bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runx2 (Runt-Related Transcription Factor 2)-Mediated Microcalcification Is a Novel Pathological Characteristic and Potential Mediator of Abdominal Aortic Aneurysm
Authors: Li Zhiqing , Zhao Zuoquan , Cai Zeyu , Sun Yong , Li Li , Yao Fang , Yang Liu , Zhou Yuan , Zhu Haibo , Fu Yi , Wang Li , Fang Wei , Chen Yabing , Kong Wei 
Published: March 2020

Objective:
Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification, as detected by fluorine-18-sodium fluoride, has recently been recognized as a valuable indicator in predicting atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification involved in the pathogenesis of AAA remains elusive.

Approach and Results:

Microcalcification was analyzed in human aneurysmal aortas histologically and in AngII (angiotensin II)-infused
ApoE
−/−
mouse aortas by fluorine-18-sodium fluoride positron emission tomography and X-ray computed tomography scanning in chronological order in live animals. AAA patients’ aortic tissue showed markedly enhanced microcalcification in the aortic media within the area proximal to elastic fiber degradation, compared with non-AAA patients. Enhanced fluorine-18-sodium fluoride uptake preceded significant aortic expansion in mice. Microcalcification-positive mice on day 7 of AngII infusion showed dramatic aortic expansion on subsequent days 14 to 28, whereas microcalcification-negative AngII-infused mice and saline-induced mice did not develop AAA. The application of hydroxyapatite, the main component of microcalcification, aggravated AngII-induced AAA formation in vivo. RNA-sequencing analysis of the suprarenal aortas of 4-day-AngII–infused
ApoE
−/−
mice and bioinformatics analysis with ChIP-Atlas database identified the potential involvement of the osteogenic transcriptional factor Runx2 (runt-related transcription factor 2) in AAA. Consistently, vascular smooth muscle cell–specific Runx2 deficiency markedly repressed AngII-induced AAA formation in the
ApoE
−/−
mice compared with the control littermates.

Conclusions:
Our studies have revealed microcalcification as a novel pathological characteristic and potential mediator of AAA, and targeting microcalcification may represent a promising strategy for AAA prevention and treatment.
Targeted Inhibition of Gut Microbial Trimethylamine N-Oxide Production Reduces Renal Tubulointerstitial Fibrosis and Functional Impairment in a Murine Model of Chronic Kidney Disease
Authors: Gupta Nilaksh , Buffa Jennifer A. , Roberts Adam B. , Sangwan Naseer , Skye Sarah M. , Li Lin , Ho Karen J. , Varga John , DiDonato Joseph A. , Tang W.H. Wilson , Hazen Stanley L. 
Published: March 2020

Objective:
Gut microbial metabolism of dietary choline, a nutrient abundant in a Western diet, produces trimethylamine (TMA) and the atherothrombosis- and fibrosis-promoting metabolite TMA-N-oxide (TMAO). Recent clinical and animal studies reveal that elevated TMAO levels are associated with heightened risks for both cardiovascular disease and incident chronic kidney disease development. Despite this, studies focusing on therapeutically targeting gut microbiota-dependent TMAO production and its impact on preserving renal function are limited.

Approach and Results:
Herein we examined the impact of pharmacological inhibition of choline diet-induced gut microbiota-dependent production of TMA, and consequently TMAO, on renal tubulointerstitial fibrosis and functional impairment in a model of chronic kidney disease. Initial studies with a gut microbial choline TMA-lyase mechanism-based inhibitor, iodomethylcholine, confirmed both marked suppression of TMA generation, and consequently TMAO levels, and selective targeting of the gut microbial compartment (ie, both accumulation of the drug in intestinal microbes and limited systemic exposure in the host). Dietary supplementation of either choline or TMAO significantly augmented multiple indices of renal functional impairment and fibrosis associated with chronic subcutaneous infusion of isoproterenol. However, the presence of the gut microbiota-targeting inhibitor iodomethylcholine blocked choline diet-induced elevation in TMAO, and both significantly improved decline in renal function, and significantly attenuated multiple indices of tubulointerstitial fibrosis. Iodomethylcholine treatment also reversed many choline diet-induced changes in cecal microbial community composition associated with TMAO and renal functional impairment.

