bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin β1D Deficiency–Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Wang Yihui , Li Chunyan , Shi Ling , Chen Xiuyu , Cui Chen , Huang Jinhua , Chen Biyi , Hall Duane D. , Pan Zhenwei , Lu Minjie , Hong Jiang , Song Long-Sheng , Zhao Shihua 
Published: March 2020

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias, and increased risk of sudden cardiac death. The guideline for management of ARVC in patients is to improve quality of life by reducing arrhythmic symptoms and to prevent sudden cardiac death. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood.

Methods:

Using protein mass spectrometry analyses, we identified that integrin β1 is downregulated in ARVC hearts without changes to Ca
2+
-handling proteins. As adult cardiomyocytes express only the β1D isoform, we generated a cardiac specific β1D knockout mouse model and performed functional imaging and biochemical analyses to determine the consequences of integrin β1D loss on function in the heart in vivo and in vitro.

Results:

Integrin β1D deficiency and RyR2 Ser-2030 hyperphosphorylation were detected by Western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found that purified integrin β1D protein could stabilize RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time. Also, β1D knockout mice exhibited normal cardiac function and morphology but presented with catecholamine-sensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca
2+
handling in β1D knockout cardiomyocytes. Mechanistically, we revealed that loss of DSP (desmoplakin) induces integrin β1D deficiency in ARVC mediated through an ERK1/2 (extracellular signal–regulated kinase 1 and 2)–fibronectin–ubiquitin/lysosome pathway.

Conclusions:
Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.
Effect of Steady and Dynamic Blood Pressure Parameters During Thrombectomy According to the Collateral Status
Authors: Maïer Benjamin , Dargazanli Cyril , Bourcier Romain , Kyheng Maëva , Labreuche Julien , Mosimann Pascal J. , Puccinelli Francesco , Taylor Guillaume , Le Guen Morgan , Riem Romuald , Desilles Jean-Philippe , Boisseau William , Fahed Robert , Redjem Hocine , Smajda Stanislas , Ciccio Gabriele , Escalard Simon , Blanc Raphaël , Piotin Michel , Lapergue Betrand , Mazighi Mikael ,   on behalf of the ASTER Trial
Published: March 2020

Background and Purpose—
Guidelines regarding blood pressure (BP) management during endovascular therapy (EVT) for anterior circulation strokes are questionable since the optimal BP target is a matter of debate. To evaluate the importance of hemodynamic control during EVT, we investigated the impact of dynamic and steady BP parameters during EVT on functional outcome (part 1) and according to the collateral status (CS; part 2).

Methods—
We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Recanalization). BP was measured noninvasively during EVT and CS assessed on the angiographic run before EVT. We studied dynamic BP parameter using BP variability (coefficient of variation) and steady BP parameter (hypotension time defined as systolic BP <140 mm Hg and mean arterial pressure <90 mm Hg). The primary outcome was favorable outcome defined as a 3-month modified Rankin Scale score between 0 and 2.

Results—

Among the 381 patients of the ASTER study, 172 patients were included in part 1 and 159 in part 2. Systolic BP, diastolic BP, and mean arterial pressure variability were negatively associated with favorable outcome regardless of CS: per 10-unit increase, adjusted odds ratios were 0.45 (95% CI, 0.20–0.98), 0.37 (95% CI, 0.19–0.72), and 0.35 (95% CI, 0.16–0.76), respectively. According to CS, the hypotension time with periprocedural mean arterial pressure <90 mm Hg was negatively associated with favorable outcome in patients with poor CS (adjusted odds ratio, 0.88 [95% CI, 0.72–1.09]) but not in patients with good CS (adjusted odds ratio, 1.24 [95% CI, 0.91–1.67];
P
het
=0.047).

Conclusions—
The CS did not modify the association between dynamic parameters and functional outcomes, but some findings suggest that the CS modifies the association between steady parameter and functional outcomes. Hypotension time according to the CS was not statistically predictive of poor outcomes but displayed a trend toward worse outcomes for patients with poor CS only.
Electrocardiographic ST-T Abnormities Are Associated With Stroke Risk in the REGARDS Study
Authors: Sawano Mitsuaki , Yuan Ya , Kohsaka Shun , Inohara Taku , Suzuki Takeki , Okamura Tomonori , Howard George , Howard Virginia J. , Judd Suzanne , Soliman Elsayed Z. , Cushman Mary 
Published: March 2020

Background and Purpose—
In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear.

Methods—
The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs.

Results—
Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05–1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00–1.62]) and did not differ by age, race, or sex.

