bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Regulation of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Plasma Levels and Its Impact on Atherosclerotic Vascular Disease Phenotypes
Authors: Pott Janne , Schlegel Valentin , Teren Andrej , Horn Katrin , Kirsten Holger , Bluecher Christina , Kratzsch Juergen , Loeffler Markus , Thiery Joachim , Burkhardt Ralph , Scholz Markus 
Published: October 2018

Background:
Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is a novel strategy to treat hypercholesterolemia and reduce cardiovascular events. However, the potential role of circulating plasma PCSK9 concentrations as a diagnostic and predictive biomarker remains uncertain as of now. Here, we aimed to identify genetic variants associated with plasma PCSK9 and investigate possible causal effects on atherosclerotic vascular disease phenotypes.

Methods:
We performed the first genome-wide association study of plasma PCSK9 levels in a cohort of suspected and confirmed coronary artery disease (LIFE-Heart; n=3290).

Results:

Several independent variants at the
PCSK9
gene locus were associated with circulating PCSK9 levels at genome-wide significance (lead SNP rs11591147, PCSK9-R46L;
P
=1.94×10
−17
). We discovered 4 independent
PCSK9
SNPs explaining 4.4% of the variance of plasma PCSK9. In addition, we identified a genome-wide significant locus at chromosome 7p22.1 (rs6957201;
P
=7.01×10
−9
) and 7 suggestive hits (
P
<1×10
−6
). Using MR (Mendelian Randomization), we detected significant causal effects of circulating PCSK9 on coronary artery disease status and severity, carotid plaques, and intima-media thickness.

Conclusions:

Variants at the
PCSK9
gene locus seem to be the major genetic determinants of plasma PCSK9 levels with 4 independent variants at the
PCSK9
gene locus expressing allelic heterogeneity. The detected MR estimates support the hypothesis of a causal effect of PCSK9 on coronary artery disease and other vascular phenotypes. Other observed genetic associations for PCSK9 require validation in independent cohorts.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT00497887.
Genetic Control of Left Atrial Gene Expression Yields Insights into the Genetic Susceptibility for Atrial Fibrillation
Authors: Hsu Jeffrey , Gore-Panter Shamone , Tchou Gregory , Castel Laurie , Lovano Beth , Moravec Christine S. , Pettersson Gosta B. , Roselli Eric E. , Gillinov A. Marc , McCurry Kenneth R. , Smedira Nicholas G. , Barnard John , Van Wagoner David R. , Chung Mina K. , Smith Jonathan D. 
Published: October 2018

Background:
Genome-wide association studies have identified 23 loci for atrial fibrillation (AF), but the mechanisms responsible for these associations, as well as the causal genes and genetic variants, remain undefined.

Methods:
To identify the effect of common genetic variants on gene expression that might explain the mechanisms linking genome-wide association loci with AF risk, we performed RNA sequencing of left atrial appendages from a biracial cohort of 265 subjects.

Results:

Combining gene expression data with genome-wide single nucleotide polymorphism data, we found that approximately two-thirds of the expressed genes were regulated in
cis
by common genetic variants at a false discovery rate of <0.05, defined as cis-expression quantitative trait loci. Twelve of 23 reported AF genome-wide association loci displayed genome-wide significant
cis
-expression quantitative trait loci, at
PRRX1
(chromosome 1q24),
SNRNP27
(1q24),
CEP68
(2p14),
FKBP7
(2q31),
KCNN2
(5q22),
FAM13B
(5q31),
CAV1
(7q31),
ASAH1
(8p22),
MYOZ1
(10q22),
C11ORF45
(11q24),
TBX5
(12q24), and
SYNE2
(14q23), suggesting that altered expression of these genes plays a role in AF susceptibility. Allelic expression imbalance was used as an independent method to characterize the cis-control of gene expression. One thousand two hundred forty-eight of 5153 queried genes had
cis
-single nucleotide polymorphisms that significantly regulated allelic expression at a false discovery rate of <0.05.

