bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital charges associated with motorcycle crash factors: a quantile regression analysis
Authors: Olsen Cody S , Thomas Andrea M , Cook Lawrence J 
Published: November 2013

BackgroundPrevious studies of motorcycle crash (MC) related hospital charges use trauma registries and hospital records, and do not adjust for the number of motorcyclists not requiring medical attention. This may lead to conservative estimates of helmet use effectiveness.MethodsMC records were probabilistically linked with emergency department and hospital records to obtain total hospital charges. Missing data were imputed. Multivariable quantile regression estimated reductions in hospital charges associated with helmet use and other crash factors.ResultsMotorcycle helmets were associated with reduced median hospital charges of $256 (42% reduction) and reduced 98th percentile of $32 390 (33% reduction). After adjusting for other factors, helmets were associated with reductions in charges in all upper percentiles studied. Quantile regression models described homogenous and heterogeneous associations between other crash factors and charges.ConclusionsQuantile regression comprehensively describes associations between crash factors and hospital charges. Helmet use among motorcyclists is associated with decreased hospital charges.
Area deprivation, individual socioeconomic status and low vision in the EPIC-Norfolk Eye Study
Authors: Yip Jennifer L Y , Luben Robert , Hayat Shabina , Khawaja Anthony P , Broadway David C , Wareham Nick , Khaw K T , Foster Paul J 
Published: November 2013

BackgroundPoor vision is associated with lower socioeconomic status, but less is known about its relationship to area deprivation.MethodsThe European Prospective Investigation into Cancer and Nutrition study Norfolk Eye Study was a cross-sectional study of 8563 participants with completed eye examinations. Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was measured using standard protocols and low vision (LV) was defined as Snellen equivalent (VA) ≤6/12 in the better eye. Uncorrected refractive error (URE) was defined as improvement of VA by 2 logarithm of the minimum angle of resolution lines with pinhole. The lowest 5% of index of multiple deprivation rank was used to define the most deprived areas. The index of multiple deprivation is a composite measure using routine data from seven domains of deprivation to identify the most disadvantaged areas in England. Logistic regression was used to examine univariable and multivariable associations with LV.ResultsNinety-six participants with missing data were excluded, leaving 8467 for analysis (98.9%). The mean age of the study group was 68.7 years (SD=8.1, range=48–92), with 55.1% women. LV was present in 263 participants (3.1%, 95% CI 2.7 to 3.5%). LV was associated with deprivation after adjusting for age, sex, education, social class and cataract surgery (OR=1.7, 95% CI 1.1 to 2.6, p=0.03), but this effect was mitigated by additionally adjusting for URE (OR=1.5, 95% CI 1.0 to 2.4, p=0.09).ConclusionsPeople with LV are more likely to live in the most deprived areas; this association was independent of socioeconomic status and partly mediated by URE. Targeting URE in deprived areas may reduce health inequalities associated with LV.
Genetic Ancestry and Risk of Mortality among U.S. Latinas with Breast Cancer
Authors: Fejerman Laura , Hu Donglei , Huntsman Scott , John Esther M. , Stern Mariana C. , Haiman Christopher A. , Pérez-Stable Eliseo J. , Ziv Elad 
Published: November 2013

