bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of increasing public participation in advance care planning: a comparison of polls in Alberta between 2007 and 2013
Authors: Simon J E , Ghosh S , Heyland D , Cooke T , Davison S , Holroyd-Leduc J , Wasylenko E , Howlett J , Fassbender K 
Published: January 2016

BackgroundAdvance care planning (ACP) encompasses both verbal and written communications expressing preferences for future health and personal care and helps prepare people for healthcare decision-making in times of medical crisis. Healthcare systems are increasingly promoting ACP as a way to inform medical decision-making, but it is not clear how public engagement in ACP activities is changing over time.MethodsRaw data from 3 independently conducted public polls on ACP engagement, in the same Canadian province, were analysed to assess whether participation in ACP activities changed over 6 years.ResultsStatistically significant increases were observed between 2007 and 2013 in: recognising the definition of ACP (54.8% to 80.3%, OR 3.37 (95% CI 2.68 to 4.24)), discussions about healthcare preferences with family (48.4% to 59.8%, OR 1.41 (95% CI 1.17 to 1.69)) and with healthcare providers (9.1% to 17.4%, OR 1.98 (95% CI 1.51 to 2.59)), written ACP plans (21% to 34.6%, OR 1.77 (95% CI 1.45 to 2.17)) and legal documentation (23.4% to 42.7%, OR 2.13 (95% CI 1.75 to 2.59)). These remained significant after adjusting for age, education and self-rated health status.ConclusionsACP engagement increased over time, although the overall frequency remains low in certain elements such as discussing ACP with healthcare providers. We discuss factors that may be responsible for the increase and provide suggestions for healthcare systems or other public bodies seeking to stimulate engagement in ACP.
Fibroblast-Mediated Collagen Remodeling Within the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by BrafV600E and Pten Loss
Authors: Jolly Lee Ann , Novitskiy Sergey , Owens Phillip , Massoll Nicole , Cheng Nikki , Fang Wei , Moses Harold L. , Franco Aime T. 
Published: January 2016

Abstract
Contributions of the tumor microenvironment (TME) to progression in thyroid cancer are largely unexplored and may illuminate a basis for understanding rarer aggressive cases of this disease. In this study, we investigated the relationship between the TME and thyroid cancer progression in a mouse model where thyroid-specific expression of oncogenic BRAF and loss of Pten (BrafV600E/Pten−/−/TPO-Cre) leads to papillary thyroid cancers (PTC) that rapidly progress to poorly differentiated thyroid cancer (PDTC). We found that fibroblasts were recruited to the TME of BrafV600E/Pten−/−/TPO-Cre thyroid tumors. Conditioned media from cell lines established from these tumors, but not tumors driven by mutant H-ras, induced fibroblast migration and proliferation in vitro. Notably, the extracellular matrix of BrafV600E/Pten−/−/TPO-Cre tumors was enriched with stromal-derived fibrillar collagen, compared with wild-type or Hras-driven tumors. Further, type I collagen enhanced the motility of BrafV600E/Pten−/−/TPO-Cre tumor cells in vitro. In clinical specimens, we found COL1A1 and LOX to be upregulated in PTC and expressed at highest levels in PDTC and anaplastic thyroid cancer. Additionally, increased expression levels of COL1A1 and LOX were associated with decreased survival in thyroid cancer patients. Overall, our results identified fibroblast recruitment and remodeling of the extracellular matrix as pivotal features of the TME in promoting thyroid cancer progression, illuminating candidate therapeutic targets and biomarkers in advanced forms of this malignancy. Cancer Res; 76(7); 1804–13. ©2016 AACR.
What Predicts an Advanced-Stage Diagnosis of Breast Cancer? Sorting Out the Influence of Method of Detection, Access to Care, and Biologic Factors
Authors: Lipscomb Joseph , Fleming Steven T. , Trentham-Dietz Amy , Kimmick Gretchen , Wu Xiao-Cheng , Morris Cyllene R. , Zhang Kun , Smith Robert A. , Anderson Roger T. , Sabatino Susan A. 
Published: January 2016

