studied. An integrin-targeting NIRF probe, IRDye 800CW-cyclic-RGD peptide (IRDye 800CW-RGD), was tested by in vivo and ex vivo NIRF imaging.
Results: We show that the IRDye 800CW-RGD peptide: (i) specifically binds to integrin receptors; (ii) is selectively localized to glioblastoma tissue with overexpressed integrin receptors and is retained over prolonged periods of time; (iii) is associated with minimal autofluorescence and photobleaching because of imaging at 800 nm; (iv) provides delineation of tumor tissue with high precision because of a high tumor-to-normal brain fluorescence ratio (79.7 ± 6.9, 31.2 ± 2.8, and 16.3 ± 1.3) in the U-87 MG, RCAS-PDGF, and TS543 models, respectively; P &lt; 0.01); and (v) enables fluorescence-guided glioblastoma resection. Importantly, small foci of residual fluorescence were observed after resection was completed using white light imaging alone, and these fluorescent foci were shown to represent residual tumor tissue by histology.
Conclusions: NIRF imaging with the IRDye 800CW-RGD probe provides a simple, rapid, low-cost, nonradioactive, and highly translatable approach for improved intraoperative glioblastoma visualization and resection. It also has the potential to serve as an imaging platform for noninvasive cancer detection and drug efficacy evaluation studies. Clin Cancer Res; 18(20); 5731–40. ©2012 AACR.
Publication and Reporting Conduct for Pharmacodynamic Analyses of Tumor Tissue in Early-Phase Oncology Trials
Authors: Freeman Georgina A. , Kimmelman Jonathan 
Published: August 2012

Abstract
Purpose: In principle, nondiagnostic biopsies for pharmacodynamic (PD) studies are carried out to inform decision-making in drug development. Because such procedures have no therapeutic value, their ethical justification requires that results be published. We aimed to assess the frequency of nonpublication of PD data in early phase cancer trials and to identify factors that prevent full publication of data.
Methods: We identified a sample of early-phase cancer trials containing invasive nondiagnostic tissue procurement for PD analysis from American Society of Clinical Oncologyand American Association for Cancer Research meeting abstracts published between 1995 and 2005. These trials were followed to publication to determine frequency of nonpublication of PD data. Corresponding authors on early-phase cancer trials using invasive nondiagnostic research procedures were also surveyed to identify factors preventing full publication of PD data.
Results: In a sample of 90 trials, 22.2% (20 trials) resulted in no trial publication. Of published trials expected to contain PD reports, 16 (17.8%) did not include any PD data, and 21 (23.3%) reported incomplete PD data. We surveyed 92 authors; nonpublication was regarded as a frequent occurrence, and the most commonly cited barrier to full publication of PD data was strategic considerations in publication (58.8% of responding authors).
Conclusions: Our results suggest ways that investigators, study planners, and reviewers can improve the burden/knowledge value balance in PD studies. Clin Cancer Res; 18(23); 6478–84. ©2012 AACR.
Genomic Estimates of Aneuploid Content in Glioblastoma Multiforme and Improved Classification
Authors: Li Bo , Senbabaoglu Yasin , Peng Weiping , Yang Min-Lee , Xu Jishu , Li Jun Z. 
Published: August 2012

Abstract
Purpose: Accurate classification of glioblastoma multiforme (GBM) is crucial for understanding its biologic diversity and informing diagnosis and treatment. The Cancer Genome Atlas (TCGA) project identified four GBM classes using gene expression data and separately identified three classes using methylation data. We sought to integrate multiple data types in GBM classification, understand biologic features of the newly defined subtypes, and reconcile with prior studies.
Experimental Design: We used allele-specific copy number data to estimate the aneuploid content of each tumor and incorporated this measure of intratumor heterogeneity in class discovery. We estimated the potential cell of origin of individual subtypes and the euploid and aneuploid fractions using reference datasets of known neuronal cell types.
Results: There exists an unexpected correlation between aneuploid content and the observed among-tumor diversity of expression patterns. Joint use of DNA and mRNA data in ab initio class discovery revealed a distinct group that resembles the Proneural subtype described in a separate study and the glioma-CpG island methylator phenotype (G-CIMP+) class based on methylation data. Three additional subtypes, Classical, Proliferative, and Mesenchymal, were also identified and revised the assignment for many samples. The revision showed stronger differences in patient outcome and clearer cell type–specific signatures. Mesenchymal GBMs had higher euploid content, potentially contributed by microglia/macrophage infiltration.
Conclusion: We clarified the confusion about the “Proneural” subtype that was defined differently in different prior studies. The ability to infer within-tumor heterogeneity improved class discovery, leading to new subtypes that are closer to the fundamental biology of GBM. Clin Cancer Res; 18(20); 5595–605. ©2012 AACR.
Variants on a Theme: A Biomarker of Crizotinib Response in ALK-Positive Non–Small Cell Lung Cancer?
Authors: Crystal Adam S. , Shaw Alice T. 
Published: August 2012

