bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic and Physicochemical Analyses Enhance the Classification of Rare Nonsynonymous Single Nucleotide Variants in Type 1 and 2 Long-QT Syndrome
Authors: Giudicessi John R. , Kapplinger Jamie D. , Tester David J. , Alders Marielle , Salisbury Benjamin A. , Wilde Arthur A.M. , Ackerman Michael J. 
Published: September 2012

Background—

Hundreds of nonsynonymous single nucleotide variants (nsSNVs) have been identified in the 2 most common long-QT syndrome-susceptibility genes (
KCNQ1
and
KCNH2
). Unfortunately, an ≈3% background rate of rare
KCNQ1
and
KCNH2
nsSNVs amongst healthy individuals complicates the ability to distinguish rare pathogenic mutations from similarly rare yet presumably innocuous variants.

Methods and Results—

In this study, 4 tools [(1) conservation across species, (2) Grantham values, (3) sorting intolerant from tolerant, and (4) polymorphism phenotyping] were used to predict pathogenic or benign status for nsSNVs identified across 388 clinically definite long-QT syndrome cases and 1344 ostensibly healthy controls. From these data, estimated predictive values were determined for each tool independently, in concert with previously published protein topology–derived estimated predictive values, and synergistically when ≥3 tools were in agreement. Overall, all 4 tools displayed a statistically significant ability to distinguish between case-derived and control-derived nsSNVs in
KCNQ1
, whereas each tool, except Grantham values, displayed a similar ability to differentiate
KCNH2
nsSNVs. Collectively, when at least 3 of the 4 tools agreed on the pathogenic status of C-terminal nsSNVs located outside the KCNH2/Kv11.1 cyclic nucleotide−binding domain, the topology-specific estimated predictive value improved from 56% to 91%.

Conclusions—
Although in silico prediction tools should not be used to predict independently the pathogenicity of a novel, rare nSNV, our results support the potential clinical use of the synergistic utility of these tools to enhance the classification of nsSNVs, particularly for Kv11.1’s difficult to interpret C-terminal region.
Guideline Adherence After ST-Segment Elevation Versus Non-ST Segment Elevation Myocardial Infarction
Authors: Somma Keith A. , Bhatt Deepak L. , Fonarow Gregg C. , Cannon Christopher P. , Cox Margueritte , Laskey Warren , Peacock W. Frank , Hernandez Adrian F. , Peterson Eric D. , Schwamm Lee , Saxon Leslie A. 
Published: September 2012

Background—
Clinical guidelines recommend similar medical therapy for patients with ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation MI (NSTEMI).

Methods and Results—

Using the Get with the Guidelines–Coronary Artery Disease registry (GWTG–CAD), we analyzed data including 72 352 patients (48 966, NSTEMI; 23 386, STEMI) from 237 US sites between May 1, 2006 and March 21, 2010. Performance and quality measures were compared between NSTEMI and STEMI patients. NSTEMI patients were older and had a higher rate of medical comorbidities compared with STEMI patients, including prior coronary artery disease (38.5% versus 24.7%;
P
<0.0001), heart failure (17.5% versus 6.2%;
P
<0.0001), hypertension (70.8% versus 59.1%;
P
<0.0001) and diabetes mellitus (34.9 versus 23.3%;
P
<0.0001). Adjusting for confounding variables, STEMI patients were more likely to receive aspirin within 24 hours 98.5% versus 97.1% (adjusted odds ratio [AOR], 1.63; 95% confidence interval [CI], 1.32–2.02), be discharged on aspirin 98.5% versus 97.3% (AOR, 1.33; 95% CI, 1.19–1.49), β-blockers 98.2% versus 96.9% (AOR, 1.48; 95% CI, 1.35–1.63), or lipid-lowering medication for low-density lipoprotein level >100 mg/dL 96.8% versus 91.0% (AOR, 1.85; 95% CI, 1.61–2.13). STEMI patients were also more likely to receive β-blockers within 24 hours of hospital arrival 93.9% versus 90.8% (AOR, 1.57; 95% CI, 1.37–1.79) and the following discharge medications: angiotensin-converting enzyme inhibitors or angiotensin receptor blocking agents 85.3% versus 77.4% (AOR, 1.62; 95% CI, 1.51–1.75), clopidogrel 85.6% versus 67.0% (AOR, 2.42; 95% CI, 2.23–2.61) or lipid-lowering medications 94.8% versus 88.0% (AOR, 1.71; 95% CI, 1.56–1.86).