Abstract
Background: Multiple studies have yielded important findings regarding the determinants of an advanced-stage diagnosis of breast cancer. We seek to advance this line of inquiry through a broadened conceptual framework and accompanying statistical modeling strategy that recognize the dual importance of access-to-care and biologic factors on stage.
Methods: The Centers for Disease Control and Prevention–sponsored Breast and Prostate Cancer Data Quality and Patterns of Care Study yielded a seven-state, cancer registry–derived population-based sample of 9,142 women diagnosed with a first primary in situ or invasive breast cancer in 2004. The likelihood of advanced-stage cancer (American Joint Committee on Cancer IIIB, IIIC, or IV) was investigated through multivariable regression modeling, with base-case analyses using the method of instrumental variables (IV) to detect and correct for possible selection bias. The robustness of base-case findings was examined through extensive sensitivity analyses.
Results: Advanced-stage disease was negatively associated with detection by mammography (P &lt; 0.001) and with age &lt; 50 (P &lt; 0.001), and positively related to black race (P = 0.07), not being privately insured [Medicaid (P = 0.01), Medicare (P = 0.04), uninsured (P = 0.07)], being single (P = 0.06), body mass index &gt; 40 (P = 0.001), a HER2 type tumor (P &lt; 0.001), and tumor grade not well differentiated (P &lt; 0.001). This IV model detected and adjusted for significant selection effects associated with method of detection (P = 0.02). Sensitivity analyses generally supported these base-case results.
Conclusions: Through our comprehensive modeling strategy and sensitivity analyses, we provide new estimates of the magnitude and robustness of the determinants of advanced-stage breast cancer.
Impact: Statistical approaches frequently used to address observational data biases in treatment-outcome studies can be applied similarly in analyses of the determinants of stage at diagnosis. Cancer Epidemiol Biomarkers Prev; 25(4); 613–23. ©2016 AACR.
The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma
Authors: Ruella Marco , Kenderian Saad S. , Shestova Olga , Fraietta Joseph A. , Qayyum Sohail , Zhang Qian , Maus Marcela V. , Liu Xiaobin , Nunez-Cruz Selene , Klichinsky Michael , Kawalekar Omkar U. , Milone Michael , Lacey Simon F. , Mato Anthony , Schuster Stephen J. , Kalos Michael , June Carl H. , Gill Saar , Wasik Mariusz A. 
Published: January 2016

Abstract
Purpose: Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner.
Experimental Design: MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models.
Results: MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P &lt; 0.005) but most mice receiving CTL019 monotherapy eventually relapsed. Therefore, we added ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P &lt; 0.05).
Conclusions: Combining CTL019 with ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684–96. ©2016 AACR.
Bazedoxifene, a new orphan drug for the treatment of bleeding in hereditary haemorrhagic telangiectasia
Authors: Zarrabeitia Roberto , Ojeda-Fernandez Luisa , Recio Lucia , Bernabéu Carmelo , Parra José , Albiñana Virginia , Botella Luisa 
Published: January 2016

SummaryHereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a dominant genetic vascular disorder. In HHT, blood vessels are weak and prone to bleeding, leading to epistaxis and anaemia, severely affecting patients’ quality of life. Development of vascular malformations in HHT patients is originated mainly by mutations in ACVRL1/ALK1 (activin receptor-like kinase type I) or Endoglin (ENG) genes. These genes encode proteins of the TGF-β signalling pathway in endothelial cells, controlling angiogenesis. Haploinsufficiency of these proteins is the basis of HHT pathogenicity. It was our objective to study the efficiency of Bazedoxifene, a selective estrogen receptor modulator (SERM) in HHT, looking for a decrease in epistaxis, and understanding the underlying molecular mechanism. Plasma samples of five HHT patients were collected before, and after 1 and 3 months of Bazedoxifene treatment. ENG and ALK1 expression in activated mononuclear cells derived from blood, as well as VEGF plasma levels, were measured. Quantification of Endoglin and ALK1 mRNA was done in endothelial cells derived from HHT and healthy donors, after in vitro treatment with Bazedoxifene. Angiogenesis was also measured by tubulogenesis and wound healing assays. Upon Bazedoxifene treatment, haemoglobin levels of HHT patients increased and the quantity and frequency of epistaxis decreased. Bazedoxifene increased Endoglin and ALK1 mRNA levels, in cells derived from blood samples and in cultured endothelial cells, promoting tube formation. In conclusion, Bazedoxifene seems to decrease bleeding in HHT by partial compensation of haploinsufficiency. The results shown here are the basis of a new orphan drug designation for HHT by the European Medicine Agency (EMA).
Low paediatric thrombin generation is caused by an attenuation of prothrombin conversion
Authors: Wagenvoord Rob , de Laat H. , Monagle Paul , Hemker H. , Ignjatovic Vera , Kremers Romy 
Published: January 2016

