bluuebunny/crossref_metadata_2025_split huggingface dataset:
The scientific agreement on firearm issues
Authors: Hemenway David , Nolan Elizabeth P 
Published: October 2016

IntroductionNo one has systematically collected the views of firearm researchers to determine if and where agreement exists on the scientific evidence about firearms and firearm violence.MethodsWe send a short monthly on-line survey to firearm researchers. Each survey asks respondents their level of agreement with a statement about firearms, their rating of the quality of the scientific evidence on the specific issue, their familiarity with that literature and their area of expertise. Survey participants are first-authors of a firearms article published in a peer-reviewed journal since 2011. For the first 15 surveys, on average, surveys were sent to 322 researchers, and 109 researchers responded (34% response rate).ResultsAmong respondents, approximately 46% were public health researchers and 32% were sociologists/criminologists. Agreement exists among firearm researchers that more guns and weaker gun laws cause serious public health problems, that the costs of gun availability are typically greater than the benefits and that stronger gun laws may improve public safety and health. 84% of researchers agreed, and only 8% disagreed with the statement ‘in the United States, having a gun in the home increases the risk of suicide’. For only three statements did most respondents rate the quality of the scientific evidence as strong or very strong. Overall, there was a higher level of agreement among public health/medicine researchers than among researchers in the other disciplines.DiscussionSurveys of researchers can provide useful information about agreement on specific issues and about the quality of the scientific evidence.
Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study
Authors: Firbank M J , Yarnall A J , Lawson R A , Duncan G W , Khoo T K , Petrides G S , O'Brien J T , Barker R A , Maxwell R J , Brooks D J , Burn D J 
Published: October 2016

ObjectiveTo assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline.MethodsFDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA.ResultsPD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score.ConclusionsReductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.
Hybrid Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Modulating Tumor Hypoxia
Authors: Abbasi Azhar Z. , Gordijo Claudia R. , Amini Mohammad Ali , Maeda Azusa , Rauth Andrew M. , DaCosta Ralph S. , Wu Xiao Yu 
Published: October 2016

AbstractHypoxia in the tumor microenvironment (TME) mediates resistance to radiotherapy and contributes to poor prognosis in patients receiving radiotherapy. Here we report the design of clinically suitable formulations of hybrid manganese dioxide (MnO2) nanoparticles (MDNP) using biocompatible materials to reoxygenate the TME by reacting with endogenous H2O2. MDNP containing hydrophilic terpolymer-protein-MnO2 or hydrophobic polymer-lipid-MnO2 provided different oxygen generation rates in the TME relevant to different clinical settings. In highly hypoxic murine or human xenograft breast tumor models, we found that administering either MDNP formulation before radiotherapy modulated tumor hypoxia and increased radiotherapy efficacy, acting to reduce tumor growth, VEGF expression, and vascular density. MDNP treatment also increased apoptosis and DNA double strand breaks, increasing median host survival 3- to 5-fold. Notably, in the murine model, approximately 40% of tumor-bearing mice were tumor-free after a single treatment with MDNPs plus radiotherapy at a 2.5-fold lower dose than required to achieve the same curative treatment without MDNPs. Overall, our findings offer a preclinical proof of concept for the use of MDNP formulations as effective radiotherapy adjuvants. Cancer Res; 76(22); 6643–56. ©2016 AACR.
AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function
Authors: Shentu Tzu-Pin , He Ming , Sun Xiaoli , Zhang Jianlin , Zhang Fan , Gongol Brendan , Marin Traci L. , Zhang Jiao , Wen Liang , Wang Yinsheng , Geary Gregory G. , Zhu Yi , Johnson David A. , Shyy John Y.-J. 
Published: October 2016

Objective—
Cortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical–actin assembly in response to pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined the hypothesis that AMPK and SIRT1 coregulate cortactin dynamics in response to shear stress.