Conclusions—
Among hospitals participating in GWTG–CAD, adherence with guideline-based medical therapy was high for patients with both STEMI and NSTEMI. Yet, there is still room for further improvement, particularly in the care of NSTEMI patients.
Left Ventricular Ejection Fraction Assessment Among Patients With Acute Myocardial Infarction and Its Association With Hospital Quality of Care and Evidence-Based Therapy Use
Authors: Miller Amy Leigh , Dib Chadi , Li Li , Chen Anita Y. , Amsterdam Ezra , Funk Marjorie , Saucedo Jorge F. , Wang Tracy Y. 
Published: September 2012

Background—
The left ventricular ejection fraction (LVEF) has prognostic and therapeutic utility after acute myocardial infarction (AMI). Although LVEF assessment is a key performance measure among AMI patients, contemporary rates of in-hospital assessment and its association with therapy use have not been well characterized.

Methods and Results—

We examined rates of in-hospital LVEF assessment among 77 982 non–ST-elevation myocardial infarction patients and 50 863 ST-elevation myocardial infarction patients in Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines between January 2007 and September 2009, after excluding patients who died in-hospital or who were transferred to another acute care facility, discharged to end-of-life care, or had missing LVEF assessment status. LVEF assessment increased significantly over time, with higher rates among ST-elevation myocardial infarction than non–ST-elevation myocardial infarction patients (95.1% versus 91.6%;
P
<0.001). Excluding patients with prior heart failure did not alter these observations. Significant interhospital variability in LVEF assessment rates was observed. Compared with patients with in-hospital LVEF assessment, patients who did not have LVEF assessed were older and more likely to have clinical comorbidities. In multivariable modeling, lower overall hospital quality of AMI care was also associated with lower likelihood of LVEF assessment (odds ratio for failure to assess LVEF, 1.09; 95% confidence interval, 1.05–1.13 per 10% decrease in defect-free care). Patients with in-hospital LVEF assessment were more likely to be discharged on evidence-based secondary prevention medication therapies compared with paients without LVEF assessment.

Conclusions—
The assessment of LVEF among patients with AMI has improved significantly over time, yet significant interhospital variability exists. Patients who did not have in-hospital LVEF assessment were less likely to receive evidence-based medications at discharge. These patients represent targets for future quality improvement efforts.
Impact of Door-to-Activation Time on Door-to-Balloon Time in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarctions
Authors: McCabe James M. , Armstrong Ehrin J. , Hoffmayer Kurt S. , Bhave Prashant D. , MacGregor John S. , Hsue Priscilla , Stein John C. , Kinlay Scott , Ganz Peter 
Published: September 2012

Background—
Little is known about the components of door-to-balloon time among patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We assessed the role of time from hospital arrival to ST-segment elevation myocardial infarction diagnosis (door-to-activation time) on door-to-balloon time in contemporary practice and evaluated factors that influence door-to-activation times.

Methods and Results—

Registry data on 347 consecutive patients diagnosed with a ST-segment elevation myocardial infarction in the emergency department over 30 months at 2 urban primary percutaneous coronary intervention centers were analyzed. The primary study end point was the time from hospital arrival to catheterization laboratory activation by the emergency department physician, and we assessed factors associated with this period. Door-to-balloon time and its other components were secondary study end points. The median door-to-activation time was 19 minutes (interquartile range, 9–54). Variation in door-to-activation times explained 93% of the variation in door-to-balloon times and demonstrated the strongest correlation with door-to-balloon times (
r
=0.97). Achieving a door-to-activation time of ≤20 minutes resulted in an 89% chance of achieving a door-to-balloon time of ≤90 minutes compared with only 28% for patients with a door-to-activation time >20 minutes. Factors significantly associated with door-to-activation time include the following: prehospital ECG use (61% shorter, 95% confidence interval, −50 to −72%;
P
<0.001) and computed tomography scan use in the emergency department (245% longer, 95% confidence interval, +50 to +399%;
P
=0.001).

Conclusions—
The interval from hospital arrival to ST-segment elevation myocardial infarction diagnosis and catheterization laboratory activation (door-to-activation time) is a strong driver of overall door-to-balloon times. Achieving a door-to-activation time ≤20 minutes was key to achieving a door-to-balloon time ≤90 minutes. Delays in door-to-activation time are not associated with delays in other aspects of the primary percutaneous coronary intervention process.
National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011
Authors: Kirley Kate , Qato Dima M. , Kornfield Rachel , Stafford Randall S. , Alexander G. Caleb 
Published: September 2012

Background—
Little is known regarding the adoption of direct thrombin inhibitors in clinical practice. We examine trends in oral anticoagulation for the prevention of thromboembolism in the United States.

