bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enoxaparin Prevents Steroid-Related Avascular Necrosis of the Femoral Head
Authors: Beckmann Rainer , Shaheen Hayfaa , Kweider Nisreen , Ghassemi Alireza , Fragoulis Athanassios , Hermanns-Sachweh Benita , Pufe Thomas , Kadyrov Mamed , Drescher Wolf 
Published: July 2014

Nontraumatic osteonecrosis of the femoral head is still a challenging problem in orthopedic surgery. It is responsible for 10% of the 500,000 hip replacement surgeries in the USA and affects relatively young, active patients in particular. Main reasons for nontraumatic osteonecrosis are glucocorticoid use, alcoholism, thrombophilia, and hypofibrinolysis (Glueck et al., 1997; Orth and Anagnostakos, 2013). One pathomechanism of steroid-induced osteonecrosis is thought to be impaired blood flow to the femoral head caused by increased thrombus formation and vasoconstriction. To investigate the preventive effect of enoxaparin on steroid-related osteonecrosis, we used male New Zealand white rabbits. Osteonecrosis was induced by methylprednisolone-injection (1×20 mg/kg body weight). Control animals were treated with phosphate-buffered saline. Treatment consisted of an injection of 11.7 mg/kg body weight of enoxaparin per day (Clexane) in addition to methylprednisolone. Four weeks after methylprednisolone-injection the animals were sacrificed. Histology (hematoxylin-eosin and Ladewig staining) was performed, and empty lacunae and histological signs of osteonecrosis were quantified. Histomorphometry revealed a significant increase in empty lacunae and necrotic changed osteocytes in glucocorticoid-treated animals as compared with the glucocorticoid- and Clexane-treated animals and with the control group. No significant difference was detected between the glucocorticoid and Clexane group and the control group. This finding suggests that cotreatment with enoxaparin has the potential to prevent steroid-associated osteonecrosis.Corrigendum to “Enoxaparin Prevents Steroid-Related Avascular Necrosis of the Femoral Head”
Radius Constants for Analytic Functions with Fixed Second Coefficient
Authors: Nargesi Mahnaz M. , Ali Rosihan M. , Ravichandran V. 
Published: July 2014

Letf(z) = z +∑n=2∞anznbe analytic in the unit disk with the second coefficienta2satisfyinga2 = 2b,0≤b≤1. Sharp radius of Janowski starlikeness is obtained for functionsfwhosenth coefficient satisfiesan≤cn+d  (c,d≥0)oran≤c/n  (c>0  and  n≥3). Other radius constants are also obtained for these functions, and connections with earlier results are made.
Antimetastatic Effects of Blocking PD-1 and the Adenosine A2A Receptor
Authors: Mittal Deepak , Young Arabella , Stannard Kimberley , Yong Michelle , Teng Michele W.L. , Allard Bertrand , Stagg John , Smyth Mark J. 
Published: July 2014

Abstract
Adenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe clinical profile of adenosine A2A receptor inhibitors (A2ARi) in Parkinson disease. Metastasis is the main cause of cancer-related deaths worldwide, and therefore we have studied experimental and spontaneous mouse models of melanoma and breast cancer metastasis to demonstrate the efficacy and mechanism of a combination of A2ARi in combination with anti-PD-1 monoclonal antibody (mAb). This combination significantly reduces metastatic burden and prolongs the life of mice compared with either monotherapy alone. Importantly, the combination was only effective when the tumor expressed high levels of CD73, suggesting a tumor biomarker that at a minimum could be used to stratify patients that might receive this combination. The mechanism of the combination therapy was critically dependent on NK cells and IFNγ, and to a lesser extent, CD8+ T cells and the effector molecule, perforin. Overall, these results provide a strong rationale to use A2ARi with anti-PD-1 mAb for the treatment of minimal residual and metastatic disease. Cancer Res; 74(14); 3652–8. ©2014 AACR.
TMEFF2 Deregulation Contributes to Gastric Carcinogenesis and Indicates Poor Survival Outcome
Authors: Sun Tiantian , Du Wan , Xiong Hua , Yu Yanan , Weng Yurong , Ren Linlin , Zhao Huijun , Wang Yingchao , Chen Yingxuan , Xu Jie , Xiang Yongbing , Qin Wenxin , Cao Weibiao , Zou Weiping , Chen Haoyan , Hong Jie , Fang Jing-Yuan 
Published: July 2014

