bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aortic distensibility is associated with both resting and hyperemic coronary blood flow
Authors: Nelson Adam J. , Puri Rishi , Nicholls Stephen J. , Dundon Benjamin K. , Richardson James D. , Sidharta Samuel L. , Teo Karen S. , Worthley Stephen G. , Worthley Matthew I. 
Published: August 2019

A large body of evidence demonstrates an independent association between arterial stiffness and prospective risk of cardiovascular events. A reduction in coronary perfusion is presumed to underscore this association; however, studies confirming this are lacking. This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR)-derived aortic distensibility (AD). Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV) and CBF [π × (diameter)2× APV × 0.125]. Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal descending aorta (DDA). Fifteen participants (53 ± 13 yr) with minor epicardial disease (maximum stenosis <30%) were enrolled. Resting CBF was 44.1 ± 11.9 mL/min, hyperemic CBF was 143.8 ± 37.4 mL/min, and CFVR was 3.15 ± 0.48. AD was 3.89 ± 1.72·10−3mmHg−1at the AA, 4.08 ± 1.80·10−3mmHg−1at the PDA, and 4.42 ± 1.67·10−3mmHg−1at the DDA. All levels of distensibility correlated with resting CBF ( R2= 0.350–0.373, P < 0.05), hyperemic CBF ( R2= 0.453–0.464, P < 0.01), and CFVR ( R2= 0.442–0.511, P < 0.01). This study demonstrates that hyperemic and, to a lesser extent resting CBF, are significantly associated with measures of aortic stiffness in patients with only minor angiographic disease. These findings provide further in vivo support for the observed prognostic capacity of large artery function in cardiovascular event prediction.NEW & NOTEWORTHY Cardiac magnetic resonance-derived aortic distensibility is associated with invasive measures of coronary blood flow. Large artery function is more strongly correlated with hyperemic than resting blood flow. Increased stiffness may represent a potential target for novel antianginal medications.
Cortical bone-derived stem cell therapy reduces apoptosis after myocardial infarction
Authors: Hobby Alexander R. H. , Sharp Thomas E. , Berretta Remus M. , Borghetti Giulia , Feldsott Eric , Mohsin Sadia , Houser Steven R. 
Published: August 2019

Ischemic heart diseases such as myocardial infarction (MI) are the largest contributors to cardiovascular disease worldwide. The resulting cardiac cell death impairs function of the heart and can lead to heart failure and death. Reperfusion of the ischemic tissue is necessary but causes damage to the surrounding tissue by reperfusion injury. Cortical bone stem cells (CBSCs) have been shown to increase pump function and decrease scar size in a large animal swine model of MI. To investigate the potential mechanism for these changes, we hypothesized that CBSCs were altering cardiac cell death after reperfusion. To test this, we performed TUNEL staining for apoptosis and antibody-based immunohistochemistry on tissue from Göttingen miniswine that underwent 90 min of lateral anterior descending coronary artery ischemia followed by 3 or 7 days of reperfusion to assess changes in cardiomyocyte and noncardiomyocyte cell death. Our findings indicate that although myocyte apoptosis is present 3 days after ischemia and is lower in CBSC-treated animals, myocyte apoptosis accounts for <2% of all apoptosis in the reperfused heart. In addition, nonmyocyte apoptosis trends toward decreased in CBSC-treated hearts, and although CBSCs increase macrophage and T-cell populations in the infarct region, the occurrence of apoptosis in CD45+ cells in the myocardium is not different between groups. From these data, we conclude that CBSCs may be influencing cardiomyocyte and noncardiomyocyte cell death and immune cell recruitment dynamics in the heart after MI, and these changes may account for some of the beneficial effects conferred by CBSC treatment. NEW & NOTEWORTHY The following research explores aspects of cell death and inflammation that have not been previously studied in a large animal model. In addition, apoptosis and cell death have not been studied in the context of cell therapy and myocardial infarction. In this article, we describe interactions between cell therapy and inflammation and the potential implications for cardiac wound healing. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/cortical-bone-derived-stem-cell-therapy-reduces-apoptosis/ .
Modeling arterial pulse waves in healthy aging: a database for in silico evaluation of hemodynamics and pulse wave indexes
Authors: Charlton Peter H. , Mariscal Harana Jorge , Vennin Samuel , Li Ye , Chowienczyk Phil , Alastruey Jordi 
Published: August 2019

