bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone‐invasive oral squamous cell carcinoma
Authors: Martin C. K. , Dirksen W. P. , Carlton M. M. , Lanigan L. G. , Pillai S. P. , Werbeck J. L. , Simmons J. K. , Hildreth B. E. , London C. A. , Toribio R. E. , Rosol T. J. 
Published: May 2013

AbstractOral squamous cell carcinoma (OSCC) is common in cats and humans and invades oral bone. We hypothesized that the cyclooxygenase (COX)‐2 inhibitor, meloxicam, with the bisphosphonate, zoledronic acid (ZOL), would inhibit tumour growth, osteolysis and invasion in feline OSCC xenografts in mice. Human and feline OSCC cell lines expressed COX‐1 and COX‐2 and the SCCF2 cells had increased COX‐2 mRNA expression with bone conditioned medium. Luciferase‐expressing feline SCCF2Luc cells were injected beneath the perimaxillary gingiva and mice were treated with 0.1 mg kg−1 ZOL twice weekly, 0.3 mg kg−1 meloxicam daily, combined ZOL and meloxicam, or vehicle. ZOL inhibited osteoclastic bone resorption at the tumour–bone interface. Meloxicam was more effective than ZOL at reducing xenograft growth but did not affect osteoclastic bone resorption. Although a synergistic effect of combined ZOL and meloxicam was not observed, combination therapy was well‐tolerated and may be useful in the clinical management of bone‐invasive feline OSCC.
Use of viscoelastic coagulation testing to monitor low molecular weight heparin administration to healthy horses
Authors: Tennent‐Brown Brett S. , Epstein Kira L. , Whelchel Dorothy D. , Giguère Steeve 
Published: May 2013

AbstractObjectivesTo evaluate the utility of thromboelastography (TEG) and Sonoclot analyses to monitor the effects of low molecular weight heparin (LMWH) administration to healthy horses.DesignRandomized crossover study.SettingLarge animal veterinary teaching hospital.AnimalsSix adult mixed breed healthy mares.InterventionsLMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 h for 3 consecutive days. Blood samples were collected before LMWH administration and then at selected time points for analysis. Thromboelastography derived R‐time (R), K‐time (K), angle (ANG), and maximum amplitude (MA), and Sonoclot activated clot time (ACT), clot rate (CR), and platelet function (PF) were measured in whole blood 30 min after sample collection. Change (Δ) and percentage change (%Δ) from baseline of each TEG and Sonoclot variable were subsequently calculated. Anti‐factor Xa activity and activated partial thromboplastin time (aPTT) were assayed in harvested plasma. The association between anti‐factor Xa activity and TEG and Sonoclot (measured and calculated) variables was assessed by calculating correlation coefficients and multiple regression analysis. The ability of measured and calculated TEG and Sonoclot variables to predict when anti‐factor Xa activity fell below suggested thromboprophylactic levels was assessed using receiver operating characteristic curve analysis.Measurements and Main ResultsThe correlation between aPTT and anti‐factor Xa activity was weak (r= 0.343). Changes in TEG and Sonoclot variables following LMWH administration were consistent with hypocoagulation. All measured and calculated TEG variables were significantly correlated with anti‐factor Xa activity. Sonoclot ACT, ΔACT, CR, ΔCR, and %ΔCR were also significantly correlated with anti‐factor Xa activity. TEG ΔR and %ΔR best predicted anti‐factor Xa activity below the suggested thromboprophylactic level.ConclusionsAlthough correlations were modest, serial measurement of TEG variables may be used to monitor LMWH therapy in horses; however, further research is required in sick horses.
The use of high‐dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog
Authors: Maton Barbara L. , Simmonds Erin E. , Lee Justine A. , Alwood Amy J. 
Published: May 2013

