bluuebunny/crossref_metadata_2025_split huggingface dataset:
von Willebrand Factor: A Central Regulator of Arteriovenous Fistula Maturation Through Smooth Muscle Cell Proliferation and Outward Remodeling
Authors: Laboyrie Suzanne L. , de Vries Margreet R. , de Jong Alwin , de Boer Hetty C. , Lalai Reshma A. , Martinez Laisel , Vazquez‐Padron Roberto I. , Rotmans Joris I. 
Published: August 2022

Background
Arteriovenous fistula (AVF) maturation failure is a main limitation of vascular access. Maturation is determined by the intricate balance between outward remodeling and intimal hyperplasia, whereby endothelial cell dysfunction, platelet aggregation, and vascular smooth muscle cell (VSMC) proliferation play a crucial role. von Willebrand Factor (vWF) is an endothelial cell–derived protein involved in platelet aggregation and VSMC proliferation. We investigated AVF vascular remodeling in vWF‐deficient mice and vWF expression in failed and matured human AVFs.

Methods and Results

Jugular‐carotid AVFs were created in wild‐type and vWF
−/−
mice. AVF flow was determined longitudinally using ultrasonography, whereupon AVFs were harvested 14 days after surgery. VSMCs were isolated from vena cavae to study the effect of vWF on VSMC proliferation. Patient‐matched samples of the basilic vein were obtained before brachio‐basilic AVF construction and during superficialization or salvage procedure 6 weeks after AVF creation. vWF deficiency reduced VSMC proliferation and macrophage infiltration in the intimal hyperplasia. vWF
−/−
mice showed reduced outward remodeling (1.5‐fold,
P
=0.002) and intimal hyperplasia (10.2‐fold,
P
<0.0001). AVF flow in wild‐type mice was incremental over 2 weeks, whereas flow in vWF
−/−
mice did not increase, resulting in a two‐fold lower flow at 14 days compared with wild‐type mice (
P
=0.016). Outward remodeling in matured patient AVFs coincided with increased local vWF expression in the media of the venous outflow tract. Absence of vWF in the intimal layer correlated with an increase in the intima‐media ratio.

Conclusions
vWF enhances AVF maturation because its positive effect on outward remodeling outweighs its stimulating effect on intimal hyperplasia.
Characterization of Polyvascular Disease in Heterozygous Familial Hypercholesterolemia: Its Association With Circulating Lipoprotein(a) Levels
Authors: Funabashi Sayaka , Kataoka Yu , Hori Mika , Ogura Masatsune , Doi Takahito , Noguchi Teruo , Harada‐Shiba Mariko 
Published: August 2022

Background
Heterozygous familial hypercholesterolemia (HeFH) more likely exhibits extensive atherosclerotic disease at multiple vascular beds. Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein that elevates HeFH‐related atherosclerotic cardiovascular disease risks. Whether circulating Lp(a) level associates with polyvascular propagation of atherosclerosis in subjects with HeFH remains uncertain.

Methods and Results

The current study analyzed 370 subjects with clinically diagnosed HeFH who received evaluation of systemic arteries. Polyvascular disease (polyVD) was defined as more than 2 coexisting atherosclerosis conditions including coronary artery disease, carotid stenosis, or peripheral artery disease. Clinical characteristics and lipid features were analyzed in subjects with HeFH and polyVD; 5.7% of patients with HeFH (21/370) had polyVD. They were more likely to have a clustering of risk factors, tendon (
P
<0.001) and skin xanthomas (
P
=0.004), and corneal arcus (
P
=0.026). Furthermore, an elevated Lp(a) level (
P
=0.006) and a greater frequency of Lp(a) level ≥50 mg/dL (
P
<0.001) were observed in subjects with HeFH and polyVD. On multivariable analysis adjusting risk factors and lipid‐lowering agents, Lp(a) ≥50 mg/dL (odds ratio [OR], 5.66 [95% CI, 1.68–19.0],
P
=0.005), age, and family history of premature coronary artery disease independently predicted polyVD in subjects with HeFH. Of note, the prevalence of polyVD rose to 33.3% in patients with HeFH and age >58 years old, family history of premature coronary artery disease, and Lp(a) ≥50 mg/dL (OR, 10.3 [95% CI, 3.12–33.4],
P
<0.001).

