bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a pulmonary nodule fact sheet on patient anxiety and knowledge: a quality improvement initiative
Authors: Koroscil Matthew T , Bowman Mitchell H , Morris Michael J , Skabelund Andrew J , Hersh Andrew M
Published: September 2018

Introduction

The utilisation of chest CT for the evaluation of pulmonary disorders, including low-dose CT for lung cancer screening, is increasing in the USA. As a result, the discovery of both screening-detected and incidental pulmonary nodules has become more frequent. Despite an overall low risk of malignancy, pulmonary nodules are a common cause of emotional distress among adult patients.

Methods

We conducted a multi-institutional quality improvement (QI) initiative involving 101 participants to determine the effect of a pulmonary nodule fact sheet on patient knowledge and anxiety. Males and females aged 35 years or older, who had a history of either screening-detected or incidental solid pulmonary nodule(s) sized 3–8 mm, were included. Prior to an internal medicine or pulmonary medicine clinic visit, participants were given a packet containing a pre-fact sheet survey, a pulmonary nodule fact sheet and a post-fact sheet survey.

Results

Of 101 patients, 61 (60.4%) worried about their pulmonary nodule at least once per month with 18 (17.8%) worrying daily. The majority 67/101 (66.3%) selected chemotherapy, chemotherapy and radiation, or radiation as the best method to cure early-stage lung cancer. Despite ongoing radiographic surveillance, 16/101 (15.8%) stated they would not be interested in an intervention if lung cancer was diagnosed. Following review of the pulmonary nodule fact sheet, 84/101 (83.2%) reported improved anxiety and 96/101 (95.0%) reported an improved understanding of their health situation. Patient understanding significantly improved from 4.2/10.0 to 8.1/10.0 (p<0.01).

Conclusion

The incorporation of a standardised fact sheet for subcentimeter solid pulmonary nodules improves patient understanding and alleviates anxiety. We plan to implement pulmonary nodule fact sheets into the care of our patients with low-risk subcentimeter pulmonary nodules.
Exact form of Maxwell’s equations and Dirac’s magnetic monopole in Fock’s nonlinear relativity
Authors: Takka N. , Bouda A.
Published: September 2018

After having obtained previously an extended first approximation of Maxwell’s equations in Fock’s nonlinear relativity, we propose here the corresponding exact form. In order to achieve this goal, we were inspired mainly by the special relativistic version of Feynman’s proof from which we constructed a formal approach more adapted to the noncommutative algebra. This reasoning lets us establish the exact form of the generalized first group of Maxwell’s equations. To deduce the second one, we have imposed the electric–magnetic duality. As in the k-Minkowski spacetime, the generalized Lorentz force depends on the mass of the particle. After having restored the R-Lorentz algebra symmetry, we have used the perturbative treatment to find the exact form of the generalized Dirac’s magnetic monopole in our context. As consequence, the Universe could locally contain the magnetic charge but in its totality it is still neutral.
Dynamical heredity from f(R)-bulk to braneworld: Curvature dynamical constraint and f(R)-unimodular gravity
Authors: Kuerten André Martorano
Published: September 2018

Recently, Borzou et al. (BSSY) generalized the Shiromizu–Maeda–Sasaki (SMS) formulation to [Formula: see text]-bulks. BSSY brane projected equation carries an additional stress tensor, besides SMS correction for Einstein’s theory on the brane. If we change this perspective, by requiring BSSY tensor in the geometrical side, acting as [Formula: see text]-brane generator, it is possible to relate [Formula: see text]-brane/bulk theories, by using curvature dynamical constraint (CDC), a concept that we developed. Since brane and bulk are [Formula: see text], 5D/4D scalar curvatures also play a dynamical role and, thus, a dynamical version to Gauss equation trace, or CDC, must be offered. We will work yet in a specific case to obtain [Formula: see text]-unimodular gravity, formally identical with that obtained by Nojiri et al. (NOO). Therefore, two applications which consider cosmological scenarios in [Formula: see text]-unimodular gravity with dark radiation correction will be offered.
Spectra (UV-Visible, IR transmission) of Sc3+, Fe3+ and Cu2+ tri-doped LiNbO3 crystals with various [Li]/[Nb] ratios
Authors: Dai Li , Han Xianbo , Shao Yu , Wang Luping , Liu Chunrui , Xu Yuheng
Published: September 2018

The Sc:Fe:Cu:LiNbO3 crystals were grown with Fe[Formula: see text](0.3 wt.%), Cu[Formula: see text](0.1 wt.%) and Sc[Formula: see text](1 mol.%) by the Czochralski method with various [Li]/[Nb] ratios (0.946, 1.05, 1.20 and 1.38). The influence of the [Li]/[Nb] ratios on the defect structure of Sc:Fe:Cu:LiNbO3 crystals was analyzed by the UV-Visible spectra and IR transmission spectra. The spectra show that the absorption edge shift to the red with [Li]/[Nb] ratios enhancing. The Sc:Fe:Cu:LiNbO3 crystals with [Li]/[Nb] ratio of 1.05 is nearly stoichiometric. A new narrow OH[Formula: see text] associated vibrational peak at 3505 cm[Formula: see text] was revealed in Sc:Fe:Cu:LiNbO3 crystals with the ratio of [Li]/[Nb] = 1.38. It is attributed to the (Sc[Formula: see text])-(OH)[Formula: see text]. The results show that the defect structure changes with the [Li]/[Nb] ratios variation.
Development of a short form of the Hong Kong Chinese orebro musculoskeletal pain screening questionnaire
Authors: Tsang Raymond C. C. , Lee Edwin W. C. , Lau Jamie S. Y. , Kwong Susane S. F. , So Eric M. L. , Wong Thomas F. Y. , Law Rainbow K. Y.
Published: September 2018

Background: The Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ) is a valid screening tool to identify those musculoskeletal patients at risk of developing chronicity and disability. A Hong Kong Chinese version of the OMPSQ (COMPSQ-HK) was developed with satisfactory construct validity and predictive validity.