Conclusions:
Selective targeting of gut microbiota-dependent TMAO generation may prevent adverse renal structural and functional alterations in subjects at risk for chronic kidney disease.
Appropriateness of Transcatheter Aortic Valve Replacement
Authors: Inohara Taku , Vemulapalli Sreekanth , Kohsaka Shun , Yashima Fumiaki , Watanabe Yusuke , Shirai Shinichi , Tada Norio , Araki Motoharu , Naganuma Toru , Yamanaka Futoshi , Ueno Hiroshi , Tabata Minoru , Mizutani Kazuki , Higashimori Akihiro , Takagi Kensuke , Yamamoto Masanori , Shimizu Hideyuki , Fukuda Keiichi , Hayashida Kentaro ,   On behalf of the OCEAN-TAVI Investigators
Published: March 2020

Background:
Transcatheter aortic valve replacement (TAVR) is widely used; however, its appropriateness is unknown. We sought to investigate the appropriateness of TAVR.

Methods and Results:

We assigned appropriateness ratings to patients undergoing TAVR for severe aortic stenosis between October 2013 and May 2017 at 14 Japanese hospitals participating in the optimized transcatheter valvular intervention-transcatheter aortic valve implantation registry according to the US appropriate use criteria for treating severe aortic stenosis. To account for the influence of uncaptured variables on appropriate use criteria ratings, we initially assigned them to a best-case scenario where they were assumed to classify a case to the most appropriate clinical scenario and then to a worst-case scenario where assumed least appropriate. Overall proportion of TAVRs classified as appropriate, maybe appropriate, or rarely appropriate was assessed. In addition, extent of hospital-level variation in rarely appropriate procedures was evaluated. Of 2036 TAVRs (median age [25th, 75th]: 85.0 years [81.0–88.0]; 70.5% female the Society of Thoracic Surgeons Predicted Risk of Mortality score: 6.2% [4.4–8.9]), in the best-case scenario, 177 (8.7%) were not successfully mapped, and 1580 (77.6%) were classified as appropriate, 180 (8.8%) as maybe appropriate, 99 (4.9%) as rarely appropriate, respectively. In the worst-case scenario, the rate of rarely appropriate increased to 6.8%. The majority of rarely appropriate TAVRs was performed in patients with moderate to severe dementia (defined as mini-mental status examination of ≤17), bicuspid aortic valve, or anticipated life expectancy <1 year. There was substantial variation in the proportion of rarely appropriate TAVR across hospitals (median rate of rarely appropriate: 4.9% [3.8–6.6] in the best-case scenario,
P
<0.001; 6.5% [5.6–8.6] in the worst-case scenario,
P
<0.001).

Conclusions:
In clinical practice, the proportion of rarely appropriate TAVRs ranged from 4.9% to 6.8% with substantial institutional variation. Our study elucidates common clinical scenarios deemed rarely appropriate and clarifies the potential targets of quality improvement.

Registration:

URL:
https://www.umin.ac.jp/ctr/index.htm
. Unique identifier: UMIN000020423.
Cold-Inducible RNA-Binding Protein Prevents an Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase
Authors: Xie Duanyang , Geng Li , Xiong Ke , Zhao Tingting , Wang Shuo , Xue Jinfeng , Wang Cheng , Wang Guanghua , Feng Zhiqiang , Zhou Huixing , Li Yini , Li Li , Liu Yi , Xue Zhigang , Yang Jian , Ma Honghui , Liang Dandan , Chen Yi-Han 
Published: March 2020

Rationale:
The stress response of heart rate, which is determined by the plasticity of the sinoatrial node (SAN), is essential for cardiac function and survival in mammals. As an RNA-binding protein, CIRP (cold-inducible RNA-binding protein) can act as a stress regulator. Previously, we have documented that CIRP regulates cardiac electrophysiology at posttranscriptional level, suggesting its role in SAN plasticity, especially upon stress conditions.

Objective:
Our aim was to clarify the role of CIRP in SAN plasticity and heart rate regulation under stress conditions.

