bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Novel Variants on 13q22.1 Are Associated with Risk of Esophageal Squamous Cell Carcinoma
Authors: Chang Jiang , Wei Lixuan , Miao Xiaoping , Yu Dianke , Tan Wen , Zhang Xuemei , Wu Chen , Lin Dongxin 
Published: August 2015

Abstract
Background: Chromosome 13q22.1 has previously been identified to be a susceptibility locus for pancreatic cancer in Chinese and European ancestry populations. This pleiotropy study aimed to identify novel variants in this region associated with susceptibility to different types of human cancer.
Method: To fine-map the 13q22.1 region, imputation analyses were conducted on the basis of the GWAS data of 2,031 esophageal squamous cell cancer (ESCC) cases and 2,044 controls and 5,930 SNPs (625 directly genotyped and 5,305 well imputed). Promising associations were then examined in ESCC (4,146 cases and 4,135 controls), gastric cardia cancer (1,894 cases and 1,912 controls), noncardia gastric cancer (1,007 cases and 2,243 controls), and colorectal cancer (1,111 cases and 1,138 controls). Fine mapping and biochemical analyses were further performed to elucidate the potential function of novel variants.
Results: Two novel variants, rs1924966 and rs115797771, were associated with ESCC risk (P = 1.37 × 10−10 and P = 2.32 × 10−10, respectively) and were also associated with risk of gastric cardia cancer (P = 0.0003 and P = 0.0018, respectively) but not gastric cancer and colorectal cancer. Fine-mapping revealed another SNP, rs58090485, in strong linkage disequilibrium with rs115797771 (r2 = 0.94). Functional analysis showed that this SNP disturbs a transcriptional repressor binding to the promoter region of KLF5, which might result in high constitutional expression of KLF5.
Conclusions: These results demonstrate that variants mapped on 13q22.1 are associated with the risk of different types of cancer.
Impact: 13q22.1 might serve as a biomarker for the identification of individuals at risk for ESCC and gastric cardia cancer. Cancer Epidemiol Biomarkers Prev; 24(11); 1774–80. ©2015 AACR.
Octreotide Long-Acting Repeatable among Elderly Patients with Neuroendocrine Tumors: A Survival Analysis of SEER-Medicare Data
Authors: Shen Chan , Shih Ya-Chen Tina , Xu Ying , Yao James C. 
Published: August 2015

Abstract
Background: Octreotide long-acting repeatable (LAR) is approved in the United States for the management of carcinoid syndromes among patients with neuroendocrine tumors (NET). The objective of our study is to evaluate the impact of octreotide LAR on overall survival (OS), as it has not been established.
Methods: NET patients of 65 years and older diagnosed between January 1999 and December 2009 were identified from the SEER-Medicare database. We compared the OS of NET patients who started octreotide LAR within 12 months of diagnosis with those who did not receive it during the same period. We conducted Kaplan–Meier estimations and Cox proportional hazard models to examine the association between octreotide LAR and OS.
Results: Among 1,176 distant stage patients, 233 (20%) received octreotide LAR within 12 months of diagnosis, compared with 2% (96 in 5,764) of local/regional stage patients. Median OS for patients who started octreotide LAR within 12 months was 35.22 months [95% confidence interval (CI), 27.96–47.77], longer than those who did not receive it (19.15 months; 95% CI, 16.36–22.80; P &lt; 0.0001). Multivariate analysis showed that octreotide LAR was associated with significant survival improvement for distant stage patients (HR, 0.68; P &lt; 0.001) and in the subgroups with (HR, 0.65; P, 0.003) and without (HR, 0.55; P, 0.002) carcinoid syndrome. No survival benefit was found among local/regional stage patients.
Conclusion: This population-based study suggests potential survival benefits of octreotide LAR among elderly distant stage NET patients, both with or without carcinoid syndrome.
Impact: The study provides population-based evidence of a positive association between octreotide LAR and overall survival among elderly distant stage NET patients. Cancer Epidemiol Biomarkers Prev; 24(11); 1656–65. ©2015 AACR.
Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Permuth-Wey Jennifer , Chen Dung-Tsa , Fulp William J. , Yoder Sean J. , Zhang Yonghong , Georgeades Christina , Husain Kazim , Centeno Barbara Ann , Magliocco Anthony M. , Coppola Domenico , Malafa Mokenge 
Published: August 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of miRNAs in the progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of miRNAs in archived preoperative plasma from individuals with pathologically confirmed IPMNs and healthy controls and discover plasma miRNAs that distinguish between IPMN patients and controls and between “malignant” and “benign” IPMNs. Using novel nCounter technology to evaluate 800 miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3–86.5, P = 0.002]. The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2- to 4-fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6–88.9, P = 0.005), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a miRNA-based blood test to aid in the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment. Cancer Prev Res; 8(9); 826–34. ©2015 AACR.
Impairment of Macrophage Cholesterol Efflux by Cholesterol Hydroperoxide Trafficking
Authors: Korytowski Witold , Wawak Katarzyna , Pabisz Pawel , Schmitt Jared C. , Chadwick Alexandra C. , Sahoo Daisy , Girotti Albert W. 
Published: August 2015