Objective: The aim of this study was to develop a 10-item short form of the COMPSQ-HK (COMPSQ-HK10) and examine its measurement properties.

Methods: The 10 items were identified from the suggestion by the original author of OMPSQ. The data of the 10 items were extracted from the main study to develop the COMPSQ-HK conducted from 2010 to 2013. The internal consistency using Cronbach’s alpha, test–retest reliability examining intraclass correlation coefficient (ICC[Formula: see text]), minimum detectable change and 95% limits of agreement, construct validity by correlating COMPSQ-HK10 with pain, disability score, kinesiophobia score and Medical Outcomes Study Short Form 12, and predictive validity investigating receiver operating characteristic (ROC) curve analyses with sick leave [Formula: see text] days and return-to-work status at one year were calculated.

Results: A total of 305 back patients and 160 neck patients were recruited with about 30% of patients lost to follow-up at one year. Both the internal consistency (Cronbach’s alpha as 0.732 to 0.757) and test–retest reliabilities (ICC[Formula: see text] as 0.868 for both back and neck patients) were satisfactory. The correlations between COMPSQ-HK10 and COMPSQ-HK for back and neck patients were excellent (Pearson [Formula: see text] as 0.919 and 0.896, respectively, [Formula: see text]). The areas under the ROC curves for back and neck patients were similar for COMPSQ-HK10 and COMPSQ-HK, ranging from 0.603 to 0.712. A cut-off score of 54 of COMPSQ-HK10 was recommended in predicting “sick leave of more than 60 days at one year” and “return to work for at least four consecutive weeks at one year”.

Conclusion: The COMPSQ-HK10 has comparable measurement properties with the COMPSQ-HK. It is recommended to use the COMPSQ-HK10 for routine screening to identify patients of back and neck pain at risk of developing chronic pain and disability.
Quantale-Valued Generalizations of Approach Groups
Authors: Ahsanullah T. M. G. , Jäger Gunther
Published: September 2018

The motive behind this paper is to generalize the concept of approach groups. In so doing, we introduce various categories, specifically, the categories of quantale-valued convergence groups, quantale-valued approach groups, quantale-valued gauge groups and quantale-valued approach system groups, and study their functorial relationships including the fact that the category of quantale-valued gauge groups as well as the category of quantale-valued approach system groups is topological over the category of groups. Besides obtaining a variety of categorical connections, we note that if the quantale is linearly ordered satisfying certain conditions, then the categories of quantale-valued approach system groups and quantale-valued gauge groups are isomorphic. Finally, we look into the embeddings of the category of quantale-valued metric groups into the categories of quantale-valued generalizations of approach groups including commutativity of some diagrams.
A Novel Ranking Approach to Solving Fully LR-Intuitionistic Fuzzy Transportation Problems
Authors: Abhishekh  , Nishad A. K.
Published: September 2018

To the extent of our knowledge, there is no method in fuzzy environment to solving the fully LR-intuitionistic fuzzy transportation problems (LR-IFTPs) in which all the parameters are represented by LR-intuitionistic fuzzy numbers (LR-IFNs). In this paper, a novel ranking function is proposed to finding an optimal solution of fully LR-intuitionistic fuzzy transportation problem by using the distance minimizer of two LR-IFNs. It is shown that the proposed ranking method for LR-intuitionistic fuzzy numbers satisfies the general axioms of ranking functions. Further, we have applied ranking approach to solve an LR-intuitionistic fuzzy transportation problem in which all the parameters (supply, cost and demand) are transformed into LR-intuitionistic fuzzy numbers. The proposed method is illustrated with a numerical example to show the solution procedure and to demonstrate the efficiency of the proposed method by comparison with some existing ranking methods available in the literature.
Computing topological polynomials of mesh-derived networks
Authors: Imran Muhammad , Baig Abdul Qudair , Rehman Shafiq Ur , Ali Haidar , Hasni Roslan
Published: September 2018

Topological descriptors are numerical parameters of a molecular graph which characterize its molecular topology and are usually graph invariant. In QSAR/QSPR study, physico-chemical properties and topological indices such as Randić, atom-bond connectivity [Formula: see text] and geometric-arithmetic (GA) index are used to predict the bioactivity of chemical compounds. Graph theory has found a considerable use in this area of research. The counting polynomials are those polynomials having at exponent the extent of a property partition and coefficients the multiplicity/occurrence of the corresponding partition. All of the studied interconnection mesh networks in this paper are motivated by the molecular structure of a Sodium chloride NaCl.