Methods and Results—
We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to quantify patterns of oral anticoagulant use among all subjects and stratified by clinical indication. We quantified oral anticoagulant expenditures using the IMS Health National Prescription Audit. Between 2007 and 2011, warfarin treatment visits declined from ≈2.1 million (M) quarterly visits to ≈1.6M visits. Dabigatran use increased from 0.062M quarterly visits (2010Q4) to 0.363M visits (2011Q4), reflecting its increasing share of oral anticoagulant visits from 3.1% to 18.9%. In contrast to warfarin, the majority of dabigatran visits have been for atrial fibrillation, though this proportion decreased from 92% (2010Q4) to 63% (2011Q4), with concomitant increases in dabigatran’s off-label use. Among atrial fibrillation visits, warfarin use decreased from 55.8% visits (2010Q4) to 44.4% (2011Q4), whereas dabigatran use increased from 4.0% to 16.9%. Of atrial fibrillation visits, the fraction not treated with any oral anticoagulants has remained unchanged at ≈40%. Expenditures related to dabigatran increased rapidly from $16M in 2010Q4 to $166M in 2011Q4, exceeding expenditures on warfarin ($144M) in 2011Q4.

Conclusions—
Dabigatran has been rapidly adopted into ambulatory practice in the United States, primarily for treatment of atrial fibrillation, but increasingly for off-label indications. We did not find evidence that it has increased overall atrial fibrillation treatment rates.
Inhaled Nitric Oxide Reduces Brain Damage by Collateral Recruitment in a Neonatal Stroke Model
Authors: Charriaut-Marlangue Christiane , Bonnin Philippe , Gharib Abdallah , Leger Pierre-Louis , Villapol Sonia , Pocard Marc , Gressens Pierre , Renolleau Sylvain , Baud Olivier 
Published: September 2012

Background and Purpose—
We recently demonstrated that endogenous nitric oxide (NO) modulates collateral blood flow in a neonatal stroke model in rats. The inhalation of NO (iNO) has been found to be neuroprotective after ischemic brain damage in adults. Our objective was to examine whether iNO could modify cerebral blood flow during ischemia–reperfusion and reduce lesions in the developing brain.

Methods—
In vivo variations in cortical NO concentrations occurring after 20-ppm iNO exposure were analyzed using the voltammetric method in P7 rat pups. Inhaled NO-mediated blood flow velocities were measured by ultrasound imaging with sequential Doppler recordings in both internal carotid arteries and the basilar trunk under basal conditions and in a neonatal model of ischemia–reperfusion. The hemodynamic effects of iNO (5 to 80 ppm) were correlated with brain injury 48 hours after reperfusion.

Results—
Inhaled NO (20 ppm) significantly increased NO concentrations in the P7 rat cortex and compensated for the blockade of endogenous NO synthesis under normal conditions. Inhaled NO (20 ppm) during ischemia increased blood flow velocities and significantly reduced lesion volumes by 43% and cellular damage. In contrast, both 80 ppm iNO given during ischemia and 5 or 20 ppm iNO given 30 minutes after reperfusion were detrimental.

Conclusions—
Our findings strongly indicate that, with the appropriate timing, 20 ppm iNO can be transported into the P7 rat brain and mediated blood flow redistribution during ischemia leading to reduced infarct volume and cell injury.
Effect of Focal Ischemia on Long Noncoding RNAs
Authors: Dharap Ashutosh , Nakka Venkata Prasuja , Vemuganti Raghu 
Published: September 2012

Background and Purpose—
Long noncoding RNAs (lncRNAs) play a significant role in cellular physiology. We evaluated the effect of focal ischemia on the expression of 8314 lncRNAs in rat cerebral cortex using microarrays.

Methods—
Ischemia was induced by transient middle cerebral artery occlusion. Genomic and transcriptomic correlates of the stroke-responsive lncRNAs and the transcription factor binding sties in their promoters were evaluated with bioinformatics.