Conclusions:
We provide a genome-wide catalog of the genetic control of gene expression in human left atrial appendage. These data can be used to confirm the relevance of genome-wide association loci and to direct future functional studies to identify the genes and genetic variants responsible for complex diseases such as AF.
Temporal Trends in Chronic Total Occlusion Interventions in Europe
Authors: Konstantinidis Nikolaos V. , Werner Gerald S. , Deftereos Spyridon , Di Mario Carlo , Galassi Alfredo R. , Buettner Joachim H. , Avran Alexandre , Reifart Nicolaus , Goktekin Omer , Garbo Roberto , Bufe Alexander , Mashayekhi Kambis , Boudou Nicolas , Meyer-Geßner Markus , Lauer Bernward , Elhadad Simon , Christiansen Evald H. , Escaned Javier , Hildick-Smith David , Carlino Mauro , Louvard Yves , Lefèvre Thierry , Angelis Lefteris , Giannopoulos Georgios , Sianos Georgios ,   on behalf of the Euro CTO Club
Published: October 2018

Background:
The study focuses on the evolution of practice, procedural outcomes, and in-hospital complications of chronic total occlusion percutaneous coronary intervention in Europe.

Methods and Results:

Data from 17 626 procedures enrolled in European Registry of Chronic Total Occlusion between January 2008 and June 2015 were assessed. The mean patient age was 63.9±10.9 years; 85% were men. Procedural success increased from 79.7% to 89.3% through the study period. Patients enrolled during the years had increasing comorbidities and lesion complexity (J-CTO score [Multicenter CTO Registry of Japan] increased from 1.76±1.03 in 2008 to 2.17±0.91 in 2015;
P
for trend, <0.001). Retrograde approach utilization steadily increased from 10.1% in 2008 to 29.9% in 2015 (
P
for trend, <0.001). Antegrade dissection reentry adoption was low, not exceeding 5.5%. In-hospital mortality decreased during the study period from 0.4% to 0.1% (
P
for trend, <0.001), whereas in-hospital complication rates remained essentially unchanged, in the range 4.4% to 5.2% (
P
for trend, 0.390).

Conclusions:
Chronic total occlusion percutaneous coronary intervention has shown a steady increase in procedural success rate over time, with unchanged complication rates, despite the increasing complexity of the lesions attempted. The J-CTO score predictive value for procedural success was low for the entire registry and had no predictive ability for the retrograde approach.
Predicting Quality of Life at 1 Year After Transcatheter Aortic Valve Replacement in a Real-World Population
Authors: Arnold Suzanne V. , Cohen David J. , Dai David , Jones Philip G. , Li Fan , Thomas Laine , Baron Suzanne J. , Frankel Naftali Z. , Strong Susan , Matsouaka Roland A. , Edwards Fred H. , Brennan J. Matthew 
Published: October 2018

Background
Among clinical trial patients at high surgical risk, a model has been developed and externally validated to estimate patient risk for poor outcomes after transcatheter aortic valve replacement (TAVR). How this model performs in lower risk and unselected patients is not known. We sought to examine and optimize the performance of the TAVR poor outcome risk model among patients in the US Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

Methods and Results

Among 13 351 patients who underwent TAVR at 252 US sites between November 9, 2011 and June 30, 2015, the rate of poor outcome at 1 year after TAVR was 38.9%, which was because of death in 20.7% and poor quality of life or quality of life decline in 18.2%. The rate of poor outcome has decreased slightly over time, from 42.0% in 2012 to 37.8% in 2015 (
P
for trend=0.076). The original TAVR poor outcome risk model did not calibrate well on this population. We then reestimated the intercept and coefficients in the model and retested model performance, after which it performed well (both overall and in subgroups), with a C index 0.65 and excellent calibration.

Conclusions
In a large cohort of unselected patients in the United States, we found that while a substantial minority of patients continue to have a poor outcome after TAVR, outcomes have slowly improved over time. After recalibration, the TAVR poor outcome risk model performed well. This model could potentially be used before TAVR to help patients have appropriate expectations of recovery.
ECMWF Activities for Improved Hurricane Forecasts
Authors: Magnusson L. , Bidlot J.-R. , Bonavita M. , Brown A. R. , Browne P. A. , De Chiara G. , Dahoui M. , Lang S. T. K. , McNally T. , Mogensen K. S. , Pappenberger F. , Prates F. , Rabier F. , Richardson D. S. , Vitart F. , Malardel S. 
Published: October 2018