Abstract
Purpose: The role and clinical implication of the transmembrane protein with EGF and two follistatin motifs 2 (TMEFF2) in gastric cancer is poorly understood.
Experimental Design: Gene expression profile analyses were performed and Gene Set Enrichment Analysis (GSEA) was used to explore its gene signatures. AGS and MKN45 cells were transfected with TMEFF2 or control plasmids and analyzed for gene expression patterns, proliferation, and apoptosis. TMEFF2 expression was knocked down with shRNAs, and the effects on genome stability were assessed. Interactions between TMEFF2 and SHP-1 were determined by mass spectrometry and immunoprecipitation assays.
Results: Integrated analysis revealed that TMEFF2 expression was significantly decreased in gastric cancer cases and its expression was negatively correlated with the poor pathologic stage, large tumor size, and poor prognosis. GSEA in The Cancer Genome Atlas (TCGA) and Jilin datasets revealed that cell proliferation, apoptosis, and DNA damage–related genes were enriched in TMEFF2 lower expression patients. Gain of TMEFF2 function decreased cell proliferation by increasing of apoptosis and blocking of cell cycle in gastric cancer cells. The protein tyrosine phosphatase SHP-1 was identified as a binding partner of TMEEF2 and mediator of TMEFF2 function. TMEFF2 expression positively correlated with SHP-1, and a favorable prognosis was more likely in patients with gastric cancer with higher levels of both TMEFF2 and SHP-1.
Conclusion: TMEFF2 acts as a tumor suppressor in gastric cancer through direct interaction with SHP-1 and can be a potential biomarker of carcinogenesis. Clin Cancer Res; 20(17); 4689–704. ©2014 AACR.
Personalized Medicine for Patients with Advanced Cancer in the Phase I Program at MD Anderson: Validation and Landmark Analyses
Authors: Tsimberidou Apostolia-Maria , Wen Sijin , Hong David S. , Wheler Jennifer J. , Falchook Gerald S. , Fu Siqing , Piha-Paul Sarina , Naing Aung , Janku Filip , Aldape Kenneth , Ye Yang , Kurzrock Razelle , Berry Donald 
Published: July 2014

Abstract
Purpose: The purpose of this study was to confirm our previous results that targeted agents matched with tumor molecular alterations were associated with improved outcomes compared with nonmatched therapy in patients with advanced cancer.
Experimental Design: Outcomes of patients who were referred for treatment on phase I clinical trials at The University of Texas MD Anderson Cancer Center (Houston, TX) from March 2011 to January 2012 were compared between those who had received targeted therapy and those for whom no targeted therapy was available. Two-month landmark analyses for overall and progression-free survival (PFS) combining previously published and validation cohort patient data were performed.
Results: In patients with one alteration, matched therapy (n = 143) compared with treatment without matching (n = 236) was associated with a higher objective response rate (12% vs. 5%; P &lt; 0.0001), longer PFS (median, 3.9 vs. 2.2 months; P = 0.001), and longer survival (median, 11.4 vs. 8.6 months; P = 0.04). In multivariate analysis, matched therapy was an independent factor predicting response (P &lt; 0.015) and PFS (P &lt; 0.004). Two-month landmark analyses in the matched therapy group demonstrated that the median survival of responders was 30.5 months compared with 11.3 months for nonresponders (P = 0.01); and the median PFS was 38.7 months compared with 5.9 months, respectively (P &lt; 0.0001). The respective values in the nonmatched therapy group were 9.8 and 9.4 months (P = 0.46) and 8.5 and 4.2 months (P = 0.18).
Conclusion: This validation analysis confirms our previous observations. In the matched therapy group, 2-month landmark analyses demonstrated that responders have longer survival and PFS than nonresponders. Clin Cancer Res; 20(18); 4827–36. ©2014 AACR.
Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders
Authors: Gandini Sara , Puntoni Matteo , Heckman-Stoddard Brandy M. , Dunn Barbara K. , Ford Leslie , DeCensi Andrea , Szabo Eva 
Published: July 2014