AbstractObjectiveTo describe the novel use of high‐dose insulin (HDI) therapy and intravenous lipid emulsion (ILE) to treat refractory, severe diltiazem toxicosis in a dog.Case SummaryA 4‐year‐old Pomeranian was presented for treatment 2.5 hours following ingestion of a diltiazem extended‐release capsule. Toxic ingestion was calculated at a maximum exposure of 79 mg/kg, with a reported canine LD50 of 50 mg/kg. Clinical signs of progressive hypotension and severe bradycardia with atrial standstill were observed, which persisted despite treatment with atropine, calcium, glucagon, and dopamine. The novel use of HDI and ILE as part of therapy for diltiazem toxicosis resulted in clinical resolution of life‐threatening signs. Within 1 hour of initiating HDI therapy, the clinical signs improved, and with continued treatment, the patient remained normotensive and survived to discharge.New or Unique Information ProvidedTo the authors’ knowledge, this is the first reported clinical case describing the use of both HDI and ILE therapy in the treatment of severe refractory diltiazem toxicosis in veterinary medicine. No significant adverse effects were observed from the treatment. In veterinary patients with severe refractory calcium channel blocker toxicosis, the use of HDI and ILE should be considered for life‐threatening clinical signs.
Adipocytokines, Inflammation, and Breast Cancer Risk in Postmenopausal Women: A Prospective Study
Authors: Gross Amy L. , Newschaffer Craig J. , Hoffman-Bolton Judith , Rifai Nader , Visvanathan Kala 
Published: May 2013

Abstract
Obesity is a known risk factor for postmenopausal breast cancer; it has been postulated that adipocytokines may mediate this association. We explored the relationship between three markers altered by obesity: leptin, adiponectin, and soluble tumor necrosis factor receptor 2 (sTNF-R2), an inflammatory marker, with breast cancer risk in postmenopausal women. A nested case–control study of postmenopausal women was conducted within CLUE II, a prospective population-based cohort. Baseline plasma levels of leptin, adiponectin, and sTNF-R2 were assayed in 272 female breast cancer cases and 272 controls matched on age, date, and hour of blood draw. Conditional logistic regression was used to estimate matched odds ratios (OR) and 95% confidence intervals (CI). sTNF-R2 and leptin were independently positively associated with breast cancer risk in adjusted models. The OR for breast cancer comparing the highest to lowest tertile was 2.44 (95% CI: 1.30–4.58) for sTNF-R2 and 1.98 (95% CI: 1.20–3.29) for leptin. While higher levels of adiponectin were protective (OR for the lowest tertile = 1.63; 95% CI: 1.02–2.60), there was no dose response. A 20% reduction in the breast cancer risk associated with overweight/obesity was observed when sTNF-R2 alone was included in multivariable models. Including both sTNF-R2 and adiponectin in the models resulted in a 29% reduction in the OR. Adipocytokines and sTNF-R2 are important factors in the etiology of postmenopausal breast cancer due to adiposity. This study informs our understanding of the relationship between obesity, inflammation, and postmenopausal breast cancer and identifies potential biomarkers. Cancer Epidemiol Biomarkers Prev; 22(7); 1319–24. ©2013 AACR.
A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602)
Authors: Slingluff Craig L. , Lee Sandra , Zhao Fengmin , Chianese-Bullock Kimberly A. , Olson Walter C. , Butterfield Lisa H. , Whiteside Theresa L. , Leming Philip D. , Kirkwood John M. 
Published: May 2013

AbstractPurpose: This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma.Experimental Design: One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CTL (12MP, group A), plus a tetanus peptide (group B), or a mixture of 6 melanoma helper peptides (6MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6 melanoma helper peptide (6MHP) alone (group D), in incomplete Freund's adjuvant plus granulocyte macrophage colony-stimulating factor. CTL responses were assessed using an in vitro-stimulated IFN-γ ELIspot assay, and HTL responses were assessed using a proliferation assay.Results: In groups A to D, respectively, CTL response rates to 12 melanoma peptides were 43%, 47%, 28%, and 5%, and HTL response rates to 6MHP were in 3%, 0%, 40%, and 41%. Best clinical response was partial response in 7 of 148 evaluable patients (4.7%) without significant difference among study arms. Median overall survival (OS) was 11.8 months. Immune response to 6 MHP was significantly associated with both clinical response (P = 0.036) and OS (P = 0.004).Conclusion: Each vaccine regimen was immunogenic, but MHPs did not augment CTL responses to 12 melanoma peptides. The association of survival and immune response to 6MHP supports further investigation of helper peptide vaccines. For patients with advanced melanoma, multipeptide vaccines should be studied in combination with other potentially synergistic active therapies. Clin Cancer Res; 19(15); 4228–38. ©2013 AACR.
Glutathione S-Transferase Mu2 Suppresses Cancer Cell Metastasis in Non–Small Cell Lung Cancer
Authors: Tang Sheau-Chung , Wu Chih-Hsien , Lai Chien-Hung , Sung Wen-Wei , Yang Wan-Jung , Tang Lee-Chun , Hsu Chung-Ping , Ko Jiunn-Liang 
Published: May 2013