Objective—
Oxidative stress associated with cardiovascular disease can produce various oxidized lipids, including cholesterol oxides, such as 7-hydroperoxide (7-OOH), 7-hydroxide (7-OH), and 7-ketone (7=O). Unlike 7=O and 7-OH, 7-OOH is redox active, giving rise to the others via potentially toxic-free radical reactions. We tested the novel hypothesis that under oxidative stress conditions, steroidogenic acute regulatory (StAR) family proteins not only deliver cholesterol to/into mitochondria of vascular macrophages, but also 7-OOH, which induces peroxidative damage that impairs early stage reverse cholesterol transport.

Approach and Results—
Stimulation of human monocyte-derived THP-1 macrophages with dibutyryl-cAMP resulted in substantial upregulation of StarD1 and ATP-binding cassette (ABC) transporter, ABCA1. Small interfering RNA–induced StarD1 knockdown before stimulation had no effect on StarD4, but reduced ABCA1 upregulation, linking the latter to StarD1 functionality. Mitochondria in stimulated StarD1-knockdown cells internalized 7-OOH slower than nonstimulated controls and underwent less 7-OOH–induced lipid peroxidation and membrane depolarization, as probed with C11-BODIPY (4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-inda-cene-3-undecanoic acid) and JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzimidazolylcarbocyanine iodide), respectively. Major functional consequences of 7-OOH exposure were (1) loss of mitochondrial CYP27A1 activity, (2) reduced 27-hydroxycholesterol (27-OH) output, and (3) downregulation of cholesterol-exporting ABCA1 and ABCG1. Consistently, 7-OOH–challenged macrophages exported less cholesterol to apoA-I or high-density lipoprotein than did nonchallenged controls. StarD1-mediated 7-OOH transport was also found to be highly cytotoxic, whereas 7=O and 7-OH were minimally toxic.

Conclusions—
This study describes a previously unrecognized mechanism by which macrophage cholesterol efflux can be incapacitated under oxidative stress–linked disorders, such as chronic obesity and hypertension. Our findings provide new insights into the role of macrophage redox damage/dysfunction in atherogenesis.
Medication Initiation Burden Required to Comply With Heart Failure Guideline Recommendations and Hospital Quality Measures
Authors: Allen Larry A. , Fonarow Gregg C. , Liang Li , Schulte Phillip J. , Masoudi Frederick A. , Rumsfeld John S. , Ho P. Michael , Eapen Zubin J. , Hernandez Adrian F. , Heidenreich Paul A. , Bhatt Deepak L. , Peterson Eric D. , Krumholz Harlan M. 
Published: August 2015

Background—
Guidelines for heart failure (HF) recommend prescription of guideline-directed medical therapy before hospital discharge; some of these therapies are included in publicly reported performance measures. The burden of new medications for individual patients has not been described.

Methods and Results—
We used Get With The Guidelines–HF registry data from 2008 to 2013 to characterize prescribing, indications, and contraindications for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, aldosterone antagonists, hydralazine/isosorbide dinitrate, and anticoagulants. The difference between a patient’s medication regimen at hospital admission and that recommended by HF quality measures at discharge was calculated. Among 158 922 patients from 271 hospitals with a primary discharge diagnosis of HF, initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was indicated in 18.1% of all patients (55.5% of those eligible at discharge were not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at admission), β-blockers in 20.3% (50.5% of eligible), aldosterone antagonists in 24.1% (87.4% of eligible), hydralazine/isosorbide dinitrate in 8.6% (93.1% of eligible), and anticoagulants in 18.0% (58.0% of eligible). Cumulatively, 0.4% of patients were eligible for 5 new medication groups, 4.1% for 4 new medication groups, 9.4% for 3 new medication groups, 10.1% for 2 new medication groups, and 22.7% for 1 new medication group; 15.0% were not eligible for new medications because of adequate prescribing at admission; and 38.4% were not eligible for any medications recommended by HF quality measures. Compared with newly indicated medications (mean, 1.45±1.23), actual new prescriptions were lower (mean, 1.16±1.00).