Conclusions—
Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.
Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction–Mediated Cell-Cell Interaction
Authors: Kikuchi-Taura Akie , Okinaka Yuka , Takeuchi Yukiko , Ogawa Yuko , Maeda Mitsuyo , Kataoka Yosky , Yasui Teruhito , Kimura Takafumi , Gul Sheraz , Claussen Carsten , Boltze Johannes , Taguchi Akihiko 
Published: March 2020

Background and Purpose—
Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. Activation of angiogenesis is believed to be one of major BM-MNC mode of actions, but the essential mechanism by which BM-MNCs activate angiogenesis have hitherto been elusive. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis.

Methods—
We have evaluated the effect of direct cell-cell interaction between BM-MNC and endothelial cell on uptake of VEGF (vascular endothelial growth factor) into endothelial cells in vitro. Cerebral ischemia model was used to evaluate the effects of direct cell-cell interaction with transplanted BM-MNC on endothelial cell at ischemic tissue.

Results—
The uptake of VEGF into endothelial cells was increased by BM-MNC, while being inhibited by blockading the gap junction. Low-molecular-weight substance was transferred from BM-MNC into endothelial cells via gap junctions in vivo, followed by increased expression of hypoxia-inducible factor-1α and suppression of autophagy in endothelial cells. The concentration of glucose in BM-MNC cytoplasm was significantly higher than in endothelial cells, and transfer of glucose homologue from BM-MNC to endothelial cells was observed.

Conclusions—
Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy.

Visual Overview—

An online
visual overview
is available for this article.
Soluble ST2 Is Associated With New Epileptiform Abnormalities Following Nontraumatic Subarachnoid Hemorrhage
Authors: Lissak India A. , Zafar Sahar F. , Westover M. Brandon , Schleicher Riana L. , Kim Jennifer A. , Leslie-Mazwi Thabele , Stapleton Christopher J. , Patel Aman B. , Kimberly W. Taylor , Rosenthal Eric S. 
Published: March 2020

Background and Purpose—
We evaluated the association between 2 types of predictors of delayed cerebral ischemia after nontraumatic subarachnoid hemorrhage, including biomarkers of the innate immune response and neurophysiologic changes on continuous electroencephalography.

Methods—
We studied subarachnoid hemorrhage patients that had at least 72 hours of continuous electroencephalography and blood samples collected within the first 5 days of symptom onset. We measured inflammatory biomarkers previously associated with delayed cerebral ischemia and functional outcome, including soluble ST2 (sST2), IL-6 (interleukin-6), and CRP (C-reactive protein). Serial plasma samples and cerebrospinal fluid sST2 levels were available in a subgroup of patients. Neurophysiologic changes were categorized into new or worsening epileptiform abnormalities (EAs) or new background deterioration. The association of biomarkers with neurophysiologic changes were evaluated using the Wilcoxon rank-sum test. Plasma and cerebrospinal fluid sST2 were further examined longitudinally using repeated measures mixed-effects models.

Results—

Forty-six patients met inclusion criteria. Seventeen (37%) patients developed new or worsening EAs, 21 (46%) developed new background deterioration, and 8 (17%) developed neither. Early (day, 0–5) plasma sST2 levels were higher among patients with new or worsening EAs (median 115 ng/mL [interquartile range, 73.8–197]) versus those without (74.7 ng/mL [interquartile range, 44.8–102];
P
=0.024). Plasma sST2 levels were similar between patients with or without new background deterioration. Repeated measures mixed-effects modeling that adjusted for admission risk factors showed that the association with new or worsening EAs remained independent for both plasma sST2 (β=0.41 [95% CI, 0.09–0.73];
P
=0.01) and cerebrospinal fluid sST2 (β=0.97 [95% CI, 0.14–1.8];
P
=0.021). IL-6 and CRP were not associated with new background deterioration or with new or worsening EAs.

Conclusions—
In patients admitted with subarachnoid hemorrhage, sST2 level was associated with new or worsening EAs but not new background deterioration. This association may identify a link between a specific innate immune response pathway and continuous electroencephalography abnormalities in the pathogenesis of secondary brain injury after subarachnoid hemorrhage.
Performance Limitations in Sensorimotor Control: Trade-Offs Between Neural Computation and Accuracy in Tracking Fast Movements
Authors: Saxena Shreya , Sarma Sridevi V. , Dahleh Munther 
Published: March 2020

