bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of dominant loop in dual loop atrial tachycardia with direct graph mapping: an alternative for entrainment mapping?
Authors: Lowie L , Van Nieuwenhuyse E , Sanchez J , Panfilov A , Knecht S , Duytschaever M , Vandersickel N 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background
Entrainment mapping (EM) is an important tool to determine the mechanism of complex reentrant atrial tachycardias (ATs), mostly to distinguish dominant from bystander reentrant loops. However, entrainment maneuvers are challenging, time consuming and risk to end the tachycardia.
Purpose
Recently, we developed a novel method Directed Graph Mapping (DGM), using concepts of network theory, allowing to automatically determine AT reentry loops from the local activation times (LAT) of any clinical mapping system. DGM showed good performance: it correctly finds ablation target (100 % success rate) on simple AT cases and could automatically determine reentry loops confirmed by the expert electrophysiologist with EM in complex AT cases. Out of 32 single loop cases, 62.5 % was identified correctly with automated DGM and out of 6 true double loop cases, 83.3 %. Lower performance for single reentry complex cases compared to EM was mainly because DGM could not distinguish the dominant loop from additional bystander loops found by DGM. Hence, the purpose of this work was to develop additional algorithms which in case of multiple found DGM loops could automatically find the dominant loop and compare it with the results of EM.
Methods
We performed multiple simulations of various types of double loop reentry on a patient specific model of the left atrium. Based on a clinical case, double loops were simulated around a scar at the anterior wall (localized reentry) and the mitral valve (MV). LAT maps were determined similar as in the clinic. By varying the size of the scar in multiple steps, we obtained a transition from a regime of a dominant loop around the scar (small scar), to a true double loop and further to a regime of a dominant loop around the MV (large scar). We developed a novel DGM algorithm to determine the dominant loop from the region of collision (ROC) found from the vector field of the wavefront graph.
The developed method was also tested on 8 clinical cases of double loop ATs with EM measurements.
Results
Our algorithm found the location of the ROC and determined the correct dominant loop in 100% of the simulated data.
We tested this on 8 clinical cases of AT, and accuracy of the method was 75 %.
Conclusions
Determining the ROC in case of multiple loops in AT could correctly determine the dominant versus bystander loop, leading to the correct ablation target, without the need for further EM.
CaMKII as a therapeutic target in catecholaminergic polymorphic ventricular tachycardia type 1
Authors: Sadredini M , Manotheepan R , Haugsten Hansen M , Frisk M , Louch WE , Lehnart SE , Anderson ME , Sjaastad I , Stokke MK 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority

Background
In catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) adrenergic activation of the cardiac ryanodine receptor (RyR2) causes spontaneous calcium release and triggers arrhythmias. Calcium/calmodulin-dependent protein kinase II (CaMKII) can contribute to such arrhythmogenic calcium release and has been proposed as a therapeutic target in CPVT1. To predict the efficacy and safety of this strategy, it is necessary to know whether the mechanism for CaMKII activation is important for its arrhythmogenic effects, and if inhibition has proarrhythmic effects. We tested (1) if oxidation of CaMKII contributes to spontaneous calcium release in CPVT1 and (2) if inhibition of CaMKII in this condition can induce calcium alternans.

Methods
Mice with the CPVT1-causative mutation RyR2-R2474S (RyR2-RS) were crossed with mice with the CaMKII M281/282V (MMVV) mutation that prevents CaMKII M281/282 oxidation, to create double mutants (RyR2-RSxMMVV). Telemetric ECG surveillance was used to study in vivo arrhythmias following an adrenergic challenge by i.p. administration of the beta-adrenoceptor agonist isoprenaline. Confocal line-scan imaging and whole-cell calcium imaging were used to study arrhythmogenic calcium release in isolated left ventricular cardiomyocytes during stimulation with isoprenaline.

