bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Dysfunction in Duchenne Muscular Dystrophy Is Less Frequent in Patients With Mutations in the Dystrophin Dp116 Coding Region Than in Other Regions
Authors: Yamamoto Tetsushi , Awano Hiroyuki , Zhang Zhujun , Sakuma Mio , Kitaaki Shoko , Matsumoto Masaaki , Nagai Masashi , Sato Itsuko , Imanishi Takamitsu , Hayashi Nobuhide , Matsuo Masafumi , Iijima Kazumoto , Saegusa Jun 
Published: October 2018

Background

Duchenne muscular dystrophy (DMD), the most common inherited muscular disease in childhood, is caused by dystrophin deficiency because of mutations in the
DMD
gene. Although DMD is characterized by fatal progressive muscle wasting, cardiomyopathy is the most important nonmuscle symptom threatening the life of patients with DMD. The relationship between cardiac involvement and dystrophin isoforms has not been analyzed.

Methods and Results

The results of 1109 echocardiograms obtained from 181 Japanese DMD patients with confirmed mutations in the
DMD
gene were retrospectively analyzed. Patients showed an age-related decline in left ventricular ejection fraction. Patients were divided by patterns of dystrophin isoform deficiency into 5 groups. The cardiac dysfunction-free survival was significantly higher in the group with mutations in the Dp116 coding region than the others, whereas no significant differences in the other 3 groups. At age 25 years, the cardiac dysfunction-free rate was 0.6 in the Dp116 group, but only 0.1 in others. PCR amplification of Dp116 transcript in human cardiac muscle indicated promoter activation.

Conclusions
Left ventricular ejection fraction in DMD declined stepwise with age. Cardiac dysfunction was less frequent in Dp116-deficient than other patients with DMD. Dp116 transcript was identified in human cardiac muscle for the first time. These results indicate that Dp116 is associated with cardiac involvement in DMD.
Genome-Wide Association Study Identifies a Novel Genetic Risk Factor for Recurrent Venous Thrombosis
Authors: de Haan Hugoline G. , van Hylckama Vlieg Astrid , Germain Marine , Baglin Trevor P. , Deleuze Jean-François , Trégouët David-Alexandre , Rosendaal Frits R. 
Published: October 2018

Background:
Genetic risk factors for a first venous thrombosis (VT) seem to have little effect on recurrence risk. Therefore, we aimed specifically to identify novel genetic determinants of recurrent VT. To date, genome-wide association studies are lacking.

Methods and Results:

We performed a genome-wide association scan in 1279 patients from the MEGA (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis) follow-up study; 832 patients who remained recurrence free during a median follow-up time of 6.1 years and 447 recurrent VT patients with a median time-to-recurrence of 2.6 years. We analyzed genotype probabilities of ≈8.6 million variants, imputed to the Genome of the Netherlands project reference panel, with a minor allele frequency ≥1% for an association with recurrent VT. One region exceeded genome-wide significance (
P
≤5×10
−
8
), mapping to the well-known factor V Leiden locus. Conditional association analyses on factor V Leiden did not yield any secondary association signals. We also identified 52 suggestive association signals (
P
<1×10
−5
) at 17 additional loci. None of these loci were previously implicated in VT risk. Replication analyses for 17 lead variants were performed in 350 patients with recurrent VT and 1866 patients with a single VT event from the MEGA follow-up study, THE-VTE (Thrombophilia, Hypercoagulability and Environmental Risks in Venous Thromboembolism) study, and LETS (Leiden Thrombophilia Study). We observed an association with recurrence for an intergenic variant at 18q22.1 with an odds ratio of 1.7 (95% confidence interval, 1.2–2.6) per copy of the minor allele.

Conclusions:
We confirmed the association of factor V Leiden and identified a novel risk locus at 18q22.1 in the first large genetic study on recurrent VT.
Genetic Reduction in Left Ventricular Protein Kinase C-α and Adverse Ventricular Remodeling in Human Subjects
Authors: Hu Ray , Morley Michael P. , Brandimarto Jeffrey , Tucker Nathan R. , Parsons Victoria A. , Zhao Sihai D. , Meder Benjamin , Katus Hugo A. , Rühle Frank , Stoll Monika , Villard Eric , Cambien François , Lin Honghuang , Smith Nicholas L. , Felix Janine F. , Vasan Ramachandran S. , van der Harst Pim , Newton-Cheh Christopher , Li Jin , Kim Cecilia E. , Hakonarson Hakon , Hannenhalli Sridhar , Ashley Euan A. , Moravec Christine S. , Tang W.H. Wilson , Maillet Marjorie , Molkentin Jeffery D. , Ellinor Patrick T. , Margulies Kenneth B. , Cappola Thomas P 
Published: October 2018

Background:

Inhibition of PKC-α (protein kinase C-α) enhances contractility and cardioprotection in animal models, but effects in humans are unknown. Genotypes at rs9912468 strongly associate with
PRKCA
expression in the left ventricle, enabling genetic approaches to measure effects of reduced PKC-α in human populations.

