bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Risk-Adjusted Survival for Melanoma Brain Metastases in the Era of Checkpoint Blockade Immunotherapies: Results from a National Cohort
Authors: Iorgulescu J. Bryan , Harary Maya , Zogg Cheryl K. , Ligon Keith L. , Reardon David A. , Hodi F. Stephen , Aizer Ayal A. , Smith Timothy R. 
Published: July 2018

Abstract
The successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated substantial promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBMs), the survival benefit of these novel therapies for MBM remains unknown. We, therefore, evaluated the characteristics, management, and overall survival (OS) of patients who presented with cutaneous MBMs during 2010 to 2015 using the National Cancer Database, which comprises 70% of all newly diagnosed U.S. cancers. OS was analyzed with risk-adjusted proportional hazards and compared by Kaplan–Meier techniques. We found that 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. Following the 2011 FDA approvals for CBI and BRAFV600-targeted therapy, MBM patients demonstrated a 91% relative increase in 4-year OS to 14.1% from 7.4% preapproval (P &lt; 0.001). Postapproval, the proportion of MBM patients who received CBI rose from 10.5% in 2011 to 34.0% in 2015 (P &lt; 0.001). Initial CBI in MBM patients displayed an improved median and 4-year OS of 12.4 months (compared with 5.2 months; P &lt; 0.001) and 28.1% (compared with 11.1%), respectively. These benefits were pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-year OS of 56.4 months (compared with 7.7 months; P &lt; 0.001) and 51.5% (compared with 16.9%), respectively. Using a large national cohort composed of a “real-life” MBM treatment population, we demonstrated the dramatic OS improvements associated with novel checkpoint blockade immunotherapies. Cancer Immunol Res; 6(9); 1039–45. ©2018 AACR.
High-Density Lipoprotein Particles, Cell-Cholesterol Efflux, and Coronary Heart Disease Risk
Authors: Asztalos Bela F. , Horvath Katalin V. , Schaefer Ernst J. 
Published: July 2018

Objective—
The cell-cholesterol efflux capacity of HDL (high-density lipoprotein) is inversely associated with coronary heart disease risk. ABCA1 (ATP-binding cassette transporter A1) plays a crucial role in cholesterol efflux from macrophages to preβ-1-HDL. We tested the hypothesis that coronary heart disease patients have functionally abnormal preβ-1-HDL.

Approach and Results—

HDL cell-cholesterol efflux capacity via the ABCA1 and the SR-BI (scavenger receptor class B type I) pathways, HDL antioxidative capacity, apo (apolipoprotein) A-I-containing HDL particles, and inflammatory- and oxidative-stress markers were measured in a case-control study of 100 coronary heart disease cases and 100 sex-matched controls. There were significant positive correlations between ABCA1-dependent cholesterol efflux and the levels of small lipid-poor preβ-1 particles (
R
2
=0.535) and between SR-BI-dependent cholesterol efflux and the levels of large lipid-rich (α-1+α-2) HDL particles (
R
2
=0.712). Cases had significantly higher (87%) preβ-1 concentrations than controls, but the functionality of their preβ-1 particles (preβ-1 concentration normalized ABCA1–dependent efflux capacity) was significantly lower (−31%). Cases had significantly lower (−12%) mean concentration of large HDL particles, but the functionality of their particles (α-1+α-2 concentration normalized SR-BI–dependent efflux capacity) was significantly higher (22%) compared with that of controls. HDL antioxidative capacity was significantly lower (−16%) in cases than in controls. There were no significant correlations between either preβ-1 functionality or large HDL particle functionality with HDL antioxidative capacity or the concentrations of inflammatory- and oxidative-stress markers.

