bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrosis of the Neonatal Mouse Heart After Cryoinjury Is Accompanied by Wnt Signaling Activation and Epicardial‐to‐Mesenchymal Transition
Authors: Mizutani Makiko , Wu Joseph C. , Nusse Roeland 
Published: March 2016

Background
The adult mammalian heart responds to cardiac injury by formation of persistent fibrotic scar that eventually leads to heart failure. In contrast, the neonatal mammalian heart reacts to injury by the development of transient fibrotic tissue that is eventually replaced by regenerated cardiomyocytes. How fibrosis occurs in the neonatal mammalian heart remains unknown. To start elucidating the molecular underpinnings of neonatal cardiac fibrosis, we investigated Wnt signaling in the neonatal heart after cryoinjury.

Methods and Results
Using expression of the Wnt target gene Axin2 as an indicator of Wnt/β‐catenin signaling activation, we discovered that epicardial cells in the ventricles are responsive to Wnt in the uninjured neonatal heart. Lineage‐tracing studies of these Wnt‐responsive epicardial cells showed that they undergo epithelial‐to‐mesenchymal transition and infiltrate into the subepicardial space and exhibit fibroblast phenotypes after injury. In addition, we showed that—similar to adult ischemic injury—neonatal cryoinjury results in activation of Wnt signaling in cardiac fibroblasts near injured areas. Furthermore, through in situ hybridization of all 19 Wnt ligands in injured neonatal hearts, we observed upregulation of Wnt ligands (Wnt2b, Wnt5a, and Wnt9a) that had not been implicated in the adult cardiac injury response.

Conclusions
These results demonstrate that cryoinjury in neonatal heart leads to the formation of fibrotic tissue that involves Wnt‐responsive epicardial cells undergoing epithelial‐to‐mesenchymal transition to give rise to fibroblasts and activation of Wnt signaling in resident cardiac fibroblasts.
Long‐Term Outcomes Among Elderly Survivors of Out‐of‐Hospital Cardiac Arrest
Authors: Chan Paul S. , McNally Bryan , Nallamothu Brahmajee K. , Tang Fengming , Hammill Bradley G. , Spertus John A. , Curtis Lesley H. 
Published: March 2016

Background
Most studies on out‐of‐hospital cardiac arrest have focused on immediate survival. However, little is known about long‐term outcomes and resource use among survivors.

Methods and Results

Within the national
CARES
registry, we identified 16 206 adults 65 years or older with an out‐of‐hospital cardiac arrest between 2005 and 2010. Among 1127 patients who were discharged alive, we evaluated whether 1‐year mortality, cumulative readmission incidence, and follow‐up inpatient costs differed according to patients’ race, sex, initial cardiac arrest rhythm, bystander delivery of cardiopulmonary resuscitation, discharge neurological status, and functional status (hospital discharge disposition). Overall 1‐year mortality after hospital discharge was 31.8%. Among survivors, there were no long‐term mortality differences by sex, race, or initial cardiac arrest rhythm, but worse functional status and severe neurological disability at discharge were associated with higher mortality. Moreover, compared with first responders, cardiopulmonary resuscitation delivered by bystanders was associated with 23% lower mortality (hazard ratio 0.77 [confidence interval 0.58–1.02]). Besides mortality, 638 (56.6%) patients were readmitted within the first year, and the cumulative readmission incidence was 197 per 100 patient‐years. Mean 1‐year inpatient costs were $23 765±41 002. Younger age, black race, severe neurological disability at discharge, and hospital disposition to a skilled nursing or rehabilitation facility were each associated with higher 1‐year inpatient costs (
P
for all <0.05).

Conclusion
Among elderly survivors of out‐of‐hospital cardiac arrest, nearly 1 in 3 patients die within the first year. Long‐term mortality and inpatient costs differed substantially by certain demographic factors, whether cardiopulmonary resuscitation was initiated by a bystander, discharge neurological status, and hospital disposition.
Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study
Authors: Mygind Naja Dam , Michelsen Marie Mide , Pena Adam , Frestad Daria , Dose Nynne , Aziz Ahmed , Faber Rebekka , Høst Nis , Gustafsson Ida , Hansen Peter Riis , Hansen Henrik Steen , Bairey Merz C. Noel , Kastrup Jens , Prescott Eva 
Published: March 2016

Background
The majority of women with angina‐like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing.

