bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a mobile app and mobile workforce to validate data about emergency public health resources
Authors: Chang Anna Marie , Leung Alison C , Saynisch Olivia , Griffis Heather , Hill Shawndra , Hershey John C , Becker Lance B , Asch David A , Seidman Ariel , Merchant Raina Martha 
Published: May 2013

BackgroundSocial media and mobile applications that allow people to work anywhere are changing the way people can contribute and collaborate.ObjectiveWe sought to determine the feasibility of using mobile workforce technology to validate the locations of automated external defibrillators (AEDs), an emergency public health resource.MethodsWe piloted the use of a mobile workforce application, to verify the location of 40 AEDs in Philadelphia county. AEDs were pre-identified in public locations for baseline data. The task of locating AEDs was posted online for a mobile workforce from October 2011 to January 2012. Participants were required to submit a mobile phone photo of AEDs and descriptions of the location.ResultsThirty-five of the 40 AEDs were identified within the study period. Most, 91% (32/35) of the submitted AED photo information was confirmed project baseline data. Participants also provided additional data such as business hours and other nearby AEDs.ConclusionsIt is feasible to engage a mobile workforce to complete health research-related tasks. Participants were able to validate information about emergency public health resources.
Anaesthetic death: who pays?
Authors: Fawcett Anne 
Published: May 2013

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved. In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘Anaesthetic death: who pays?’, was presented and discussed by Anne Fawcett. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue. Discussion of the dilemma ‘Is flirting with clients taboo?’, which was published in the April issue of In Practice, appears on page 287.The series is being coordinated by Siobhan Mullan, of the University of Bristol. It is hoped it will provide a framework that will help practices find solutions when facing similar dilemmas.
Epidemiological evidence on association between ambient air pollution and stroke mortality
Authors: Qian Yifeng , Zhu Meiying , Cai Binxin , Yang Qing , Kan Haidong , Song Guixiang , Jin Wenzheng , Han Ming , Wang Chunfang 
Published: May 2013

BackgroundInconsistent results have been found on the association between air pollution and stroke mortality. Additionally, evidence on people who are potentially sensitive to air pollution-associated stroke mortality is limited.MethodsDaily stroke mortality of adults aged over 65 between 2003 and 2008 in Shanghai, China were collected. The time-stratified case-crossover approach was used to assess the association between daily concentrations of air pollutants including particles with size <10 µm, sulfur dioxide (SO2) and nitrogen dioxide (NO2) and stroke mortality.ResultsBoth total-stroke and ischaemic-stroke mortalities were found to be significantly associated with all three air pollutants. Haemorrhagic stroke was significantly associated with SO2and NO2only. Substantial differences were observed for effect estimates of ischaemic-stroke mortality in relation to NO2among people with cardiac diseases compared with those without; for an increase of 10 μg/m3in NO2, the increase in ischaemic-stroke mortality was 7.05% (95% CI 1.92% to 12.17%) for people with comorbid cardiac diseases versus 0.60% (95% CI −0.49% to 1.68%) for those without. We did not find evidence of effect modification by hypertension and diabetes.ConclusionsThis study provides new evidence for the association between exposure to ambient air pollution and stroke mortality. Our results also suggest that underlying cardiac disorder may increase the risk for ischaemic-stroke mortality in relation to air pollution exposure, especially NO2..
Enhanced Inhibition of ERK Signaling by a Novel Allosteric MEK Inhibitor, CH5126766, That Suppresses Feedback Reactivation of RAF Activity
Authors: Ishii Nobuya , Harada Naoki , Joseph Eric W. , Ohara Kazuhiro , Miura Takaaki , Sakamoto Hiroshi , Matsuda Yutaka , Tomii Yasushi , Tachibana-Kondo Yukako , Iikura Hitoshi , Aoki Toshihiro , Shimma Nobuo , Arisawa Mikio , Sowa Yoshihiro , Poulikakos Poulikos I. , Rosen Neal , Aoki Yuko , Sakai Toshiyuki 
Published: May 2013

