bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent Temozolomide and Dose-Escalated Intensity-Modulated Radiation Therapy in Newly Diagnosed Glioblastoma
Authors: Tsien Christina I. , Brown Doris , Normolle Daniel , Schipper Matthew , Piert Morand , Junck Larry , Heth Jason , Gomez-Hassan Diana , Ten Haken Randall K. , Chenevert Thomas , Cao Yue , Lawrence Theodore 
Published: November 2011

Abstract
Purpose: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of 11C methionine PET (MET-PET) imaging in predicting recurrence.
Experimental Design: Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m2) followed by adjuvant cyclic temozolomide (200 mg/m2 d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure.
Results: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0–32.5) and 9.0 (6.0–11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P &lt; 0.001).
Conclusions: Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions. Clin Cancer Res; 18(1); 273–9. ©2011 AACR.
Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma
Authors: Carbone Michele , Yang Haining 
Published: November 2011

Abstract
Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-κB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16INK4a and p14ARF are frequently inactivated in human mesothelioma, and ∼50% of mesotheliomas contain the NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except possibly for a small subset of patients who benefit from certain therapies. Recent studies have shown the importance of asbestos-induced inflammation in the initiation and growth of mesothelioma, and HMGB1 and Nalp3 inflammasome have been identified as key initiators of this process. Asbestos induces cell necrosis, causing the release of HMGB1, which in turn may activate Nalp3 inflammasome, a process that is enhanced by asbestos-induced production of reactive oxygen species. HMGB1 and Nalp3 induce proinflammatory responses and lead to interleukin-1β and TNF-α secretion and NF-κB activity, thereby promoting cell survival and tumor growth. Novel strategies that interfere with asbestos- and erionite-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including genetically predisposed individuals, and/or inhibit tumor growth. The very recent discovery that germline BAP1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma, and melanocytic tumors provides researchers with a novel target for prevention and early detection. Clin Cancer Res; 18(3); 598–604. ©2011 AACR.
Lung Cancer in Mice Induced by the Jaagsiekte Sheep Retrovirus Envelope Protein Is Not Maintained by Rare Cancer Stem Cells, but Tumorigenicity Does Correlate with Wnt Pathway Activation
Authors: Vaughan Andrew E. , Halbert Christine L. , Wootton Sarah K. , Miller A. Dusty 
Published: November 2011

Abstract
JSRV, a simple beta-retrovirus, is the etiologic agent of ovine pulmonary adenocarcinoma, a form of non–small cell lung cancer in sheep and goats. It has been shown that the envelope protein alone is sufficient to induce tumorigenesis in the lungs of mice when delivered via an adeno-associated viral vector. Here, we tested the hypothesis that JSRV envelope–induced tumors are maintained by a small population of tumor-initiating cells, termed cancer stem cells. To test this hypothesis, dissociated cancer cells were sorted from envelope-induced tumors in mouse lung based on the putative stem cell markers Sca-1, CD34, and CD133, the pluripotency-associated transcription factor Oct4, and the level of Wnt signaling. No association with increased tumor-initiating capacity was found with any of the cell-surface markers. In addition, we were unable to detect any evidence of Oct4 expression in tumor-bearing mouse lung. However, tumor cells possessing an active Wnt signaling pathway did show a significant correlation with increased tumor formation upon transplantation. Limiting dilution transplant analysis suggests the existence of a large fraction of cells with the ability to propagate tumor growth, with increasing tumor initiation potential correlating with activated Wnt signaling. Mol Cancer Res; 10(1); 86–95. ©2011 AACR.
Remote-Controlled Magnetic Navigation and Ablation With 3D Image Integration as an Alternative Approach in Patients With Intra-Atrial Baffle Anatomy
Authors: Ernst Sabine , Babu-Narayan Sonya V. , Keegan Jennifer , Horduna Irina , Lyne Jonathan , Till Janice , Kilner Philip J. , Pennell Dudley , Rigby Michael L. , Gatzoulis Michael A. 
Published: November 2011

Background—
Improvement in outcome of infants born with congenital heart defects has been accompanied by an increasing frequency of late arrhythmias. Ablation is difficult because of multiple tachycardias in the presence of complex anatomy with limited accessibility. We report on remote-controlled ablation using magnetic navigation in conjunction with 3D image integration in patients with previous intra-atrial baffle procedures.