Results
As expected, RyR2-RS mice exhibited more arrhythmic events and spontaneous calcium release (i.e. calcium sparks and calcium waves) compared to wild-type mice. Treatment of RyR2-RS cardiomyocytes with either the CaMKII inhibitor KN-93 or the antioxidant n-acetyl-cysteine reduced spontaneous calcium release (i.e. calcium sparks and calcium waves, for KN-93 and n-acetyl-cysteine, respectively). Interestingly, CaMKII inhibition by KN-93 also increased both incidence and degree of arrhythmogenic calcium alternans in RyR2-RS cardiomyocytes. This adverse effect was a result of prolonged refractoriness of calcium release. Furthermore, to test whether the protective effect of antioxidant treatment in RyR2-RS was mediated via CaMKII oxidation, we compared arrhythmias and spontaneous calcium release (i.e. calcium waves) in RyR2-RSxMMVV with RyR2-RS. However, these two genotypes did not differ in either incidence or severity of arrhythmias, and showed similar degree of spontaneous calcium release.

Conclusions
Inhibition of CaMKII protects against spontaneous calcium release in CPVT1, and is a promising therapeutic strategy. However, the fact that such inhibition also induces calcium alternans needs further exploration. Antioxidative agents also attenuate arrhythmogenic calcium release in CPVT1 cardiomyocytes, but this effect does not seem to involve the M281/282 CaMKII oxidation site. Future studies should explore other oxidation sites.
Is selective late sodium current inhibition different from class I/B antiarrhythmic action? Comparison of the effects of GS967 to mexiletine in canine ventricular myocardium
Authors: Horvath B , Khan MN , Hezso T , Dienes C , Kovacs Z , Kiss D , Prorok J , Arpadffy-Lovas T , Varga R , Fujii E , Topal L , Kistamas K , Varro A , Virag L 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): National Research, Development and Innovation Office New National Excellence Programme
Enhancement of the late Na+ current (INa,late) increases arrhythmia propensity in the heart, while suppression of the current is antiarrhythmic. GS-458967 (GS) is an agent considered to be a selective blocker of INa,late. In the present study, effects of GS967 on INa,late, on L-type calcium current (ICaL), and on action potential (AP) morphology were studied in canine ventricular myocytes by using conventional voltage clamp, action potential voltage clamp and sharp microelectrode techniques. These effects of GS were compared to tetrodotoxin (TTX) and to the class I/B antiarrhythmic compound mexiletine.
GS (1 μM), mexiletine (40 μM) and TTX (10 μM) dissected largely similarly shaped inward currents under action potential voltage clamp conditions. In case of GS and mexiletine, the amplitude and integral of this inward current was significantly smaller when measured in the presence of 1 μM nisoldipine, while no difference was observed in case of TTX. Under conventional voltage clamp conditions, INa,late was significantly reduced by 1 μM GS and 40 μM mexiletine (about 79% and 63% reduction of current integrals, respectively). The integral of ICa,L was moderately but significantly decreased by both drugs (reduction of 9% and 14%, respectively). These changes were associated with a faster inactivation of ICa,L.
Drug effects on early Na+ current (INa,early) were assessed by analyzing the maximal rate of depolarization (V + max) in multicellular preparations. Both GS and mexiletine showed fast onset and offset kinetics: 110 ms and 289 ms offset time constants, respectively, as determined from V + max measurements in right ventricular papillary muscles, while the onset kinetics was characterized by 5.3 AP and 2.6 AP lengths, respectively, at 2.5 Hz.
Effects on beat-to-beat variability of AP duration (APD) was studied in isolated myocytes. Short-term variability was significantly decreased by both GS and mexiletine (average reduction of 42% and 24%, respectively) while they caused similar shortening of the APD.
The electrophysiological effects of GS are similar to those of mexiletine, but with a somewhat faster offset kinetics of V + max block. However, since GS reduced V+ max and INa,late in the same concentration, the currently accepted view that GS that selectively blocks INa,late has to be questioned and it is suggested that GS should be classified as a class I/B (or I/B + IV) antiarrhythmic agent.
How does the level of pulmonary venous isolation compare between pulsed field ablation and thermal energy ablation (radiofrequency, cryo, or laser)?
Authors: Kawamura Iwanari , Neuzil Petr , Shivamurthy Poojita , Kuroki Kenji , Lam Jeff , Musikantow Daniel , Chu Edward , Turagam Mohit K , Minami Kentro , Funasako Moritoshi , Petru Jan , Choudry Subbarao , Miller Marc A , Langan Marie-Noelle , Whang William , Dukkipati Srinivas R , Koruth Jacob S , Reddy Vivek Y 
Published: May 2021

