bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep Disordered Breathing Is Highly Prevalent in Patients with Lung Cancer: Results of the Sleep Apnea in Lung Cancer Study
Authors: Cabezas Elena , Pérez-Warnisher M. Teresa , Troncoso Maria Fernanda , Gómez Teresa , Melchor Rosario , Pinillos Erwin Javier , El Hachem Abdul , Gotera Carolina , Rodríguez Paula , Mahillo Fernández Ignacio , Martínez-García Miguel Ángel ,   González-Mangado, Peces-Barba German , Seijo Luis M. 
Published: September 2018

<b><i>Background:</i></b> Obstructive sleep apnea (OSA) has been linked to tumorigenesis and tumor progression. <b><i>Objectives:</i></b> The Sleep Apnea in Lung Cancer (SAIL) study (NCT02764866) was designed to determine the prevalence of OSA in patients with lung cancer. <b><i>Methods:</i></b> Cross-sectional study including consecutive patients with newly diagnosed lung cancer. All patients were offered home sleep apnea testing (HSAT) and administered a sleep-specific questionnaire prior to initiating oncologic treatment. Sleep study-related variables, symptoms, and epidemiologic data as well as cancer related variables were recorded. <b><i>Results:</i></b> Eighty-three patients were enrolled in the SAIL study. Sixty-six completed HSAT. The mean age was 68 ± 11 years and 58% were male with a mean body mass index of 28.1 ± 5.4. Forty-seven percent were current smokers, 42% former smokers, and 11% never smokers with a median tobacco consumption of 51 pack-years. Fifty percent had COPD with a mean FEV1 of 83 ± 22.6% of predicted and a mean DLCO of 85.5 ± 20.1%. Adenocarcinoma was the most common histologic type (46.7%), followed by squamous cell (16.7%) and small cell (16.7%). Most patients were diagnosed at an advanced stage (65% in stages III–IV). The vast majority (80%) had OSA (apnea-hypopnea index [AHI] &#x3e; 5), and 50% had moderate to severe OSA (AHI &#x3e; 15) with a mean Epworth Sleepiness Score of 7.43 ± 3.85. Significant nocturnal hypoxemia was common (Median T90: 10.9% interquartile range 2.4–42.2). <b><i>Conclusions:</i></b> Sleep apnea and nocturnal hypoxemia are highly prevalent in patients with lung cancer.
Aging Modulates the Influence of Arginase on Endothelial Dysfunction in Obesity
Authors: Masi Stefano , Colucci Rocchina , Duranti Emiliano , Nannipieri Monica , Anselmino Marco , Ippolito Chiara , Tirotta Erika , Georgiopoulos Georgios , Garelli Francesca , Nericcio Anna , Segnani Cristina , Bernardini Nunzia , Blandizzi Corrado , Taddei Stefano , Virdis Agostino 
Published: September 2018

Objective—
Arginase can reduce NO availability. In this study, we explored arginase as a determinant of endothelial dysfunction in small arteries from obese patients and its relationship with aging and microvascular remodeling.

Approach and Results—

Small arteries were dissected after subcutaneous fat biopsies and evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation was assessed by acetylcholine, repeated under L-NAME (
N

G
-nitro-L-arginine-methyl ester), N(ω)-hydroxy-nor-
l
-arginine (arginase inhibitor) and gp91ds-tat (NADPH [nicotinamide adenine dinucleotide phosphate oxidase] oxidase inhibitor) in vessels from young (age <30 years) control and obese and old (>30 years) control and obese subjects. Media-lumen ratio and amount of vascular wall fibrosis were used as markers of vascular remodeling. Amount of vascular superoxide anions and NO production were determined with immunofluorescence, whereas arginase expression was quantified using Western blot and quantitative polymerase chain reaction. Obese and older age groups had lower vascular NO, as well as higher media-lumen ratio, wall fibrosis, intravascular superoxide, and blunted inhibitory effect of L-NAME on acetylcholine versus controls and younger age groups. N(ω)-hydroxy-nor-
l
-arginine restored the acetylcholine-induced vasodilation in young and, to a lesser extent, in old obese subjects. This effect was abolished by addition of L-NAME. Gp91ds-tat increased the vasodilatory response to N(ω)-hydroxy-nor-
l
-arginine in old obese. Superoxide anions and arginase I/II levels were higher in the vascular wall of obese versus controls.