Abstract
Tumors with mutant RAS are often dependent on extracellular signal–regulated kinase (ERK) signaling for growth; however, MEK inhibitors have only marginal antitumor activity in these tumors. MEK inhibitors relieve ERK-dependent feedback inhibition of RAF and cause induction of MEK phosphorylation. We have now identified a MEK inhibitor, CH5126766 (RO5126766), that has the unique property of inhibiting RAF kinase as well. CH5126766 binding causes MEK to adopt a conformation in which it cannot be phosphorylated by and released from RAF. This results in formation of a stable MEK/RAF complex and inhibition of RAF kinase. Consistent with this mechanism, this drug does not induce MEK phosphorylation. CH5126766 inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity as well. These results suggest that relief of RAF feedback limits pathway inhibition by standard MEK inhibitors. CH5126766 represents a new type of MEK inhibitor that causes MEK to become a dominant-negative inhibitor of RAF and that, in doing so, may have enhanced therapeutic activity in ERK-dependent tumors with mutant RAS. Cancer Res; 73(13); 4050–60. ©2013 AACR.
ETS2 Mediated Tumor Suppressive Function and MET Oncogene Inhibition in Human Non–Small Cell Lung Cancer
Authors: Kabbout Mohamed , Garcia Melinda M. , Fujimoto Junya , Liu Diane D. , Woods Denise , Chow Chi-Wan , Mendoza Gabriela , Momin Amin A. , James Brian P. , Solis Luisa , Behrens Carmen , Lee J. Jack , Wistuba Ignacio I. , Kadara Humam 
Published: May 2013

Abstract
Purpose: The ETS2 transcription factor is an evolutionarily conserved gene that is deregulated in cancer. We analyzed the transcriptome of lung adenocarcinomas and normal lung tissue by expression profiling and found that ETS2 was significantly downregulated in adenocarcinomas. In this study, we probed the yet unknown functional role of ETS2 in lung cancer pathogenesis.
Experimental Design: Lung adenocarcinomas (n = 80) and normal lung tissues (n = 30) were profiled using the Affymetrix Human Gene 1.0 ST platform. Immunohistochemical (IHC) analysis was conducted to determine ETS2 protein expression in non–small cell lung cancer (NSCLC) histologic tissue specimens (n = 201). Patient clinical outcome, based on ETS2 IHC expression, was statistically assessed using the log-rank and Kaplan–Meier tests. RNA interference and overexpression strategies were used to assess the effects of ETS2 expression on the transcriptome and on various malignant phenotypes.
Results: ETS2 expression was significantly reduced in lung adenocarcinomas compared with normal lung (P &lt; 0.001). Low ETS2 IHC expression was a significant predictor of shorter time to recurrence in NSCLC (P = 0.009, HR = 1.89) and adenocarcinoma (P = 0.03, HR = 1.86). Moreover, ETS2 was found to significantly inhibit lung cancer cell growth, migration, and invasion (P &lt; 0.05), and microarray and pathways analysis revealed significant (P &lt; 0.001) activation of the HGF pathway following ETS2 knockdown. In addition, ETS2 was found to suppress MET phosphorylation and knockdown of MET expression significantly attenuated (P &lt; 0.05) cell invasion mediated by ETS2-specific siRNA. Furthermore, knockdown of ETS2 augmented HGF-induced MET phosphorylation, cell migration, and invasion.
Conclusion(s): Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene. Clin Cancer Res; 19(13); 3383–95. ©2013 AACR.
Dietary Chemopreventative Benzyl Isothiocyanate Inhibits Breast Cancer Stem Cells In Vitro and In Vivo
Authors: Kim Su-Hyeong , Sehrawat Anuradha , Singh Shivendra V. 
Published: May 2013