In this paper, Omega, Sadhana and PI polynomials are computed for mesh-derived networks. These polynomials were proposed on the ground of quasi-orthogonal cut edge strips in polycyclic graphs. These polynomials count equidistant and non-equidistant edges in graphs. Moreover, the analytical closed formulas of these polynomials for mesh-derived networks are computed for the first time.
Duadic negacyclic codes over a finite non-chain ring
Authors: Goyal Mokshi , Raka Madhu
Published: September 2018

Let [Formula: see text] be a polynomial of degree [Formula: see text] which splits into distinct linear factors over a finite field [Formula: see text]. Let [Formula: see text] be a finite non-chain ring. In an earlier paper, we studied duadic and triadic codes over [Formula: see text] and their Gray images. Here, we study duadic negacyclic codes of Type I and Type II over the ring [Formula: see text], their extensions and their Gray images. As a consequence some self-dual, isodual, self-orthogonal and complementary dual (LCD) codes over [Formula: see text] are constructed. Some examples are also given to illustrate this.
RFI and Remote Sensing of the Earth From Space
Authors: Le Vine David M.
Published: September 2018

Passive microwave remote sensing of the Earth from space provides information essential for understanding the Earth’s environment and its evolution. Parameters such as soil moisture, sea surface temperature and salinity, and profiles of atmospheric temperature and humidity are measured at frequencies determined by the physics (e.g. sensitivity to changes in desired parameters) and by the availability of suitable spectrum free from interference. Interference from man-made sources (radio frequency interference) is an impediment that in many cases limits the potential for accurate measurements from space. A review is presented here of the frequencies employed in passive microwave remote sensing of the Earth from space and of the associated experience with RFI and contemporary approaches to address the problem.
Cratonic basin formation: a case study of the Parnaíba Basin of Brazil
Authors: Daly M. C. , Fuck R. A. , Julià J. , Macdonald D. I. M. , Watts A. B.
Published: September 2018

Cratonic basins comprise a significant component of the Earth's continental crust and surface geology. Their subcircular form and large areas of flat-lying, largely undeformed sedimentary rocks characterize the central regions of many continents, and are also a significant habitat for water, mineral and petroleum resources. These basinal regions have been extensively studied, yet there is little consensus on the driving mechanism of their subsidence or their greater tectonic context. Here we present the results of an integrated basin analysis of the Paleozoic–Early Mesozoic Parnaíba cratonic basin of NE Brazil. The analysis integrates existing geological and geophysical data, and a new deep-crustal geophysical dataset, to determine the deep structure of the basin and the underlying crust and mantle. Several major features have emerged from this which constrain the basins genesis: (1) continental–shallow-marine stratigraphy characterized by an exponentially decreasing tectonic subsidence with a relatively long time constant of the order of 70–90 myr; (2) a complex Proterozoic–Early Paleozoic basement that comprises at least three major crustal blocks defined by seismic facies and conductivity contrasts with no evidence of an extensive rift system beneath the basin; (3) a mid-crustal fabric that appears to define the top of a dense and seismically fast lower crust (
V
p
6.7–6.8 km s
−1
and
V
s
3.7–3.8 km s
−1
) and upper mantle (
V
p
8.2–8.4 km s
−1
) directly beneath the basin, and which correlates with a sediment-corrected Bouger gravity anomaly high of +40–60 mGal; (4) a Moho that is generally as deep or deeper beneath the basin (40–45 km) than its surrounding region (34–40 km), and which appears stepped at the terrane boundaries; (5) a relatively conductive crust and upper mantle beneath the basin, and relatively resistive crust along the boundaries of the basement blocks; and (6) igneous events immediately before and after formation of the cratonic megasequence and a geochemically enriched mantle beneath the basin that sourced two major episodes of Mesozoic igneous intrusions. These latter events are responsible for the development of an atypical gas-prone petroleum system dependent on local magmatic events for heat generation and trapping configurations. The data describing these features are presented and discussed, and their implications used to draw conclusions about the formation of the Parnaíba Basin specifically and cratonic basins more generally.
Editing Fluid Animation Using Flow Interpolation
Authors: Sato Syuhei , Dobashi Yoshinori , Nishita Tomoyuki
Published: September 2018

The computational cost for creating realistic fluid animations by numerical simulation is generally expensive. In digital production environments, existing precomputed fluid animations are often reused for different scenes in order to reduce the cost of creating scenes containing fluids. However, applying the same animation to different scenes often produces unacceptable results, so the animation needs to be edited. In order to help animators with the editing process, we develop a novel method for synthesizing the desired fluid animations by combining existing flow data. Our system allows the user to place flows at desired positions and combine them. We do this by interpolating velocities at the boundaries between the flows. The interpolation is formulated as a minimization problem of an energy function, which is designed to take into account the inviscid, incompressible Navier-Stokes equations. Our method focuses on smoke simulations defined on a uniform grid. We demonstrate the potential of our method by showing a set of examples, including a large-scale sandstorm created from a few flow data simulated in a small-scale space.
Hemodynamic forces using four-dimensional flow MRI: an independent biomarker of cardiac function in heart failure with left ventricular dyssynchrony?
Authors: Arvidsson Per M. , Töger Johannes , Pedrizzetti Gianni , Heiberg Einar , Borgquist Rasmus , Carlsson Marcus , Arheden Håkan
Published: September 2018