Conclusions—
HDL cell-cholesterol efflux capacity is significantly influenced by both the concentration and the functionality of specific HDL particles participating in cell-cholesterol efflux. Coronary heart disease patients have higher than normal preβ-1 concentrations with decreased functionality and lower than normal large HDL particle concentrations with enhanced functionality.
Thirty-Second Gold Standard Definition of Atrial Fibrillation and Its Relationship With Subsequent Arrhythmia Patterns
Authors: Steinberg Jonathan S. , O’Connell Heather , Li Shelby , Ziegler Paul D. 
Published: July 2018

Background:
The Heart Rhythm Society consensus statement arbitrarily defines atrial fibrillation (AF) ablation failure as any episode ≥30 seconds. However, if brief AF events are not correlated to longer events, the rationale for this end point is questionable. We determined the impact of AF episode duration threshold on AF incidence and burden.

Methods:
Patients with a pacemaker in a prospective registry with device-detected AF and follow-up >30 days were analyzed. AF patterns were calculated for various AF duration thresholds (30 s; 2 and 6 minutes; 3.8, 5.5, and 24 hours) selected based on published consensus statements, established evidence of stroke risk, and device capabilities. Freedom from AF postdevice implant at each AF episode duration threshold was assessed, as was overall AF burden.

Results:

Among 615 patients with pacemaker (aged 72.0±11.8 years, 54.2% male, follow-up 3.7±2.2 years) with device-detected AF, 599 had ≥1 AF episode of ≥30 seconds duration (median, 22 episodes). At 12 months, freedom from AF was 25.5%, 30.1%, 34.6%, 52.6%, 56.5%, and 73.1% for duration thresholds of 30 seconds, 2 minutes, 6 minutes, 3.8 hours, 5.5 hours, and 24 hours, respectively. Of patients with a first episode of 30 seconds to 2 minutes, 35.8% were free from subsequent episode >2 minutes at 180 days. Median AF burden was significantly less for patients with first episodes between 30 seconds and 3.8 hours versus >3.8 hours (0.2% versus 9.5%, respectively;
P
<0.0001).

Conclusions:
Small differences in AF episode duration definition can significantly affect the perceived incidence of AF and impact reported outcomes, including AF ablation success. An initial AF episode of 30 seconds does not predict clinically meaningful AF patterns.
Lifetime Risk of Atrial Fibrillation by Race and Socioeconomic Status
Authors: Mou Liping , Norby Faye L. , Chen Lin Y. , O’Neal Wesley T. , Lewis Tené T. , Loehr Laura R. , Soliman Elsayed Z. , Alonso Alvaro 
Published: July 2018

Background:
Limited information exists on the lifetime risk of atrial fibrillation (AF) in African Americans and by socioeconomic status.

Methods:
We studied 15 343 participants without AF at baseline from the ARIC (Atherosclerosis Risk in Communities) cohort recruited in 1987 to 1989 from 4 communities in the United States when they were 45 to 64 years of age. Participants have been followed through 2014. Incidence rates of AF were calculated dividing the number of new cases by person-years of follow-up. Lifetime risk of AF was estimated by a modified Kaplan-Meier method considering death as a competing risk. Participants’ family income and education were obtained at baseline.

Results:
We identified 2760 AF cases during a mean follow-up of 21 years. Lifetime risk of AF was 36% (95% confidence interval, 32%–38%) in white men, 30% (95% confidence interval, 26%–32%) in white women, 21% (95% confidence interval, 13%–24%) in African American men, and 22% (95% confidence interval, 16%–25%) in African American women. Regardless of race and sex, incidence rates of AF decreased from the lowest to the highest categories of income and education. In contrast, lifetime risk of AF increased in individuals with higher income and education in most sex-race groups. Cumulative incidence of AF was lower in those with higher income and education compared with their low socioeconomic status counterparts through earlier life but was reversed after age 80.