Methods and Results:

Telemetric ECG monitoring demonstrated an excessive acceleration of heart rate under isoprenaline stimulation in conscious CIRP-KO (knockout) rats. Patch-clamp analysis and confocal microscopic Ca
2+
imaging of isolated SAN cells demonstrated that isoprenaline stimulation induced a faster spontaneous firing rate in CIRP-KO SAN cells than that in WT (wild type) SAN cells. A higher concentration of cAMP—the key mediator of pacemaker activity—was detected in CIRP-KO SAN tissues than in WT SAN tissues. RNA sequencing and quantitative real-time polymerase chain reaction analyses of single cells revealed that the 4B and 4D subtypes of PDE (phosphodiesterase), which controls cAMP degradation, were significantly decreased in CIRP-KO SAN cells. A PDE4 inhibitor (rolipram) abolished the difference in beating rate resulting from CIRP deficiency. The mechanistic study showed that CIRP stabilized the mRNA of
Pde4b
and
Pde4d
by direct mRNA binding, thereby regulating the protein expression of PDE4B and PDE4D at posttranscriptional level.

Conclusions:
CIRP acts as an mRNA stabilizer of specific PDEs to control the cAMP concentration in SAN, maintaining the appropriate heart rate stress response.
Exercise Capacity, Coronary Artery Fatty Plaque, Coronary Calcium Score, and Cardiovascular Events in Subjects With Stable Coronary Artery Disease
Authors: Malik Abdulaziz , Kanduri Jaya S. , Asbeutah Abdul Aziz A. , Khraishah Haitham , Shen Changyu , Welty Francine K. 
Published: March 2020

Background

Aerobic exercise capacity is inversely associated with cardiovascular and all‐cause mortality in men and women without coronary artery disease (
CAD
); however, a higher amount of vigorous exercise is associated with a J‐shaped relationship in
CAD
patients. Therefore, the optimal type and amount of exercise for
CAD
patients is unclear. Coronary artery calcification (
CAC
) is associated with increased cardiovascular disease (
CVD
) events and mortality. Fatty plaque is more likely to rupture and cause coronary events than other types. We examined the association between exercise capacity, fatty plaque,
CAC
score and
CVD
events in
CAD
patients.

Methods and Results

A total of 270 subjects with stable
CAD
were divided into tertiles based on metabolic equivalents of task (
MET
s) calculated from exercise treadmill testing. Self‐reported exercise was obtained. Coronary computed tomographic angiography measured coronary plaque volume and
CAC
score. After adjustment, fatty plaque volume was not different among the 3
MET
groups. For each 1
MET
increase,
CAC
was 66.2 units lower (
P
=0.017). Those with
CAC
>400 and ≥8.2
MET
s had fewer
CVD
events over 30 months compared to <8.2
MET
s (
P
=0.037). Of moderate intensity exercisers (median, 240 min/wk; 78% walking only), 62.4% achieved ≥8.2
MET
s and lower
CAC
scores (
P
=0.07). Intensity and duration of exercise had no adverse impact on coronary plaque or
CVD
events.

Conclusions

Achieving ≥8.2
MET
s with moderate exercise intensity and volume as walking resulted in lower
CAC
scores and fewer
CVD
events. Therefore, vigorous exercise intensity and volume may not be needed for
CAD
patients to derive benefit.

Registration

URL
:
https://www.clinicaltrials.gov
; Unique Identifier:
NCT
01624727.
Clinical Potential of Targeting Fibroblast Growth Factor‐23 and αKlotho in the Treatment of Uremic Cardiomyopathy
Authors: Law Jonathan P. , Price Anna M. , Pickup Luke , Radhakrishnan Ashwin , Weston Chris , Jones Alan M. , McGettrick Helen M. , Chua Winnie , Steeds Richard P. , Fabritz Larissa , Kirchhof Paulus , Pavlovic Davor , Townend Jonathan N. , Ferro Charles J. 
Published: March 2020

Abstract
Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor‐23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor‐23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end‐stage renal disease.
Four Beasts and a Baby
Authors: Djurslev Christian Thrue 
Published: March 2020