Conclusions—
Arginase contributes to microvascular endothelial dysfunction in obesity. Its impact is reduced by aging because of higher levels of vascular oxidative stress. Obesity is accompanied by accelerated microvascular remodeling, the extent of which is related to the amount of arginase in the vascular wall.
Loss of EMILIN-1 Enhances Arteriolar Myogenic Tone Through TGF-β (Transforming Growth Factor-β)–Dependent Transactivation of EGFR (Epidermal Growth Factor Receptor) and Is Relevant for Hypertension in Mice and Humans
Authors: Carnevale Daniela , Facchinello Nicola , Iodice Daniele , Bizzotto Dario , Perrotta Marialuisa , De Stefani Diego , Pallante Fabio , Carnevale Lorenzo , Ricciardi Franco , Cifelli Giuseppe , Da Ros Francesco , Casaburo Manuel , Fardella Stefania , Bonaldo Paolo , Innocenzi Gualtiero , Rizzuto Rosario , Braghetta Paola , Lembo Giuseppe , Bressan Giorgio M. 
Published: September 2018

Objective—

EMILIN-1 (elastin microfibrils interface located protein-1) protein inhibits pro–TGF-β (transforming growth factor-β) proteolysis and limits TGF-β bioavailability in vascular extracellular matrix.
Emilin1
−/−
null mice display increased vascular TGF-β signaling and are hypertensive. Because EMILIN-1 is expressed in vessels from embryonic life to adulthood, we aimed at unravelling whether the hypertensive phenotype of
Emilin1
−/−
null mice results from a developmental defect or lack of homeostatic role in the adult.

Approach and Results—
By using a conditional gene targeting inactivating EMILIN-1 in smooth muscle cells of adult mice, we show that increased blood pressure in mice with selective smooth muscle cell ablation of EMILIN-1 depends on enhanced myogenic tone. Mechanistically, we unveil that higher TGF-β signaling in smooth muscle cells stimulates HB-EGF (heparin-binding epidermal growth factor) expression and subsequent transactivation of EGFR (epidermal growth factor receptor). With increasing intraluminal pressure in resistance arteries, the cross talk established by TGF-β and EGFR signals recruits TRPC6 (TRP [transient receptor potential] classical type 6) and TRPM4 (TRP melastatin type 4) channels, lastly stimulating voltage-dependent calcium channels and potentiating myogenic tone. We found reduced EMILIN-1 and enhanced myogenic tone, dependent on increased TGF-β-EGFR signaling, in resistance arteries from hypertensive patients.

Conclusions—
Taken together, our findings implicate an unexpected role of the TGF-β-EGFR pathway in hypertension with current translational perspectives.
SM22α (Smooth Muscle Protein 22-α) Promoter-Driven IGF1R (Insulin-Like Growth Factor 1 Receptor) Deficiency Promotes Atherosclerosis
Authors: Sukhanov Sergiy , Higashi Yusuke , Shai Shaw-Yung , Snarski Patricia , Danchuk Svitlana , D’Ambra Veronica , Tabony Michael , Woods T. Cooper , Hou Xuwei , Li Zhaohui , Ozoe Atsufumi , Chandrasekar Bysani , Takahashi Shin-Ichiro , Delafontaine Patrice 
Published: September 2018

Objective—

IGF-1 (insulin-like growth factor 1) is a major autocrine/paracrine growth factor, which promotes cell proliferation, migration, and survival. We have shown previously that IGF-1 reduced atherosclerosis and promoted features of stable atherosclerotic plaque in Apoe
−/
−
mice—an animal model of atherosclerosis. The aim of this study was to assess effects of smooth muscle cell (SMC) IGF-1 signaling on the atherosclerotic plaque.