Abstract
Glutathione S-transferase mu2 (GST-M2) is a phase II detoxification enzyme. Low expression of GST-M2 in lung cancers is due to hypermethylation of its promoter. Lung cancer with the GST mu-null genotype is associated with shorter survival. However, a correlation between GST-M2 and important clinical parameters, as well as the migration of GST-M2–defective cells in lung cancer, has not been established. In the present study, we investigate the role of GST-M2 in cell migration and actin disassembly in lung cancer cells. GST-M2 and CCN2 mRNA levels were significantly reduced in non–small cell lung cancer (NSCLC) tumors when compared with matched normal lung tissues in 82 patients with NSCLC. We found that high expressions of both GST-M2 and CCN2 are correlated with favorable survival of patients with lung cancer when compared with similar patients without GST-M2 or CCN2 expression. GST-M2 can induce CCN2 expression by driving the CCN2 proximal promoter. Overexpression of GST-M2 decreases the formation of filopodia, resulting in remodeling of the reorganized cytoskeletons. Overexpression of GST-M2 significantly suppressed cancer cell migration on wound-healing assay. In addition, overexpression of GST-M2 dramatically reduced tumor growth and metastasis in a xenograft mouse model. These data highlight the potential of GST-M2 as a novel tumor suppressor. GST-M2 increases the expression of CCN2 in lung cancer cells, which inhibits cancer cell migration in lung cancer and animal models. Mol Cancer Res; 11(5); 518–29. ©2013 AACR.
A Tale of Metabolites: The Cross-Talk between Chromatin and Energy Metabolism
Authors: Martinez-Pastor Barbara , Cosentino Claudia , Mostoslavsky Raul 
Published: May 2013

Abstract
Mitochondrial metabolism influences histone and DNA modifications by retrograde signaling and activation of transcriptional programs. Considering the high number of putative sites for acetylation and methylation in chromatin, we propose in this perspective article that epigenetic modifications might impinge on cellular metabolism by affecting the pool of acetyl-CoA and S-adenosylmethionine. Cancer Discov; 3(5); 497–501. ©2013 AACR.
Déjà Vu: EGF Receptors Drive Resistance to BRAF Inhibitors
Authors: Girotti Maria Romina , Marais Richard 
Published: May 2013

Abstract
Summary: The promise of personalized medicine is upon us, and in some cancers, targeted therapies are rapidly becoming the mainstay of treatment for selected patients based on their molecular profile. The protein kinase BRAF is a driver oncogene in both thyroid cancer and melanoma, but while drugs that target BRAF and its downstream signaling pathway are effective in melanoma, they are ineffective in thyroid cancer. In this issue of Cancer Discovery, Montero-Conde and colleagues investigate why thyroid cancer is resistant to BRAF inhibitors despite the presence of BRAF mutation. Cancer Discov; 3(5); 487–90. ©2013 AACR.
See related article by Montero-Conde et al., p. 520
Long-Term Outcomes After Invasive Management for Older Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Roe Matthew T. , Li Shuang , Thomas Laine , Wang Tracy Y. , Alexander Karen P. , Ohman E. Magnus , Peterson Eric D. 
Published: May 2013

Background—
Early invasive management is recommended for patients with non–ST-segment elevation myocardial infarction (MI), but the incidence of long-term outcomes after early catheterization among older patients and the relationship of revascularization procedures with outcomes in this population have not been described.