Abstract
The present article hypothesizes that a bizarre omen story of Alexander’s death belongs in a Hellenistic literary context rather than a historical Babylonian one. Several texts, including the Greek Alexander Romance (3.30), relate the birth omen of a stillborn child with living animals for his lower body. The court of Alexander decides to burn the portent. I suggest that the omen should be read as a manifestation of a teras in the Greek paradigm. In support of this argument, I offer comparable evidence from numerous sources, including iconographical material and the animal prophecies, primarily from the Old Testament Book of Daniel. The article ends with some thoughts on how this teras interpretation of the omen story exposes the tale as a Hellenistic construct.
<p><strong>Two species of nivicolous myxomycetes that formed fruiting bodies during three spring seasons in the lowlands of the Eastern Ukraine</strong></p>
Authors: YATSIUK IRYNA , LEONTYEV DMITRY 
Published: March 2020

Two species of nivicolous myxomycetes, Lamproderma pseudomaculatum and Lamproderma aff. pulchellum, previously considered as strictly montane, are reported from the lowlands (116–192 m a.s.l.) of the eastern Ukraine during three spring seasons. Lowland collections of L. aff. pulchellum show comparatively low genetic similarity with specimens of this species collected at high elevations and may represent a new taxon. Autumn frosts, which occurred before the formation of a stable snow cover, as well as the limited number of days with snow cover exceeding 30 cm, did not prevent the abundant fruiting of these myxomycetes.
The Interaction between Moist Convection and the Atmospheric Circulation in the Tropics
Authors: Tomassini Lorenzo 
Published: March 2020

AbstractTheories of the interaction between moist convection and the atmospheric circulation in the tropics are reviewed. Two main schools of thought are highlighted: (i) one that emphasizes the lower-level control of convection through moisture convergence and variations in convective inhibition, and (ii) one that sees convection as an adjustment process in reaction to larger-scale instabilities, referred to as convective quasi-equilibrium theory. Conceptually the two views consider moist convection to have fundamentally different roles in the tropical circulation. In one case the presence of low-level inhibition and the conditional nature of the atmospheric instability allows for convective vertical motion and latent heating to drive and reinforce synoptic-scale disturbances and overturning circulations; in the other case, because low-level inhibition is not acknowledged to be a widespread controlling barrier, convection is believed to balance and dampen vertical instabilities at the rate they are created by larger-scale processes over the vertical extent of the atmosphere. More recently, investigations of the moisture dynamics surrounding organized convective structures have led to an emerging consensus on the theory of convection–circulation coupling in the tropics that acknowledges the important role of lower- to midtropospheric moisture variations, and the significance of moist convection and convective clouds for initiating and establishing circulations. However, the implementation of these new insights in numerical models lags behind. This is exemplified by the apparent inadequacy of climate models to correctly represent decadal variability in the tropical Pacific, a fact that potentially has implications for the confidence in climate change projections based on such models.
Asymptotic Models for Tropical Intraseasonal Oscillations and Geostrophic Balance
Authors: Stechmann Samuel N. , Hottovy Scott 
Published: March 2020

AbstractIn the tropics, rainfall is coupled with waves in the form of, for example, convectively coupled equatorial waves (CCEWs) and the Madden–Julian oscillation (MJO). In perhaps the simplest viewpoint of CCEWs, the effects of moisture and convective adjustment can predict the basic aspects of their propagation and structure: reduced propagation speeds and reduced meridional length scales. Here, a similar simple viewpoint is investigated for the MJO’s propagation and structure. To do this investigation, budget analyses of a model MJO are first presented to illustrate and motivate the asymptotic scaling assumptions. Asymptotic models are then derived for the MJO. In brief, the structure of the asymptotic MJO is described by a tropical geostrophic balance, and the slow propagation arises from the dynamics of moist static energy. To be specific, if the moist static energy has a background vertical gradient that is asymptotically weak (i.e., a moist stability that is nearly neutral), then it supports a slowly propagating wave. Beyond these main aspects, other processes also have an influence, such as eddy diffusion of moisture. In comparing the simple viewpoints of CCEWs and the MJO, one main difference is in the propagation speeds: relative to a dry wave speed of 50 m s−1, the MJO has a speed of 5 m s−1, resulting from a reduction factor of 0.1 related to moist stability, whereas the basic CCEW speed is 15 m s−1, resulting from a reduction factor of the square root of 0.1, related to the square root of the moist stability.
Reasons for the Weakening of Tropical Depressions in the South China Sea
Authors: Zhong Rui , Xu Shibin , Huang Fei , Wu Xin 
Published: March 2020