Abstract
Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 5% of non–small cell lung carcinoma patients and confer sensitivity to ALK inhibitors such as crizotinib. The particular ALK fusion expressed may have an impact on protein stability and sensitivity to crizotinib, and this may underlie the heterogeneity in responses observed in the clinic. Clin Cancer Res; 18(17); 4479–81. ©2012 AACR.
Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer
Authors: Juvekar Ashish , Burga Laura N. , Hu Hai , Lunsford Elaine P. , Ibrahim Yasir H. , Balmañà Judith , Rajendran Anbazhagan , Papa Antonella , Spencer Katherine , Lyssiotis Costas A. , Nardella Caterina , Pandolfi Pier Paolo , Baselga José , Scully Ralph , Asara John M. , Cantley Lewis C. , Wulf Gerburg M. 
Published: August 2012

Abstract
There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in a MMTV-CreBrca1f/fTrp53+/− mouse model of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation, and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK pathway at the “pushing margin.” Surprisingly, PI3K inhibition increased indicators of DNA damage, poly-ADP-ribosylation (PAR), and γ-H2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. The PARP inhibitor olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and olaparib delayed tumor doubling to more than 70 days in the mouse model and more than 50 days in xenotransplants from human BRCA1-related tumors, suggesting that combined PI3K and PARP inhibition might be an effective treatment of BRCA1-related tumors.
Significance: Current treatment options for triple-negative breast cancer are limited to chemotherapeutic regimens that have considerable toxicity and are not curative. We report here that the combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1-related breast cancers, making this a candidate combination to be tested in human clinical trials. Cancer Discov; 2(11); 1048–63. ©2012 AACR.
Read the Commentary on this article by Rehman et al., p. 982.
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A Simple Echocardiographic Prediction Rule for Hemodynamics in Pulmonary Hypertension
Authors: Opotowsky Alexander R. , Ojeda Jason , Rogers Frances , Prasanna Vikram , Clair Mathieu , Moko Lilamarie , Vaidya Anjali , Afilalo Jonathan , Forfia Paul R. 
Published: August 2012

Background—
Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly because of elevated left-sided filling pressure is critical.

Methods and Results—

We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH attributed to pulmonary vascular disease (PH
PVD
, defined as pulmonary artery wedge pressure [PAWP]≤15 mm Hg and PVR>3 WU). Age averaged 61.3±14.8 years, μPAWP and PVR were 16.4±7.1 mm Hg and 6.3±4.0 WU, respectively, and 52 (48.1%) patients fulfilled PH
PVD
hemodynamic criteria. The derived prediction rule ranged from –2 to +2 with higher scores suggesting higher probability of PH
PVD
: +1 point for left atrial anterior–posterior dimension <3.2 cm; +1 for presence of a mid systolic notch or acceleration time <80 ms; –1 for lateral mitral E:e′>10; –1 for left atrial anterior-posterior dimension >4.2 cm. PVR increased stepwise with score (for –2, 0, and +2, μPVR were 2.5, 4.5, and 8.1 WU, respectively), whereas the inverse was true for pulmonary artery wedge pressure (corresponding μPAWP were 21.5, 16.5, and 10.4 mm Hg). Among subjects with complete data, the score had an area under the curve (AUC) of 0.921 for PH
PVD
. A score ≥0 had 100% sensitivity and 69.3% positive predictive value for PH
PVD
, with 62.3% specificity. No patients with a negative score had PH
PVD
. Patients with a negative score and acceleration time >100 ms had normal PVR (μPVR=1.8 WU, range=0.7–3.2 WU).