Methods and Results—

Using data from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) registry, we linked 19 336 older patients (≥65 years) with non–ST-segment elevation MI found to have significant coronary disease during catheterization and who survived through 30 days posthospital discharge to Medicare/Medicaid data. All-cause mortality, readmission for MI, readmission for stroke, and use of repeat revascularization procedures were tracked for a median of 1181 days. Outcome comparisons were stratified by use of percutaneous coronary intervention (PCI; n=11 766, 60.8%) or coronary artery bypass grafting (n=3515, 18.2%) performed during the index hospitalization and through 30 days postdischarge, as well as by medical management without revascularization (n=4055, 21.0%). During follow-up, ≈17% of patients underwent PCI (most commonly in patients initially treated with PCI), and only 3% of patients underwent coronary artery bypass grafting. Compared with an unadjusted long-term mortality cumulative incidence through 5 years of 50% in the medical management group, mortality was lower in the PCI group (33.5%; adjusted hazard ratio, 0.75; 95% confidence interval, 0.70–0.79) and lowest in the coronary artery bypass grafting group (24.2%; adjusted hazard ratio, 0.52; 95% confidence interval, 0.47–0.57;
P
<0.001 for 3-way comparisons). The unadjusted cumulative incidence of the composite of death, readmission for MI, or readmission for stroke at 5 years was 62.4%, 44.9%, and 33.0% for medical management, PCI, and coronary artery bypass grafting, respectively.

Conclusions—
Older patients with non–ST-segment elevation MI with significant coronary disease face high long-term risks for mortality and nonfatal cardiovascular outcomes after early catheterization that differ by type of revascularization procedure performed. These findings can help guide the design of studies evaluating long-term therapies among elderly post-MI patients.
Cilostazol Reduces Angiographic Restenosis After Endovascular Therapy for Femoropopliteal Lesions in the Sufficient Treatment of Peripheral Intervention by Cilostazol Study
Authors: Iida Osamu , Yokoi Hiroyoshi , Soga Yoshimitsu , Inoue Naoto , Suzuki Kenji , Yokoi Yoshiaki , Kawasaki Daizo , Zen Kan , Urasawa Kazushi , Shintani Yoshiaki , Miyamoto Akira , Hirano Keisuke , Miyashita Yusuke , Tsuchiya Taketsugu , Shinozaki Norihiko , Nakamura Masato , Isshiki Takaaki , Hamasaki Toshimitsu , Nanto Shinsuke 
Published: May 2013

Background—
It remains unclear whether cilostazol, which has been shown to improve the clinical outcomes of endovascular therapy for femoropopliteal lesions, also reduces angiographic restenosis.

Methods and Results—

The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study investigated whether cilostazol reduces the 12-month angiographic restenosis rate after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Two hundred patients with femoropopliteal lesions treated from March 2009 to April 2011 at 13 cardiovascular centers were randomly assigned 1:1 to receive oral aspirin with or without cilostazol. The primary end point was 12-month angiographic restenosis rate. Secondary end points were the restenosis rate on duplex ultrasound, the rate of major adverse cardiac events, and target lesion event-free survival. Researchers evaluated all follow-up data and assessed the end points in a blinded fashion. The mean lesion length and reference vessel diameter at the treated segment were 128±86 mm and 5.4±1.4 mm, respectively. The frequency of stent used was similar between groups (88% versus 90% in the cilostazol and noncilostazol group, respectively,
P
=0.82). During the 12-month follow-up period, 11 patients died and 152 patients (80%) had evaluable angiographic data at 12 months. The angiographic restenosis rate at 12 months was 20% (15/75) in the cilostazol group versus 49% (38/77) in the noncilostazol group (
P
=0.0001) by intention-to-treat analysis. The cilostazol group also had a significantly higher event-free survival at 12 months (83% versus 71%,
P
=0.02), although cardiovascular event rates were similar in both groups.

Conclusions—
Cilostazol reduced angiographic restenosis after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00912756; and URL:
https://www.umin.ac.jp
. Unique identifier: UMIN000002091.
Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement
Authors: Van Mieghem Nicolas M. , Schipper Marguerite E.I. , Ladich Elena , Faqiri Elham , van der Boon Robert , Randjgari Abas , Schultz Carl , Moelker Adriaan , van Geuns Robert-Jan , Otsuka Fumiyuki , Serruys Patrick W. , Virmani Renu , de Jaegere Peter P. 
Published: May 2013

Background—
Recent transcatheter aortic valve replacement studies have raised concerns about adverse cerebrovascular events. The etiopathology of the embolized material is currently unknown.