AbstractThe frequency and location distribution of tropical depressions (TDs) from 1979 to 2017 in the South China Sea (SCS) are statistically analyzed based on the best track data of tropical cyclones (TCs) from the Shanghai Typhoon Institute, China Meteorological Administration (CMA-STI). ECMWF interim reanalysis data (ERA-Interim) are used to investigate the reasons for the weakening of TDs in this study. The results show that there are 4.8 TDs formed in the SCS per year, and these TDs can be separated into 3.2 developing cases (DTDs) and 1.6 nondeveloping cases (NTDs) according to whether they intensify into tropical storms. Further objective classification by the multivariable-time empirical orthogonal function (MVT-EOF) method finds that the weakening cases in the positive-PC1 (the first principle component) mode occur in May–September, with the reason for weakening being a shortage of moisture. The decrease of westerly wind south of the NTDs reduces the water vapor transportation from the Indian Ocean. Binary TCs in the northwestern Pacific acquire water vapor from the eastern boundary of the SCS NTDs. Meanwhile, the weak high-level divergence and low-level convergence are not enough for the accumulation of local moisture and maintaining local convections inside the NTDs. The weakening cases in negative-PC1 mode occur in October–December with the reason for weakening being the invasion of cold air from the north. Strong cold air advection in the lower troposphere increases the vertical wind shear in front of the NTDs, and sharply reduce sensible and latent heat flux as well. Seasonal dependence exists in the causes of the SCS NTDs weakening.
Peripheral bronchial luminal conspicuity on dynamic-ventilation computed tomography: association with radiation doses and temporal resolution by using an ex vivo porcine lung phantom
Authors: Nagatani Yukihiro , Yoshigoe Makoto , Tsukagoshi Shinsuke , Ushio Noritoshi , Ohashi Kohei , Nitta Norihisa , Kimoto Tatsuya , Uranishi Ayumi , Sato Shigetaka , Mayumi Masayuki , Yamashiro Tsuneo , Moriya Hiroshi , Murata Kiyoshi , Watanabe Yoshiyuki ,   for the investigators of ACTIve study group
Published: March 2020

Background It is still unclear which image reconstruction algorithm is appropriate for peripheral bronchial luminal conspicuity (PBLC) on dynamic-ventilation computed tomography (DVCT). Purpose To assess the influence of radiation doses and temporal resolution (TR) on the association between movement velocity (MV) and PBLC on DVCT. Material and Methods An ex vivo porcine lung phantom with simulated respiratory movement was scanned by 320-row CT at 240 mA and 10 mA. Peak and dip CT density and luminal area adjusted by values at end-inspiration (CTDpeak and CTDdip, luminal area ratio [LAR]) for PBLC and MVs were measured and visual scores (VS) were obtained at 12 measurement points on 13 frame images obtained at half and full reconstructions (TR 340 and 190 ms) during expiration. Size-specific dose estimate (SSDE) was applied to presume radiation dose. VS, CTDpeak, CTDdip, LAR, and their cross-correlation coefficients with MV (CCC) were compared among four methods with combinations of two reconstruction algorithms and two doses. Results The dose at 10 mA was presumed as 26 mA by SSDE for standard proportion adults. VS, CTDdip, CTDpeak, and LAR with half reconstruction at 10 mA (2.52 ± 0.59, 1.016 ± 0.221, 0.948 ± 0.103, and 0.990 ± 0.527) were similar to those at 240 mA except for VS, and different from those with full reconstruction at both doses (2.24 ± 0.85, 0.830 ± 0.209, 0.986 ± 0.065, and 1.012 ± 0.438 at 240 mA) ( P < 0.05). CCC for CTDdip with half reconstruction (–0.024 ± 0.552) at 10 mA was higher compared with full reconstruction (–0.503 ± 0.291) ( P < 0.05). Conclusion PBLC with half reconstruction at 10 mA was comparable to that at 240 mA and better than those with full reconstruction on DVCT.