Conclusions
An increased level of circulating Lp(a) levels predicted concomitance of polyVD in patients with HeFH. The current findings suggest subjects with HeFH and Lp(a) ≥50 mg/dL as a high‐risk category who require meticulous screening of systemic vascular beds.
Prevalence of Mitral Annulus Disjunction and Mitral Valve Prolapse in Patients With Idiopathic Ventricular Fibrillation
Authors: Groeneveld Sanne A. , Kirkels Feddo P. , Cramer Maarten J. , Evertz Reinder , Haugaa Kristina H. , Postema Pieter G. , Prakken Niek H. J. , Teske Arco J. , Wilde Arthur A. M. , Velthuis Birgitta K. , Nijveldt Robin , Hassink Rutger J. 
Published: August 2022

Background
Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with ventricular fibrillation of which the origin is not identified after extensive evaluations. Recent studies suggest an association between mitral annulus disjunction (MAD), mitral valve prolapse (MVP), and ventricular arrhythmias. The prevalence of MAD and MVP in patients with IVF in this regard is not well established. We aimed to explore the prevalence of MAD and MVP in a consecutive cohort of patients with IVF compared with matched controls.

Methods and Results

In this retrospective, multicenter cohort study, cardiac magnetic resonance images from patients with IVF (ie, negative for ischemia, cardiomyopathy, and channelopathies) and age‐ and sex‐matched control subjects were analyzed for the presence of MAD (≥2 mm) and MVP (>2 mm). In total, 72 patients (mean age 39±14 years, 42% women) and 72 control subjects (mean age 41±11 years, 42% women) were included. MAD in the inferolateral wall was more prevalent in patients with IVF versus healthy controls (7 [11%] versus 1 [1%],
P
=0.024). MVP was only seen in patients with IVF and not in controls (5 [7%] versus 0 [0%],
P
=0.016). MAD was observed in both patients with (n=4) and without (n=3) MVP.

Conclusions
Inferolateral MAD and MVP were significantly more prevalent in patients with IVF compared with healthy controls. The authors advocate that evaluation of the mitral valve region deserves extra attention in the extensive screening of patients with unexplained cardiac arrest. These findings support further exploration of the pathophysiological mechanisms underlying a subset of IVF that associates with MAD and MVP.
Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach
Authors: Hoek Anna G. , van Oort Sabine , Elders Petra J. M. , Beulens Joline W. J. 
Published: August 2022

Background
We investigated the causal associations between the genetic liability to cardiovascular and lifestyle risk factors and peripheral artery disease (PAD), using a Mendelian randomization approach.

Methods and Results

We performed a 2‐sample inverse‐variance weighted Mendelian randomization analysis, multiple sensitivity analyses to assess pleiotropy and multivariate Mendelian randomization analyses to assess mediating/confounding factors. European‐ancestry genomic summary data (
P
<5×10
−8
) for type 2 diabetes, lipid‐fractions, smoking, alcohol and coffee consumption, physical activity, sleep, and education level were selected. Genetic associations with PAD were extracted from the Million‐Veteran‐Program genome‐wide association studies (cases=31 307, controls=211 753, 72% European‐ancestry) and the GoLEAD‐SUMMIT genome‐wide association studies (11 independent genome‐wide association studies, European‐ancestry, cases=12 086, controls=449 548). Associations were categorized as robust (Bonferroni‐significant (
P
<0.00294), consistent over PAD‐cohorts/sensitivity analyses), suggestive (
P
value: 0.00294–0.05, associations in 1 PAD‐cohort/inconsistent sensitivity analyses) or not present. Robust evidence for genetic liability to type 2 diabetes, smoking, insomnia, and inverse associations for higher education level with PAD were found. Suggestive evidence for the genetic liability to higher low‐density lipoprotein cholesterol, triglyceride‐levels, alcohol consumption, and inverse associations for high‐density lipoprotein cholesterol, and increased sleep duration were found. No associations were found for physical activity and coffee consumption. However, effects fully attenuated for low‐density lipoprotein cholesterol and triglycerides after correcting for apoB, and for insomnia after correcting for body mass index and lipid‐fractions. Nonsignificant attenuation by potential mediators was observed for education level and type 2 diabetes.