SummaryThrombin generation (TG) is decreased in children. TG is determined by two underlying processes: the conversion of prothrombin to thrombin and the inactivation of thrombin. Therefore, lower TG capacity in children can either be caused by a reduction of prothrombin conversion, an increase of thrombin inactivation, or both. In 36 children and 8 adults, TG and the factors that determine thrombin inactivation (antithrombin, α2 Macroglobulin (α2M) and fibrinogen) were measured. Prothrombin conversion, thrombin inhibitor complex formation, and the overall thrombin decay capacity were determined. In silico modelling was performed to determine the contribution prothrombin conversion and thrombin inactivation to deviant paediatric TG. Both the amount of prothrombin converted and the maximal prothrombin conversion rate are significantly reduced in children as compared to adults. This is partly due to the prothrombin levels being lower and partly to a lower prothrombin conversion rate. The overall thrombin decay capacity is not significantly different in children, but α2Macroglobulin plays a more important role than it does in adults. In silico experiments demonstrate that reduced prothrombin conversion and to a lesser extent elevated α2M levels provide an explanation for low TG in children. Young age has a dual effect on prothrombin conversion. Lower plasma prothrombin levels result in decreased prothrombin conversion but the rate of prothrombin conversion is also decreased, i. e. the development of prothrombinase is lower than in adults.
Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure
Authors: Bedi Kenneth C. , Snyder Nathaniel W. , Brandimarto Jeffrey , Aziz Moez , Mesaros Clementina , Worth Andrew J. , Wang Linda L. , Javaheri Ali , Blair Ian A. , Margulies Kenneth B. , Rame J. Eduardo 
Published: January 2016

Background—
The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se.

Methods and Results—
We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl-CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of β-hydroxybutyrate and acetoacetate.

Conclusions—
These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart.
Forced Expiratory Volume in the First Second and Aldosterone as Mediators of Smoking Effect on Stroke in African Americans: The Jackson Heart Study
Authors: Wang Wei , Shen Gui , Shahar Eyal , Bidulescu Aurelian , Kimberly W. Taylor , Sheth Kevin N. , Campbell Brenda W. , Horbal Steven , Correa Adolfo , Griswold Michael E. 
Published: January 2016

Background

Cigarette smoking is a risk factor for stroke, but the mechanisms by which smoking contributes to stroke are not well understood. This study aimed to evaluate the roles of lung function (represented by forced expiratory volume in the first second (FEV
1
)) and aldosterone as potential mediators of the association of smoking with stroke.

Methods and Results

The data were derived from 5010 Jackson Heart Study participants who had mean follow‐up of 97.9 months. Using the Cox proportional hazards model, we estimated the hazard ratios of smoking for total stroke with and without adjustment for FEV
1
and/or aldosterone at baseline after controlling for the confounders. The hazard ratio for current smoking (versus never smoking) was 2.70 (95% CI 1.71 to 4.25) for total stroke after adjustment for the confounders. Additional adjustment for FEV
1
and aldosterone reduced the hazard ratio to 2.32 (95% CI 1.42 to 3.79), suggesting that 22.4% of the excess risk of current smoking for total stroke is mediated by these factors. FEV
1
and aldosterone account for 13.1% and 12.1%, respectively, of the excess risk. The
hazard ratio for
FEV
1
increased (0.61 versus 0.65) after including systemic inflammatory marker C‐reactive protein, and the hazard ratios for aldosterone were comparable for the models that included all confounders and smoking status with or without different blood pressure measurements.

Conclusions
Our findings suggest that the difference in stroke risk between current and never smokers may develop partially through pathways involving lung function and aldosterone and that the mediation effect through aldosterone is independent of blood pressure.
Mesoscale Climatology and Variation of Surface Winds over the Chukchi–Beaufort Coastal Areas
Authors: Zhang Jing , Liu Fuhong , Tao Wei , Krieger Jeremy , Shulski Martha , Zhang Xiangdong 
Published: January 2016

Abstract
The detailed mesoscale climatology of surface winds in the Chukchi–Beaufort Seas and adjacent Arctic Slope region is analyzed using the recently developed Chukchi–Beaufort High-Resolution Atmospheric Reanalysis (CBHAR). Within the study area, surface winds are mainly driven by the prevailing synoptic weather patterns of the Beaufort high and Aleutian low and are further modulated by local geographic features through thermodynamic and dynamic processes. Sea breezes, up- or downslope winds, and the mountain barrier jets are all clearly captured by CBHAR. Sea breezes emerge in June–September and last most of the day, with a maximum spatial extent 100 km inland and 50 km offshore and maximum speed around 1–3 m s−1 in the late afternoon [~1500 Alaska standard time (AKST)]. Thermodynamic impacts of mountains on the surface winds vary from time to time. Drainage flows begin to build at the mountaintop in September and reach the strongest during November–February, occupying the entire slope. Upslope winds demonstrate a clear diurnal cycle during summer, starting to build around 0900 local time, reaching the maximum strength around 1500 local time and continuing until 2100 local time. The mountain barrier jets (MBJs) are found to be most active around the Chukotka Mountains during cold seasons. Both sea breezes and MBJs are also subject to variations and changes in response to adjusted large-scale atmosphere circulation. Storm activities can inhibit the development of sea breezes. Different responses from the Beaufort high and Aleutian low to anomalies in large-scale circulations play a vital role in the variations of MBJ activities over the Chukotka Mountains.
Dependence of Model Energy Spectra on Vertical Resolution
Authors: Waite Michael L. 
Published: January 2016