Abstract

Aims
We studied the extent/area of electrical pulmonary vein isolation (PVI) after either pulsed field ablation (PFA) using a pentaspline catheter or thermal ablation technologies.

Methods and results
In a clinical trial (NCT03714178), paroxysmal atrial fibrillation (PAF) patients underwent PVI with a multi-electrode pentaspline PFA catheter using a biphasic waveform, and after 75 days, detailed voltage maps were created during protocol-specified remapping studies. Comparative voltage mapping data were retrospectively collected from consecutive PAF patients who (i) underwent PVI using thermal energy, (ii) underwent reablation for recurrence, and (iii) had durably isolated PVs. The left and right PV antral isolation areas and non-ablated posterior wall were quantified. There were 20 patients with durable PVI in the PFA cohort, and 39 in the thermal ablation cohort [29 radiofrequency ablation (RFA), 6 cryoballoon, and 4 visually guided laser balloon]. Pulsed field ablation patients were younger with shorter follow-up. Left atrial diameter and ventricular systolic function were preserved in both cohorts. There was no significant difference between the PFA and thermal ablation cohorts in either the left- and right-sided PV isolation areas, or the non-ablated posterior wall area. The right superior PV isolation area was smaller with PFA than RFA, but this disappeared after propensity score matching. Notch-like normal voltage areas were seen at the posterior aspect of the carina in the balloon sub-cohort, but not the PFA or RFA cohorts.

Conclusion
Catheter-based PVI with the pentaspline PFA catheter creates chronic PV antral isolation areas as encompassing as thermal energy ablation.
The bound executive: Emergency powers during the pandemic
Authors: Ginsburg Tom , Versteeg Mila 
Published: May 2021

Abstract
Emergency governance, we are often told, is executive governance. Only the executive has the information, decisiveness, and speed to respond to crises, and so the executive is not capable of being effectively constrained by other branches. Ordinary checks and balances, then, are believed to effectively disappear during a crisis. Referring to the classic theorist of emergency rule, conventional accounts describe crisis governance as “Schmittian” and “post-Madisonian,” characterized by an unbound executive that faces few, if any, legal constraints. This article interrogates these propositions using evidence from how countries responded to the 2020 global pandemic during the critical first few months. It presents data from an original and global survey of over one hundred countries to evaluate the nature of emergency powers during the pandemic. This article finds that, contrary to the conventional wisdom, courts, legislatures, and subnational governments have played important roles in constraining national executives. Courts have insisted on procedural integrity of invocations of emergency, engaged in substantive review of rights restrictions, and in some cases demanded that government take affirmative steps to combat the COVID-19 virus and its effects. Legislatures have played a role in providing oversight and, in many cases, in producing new legislation that responds to the current crisis. Subnational governments, too, have pushed back against central authorities, engaging in valuable checks and balances that shaped the response. Taken together, these findings suggest that, during COVID, emergency governance has been closer to the Madisonian ideal of strong checks and balances than to Schmittian accounts of an unbound executive. This article considers the implications of these findings for theories of emergency governance, arguing that the conventional theories are based on one particular type of crisis—a national security crisis—and therefore their insights may be ill-suited to other kinds of emergencies, such as a pandemic.
Cellular Activation, Differentiation, and Proliferation Influence the Dynamics of Genetically Intact Proviruses Over Time
Authors: Horsburgh Bethany A , Hiener Bonnie , Fisher Katie , Lee Eunok , Morgan Hannah , Eden John-Sebastian , von Stockenstrom Susanne , Odevall Lina , Milush Jeffrey M , Hoh Rebecca , Fromentin Rémi , Chomont Nicolas , Hecht Frederick M , Schlub Timothy E , Deeks Steven G , Palmer Sarah 
Published: May 2021