Abstract
Multiple studies have reported that Latina women in the United States are diagnosed with breast cancer at more advanced stages and have poorer survival than non-Latina White women. However, Latinas are a heterogeneous group with individuals having different proportions of European, Indigenous American, and African genetic ancestry. In this study, we evaluated the association between genetic ancestry and survival after breast cancer diagnosis among 899 Latina women from the San Francisco Bay area. Genetic ancestry was estimated from single-nucleotide polymorphisms from an Affymetrix 6.0 array and we used Cox proportional hazards models to evaluate the association between genetic ancestry and breast cancer–specific mortality (tests were two-sided). Women were followed for an average of 9 years during which 75 died from breast cancer. Our results showed that Individuals with higher Indigenous American ancestry had increased risk of breast cancer-specific mortality [HR: 1.57 per 25% increase in Indigenous American ancestry; 95% confidence interval (CI): 1.08–2.29]. Adjustment for demographic factors, tumor characteristics, and some treatment information did not explain the observed association (HR: 1.75; 95%CI, 1.12–2.74). In an analysis in which ancestry was dichotomized, the hazard of mortality showed a two-fold increase when comparing women with less than 50% Indigenous American ancestry to women with 50% or more [HR, 1.89, 95%CI, 1.10–3.24]. This was also reflected by Kaplan–Meier survival estimates (P for log-rank test of 0.003). Overall, results suggest that genetic factors and/or unmeasured differences in treatment or access to care should be further explored to understand and reduce ethnic disparities in breast cancer outcomes. Cancer Res; 73(24); 7243–53. ©2013 AACR.
Phase II Study of the Oral MEK Inhibitor Selumetinib in Advanced Acute Myelogenous Leukemia: A University of Chicago Phase II Consortium Trial
Authors: Jain Nitin , Curran Emily , Iyengar Neil M. , Diaz-Flores Ernesto , Kunnavakkam Rangesh , Popplewell Leslie , Kirschbaum Mark H. , Karrison Theodore , Erba Harry P. , Green Margaret , Poire Xavier , Koval Greg , Shannon Kevin , Reddy Poluru L. , Joseph Loren , Atallah Ehab L. , Dy Philip , Thomas Sachdev P. , Smith Scott E. , Doyle L. Austin , Stadler Walter M. , Larson Richard A. , Stock Wendy , Odenike Olatoyosi 
Published: November 2013

Abstract
Purpose: The clinical relevance of targeting the RAS/RAF/MEK/ERK pathway, activated in 70% to 80% of patients with acute myelogenous leukemia (AML), is unknown.
Experimental Design: Selumetinib is an oral small-molecule inhibitor of MAP–ERK kinase (MEK)-1/2. Forty-seven patients with relapsed/refractory AML or 60 years old or more with untreated AML were enrolled on a phase II study. Patients were stratified by FLT3 ITD mutation status. The primary endpoint was response rate (complete, partial, and minor). Leukemia cells were analyzed for extracellular signal—regulated kinase (ERK) and mTOR phosphorylation.
Results: Common drug-related toxicities were grade 1–2 diarrhea, fatigue, nausea, vomiting, and skin rash. In the FLT3 wild-type cohort, six of 36 (17%) patients had a response [one partial response, three minor responses, two unconfirmed minor responses (uMR)]. No patient with FLT3 ITD responded. NRAS and KRAS mutations were detected in 7% and 2% of patients, respectively. The sole patient with KRAS mutation had uMR with hematologic improvement in platelets. Baseline p-ERK activation was observed in 85% of patients analyzed but did not correlate with a response. A single-nucleotide polymorphism (SNP) rs3733542 in exon 18 of the KIT gene was detected in significantly higher number of patients with response/stable disease compared with nonresponders (60% vs. 23%; P = 0.027).
Conclusions: Selumetinib is associated with modest single-agent antileukemic activity in advanced AML. However, given its favorable toxicity profile, combination with drugs that target other signaling pathways in AML should be considered. The potential association of SNP rs3733542 in exon 18 of the KIT gene with antileukemic activity of selumetinib is intriguing, but will require validation in larger trials. Clin Cancer Res; 20(2); 490–8. ©2013 AACR.
Neoadjuvant Imatinib in Advanced Primary or Locally Recurrent Dermatofibrosarcoma Protuberans: A Multicenter Phase II DeCOG Trial with Long-term Follow-up
Authors: Ugurel Selma , Mentzel Thomas , Utikal Jochen , Helmbold Peter , Mohr Peter , Pföhler Claudia , Schiller Meinhard , Hauschild Axel , Hein Rüdiger , Kämpgen Eckhardt , Kellner Ivonne , Leverkus Martin , Becker Jürgen C. , Ströbel Philip , Schadendorf Dirk 
Published: October 2013