Conclusions—
We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics, facilitates improved screening and focused clinical investigation for PH diagnosis and management.
Periprocedural Heparin Bridging in Patients Receiving Vitamin K Antagonists
Authors: Siegal Deborah , Yudin Jovana , Kaatz Scott , Douketis James D. , Lim Wendy , Spyropoulos Alex C. 
Published: August 2012

Background—
Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established.

Methods and Results—
MEDLINE, EMBASE, and Cochrane databases (2001–2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (κ=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0–3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0–1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42–1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00–9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52–8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04–2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27–4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non–vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses.

Conclusions—
Vitamin K antagonist–treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging.
CO2 Snow Deposition in Antarctica to Curtail Anthropogenic Global Warming
Authors: Agee Ernest , Orton Andrea , Rogers John 
Published: August 2012

AbstractA scientific plan is presented that proposes the construction of carbon dioxide (CO2) deposition plants in the Antarctic for removing CO2 gas from Earth’s atmosphere. The Antarctic continent offers the best environment on Earth for CO2 deposition at 1 bar of pressure and temperatures closest to that required for terrestrial air CO2 “snow” deposition—133 K. This plan consists of several components, including 1) air chemistry and CO2 snow deposition, 2) the deposition plant and a closed-loop liquid nitrogen refrigeration cycle, 3) the mass storage landfill, 4) power plant requirements, 5) prevention of dry ice sublimation, and 6) disposal (or use) of thermal waste. Calculations demonstrate that this project is worthy of consideration, whereby 446 deposition plants supported by sixteen 1200-MW wind farms can remove 1 billion tons (1012 kg) of carbon (1 GtC) annually (a reduction of 0.5 ppmv), which can be stored in an equivalent “landfill” volume of 2 km × 2 km × 160 m (insulated to prevent dry ice sublimation). The individual deposition plant, with a 100 m × 100 m × 100 m refrigeration chamber, would produce approximately 0.4 m of CO2 snow per day. The solid CO2 would be excavated into a 380 m × 380 m × 10 m insulated landfill, which would allow 1 yr of storage amounting to 2.24 × 10−3 GtC. Demonstrated success of a prototype system in the Antarctic would be followed by a complete installation of all 446 plants for CO2 snow deposition and storage (amounting to 1 billion tons annually), with wind farms positioned in favorable coastal regions with katabatic wind currents.
High-Resolution Vertical Profiles of X-Band Polarimetric Radar Observables during Snowfall in the Swiss Alps
Authors: Schneebeli Marc , Dawes Nicholas , Lehning Michael , Berne Alexis 
Published: August 2012

AbstractAn X-band polarimetric radar was deployed in the eastern Swiss Alps at an altitude of 2133 m. Radar measurements were complemented with several weather stations deployed in an altitude range from 1500 to 3100 m as well as with a fixed GPS ground station that was used to infer integrated water vapor estimates. Around 8000 vertical profiles of polarimetric radar observables above the melting layer collected during two months are analyzed. First, the behavior of the mean profiles of reflectivity at horizontal polarization Zh, differential reflectivity Zdr, copolar cross correlation ρhv, and specific differential phase shift Kdp are interpreted from a microphysical point of view. It is shown that the whole evolution of snowflakes, from pristine crystals at temperatures around −30°C to dendritic crystals around −15°C, to large aggregates around 0°C, is well captured by the polarimetric radar variables. In a second step, the profiles are analyzed as functions of high and low water vapor and snow accumulation conditions. It is found that the vertical profiles of polarimetric radar variables have distinct features in low versus high water vapor conditions. High water vapor conditions appear to favor the occurrence of crystal aggregates at high altitudes/low temperatures. It is shown with a hydrometeor identification scheme that graupel-like particles are found to be dominant right above the melting layer for snow events with high accumulation intensities. The present analyses show that measurements from X-band dual-polarization radar can be useful to characterize the dominant microphysical processes during precipitation in mountainous regions.
Influence of ENSO on the Diurnal Cycle of Rainfall over the Maritime Continent and Australia
Authors: Rauniyar Surendra P. , Walsh Kevin J. E. 
Published: August 2012