Abstract
Human immunodeficiency virus (HIV) persists in cells despite antiretroviral therapy; however, the influence of cellular mechanisms such as activation, differentiation, and proliferation upon the distribution of proviruses over time is unclear. To address this, we used full-length sequencing to examine proviruses within memory CD4+ T-cell subsets longitudinally in 8 participants. Over time, the odds of identifying a provirus increased in effector and decreased in transitional memory cells. In all subsets, more activated (HLA-DR–expressing) cells contained a higher frequency of intact provirus, as did more differentiated cells such as transitional and effector memory subsets. The proportion of genetically identical proviruses increased over time, indicating that cellular proliferation was maintaining the persistent reservoir; however, the number of genetically identical proviral clusters in each subset was stable. As such, key biological processes of activation, differentiation, and proliferation influence the dynamics of the HIV reservoir and must be considered during the development of any immune intervention.
A mutant equipped with a regenerated disulphide for the missing His loop of a serine protease zymogen in the horseshoe crab coagulation cascade
Authors: Yamashita Keisuke , Takeshita Naoki , Arita Aina , Shibata Toshio , Kobayashi Yuki , Kawabata Shun-ichiro 
Published: May 2021

AbstractThe lipopolysaccharide (LPS)-triggered coagulation cascade in horseshoe crabs is composed of three zymogens belonging to the trypsinogen family: prochelicerase C, prochelicerase B (proB) and the proclotting enzyme (proCE). Trypsinogen-family members contain three conserved disulphides located around the active site. While it is known that proB evolutionarily lost one of the disulphides, the His-loop disulphide, the roles of the missing His-loop disulphide in proB remain unknown. Here, we prepared a proB mutant, named proB-murasame, equipped with a regenerated His-loop disulphide. The activation rate by upstream α-chelicerase C for proB-murasame was indistinguishable from that for wild-type (WT) proB. The resulting protease chelicerase B-murasame exhibited an 8-fold higher kcat value for downstream proCE than WT chelicerase B, whereas the Km value of chelicerase B-murasame was equivalent to that of WT chelicerase B. WT serpins-1, -2 and -3, identified as scavengers for the cascade, had no reactivity against WT chelicerase B, whereas chelicerase B-murasame was inhibited by WT serpin-2, suggesting that WT chelicerae B may trigger as-yet-unsolved phenomena after performing its duty in the cascade. The reconstituted LPS-triggered cascade containing proB-murasame exhibited ∼5-fold higher CE production than that containing WT proB. ProB-murasame might be used as a high value-adding reagent for LPS detection.
Hospital staff perspectives: medication reconciliation responsibility and barriers at a tertiary teaching hospital in Jordan
Authors: Ibrahim Seliman M , Abu Hamour Khawla , Mahfouz Farah Abu , Abdel Jalil Mariam H , Hammad Eman A 
Published: May 2021

Abstract

Objectives
To explore hospital staff perspective on the responsibility and barriers to medicine reconciliation (MedRec) at a leading internationally renowned teaching hospital in Jordan.

Methods
A cross-sectional study using a self-completed questionnaire was conducted at Jordan University Hospital (JUH). The target sample was members of the health team caring for patients across various locations and settings. A convenient sample of physicians, pharmacists and nurses was targeted. Those were approached at various days, shifts, locations to scop various views and practices across JUH.

Key findings
Two hundred questionnaires were included in the analysis, of which 41 (20.5%) completed by physicians, 23 (11.5%) by pharmacists and 136 (68.0%) by nurses. For most steps, physicians were seen as the prim responsible health providers. Nurse perceived their role to come second. Whilst pharmacists perceived limited or no role of nurses in a number of steps. The main barriers reported are heavy workload 158 (79%), followed by lack of time 152 (76%) and communication between health care providers 140 (70%). Pharmacists highlighted lack of knowledge, clarity and training as leading barriers too.