Conclusions—
A quarter of patients hospitalized with HF need to start >1 medication to meet HF quality measures. Systems for addressing medication initiation and managing polypharmacy are central to HF transitional care.
Use of the Wearable Cardioverter Defibrillator in High-Risk Cardiac Patients
Authors: Kutyifa Valentina , Moss Arthur J. , Klein Helmut , Biton Yitschak , McNitt Scott , MacKecknie Bonnie , Zareba Wojciech , Goldenberg Ilan 
Published: August 2015

Background—
Prospective data on the safety and efficacy of the wearable cardioverter defibrillator (WCD) in a real-world setting are lacking. The Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II) Registry was designed to provide real-world data on the WCD as a strategy during a period of risk stratification.

Methods and Results—

The WEARIT-II Registry enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD between August 2011 and February 2014. Clinical data, arrhythmia events, implantable cardioverter defibrillator implantation, and improvement in ejection fraction were captured. The median age was 62 years; the median ejection fraction was 25%. The median WCD wear time was 90 days, with median daily use of 22.5 hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41 patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%) received inappropriate WCD therapy. The rate of sustained ventricular tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy and congenital/inherited heart disease, and 1% among nonischemic patients (
P
=0.02). At the end of WCD use, 840 patients (42%) were implanted with an implantable cardioverter defibrillator. The most frequent reason not to implant an implantable cardioverter defibrillator following WCD use was improvement in ejection fraction.

Conclusions—
The WEARIT-II Registry demonstrates a high rate of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are not eligible for an implantable cardioverter defibrillator, and suggests that the WCD can be safely used to protect patients during this period of risk assessment.
Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction
Authors: Joshi Nikhil V. , Toor Iqbal , Shah Anoop S. V. , Carruthers Kathryn , Vesey Alex T. , Alam Shirjel R. , Sills Andrew , Hoo Teng Y. , Melville Adam J. , Langlands Sarah P. , Jenkins William S. A. , Uren Neal G. , Mills Nicholas L. , Fletcher Alison M. , van Beek Edwin J. R. , Rudd James H. F. , Fox Keith A. A. , Dweck Marc R. , Newby David E. 
Published: August 2015

Background
Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.

Methods and Results

Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F‐fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F‐fluorodeoxyglucose uptake (tissue‐to‐background ratio 2.15±0.30 versus 1.84±0.18,
P
<0.0001) and plasma C‐reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL,
P
=0.0005) despite having similar aortic (
P
=0.12) and less coronary (
P
=0.006) atherosclerotic burden and similar paraspinal muscular 18F‐fluorodeoxyglucose uptake (
P
=0.52). Patients with
ST
‐segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L,
P
<0.0001) and greater aortic 18F‐fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21,
P
=0.03) than those with non–
ST
‐segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F‐fluorodeoxyglucose uptake (
r
=0.43,
P
=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19],
P
=0.001), but not late, recurrent MI.

Conclusions
The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01749254.
Automated Retrieval of Cloud and Aerosol Properties from the ARM Raman Lidar. Part II: Extinction
Authors: Thorsen Tyler J. , Fu Qiang 
Published: August 2015

AbstractA feature detection and extinction retrieval (FEX) algorithm for the Atmospheric Radiation Measurement Program’s (ARM) Raman lidar (RL) has been developed. Presented here is Part II of the FEX algorithm: the retrieval of cloud and aerosol extinction profiles. The directly retrieved extinction profiles using the Raman method are supplemented by other retrieval methods developed for elastic backscatter lidars. Portions of features where the extinction-to-backscatter ratios (i.e., lidar ratios) can be obtained are used to infer the lidar ratios for the regions where no such estimate can be made. When neither directly retrieved nor an inferred value can be determined, a climatological lidar ratio is used. This best-estimate approach results in the need to use climatological lidar ratios for less than about 5% of features, except for thin cirrus at the ARM tropical western Pacific Darwin site, where above 12 km, about 20% of clouds use a climatological lidar ratio. A classification of feature type is made, guided by the atmosphere’s thermodynamic state and the feature’s scattering properties: lidar ratio, backscatter, and depolarization. The contribution of multiple scattering is explicitly considered for each of the ARM RL channels. A comparison between aerosol optical depth from FEX and that from collocated sun photometers over multiple years at two ARM sites shows an agreement (in terms of bias error) of about −0.3% to −4.3% (relative to the sun photometer).
Insight into the Kinematic and Microphysical Processes that Control Lightning Jumps
Authors: Schultz Christopher J. , Carey Lawrence D. , Schultz Elise V. , Blakeslee Richard J. 
Published: August 2015