Abstract
Previous meta-analyses have shown that the antidiabetic agent metformin is associated with reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models and recent epidemiologic studies. We performed a meta-analysis with a focus on confounders and biases, including body mass index (BMI), study type, and time-related biases. We identified 71 articles published between January 1, 1966, and May 31, 2013, through Pubmed, ISI Web of Science (Science Citation Index Expanded), Embase, and the Cochrane library that were related to metformin and cancer incidence or mortality. Study characteristics and outcomes were abstracted for each study that met inclusion criteria. We included estimates from 47 independent studies and 65,540 cancer cases in patients with diabetes. Overall cancer incidence was reduced by 31% [summary relative risk (SRR), 0.69; 95% confidence interval (CI), 0.52–0.90], although between-study heterogeneity was considerable (I2 = 88%). Cancer mortality was reduced by 34% (SRR, 0.66; 95% CI, 0.54–0.81; I2 = 21%). BMI-adjusted studies and studies without time-related biases also showed significant reduction in cancer incidence (SRR, 0.82; 95% CI, 0.70–0.96 with I2 = 76% and SRR, 0.90; 95% CI, 0.89–0.91 with I2 = 56%, respectively), albeit with lesser magnitude (18% and 10% reduction, respectively). However, studies of cancer mortality and individual organ sites did not consistently show significant reductions across all types of analyses. Although these associations may not be causal, our results show that metformin may reduce cancer incidence and mortality in patients with diabetes However, the reduction seems to be of modest magnitude and not affecting all populations equally. Clinical trials are needed to determine if these observations apply to nondiabetic populations and to specific organ sites. Cancer Prev Res; 7(9); 867–85. ©2014 AACR.
Prediction of 30-Year Risk for Cardiovascular Mortality by Fitness and Risk Factor Levels
Authors: Wickramasinghe Chanaka D. , Ayers Colby R. , Das Sandeep , de Lemos James A. , Willis Benjamin L. , Berry Jarett D. 
Published: July 2014

Background—
Fitness and traditional risk factors have well-known associations with cardiovascular disease (CVD) death in both short-term (10 years) and across the remaining lifespan. However, currently available short-term and long-term risk prediction tools do not incorporate measured fitness.

Methods and Results—

We included 16 533 participants from the Cooper Center Longitudinal Study (CCLS) without prior CVD. Fitness was measured using the Balke protocol. Sex-specific fitness levels were derived from the Balke treadmill times and categorized into low, intermediate, and high fit according to age- and sex-specific treadmill times. Sex-specific 30-year risk estimates for CVD death adjusted for competing risk of non-CVD death were estimated using the cause-specific hazards model and included age, body mass index, systolic blood pressure, fitness, diabetes mellitus, total cholesterol, and smoking. During a median follow-up period of 28 years, there were 1123 CVD deaths. The 30-year risk estimates for CVD mortality derived from the cause-specific hazards model demonstrated overall good calibration (Nam-D’Agostino χ
2
[men,
P
=0.286; women,
P
=0.664] and discrimination (
c
statistic; men, 0.81 [0.80–0.82] and women, 0.86 [0.82–0.91]). Across all risk factor strata, the presence of low fitness was associated with a greater 30-year risk for CVD death.

Conclusions—
Fitness represents an important additional covariate in 30-year risk prediction functions that may serve as a useful tool in clinical practice.
Socioeconomic Inequality and Peripheral Artery Disease Prevalence in US Adults
Authors: Pande Reena L. , Creager Mark A. 
Published: July 2014

Background—
Lower socioeconomic status is associated with cardiovascular disease. We sought to determine whether there is a higher prevalence of peripheral artery disease (PAD) in individuals with lower socioeconomic status.

Methods and Results—

We analyzed data from the National Health and Nutrition Examination Survey 1999 to 2004. PAD was defined based on an ankle–brachial index ≤0.90. Measures of socioeconomic status included poverty–income ratio, a ratio of self-reported income relative to the poverty line, and attained education level. Of 6791 eligible participants, overall weighted prevalence of PAD was 5.8% (SE, 0.3). PAD prevalence was significantly higher in individuals with low income and lower education. Individuals in the lowest of the 6 poverty–income ratio categories had more than a 2-fold increased odds of PAD compared with those in the highest poverty–income ratio category (odds ratio, 2.69; 95% confidence interval, 1.80–4.03;
P
<0.0001). This association remained significant even after multivariable adjustment (odds ratio, 1.64; 95% confidence interval, 1.04–2.6;
P
=0.034). Lower attained education level also associated with higher PAD prevalence (odds ratio, 2.8; 95% confidence interval, 1.96–4.0;
P
<0.0001) but was no longer significant after multivariable adjustment.