Results—
Three hundred fifty-nine lncRNAs were upregulated (>2-fold) and 84 were downregulated (<0.5-fold) at 3 hours to 12 hours of reperfusion after middle cerebral artery occlusion compared with sham. Sixty-two stroke-responsive lncRNAs showed >90% sequence homology with exons of protein-coding genes. Promoters of stroke-responsive lncRNA genes and their homologous protein-coding genes showed highly overlapping transcription factor binding sites. Despite presence of open reading frames, lncRNAs did not form any product when subjected to in vitro translation.

Conclusions—
Stroke significantly alters cerebral lncRNA expression profiles.
Arterial Stiffness and Progressive Neurological Deficit in Patients With Acute Deep Subcortical Infarction
Authors: Saji Naoki , Kimura Kazumi , Kawarai Toshitaka , Shimizu Hirotaka , Kita Yasushi 
Published: September 2012

Background and Purpose—
The mechanism of progressive neurological deficit (PND) in patients with ischemic stroke remains unclear. The aim of this study was to clarify whether arterial stiffness, a marker of vascular endothelial impairment and arteriosclerosis, is associated with PND in patients with acute deep subcortical infarction.

Methods—
We evaluated 156 consecutive first-ever ischemic stroke patients with acute deep subcortical infarction. PND was defined as an increment of ≥2 points in the National Institute of Health Stroke Scale score or an increase of ≥1 point in the limb weakness score within 7 days of stroke onset. Patients were assessed for risk factors, and infarct size was measured on initial diffusion-weighted magnetic resonance imaging. We measured brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness. We divided patients into 2 groups according to the presence or absence of PND to compare their clinical characteristics.

Results—
Fifty-two patients (33%) had PND, and baPWV was significantly higher in patients with than in those without PND. The baPWV cut-off value for PND was 18.24 m/s, with 90% sensitivity and 47% specificity. In multivariable logistic regression analysis, high baPWV (≥18.24 m/s; odds ratio, 8.22; 95% confidence interval, 2.55–31.9), large infarct size (≥15 mm; odds ratio, 2.76; 95% confidence interval, 1.01–7.92), and ≥3 infarct slices on serial axial diffusion-weighted imaging (odds ratio, 3.38; 95% confidence interval, 1.22–10.0) were independently associated with PND.

Conclusions—
Arterial stiffness indicated by baPWV is independently associated with PND in patients with acute deep subcortical infarction.
Applicability of the Normalized Difference Vegetation Index (NDVI) in Index-Based Crop Insurance Design
Authors: Turvey Calum G. , Mclaurin Megan K. 
Published: September 2012

Abstract
Index insurance is becoming increasingly popular because of its ability to provide low-cost, relatively easy to implement agricultural insurance for vegetation types whose productivity has been notoriously difficult to measure and to farmers in less-developed nations where traditional crop insurance schemes are not reasonable to implement. This study examines if the remotely sensed normalized difference vegetation index (NDVI) can be an effective basis for index-based crop insurance over a diverse set of locations. To do this the authors compare Advanced Very High Resolution Radiometer (AVHRR) values to cumulative precipitation, extreme heat, and crop yields for 60 locations across the United States for the years 1982–2003. Quadratic regression equations are used to explore these relationships. The findings suggest that the relationship between NDVI, precipitation, extreme heat, and crop yields is highly variable and dependent on location-specific characteristics. Without site-specific calibration, NDVI should not be widely applied to index-based insurance product design. However, NDVI may still be a useful tool in insurance design under certain circumstances. This may be disappointing to proponents of NDVI as a risk transfer mechanism but the authors believe it important to report negative results as a caveat, and to give researchers and practitioners pause before investing time and money into the proposition.
Physical activity and psychological distress amongst Vietnamese living in the Mekong Delta
Authors: Rees Susan , Silove Derrick , Chey Tien , Steel Zachary , Bauman Adrian , Phan Thuy 
Published: September 2012