Methods and Results:

We analyzed the
cis
expression quantitative trait locus for
PRKCA
marked by rs9912468 using 313 left ventricular specimens from European Ancestry patients. The forward strand minor allele (G) at rs9912468 is associated with reduced PKC-α transcript abundance (1.7-fold reduction in minor allele homozygotes,
P
=1×10
−41
). This association was cardiac specific in expression quantitative trait locus data sets that span 16 human tissues. Cardiac epigenomic data revealed a predicted enhancer in complete (
R
2
=1.0) linkage disequilibrium with rs9912468 within intron 2 of
PRKCA.
We cloned this region and used reporter constructs to verify cardiac-specific enhancer activity in vitro in cardiac and noncardiac cells and in vivo in zebrafish. The
PRKCA
enhancer contains 2 common genetic variants and 4 haplotypes; the haplotype correlated with the rs9912468 PKC-α–lowering allele (G) showed lowest activity. In contrast to previous reports in animal models, the PKC-α–lowering allele is associated with adverse left ventricular remodeling (higher mass, larger diastolic dimension), reduced fractional shortening, and higher risk of dilated cardiomyopathy in human populations.

Conclusions:
These findings support PKC-α as a regulator of the human heart but suggest that PKC-α inhibition may adversely affect the left ventricle depending on timing and duration. Pharmacological studies in human subjects are required to discern potential benefits and harms of PKC-α inhibitors as an approach to treat heart disease.
Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities)
Authors: Roetker Nicholas S. , Pankow James S. , Bressler Jan , Morrison Alanna C. , Boerwinkle Eric 
Published: October 2018

Background:
DNA methylation-based patterns of biological aging, known as epigenetic age acceleration, are predictive of all-cause mortality, but little is known about their association with cardiovascular disease (CVD).

Methods:
We estimated 2 versions of epigenetic age acceleration (Horvath and Hannum) using whole-blood samples from 2543 blacks. Linear and Cox proportional hazards regression, respectively, were used to assess the association of age acceleration with carotid intima–media thickness (cross-sectionally) and incident cardiovascular events, including CVD mortality, myocardial infarction, fatal coronary heart disease, peripheral arterial disease, and heart failure, during a median 21-year follow-up. All models were adjusted for chronological age and traditional CVD risk factors.

Results:

In comparison to chronological age, the 2 measures of epigenetic age acceleration were weaker, but independent, potential risk markers for subclinical atherosclerosis and most incident cardiovascular outcomes, including fatal coronary heart disease, peripheral arterial disease, and heart failure. For example, each 5-year increment of epigenetic age acceleration was associated with an average of 0.01 mm greater carotid intima–media thickness (each
P
≤0.01), and the hazard ratios (95% confidence intervals) of fatal coronary heart disease per 5-year increment in Horvath and Hannum age acceleration were 1.17 (1.02–1.33) and 1.22 (1.04–1.44), respectively.

Conclusions:
In this sample of blacks, increased epigenetic age acceleration in whole blood was a potential risk marker for incident fatal coronary heart disease, peripheral arterial disease, and heart failure independently of chronological age and traditional CVD risk factors. DNA methylation–based measures of biological aging may help to identify new pathophysiological mechanisms contributing to the development of CVD.
Partitioning the Pleiotropy Between Coronary Artery Disease and Body Mass Index Reveals the Importance of Low Frequency Variants and Central Nervous System–Specific Functional Elements
Authors: Nikpay Majid , Turner Adam W , McPherson Ruth 
Published: October 2018

Background:
The objective of this study is to investigate the extent and nature of pleiotropy between coronary artery disease (CAD) and body mass index (BMI).

Methods:
We examined the contribution of genome-wide single-nucleotide polymorphisms (minor allele frequency ≥0.01) to co-occurrence of CAD and BMI in a sample of genetically unrelated 8041 subjects (genetic resemblance ≤0.025) of European ancestry using mixed-linear-models. We further partitioned the estimated pleiotropy according to biological features to gain insight into the nature of pleiotropy between CAD and BMI.