Conclusions—
Low income and lower attained education level are associated with PAD in US adults. These data suggest that individuals of lower socioeconomic status remain at high risk and highlight the need for education and advocacy efforts focused on these at-risk populations.
Quality-of-Life Outcomes With a Disodium EDTA Chelation Regimen for Coronary Disease
Authors: Mark Daniel B. , Anstrom Kevin J. , Clapp-Channing Nancy E. , Knight J. David , Boineau Robin , Goertz Christine , Rozema Theodore C. , Liu Diane M. , Nahin Richard L. , Rosenberg Yves , Drisko Jeanne , Lee Kerry L. , Lamas Gervasio A. 
Published: July 2014

Background—

The National Institutes of Health–funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stable coronary disease patients aged ≥50 years who were ≥6 months post–myocardial infarction (2003–2010) to 40 infusions of a multicomponent EDTA chelation solution or placebo. Chelation reduced the primary composite end point of mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio, 0.82; 95% confidence interval, 0.69–0.99;
P
=0.035).

Methods and Results—

In a randomly selected subset of 911 patients, we prospectively collected a battery of quality-of-life (QOL) instruments at baseline and at 6, 12, and 24 months after randomization. The prespecified primary QOL measures were the Duke Activity Status Index (Table I in the Data Supplement) and the Medical Outcomes Study Short-Form 36 Mental Health Inventory-5. All comparisons were by intention to treat. Baseline clinical and QOL variables were well balanced in the 451 patients randomized to chelation and in the 460 patients randomized to placebo. The Duke Activity Status Index improved in both groups during the first 6 months of therapy, but we found no evidence for a treatment-related difference (mean difference [chelation−placebo] during follow-up, 0.9 [95% confidence interval, −0.7 to 2.6;
P
=0.27]). There was no statistically significant evidence of a treatment-related difference in the Mental Health Inventory-5 during follow-up (mean difference, 1.0; 95% confidence interval, −0.1 to 2.0;
P
=0.08). None of the secondary QOL measures showed a consistent treatment-related difference.

Conclusions—
In stable, predominantly asymptomatic coronary disease patients with a history of myocardial infarction, EDTA chelation therapy did not have a detectable effect on QOL during 2 years of follow-up.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00044213.
Bone Marrow Cell Transplantation Time-Dependently Abolishes Efficacy of Granulocyte Colony-Stimulating Factor After Stroke in Hypertensive Rats
Authors: Pösel Claudia , Scheibe Johanna , Kranz Alexander , Bothe Viktoria , Quente Elfi , Fröhlich Wenke , Lange Franziska , Schäbitz Wolf-Rüdiger , Minnerup Jens , Boltze Johannes , Wagner Daniel-Christoph 
Published: July 2014

Background and Purpose—
We aimed to determine a possible synergistic effect of granulocyte colony-stimulating factor (G-CSF) and bone marrow–derived mononuclear cells (BM MNC) after stroke in spontaneously hypertensive rats.

Methods—
Male spontaneously hypertensive rats were subjected to middle cerebral artery occlusion and randomly assigned to daily injection of 50 μg/kg G-CSF for 5 days starting 1 hour after stroke (groups 1, 2, and 3) with additional intravenous transplantation of 1.5×10E7 BM MNC per kilogram at 6 hours (group 2) or 48 hours (group 3) after stroke, or control treatment (group 4). Circulating leukocyte counts and functional deficits, infarct volume, and brain edema were repeatedly assessed in the first week and first month.

Results—
G-CSF treatment led to a significant neutrophilia, to a reversal of postischemic depression of circulating leukocytes, and to a significantly improved functional recovery without affecting the infarct volume or brain edema. BM MNC cotransplantation was neutral after 6 hours, but reversed the functional effect of G-CSF after 48 hours. Short-term investigation of combined G-CSF and BM MNC treatment at 48 hours indicated splenic accumulation of granulocytes and transplanted cells, accompanied by a significant rise of granulocytes in the circulation and the ischemic brain.

Conclusions—
G-CSF improved functional recovery in spontaneously hypertensive rats, but this effect was abolished by cotransplantation of BM MNC after 48 hours. In the spleen, transplanted cells may hinder the clearance of granulocytes that were massively increased by G-CSF. Increased circulation and infiltration of granulocytes into the ischemic brain may be detrimental for stroke outcome.
Rivaroxaban and Apixaban Reduce Hemorrhagic Transformation After Thrombolysis by Protection of Neurovascular Unit in Rat
Authors: Kono Syoichiro , Yamashita Toru , Deguchi Kentaro , Omote Yoshio , Yunoki Taijun , Sato Kota , Kurata Tomoko , Hishikawa Nozomi , Abe Koji 
Published: July 2014

Background and Purpose—
This study aimed to assess the risk and benefit of tissue-type plasminogen activator treatment after oral anticoagulation with rivaroxaban or apixaban compared with warfarin or placebo.