Abstract
A small subset of mammary tumor-initiating cells (also known as breast cancer stem cells; bCSC), characterized by expression of different markers [CD44high/CD24low/epithelial-specific antigen (ESA)+], aldehyde dehydrogenase-1 (ALDH1) activity, and ability to form mammospheres under ultra-low attachment culture conditions, are suspected to evade conventional therapies leading to disease recurrence. Elimination of both therapy-sensitive epithelial tumor cells and therapy-resistant bCSC is therefore necessary for prevention of breast cancer. We have shown previously that a nontoxic small-molecule constituent of edible cruciferous vegetables (benzyl isothiocyanate; BITC) inhibits mammary cancer development in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice by causing epithelial tumor cell apoptosis. The present study shows efficacy of BITC against bCSC in vitro and in vivo. Mammosphere formation frequency and CD44high/CD24low/ESA+ and/or ALDH1+ populations in cultured MCF-7 (estrogen receptor–positive) and SUM159 (triple-negative) human breast cancer cells were decreased significantly in the presence of plasma achievable concentrations of BITC. BITC administration in the diet (3 μmol BITC/g diet for 29 weeks) resulted in a marked decrease in bCSCs in the MMTV-neu mice tumors in vivo. Overexpression of full-length Ron as well as its truncated form (sfRon), but not urokinase-type plasminogen activator receptor, conferred near complete protection against BITC-mediated inhibition of bCSCs in MCF-7 cells. The BITC treatment downregulated protein levels of Ron and sfRon in cultured breast cancer cells and in tumor xenografts. Ron overexpression resulted in upregulation of bCSC-associated genes Oct-4, SOX-2, and Nanog. In conclusion, the present study indicates that BITC treatment eliminates bCSCs in vitro and in vivo. Cancer Prev Res; 6(8); 782–90. ©2013 AACR.
Endothelial Protease Nexin-1 Is a Novel Regulator of A Disintegrin and Metalloproteinase 17 Maturation and Endothelial Protein C Receptor Shedding via Furin Inhibition
Authors: Boulaftali Yacine , François Déborah , Venisse Laurence , Jandrot-Perrus Martine , Arocas Véronique , Bouton Marie-Christine 
Published: May 2013

Objective—
Human protein C is a plasma serine protease that plays a key role in hemostasis, and activated protein C (aPC) is known to elicit protective responses in vascular endothelial cells. This cytoprotective activity requires the interaction of the protease with its cell membrane receptor, endothelial protein C receptor. However, the mechanisms regulating the beneficial cellular effects of aPC are not well known. We aimed to determine whether a serine protease inhibitor called protease nexin-1 (PN-1) or serpinE2, expressed by vascular cells, can modulate the effect of aPC on endothelial cells.

Approach and Results—
We found that vascular barrier protective and antiapoptotic activities of aPC were reduced both in endothelial cells underexpressing PN-1 and in endothelial cells whose PN-1 function was blocked by a neutralizing antibody. Our in vitro data were further confirmed in vivo. Indeed, we found that vascular endothelial growth factor–mediated hyperpermeability in the skin of mice was markedly reduced by local intradermal injection of aPC in wild-type mice but not in PN-1–deficient mice. Furthermore, we demonstrated a previously unknown protective role of endothelial PN-1 on endothelial protein C receptor shedding. We provided evidence that PN-1 inhibits furin, a serine protease that activates a disintegrin and metalloproteinase 17 involved in the shedding of endothelial protein C receptor. We indeed evidenced a direct interaction between PN-1 and furin in endothelial cells.

Conclusions—
Our results thus demonstrate an original role of PN-1 as a furin convertase inhibitor, providing new insights for understanding the regulation of endothelial protein C receptor–dependent aPC endothelial protective effects.
Echocardiographic Assessment of Cardiac Valvular Regurgitation With Lorcaserin From Analysis of 3 Phase 3 Clinical Trials
Authors: Weissman Neil J. , Sanchez Matilde , Koch Gary G. , Smith Steven R. , Shanahan William R. , Anderson Christen M. 
Published: May 2013

Background—

Lorcaserin is a selective 5-HT
2C
agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT
2C
agonism would avoid valvular heart disease.