Methods and Results

After screening 3568 women, 963 women with angina‐like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age (
SD
) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high‐dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve (
CFVR
) by Doppler examination of the left anterior descending coronary artery.
CFVR
was successfully measured in 919 (95%) women. Median (
IQR
)
CFVR
was 2.33 (1.98–2.76), and 241 (26%) had markedly impaired
CFVR
(<2). In multivariable regression analysis, predictors of impaired
CFVR
were age (
P
<0.01), hypertension (
P
=0.02), current smoking (
P
<0.01), elevated heart rate (
P
<0.01), and low high‐density lipoprotein cholesterol (
P
=0.02), but these variables explained only a little of the
CFVR
variation (
r
2
=0.09).
CFVR
was not associated with chest pain characteristics or results from diagnostic stress testing.

Conclusion

Impaired
CFVR
was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris.
CFVR
was associated with few cardiovascular risk factors, suggesting that
CFVR
is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired
CFVR
.
Intercellular Adhesion Molecule 1 Regulates Left Ventricular Leukocyte Infiltration, Cardiac Remodeling, and Function in Pressure Overload–Induced Heart Failure
Authors: Salvador Ane M. , Nevers Tania , Velázquez Francisco , Aronovitz Mark , Wang Bonnie , Abadía Molina Ana , Jaffe Iris Z. , Karas Richard H. , Blanton Robert M. , Alcaide Pilar 
Published: March 2016

Background

Left ventricular dysfunction and heart failure are strongly associated in humans with increased circulating levels of proinflammatory cytokines, T cells, and soluble intercellular cell adhesion molecule 1 (
ICAM
1). In mice, infiltration of T cells into the left ventricle contributes to pathological cardiac remodeling, but the mechanisms regulating their recruitment to the heart are unclear. We hypothesized that
ICAM
1 regulates cardiac inflammation and pathological cardiac remodeling by mediating left ventricular T‐cell recruitment and thus contributing to cardiac dysfunction and heart failure.

Methods and Results

In a mouse model of pressure overload–induced heart failure, intramyocardial endothelial
ICAM
1 increased within 48 hours in response to thoracic aortic constriction and remained upregulated as heart failure progressed.
ICAM
1‐deficient mice had decreased T‐cell and proinflammatory monocyte infiltration in the left ventricle in response to thoracic aortic constriction, despite having numbers of circulating T cells and activated T cells in the heart‐draining lymph nodes that were similar to those of wild‐type mice.
ICAM
1‐deficient mice did not develop cardiac fibrosis or systolic and diastolic dysfunction in response to thoracic aortic constriction. Exploration of the mechanisms regulating
ICAM
1 expression revealed that endothelial
ICAM
1 upregulation and T‐cell infiltration were not mediated by endothelial mineralocorticoid receptor signaling, as demonstrated in thoracic aortic constriction studies in mice with endothelial mineralocorticoid receptor deficiency, but rather were induced by the cardiac cytokines interleukin 1β and 6.

Conclusions

ICAM
1 regulates pathological cardiac remodeling by mediating proinflammatory leukocyte infiltration in the left ventricle and cardiac fibrosis and dysfunction and thus represents a novel target for treatment of heart failure.
Optimal Force–Time Integral for Pulmonary Vein Isolation According to Anatomical Wall Thickness Under the Ablation Line
Authors: Chikata Akio , Kato Takeshi , Sakagami Satoru , Kato Chieko , Saeki Takahiro , Kawai Keiichi , Takashima Shin‐ichiro , Murai Hisayoshi , Usui Soichiro , Furusho Hiroshi , Kaneko Shuichi , Takamura Masayuki 
Published: March 2016

Background

Low contact force and force–time integral (
FTI
) during catheter ablation are associated with ineffective lesion formation, whereas excessively high contact force and
FTI
may increase the risk of complications. We sought to evaluate the optimal
FTI
for pulmonary vein (
PV
) isolation based on atrial wall thickness under the ablation line.