Results:

We found significant (
P
<0.0001) positive genetic correlation between CAD and BMI (
r

g

=0.60). The estimated pleiotropy explained 68% of phenotypic correlation, and it was not proportionally distributed across the chromosomes; notably, chromosome 10 contributed more; whereas, chromosomes 11 and 14 contributed less to pleiotropy than expected given their chromosomal length. We noted that a large proportion (63%;
P
=0.002) of the pleiotropy is attributed to single-nucleotide polymorphisms with low allele frequency (minor allele frequency <0.05). Of note, pleiotropy was enriched among central nervous system genes and genes of metabolic pathways. Further analyses revealed that these effects are more pronounced in the proopiomelanocortin pathway and genes involved in carbohydrate metabolism. After genome-wide association study meta-analysis, only single-nucleotide polymorphisms downstream of the
MC4R
gene were found concordantly associated with (
P
<5×10
–8
) BMI and CAD with lead single-nucleotide polymorphism being rs663129 (combined
P
=2.7×10
–65
). Finally, partitioning the pleiotropy according to functional elements pointed to the importance of superenhancers and notably brain-specific superenhancers.

Conclusions:
Genome-wide pleiotropy substantially contributes to co-occurrence of CAD and obesity, and it is highly enriched among low frequency variants and central nervous system–specific functional elements.
Automated Satellite-Based Landslide Identification Product for Nepal
Authors: Fayne Jessica V. , Ahamed Aakash , Roberts-Pierel Justin , Rumsey Amanda C. , Kirschbaum Dalia 
Published: October 2018

Abstract
Landslide event inventories are a vital resource for landslide susceptibility and forecasting applications. However, landslide inventories can vary in accuracy, availability, and timeliness as a result of varying detection methods, reporting, and data availability. This study presents an approach to use publicly available satellite data and open-source software to automate a landslide detection process called the Sudden Landslide Identification Product (SLIP). SLIP utilizes optical data from the Landsat-8 Operational Land Imager sensor, elevation data from the Shuttle Radar Topography Mission, and precipitation data from the Global Precipitation Measurement mission to create a reproducible and spatially customizable landslide identification product. The SLIP software applies change-detection algorithms to identify areas of new bare-earth exposures that may be landslide events. The study also presents a precipitation monitoring tool that runs alongside SLIP called the Detecting Real-Time Increased Precipitation (DRIP) model that helps to identify the timing of potential landslide events detected by SLIP. Using SLIP and DRIP together, landslide detection is improved by reducing problems related to accuracy, availability, and timeliness that are prevalent in the state of the art for landslide detection. A case study and validation exercise in Nepal were performed for images acquired between 2014 and 2015. Preliminary validation results suggest 56% model accuracy, with errors of commission often resulting from newly cleared agricultural areas. These results suggest that SLIP is an important first attempt in an automated framework that can be used for medium-resolution regional landslide detection, although it requires refinement before being fully realized as an operational tool.
Using Neural Networks to Correct Historical Climate Observations
Authors: Leahy Thomas P. , Llopis Francesc Pons , Palmer Matthew D. , Robinson Niall H. 
Published: October 2018

AbstractBiases in expendable bathythermograph (XBT) instruments have emerged as a leading uncertainty in reconstructions of historical ocean heat content change and therefore climate change. Corrections for these biases depend on the type of XBT used; however, this is unspecified for 52% of the historical XBT profiles in the World Ocean Database. Here, we use profiles of known XBT type to train a neural network that can classify probe type based on three covariates: profile date, maximum recorded depth, and country of origin. Whereas previous studies have shown an average classification skill of 77%, falling below 50% for some periods, our new algorithm maintains an average skill of 90%, with a minimum of 70%. Our study illustrates the potential for successfully applying machine learning approaches in a wide variety of instrument classification problems in order to promote more homogeneous climate data records.
Geographic and Racial Disparities in Infant Hearing Loss
Authors: Lantos Paul M. , Maradiaga‐Panayotti Gabriela , Barber Xavier , Raynor Eileen , Tucci Debara , Hoffman Kate , Permar Sallie R. , Jackson Pearce , Hughes Brenna L. , Kind Amy , Swamy Geeta K. 
Published: October 2018

ObjectiveApproximately 1 to 2 of every 1000 American newborns has hearing loss identified by newborn screening. This study was designed to determine if infant hearing loss is more common in socioeconomically disadvantaged communities.Study DesignIn this retrospective study, we analyzed electronic medical record data using geostatistical models.SettingInfants were residents of Durham County, North Carolina, born in 2 hospitals of the Duke University Health System. This county includes the city of Durham and surrounding suburban and rural communities.Subjects and MethodsSubjects were hearing‐screened newborns, born between 2005 and 2016, whose residential address was in Durham County, North Carolina. This was a retrospective study using medical record data. We used Bayesian regression models with smoothing of coordinate date to identify both spatial and nonspatial predictors of infant hearing loss.ResultsWe identified 19,348 infants from Durham County, of whom 675 had failed initial hearing screening and 191 had hearing loss confirmed on follow‐up. Hearing loss was significantly associated with minority race (odds ratio [OR], 2.45; 95% confidence interval, 1.97‐3.06), as well as lower gestational age and maternal sexually transmitted infections. We identified significant geographic heterogeneity, with a higher probability of hearing loss in poorer urban neighborhoods (local OR range, 0.59‐1.39). Neighborhood disadvantage was a significant predictor of hearing loss, as was high local seroprevalence of cytomegalovirus (CMV) among pregnant women.ConclusionsUrban, low‐income neighborhoods have a high prevalence of infant hearing loss compared with more affluent surrounding communities, particularly among minorities. This distribution may be attributable to congenital CMV infection.
Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus
Authors: Kuo Phoebe , Torabi Sina J. , Kraus Dennis , Judson Benjamin L. 
Published: October 2018