Conclusions
Detrimental effects of smoking and type 2 diabetes, but not of low‐density lipoprotein cholesterol and triglycerides, on PAD were confirmed. Lower education level and insomnia were identified as novel risk factors for PAD; however, complete mediation for insomnia and incomplete mediation for education level by downstream risk factors was observed.
What Does the ‘Responsibility to Protect’ Require of States in Ukraine?
Authors: Barber Rebecca 
Published: August 2022

Abstract
This article considers what the responsibility to protect populations from atrocity crimes (R2P) requires States to do in Ukraine. It begins by considering how the R2P’s ‘three-pillar’ implementation strategy is to be understood in relation to a situation in which atrocities are being perpetrated not by a State against its own population but by an aggressor State; and then considers the parallels between what is required of States by the political commitment to the R2P, and what is required by the legal obligations to prevent genocide and to cooperate to end serious breaches of peremptory norms. The second part of the article then considers a series of options that may be pursued by States in fulfilment of their R2P and corresponding legal obligations, from options falling short of military intervention (including legal proceedings, economic and diplomatic sanctions and military assistance) through to the possibilities of unilateral military intervention and UN peacekeeping.
Tropical Anomalies Associated with the Interannual Variability of the Cross-Equatorial Flows over the Maritime Continent in Boreal Summer
Authors: Zhao Xiaoxuan , Lu Riyu , Dong Buwen , Hong Xiaowei , Liu Junqi , Sun Jianqi 
Published: August 2022

Abstract
In this study, we investigate circulation, convection, and sea surface temperature (SST) anomalies associated with interannual variability of the cross-equatorial flow (CEF) intensity over the Maritime Continent (MC) in boreal summer. Observational diagnostics show that strengthened CEF is associated with large-scale circulation anomalies featuring weakened Walker circulation, upper-level northeasterly anomalies across the MC, and lower-level cyclonic anomalies over the tropical western North Pacific (WNP). Further analyses indicate that strengthened CEF is associated with both La Niña–like SST anomalies in the preceding winter and El Niño–like SST anomalies in the simultaneous summer. These relationships between CEF and ENSO are established by two key convection regions: enhanced convection over WNP and depressed convection over the MC. A linear baroclinic model is applied here to further discuss the causality between circulation and convection. Results suggest that both the WNP heating and MC cooling can induce the strengthened CEF. Moreover, the stability of the relationship between CEF and El Niño–Southern Oscillation (ENSO) is also discussed. Results show that the relationship between CEF and SST anomalies in the simultaneous summer is stable and remains significant, whereas that between CEF and SST anomalies in the preceding winter experienced a decadal strengthening around 1997/98 from insignificant to significant. After 1998, the preceding winter ENSO is followed by strong summer SST anomalies in the MC that significantly affect CEF via modulating local convection. However, this ENSO–summer MC SST relationship is weak before 1997, failing to establish the relationship between the preceding ENSO and CEF.
ENSO Asymmetry in CMIP6 Models
Authors: Zhao Yaodi , Sun De-Zheng 
Published: August 2022

Abstract
An interesting aspect of the El Niño–Southern Oscillation (ENSO) phenomenon is the asymmetry between its two phases. This paper evaluates the simulations of this property of ENSO by the Coupled Model Intercomparison Project phase 6 (CMIP6) models. Both the surface and subsurface signals of ENSO are examined for this purpose. The results show that the models still underestimate ENSO asymmetry as shown in the SST field, but do a better job in the subsurface. A much weaker negative feedback from the net surface heat flux during La Niña in the models is identified as a factor causing the degradation of the ENSO asymmetry at the surface. The simulated asymmetry in the subsurface is still weaker than the observations owing to a weaker dynamic coupling between the atmosphere and ocean. Consistent with the finding of a weaker dynamic coupling strength, the precipitation response to the SST changes is also found to be weaker in the models. The results underscore that a more objective assessment of the simulation of ENSO by climate models may have to involve the examination of the subsurface signals. Future improvements in simulating ENSO will likely require a better simulation of the surface heat flux feedback from the atmosphere as well as the dynamical coupling strength between the atmosphere and ocean.