Conclusions:
Lifetime risk of AF in the ARIC cohort was ≈1 in 3 among whites and 1 in 5 among African Americans. Socioeconomic status was inversely associated with cumulative incidence of AF before the last decades of life.
Myocardial Scar and Mortality in Severe Aortic Stenosis
Authors: Musa Tarique A. , Treibel Thomas A. , Vassiliou Vassiliou S. , Captur Gabriella , Singh Anvesha , Chin Calvin , Dobson Laura E. , Pica Silvia , Loudon Margaret , Malley Tamir , Rigolli Marzia , Foley James R.J. , Bijsterveld Petra , Law Graham R. , Dweck Marc R. , Myerson Saul G. , McCann Gerry P. , Prasad Sanjay K. , Moon James C. , Greenwood John P. 
Published: July 2018

Background:
Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality.

Methods:
In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years.

Results:

Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm
2
/m
2
; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11–2.04;
P
=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03–1.22;
P
=0.007), and scar presence (HR, 2.39; 95% CI, 1.40–4.05;
P
=0.001). Scar independently predicted all-cause (26.4% versus 12.9%;
P
<0.001) and cardiovascular (15.0% versus 4.8%;
P
<0.001) mortality, regardless of intervention (transcatheter AVR,
P
=0.002; surgical AVR,
P
=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05–1.17;
P
<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01–1.17;
P
<0.001).

Conclusions:
In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.
Gastrin Protects Against Myocardial Ischemia/Reperfusion Injury via Activation of RISK (Reperfusion Injury Salvage Kinase) and SAFE (Survivor Activating Factor Enhancement) Pathways
Authors: Yang Xiaoli , Yue Rongchuan , Zhang Jun , Zhang Xiaoqun , Liu Yukai , Chen Caiyu , Wang Xinquan , Luo Hao , Wang Wei Eric , Chen Xiongwen , Wang Huixia Judy , Jose Pedro A. , Wang Hongyong , Zeng Chunyu 
Published: July 2018

Background
Ischemia/reperfusion injury (IRI) is one of the most predominant complications of ischemic heart disease. Gastrin has emerged as a regulator of cardiovascular function, playing a key protective role in hypoxia. Serum gastrin levels are increased in patients with myocardial infarction, but the pathophysiogical significance of this finding is unknown. The purpose of this study was to determine whether and how gastrin protects cardiac myocytes from IRI.

Methods and Results

Adult male Sprague‐Dawley rats were used in the experiments. The hearts in living rats or isolated Langendorff‐perfused rat hearts were subjected to ischemia followed by reperfusion to induce myocardial IRI. Gastrin, alone or with an antagonist, was administered before the induction of myocardial IRI. We found that gastrin improved myocardial function and reduced the expression of myocardial injury markers, infarct size, and cardiomyocyte apoptosis induced by IRI. Gastrin increased the phosphorylation levels of
ERK
1/2 (extracellular signal‐regulated kinase 1/2), AKT (protein kinase B), and
STAT
3 (signal transducer and activator of transcription 3), indicating its ability to activate the
RISK
(reperfusion injury salvage kinase) and
SAFE
(survivor activating factor enhancement) pathways. The presence of inhibitors of
ERK
1/2,
AKT
, or
STAT
3 abrogated the gastrin‐mediated protection. The protective effect of gastrin was via CCK2R (cholecystokinin 2 receptor) because the
CCK
2R blocker
CI
988 prevented the gastrin‐mediated protection of the heart with IRI. Moreover, we found a negative correlation between serum levels of cardiac troponin I and gastrin in patients with unstable angina pectoris undergoing percutaneous coronary intervention, suggesting a protective effect of gastrin in human cardiomyocytes.

Conclusions

These results indicate that gastrin can reduce myocardial IRI by activation of the
RISK
and
SAFE
pathways.
Targeting Chemokine Receptor CXCR4 and Translocator Protein for Characterization of High-Risk Plaque in Carotid Stenosis Ex Vivo
Authors: Grosse Gerrit M. , Bascuñana Pablo , Schulz-Schaeffer Walter J. , Teebken Omke E. , Wilhelmi Mathias , Worthmann Hans , Ross Tobias L. , Wester Hans-Jürgen , Kropf Saskia , Derlin Thorsten , Bengel Frank M. , Bankstahl Jens P. , Weissenborn Karin 
Published: July 2018

Background and Purpose—
This pilot study aims to demonstrate the feasibility of targeting molecular characteristics of high-risk atherosclerotic plaque in symptomatic and asymptomatic carotid stenosis (CS), that is, upregulation of the translocator protein (TSPO) and the chemokine receptor type 4 (CXCR4), by means of molecular imaging.