Methods and Results—
Thirteen patients (8 male; age, 30.5±8 years) with supraventricular tachycardia (SVT) underwent catheter ablation. Group A had a medical history of a Mustard or Senning operation, whereas group B had undergone total cavopulmonary connection. A total of 26 tachycardias were treated in 17 procedures (median cycle length of 280 ms). Group A patients had more inducible SVTs than group B, and all index SVTs were located in the remainder of the morphological right atrium in all but 1 patient. Retrograde access through the aorta was performed and led to successful ablation, using magnetic navigation with a very low total radiation exposure (median of 3.8 minutes in group A versus 5.9 minutes in group B). Only 1 of 13 patients continued to have short-lasting SVTs despite 3 ablation procedures during a median follow-up time of >200 days.

Conclusions—
Remote-controlled catheter ablation by magnetic navigation in combination with accurate 3D image integration allowed safe and successful elimination of SVTs, using an exclusively retrograde approach, resulting in low radiation exposure for patients after intra-atrial baffle procedures (Mustard, Senning, or total cavopulmonary connection).
Statin Use in Outpatients With Obstructive Coronary Artery Disease
Authors: Arnold Suzanne V. , Spertus John A. , Tang Fengming , Krumholz Harlan M. , Borden William B. , Farmer Steven A. , Ting Henry H. , Chan Paul S. 
Published: November 2011

Background—
Clinical trials have shown that statin therapy reduces cardiovascular morbidity and mortality in patients with coronary artery disease (CAD), even among patients with low-density lipoprotein cholesterol levels <100 mg/dL. We sought to determine the extent to which patients with obstructive CAD in routine outpatient care are treated with statins, nonstatins, or no lipid-lowering therapy.

Methods and Results—
Within the American College of Cardiology's Practice Innovation and Clinical Excellence (PINNACLE) outpatient registry, we examined rates of treatment with statin and nonstatin medications in 38 775 outpatients with obstructive CAD (history of myocardial infarction or coronary revascularization) and without documented contraindications to statin therapy. Among these patients, 30 160 (77.8%) were prescribed statins, 2042 (5.3%) were treated only with nonstatin lipid-lowering medications, and 6573 (17.0%) were untreated. Lack of medical insurance was associated with no statin treatment, and male sex, coexisting hypertension, and a recent coronary revascularization were associated with statin treatment. Among those not on any lipid-lowering therapy, low-density lipoprotein cholesterol levels were available for 51.2% (3365/6573). Among these untreated patients, low-density lipoprotein cholesterol levels were <100 mg/dL in 1794 patients (53.3%) and ≥100 mg/dL in 1571 patients (46.7%).

Conclusions—
Despite robust clinical trial evidence, a substantial number of patients with obstructive CAD remain untreated with statins. A small proportion were treated with nonstatin therapy, and 1 in 6 patients was simply untreated; half of the untreated patients had low-density lipoprotein cholesterol values <100 mg/dL. These findings illustrate important opportunities to improve lipid management in outpatients with obstructive CAD.
Mild Retinopathy Is a Risk Factor for Cardiovascular Mortality in Japanese With and Without Hypertension
Authors: Sairenchi Toshimi , Iso Hiroyasu , Yamagishi Kazumasa , Irie Fujiko , Okubo Yoshiro , Gunji Junko , Muto Takashi , Ota Hitoshi 
Published: November 2011

Background—
It is unclear whether mild hypertensive retinopathy is a risk factor for mortality. This study examined whether mild hypertensive retinopathy could be a risk factor for cardiovascular mortality in subjects with and without hypertension.