Conclusions
Physicians are perceived as the leading provider responsible for all MedRec steps. MedRec as a process involve overlapping functions with various skill-based steps. A number of steps allocated potentially to nurses or pharmacists, particularly comparing different sources of information, constructing medication lists or written summaries upon discharge. Barriers to MedRec might be overcome by interdisciplinary discussions and mapping MedRec process clearly.
In the Middle of What? A Fresh Analysis of the Language Attested in the Judaeo-Arabic Commentary on Pirqê ’Āvō

T

(The Sayings of the Fathers), Middle Arabic and Implications for the Study of Arabic Linguistic History
Authors: Stokes Phillip W 
Published: May 2021

Abstract
While recent scholarship on Middle Arabic recognizes a spectrum of varieties from which authors might draw in their compositions, there is still a tendency to place the ends of the spectrum of linguistic features which any Middle Arabic author might employ as dialectal on the one hand and a homogeneous Classical Arabic on the other. In this paper, I challenge the contours of this spectrum by contextualizing the language of a thirteenth-century Judaeo-Arabic text from Egypt—the ‘Commentary on the Sayings of the Fathers’—within previously and contemporarily attested literary and performative traditions, drawing especially on Quranic reading traditions, as well as vocalized Judaeo-Arabic and Christian texts. I highlight important parallels between these traditions and features attested in this text. I conclude that to properly understand the linguistic choices that authors made, we must avoid anachronisms about the range of linguistic variation available to composers, and assumptions about the prestige associated with those variants.
Preoperative Radiographic Evaluation of Thoracic Flexibility and Compensation for Adult Spinal Deformity Surgery. How to Select Optimal Upper Instrumented Vertebra to Prevent Proximal Junctional Kyphosis
Authors: Ohba Tetsuro , Koji Fujita , Koyama Kensuke , Oba Hiroki , Oda Kotaro , Tanaka Nobuki , Haro Hirotaka 
Published: May 2021

Study Design.
Retrospective study of a cohort of consecutive patients.

Objective.
The aim of this study was to clarify the usefulness and value of the difference in thoracic kyphosis (ΔTK) angle in various positions by imaging the patient standing, prone, and supine to evaluate TK flexibility and compensation, and to establish optimal radiography to determine an appropriate thoracic level for upper instrumented vertebra (UIV) because a strategy to select an appropriate level to avoid proximal junctional kyphosis (PJK) remains elusive.

Summary of Background Data.
Postoperative reciprocal progression of TK is a significant risk factor for PJK. However, how to predict and prevent postoperative reciprocal progression of TK remains unclear. We hypothesized that preoperative evaluation of both TK flexibility and compensation is essential to predict PJK and determine the UIV level.

Methods.
We included 144 consecutive patients with adult spinal deformity (ASD), ≥2 years’ follow-up, and UIV Th9–11 in this retrospective cohort study. TK was measured from images with patients standing, prone, and supine. Supine ΔTK was calculated as standing TK– supine TK. Prone ΔTK was calculated as standing TK – prone TK. Receiver-operating characteristic (ROC) curves were analyzed to determine the thresholds of supine ΔTK and prone ΔTK for PJK occurrence.

Results.
PJK was observed in 64 of 144 (44%) patients 2 years postoperatively. Prone and supine ΔTKs were significantly larger in patients with PJK. A significant positive correlation between prone ΔTK and supine ΔTK was observed. When data from patients with and without PJK were plotted separately, a significantly higher proportion of patients with PJK had large prone and supine ΔTKs. The cutoff values of prone and supine ΔTKs for PJK risk were determined using ROC curve analysis.

Conclusion.
Because of their significantly high risk for PJK, in patients with ASD and prone ΔTK >11.5° and supine ΔTK >18.5°, the upper-thoracic spine should be considered for UIV.

Level of Evidence: 3