Patients with heart failure with left ventricular (LV) dyssynchrony often do not respond to cardiac resynchronization therapy (CRT), indicating that the pathophysiology is insufficiently understood. Intracardiac hemodynamic forces computed from four-dimensional (4-D) flow MRI have been proposed as a new measure of cardiac function. We therefore aimed to investigate how hemodynamic forces are altered in LV dyssynchrony. Thirty-one patients with heart failure and LV dyssynchrony and 39 control subjects underwent cardiac MRI with the acquisition of 4-D flow. Hemodynamic forces were computed using Navier-Stokes equations and integrated over the manually delineated LV volume. The ratio between transverse (lateral-septal and inferior-anterior) and longitudinal (apical-basal) forces was calculated for systole and diastole separately and compared with QRS duration, aortic valve opening delay, global longitudinal strain, and ejection fraction (EF). Patients exhibited hemodynamic force patterns that were significantly altered compared with control subjects, including loss of longitudinal forces in diastole (force ratio, control subjects vs. patients: 0.32 vs. 0.90, P < 0.0001) and increased transverse force magnitudes. The systolic force ratio was correlated with global longitudinal strain and EF ( P < 0.01). The diastolic force ratio separated patients from control subjects (area under the curve: 0.98, P < 0.0001) but was not correlated to other dyssynchrony measures ( P > 0.05 for all). Hemodynamic forces by 4-D flow represent a new approach to the quantification of LV dyssynchrony. Diastolic force patterns separate healthy from diseased ventricles. Different force patterns in patients indicate the possible use of force analysis for risk stratification and CRT implantation guidance.

NEW & NOTEWORTHY In this report, we demonstrate that patients with heart failure with left ventricular dyssynchrony exhibit significantly altered hemodynamic forces compared with normal. Force patterns in patients mechanistically reflect left ventricular dysfunction on the organ level, largely independent of traditional dyssynchrony measures. Force analysis may help clinical decision making and could potentially be used to improve therapy outcomes.
Chronic stimulation of the sigma-1 receptor ameliorates autonomic nerve dysfunction and atrial fibrillation susceptibility in a rat model of depression
Authors: Liu Xin , Qu Chuan , Yang Hongjie , Shi Shaobo , Zhang Cui , Zhang Yan , Liang Jinjun , Yang Bo
Published: September 2018

The present study aimed to assess the effect of sigma-1 receptor (S1R) stimulation on autonomic nerve dysfunction and susceptibility to atrial fibrillation (AF) in a rat depression model. Male rats were randomly divided into one of the following four treatment groups: saline [control (CTL)]; saline + intragastric administration of SA4503, an agonist of S1R (CTS); chronic unpredictable mild stress (CUMS) to produce depression (MDD); and CUMS + intragastric administration of SA4503 (MDS). Depression-like behaviors, such as reduced sucrose preference, decreased body weight gain, and increased immobility time during forced swimming, improved in the MDS group after 4 wk of SA4503 treatment. Compared with rats in the CTL group, rats in the MDD group showed significantly augmented sympathetic activity, reduced parasympathetic activity, decreased heart rate variability, and lowered S1R expression in the atrium and hippocampus (all P < 0.01). However, rats in the MDS group showed mitigated aforementioned alterations and improved electrical remodeling compared with rats in the MDD group (all P < 0.01). Furthermore, rats in the MDS group showed shortened activation latencies, increased effective refractory periods, and lowered frequency of AF incidence duration and fibrosis compared with rats in the MDD group (all P < 0.01). The results indicate that S1R stimulation reduces sympathetic activity and susceptibility to AF by improving depressive behaviors, modulating cardiac autonomic nerve balance, lightening nerve remodeling, and upregulating S1R and ion channel protein expression.

NEW & NOTEWORTHY Chronic stimulation of the sigma-1 receptor (S1R) ameliorates depression-induced autonomic nerve dysfunction by modulating the imbalance between overactivated sympathetic activity and decreased vagal activity. Chronic S1R stimulation alleviates atrial electrical remodeling, fibrosis, and susceptibility to atrial fibrillation (AF). The S1R agonist may target the underlying mechanisms related to AF occurrence. The results indicate that the S1R could be a potential clinical target for atrial arrhythmia, especially when it is combined with major depressive disorders.
Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for Pancreatic Cancer Therapy
Authors: Wang Wei , Qin Jiang-Jiang , Voruganti Sukesh , Nijampatnam Bhavitavya , Velu Sadanandan E. , Ruan Ke-He , Hu Ming , Zhou Jianwei , Zhang Ruiwen
Published: September 2018

Overexpression and activation of the murine double minute 2 (MDM2) or nuclear factor of activated T cells 1 (NFAT1) oncoproteins frequently occur in pancreatic cancer. Most MDM2 inhibitors under development target MDM2–p53 binding and have little or no effect on cancers without functional p53, including pancreatic cancer. Some available compounds indirectly inhibit NFAT1 activity by interfering with calcineurin activity, but there are currently no specific inhibitors against NFAT1. Here we performed a high-throughput virtual and cell-based screening to yield a lead compound (MA242) that can directly bind both MDM2 and NFAT1 with high affinity, induce their protein degradation, and inhibit NFAT1-mediated transcription of MDM2. As a result of this binding, MA242 decreased cell proliferation and induced apoptosis in pancreatic cancer cell lines regardless of p53 status. MA242 alone or in combination with gemcitabine inhibited pancreatic tumor growth and metastasis without any host toxicity. Our data indicate that targeting both MDM2 and NFAT1 represents a novel and effective strategy to treat pancreatic cancer.