Methods and Results

Contact force parameters and
FTI
during anatomical ipsilateral
PV
isolation for atrial fibrillation and atrial wall thickness were assessed retrospectively in 59 consecutive patients for their first
PV
isolation procedure. The
PV
antrum was divided into 8 segments, and the wall thickness of each segment under the ablation line was determined using multidetector computed tomography. The
FTI
for each ablation point was divided by the wall thickness of the
PV
antrum segment where each point was located to obtain
FTI
/wall thickness. In total, 5335 radiofrequency applications were delivered, and 85 gaps in
PV
isolation ablation lines and 15 dormant conductions induced by adenosine were detected. The gaps or dormant conductions were significantly associated with low contact force, radiofrequency duration,
FTI
, and
FTI
/wall thickness. Among them,
FTI
/wall thickness had the best prediction value for gaps or dormant conductions by receiver operating characteristic curve analysis.
FTI
/wall thickness of <76.4 gram‐seconds per millimeter (gs/mm) predicted gaps or dormant conductions with sensitivity (88.0%) and specificity (83.6%), and
FTI
/wall thickness of <101.1 gs/mm was highly predictive (sensitivity 97.0%; specificity 69.6%).

Conclusions

FTI
/wall thickness is a strong predictor of gap and dormant conduction formation in
PV
isolation. An
FTI
/wall thickness ≈100 gs/mm could be a suitable target for effective ablation.
Associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence: A systematic review and meta-analysis
Authors: Oo Khine Zin , Aung Ye Kyaw , Jenkins Mark A , Win Aung Ko 
Published: March 2016

Objective: The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene ( 5HTT) may increase the risk of major depressive disorder and alcohol dependence. Previous estimates of the association of the S allele of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence have been inconsistent. Methods: For the systematic review, we used PubMed MEDLINE and Discovery of The University of Melbourne to search for all relevant case-control studies investigating the associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence. Summary odds ratios (OR) and their 95% confidence intervals (CI) were estimated. To investigate whether year of publication, study population or diagnostic criteria used were potential sources of heterogeneity, we performed meta-regression analyses. Publication bias was assessed using Funnel plots and Egger’s statistical tests. Results: We included 23 studies of major depressive disorder without alcohol dependence containing 3392 cases and 5093 controls, and 11 studies of alcohol dependence without major depressive disorder containing 2079 cases and 2273 controls. The summary OR for homozygote carriers of the S allele of 5HTTLPR polymorphism compared with heterozygote and non-carriers combined (SS vs SL+LL genotype) was 1.33 (95% CI = [1.19, 1.48]) for major depressive disorder and 1.18 (95% CI = [1.01, 1.38]) for alcohol dependence. The summary OR per S allele of 5HTTLPR polymorphism was 1.16 (95% CI = [1.08, 1.23]) for major depressive disorder and 1.12 (95% CI = [1.01, 1.23]) for alcohol dependence. Meta-regression models showed that the associations did not substantially change after adjusting for year of publication, study population and diagnostic criteria used. There was no evidence for publication bias of the studies included in our meta-analysis. Conclusions: Our meta-analysis confirms that individuals with the homozygous S allele of 5HTTLPR polymorphism are at increased risks of major depressive disorder as well as alcohol dependence. Further studies are required to investigate the association between 5HTTLPR polymorphism and the comorbidity of major depressive disorder and alcohol dependence as well as gene × environmental interactions.
Impact of Nodal Level Distribution on Survival in Oral Cavity Squamous Cell Carcinoma
Authors: Marchiano Emily , Patel Tapan D. , Eloy Jean Anderson , Baredes Soly , Park Richard Chan Woo 
Published: March 2016