Approach and Results—

Analysis of the ability of AMPK to phosphorylate recombinant cortactin and oligopeptides whose sequences matched AMPK consensus sequences in cortactin pointed to Thr-401 as the site of AMPK phosphorylation. Mass spectrometry confirmed Thr-401 as the site of AMPK phosphorylation. Immunoblot analysis with AMPK siRNA and SIRT1 siRNA in human umbilical vein ECs and EC-specific AMPKα2 knockout mice showed that AMPK phosphorylation of cortactin primes SIRT1 deacetylation in response to shear stress. Immunoblot analyses with cortactin siRNA in human umbilical vein ECs, phospho-deficient T401A and phospho-mimetic T401D mutant, or aceto-deficient (9K/R) and aceto-mimetic (9K/Q) showed that cortactin regulates endothelial nitric oxide synthase activity. Confocal imaging and sucrose-density gradient analyses revealed that the phosphorylated/deacetylated cortactin translocates to the EC periphery facilitating endothelial nitric oxide synthase translocation from lipid to nonlipid raft domains. Knockdown of cortactin in vitro or genetic reduction of cortactin expression in vivo in mice substantially decreased the endothelial nitric oxide synthase–derived NO bioavailability. In vivo, atherosclerotic lesions increase in ApoE
–
/–
/cortactin
+/–
mice, when compared with ApoE
–/–
/cortactin
+/+
littermates.

Conclusions—
AMPK phosphorylation of cortactin followed by SIRT1 deacetylation modulates the interaction of cortactin and cortical–actin in response to shear stress. Functionally, this AMPK/SIRT1 coregulated cortactin–F-actin dynamics is required for endothelial nitric oxide synthase subcellular translocation/activation and is atheroprotective.
Farnesoid X Receptor and Its Ligands Inhibit the Function of Platelets
Authors: Moraes Leonardo A. , Unsworth Amanda J. , Vaiyapuri Sakthivel , Ali Marfoua S. , Sasikumar Parvathy , Sage Tanya , Flora Gagan D. , Bye Alex P. , Kriek Neline , Dorchies Emilie , Molendi-Coste Olivier , Dombrowicz David , Staels Bart , Bishop-Bailey David , Gibbins Jonathan M. 
Published: October 2016

Objective—
Although initially seemingly paradoxical because of the lack of nucleus, platelets possess many transcription factors that regulate their function through DNA-independent mechanisms. These include the farnesoid X receptor (FXR), a member of the superfamily of ligand-activated transcription factors, that has been identified as a bile acid receptor. In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6α-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically.

Approach and Results—

FXR ligands inhibited the activation of platelets in response to stimulation of collagen or thrombin receptors, resulting in diminished intracellular calcium mobilization, secretion, fibrinogen binding, and aggregation. Exposure to FXR ligands also reduced integrin α
IIb
β
3
outside-in signaling and thereby reduced the ability of platelets to spread and to stimulate clot retraction. FXR function in platelets was found to be associated with the modulation of cyclic guanosine monophosphate levels in platelets and associated downstream inhibitory signaling. Platelets from FXR-deficient mice were refractory to the actions of FXR agonists on platelet function and cyclic nucleotide signaling, firmly linking the nongenomic actions of these ligands to the FXR.

Conclusions—
This study provides support for the ability of FXR ligands to modulate platelet activation. The atheroprotective effects of GW4064, with its novel antiplatelet effects, indicate FXR as a potential target for the prevention of atherothrombotic disease.
Dying With a Left Ventricular Assist Device as Destination Therapy
Authors: Dunlay Shannon M. , Strand Jacob J. , Wordingham Sara E. , Stulak John M. , Luckhardt Angela J. , Swetz Keith M. 
Published: October 2016

Background—
Despite the ability of left ventricular assist device as destination therapy (DT-LVAD) to prolong survival for many patients with advanced heart failure, little is known about the eventual end-of-life care that patients with DT-LVAD receive.

Methods and Results—
All patients undergoing DT-LVAD at the Mayo Clinic in Rochester, Minnesota, from January 1, 2007, to September 30, 2014, who subsequently died before July 1, 2015, were included. Information about end-of-life care was obtained from documentation in the electronic medical record. Of 89 patients who died with a DT-LVAD, the median (25th–75th percentile) time from left ventricular assist device implantation to death was 14 (4–31) months. The most common causes of death were multiorgan failure (26%), hemorrhagic stroke (24%), and progressive heart failure (21%). Nearly half (46%) of the patients saw palliative care within 1 month before death; however, only 13 (15%) patients enrolled in hospice a median 11 (range 1–315) days before death. Most patients (78%) died in the hospital, of which 88% died in the intensive care unit. In total, 49 patients had their left ventricular assist device deactivated before death, with all but 3 undergoing deactivation in the hospital. Most patients died within an hour of left ventricular assist device deactivation and all within 26 hours.