Significance: These findings suggest that pharmacological inhibition of both MDM2 and NFAT1 is a promising strategy for the treatment of pancreatic cancer, even in tumors lacking functional p53. Cancer Res; 78(19); 5656–67. ©2018 AACR.
Microvascular Loss and Diastolic Dysfunction in Severe Symptomatic Cardiac Allograft Vasculopathy
Authors: Daud Anees , Xu David , Revelo Monica P. , Shah Zubair , Drakos Stavros G. , Dranow Elizabeth , Stoddard Gregory , Kfoury Abdallah G. , Hammond M. Elizabeth H. , Nativi-Nicolau Jose , Alharethi Rami , Miller Dylan V. , Gilbert Edward M. , Wever-Pinzon Omar , McKellar Stephen H. , Afshar Kia , Khan Farman , Fang James C. , Selzman Craig H. , Stehlik Josef
Published: September 2018

Background:

Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV.

Methods and Results:

The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness (
P
<0.05).

Conclusions:

Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.
Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement
Authors: Herrmann Sebastian , Fries Bastian , Salinger Tim , Liu Dan , Hu Kai , Gensler Daniel , Strotmann Jörg , Christa Martin , Beer Meinrad , Gattenlöhner Stefan , Störk Stefan , Voelker Wolfram , Bening Constanze , Lorenz Kristina , Leyh Rainer , Frantz Stefan , Ertl Georg , Weidemann Frank , Nordbeck Peter
Published: September 2018

Background

Long-term data on evolution and clinical impact of myocardial fibrosis in valvular heart disease are scarce.

Methods and Results

In this 10 years’ extension of a prospective study in patients undergoing conventional aortic valve replacement because of symptomatic severe aortic valve stenosis, the impact of myocardial replacement fibrosis (MRF) on long-term outcome was assessed. Endomyocardial biopsies were acquired during aortic valve replacement in 58 consecutive patients. MRF was graded using the calculated percentage area of fibrosis and patients categorized as severe (n=21), mild (n=15), and no fibrosis (n=22). Echocardiography including strain imaging, as well as cardiovascular magnetic resonance, to assess late gadolinium enhancement was performed at baseline, 1, and 10 years after aortic valve replacement. Death of any cause occurred in 21 patients (38.9%): 3 (14.3%) in the group without MRF, 6 (42.9%) in the mild MRF group, and 12 (63.2%) in the severe MRF group (
P
=0.006), resulting in the lowest cumulative survival for patients with severe MRF (log-rank
P
=0.003). In the group without MRF, none died of cardiovascular cause. MRF was found to be an independent predictor of survival (hazard ratio, 1.271; 95% CI, 1.032–1.564;
P
=0.024).

Conclusions

This 10-year follow-up study underlines the profound impact of replacement fibrosis with regard to cardiac and all-cause mortality in patients undergoing aortic valve replacement for severe aortic valve stenosis. Integrating cardiovascular magnetic resonance and echocardiographic functional imaging beyond ejection fraction quantification could help in clinical decision making to stratify patient prognosis with regard to myocardial longitudinal function and prevalence of replacement fibrosis.
3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography Depicts Heterogeneous Proliferation Pathology in Idiopathic Pulmonary Arterial Hypertension Patient Lung
Authors: Ashek Ali , Spruijt Onno A. , Harms Hendrik J. , Lammertsma Adriaan A. , Cupitt John , Dubois Olivier , Wharton John , Dabral Swati , Pullamsetti Soni Savai , Huisman Marc C. , Frings Virginie , Boellaard Ronald , de Man Frances S. , Botros Lisa , Jansen Samara , Vonk Noordegraaf Anton , Wilkins Martin R. , Bogaard Harm J. , Zhao Lan
Published: September 2018

Background:

Pulmonary vascular cell hyperproliferation is characteristic of pulmonary vascular remodeling in pulmonary arterial hypertension. A noninvasive imaging biomarker is needed to track the pathology and assess the response to novel treatments targeted at resolving the structural changes. Here, we evaluated the application of radioligand 3′-deoxy-3′-[18F]-fluorothymidine (
18
FLT) using positron emission tomography.

Methods and Results:

We performed dynamic
18
FLT positron emission tomography in 8 patients with idiopathic pulmonary arterial hypertension (IPAH) and applied in-depth kinetic analysis with a reversible 2-compartment 4k model. Our results show significantly increased lung
18
FLT phosphorylation (k
3
) in patients with IPAH compared with nonpulmonary arterial hypertension controls (0.086±0.034 versus 0.054±0.009 min
−1
;
P
<0.05). There was heterogeneity in the lung
18
FLT signal both between patients with IPAH and within the lungs of each patient, compatible with histopathologic reports of lungs from patients with IPAH. Consistent with
18
FLT positron emission tomographic data, TK1 (thymidine kinase 1) expression was evident in the remodeled vessels in IPAH patient lung. In addition, hyperproliferative pulmonary vascular fibroblasts isolated from patients with IPAH exhibited upregulated expression of TK1 and the thymidine transporter, ENT1 (equilibrative nucleoside transporter 1). In the monocrotaline and SuHx (Sugen hypoxia) rat pulmonary arterial hypertension models, increased lung
18
FLT uptake was strongly associated with peripheral pulmonary vascular muscularization and the proliferation marker, Ki-67 score, together with prominent TK1 expression in remodeled vessels. Importantly, lung
18
FLT uptake was attenuated by 2 antiproliferative treatments: dichloroacetate and the tyrosine kinase inhibitor, imatinib.