Approach and Results—

We generated Apoe
−/−
mice with IGF1R (IGF-1 receptor) deficiency in SMC and fibroblasts (SM22α [smooth muscle protein 22 α]-CreKI/IGF1R-flox mice). IGF1R was decreased in the aorta and adventitia of SM22α-CreKI/IGF1R-flox mice and also in aortic SMC, embryonic, skin, and lung fibroblasts isolated from SM22α-CreKI/IGF1R-flox mice. IGF1R deficiency downregulated collagen mRNA-binding protein LARP6 (La ribonucleoprotein domain family, member 6) and vascular collagen, and mice exhibited growth retardation. The high-fat diet–fed SM22α-CreKI/IGF1R-flox mice had increased atherosclerotic burden and inflammatory responses. α-SMA (α-smooth muscle actin)–positive plaque cells had reduced proliferation and elevated apoptosis. SMC/fibroblast-targeted decline in IGF-1 signaling decreased atherosclerotic plaque SMC, markedly depleted collagen, reduced plaque fibrous cap, and increased plaque necrotic cores. Aortic SMC isolated from SM22α-CreKI/IGF1R-flox mice had decreased cell proliferation, migration, increased sensitivity to apoptosis, and these effects were associated with disruption of IGF-1–induced Akt signaling.

Conclusions—
IGF-1 signaling in SMC and in fibroblast is a critical determinant of normal vascular wall development and atheroprotection.
Lp(a) [Lipoprotein(a)]-Related Risk of Heart Failure Is Evident in Whites but Not in Other Racial/Ethnic Groups
Authors: Steffen Brian T. , Duprez Daniel , Bertoni Alain G. , Guan Weihua , Tsai Michael Y. 
Published: September 2018

Objective—
Lp(a) [lipoprotein(a)] levels vary by race/ethnicity and were recently found to be associated with risk of heart failure (HF). We aimed to determine whether Lp(a)-related risk of HF is similar across different races and whether Lp(a) may further be related to HF with reduced ejection fraction or HF with preserved ejection fraction (HFpEF).

Approach and Results—

In 6809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years and free of cardiovascular disease, 308 incident HF events occurred during a median 13-year follow-up. Baseline Lp(a) concentrations were determined by immunoassay. Incident HF was adjudicated, distinguishing HF with reduced ejection fraction (ejection fraction, <45%) from HFpEF (ejection fraction, ≥45%). Cox regression assessed relations between Lp(a) and HF risk among 4 races/ethnicities. Lp(a) was examined as a continuous variable (per log unit) and using clinical cutoff values, 30 and 50 mg/dL. Lp(a) was related to greater risk of HF in whites alone: per log unit Lp(a) (hazard ratio [HR], 1.20;
P
=0.02); Lp(a) ≥30 mg/dL (HR, 1.69;
P
=0.01), Lp(a) ≥50 mg/dL (HR, 1.87;
P
=0.006). No significant relations were found in black, Hispanic, or Chinese participants, and significant race interactions were observed. Lp(a) was additionally related to greater risk of HFpEF in white participants: per log unit Lp(a) (HR, 1.48;
P
=0.001), Lp(a) ≥30 mg/dL (HR, 2.15;
P
=0.01), Lp(a) ≥50 mg/dL (HR, 2.60;
P
=0.004). Lp(a)-related risk of HF and HFpEF in whites was independent of aortic valve disease.

Conclusions—
In a multiethnic sample, Lp(a)-related risks of HF and HFpEF were only evident in white participants. If confirmed, these findings have implications in further Lp(a) research and clinical practice.
Associations of Circulating Protein Levels With Lipid Fractions in the General Population
Authors: Figarska Sylwia M. , Gustafsson Stefan , Sundström Johan , Ärnlöv Johan , Mälarstig Anders , Elmståhl Sölve , Fall Tove , Lind Lars , Ingelsson Erik 
Published: September 2018

Objective—
Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.

Approach and Results—

We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a
P
value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima–Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.

Conclusions—
Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.
Childhood Fat and Lean Mass
Authors: Sletner Line , Mahon Pamela , Crozier Sarah R. , Inskip Hazel M. , Godfrey Keith M. , Chiesa Scott , Bhowruth Devina J. , Charakida Marietta , Deanfield John , Cooper Cyrus , Hanson Mark 
Published: September 2018

Objective—

Childhood body mass index (BMI) has been related to vascular structure and function. However, little is known about the differing contributions of fat and lean mass to this relationship. Our objectives were to relate the fat and lean mass (bone excluded) components of BMI (fat mass index and lean mass index; mass [kg]/height [m]
2
) to vascular measures in prepubertal children.