The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25–75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.
Global Reach 2018: reduced flow-mediated dilation stimulated by sustained increases in shear stress in high-altitude excessive erythrocytosis
Authors: Tremblay Joshua C. , Coombs Geoff B. , Howe Connor A. , Vizcardo-Galindo Gustavo A. , Figueroa-Mujíca Rómulo J. , Bermudez Daniela , Tymko Michael M. , Villafuerte Francisco C. , Ainslie Philip N. , Pyke Kyra E. 
Published: August 2019

Excessive erythrocytosis [EE; hemoglobin concentration (Hb) ≥ 21 g/dL in adult men] is a maladaptive high-altitude pathology associated with increased cardiovascular risk and reduced reactive hyperemia flow-mediated dilation (FMD); however, whether a similar impairment occurs in response to more commonly encountered sustained increases in shear stress [sustained stimulus (SS)-FMD] over a range of overlapping stimuli is unknown. We characterized SS-FMD in response to handgrip exercise in Andeans with and without EE in Cerro de Pasco, Peru (4,330 m). Andean highlanders with EE ( n = 17, Hb = 23.2 ± 1.2 g/dL) and without EE ( n = 23, Hb = 18.7 ± 1.9 g/dL) performed 3 min of rhythmic handgrip exercise at 20, 35, and 50% of maximum voluntary contraction (MVC). Duplex ultrasound was used to continuously record blood velocity and diameter in the brachial artery, and blood viscosity was measured to accurately calculate shear stress. Although baseline shear stress did not differ, Andeans with EE had 22% lower shear stress than Andeans without at 50% MVC ( P = 0.004). At 35 and 50% MVC, SS-FMD was 2.1 ± 2.0 and 2.8 ± 2.7% in Andeans with EE compared with 4.1 ± 3.4 and 7.5 ± 4.5% in those without ( P = 0.048 and P < 0.001). The stimulus-response slope (∆shear stress vs. ∆diameter) was lower in Andeans with EE compared with Andeans without ( P = 0.028). This slope was inversely related to Hb in Andeans with EE ( r2 = 0.396, P = 0.007). A reduced SS-FMD in response to small muscle mass exercise in Andeans with EE indicates a generalized reduction in endothelial sensitivity to shear stress, which may contribute to increased cardiovascular risk in this population. NEW & NOTEWORTHY High-altitude excessive erythrocytosis (EE; hemoglobin concentration ≥ 21 g/dL) is a maladaptation to chronic hypoxia exposure and is associated with increased cardiovascular risk. We examined flow-mediated dilation (FMD) in response to sustained elevations in shear stress achieved using progressive handgrip exercise [sustained stimulus (SS)-FMD] in Andean highlanders with and without EE at 4,330 m. Andeans with EE demonstrated lower SS-FMD compared with those without. Heightened hemoglobin concentration was related to lower SS-FMD in Andeans with EE.
Quantitative Ultrasound Spectroscopy for Differentiation of Hepatocellular Carcinoma from At-Risk and Normal Liver Parenchyma
Authors: Durot Isabelle , Sigrist Rosa M.S. , Kothary Nishita , Rosenberg Jarrett , Willmann Jürgen K. , El Kaffas Ahmed 
Published: August 2019

Abstract

Purpose:
Quantitative ultrasound approaches can capture tissue morphologic properties to augment clinical diagnostics. This study aims to clinically assess whether quantitative ultrasound spectroscopy (QUS) parameters measured in hepatocellular carcinoma (HCC) tissues can be differentiated from those measured in at-risk or healthy liver parenchyma.