Abstract
This study examines the influence of ENSO on the diurnal cycle of rainfall during boreal winter for the period 1998–2010 over the Maritime Continent (MC) and Australia using Tropical Rainfall Measuring Mission (TRMM) and reanalysis data. The diurnal cycles are composited for the ENSO cold (La Niña) and warm (El Niño) phases. The k-means clustering technique is then applied to group the TRMM data into six clusters, each with a distinct diurnal cycle. Despite the alternating patterns of widespread large-scale subsidence and ascent associated with the Walker circulation, which dominates the climate over the MC during the opposing phases of ENSO, many of the islands of the MC show localized differences in rainfall anomalies that depend on the local geography and orography. While ocean regions mostly experience positive rainfall anomalies during La Niña, some local regions over the islands have more rainfall during El Niño. These local features are also associated with anomalies in the amplitude and characteristics of the diurnal cycle in these regions. These differences are also well depicted in large-scale dynamical fields derived from the interim ECMWF Re-Analysis (ERA-Interim).
Tracing Southwest Pacific Bottom Water Using Potential Vorticity and Helium-3
Authors: Downes Stephanie M. , Key Robert M. , Orsi Alejandro H. , Speer Kevin G. , Swift James H. 
Published: August 2012

Abstract
This study uses potential vorticity and other tracers to identify the pathways of the densest form of Circumpolar Deep Water in the South Pacific, termed “Southwest Pacific Bottom Water” (SPBW), along the 28.2 kg m−3 surface. This study focuses on the potential vorticity signals associated with three major dynamical processes occurring in the vicinity of the Pacific–Antarctic Ridge: 1) the strong flow of the Antarctic Circumpolar Current (ACC), 2) lateral eddy stirring, and 3) heat and stratification changes in bottom waters induced by hydrothermal vents. These processes result in southward and downstream advection of low potential vorticity along rising isopycnal surfaces. Using δ3He released from the hydrothermal vents, the influence of volcanic activity on the SPBW may be traced across the South Pacific along the path of the ACC to Drake Passage. SPBW also flows within the southern limb of the Ross Gyre, reaching the Antarctic Slope in places and contributes via entrainment to the formation of Antarctic Bottom Water. Finally, it is shown that the magnitude and location of the potential vorticity signals associated with SPBW have endured over at least the last two decades, and that they are unique to the South Pacific sector.
Internal Bores and Breaking Internal Tides on the Oregon Continental Slope
Authors: Martini Kim I. , Alford Matthew H. , Kunze Eric , Kelly Samuel M. , Nash Jonathan D. 
Published: August 2012

AbstractObservations of breaking internal tides on the Oregon continental slope during a 40-day deployment of 5 moorings along 43°12′N are presented. Remotely generated internal tides shoal onto the slope, steepen, break, and form turbulent bores that propagate upslope independently of the internal tide. A high-resolution snapshot of a single bore is captured from lowered acoustic Doppler current profilers (LADCP)/CTD profiles in a 25-h time series at 1200 m. The bore is cold, salty, over 100 m tall, and has a turbulent head where instantaneous dissipation rates are enhanced (ε &gt; 10−6 W kg−1) and sediment is resuspended. At the two deepest slope moorings (1452 and 1780 m), similar borelike phenomena are observed in near-bottom high-resolution temperature time series. Mean dissipation rates and diapycnal diffusivities increase by a factor of 2 when bores are present ( W kg−1 and m s−1) and observed internal tides are energetic enough to drive these enhanced dissipation rates. Globally, the authors estimate an average of 1.3 kW m−1 of internal tide energy flux is directed onto continental slopes. On the Oregon slope, internal tide fluxes are smaller, suggesting that it is a relatively weak internal tide sink. Mixing associated with the breaking of internal tides is therefore likely to be larger on other continental slopes.
Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats
Authors: El-Shinnawy Nashwa A , Abd-Elmageid Samira A , Alshailabi Eda MA 
Published: August 2012

The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.