Approach and Results—
In the UK Southampton Women’s Survey mother-offspring cohort, 983 children had dual x-ray absorptiometry and vascular measurements at 8 to 9 years. Using linear regression analyses, we found that most vascular measures were related to BMI, but fat and lean mass contributed differently. Systolic blood pressure was positively associated with both fat mass index (β=0.91 [95% CI, 0.52–1.30] mm Hg) and lean mass index (β=2.16 [95% CI, 1.47–2.85] mm Hg), whereas pulse rate was positively associated with fat mass index (β=0.93 [95% CI, 0.48–1.38] b/min) but negatively associated with lean mass index (β=−1.79 [95% CI, −2.59 to −0.99] b/min). The positive relation between BMI and carotid intima-media thickness was mainly due to a positive association with lean mass index (β=0.013 [95% CI, 0.008–0.019] mm). Carotid-femoral pulse wave velocity, but not carotid-radial pulse wave velocity, was positively associated with fat mass index (β=0.06 [95% CI, 0.03–0.09] m/s). For systolic blood pressure, carotid-femoral pulse wave velocity and reactive hyperemia significant interactions indicated that the association with fat mass depended on the amount of lean mass.

Conclusions—
In prepubertal children, differences in vascular structure and function in relation to BMI probably represent combinations of adverse effects of fat mass, adaptive effects of body size, and relatively protective effects of lean mass.
Inhibition of Vascular Calcification
Authors: Liu Lipei , Zeng Peng , Yang Xiaoxiao , Duan Yajun , Zhang Wenwen , Ma Chuanrui , Zhang Xiaomeng , Yang Shu , Li Xiaoju , Yang Jie , Liang Yu , Han Hao , Zhu Yan , Han Jihong , Chen Yuanli 
Published: September 2018

Objective—

Vascular calcification is a major risk factor for rupture of atherosclerotic plaques. High expression of BMP2 (bone morphogenetic protein 2) in lesions suggests its importance in vascular calcification during atherosclerosis. Teniposide is a Topo II (DNA topoisomerase II) inhibitor and is used for cancer treatment. Previously, we reported that teniposide activated macrophage ABCA1 (ATP-binding cassette transporter A1) expression and free cholesterol efflux indicating Topo II inhibitors may demonstrate antiatherogenic properties. Herein, we investigated the effects of teniposide on the development of atherosclerosis and vascular calcification in apoE
−/−
(apoE deficient) mice.

Approach and Results—

apoE
−/−
mice were fed high-fat diet containing teniposide for 16 weeks, or prefed high-fat diet for 12 weeks followed by high-fat diet containing teniposide for 4 weeks. Atherosclerosis and vascular calcification were determined. Human aortic smooth muscle cells were used to determine the mechanisms for teniposide-inhibited vascular calcification. Teniposide reduced atherosclerotic lesions. It also substantially reduced vascular calcification without affecting bone structure. Mechanistically, teniposide reduced vascular calcification by inactivating BMP2/(pi-Smad1/5/8 [mothers against decapentaplegic homolog 1, 5, and 8])/RUNX2 (runt-related transcription factor 2) axis in a p53-dependent manner. Furthermore, activated miR-203-3p by teniposide functioned as a link between activated p53 expression and inhibited BMP2 expression in inhibition of calcification.