Conclusions:

Dynamic
18
FLT positron emission tomography imaging can be used to report hyperproliferation in pulmonary hypertension and merits further study to evaluate response to treatment in patients with IPAH.
Coronary Computed Tomography Angiography–Specific Definitions of High-Risk Plaque Features Improve Detection of Acute Coronary Syndrome
Authors: Bittner Daniel O. , Mayrhofer Thomas , Puchner Stefan B. , Lu Michael T. , Maurovich-Horvat Pal , Ghemigian Khristine , Kitslaar Pieter H. , Broersen Alexander , Bamberg Fabian , Truong Quynh A. , Schlett Christopher L. , Hoffmann Udo , Ferencik Maros
Published: September 2018

Background

High-risk plaque (HRP) features as detected by coronary computed tomography angiography (CTA) predict acute coronary syndrome (ACS). We sought to determine whether coronary CTA-specific definitions of HRP improve discrimination of patients with ACS as compared with definitions from intravascular ultrasound (IVUS).

Methods and Results

In patients with suspected ACS, randomized to coronary CTA in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial, we retrospectively performed semiautomated quantitative analysis of HRP (including remodeling index, plaque burden as derived by plaque area, low computed tomography attenuation plaque volume) and degree of luminal stenosis and analyzed the performance of traditional IVUS thresholds to detect ACS. Furthermore, we derived CTA-specific thresholds in patients with ACS to detect culprit lesions and applied those to all patients to calculate the discriminatory ability to detect ACS in comparison to IVUS thresholds.

Of 472 patients, 255 patients (56±7.8 years; 63% men) had coronary plaque. In 32 patients (6.8%) with ACS, culprit plaques (n=35) differed from nonculprit plaques (n=172) with significantly greater values for all HRP features except minimal luminal area (significantly lower; all
P
<0.01). IVUS definitions showed good performance while minimal luminal area (odds ratio: 6.82;
P
=0.014) and plaque burden (odds ratio: 5.71;
P
=0.008) were independently associated with ACS but not remodeling index (odds ratio: 0.78;
P
=0.673). Optimized CTA-specific thresholds for plaque burden (area under the curve: 0.832 versus 0.676) and degree of stenosis (area under the curve: 0.826 versus 0.721) showed significantly higher diagnostic performance for ACS as compared with IVUS-based thresholds (all
P
<0.05) with borderline significance for minimal luminal area (area under the curve: 0.817 versus 0.742;
P
=0.066).

Conclusions

CTA-specific definitions of HRP features may improve the discrimination of patients with ACS as compared with IVUS-based definitions.

CLINICAL TRIAL REGISTRATION

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01084239
Benefit and Risk of Prolonged DAPT After Coronary Stenting in Women
Authors: Berry Natalia C. , Kereiakes Dean J. , Yeh Robert W. , Steg P. Gabriel , Cutlip Donald E. , Jacobs Alice K. , Abbott J. Dawn , Hsieh Wen-Hua , Massaro Joseph M. , Mauri Laura ,   on behalf of the DAPT Study Investigators
Published: September 2018

Background:

Women may derive differential benefit from prolonged DAPT (dual antiplatelet therapy) after coronary stenting than men. We assessed whether the risks/benefits of prolonged DAPT differ between women and men.

Methods and Results:

The DAPT study was a randomized double-blind, placebo-controlled trial comparing continued thienopyridine versus placebo beyond 12 months after coronary stenting. We compared rates of myocardial infarction, stent thrombosis, major adverse cardiovascular and cerebrovascular events, and bleeding by sex and randomized treatment. Of 11 648 patients, women (N=2925) were older, with higher prevalence of diabetes mellitus and lower rates of acute coronary syndrome than men. At 12 to 30 months, women had similar adjusted ischemic and bleeding events as men. The effects of continued thienopyridine therapy did not differ significantly by sex for stent thrombosis (women: hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.22–1.36; men: HR, 0.26; 95% CI, 0.15–0.44; interaction
P
=0.17), myocardial infarction (women: HR, 0.75; 95% CI, 0.50–1.14; men: HR, 0.46; 95% CI, 0.36–0.60; interaction
P
=0.052), major adverse cardiovascular and cerebrovascular events (women: HR, 0.87; 95% CI, 0.62–1.22; men: HR, 0.70; 95% CI, 0.58–0.85; interaction
P
=0.26), and bleeding (women: HR, 1.45; 95% CI, 0.88–2.40; men: HR, 1.78; 95% CI, 1.28–2.49; interaction
P
=0.50).