Conclusions—
In contrast to the general heart failure population, most patients with DT-LVAD die in the hospital and few use hospice. Further work is needed to understand these differences and to determine whether patients with DT-LVAD are receiving optimal end-of-life care.
Influence of Ethnicity, Age, and Time on Sex Disparities in Long‐Term Cause‐Specific Mortality After Acute Myocardial Infarction
Authors: Gao Fei , Lam Carolyn S.P. , Yeo Khung Keong , Machin David , de Carvalho Leonardo P. , Sim Ling Ling , Koh Tian Hai , Foo David , Ong Hean Yee , Tong Khim Leng , Tan Huay Cheem , Earnest Arul , Chua Terrance , Chan Mark Yan Yee 
Published: October 2016

Background
We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort.

Methods and Results

For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22–101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age‐adjusted hazard ratio [
HR
] 1.3, 95% CI 1.2–1.4) but a similar risk of noncardiovascular death (
HR
0.9, 95%
CI
0.8–1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (
HR
1.4, 95%
CI
1.2–1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (
HR
3.4 [95%
CI
1.9–6.0] versus
HR
1.5 [95%
CI
0.6–3.6] for Indian women). Compared with same‐age Malay men, Malay women aged 22 to 49 years had a 2.5‐fold (95%
CI
1.6–3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the
HR
comparing cardiovascular death of Indian women and men decreased from 1.9 (95%
CI
1.5–2.4) at 30 days to 0.9 (95%
CI
0.5–1.6) at 10 years.

Conclusion
Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.
LIM Domain Only 2 Regulates Endothelial Proliferation, Angiogenesis, and Tissue Regeneration
Authors: Meng Shu , Matrone Gianfranco , Lv Jie , Chen Kaifu , Wong Wing Tak , Cooke John P. 
Published: October 2016

Background

LIM
domain only 2 (
LMO
2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized.

Methods and Results

In vitro loss‐ and gain‐of‐function studies on
LMO
2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (
KD
) of
LMO
2, respectively.
LMO
2
KD
significantly impaired endothelial proliferation.
LMO
2 controls endothelial G1/S transition through transcriptional regulation of cyclin‐dependent kinase 2 and 4 as determined by reverse transcription polymerase chain reaction (PCR), western blot, and chromatin immunoprecipitation, and also influences the expression of Cyclin D1 and Cyclin A1.
LMO
2
KD
also impaired angiogenesis by reducing transforming growth factor‐β (TGF‐β) expression, whereas supplementation of exogenous
TGF‐
β restored defective network formation in
LMO
2
KD
human umbilical vein endothelial cells. In a zebrafish model of caudal fin regeneration,
RT
‐
PCR
revealed that the lmo2 (zebrafish gene) gene was upregulated at day 5 postresection. The
KD
of lmo2 by vivo‐morpholino injections in adult
Tg
(
fli1:egfp)

y1

zebrafish reduced 5‐bromo‐2′‐deoxyuridine incorporation in endothelial cells, impaired neoangiogenesis in the resected caudal fin, and substantially delayed fin regeneration.

Conclusions

The transcriptional factor
LMO
2 regulates endothelial proliferation and angiogenesis in vitro. Furthermore,
LMO
2 is required for angiogenesis and tissue healing in vivo. Thus,
LMO
2 is a critical determinant of vascular and tissue regeneration.
Meta‐Analysis of Potassium Intake and the Risk of Stroke
Authors: Vinceti Marco , Filippini Tommaso , Crippa Alessio , de Sesmaisons Agnès , Wise Lauren A. , Orsini Nicola 
Published: October 2016

Background
The possibility that lifestyle factors such as diet, specifically potassium intake, may modify the risk of stroke has been suggested by several observational cohort studies, including some recent reports. We performed a systematic review and meta‐analysis of existing studies and assessed the dose–response relation between potassium intake and stroke risk.