Experimental Design:
This prospective Health Insurance Portability and Accountability Act (HIPAA)–compliant study was approved by the Institutional Review Board. Fifteen patients with HCC, 15 non-HCC patients with chronic liver disease, and 15 healthy volunteers were included (31.1% women; 68.9% men). Ultrasound radiofrequency data were acquired in each patient in both liver lobes at two focal depths (3/9 cm). Region of interests (ROIs) were drawn on HCC and liver parenchyma. The average normalized power spectrum for each ROI was extracted, and a linear regression was fit within the −6 dB bandwidth, from which the midband fit (MBF), spectral intercept (SI), and spectral slope (SS) were extracted. Differences in QUS parameters between the ROIs were tested by a mixed-effects regression.

Results:
There was a significant intraindividual difference in MBF, SS, and SI between HCC and adjacent liver parenchyma (P &lt; 0.001), and a significant interindividual difference between HCC and at-risk and healthy non-HCC parenchyma (P &lt; 0.001). In patients with HCC, cirrhosis (n = 13) did not significantly change any of the three parameters (P &gt; 0.8) in differentiating HCC from non-HCC parenchyma. MBF (P = 0.12), SI (P = 0.33), and SS (P = 0.57) were not significantly different in non-HCC tissue among the groups.

Conclusions:
The QUS parameters are significantly different in HCC versus non-HCC liver parenchyma, independent of underlying cirrhosis. This could be leveraged for improved HCC detection with ultrasound in the future.
Intron 1–Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins
Authors: Jameson Nathan M. , Ma Jianhui , Benitez Jorge , Izurieta Alejandro , Han Jee Yun , Mendez Robert , Parisian Alison , Furnari Frank 
Published: August 2019

Abstract

The epidermal growth factor receptor (EGFR) is overexpressed in numerous solid tumors and is the subject of extensive therapeutic efforts. Much of the research on EGFR is focused on protein dynamics and downstream signaling; however, few studies have explored its transcriptional regulation. Here, we identified two enhancers (CE1 and CE2) present within the first intron of the EGFR gene in models of glioblastoma (GBM) and head and neck squamous cell carcinoma (HNSCC). CE1 and CE2 contain open chromatin and H3K27Ac histone marks, enhance transcription in reporter assays, and interact with the EGFR promoter. Enhancer genetic deletion by CRISPR/Cas9 significantly reduces EGFR transcript levels, with double deletion exercising an additive effect. Targeted repression of CE1 and CE2 by dCas9-KRAB demonstrates repression of transcription similar to that of genomic deletion. We identify AP-1 transcription factor family members in concert with BET bromodomain proteins as modulators of CE1 and CE2 activity in HNSCC and GBM through de novo motif identification and validate their presence. Genetic inhibition of AP-1 or pharmacologic disruption of BET/AP-1 binding results in downregulated EGFR protein and transcript levels, confirming a role for these factors in CE1 and CE2. Our results identify and characterize these novel enhancers, shedding light on the role that epigenetic mechanisms play in regulating EGFR transcription in EGFR-dependent cancers.

Implications:
We identify critical constituent enhancers present in the first intron of the EGFR gene, and provide a rationale for therapeutic targeting of EGFR intron 1 enhancers through perturbation of AP-1 and BET in EGFR-positive malignancies.
Genetically Determined Uric Acid and the Risk of Cardiovascular and Neurovascular Diseases: A Mendelian Randomization Study of Outcomes Investigated in Randomized Trials
Authors: Efstathiadou Anthoula , Gill Dipender , McGrane Frances , Quinn Terence , Dawson Jesse 
Published: August 2019

Background
Higher serum uric acid levels are associated with cardiovascular and neurovascular disease, but whether these relationships are causal is not known. We applied Mendelian randomization approaches to assess the association between genetically determined uric acid levels and outcomes under study in large clinical trials.