Objective: Regular physical activity may be an important contributor to psychological well-being. This link has not been explored in ethnically distinct, low- and middle-income countries (LMIC), especially in countries affected by war. This study aimed to examine the relationship between physical activity and levels of psychological distress in an epidemiological cross-representative sample of Vietnamese living in the Mekong Delta region of Vietnam. Methods: The sample was drawn from an urban (Cần Thơ City) and a rural (Hậ u Giang) region, using a multi-stage probabilistic cluster sampling frame. The measures applied included the Composite International Diagnostic Interview (CIDI 2.0) yielding 12-month prevalence rates of common mental disorders, including anxiety, mood and substance use disorders; the Phan Vietnamese Psychiatric Scale (PVPS), a culturally specific self-report measure; and the Harvard Trauma Questionnaire. The Global Physical Activity Questionnaire (GPAQ version 1) was used to measure activity. Analyses were conducted using SAS software v.9.1.3. The population was assigned to three (high, moderate and low) physical activity levels. Analyses included chi-square tests and univariable and multivariable logistic models. Results: Physical activity was greater in males, the middle-aged group (30–54 years), those who were married, the rural population, less educated individuals and those who were employed. High physical activity was significantly associated with low levels of psychological distress (indexed by a combination of CIDI and PVPS cases identified) when controlling for socio-demographic factors and number of medical conditions). Membership of the lowest of the three physical activity groups was associated with a psychological distress odds ratio of 2.19 (95% CI 1.28–3.75). The results remained consistent when analyses were undertaken separately for males and females. Conclusions: Low levels of physical activity appear to be associated with greater psychological distress in the Mekong Delta of Vietnam. The association remained after adjusting for the influence of socio-demographic characteristics, exposure to past trauma, urban–rural residency and the presence of self-reported physical disorders. These data provide a foundation for exploring the role of physical activity as an adjunct to conventional interventions for common mental disorders in resource-poor LMIC countries.
Breastfeeding is associated with lower risk for multiple sclerosis
Authors: Conradi Silja , Malzahn Uwe , Paul Friedemann , Quill Sabine , Harms Lutz , Then Bergh Florian , Ditzenbach Anna , Georgi Thomas , Heuschmann Peter , Rosche Berit 
Published: September 2012

Background: Multiple sclerosis (MS) is an autoimmune disease with known genetic and environmental susceptibility factors. Breastfeeding has been shown to be protective in other autoimmune diseases. Objective: This case-control study analyzed the association of breastfeeding in infancy on the risk of developing MS. Methods: A case-control study was performed in Berlin of 245 MS patients and 296 population-based controls, who completed a standardized questionnaire on their history and duration of breastfeeding in infancy and demographic characteristics. Univariable and multivariable logistic regression analysis was performed to investigate the association between breastfeeding and MS. The multivariate model was adjusted for age, gender, number of older siblings, number of inhabitants in place of domicile between ages 0 and 6 (categorized in each case), and daycare attendance between ages 0 and 3. Results: In multivariable analysis, breastfeeding showed an independent association with MS (adjusted OR 0.58; p = 0.028). However, with no breastfeeding as reference, the protective effect only emerges after four months of breastfeeding (multivariable analysis for ≤ four months adjusted OR 0.87; p = 0.614 and for > four months OR 0.51; p = 0.016). Conclusion: The results of this case-control study support the hypothesis that breastfeeding is associated with a lower risk of MS. These results are in line with findings of previous studies on other autoimmune diseases, in which breastfeeding was shown to have protective effects.
Teen pregnancy and parenting: a qualitative study into attitudes and behaviours of teenaged long-term Hispanics in New Mexico
Authors: Osuchowski-Sanchez Mary Ann , Tigges Beth , Mendelson Cindy , Lobo Marie , Clark Lauren 
Published: September 2012

Introduction: Teen pregnancy in Hispanic youth is a poorly understood phenomenon with numerous and overlapping sociocultural influences. Hispanics have had the highest teen pregnancy rates in the United States since 1995 and pregnancy rates that have declined much more slowly when compared to every other ethnic group. Literature investigating long-term Hispanic youth of the United States and the factors influencing their decision-making processes and sexual behaviours is limited. Purpose: This study aimed to explore and describe attitudes and behaviours related to teen pregnancy and parenting in Hispanic female teens from long-term families in New Mexico, whose primary language was English and who have experienced pregnancy and motherhood in the 12 months prior to participation. Methods: This was a focused-ethnographic qualitative study conducted in areas of New Mexico with high rates of teen pregnancy and where the population is majority Hispanic with long-term residency. Data were collected in interviews with 10 adolescent mothers and 10 adults, and through participant observation. Data were analysed inductively through immersion and crystallisation. Results: Key findings of the study include chaos/instability characterising the homes of youth, low levels of communication related to reproductive issues, disappointment expressed by families and community in response to teen pregnancy and community goals for the future. Conclusions: The study results will aid in increasing the knowledge base related to long-term Hispanic youth and the many sociocultural factors affecting their sexual decisions and behaviours.