Methods and Results—
In this cohort study, 87 890 individuals (29 917 men and 57 973 women) 40 to 79 years of age in 1993 were followed up until 2008. Retinal photography was classified as normal, grade 1, or grade 2 based on the Keith-Wagener-Barker system. Risk ratios for all-cause and cause-specific mortality for each classification were calculated with Cox proportional hazards regression models. Covariates included age, systolic blood pressure, antihypertensive medication use, and other cardiovascular risk factors. Multivariable hazard ratios for total cardiovascular disease mortality were 1.24 (95% confidence interval [CI], 1.12–1.38) and 1.23 (95% CI, 1.03–1.47) for grades 1 and 2 among men and 1.12 (95% CI, 1.01–1.24) and 1.44 (95% CI, 1.24–1.68) for grades 1 and 2 among women, respectively. Hazard ratios for total stroke mortality were 1.31 (95% CI, 1.13–1.53) and 1.38 (95% CI, 1.08–1.77) for grades 1 and 2 among men and 1.30 (95% CI, 1.12–1.50) and 1.70 (95% CI, 1.36–2.11) for grades 1 and 2 among women, respectively. For both hypertensive and normotensive subjects of each sex, multivariable hazard ratios for all-cause mortality, total cardiovascular mortality, and total stroke mortality were significantly higher for grade 1 or 2 compared with normal.

Conclusions—
Mild hypertensive retinopathy is a risk factor for cardiovascular mortality independently of cardiovascular risk factors among men and women with and without hypertension.
Multiscale Waves in an MJO Background and Convective Momentum Transport Feedback
Authors: Khouider Boualem , Han Ying , Majda Andrew J. , Stechmann Samuel N. 
Published: November 2011

Abstract
The authors use linear analysis for a simple model to study the evolution of convectively coupled waves (CCWs) in a background shear and background moisture mimicking the observed structure of the Madden–Julian oscillation (MJO). This is motivated by the observation, in an idealized setting, of intraseasonal two-way interactions between CCWs and a background wind. It is found here that profiles with a bottom-heavy moisture content are more favorable to the development of mesoscale/squall line–like waves whereas synoptic-scale CCWs are typically more sensitive to the shear strength. The MJO envelope is thus divided into three regions, in terms of the types of CCWs that are favored: an onset region in front that is favorable to Kelvin waves, a mature or active region in the middle in which squall lines are prominent, and the stratiform and decay phase region in the back that is favorable to westward inertia–gravity (WIG) waves. A plausible convective momentum transport (CMT) feedback is then provided according to the results of the idealized two-way interaction model. The active region, in particular, coincides with the westerly wind burst where both Kelvin waves and squall lines are believed to play a significant role in both the deceleration of low-/high-level easterly/westerly winds and the acceleration of low-/high-level westerly/easterly winds. The WIG waves in the wake could be a precursor for a subsequent MJO event through the acceleration of low-/high-level easterly/westerly winds, which in turn favor Kelvin waves, and the cycle repeats. These results open interesting directions for future studies using observations and/or detailed numerical simulations using the full primitive equation.
Fear of Crime in Belgrade
Authors: Nikolic-Ristanovic Vesna 
Published: November 2011

This paper reports research findings from the capital city of Yugoslavia, Belgrade. Both fear of crime and opportunity theory suggestions were tested. Differences in victimization experience influencing day/night time fear of crime, as well as differences in day/night time fear of crime influences on routine activities, were examined. Other factors influencing fear of specific crimes were examined. The research was carried out on a random sample comprising 400 respondents living in four Belgrade municipalities. The results of this research show that there exists a feeling of unsafeness in relation to criminal behavior. This feeling, of fear of crime, is more strongly felt at night than in daytime, and to a large extent represents a reflection of the objective risk of victimization. This is especially true of people who indicated fear of daytime crime. People tend to constrain and/or change their routine activities as a consequence of fear of crime; this tendency positively correlates with their level of fear. People who are afraid of daytime crime are more often constrained in their behavior than are those who fear night time crime.
The relationship between tissue factor and cancer progression: insights from bench and bedside
Authors: van den Berg Yascha W. , Osanto Susanne , Reitsma Pieter H. , Versteeg Henri H. 
Published: November 2011