Significance Statement
The ENSO phenomenon affects weather and climate worldwide. An interesting aspect of this phenomenon is the asymmetry between its two phases. Previous studies have reported a weaker asymmetry in the simulations by climate models. But these studies have focused on the ENSO asymmetry at the surface. Here by examining the ENSO asymmetry at the surface and the subsurface, we have found that ENSO asymmetry is better simulated in the subsurface than at the surface. We have also identified factors that are responsible for the degradation of the ENSO asymmetry at the surface as well as the remaining weakness in the subsurface, pointing out specific pathways to take to further improve ENSO simulations by coupled climate models.
Seasonality and Variability of Snowfall to Total Precipitation Ratio over High Mountain Asia Simulated by the GFDL High-Resolution AM4
Authors: Dong Wenhao , Ming Yi 
Published: August 2022

Abstract
The ratio of snowfall to total precipitation (S/P ratio) is an important metric that is widely used to detect and monitor hydrologic responses to climate change over mountainous areas. Changes in the S/P ratio over time have proved to be reliable indicators of climatic warming. In this study, the seasonality and interannual variability of monthly S/P ratios over High Mountain Asia (HMA) have been examined during the period 1950–2014 based on a three-member ensemble of simulations using the latest GFDL AM4 model. The results show a significant decreasing trend in S/P ratios during the analysis period, which has mainly resulted from reductions in snowfall, with increases in total precipitation playing a secondary role. Significant regime shifts in S/P ratios are detected around the mid-1990s, with rainfall becoming the dominant form of precipitation over HMA after the changepoints. Attribution analysis demonstrates that increases in rainfall during recent decades were primarily caused by a transformation of snowfall to rainfall as temperature warmed. A logistic equation is used to explore the relationship between the S/P ratio and surface temperature, allowing calculation of a threshold temperature at which the S/P ratio equals 50% (i.e., precipitation is equally likely to take the form of rainfall or snowfall). These temperature thresholds are higher over higher elevations. This study provides an extensive evaluation of simulated S/P ratios over the HMA that helps clarify the seasonality and interannual variability of this metric over the past several decades. The results have important socioeconomic and environmental implications, particularly with respect to water management in Asia under climate change.
Seasonal and Year-To-Year Variability of Boundary Currents and Eddy Salt Flux along the Eastern and Southern Coasts of Sri Lanka Observed by PIES and Satellite Measurements
Authors: Anutaliya A. , Send U. , McClean J. L. , Sprintall J. , Lankhorst M. , Lee C. M. , Rainville L. , Priyadarshani W. N. C. , Jinadasa S. U. P. 
Published: August 2022

Abstract
Boundary currents along the Sri Lankan eastern and southern coasts serve as a pathway for salt exchange between the Bay of Bengal and the Arabian Sea basins in the northern Indian Ocean, which are characterized by their contrasting salinities. Measurements from two pairs of pressure-sensing inverted echo sounders (PIES) deployed along the Sri Lankan eastern and southern coasts as well as satellite measurements are used to understand the variability of these boundary currents and the associated salt transport. The volume transport in the surface (0–200-m depth) layer exhibits a seasonal cycle associated with the monsoonal wind reversal and interannual variability associated with the Indian Ocean dipole (IOD). In this layer, the boundary currents transport low-salinity water out of the Bay of Bengal during the northeast monsoon and transport high-salinity water into the Bay of Bengal during the fall monsoon transition of some years (e.g., 2015 and 2018). The Bay of Bengal salt input increases during the 2016 negative IOD as the eastward flow of high-salinity water during the fall monsoon transition intensifies, whereas the effect of the 2015/16 El Niño on the Bay of Bengal salt input is still unclear. The time-mean eddy salt flux over the upper 200 m estimated for the April 2015–March 2019 period along the eastern coast accounts for 9% of the salt budget required to balance an estimated 0.13 Sv (1 Sv ≡ 106 m3 s−1) of annual freshwater input into the Bay of Bengal. The time-mean eddy salt flux over the upper 200 m estimated for the December 2015–November 2019 period along the southern coast accounts for 27% of that same salt budget.

Significance Statement
In the northern Indian Ocean, the highly saline Arabian Sea undergoes extreme evaporation while the Bay of Bengal (BoB) receives excess freshwater input. The focus of this study is the role of the observed time-variable circulation around Sri Lanka that permits the exchange between these basins to maintain their salinity distributions. The circulation fluctuates seasonally following the monsoon wind reversal and interannually in response to large-scale climate modes. The BoB freshwater export around Sri Lanka occurs during the northeast monsoon, whereas saline water import occurs during the fall monsoon transition of some years. However, rapid changes in both water volume transport and salt exchange can occur. The circulation over 0–200-m depth transports ∼9%–27% of the BoB salt budget.
The evolution of charcoal-burning suicide: A systematic scoping review
Authors: Yeung Cheuk Yui , Men Vera Yu , Yip Paul Siu Fai 
Published: August 2022