Conclusions:

Women had similar late risks of ischemia and bleeding as men after coronary stent procedures.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00977938.
Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease
Authors: Li Zhen , Polhemus David J. , Lefer David J.
Published: September 2018

Hydrogen sulfide (H
2
S)—a potent gaseous signaling molecule—has emerged as a critical regulator of cardiovascular homeostasis. H
2
S is produced enzymatically by 3 constitutively active endogenous enzymes in all mammalian species. Within the past 2 decades, studies administering H
2
S-donating agents and the genetic manipulation of H
2
S-producing enzymes have revealed multiple beneficial effects of H
2
S, including vasodilation, activation of antiapoptotic and antioxidant pathways, and anti-inflammatory effects. More recently, the heightened enthusiasm in this field has shifted to the development of novel H
2
S-donating agents that exert favorable pharmacological profiles. This has led to the discovery of novel H
2
S-mediated signaling pathways. This review will discuss recently developed H
2
S therapeutics, introduce signaling pathways that are influenced by H
2
S-dependent sulfhydration, and explore the dual-protective effect of H
2
S in cardiorenal syndrome.
“Life's Simple 7” and Long‐Term Mortality After Stroke
Authors: Lin Michelle P. , Ovbiagele Bruce , Markovic Daniela , Towfighi Amytis
Published: September 2018

Background

The American Heart Association developed criteria dubbed “Life's Simple 7” defining ideal cardiovascular health: not smoking, regular physical activity, healthy diet, maintaining normal weight, and controlling cholesterol, blood pressure, and blood glucose levels. The impact of achieving these metrics on survival after stroke is unknown. We aimed to determine
cardiovascular
health scores among stroke survivors in the United States and to assess the link between
cardiovascular
health score and all‐cause mortality after stroke.

Methods and Results

We assessed
cardiovascular
health metrics among a nationally representative sample of
US
adults with stroke (n=420) who participated in the National Health and Nutrition Examination Surveys in 1988–1994 (with mortality assessment through 2006). We determined cumulative all‐cause mortality by
cardiovascular
health score under the Cox proportional hazards model after adjusting for sociodemographic characteristics and comorbidities. No stroke survivors met all 7 ideal health metrics. Over a median duration of 98 months (range, 53–159), there was an inverse dose‐dependent relationship between number of ideal lifestyle metrics met and 10‐year adjusted mortality: 0 to 1: 57%; 2: 48%; 3: 43%; 4: 36%; and ≥5: 30%. Those who met ≥4 health metrics had lower all‐cause mortality than those who met 0 to 1 (hazard ratio, 0.51; 95% confidence interval, 0.28–0.92). After adjusting for sociodemographics, higher health score was associated with lower all‐cause mortality (trend
P
‐value, 0.022).

Conclusions

Achieving a greater number of ideal
cardiovascular
health metrics is associated with lower long‐term risk of dying after stroke. Specifically targeting “Life's Simple 7” goals might have a profound impact, extending survival after stroke.
Anti‐α4 Integrin Antibody Blocks Monocyte/Macrophage Traffic to the Heart and Decreases Cardiac Pathology in a SIV Infection Model of AIDS
Authors: Walker Joshua A. , Beck Graham A. , Campbell Jennifer H. , Miller Andrew D. , Burdo Tricia H. , Williams Kenneth C.
Published: September 2018

Background

Cardiovascular disease (CVD), myocarditis and fibrosis are comorbidities of HIV
+
individuals on durable antiretroviral therapy (ART). Although mechanisms for these vary, monocytes/macrophages are increasingly demonstrated to be key players.

Methods and Results

We directly blocked monocyte/macrophage traffic to the heart in an SIV model of AIDS using an anti‐alpha‐4 integrin antibody (natalizumab). Nineteen Rhesus macaques were SIVmac251 infected and CD8‐lymphocyte depleted for the development of rapid AIDS. Ten animals received natalizumab once a week, for 3 weeks, and were sacrificed 1 week later. Six animals began treatment at the time of infection (early) and the remaining 4 began treatment 28 days post‐infection (late), a time point we have previously established when significant cardiac inflammation occurs. Nine animals were untreated controls; of these, 3 were sacrificed early and 6 were sacrificed late. At necropsy, we found decreased SIV‐associated cardiac pathology in late natalizumab‐treated animals, compared to untreated controls. Early and late treatment resulted in significant reductions in numbers of CD163
+
and CD68
+
macrophages in cardiac tissues, compared to untreated controls, and a trend in decreasing numbers of newly recruited MAC387
+
and BrdU
+
(recruited) monocytes/macrophages. In late treated animals, decreased macrophage numbers in cardiac tissues correlated with decreased fibrosis. Early and late treatment resulted in decreased cardiomyocyte damage.

Conclusions

These data demonstrate a role for macrophages in the development of cardiac inflammation and fibrosis, and suggest that blocking monocyte/macrophage traffic to the heart can alleviate HIV‐ and SIV‐associated myocarditis and fibrosis. They underscore the importance of targeting macrophage activation and traffic as an adjunctive therapy in HIV infection.
Sex Differences in Long‐Term Outcomes With Cardiac Resynchronization Therapy in Mild Heart Failure Patients With Left Bundle Branch Block
Authors: Biton Yitschak , Zareba Wojciech , Goldenberg Ilan , Klein Helmut , McNitt Scott , Polonsky Bronislava , Moss Arthur J. , Kutyifa Valentina ,   the MADIT‐CRT Executive Committee
Published: September 2018

Background

Previous studies have shown conflicting results regarding the benefit of cardiac resynchronization therapy (
CRT
) by sex and
QRS
duration.