AbstractMany high-resolution atmospheric models can reproduce the qualitative shape of the atmospheric kinetic energy spectrum, which has a power-law slope of −3 at large horizontal scales that shallows to approximately −5/3 in the mesoscale. This paper investigates the possible dependence of model energy spectra on the vertical grid resolution. Idealized simulations forced by relaxation to a baroclinically unstable jet are performed for a wide range of vertical grid spacings Δz. Energy spectra are converged for Δz 200 m but are very sensitive to resolution with 500 m ≤ Δz ≤ 2 km. The nature of this sensitivity depends on the vertical mixing scheme. With no vertical mixing or with weak, stability-dependent mixing, the mesoscale spectra are artificially amplified by low resolution: they are shallower and extend to larger scales than in the converged simulations. By contrast, vertical hyperviscosity with fixed grid-scale damping rate has the opposite effect: underresolved spectra are spuriously steepened. High-resolution spectra are converged except for the stability-dependent mixing case, which are damped by excessive mixing due to enhanced shear over a wide range of horizontal scales. It is shown that converged spectra require resolution of all vertical scales associated with the resolved horizontal structures: these include quasigeostrophic scales for large-scale motions with small Rossby number and the buoyancy scale for small-scale motions at large Rossby number. It is speculated that some model energy spectra may be contaminated by low vertical resolution, and it is recommended that vertical-resolution sensitivity tests always be performed.
A population study of correlates of social participation in older adults with age-related vision loss
Authors: Cimarolli Verena R , Boerner Kathrin , Reinhardt Joann P , Horowitz Amy , Wahl Hans-Werner , Schilling Oliver , Brennan-Ing Mark 
Published: January 2016

Objective: To examine personal characteristics, disease-related impairment variables, activity limitations, and environmental factors as correlates of social participation in older adults with vision loss guided by the World Health Organization’s International Classification of Functioning, Disability and Health Model. Design: Baseline data of a larger longitudinal study. Setting: Community-based vision rehabilitation agency. Subjects: A total of 364 older adults with significant vision impairment due to age-related macular degeneration. Main Measures: In-person interviews assessing social participation (i.e. frequency of social support contacts, social/leisure challenges faced due to vision loss, and of social support provided to others) and hypothesized correlates (e.g. visual acuity test, Functional Vision Screening Questionnaire, ratings of attachment to house and neighborhood, environmental modifications in home). Results: Regression analyses showed that indicators of physical, social, and mental functioning (e.g. better visual function, fewer difficulties with instrumental activities of daily living, fewer depressive symptoms) were positively related to social participation indicators (greater social contacts, less challenges in social/leisure domains, and providing more support to others). Environmental factors also emerged as independent correlates of social participation indicators when functional variables were controlled. That is, participants reporting higher attachment to their neighborhood and better income adequacy reported having more social contacts; and those implementing more environmental strategies were more likely to report greater challenges in social and leisure domains. Better income adequacy and living with more people were related to providing more social support to others. Conclusion: Environmental variables may play a role in the social participation of older adults with age-related macular degeneration.
Effects of inspiratory muscle training on pulmonary function, respiratory muscle strength and functional capacity in patients with atrial fibrillation: a randomized controlled trial
Authors: Zeren Melih , Demir Rengin , Yigit Zerrin , Gurses Hulya N 
Published: January 2016

Objective: To investigate the effects of inspiratory muscle training on pulmonary function, respiratory muscle strength and functional capacity in patients with atrial fibrillation. Design: Prospective randomized controlled single-blind study. Setting: Cardiology department of a university hospital. Subjects: A total of 38 patients with permanent atrial fibrillation were randomly allocated to either a treatment group ( n = 19; age 66.2 years (8.8)) or a control group ( n = 19; age 67.1 years (6.4)). Methods: The training group received inspiratory muscle training at 30% of maximal inspiratory pressure for 15 minutes twice a day, 7 days a week, for 12 weeks alongside the standard medical treatment. The control group received standard medical treatment only. Spirometry, maximal inspiratory and expiratory pressures and 6-minute walking distance was measured at the beginning and end of the study. Results: There was a significant increase in maximal inspiratory pressure (27.94 cmH2O (8.90)), maximal expiratory pressure (24.53 cmH2O (10.34)), forced vital capacity (10.29% (8.18) predicted), forced expiratory volume in one second (13.88% (13.42) predicted), forced expiratory flow 25%–75% (14.82% (12.44) predicted), peak expiratory flow (19.82% (15.62) predicted) and 6-minute walking distance (55.53 m (14.13)) in the training group ( p < 0.01). No significant changes occurred in the control group ( p > 0.05). Conclusion: Inspiratory muscle training can improve pulmonary function, respiratory muscle strength and functional capacity in patients with atrial fibrillation.