Methods and Results
We used 28 genetic variants related to serum uric acid as instruments to perform a range of 2‐sample Mendelian randomization methods. Our analysis had statistical power to detect clinically relevant effects of genetically determined serum uric acid levels on the considered clinical outcomes; cognitive function, Alzheimer disease, coronary heart disease, myocardial infarction, systolic blood pressure, and stroke. There was some suggestive evidence for an association between higher genetically determined serum uric acid and cognitive function. There was also some suggestive evidence of a relationship between coronary heart disease, systolic blood pressure, and the serum uric acid genetic instruments, but likely related to genetic pleiotropy. Overall, there was no consistent evidence of a clinically relevant effect of genetically determined serum uric acid on any of the considered outcomes.

Conclusions
This Mendelian randomization study does not support a clinically relevant causal effect of genetically determined serum urate on a range of cardiovascular and neurovascular outcomes. The weak association of genetically determined serum urate with coronary heart disease and systolic blood pressure may be because of pleiotropic effects. If urate lowering drugs such as allopurinol are found to affect these outcomes in clinical trials, then the effects may be mediated through urate independent mechanisms.
Leptin is involved in acrosome reaction by facilitating activation of MAPK cascades in the Chinese mitten crab, Eriocheir sinensis
Authors: Li Qing , Zhao Haitao , He Lin , Yang Hongdan , Wang Qun 
Published: August 2019

Abstract
The role of leptin has been documented in several studies, including activated threonine phosphorylation of extracellular signal-regulated kinase (ERK1/2) in the reproduction of rodents and humans. Our previous studies have demonstrated that mitogen-activated protein kinase (MAPK) cascades ERK, P38, and c-Jun N-terminal kinase (JNK) are involved in the spermatogenesis and acrosome reaction of Eriocheir sinensis. Therefore, the aim of this study was to investigate the expression of leptin and its receptor (LepR), and the effect of leptin on MAPK cascades during calcium ionophore A23187-induced spermatozoa acrosome reaction in crabs. Successful western blotting revealed a 16 kDa band for leptin, and 120 kDa and 90 kDa bands for the obese receptor (LepR), respectively, in the tested male reproductive tissues. Both leptin and LepR were localized at the pro-acrosomal vesicle and apical cap (AC) of spermatids, suggesting their role in the subsequent acrosome reaction. Moreover, acrosome reaction can be enhanced by leptin, and this effect decreased due to the anti-LepR antibody. Afterwards, we investigated the effects of leptin on MAPK cascades. The results showed that leptin mainly activated the phosphorylation of ERK, P38 and JNK proteins in the apical cap during the acrosome reaction in crab spermatozoa. This study addresses the role of leptin on spermatozoa, and suggests that leptin may induce molecular changes associated with spermatozoa during acrosome reaction.
Essays on Paula Rego
Authors: Lisboa Maria Manuel 
Published: August 2019