Methods—

In a translational setting, specimens of carotid plaques of patients with symptomatic and asymptomatic CS obtained by carotid endarterectomy were analyzed for the presence of TSPO and CXCR4 by autoradiography, using the positron emission tomography tracers
18
F-GE180 and
68
Ga-Pentixafor and evaluated by histopathology. In addition,
68
Ga-Pentixafor positron emission tomography/computed tomography was performed in a patient with high-grade CS.

Results—

Distinct patterns of upregulation of TSPO (
18
F-GE180 uptake) and CXCR4 (
68
Ga-Pentixafor uptake) were identified in carotid plaque by autoradiography. The spatial distribution was associated with specific histological hallmarks that are established features of high-risk plaque: TSPO upregulation correlated with activated macrophages infiltration, whereas CXCR4 upregulation also corresponded to areas of intraplaque hemorrhage.
68
Ga-Pentixafor uptake was significantly higher in plaques of symptomatic compared with asymptomatic CS. Clinical positron emission tomography revealed marked
68
Ga-Pentixafor uptake in carotid plaque of a patient with high-grade CS.

Conclusions—
Clinical imaging of molecular signatures of high-risk atherosclerotic plaque is feasible and may become a promising diagnostic tool for comprehensive characterization of carotid disease. This methodology provides a platform for future studies targeting carotid plaque.
Object-Based Verification of a Prototype Warn-on-Forecast System
Authors: Skinner Patrick S. , Wheatley Dustan M. , Knopfmeier Kent H. , Reinhart Anthony E. , Choate Jessica J. , Jones Thomas A. , Creager Gerald J. , Dowell David C. , Alexander Curtis R. , Ladwig Therese T. , Wicker Louis J. , Heinselman Pamela L. , Minnis Patrick , Palikonda Rabindra 
Published: July 2018

AbstractAn object-based verification methodology for the NSSL Experimental Warn-on-Forecast System for ensembles (NEWS-e) has been developed and applied to 32 cases between December 2015 and June 2017. NEWS-e forecast objects of composite reflectivity and 30-min updraft helicity swaths are matched to corresponding reflectivity and rotation track objects in Multi-Radar Multi-Sensor system data on space and time scales typical of a National Weather Service warning. Object matching allows contingency-table-based verification statistics to be used to establish baseline performance metrics for NEWS-e thunderstorm and mesocyclone forecasts. NEWS-e critical success index (CSI) scores of reflectivity (updraft helicity) forecasts decrease from approximately 0.7 (0.4) to 0.4 (0.2) over 3 h of forecast time. CSI scores decrease through the forecast period, indicating that errors do not saturate during the 3-h forecast. Lower verification scores for rotation track forecasts are primarily a result of a high-frequency bias. Comparison of different system configurations used in 2016 and 2017 shows an increase in skill for 2017 reflectivity forecasts, attributable mainly to improvements in the forecast initial conditions. A small decrease in skill in 2017 rotation track forecasts is likely a result of sample differences between 2016 and 2017. Although large case-to-case variation is present, evidence is found that NEWS-e forecast skill improves with increasing object size and intensity.
Tetramethylpyrazine protects against high glucose-induced vascular smooth muscle cell injury through inhibiting the phosphorylation of JNK, p38MAPK, and ERK
Authors: Liu Yutao , Li Xu , Jiang Shanling , Ge Quanli 
Published: July 2018