AbstractTropical cyclones are some of the most devastating natural hazards and the “three beasts”—Harvey, Irma, and Maria—during the Atlantic hurricane season 2017 are recent examples. The European Centre for Medium-Range Weather Forecasts (ECMWF) is working on fulfilling its 2016–25 strategy in which early warnings for extreme events will be made possible by a high-resolution Earth system ensemble forecasting system. Several verification reports acknowledge deterministic and probabilistic tropical cyclone tracks from ECMWF as world leading. However, producing reliable intensity forecasts is still a difficult task for the ECMWF global forecasting model, especially regarding maximum wind speed. This article will put the ECMWF strategy into a tropical cyclone perspective and highlight some key research activities, using Harvey, Irma, and Maria as examples. We describe the observation usage around tropical cyclones in data assimilation and give examples of their impact. From a model perspective, we show the impact of running at 5-km resolution and also the impact of applying ocean coupling. Finally, we discuss the future challenges to tackle the errors in intensity forecasts for tropical cyclones.
Oral Sensory-Motor Intervention for Children and Adolescents (3-18 Years) With Dysphagia or Impaired Saliva Control Secondary to Congenital or Early-Acquired Disabilities: A Review of the Literature, 2000 to 2016
Authors: Sjögreen Lotta , Gonzalez Lindh Margareta , Brodén Madeleine , Krüssenberg Corinna , Ristic Irvina , Rubensson Agneta , McAllister Anita 
Published: October 2018

Objectives: Dysphagia and impaired saliva control are common in children and adolescents with congenital and developmental disabilities. The aim of the present review was to investigate the evidence base for oral sensory-motor interventions in children and adolescents with dysphagia or impaired saliva control secondary to congenital or early-acquired disabilities and to make recommendations regarding methods for intervention. Methods: A review of the literature from 2000 to 2016, including oral sensory-motor intervention studies for children and adolescents (3-18 years of age) with dysphagia or impaired saliva control secondary to congenital or early-acquired disabilities, was performed. The literature search included the PubMed, CINAHL, Medline, SpeechBITE, OVID, ERIC, Cochrane, and Google Scholar databases. Primary studies were evaluated on a 4-grade scale using the Grading of Recommendations Assessment, Development and Evaluation. Results: Twenty primary studies of oral sensory-motor interventions for dysphagia and 6 studies for the treatment of impaired saliva control fulfilled the inclusion criteria. Of these, 3 were randomized, controlled trials. Five systematic reviews and 16 narrative reviews were also included. Limited and moderately strong recommendations were made on the basis of the grading results from the primary studies. The studies reported good results, but study design was often insufficient, and the study groups were small. The systematic reviews confirmed the lack of high scientific support for oral sensory-motor interventions in children and adolescents with congenital and developmental disabilities. Conclusions: There is an urgent need for high-quality studies that could serve as the basis for strong recommendations relating to oral sensory-motor interventions for children with dysphagia and impaired saliva control.
Polysomnographic Findings in Patients With Chronic Tinnitus
Authors: Teixeira Liane Sousa , Oliveira Carlos Augusto Costa , Granjeiro Ronaldo Campos , Petry Carine , Travaglia Adra Brasil Leitão , Bahmad Fayez 
Published: October 2018

Objectives: Tinnitus is an auditory sensation in the absence of any external stimulus. It has a negative impact on quality of life and interferes with concentration, sleep, social activities, and even emotional stability. The aim of this study was to compare sleep architecture in patients with and without chronic subjective tinnitus. Methods: This was an observational, noninterventional, and prospective study. The sample consisted of 50 individuals of both sexes aged 20 to 60 years. Twenty-five patients with tinnitus constituted the study group, and for comparison, a control group consisting of 25 patients without reported tinnitus was formed. The patients underwent polysomnography and were administered the Epworth Sleepiness Scale, Tinnitus Handicap Inventory, and visual analog scales. Results: The group with tinnitus had higher mean values in sleep stages 1 and 2, and lower mean values in stage 3 and in rapid eye movement (REM) sleep, compared with the control group, and this difference was significant only for REM sleep ( P = .031). This demonstrates that patients with tinnitus remained longer in shallow sleep and spent less time in deep sleep (stage 3) and REM sleep. Conclusions: This study shows that patients with tinnitus have significant alterations in REM sleep latency as well as the REM sleep phase.
Racial/Ethnic Disparities in Influenza Vaccination Coverage Among US Adolescents, 2010-2016
Authors: Webb Noah S. , Dowd-Arrow Benjamin , Taylor Miles G. , Burdette Amy M. 
Published: October 2018