ObjectiveRegional lymph node metastasis is an important prognostic factor in squamous cell carcinoma of the head and neck, decreasing survival by up to 50%. Oral cavity squamous cell carcinoma (OC‐SCCa) most commonly spreads to levels I, II, and III.Study DesignRetrospective analysis of a population‐based tumor registry.SettingAcademic medical center.Subjects and MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of OC‐SCCa from 2004 to 2011 (22,973 cases). Resulting data including patient demographics, clinicopathological features, topographical distribution of nodal metastasis, and survival based on lymph node level involvement were analyzed.ResultsIn total, 8281 patients were identified with OC‐SCCa who underwent neck dissection. Level I, closely followed by levels II and III, represented the most commonly involved nodal basins. The 5‐year disease‐specific survival (DSS) for patients with only level I, II, or III was 42.0% compared with 30.6% for the level IV group (P <. 0001) and 26.4% for the level V group (P <. 0001). Surgery with adjuvant radiotherapy improved 5‐year DSS for patients with level I to III, level IV, and level V neck disease compared with surgery alone (50.7% vs 48.6%, P =. 0109; 39.9% vs 23.2%, P <. 0001; and 33.3% vs 9.1%, P =. 0005, for levels I‐III, IV, and V, respectively).ConclusionOral cavity squamous cell carcinoma most commonly involves nodal levels I, II, and III. Involvement of nodal level IV or V portends a worse prognosis than patients with only level I to III disease, and multimodality therapy should be considered for these patients.
Clinical Examination of Tissue Eosinophilia in Patients with Chronic Rhinosinusitis and Nasal Polyposis
Authors: Gitomer Sarah A. , Fountain Cynthia R. , Kingdom Todd T. , Getz Anne E. , Sillau Stefan H. , Katial Rohit K. , Ramakrishnan Vijay R. 
Published: March 2016

Objective(1) Describe clinical and histopathologic findings in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). (2) Determine if tissue and serum eosinophilia predicts disease severity in CRSwNP.Study DesignCase series with chart review.SettingAcademic hospital specializing in respiratory and allergic disease.SubjectsPatients with CRSwNP treated from 2008 to 2010.MethodsClinical data were collected; sinus computed tomography (CT) scans were scored according to the Lund‐Mackay system; and surgical specimens were evaluated for degree of tissue eosinophilia. Statistical analysis was performed to compare eosinophilia with indicators of disease severity.ResultsSeventy CRSwNP patients were included, with a mean Lund‐Mackay score of 16.7; 62.1% of patients had severe asthma, and 62.9% were aspirin sensitive. Elevated tissue eosinophil level did not correlate with medication usage, olfactory symptoms, or Lund‐Mackay scores, nor did it correlate with presence of asthma or aspirin‐sensitivity (P =. 09). Patients with mild asthma had significantly more tissue eosinophils versus patients with severe asthma, possibly because of the high amount of chronic corticosteroid use in severe asthmatics. There was no correlation between tissue and serum eosinophil counts (P =. 97), but there was a significant positive correlation between CT score and peripheral eosinophil level (P <. 05).ConclusionsHigher serum eosinophil levels may indicate more extensive mucosal disease as measured on CT scan. Neither serum nor tissue eosinophilia predicted disease severity in our retrospective analysis of CRSwNP patients, and serum eosinophil level did not serve as a marker of tissue eosinophilia.
Purchase Preference Factors for Traditional Rural Retailers: A Cross-sectional Conceptual Study
Authors: Sarkar Dev Narayan , Kundu Kaushik , Chaudhuri Himadri Roy 
Published: March 2016