Methods and Results

We reviewed the observational cohort studies addressing the relation between potassium intake, and incidence or mortality of total stroke or stroke subtypes published through August 6, 2016. We carried out a meta‐analysis of 16 cohort studies based on the relative risk (
RR
) of stroke comparing the highest versus lowest intake categories. We also plotted a pooled dose–response curve of
RR
of stroke according to potassium intake. Analyses were performed with and without adjustment for blood pressure. Relative to the lowest category of potassium intake, the highest category of potassium intake was associated with a 13% reduced risk of stroke (
RR
=0.87, 95%
CI
0.80–0.94) in the blood pressure–adjusted analysis. Summary
RR
s tended to decrease when original estimates were unadjusted for blood pressure. Analysis for stroke subtypes yielded comparable results. In the spline analysis, the pooled
RR
was lowest at 90 mmol of potassium daily intake (
RR
s=0.78, 95%
CI
0.70–0.86) in blood pressure–adjusted analysis, and 0.67 (95%
CI
0.57–0.78) in unadjusted analysis.

Conclusions
Overall, this dose–response meta‐analysis confirms the inverse association between potassium intake and stroke risk, with potassium intake of 90 mmol (≈3500 mg)/day associated with the lowest risk of stroke.
Cost-Effectiveness of Endovascular Stroke Therapy
Authors: Kunz Wolfgang G. , Hunink M.G. Myriam , Sommer Wieland H. , Beyer Sebastian E. , Meinel Felix G. , Dorn Franziska , Wirth Stefan , Reiser Maximilian F. , Ertl-Wagner Birgit , Thierfelder Kolja M. 
Published: October 2016

Background and Purpose—
Endovascular therapy in addition to standard care (EVT+SC) has been demonstrated to be more effective than SC in acute ischemic large vessel occlusion stroke. Our aim was to determine the cost-effectiveness of EVT+SC depending on patients’ initial National Institutes of Health Stroke Scale (NIHSS) score, time from symptom onset, Alberta Stroke Program Early CT Score (ASPECTS), and occlusion location.

Methods—
A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with both strategies applied in a US setting. Model input parameters were obtained from the literature, including recently pooled outcome data of 5 randomized controlled trials (ESCAPE [Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke], EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial], MR CLEAN [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], REVASCAT [Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset], and SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment]). Probabilistic sensitivity analysis was performed to estimate uncertainty of the model results. Net monetary benefits, incremental costs, incremental effectiveness, and incremental cost-effectiveness ratios were derived from the probabilistic sensitivity analysis. The willingness-to-pay was set to $50 000/QALY.

Results—
Overall, EVT+SC was cost-effective compared with SC (incremental cost: $4938, incremental effectiveness: 1.59 QALYs, and incremental cost-effectiveness ratio: $3110/QALY) in 100% of simulations. In all patient subgroups, EVT+SC led to gained QALYs (range: 0.47–2.12), and mean incremental cost-effectiveness ratios were considered cost-effective. However, subgroups with ASPECTS ≤5 or with M2 occlusions showed considerably higher incremental cost-effectiveness ratios ($14 273/QALY and $28 812/QALY, respectively) and only reached suboptimal acceptability in the probabilistic sensitivity analysis (75.5% and 59.4%, respectively). All other subgroups had acceptability rates of 90% to 100%.

Conclusions—
EVT+SC is cost-effective in most subgroups. In patients with ASPECTS ≤5 or with M2 occlusions, cost-effectiveness remains uncertain based on current data.
Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation
Authors: Bonde Anders Nissen , Lip Gregory Y.H. , Kamper Anne-Lise , Fosbøl Emil L. , Staerk Laila , Carlson Nicholas , Torp-Pedersen Christian , Gislason Gunnar , Olesen Jonas Bjerring 
Published: October 2016

Background and Purpose—
We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups.

Methods—
We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR.

Results—

A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97–1.56), 1.26 (95% CI, 1.14–1.40), 1.18 (95% CI, 1.07–1.31), 1.11 (95% CI, 0.87–1.42), 2.01 (95% CI, 1.14–3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and <15 mL/min per 1.73 m
2
, respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m
2
; hazard ratios 0.57 (95% CI, 0.43–0.76), 0.57 (95% CI, 0.51–0.64), 0.48 (95% CI, 0.44–0.54), 0.60 (95% CI, 0.45–0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m
2
, respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR<15 mL/min per 1.73 m
2
; hazard ratio 1.18 (95% CI, 0.58–2.40).

Conclusions—

In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m
2
.