Abstract
Purpose: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor. COL1A1–PDGFB gene fusion is frequent in DFSP, rendering tumor cell proliferation and survival dependent on PDGFRβ (platelet-derived growth factor receptor β) signaling. This trial investigated imatinib as neoadjuvant treatment of DFSP, including long-term follow-up.
Experimental Design: The primary endpoint of this multicenter phase II trial was response; secondary endpoints were safety, tumor relapse, and response biomarkers. Patients with advanced primary or locally recurrent DFSP and measurable disease by RECIST (response evaluation criteria in solid tumors) were eligible and received imatinib 600 mg/d until definitive surgery with histopathologic proof of tumor-free margins.
Results: Sixteen patients received imatinib, and 14 patients were evaluable for all endpoints. Median treatment duration was 3.1 months; median tumor shrinkage was 31.5%. Best overall response was 7.1% complete response (CR), 50.0% partial response (PR), 35.7% stable disease, and 7.1% progressive disease (PD). Toxicity was moderate with 25.0% grade 3 and 4 events. During a median follow-up of 6.4 years, one patient developed secondary resistance to imatinib but responded to second-line sunitinib. This patient also presented local recurrence, distant metastasis, and death from DFSP. Exploratory analysis showed that response to imatinib was associated with decreased tumor cellularity and formation of strong hyalinic fibrosis. Weak PDGFRB phosphorylation and pigmented-type DFSP were associated with nonresponse. Additional to PDGFRB, the kinases EGFR and insulin receptor were found activated in a high percentage of DFSPs.
Conclusion: The neoadjuvant use of imatinib 600 mg/d in DFSP is efficacious and well tolerated. Long-term follow-up results do not definitely support smaller surgical margins after successful imatinib pretreatment, and presume that secondary resistance to imatinib might promote accelerated disease progression. Clin Cancer Res; 20(2); 499–510. ©2013 AACR.
ERK-Dependent Downregulation of Skp2 Reduces Myc Activity with HGF, Leading to Inhibition of Cell Proliferation through a Decrease in Id1 Expression
Authors: Li Xiaoran , Bian Ying , Takizawa Yuri , Hashimoto Tomio , Ikoma Toshiyuki , Tanaka Junzo , Kitamura Naomi , Inagaki Yutaka , Komada Masayuki , Tanaka Toshiaki 
Published: November 2013

Abstract
Hepatocyte growth factor (HGF) has an inhibitory effect on human HepG2 hepatoma cell proliferation. Previously, it was shown that HGF treatment downregulated Id1 and upregulated p16INK4a in an ERK-dependent manner, leading to the inhibition of cellular proliferation. Here, new insight suggests that Skp2, an SCF complex component and potential prognosticator in cancer, is downregulated by injection of HGF into established HepG2 xenograft tumors. The downregulation was evident at both the mRNA and protein level and in an ERK-dependent manner. Critically, high expression of Skp2 restored HGF-inhibited cell proliferation, indicating that the inhibitory effect of HGF required the downregulation of Skp2. However, downregulation was not involved in the HGF-induced upregulation of a CDK inhibitor, p27Kip1, a known SCF-Skp2 target. Instead, data revealed that Skp2 regulated Myc activity, which has oncogenic potential in the generation of hepatocellular carcinoma. Elevated expression of Skp2 or a mutant that is unable to associate with the SCF complex was capable of activating Myc, suggesting that Skp2 does not act on Myc as a component of the SCF complex, and thus functions as an activator of Myc independent of its role in ubiquitination. Furthermore, Skp2 regulated Id1 expression by regulating Myc activity, and the regulation of Skp2 is involved in the activity of p16 promoter through regulation of Id1 expression. Overall, these mechanistic findings provide the first evidence that ERK-dependent downregulation of Skp2 reduced Myc activity, leading to HGF-induced inhibition of cell proliferation through decreased Id1 expression.
Implications: This study elucidates the molecular details of HGF-induced inhibition of cellular proliferation in liver cancer cells. Mol Cancer Res; 11(11); 1437–47. ©2013 AACR.
Third generation P2Y12 antagonists inhibit platelet aggregation more effectively than clopidogrel in a myocardial infarction registry
Authors: Diehl Philipp , Schnabel Katharina , Weik Patrick , Zhou Qian , Bode Christoph , Moser Martin , Olivier Christoph B. 
Published: October 2013