Methods—
Pretreatment with warfarin (0.2 mg/kg per day), rivaroxaban (2 mg/kg per day), apixaban (10 mg/kg per day), or vehicle (0.5% carboxymethyl cellulose sodium salt) was performed for 7 days. Transient middle cerebral artery occlusion was then induced for 120 minutes, followed by reperfusion with tissue-type plasminogen activator (10 mg/kg per 10 mL). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. Twenty-four hours after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and matrix metalloproteinase-9 activity was measured by zymography.

Results—
The paraparesis score was significantly improved in the rivaroxaban-pretreated group compared with the warfarin-pretreated group. Intracerebral hemorrhage was observed in the warfarin-pretreated group, and this was reduced in the rivaroxaban and apixaban-pretreated groups compared with the vehicle group. Marked dissociation of astrocyte foot processes and the basal lamina or pericytes was observed in the warfarin-pretreated group, and this was improved in the rivaroxaban and apixaban-pretreated groups. Furthermore, activation of matrix metalloproteinase-9 in the ipsilateral warfarin-pretreated brain was greatly reduced in rivaroxaban- and apixaban-pretreated rats.

Conclusions—
This study shows a lower risk of intracerebral hemorrhage after tissue-type plasminogen activator treatment in rats with ischemic stroke that are pretreated with rivaroxaban and apixaban compared with pretreatment with warfarin. Reducing neurovascular dissociation by rivaroxaban and apixaban compared with warfarin could partly explain a reduction in hemorrhagic complications reported in clinical studies.
Hemodynamic Quantification in Brain Arteriovenous Malformations With Time-Resolved Spin-Labeled Magnetic Resonance Angiography
Authors: Raoult Hélène , Bannier Elise , Maurel Pierre , Neyton Clément , Ferré Jean-Christophe , Schmitt Peter , Barillot Christian , Gauvrit Jean-Yves 
Published: July 2014

Background and Purpose—
Unenhanced time-resolved spin-labeled magnetic resonance angiography enables hemodynamic quantification in arteriovenous malformations (AVMs). Our purpose was to identify quantitative parameters that discriminate among different AVM components and to relate hemodynamic patterns with rupture risk.

Methods—

Sixteen patients presenting with AVMs (7 women, 9 men; mean age 37.1±15.9 years) were assigned to the high rupture risk or low rupture risk group according to anatomic AVM characteristics and rupture history. High temporal resolution (<70 ms) unenhanced time-resolved spin-labeled magnetic resonance angiography was performed on a 3-T MR system. After dedicated image processing, hemodynamic quantitative parameters were computed.
T
tests were used to compare quantitative parameters among AVM components, between the high rupture risk and low rupture risk groups, and between the hemorrhagic and nonhemorrhagic groups.

Results—

Among the quantitative parameters, time-to-peak (
P
<0.001) and maximum outflow gradient (
P
=0.01) allowed discriminating various intranidal flow patterns with significantly different values between feeding arteries and draining veins. With 9 AVMs classified into the high rupture risk group (whose 6 were hemorrhagic) and 7 into the low rupture risk group, the observed venous-to-arterial time-to-peak ratio was significantly lower in the high rupture risk (
P
=0.003) and hemorrhagic (
P
=0.001) groups.

Conclusions—
Unenhanced time-resolved spin-labeled magnetic resonance angiography allows AVM-specific combined anatomic and quantitative analysis of AVM hemodynamics.
Two new Sabicea (Rubiaceae) species from West Central Africa: Sabicea bullata and Sabicea urniformis
Authors: Zemagho Lise , Lachenaud Olivier , Dessein Steven , Liede-Schumann Sigrid , Sonké Bonaventure 
Published: July 2014

Two distinctive new species of Sabicea (Rubiaceae) from the Lower Guinea region are described and illustrated. Sabicea bullata is easily recognized by its cordate leaves, which are strongly bullate above, and its sessile glomerulate inflorescences. It is restricted to the Rumpi Hills and Bakossi Mountains, in southwestern Cameroon. Sabicea urniformis, from southern Gabon and Congo-Brazzaville, is remarkable in having discolorous leaves and an urn-shaped involucre with bracts shortly connate at the base. Detailed descriptions and botanical drawings are provided, conservation status assessed and taxonomic affinities discussed.