ObjectiveIn advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus.Study DesignSecondary database analysis.SettingNational Cancer Database (NCDB).Subjects and MethodsIn total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan‐Meier analyses were compared by log‐rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison.ResultsTwenty‐three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log‐rank test comparing induction to adjuvant chemotherapy was not significant (P =. 076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076‐4.937; P =. 032).ConclusionInduction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.
The Effect of Sphenopalatine Block on the Postoperative Pain of Endoscopic Sinus Surgery: A Meta‐analysis
Authors: Kim Do Hyun , Kang Haram , Hwang Se Hwan 
Published: October 2018

ObjectivesThe use of sphenopalatine ganglion block (SPGB) with a local anesthetic to decrease postoperative pain after endoscopic sinus surgery (ESS) is controversial. We investigated the role of a perioperative SPB to minimize postoperative pain related to ESS in patients with chronic sinusitis through a systematic review of the relevant literature.Data SourcesPubMed, SCOPUS, Google Scholar, Embase, and the Cochrane Register of Controlled Trials.Review MethodsWe screened the relevant literature published before June 2018. Eight articles that compared perioperative SPGB (treatment group) with a placebo or no treatment (control group) were included for this analysis of the outcomes, which included perioperative morbidities in ESS. For quantitative variables, the standardized mean difference was applied to standardize and summate the results of the studies, and the odds ratio was used in outcome of incidence analysis.ResultsIntraoperative bleeding (P <. 0001), postoperative pain (P =. 0001), nausea and vomiting (P =. 0117), and recovery from sedation (P <. 0001) in the treatment group were significantly reduced compared with the control group. No significant adverse effects were reported in the enrolled studies. In subgroup analyses according to the SPGB approach (transoral or transnasal), the transnasal approach showed higher positive effects on intraoperative bleeding and postoperative pain compared to the transoral approach.ConclusionIn our study, SPGB combined with a local anesthetic for ESS effectively reduced intra‐and postoperative morbidities. This procedure showed no significant adverse effects. Given the ease and effectiveness of this procedure, the transnasal approach should be highly recommended as a routine procedure compared to the transoral approach.
Awareness and understanding of dementia in South Asians: A synthesis of qualitative evidence
Authors: Hossain Muhammad , Crossland John , Stores Rebecca , Dewey Ann , Hakak Yohai 
Published: October 2018

Background Despite a growing elderly South Asian population, little is known about the experience of diagnosis and care for those living with dementia. There have been a number of individual qualitative studies exploring the experiences of South Asian people living with dementia and their carers across different contexts. There has also been a growing interest in synthesizing qualitative research to systematically integrate qualitative evidence from multiple studies to tell us more about a topic at a more abstract level than single studies alone. The aim of this qualitative synthesis was to clearly identify the gaps in the literature and produce new insights regarding the knowledge and understanding of the attitudes, perceptions, and beliefs of the South Asian community about dementia. Methods Following a systematic search of the literature, included qualitative studies were assessed by two independent reviewers for methodological quality. Data were extracted and pooled using the Joanna Briggs Institute Qualitative Assessment and Review Instrument (QARI). Findings were synthesized using the Joanna Briggs Institute approach to qualitative synthesis by meta-aggregation. Results Seventeen papers were critically appraised, with 13 meeting the inclusion criteria. Participants were mostly of South Asians of Indian background; followed by Pakistani with a few Sri Lankans. Missing South Asian countries from the current evidence base included those from Bangladesh, Bhutan, Maldives, and Nepal. Three meta-synthesis themes emerged from the analysis: (1) a poor awareness and understanding of dementia, (2) the experience of caregiving, and (3) the attitudes toward dementia care provision. Conclusions A consistent message from this qualitative synthesis was the limited knowledge and understanding of dementia amongst the South Asians. Whilst symptoms of dementia such as ‘memory loss’ were believed to be a part of a normal ageing process, some South Asian carers viewed dementia as demons or God’s punishments. Most studies reported that many South Asians were explicit in associating stigmas with dementia.