SummaryThe current standard of antiplatelet therapy of patients after myocardial infarction includes the P2Y12 receptor antagonists clopidogrel, prasugrel or ticagrelor. This study aimed to compare the antiplatelet effect of clopidogrel, prasugrel and ticagrelor in patients after myocardial infarction. In a single-centre registry the antiplatelet effect of clopidogrel, prasugrel and ticagrelor was investigated by aggregometry in patients after myocardial infarction. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 μM). To specifically quantify the effect of P2Y12 antagonists, whole blood was stimulated with 6.4 μM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP ratio to reflect an individual degree of P2Y12-dependent platelet inhibition. Platelet function of 238 patients was analysed [clopidogrel (n=58), prasugrel (n=65), ticagrelor (n=115)]. The r-ADP-agg was 35 ± 14% for patients receiving clopidogrel, 28 ± 10% for patients receiving prasugrel and 26 ± 11% for patients receiving ticagrelor. The r-ADP-agg was significantly lower in patients treated with prasugrel (p=0.0024) or ticagrelor (p<0.0001) compared to clopidogrel. There was no significant difference between patients receiving prasugrel or ticagrelor (p=0.2559). In conclusion, prasugrel and ticagrelor provide a stronger platelet inhibition compared to clopidogrel in patients after myocardial infarction. No significant difference in platelet inhibition was detected between prasugrel and ticagrelor. (registry for patients after Myocardial Infarction Treated with AntiPlatelet agents; DRKS00003146).
Age-Related Changes in Aortic Valve Hemostatic Protein Regulation
Authors: Balaoing Liezl R. , Post Allison D. , Liu Huiwen , Minn Kyung Taeck , Grande-Allen K. Jane 
Published: November 2013

Objective—
Although valvular endothelial cells have unique responses compared with vascular endothelial cells, valvular regulation of hemostasis is not well-understood. Heart valves remodel throughout a person’s lifetime, resulting in changes in extracellular matrix composition and tissue mechanical properties that may affect valvular endothelial cell hemostatic function. This work assessed valvular endothelial cell regulation of hemostasis in situ and in vitro as a function of specimen age.

Approach and Results—
Porcine aortic valves were assigned to 1 of 3 age groups: Young (YNG) (6 weeks); Adult (ADT) (6 months); or Elderly (OLD) (2 years). Histological examination of valves showed that secreted thrombotic/antithrombotic proteins localize at the valve endothelium and tissue interior. Gene expression and immunostains for von Willebrand factor (VWF), tissue factor pathway inhibitor, and tissue plasminogen activator in YNG porcine aortic valve endothelial cells were higher than they were for OLD, whereas plasminogen activator inhibitor 1 levels in OLD were higher than those for YNG and ADT. Histamine-stimulated YNG porcine aortic valve endothelial cells released higher concentrations of VWF proteins than OLD, and the fractions of VWF-140 fragments was not different between age groups. A calcific aortic valve disease in vitro model using valvular interstitial cells confirmed that VWF in culture significantly increased valvular interstitial cell nodule formation and calcification.