Introduction: Suicide by charcoal burning has accounted for more than 100,000 deaths. It has become an increasingly common suicide method in Hong Kong since first reported in 1998, and it has spread into South Korea, Taiwan, Japan and other countries. This systematic scoping review aimed to explore current evidence on trends, risk factors, impact of media and prevention strategies for this suicide method, and to identify research gaps. Methods: A search for articles published from January 1998 to June 2021 was conducted through electronic databases (MEDLINE, EMBASE, SCOPUS and PsycINFO) with the keywords (suicide*) AND (charcoal). Articles describing prevalence, trends, characteristics, risk factors and prevention strategies of charcoal burning suicide deaths were included. Non-peer-reviewed articles, non-English articles, commentaries/editorials/letters, poster abstracts, reviews, meta-analyses and studies that documented only charcoal burning suicide attempters/survivors were excluded. Results: Eighty-eight studies were identified, most from East Asia. Charcoal burning suicide rates in Hong Kong, Taiwan and Japan has passed the peak, while continuing to increase in South Korea. Risk factors are changing and not static. Media appears to play an important role in triggering and spreading information. Restricting access to charcoal, and raising public awareness have been effective in the short term in preventing charcoal burning suicide, but there is little information on their long-term effectiveness or sustainability. Discussion: More research is required to update the development and dynamic changes of charcoal burning suicide and the contributing factors. The evidence from this review may assist in detecting and intervening early for future novel suicide methods.
Longitudinal Impacts of Simulated Long-Duration Spaceflight Missions on Operationally Relevant Measures of Human Performance Using a Portable Simulation Platform
Authors: Stankovic Aleksandra S. , Pryputniewicz Alyssa , Holder Sherrie , York Stephen P. , Handley Patrick M. , Karasinski John A. , Robinson Stephen K. , West John J. , Duda Kevin R. 
Published: August 2022

Objective This project quantifies operationally relevant measures of flight performance and workload in a high-fidelity long-duration spaceflight analog, longitudinally across mission duration, using a portable simulation platform. Background Real-time performance measures allow for the objective assessment of task performance and the timely identification of performance degradations. Methods Measures of flight performance on a piloted lunar lander task were collected on 32 total crewmembers across 8 simulated space missions of 45 days each (623 total sessions). Results Mission duration demonstrated a significant effect on measures of flight performance across all campaigns. Flight measures showed a general pattern of peaking in accuracy during the middle-late quartiles of overall mission time, then degrading again towards baseline. On the workload measure, however, a general linear decrease in workload consistent with progressive task learning was observed in both campaigns. Conclusion This investigation demonstrated the disruptive effect of time in mission on some, but not all, aspects of task performance. While mission interval differentially impacted measures of flight accuracy, workload, by contrast, seemed to steadily decrease with in-mission time. Application While more work is needed, the observed discrepancy between progression of flight performance and workload assessment highlights the importance of sensitive and specific measurement tools for the tracking of distinct performance metrics.
Geometrical Effects of Two Different Space Closing Loops and Its Forces and Moments—A FEM Study
Authors: Arathi Gurunath Nupur , Bharadwaj Rekha , Venkateswaran Sundaram , Krishnaswamy Nathamuni Rengarajan 
Published: August 2022

Objective To evaluate the geometrical effects of double keyhole loop (DKHL) and T-loop and its forces and moments during en mass space closure using finite element method. Materials and Methods A 3-dimensional finite element model of maxillary arch was created and stimulated for first premolar extraction case with 0.022 slot Roth prescription bracket. DKHL and T-loop arch wire were created using 19×25 stainless steel and was opened 1 mm for activation using 2 different methods. The study was divided into 2 groups based on the loop design, method of activation, and degree of Gable bend. The stress distribution, tooth displacement, and moment-force ratio were calculated. Result The overall stress distribution was more or less uniform in all the groups. However, maximum von Mises stress was observed in the second premolar region for both the groups. There was greater torque and vertical control in the anterior segment and better anchorage control in posterior segment with increase in degree of Gable bend for both the loops activated using ligature tie. Moment-force ratio of 8-10 was achieved for both the loops. Conclusion Therefore, DKHL was as efficient as T-loop in producing the desirable biomechanical properties during en mass space closure.