Methods and Results—

Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration–defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, −0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (
P
=0.02 and
P
=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration–defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves.

Conclusions—
In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.
Quantifying Options for Reducing Coronary Heart Disease Mortality By 2020
Authors: Huffman Mark D. , Lloyd-Jones Donald M. , Ning Hongyan , Labarthe Darwin R. , Guzman Castillo Maria , O’Flaherty Martin , Ford Earl S. , Capewell Simon 
Published: May 2013

Background—
The American Heart Association (AHA) 2020 Strategic Impact Goal proposes a 20% improvement in cardiovascular health of all Americans. We aimed to estimate the potential reduction in coronary heart disease (CHD) deaths.

Methods and Results—
We used data on 40 373 adults free of cardiovascular disease from the National Health and Nutrition Examination Survey (NHANES; 1988–2010). We quantified recent trends for 6 metrics (total cholesterol, systolic blood pressure, physical inactivity, smoking, diabetes mellitus, and obesity) and generated linear projections to 2020. We projected the expected number of CHD deaths in 2020 if 2006 age- and sex-specific CHD death rates remained constant, which would result in ≈480 000 CHD deaths in 2020 (12% increase). We used the previously validated IMPACT CHD model to project numbers of CHD deaths in 2020 under 2 different scenarios: (1) Assuming a 20% improvement in each cardiovascular health metric, we project 365 000 CHD deaths in 2020 (range 327 000–403 000) a 24% decrease reflecting modest reductions in total cholesterol (−41 000), systolic blood pressure (−36 000), physical inactivity (−12 000), smoking (−10 000), diabetes mellitus (−10 000), and obesity (−5000); (2) Assuming that recent risk factor trends continue to 2020, we project 335 000 CHD deaths (range 274 000–386 000), a 30% decrease reflecting improvements in total cholesterol, systolic blood pressure, smoking, and physical activity (≈167 000 fewer deaths), offset by increases in diabetes mellitus and body mass index (≈24 000 more deaths).

Conclusions—
Two contrasting scenarios of change in cardiovascular health metrics could prevent 24% to 30% of the CHD deaths expected in 2020, though with differing effects by age. Unfavorable continuing trends in obesity and diabetes mellitus would have substantial adverse effects. This analysis demonstrates the utility of modelling to inform health policy.
Incidence of First Stroke
Authors: Hilmarsson Agust , Kjartansson Olafur , Olafsson Elias 
Published: May 2013

Background and Purpose—
Iceland is an island in the North Atlantic with ≈319 000 inhabitants. The study determines the incidence of first stroke in the adult population of Iceland during 12 months, which has not been previously reported in the entire Icelandic population.

Methods—
The study population consisted of all residents of Iceland, aged ≥18 years, during the 12-month study period. Cases were identified by multiple overlapping approaches. Medical records were reviewed to verify diagnosis, to determine stroke subtype and to determine selected risk factors.

Results—
A total of 343 individuals, aged ≥18 years, had a first stroke during the study period. Incidence was 144 per 100 000 person years; 81% ischemic infarction; 9% intracerebral hemorrhage; 7% subarachnoid hemorrhage; and 3% unknown. Fifty percent of the individuals were men. Mean age for ischemic infarction and intracerebral hemorrhage was 71 years for men and 73 years for women. Atrial fibrillation was previously known in 18% with first ischemic stroke or intracerebral hemorrhage and another 6% were diagnosed on routine admission ECG. Long-term ECG study (24 hours) found that 12% (18/154) of the remaining individuals had paroxysmal atrial fibrillation.