Methods and Results—
A total of 40 patients underwent transcatheter aortic valve replacement with the use of a dual filter–based embolic protection device (Montage Dual Filter System, Claret Medical, Inc). Macroscopic material liberated during the transcatheter aortic valve replacement procedure was captured in the device filter baskets in 30 (75%) patients and sent for histopathologic analysis. The captured material varied in size from 0.15 to 4.0 mm. Amorphous calcified material (size, 0.55–1.8 mm) was identified in 5 patients (17%). In 8 patients (27%), the captured material (size, 0.25–4.0 mm) contained valve tissue composed of loose connective tissue (collagen and elastic fibers) with focal areas of myxoid stroma, with or without coverage by endothelial cells and intermixed with fibrin. In another 13 (43%) patients, collagenous tissue, which may represent elements of vessel wall and valvelike structures, was identified. In 9 patients (30%), thrombotic material was intermixed with neutrophils (size, 0.15–2.0 mm). Overall, thrombotic material was found in 52% of patients, and tissue fragments compatible with aortic valve leaflet or aortic wall origin were found in 52% (21/40) of patients.

Conclusions—
Embolic debris traveling to the brain was captured in 75% of transcatheter aortic valve replacement procedures where a filter-based embolic protection device was used. The debris consisted of fibrin, or amorphous calcium and connective tissue derived most likely from either the native aortic valve leaflets or aortic wall.
Long-Term Cognitive Impairment After First-Ever Ischemic Stroke in Young Adults
Authors: Schaapsmeerders Pauline , Maaijwee Noortje A.M. , van Dijk Ewoud J. , Rutten-Jacobs Loes C.A. , Arntz Renate M. , Schoonderwaldt Hennie C. , Dorresteijn Lucille D.A. , Kessels Roy P.C. , de Leeuw Frank-Erik 
Published: May 2013

Background and Purpose—
Up to 14% of all ischemic strokes occur in young adults (<50 years). Poststroke cognitive performance is a decisive determinant of their quality of life. However, virtually no studies report on cognition after young stroke, especially not on the long term. This long-term perspective is important because young patients have a long life expectancy during which they start forming a family, have an active social life, and make decisive career moves. We aimed to evaluate the long-term cognitive outcome.

Methods—

All consecutive patients between January 1, 1980, and November 1, 2010, with a first-ever young ischemic stroke were recruited for cognitive assessment, using a matched stroke-free population as a reference. Composite
Z
scores for 7 cognitive domains were calculated and the ANCOVA model was used (Bonferroni correction). A below average performance was defined as >1.0 SD below the age-adjusted mean of the controls and cognitive impairment as >1.5 SD.

Results—
Two hundred seventy-seven patients and 146 matched controls completed cognitive assessment (mean follow-up, 11.0 years, SD, 8.2; age, 50.9 years, SD, 10.3). Long-term cognitive outcome after an ischemic stroke was worse in most cognitive domains compared with a nonstroke population. Up to 50% of the patients had a below average performance or cognitive impairment. Deficits in processing speed, working memory, and attention were most common.

Conclusions—
Even 11 years after ischemic stroke in young adults, a substantial proportion of patients must cope with permanent cognitive deficits. These results have implications for information given to patients and rehabilitation services.
Religious-Zionist Attitudes Towards the Peace Process
Authors: Gross Zehavit 
Published: May 2013

Abstract
The aim of this article is to analyse the attitudes of Religious-Zionists toward the Middle East peace process. The Religious-Zionist movement served as the flag-bearer for Jewish settlement in the occupied territories of Judea, Samaria and Gaza and the principal reserve of the settler population. The tragedy of Religious-Zionism may well be its desire to integrate within and benefit from historical realities originating in relative, pragmatic conceptions, along with its refusal or inability to liberate itself of thinking tools, conceptions and norms belonging to a theological, a-historical world controlled by absolute values and dreams. The dominant trend in Religious-Zionism was found to have a direct influence on the nature of Jewish public discourse and is expected to influence the shaping of Jewish society and culture in the State of Israel after the peace agreements are signed.