Objective: Although research suggests racial/ethnic disparities in influenza vaccination and mortality rates, few studies have examined racial/ethnic trends among US adolescents. We used national cross-sectional data to determine (1) trends in influenza vaccination rates among non-Hispanic white (hereinafter, white), non-Hispanic black (hereinafter, black), and Hispanic adolescents over time and (2) whether influenza vaccination rates among adolescents varied by race/ethnicity. Methods: We analyzed provider-reported vaccination histories for 2010-2016 from the National Immunization Survey–Teen. We used binary logistic regression models to determine trends in influenza vaccination rates by race/ethnicity for 117 273 adolescents, adjusted for sex, age, health insurance, physician visit in the previous 12 months, vaccination facility type, poverty status, maternal education level, children in the household, maternal marital status, maternal age, and census region of residence. We calculated adjusted probabilities for influenza vaccination for each racial/ethnic group, adjusted for the same demographic characteristics. Results: Compared with white adolescents, Hispanic adolescents had higher odds (adjusted odds ratio [aOR] = 1.11; 95% confidence interval [CI], 1.06-1.16) and black adolescents had lower odds (aOR = 0.95; 95% CI, 0.90-1.00) of vaccination. Compared with white adolescents, Hispanic adolescents had significantly higher adjusted probabilities of vaccination for 2011-2013 (2011: 0.22, P < .001; 2012: 0.23, P < .001; 2013: 0.26, P < .001). Compared with white adolescents, black adolescents had significantly lower probabilities of vaccination for 2016 (2016: 0.21, P < .001). Conclusions: Targeted interventions are needed to improve adolescent influenza vaccination rates and reduce racial/ethnic disparities in adolescent vaccination coverage.
Mental adjustment to cancer and quality of life among women living with breast cancer in Ghana
Authors: Kugbey Nuworza , Meyer-Weitz Anna , Oppong Asante Kwaku 
Published: October 2018

Objective This study examined whether cancer-specific coping strategies have any significant influence on the quality of life of 205 women living with breast cancer in Ghana. Methods Using a cross-sectional survey design, participants were administered questionnaires which measured their cancer-specific coping strategies and health-related quality of life. Results Correlation analysis showed that helplessness-hopelessness negatively correlated with physical wellbeing, emotional wellbeing, functional wellbeing, and breast cancer additional concerns. Anxious preoccupation negatively correlated with all the domains of quality of life, whereas fighting spirit was positively correlated with emotional and functional wellbeing. Cognitive avoidance was positively correlated with functional wellbeing, while fatalism was positively related with all the domains of quality of life. Regression analysis revealed that anxious preoccupation predicted significant decreases in all the domains of quality of life, while helplessness-hopelessness predicted significant decreases in emotional and functional wellbeing domains. However, cognitive avoidance predicted significant increase in the functional domain of quality of life. Conclusion These findings underscore the need for psychosocial support for breast cancer patients to adopt effective coping strategies to deal with their challenges in managing their illness.
Prevalence of vitamin D deficiency in Iran: A systematic review and meta-analysis
Authors: Vatandost Salam , Jahani Marzieh , Afshari Ali , Amiri Mohammad Reza , Heidarimoghadam Rashid , Mohammadi Younes 
Published: October 2018

Background: The prevalence of vitamin D deficiency in the Iranian community is very high. Women and older people are at the higher risk of vitamin D deficiency. Aim: This study aimed to estimate the prevalence of vitamin D deficiency in Iran by combining the results of various studies. Methods: This was a systematic review and meta-analysis. Separate strategies were developed for search in national databases (Irandoc, Magiran, SID) and international databases (Web of Science, PubMed, and Scopus) using the keywords of “vitamin D deficiency,” “Iran,” and “prevalence.” The titles and abstracts of the articles were screened and related full texts were appraised. Those articles that met inclusion criteria were selected for meta-analysis. The heterogeneity of the articles was assessed via the Chi-square test. They were combined using the random-effect approach. In addition, the groups were categorized and analyzed in terms of age and gender. Results: Of 639 articles, 30 articles with a sample size of 26,042 people were included for data analysis. The overall prevalence of vitamin D deficiency was reported as 0.56. Subgroup analysis showed that 0.64 of women and 0.44 of men were suffering from vitamin D deficiency. The prevalence of vitamin D deficiency in the age groups under 20, 20–50, and over 50 years was 0.56.4, 0.72.4, and 0.59.8, respectively. Conclusions: The Iranian Ministry of Health is expected to design strategies to improve the status of vitamin D at the national level.
Association between serum copper levels and lung cancer risk: A meta-analysis
Authors: Zhang Xiaping , Yang Qun 
Published: October 2018

