bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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.
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

AbstractOverexpression 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.
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.
“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.