AbstractIt is now widely recognized that a strong correlation exists between cancer and aberrant hemostasis. Patients with various types of cancers, including pancreatic, colorectal, and gastric cancer, often develop thrombosis, a phenomenon commonly referred to as Trousseau syndrome. Reciprocally, components from the coagulation cascade also influence cancer progression. The primary initiator of coagulation, the transmembrane receptor tissue factor (TF), has gained considerable attention as a determinant of tumor progression. On complex formation with its ligand, coagulation factor VIIa, TF influences protease-activated receptor-dependent tumor cell behavior, and regulates integrin function, which facilitate tumor angiogenesis both in vitro and in mouse models. Furthermore, evidence exists that an alternatively spliced isoform of TF also affects tumor growth and tumor angiogenesis. In patient material, TF expression and TF cytoplasmic domain phosphorylation correlate with disease outcome in many, but not in all, cancer subtypes, suggesting that TF-dependent signal transduction events are a potential target for therapeutic intervention in selected types of cancer. In this review, we summarize our current understanding of the role of TF in tumor growth and metastasis, and speculate on anticancer therapy by targeting TF.
The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia
Authors: Polak Roel , Buitenhuis Miranda 
Published: November 2011

AbstractAn important mediator of cytokine signaling implicated in regulation of hematopoiesis is the PI3K/protein kinase B (PKB/c-Akt) signaling module. Constitutive activation of this signaling module has been observed in a large group of leukemias. Because activation of this signaling pathway has been demonstrated to be sufficient to induce hematologic malignancies and is thought to correlate with poor prognosis and enhanced drug resistance, it is considered to be a promising target for therapy. A high number of pharmacologic inhibitors directed against either individual or multiple components of this pathway have already been developed to improve therapy. In this review, the safety and efficacy of both single and dual-specificity inhibitors will be discussed as well as the potential of combination therapy with either inhibitors directed against other signal transduction molecules or classic chemotherapy.
Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model
Authors: Chung Joo Hee , Choi Hee Jung , Kim Soo Young , Hong Kwan Soo , Min Soo Kee , Nam Myung Hee , Kim Chan Wha , Koh Young Ho , Seo Jong Bok 
Published: November 2011

Abstract

Background
To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders.

Results
By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models.

Conclusions
UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.
A 48 SNP set for grapevine cultivar identification
Authors: Cabezas José A , Ibáñez Javier , Lijavetzky Diego , Vélez Dolores , Bravo Gema , Rodríguez Virginia , Carreño Iván , Jermakow Angelica M , Carreño Juan , Ruiz-García Leonor , Thomas Mark R , Martinez-Zapater José M 
Published: November 2011

AbstractBackgroundRapid and consistent genotyping is an important requirement for cultivar identification in many crop species. Among them grapevine cultivars have been the subject of multiple studies given the large number of synonyms and homonyms generated during many centuries of vegetative multiplication and exchange. Simple sequence repeat (SSR) markers have been preferred until now because of their high level of polymorphism, their codominant nature and their high profile repeatability. However, the rapid application of partial or complete genome sequencing approaches is identifying thousands of single nucleotide polymorphisms (SNP) that can be very useful for such purposes. Although SNP markers are bi-allelic, and therefore not as polymorphic as microsatellites, the high number of loci that can be multiplexed and the possibilities of automation as well as their highly repeatable results under any analytical procedure make them the future markers of choice for any type of genetic identification.ResultsWe analyzed over 300 SNP in the genome of grapevine using a re-sequencing strategy in a selection of 11 genotypes. Among the identified polymorphisms, we selected 48 SNP spread across all grapevine chromosomes with allele frequencies balanced enough as to provide sufficient information content for genetic identification in grapevine allowing for good genotyping success rate. Marker stability was tested in repeated analyses of a selected group of cultivars obtained worldwide to demonstrate their usefulness in genetic identification.ConclusionsWe have selected a set of 48 stable SNP markers with a high discrimination power and a uniform genome distribution (2-3 markers/chromosome), which is proposed as a standard set for grapevine (Vitis viniferaL.) genotyping. Any previous problems derived from microsatellite allele confusion between labs or the need to run reference cultivars to identify allele sizes disappear using this type of marker. Furthermore, because SNP markers are bi-allelic, allele identification and genotype naming are extremely simple and genotypes obtained with different equipments and by different laboratories are always fully comparable.