Executive Summary A scrutiny of existing literature suggests that traditional rural retailers are important for the success of rural marketing efforts in developing nations. The present study attempts to decipher the indications on the factors that could possibly influence purchase preferences of rural traditional retailers through the use of statistical methods of content analysis. The purpose of the study is to identify the factors that influence purchase preference, analyse the temporal movement of conceptualizations of these factors, and determine whether academic thought on this topic has a conceptual core. This research work presents a longitudinal analysis of the factors over a period of 40 years: the need for information and training on new products and their selling techniques seem to maintain the same significance throughout the study period; the need for discounts has maintained almost a uniform ranking over the period of study; there is also a relative stability in the need for regular/frequent service; doorstep delivery had the highest ranking in the first period, which is probably owing to the relative weakness of delivery systems during the early phase of rural marketing; the requirement for credit seems to increase from the first period to the second period and then decrease. The factor of margins and commissions seems highly ranked only in the second period. Dimension reduction technique and frequency tabulations are the methods used for content analysis. The core concepts indicate that a traditional rural retailer can possibly be persuaded to purchase high-demand products and brands, through the provision of credit, discounts, quantity discount schemes, margins and commissions, by using local distributors and by appointment of local company staff to provide regular service. The analysis has yielded two discernible conceptual clusters: high-demand products and brands and credit; and doorstep delivery and regular service. The clusters that emerge during the content analysis of traditional rural retailers’ purchase preference factors reflect the exact content from conclusions in at least one research paper that is not used (to prevent cyclic conclusions) during the content-analysis process. The result confirms that researchers have been moving on similar lines in their conceptualizations of the purchase preference factors of traditional rural retailers.
Celecoxib versus diclofenac for the treatment of ankylosing spondylitis: 12-week randomized study in Norwegian patients
Authors: Walker Chris , Essex Margaret N , Li Chunming , Park Peter W 
Published: March 2016

Objective To compare the efficacy and safety of two different doses of celecoxib and diclofenac in the treatment of Norwegian patients with ankylosing spondylitis. Methods In this 12-week, double-blind, non-inferiority trial patients were randomized to 200 mg once daily (qd) celecoxib, 400 mg qd celecoxib, or 50 mg three times daily (tid) diclofenac. The primary objective compared patients’ assessments of Global Pain Intensity, measured on a visual analogue scale. Results A total of 330 patients were randomized (200 mg celecoxib, n = 107; 400 mg celecoxib, n = 108; diclofenac, n = 115). Least squares mean changes in Global Pain Intensity at 12 weeks were −25.8 mm, −30.6 mm and −28.2 mm, respectively. Both celecoxib treatment groups were non-inferior to diclofenac. More patients in the 400 mg celecoxib group met the Assessments in Ankylosing Spondylitis 20 responder criteria at Week 12 (60.2%) than in the celecoxib 200 mg (51.4%) and the diclofenac 50 mg (57.4%) groups. Adverse events were mild-to-moderate in severity, with dyspepsia and diarrhoea the most commonly reported. Conclusions Celecoxib and diclofenac both provided pain reduction, in addition to improvements in disease activity and functional capacity, in patients with ankylosing spondylitis.
Disability and Mental Disorders in the Canadian Armed Forces
Authors: Weeks Murray , Garber Bryan G. , Zamorski Mark A. 
Published: March 2016

Objectives: The initial goal was to validate the use of a self-report measure of disability in the Canadian Armed Forces (CAF). The main goal was to document the extent of disability in personnel with and without mental disorders. Methods: Data were obtained from the 2013 Canadian Forces Mental Health Survey; the sample included 6700 Regular Forces personnel. Disability was measured with the 12-item version of the World Health Organization Disability Assessment Schedule (WHODAS-2); established cut points were used to demarcate severe, moderate, minimal, and no disability. The following recent (past-year) and remote (lifetime but not past-year) disorders were assessed with diagnostic interviews: posttraumatic stress disorder, major depressive episode, generalized anxiety disorder, panic disorder, and alcohol use disorder. Results: The WHODAS-2 showed good internal consistency (α = 0.89) and a 1-factor structure. Most personnel had no disability (59.2%) or minimal disability (30.8%). However, an important minority had moderate or severe disability (8.4% and 1.6%, respectively). Individuals with recent disorders reported greater disability than those without lifetime disorders, although many had minimal or no disability (41.2% and 24.7%, respectively). Disability increased with the number of recent disorders. Relative to those without lifetime disorders, individuals with remote disorders showed slightly greater disability, but most had no disabilty (57.1%) or minimal disability (35.0%). Conclusions: The 12-item WHODAS-2 is a valid measure of disability in the CAF. Mental disorders may be important drivers of disability in this population, although limited residual disability is seen in individuals with remote disorders.