Methods and Results

In the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (
MADIT
‐
CRT
), we evaluated long‐term clinical outcome of heart failure (
HF
) or death, death, and
HF
alone by sex and
QRS
duration (dichotomized at 150 ms) in left bundle‐branch block patients with
CRT
with defibrillator backup (
CRT
‐D) versus implantable cardioverter‐defibrillator (
ICD
) only. There were 394 women (31%) and 887 men with left bundle‐branch block. During the median follow‐up of 5.6 years, women derived greater clinical benefit from
CRT
‐D compared with implantable cardioverter‐defibrillator only, with a significant 71% reduction in
HF
or death (hazard ratio [
HR
] 0.29,
P
<0.001) and a 77% reduction in
HF
alone (
HR
0.23,
P
<0.001) compared with men, who had a 41% reduction in
HF
or death (
HR
0.59,
P
<0.001) and a 50% reduction in
HF
alone (
HR
0.50,
P
<0.001) (all sex‐by‐treatment interaction
P
<0.05). Men and women had similar reduction in long‐term mortality with
CRT
‐D versus implantable cardioverter‐defibrillator only (men:
HR
0.70,
P
=0.03; women:
HR
0.59,
P
=0.04). The incremental benefit of
CRT
‐D in women for
HF
or death and
HF
alone was consistent with
QRS
<150 or >150 ms.

Conclusions

During long‐term follow‐up of mild
HF
patients with left ventricular dysfunction and wide
QRS
, both women and men with left bundle‐branch block derived sustained benefit from
CRT
‐D versus implantable cardioverter‐defibrillator only, with significant reduction in
HF
or death,
HF
alone, and all‐cause mortality regardless of
QRS
duration. There is an incremental benefit with
CRT
‐D in women for the end points of
HF
or death and
HF
alone.

Clinical Trial Registration

URL:
https://clinicaltrials.gov/
. Unique identifiers: NCT00180271, NCT01294449, and NCT02060110.
Effects of Exercise Training on Cardiorespiratory Fitness and Biomarkers of Cardiometabolic Health: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Lin Xiaochen , Zhang Xi , Guo Jianjun , Roberts Christian K. , McKenzie Steve , Wu Wen‐Chih , Liu Simin , Song Yiqing
Published: September 2018

Background

Guidelines recommend exercise for cardiovascular health, although evidence from trials linking exercise to cardiovascular health through intermediate biomarkers remains inconsistent. We performed a meta‐analysis of randomized controlled trials to quantify the impact of exercise on cardiorespiratory fitness and a variety of conventional and novel cardiometabolic biomarkers in adults without cardiovascular disease.

Methods and Results

Two researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random‐effects meta‐analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high‐density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment–insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin‐18 and lower levels of leptin, fibrinogen, and angiotensin II. In addition, we found that the exercise effects were modified by age, sex, and health status such that people aged <50 years, men, and people with type 2 diabetes, hypertension, dyslipidemia, or metabolic syndrome appeared to benefit more.

Conclusions

This meta‐analysis showed that exercise significantly improved cardiorespiratory fitness and some cardiometabolic biomarkers. The effects of exercise were modified by age, sex, and health status. Findings from this study have significant implications for future design of targeted lifestyle interventions.
Clinical Utility of Ventricular Repolarization Dispersion for Real‐Time Detection of Non‐ST Elevation Myocardial Infarction in Emergency Departments
Authors: Al‐Zaiti Salah S. , Callaway Clifton W. , Kozik Teri M. , Carey Mary G. , Pelter Michele M.
Published: September 2018

Background

A specific electrocardiographic (
ECG
) marker of ischemia would greatly improve the speed and accuracy of detecting and treating non‐
ST
elevation myocardial infarction (
NSTEMI
). We hypothesize that ischemia induces ventricular repolarization dispersion (
VRD
), altering the T‐wave before any
ST
segment deviation. We sought to evaluate the clinical utility of
VRD
to (1) detect
NSTEMI
cases in the emergency department (
ED
) and (2) identify
NSTEMI
cases at high risk for in‐hospital major adverse cardiac events (
MACEs
).

Methods and Results

We continuously recorded 12‐lead Holter
ECG
s from chest pain patients upon their arrival to the
ED
.
VRD
was quantified using principal component analysis of the 12‐lead
ECG
to compute a T‐wave complexity ratio (ie, ratio of second to first eigenvectors of repolarization). Clinical outcomes were obtained from hospital records
.
The sample was composed mainly of older males (n=369; ages 63±12 years; 63% males), and 92 (25%) had
NSTEMI
and 26 (7%) had
MACEs
. Baseline T‐wave complexity ratio modestly correlated with peak troponin levels (
r
=0.41;
P
<0.001) and was a good classifier of
NSTEMI
events (area under the curve=0.70). An increased T‐wave complexity ratio on the presenting
ECG
was strongly associated with
NSTEMI
(odds ratio [
OR]
=3.8 [2.1 to 5.8]) and in‐hospital
MACE
(
OR
=8.2 [3.1 to 21.5]).

Conclusions

A simple measure of global
VRD
on the presenting 12‐lead
ECG
correlates with ischemic myocardial injury and can discriminate
NSTEMI
cases very early during evaluation. Prospective studies should validate these findings and test whether
VRD
can guide therapy.