Conclusions—
Our study demonstrates that teniposide reduces vascular calcification by regulating p53-(miR-203-3p)-BMP2 signaling pathway, which contributes to the antiatherogenic properties of Topo II inhibitors.
On the Choice of Momentum Control Variables and Covariance Modeling for Mesoscale Data Assimilation
Authors: Xu Qin 
Published: September 2018

Abstract
For mesoscale variational data assimilation with high-resolution observations, there has been an issue concerning the choice of momentum control variables and related covariance modeling. This paper addresses the theoretical aspect of this issue. First, relationships between background error covariance functions for differently chosen momentum control variables are derived, and different choices of momentum control variables are proven to be theoretically equivalent in the sense that they lead to the same optimally analyzed incremental wind field in the limit of infinitely high spatial resolution provided their error covariance functions satisfy the derived relationships. It is then shown that when the velocity potential χ and streamfunction ψ are used as momentum control variables with their background error autocovariance functions modeled by single-Gaussian functions, the derived velocity autocovariance functions contain significant negative sidelobes. These negative sidelobes can represent background wind error structures associated with baroclinic waves on the synoptic scale but become unrepresentative on the mesoscale. To reduce or remove these negative sidelobes for mesoscale variational data assimilation, Gaussian functions are used with two types of modifications to model the velocity covariance functions in consistency with the assumed homogeneity and isotropy in variational data assimilation. In this case, the random (χ, ψ) background error fields have no classically valid homogeneous and isotropic covariance functions, but generalized (χ, ψ) covariance functions can be derived from the modified velocity covariance functions for choosing (χ, ψ) as momentum control variables. Mathematical properties of generalized covariance functions are explored with physical interpretations. Their important implications are discussed for mesoscale data assimilation.
A Tropical Stochastic Skeleton Model for the MJO, El Niño, and Dynamic Walker Circulation: A Simplified GCM
Authors: Thual Sulian , Majda Andrew J. , Chen Nan 
Published: September 2018

AbstractA simple dynamical stochastic model for the tropical ocean atmosphere is proposed that captures qualitatively major intraseasonal to interannual processes altogether including El Niño–Southern Oscillation (ENSO), the Madden–Julian oscillation (MJO), the associated wind bursts, and the background dynamic Walker circulation. Such a model serves as a prototype “skeleton” for general circulation models (GCMs) that solve similar dynamical interactions across several spatiotemporal scales but usually show common and systematic biases in representing tropical variability as a whole. The most salient features of ENSO, the wind bursts, and the MJO are captured altogether including their overall structure, evolution, and fundamental interactions in addition to their intermittency, diversity, and energy distribution across scales. Importantly, the intraseasonal wind bursts and the MJO are here solved dynamically, which provides their upscale contribution to the interannual flow as well as their modulation in return in a more explicit way. This includes a realistic onset of El Niño events with increased wind bursts and MJO activity starting in the Indian Ocean to the western Pacific and expanding eastward toward the central Pacific, as well as significant interannual modulation of the characteristics of intraseasonal variability. A hierarchy of cruder model versions is also analyzed in order to highlight fundamental concepts related to the treatment of multiple time scales, main convective nonlinearities, and the associated stochastic convective parameterizations. The model developed here also should be useful to diagnose, analyze, and help eliminate the strong tropical biases that exist in current operational models.
Using the variance function to generalize Bland–Altman analysis
Authors: Sadler William A 
Published: September 2018

Background Bland–Altman analysis is a popular and widely used method for assessing the level of agreement between two analytical methods. An important assumption is that paired method differences exhibit approximately constant (homogeneous) scatter when plotted against pair means. This allows estimation of limits of agreement which retain validity across the entire range of mean values. In practice, pair differences often increase systematically with the mean and Bland and Altman used log transformed data to achieve approximately homogeneous scatter. Unfortunately, a logarithmic transformation fails when data are located near the detection limit of an assay (a region that is often of considerable clinical importance). Methods Simulated thyrotropin data are used to illustrate how a variance function, estimated from pair differences, can be used to transform problematic data into a form suitable for traditional Bland–Altman analysis. Simulated and real data sets are used in a supplementary file to illustrate and offer practical solutions to potential problems. Results Following transformation by variance function, Bland–Altman results can be readily interpreted by back-transformation either to the original measurement scale or as percentage values. Limits of agreement are no longer horizontal straight lines, but their shapes simply reflect error characteristics which are (or should be) thoroughly familiar to laboratory analysts. Conclusions The method is completely general and in principle requires only the estimation of a variance function that reliably describes the relationship between the variances of pair differences and their mean values. A computer program is available which performs the necessary calculations.