In these powerful and stylishly written essays, Maria Manuel Lisboa dissects the work of Paula Rego, the Portuguese-born artist considered one of the greatest artists of modern times. Focusing primarily on Rego’s work since the 1980s, Lisboa explores the complex relationships between violence and nurturing, power and impotence, politics and the family that run through Rego’s art.
Taking a historicist approach to the evolution of the artist’s work, Lisboa embeds the works within Rego’s personal history as well as Portugal’s (and indeed other nations’) stories, and reveals the interrelationship between political significance and the raw emotion that lies at the heart of Rego’s uncompromising iconographic style. Fundamental to Lisboa’s analysis is an understanding that apparent opposites – male and female, sacred and profane, aggression and submissiveness – often co-exist in Rego’s work in a way that is both disturbing and destabilising.
This collection of essays brings together both unpublished and previously published work to make a significant contribution to scholarship about Paula Rego. It will also be of interest to scholars and students of contemporary painting, Portuguese and British feminist art, and the political and ideological aspects of the visual arts.
New Era of Air Quality Monitoring from Space: Geostationary Environment Monitoring Spectrometer (GEMS)
Authors: Kim Jhoon , Jeong Ukkyo , Ahn Myoung-Hwan , Kim Jae H. , Park Rokjin J. , Lee Hanlim , Song Chul Han , Choi Yong-Sang , Lee Kwon-Ho , Yoo Jung-Moon , Jeong Myeong-Jae , Park Seon Ki , Lee Kwang-Mog , Song Chang-Keun , Kim Sang-Woo , Kim Young Joon , Kim Si-Wan , Kim Mijin , Go Sujung , Liu Xiong , Chance Kelly , Chan Miller Christopher , Al-Saadi Jay , Veihelmann Ben , Bhartia Pawan K. , Torres Omar , Abad Gonzalo González , Haffner David P. , Ko Dai Ho , Lee Seung Hoon , Woo Jung-Hun , Chong Heesung , Park Sang Seo , Nicks Dennis , Choi Won Jun , Moon Kyung-Jung , Cho Ara , Yoon Jongmin , Kim Sang-kyun , Hong Hyunkee , Lee Kyunghwa , Lee Hana , Lee Seoyoung , Choi Myungje , Veefkind Pepijn , Levelt Pieternel F. , Edwards David P. , Kang Mina , Eo Mijin , Bak Juseon , Baek Kanghyun , Kwon Hyeong-Ahn , Yang Jiwon , Park Junsung , Han Kyung Man , Kim Bo-Ram , Shin Hee-Woo , Choi Haklim , Lee Ebony , Chong Jihyo , Cha Yesol , Koo Ja-Ho , Irie Hitoshi , Hayashida Sachiko , Kasai Yasko , Kanaya Yugo , Liu Cheng , Lin Jintai , Crawford James H. , Carmichael Gregory R. , Newchurch Michael J. , Lefer Barry L. , Herman Jay R. , Swap Robert J. , Lau Alexis K. H. , Kurosu Thomas P. , Jaross Glen , Ahlers Berit , Dobber Marcel , McElroy C. Thomas , Choi Yunsoo 
Published: August 2019

AbstractThe Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in February 2020 to monitor air quality (AQ) at an unprecedented spatial and temporal resolution from a geostationary Earth orbit (GEO) for the first time. With the development of UV–visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O3, NO2, SO2, HCHO, CHOCHO, and aerosols) can be obtained. To date, all the UV–visible satellite missions monitoring air quality have been in low Earth orbit (LEO), allowing one to two observations per day. With UV–visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be on board the Geostationary Korea Multi-Purpose Satellite 2 (GEO-KOMPSAT-2) satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager 2 (GOCI-2). These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA’s Tropospheric Emissions: Monitoring of Pollution (TEMPO) and ESA’s Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS).
Paleodust Insights into Dust Impacts on Climate
Authors: Albani Samuel , Mahowald Natalie M. 
Published: August 2019

AbstractMineral dust acts both as a tracer and a forcing agent of climate change. Past dust variability, imprinted in paleodust records from natural archives, offers the unique opportunity to reconstruct the global dust cycle within a range of possibilities that plausibly encompass future variations in response to climate change and land-cover and land-use changes. Dust itself has direct and indirect feedbacks on the climate system, through impacts on the atmosphere radiative budget and the carbon cycle. Starting from well-constrained reconstructions of the present and past dust cycle, we focus on quantifying dust direct impacts on the atmospheric radiation. We discuss the intrinsic effects of dust onto climate, and how changes in the global dust budget and surface conditions modulate the effective impacts on surface temperatures and precipitation. Most notably, the presence of dust tends to enhance the West African monsoon and warm the Arctic. We also highlight how different choices in terms of dust optical properties and size distributions may yield opposite results, and what are the observational constraints we can use to make an informed choice of model parameters. Finally, we discuss how dust variability might have influenced ongoing climate transitions in the past. In particular we found that a reduction in dust load, along with a reduced cryosphere cover, acted to offset Arctic warming during the deglaciation, potentially playing a role in shaping the Northern Hemisphere deglacial dynamics.