Conclusions—
Incidence of first stroke in Iceland is similar to other Western countries. The high number of paroxysmal atrial fibrillation found during the 24-hour ECG suggests that atrial fibrillation may be underdiagnosed in patients with stroke.
Trends in Risk Factor Prevalence and Management Before First Stroke
Authors: Marshall Iain J. , Wang Yanzhong , McKevitt Christopher , Rudd Anthony G. , Wolfe Charles D.A. 
Published: May 2013

Background and Purpose—
Vascular risk factors are suboptimally managed internationally. This study investigated time trends in risk factors diagnosed before stroke and their treatment, and factors associated with appropriate medication use.

Methods—
A total of 4416 patients with a first stroke were registered in the population-based South London Stroke Register from 1995 to 2011. Previously diagnosed risk factors and usual medications were collected from patients’ primary care and hospital records. Trends and associations were assessed using multivariate logistic regression.

Results—

Seventy-two percent of patients were diagnosed previously with 1 or more risk factors; 30% had diagnosed risk factors that were untreated. Hypercholesterolemia increased significantly during the study period; myocardial infarction and transient ischemic attack prevalences decreased. Antiplatelet prescription increased in atrial fibrillation (AF), myocardial infarction, and transient ischemic attack (AF, 37%–51%,
P
<0.001; myocardial infarction, 48%–69%,
P
<0.001; transient ischemic attack, 49%–61%,
P
=0.015). Anticoagulant prescription for AF showed a nonsignificant increase (12%–23%;
P
=0.059). Fewer older patients with AF were prescribed anticoagulants (age, >85 versus <65 years; adjusted relative risk, 0.19; 95% confidence interval, 0.08–0.41). Black ethnicity (adjusted relative risk, 1.17; 95% confidence interval, 1.10–1.23) and female sex (adjusted relative risk, 1.09; 95% confidence interval, 1.03–1.15) were associated with increased antihypertensive drug prescription; other medications did not vary by ethnicity or sex.

Conclusions—
Antiplatelet and cholesterol-lowering treatment prescribing have improved significantly over time; however, only a minority with AF received anticoagulants, and this did not improve significantly. Overall, 30% of strokes occurred in patients with previously diagnosed but untreated risk factors.
Transcranial Laser Therapy and Infarct Volume
Authors: Kasner Scott E. , Rose David Z. , Skokan Alexander , Walker Michael G. , Shi Jing , Streeter Jackson 
Published: May 2013

Background and Purpose—
Two randomized trials suggested that transcranial laser therapy (TLT) may benefit patients with acute ischemic stroke, although efficacy has not been confirmed. Supportive proof of concept could be demonstrated if TLT reduces the volume of cortical infarction.

Methods—
The NeuroThera Efficacy and Safety Trial-2 (NEST-2) was a randomized trial of TLT versus sham in patients with acute ischemic stroke treated within 24 hours of onset. Infarct volumes were measured quantitatively and semiquantitatively on all protocol-required computed tomography (or MRI, if clinically indicated) scans performed on day 5 (±2). Two approaches assessed treatment effects on cortex: (1) indirectly, by analyzing total infarct volume among patients with clinical presentations suggesting cortical involvement; and (2) directly, by assessing the cortical Alberta Stroke Program Early CT Score (cASPECTS) components (M1-M6, anterior, posterior) on a 0- to 8-point modified scale.

Results—

A total of 640 subjects had scans (576 computed tomography, 64 MRI) on day 5. The reliability of ASPECTS (intraclass correlation coefficient=0.85) and cASPECTS (intraclass correlation coefficient=0.82) was excellent, and total ASPECTS was correlated with total infarct volume (
r
=0.71). In the overall study population, there was no impact of TLT on total infarct volume (
P
=0.30), total ASPECTS (
P
=0.85), or cASPECTS (
P
=0.89). Similarly, no effect was seen in any of the following prespecified subgroups selected to indicate cortical involvement: baseline National Institutes of Health Stroke Scale score >10, Oxfordshire Total Anterior Circulation Syndrome, subjects with aphasia or extinction at baseline, or subjects with radiographic involvement of cortex.

Conclusions—
TLT was not associated with a reduction in overall or cortical infarct volume as measured on computed tomography in the subacute phase.