Objectives High glucose-induced alterations in vascular smooth muscle cell behavior have not been fully characterized. We explored the protective mechanism of tetramethylpyrazine (TMP) on rat smooth muscle cell injury induced by high glucose via the mitogen-activated protein kinase (MAPK) signaling pathway. Methods Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were divided into control, high glucose (HG), and pre-hatching TMP groups. The effect of different glucose concentrations on cell viability and on the migration activity of VSMC cells was examined using MTT analysis and the wound scratch assay, respectively. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using enzyme-linked immunoassays. The levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38MAPK, and MAPK phosphorylation were assessed by western blotting. Results Cell proliferation was remarkably increased by increased glucose concentrations. Compared with the HG group, the migratory ability of VSMC cells was reduced in the presence of TMP. TMP also decreased the MDA content in the supernatant, but significantly increased the SOD activity. Western blotting showed that TMP inhibited the phosphorylation of JNK, p38MAPK, and ERK. Conclusions TMP appears to protect against HG-induced VSMC injury through inhibiting reactive oxygen species overproduction, and p38MAPK/JNK/ERK phosphorylation.
Knowledge database assisted gene marker selection for chronic lymphocytic leukemia
Authors: Xiang Xixi , Wang Yu-Ping , Cao Hongbao , Zhang Xi 
Published: July 2018

Objective To investigate whether previously curated chronic lymphocytic leukemia (CLL) risk genes could be leveraged in gene marker selection for the diagnosis and prediction of CLL. Methods A CLL genetic database (CLL_042017) was developed through a comprehensive CLL-gene relation data analysis, in which 753 CLL target genes were curated. Expression values for these genes were used for case-control classification of four CLL datasets, with a sparse representation-based variable selection (SRVS) approach employed for feature (gene) selection. Results were compared with outcomes obtained by using analysis of variance (ANOVA)-based gene selection approaches. Results For each of the four datasets, SRVS selected a subset of genes from the 753 CLL target genes, resulting in significantly higher classification accuracy, compared with randomly selected genes (100%, 100%, 93.94%, 89.39%). The SRVS method outperformed ANOVA in terms of classification accuracy. Conclusion Gene markers selected from the 753 CLL genes could enable significantly greater accuracy in the prediction of CLL. SRVS provides an effective method for gene marker selection.
Epidemiology of migraine in men: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study
Authors: Scher Ann I , Wang Shuu-Jiun , Katsarava Zaza , Buse Dawn C , Fanning Kristina M , Adams Aubrey Manack , Lipton Richard B 
Published: July 2018

Objective To assess migraine epidemiology in men by examining gender differences in disease presentation, comorbidities, and prognosis. Patients and methods The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal survey of US adults with migraine identified by web questionnaire. Data were stratified by gender, collected between September 2012–November 2013, and included sociodemographics, headache features, Migraine Disability Assessment, Migraine Symptom Severity Score, Allodynia Symptom Checklist, and comorbidities. Discrete time hazard models addressed 1-year likelihood of transition from episodic to chronic migraine headache frequency. Results Of the 16,789 migraine respondents, 4294 were men (25.6%). Compared to women, men were slightly older at onset of their headaches (mean 24.1 vs. 22.3 years) and had fewer headache days/month (4.3 vs. 5.3 days), slightly less severe attacks (Migraine Symptom Severity Score, 21.6 vs. 22.6), reduced frequencies of grade IV Migraine Disability Assessment scores (15.7% vs. 24.1%), allodynia (32.6% vs. 49.7%), chronic migraine (6.5% vs. 9.6%, each p < 0.001), and common comorbidities. Men were less likely to report consulting a doctor for their headaches and receiving a migraine diagnosis if they consulted. Men and women with episodic migraine had similar crude 1-year risk of chronic migraine onset. Controlling for known risk factors (i.e. depression, headache frequency, allodynia), men had greater likelihood of chronic migraine onset at 6, 9, and 12 months (each p < 0.05). Conclusions Findings confirmed gender differences. Men with migraine generally have less severe attacks and disability and are less likely to receive a diagnosis than women with migraine. Prognostic factors may be better understood for women than men.