AbstractThe ability to move fast and accurately track moving objects is fundamentally constrained by the biophysics of neurons and dynamics of the muscles involved. Yet the corresponding trade-offs between these factors and tracking motor commands have not been rigorously quantified. We use feedback control principles to quantify performance limitations of the sensorimotor control system (SCS) to track fast periodic movements. We show that (1) linear models of the SCS fail to predict known undesirable phenomena, including skipped cycles, overshoot and undershoot, produced when tracking signals in the “fast regime,” while nonlinear pulsatile control models can predict such undesirable phenomena, and (2) tools from nonlinear control theory allow us to characterize fundamental limitations in this fast regime. Using a validated and tractable nonlinear model of the SCS, we derive an analytical upper bound on frequencies that the SCS model can reliably track before producing such undesirable phenomena as a function of the neurons' biophysical constraints and muscle dynamics. The performance limitations derived here have important implications in sensorimotor control. For example, if the primary motor cortex is compromised due to disease or damage, the theory suggests ways to manipulate muscle dynamics by adding the necessary compensatory forces using an assistive neuroprosthetic device to restore motor performance and, more important, fast and agile movements. Just how one should compensate can be informed by our SCS model and the theory developed here.
Comparison of Different Spike Train Synchrony Measures Regarding Their Robustness to Erroneous Data From Bicuculline-Induced Epileptiform Activity
Authors: Ciba Manuel , Bestel Robert , Nick Christoph , de Arruda Guilherme Ferraz , Peron Thomas , Henrique Comin César , Costa Luciano da Fontoura , Rodrigues Francisco Aparecido , Thielemann Christiane 
Published: March 2020

Abstract
As synchronized activity is associated with basic brain functions and pathological states, spike train synchrony has become an important measure to analyze experimental neuronal data. Many measures of spike train synchrony have been proposed, but there is no gold standard allowing for comparison of results from different experiments. This work aims to provide guidance on which synchrony measure is best suited to quantify the effect of epileptiform-inducing substances (e.g., bicuculline, BIC) in in vitro neuronal spike train data. Spike train data from recordings are likely to suffer from erroneous spike detection, such as missed spikes (false negative) or noise (false positive). Therefore, different timescale-dependent (cross-correlation, mutual information, spike time tiling coefficient) and timescale-independent (Spike-contrast, phase synchronization (PS), A-SPIKE-synchronization, A-ISI-distance, ARI-SPIKE-distance) synchrony measures were compared in terms of their robustness to erroneous spike trains. For this purpose, erroneous spike trains were generated by randomly adding (false positive) or deleting (false negative) spikes (in silico manipulated data) from experimental data. In addition, experimental data were analyzed using different spike detection threshold factors in order to confirm the robustness of the synchrony measures. All experimental data were recorded from cortical neuronal networks on microelectrode array chips, which show epileptiform activity induced by the substance BIC. As a result of the in silico manipulated data, Spike-contrast was the only measure that was robust to false-negative as well as false-positive spikes. Analyzing the experimental data set revealed that all measures were able to capture the effect of BIC in a statistically significant way, with Spike-contrast showing the highest statistical significance even at low spike detection thresholds. In summary, we suggest using Spike-contrast to complement established synchrony measures because it is timescale independent and robust to erroneous spike trains.
Developmental costs of yellow colouration in fire salamanders and experiments to test the efficiency of yellow as a warning colouration
Authors: Caspers Barbara A. , Krause E. Tobias , Hermanski Isabelle , Wiesbrock Christopher , Kastrup Friedrich-Wilhelm , Steinfartz Sebastian 
Published: March 2020

Abstract
Warning colouration reduces predation risk by signalling or mimicking the unpleasantness of prey and therefore increases survival. We tested in two experiments the evolutionary costs and benefits of the yellow colour pattern in fire salamanders (Salamandra salamandra), which display a yellow/black colour pattern usually associated with toxic alkaloids. Our first experiment aimed to test whether the development of colouration is condition dependent and thus related to developmental costs, i.e. influenced by resource availability during the developmental process. Therefore, we reared fire salamander larvae under different nutritional conditions and compared the relative amount of yellow they developed after metamorphosis. Fire salamander larvae reared under limited food conditions had a lower proportion of yellow following metamorphosis than control larvae reared under superior food conditions. In a second experiment we tested whether the proportion of yellow has an impact on the risk of being attacked using artificial models. We tested, in salamander-free and salamander-occupied natural habitats, whether artificial clay models with different proportions of yellow and black receive different attack rates from potential predators (birds, mammals, insects). In clay models the proportion of yellow and the site had a significant effect on predation risk. Models with larger amounts of yellow had fewer bite marks from predators such as carabid beetles and birds, but only in sympatry with salamanders. In conclusion, the early expression of conspicuous colouration seems to be condition dependent and therefore potentially costly. Furthermore, the yellow colouration of fire salamanders act as a signal that potentially reduces their risk of being attacked by predators. Thus, the yellow colouration of fire salamanders seems to represent an adaptive trait that reduces the risk of predation, which can be expressed in higher quantity by individuals of a certain condition.
The Wave Climate of the Southern Ocean
Authors: Young Ian R. , Fontaine Emmanuel , Liu Qingxiang , Babanin Alexander V. 
Published: March 2020