Conclusions—
Hemostatic protein regulation in aortic valve tissues and in valvular endothelial cells changes with age. The presence of VWF and other potential hemostatic proteins increase valvular interstitial cell calcification in vitro. Therefore, the increased capacity of elderly valves to sequester the hemostatic proteins, together with age-associated loss of extracellular matrix organization, warrants investigation into potential role of these proteins in the formation of calcific nodules.
MicroRNA miR-27b Rescues Bone Marrow–Derived Angiogenic Cell Function and Accelerates Wound Healing in Type 2 Diabetes Mellitus
Authors: Wang Jie-Mei , Tao Jun , Chen Dan-Dan , Cai Jing-Jing , Irani Kaikobad , Wang Qinde , Yuan Hong , Chen Alex F. 
Published: November 2013

Objective—
Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell–mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow–derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice.

Approach and Results—

BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66
shc
and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66
shc
, and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice.

Conclusions—
miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.
Carotid Atherosclerosis Predicts Future Myocardial Infarction But Not Venous Thromboembolism
Authors: Hald Erin M. , Lijfering Willem M. , Mathiesen Ellisiv B. , Johnsen Stein Harald , Løchen Maja-Lisa , Njølstad Inger , Wilsgaard Tom , Rosendaal Frits R. , Brækkan Sigrid K. , Hansen John-Bjarne 
Published: November 2013

Objective—
Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks.

Approach and Results—

Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromsø Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (
P
for trend <0.001) and with increasing total plaque area (
P
for trend <0.001), but neither intima-media thickness (
P
for trend=0.94) nor total plaque area (
P
for trend=0.45) was associated with VTE risk in multivariable-adjusted analysis.

Conclusions—
In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis.
Meta-analysis of the Efficacy of Different Training Strategies in Animal Models of Ischemic Stroke
Authors: Schmidt Antje , Wellmann Jürgen , Schilling Matthias , Strecker Jan-Kolja , Sommer Clemens , Schäbitz Wolf-Rüdiger , Diederich Kai , Minnerup Jens 
Published: November 2013

Background and Purpose—
Although several studies have shown beneficial effects of training in animal stroke models, the most effective training strategy and the optimal time to initiate training have not been identified. The present meta-analysis was performed to compare the efficacy of different training strategies and to determine the optimal time window for training in animal stroke models.

Methods—
We searched the literature for studies analyzing the efficacy of training in animal models of ischemic stroke. Training was categorized into forced physical training, voluntary physical training, constraint-induced movement therapy, and skilled reaching training. Two reviewers independently extracted data on study quality, infarct size, and neurological outcome. Data were pooled by means of a meta-analysis.

Results—
Thirty-five studies with >880 animals were included. A meta-analysis of all treatments showed that training reduced the infarct volume by 14% (95% confidence interval, 2%–25%) and improved the cognitive function by 33% (95% confidence interval, 8%–50%), the neuroscore by 13.4% (95% confidence interval, 1.5%–25.3%), and the running function by 6.6% (95% confidence interval, 1.4%–11.9%). Forced physical training reduced the infarct volume and enhanced the running function most effectively, whereas skilled reaching training improved the limb function most effectively. A meta-regression illustrated that training was particularly efficacious when initiated between 1 and 5 days after stroke onset.

Conclusions—
Our meta-analysis confirms that training reduces the infarct volume and improves the functional recovery in animal stroke models. Forced physical training and skilled reaching training were identified as particularly effective training strategies. The efficacy of training is time dependent.
First records of the antlion genus Solter Navás from southern Africa, with description of a new species (Neuroptera: Myrmeleontidae: Myrmecaelurini)
Authors: MANSELL MERVYN W. 
Published: October 2013

A new species of Solter Navás is described from South Africa, representing the first record of this genus from Africa south of the equator. This is a significant extension to the known distribution range of this predominantly Palaearctic genus. The species described here is characteristically reddish brown with a banded abdomen, and was recorded at three localities in arid rocky areas in the Northern Cape Province of South Africa.