Objective To evaluate the association between serum copper levels and lung cancer risk. Methods We searched the electronic PubMed, WanFang, CNKI, and SinoMed databases to identify studies including information on serum copper levels and lung cancer. Standard mean differences and corresponding 95% confidence intervals were calculated using Stata 12.0 software. We performed a meta-analysis on the identified studies overall and according to geographic location. We also evaluated heterogeneity among the studies and the occurrence of publication bias. Results Thirty-three articles including 3026 cases and 9439 controls were included in our study. The combined results showed that serum copper levels were higher in patients with lung cancer compared with controls without lung cancer, though the results showed high heterogeneity. In a subgroup analysis according to geographic location, significant associations between copper levels and lung cancer were found for both Asian and European populations. No publication bias was detected in this meta-analysis. Conclusions High serum copper levels could increase the risk of lung cancer, suggesting that environmental copper exposure may be a risk factor for the development of lung cancer.
Survey of Australian psychiatrists’ and psychiatry trainees’ knowledge about and attitudes towards medicinal cannabinoids
Authors: Jacobs Nathan I , Montebello Mark , Monds Lauren A , Lintzeris Nicholas 
Published: October 2018

Objective: To assess Australian psychiatrists’ and psychiatry trainees’ knowledge about and attitudes towards medicinal cannabinoids, given the recent relaxation of cannabinoid-prescribing laws in Australia. Method: All Australian members of the Royal Australian and New Zealand College of Psychiatrists were invited to participate in an anonymous, 64-item online questionnaire, through Royal Australian and New Zealand College of Psychiatrists’ newsletters. The questionnaire ran for a 10-week period from March to May 2017. Participants were asked about their knowledge of the evidence for and against prescribing pharmaceutical-grade cannabidiol and tetrahydrocannabinol, and their concerns about prescribing medicinal cannabinoids. Results: In total, 88 doctors responded to the survey, with 55 completing all items (23 psychiatrists, 32 trainees). Overall, 54% of respondents would prescribe medicinal cannabinoids if it was legal to do so. Participants believed there was evidence for the use of cannabidiol and tetrahydrocannabinol in treating childhood epilepsy, chronic pain, and nausea and vomiting. They were most concerned about medicinal cannabinoids leading to psychotic symptoms, addiction and dependence, apathy and recreational use. Conclusions: Our sample of Australian psychiatrists and trainees were aware of the main clinical indications for medicinal cannabinoids, but were poor at differentiating between the indications for cannabidiol versus tetrahydrocannabinol. Further education about medicinal cannabinoids appears necessary.
The Influence of Latino Symptom Experience on Participation in Usual Activities and Satisfaction With Participation in Social Roles
Authors: Koleck Theresa A. , Suero-Tejeda Niurka , Bakken Suzanne 
Published: October 2018

Introduction: Little is known about the Latino symptom experience and how symptoms influence participation in usual activities and satisfaction with participation in social roles. Method: Secondary analysis of survey data collected in community and clinic settings was conducted. Data were collected using Health-Related Quality of Life 30-day items and Patient Reported Outcome Measurement System symptom status scales. Descriptive statistics and univariate linear and multiple linear regression models were computed. Results: Participants ( N = 2,974) were primarily female and Dominican. Most surveys were completed in Spanish and in the community setting; and the clinic sample had more symptoms. In the multiple linear regression for participation in usual activities, as the number of days with symptoms increased, the number of days that poor physical or mental health influenced participation in usual activities increased. In addition, for satisfaction with participation in social roles, as the number of days with pain and levels of depression and anxiety increased, the levels of satisfaction decreased. Spanish survey administration was associated with decreased levels of satisfaction; and recruitment setting was not a significant predictor. Conclusion: The study addressed multiple knowledge gaps about the Latino symptom experience.