AbstractThe wave climate of the Southern Ocean is investigated using a combined dataset from 33 years of altimeter data, in situ buoy measurements at five locations, and numerical wave model hindcasts. The analysis defines the seasonal variation in wind speed and significant wave height, as well as wind speed and significant wave height for a 1-in-100-year return period. The buoy data include an individual wave with a trough to crest height of 26.4 m and suggest that waves in excess of 30 m would occur in the region. The extremely long fetches, persistent westerly winds, and procession of low pressure systems that traverse the region generate wave spectra that are unique. These spectra are unimodal but with peak frequencies that propagate much faster than the local wind. This situation results in a unique energy balance in which waves at the spectra peak grow as a result of nonlinear transfer without any input from the local wind.
Hybrid Gain Data Assimilation Using Variational Corrections in the Subspace Orthogonal to the Ensemble
Authors: Chang Chih-Chien , Penny Stephen G. , Yang Shu-Chih 
Published: March 2020

AbstractThe viability of a parameterless hybrid data assimilation algorithm is investigated. As an alternative to the traditional hybrid covariance scheme, hybrid gain data assimilation (HGDA) was proposed to blend the gain matrix derived from the variational method and the ensemble-based Kalman filter (EnKF). A previously proposed HGDA algorithm uses a two-step process applying the EnKF with a variational update. The algorithm is modified here to limit the variational correction to the subspace orthogonal to the ensemble perturbation subspace without the use of a hybrid weighting parameter, as the optimization of such a parameter is nontrivial. The modified HGDA algorithm is investigated with a quasigeostrophic (QG) model. Results indicate that when the climatological background error covariance matrix B and the observation error covariance R are well estimated, state estimates from the parameterless HGDA are more accurate than the parameter-dependent HGDA. The parameterless HGDA not only has potential advantages over the standard HGDA as an online data assimilation algorithm but can also serve as a valuable diagnostic tool for tuning the B and R matrices. It is also found that in this QG model, the empirically best static B matrix for the stand-alone 3DVAR has high variance at larger spatial scales, which degrades the accuracy of the HGDA systems and may not be the best choice for hybrid methods in general. A comparison of defining the orthogonal subspace globally or locally demonstrates that global orthogonality is more advantageous for stabilizing the hybrid system and maintains large-scale balances.
A Quality Assessment of the Real-Time Mesoscale Analysis (RTMA) for Aviation
Authors: Morris Matthew T. , Carley Jacob R. , Colón Edward , Gibbs Annette , De Pondeca Manuel S. F. V. , Levine Steven 
Published: March 2020

Abstract
Missing observations at airports can cause delays in commercial and general aviation in the United States owing to Federal Aviation Administration (FAA) safety regulations. The Environmental Modeling Center (EMC) has provided interpolated temperature data from the National Oceanic and Atmospheric Administration’s Real-Time Mesoscale Analysis (RTMA) at airport locations throughout the United States since 2015, with these data substituting for missing temperature observations and mitigating impacts on air travel. A quality assessment of the RTMA is performed to determine if the RTMA could be used in a similar fashion for other weather observations, such as 10-m wind, ceiling, and visibility. Retrospective, data-denial experiments are used to perform the quality assessment by withholding observations from FAA-specified airports. Outliers seen in the RTMA ceiling and visibility analyses during events meeting or exceeding instrument flight rules suggest the RTMA should not be substituted for missing ceiling and visibility observations at this time. The RTMA is a suitable replacement for missing temperature observations for a subset of airports throughout most of the CONUS and Alaska, but not at all stations. Likewise, the RTMA is a suitable substitute for missing surface pressure observations at a subset of airports, with notable exceptions in regions of complex terrain. The RTMA may also be a suitable substitute for missing wind speed observations, provided the wind speed is ≤15 kt (1 kt ≈ 0.51 m s−1). Overall, these results suggest the potential for RTMA to substitute for additional missing observations while highlighting priority areas of future work for improving the RTMA.