AbstractA detailed case study analysis of four thunderstorms is performed using polarimetric and multi-Doppler capabilities to provide specificity on the physical and dynamical drivers behind lightning jumps. The main differences between small increases in the total flash rate and a lightning jump are the increases in graupel mass and updraft volumes ≥10 m s−1 between the −10° and −40°C isotherms. Updraft volumes ≥10 m s−1 increased in magnitude at least 3–5 min in advance of the increase in both graupel mass and total flash rate. Updraft volumes ≥10 m s−1 are more robustly correlated to total flash rate than maximum updraft speed over a thunderstorm’s entire life cycle. However, peak updraft speeds increase prior to 8 of the 12 lightning jumps examined. Decreases in mean and median flash footprint size during increases in total lightning are observed in all four thunderstorms and are most notable during development stages within the most intense storms. However, this inverse relationship breaks down on larger storm scales as storms mature and anvils and stratiform regions developed with time. Promisingly, smaller flash sizes are still collocated with the strongest updraft speeds, while larger flash sizes are observed within weaker updraft regions. The results herein emphasize the following for lightning jump applications: both the lightning jump sigma level and the resultant magnitude of the total flash rate must be employed in conjunction to assess storm intensity using lightning data. The sigma-level magnitude of the lightning jump is the early warning that indicates that rapid intensification is occurring, while the magnitude of the total flash rate provides insight into the size and maintenance of the updraft volume and graupel mass. These cases serve as conceptual models for future applications of the lightning jump algorithm for hazardous weather monitoring.
The Chronic Detrimental Impact of Interruptions in a Simulated Submarine Track Management Task
Authors: Loft Shayne , Sadler Andreas , Braithwaite Janelle , Huf Samuel 
Published: August 2015

Objective: The objective of this article is to examine the extent to which interruptions negatively impact situation awareness and long-term performance in a submarine track management task where pre- and postinterruption display scenes remained essentially identical. Background: Interruptions in command and control task environments can degrade performance well beyond the first postinterruption action typically measured for sequential static tasks, because individuals need to recover their situation awareness for multiple unfolding display events. Participants in the current study returned to an unchanged display scene following interruption and therefore could be more immune to such long-term performance deficits. Method: The task required participants to monitor a display to detect contact heading changes and to make enemy engagement decisions. Situation awareness (Situation Present Assessment Method) and subjective workload (NASA–Task Load Index) were measured. The interruption replaced the display for 20 s with a blank screen, during which participants completed a classification task. Results: Situation awareness after returning from interruption was degraded. Participants were slower to make correct engagement decisions and slower and less accurate in detecting heading changes, despite these task decisions being made at least 40 s following the interruption. Conclusion: Interruptions negatively impacted situation awareness and long-term performance because participants needed to redetermine the location and spatial relationship between the displayed contacts when returning from interruption, either because their situation awareness for the preinterruption scene decayed or because they did not encode the preinterruption scene. Application: Interruption in work contexts such as submarines is unavoidable, and further understanding of how operators are affected is required to improve work design and training.
Trust in and legitimacy of the police among American college students
Authors: Lee Heeuk D , Boateng Francis D , Marenin Otwin 
Published: August 2015

The purpose of this study is to assess whether police fairness, effectiveness, assistance and fear of crime variables help explain trust in the police among university students. Five hundred questionnaires were distributed to all students in randomly selected summer courses offered by the university in 2012; 414 questionnaires were filled and returned, yielding a response rate of about 83%. Ordinary least square regression was used to estimate the effects of our independent variables on college students’ trust in the police. The results show that police fairness and police assistance were significantly related to trust in the police after accounting for respondents’ demographic characteristics. However, fear of crime and police effectiveness did not predict students’ trust in the police. This study was carried out on a sample of college students in one Carnegie 1 institution, thus findings have limited generalisability and need to be interpreted with caution. Our research and findings add another small piece to the theoretical confusion, and inconsistent findings, on the topics of factors supporting trust in the police which now characterises the literature, but do not undermine the basic policy value of procedural justice. This study can provide useful references for policing scholars, policy makers and police practitioners.