bluuebunny/crossref_metadata_2025_split huggingface dataset:
863Leadless endocardial pacing improves symptoms in patients with failed conventional CRT implant in long term follow up
Authors: Seifert M , Butter C , Reddy V , Neuzil P , Rinaldi A , James S , Turley A , Betts T , Arnold M , Riahi S , Delnoy P , Boersma L , Biffi M , Van Erven L , Schilling R 
Published: June 2020

Abstract

Funding Acknowledgements
EBR Systems, Inc

OnBehalf
WiSE-CRT and LV-SELECT study and POST-M REGISTRY

Background
The WiSE-CRT (Wireless stimulation endocardial) system has advantages over conventional epicardial CRT. Whenever conventional CRT failed to implant or failed to echocardiographic response, the WiSE-CRT was implanted as part of the WiSE CRT study (N = 13), as part of the LV-SELECT study (N = 35) or as part of the POST-M REGISTRY (N = 117) over the last 8 years. All these studies have reported high rates of clinical and echocardiographic response compared to conventional CRT.

Objectives
The purpose of this analysis was to determine the safety and clinical response in the largest available number of implanted patients (pts) with long term follow up of 2 years and the first, second and third generation of WiSE-CRT devices.

Method
All pts undergoing a WiSE-CRT implantation as part of the WiSE CRT study (N = 13), as part of the LV-SELECT study (N = 35) or as part of the POST-M REGISTRY (N = 117) were analysed (N = 165). Pts were followed-up for 24 months and considered CRT responders if an improvement in NYHA ≥ 1 class from baseline (pre-implant) was achieved.

Results
In total, 165 pts were implanted, demographics include: 68.2 ± 9.6 year’s old, 81.8% male, 49.7% with history of AFib and 54.5% non-ischaemic aetiology. The mean intrinsic QRS duration was 165.0 ± 32.3 msec (28 pts pace-maker dependent). 161 pts had the system successfully implanted with no major complications, 3 (1.8%) pts developed a pericardial effusion and 1 (0.6%) electrode was lost during implantation and recovered surgically. During the 24-month follow-up period, 20 (12.1%) pts died from any cause, 4 (2.4%) pts developed TIA or Stroke and 15 (9.1%) pts had pocket or transmitter infection. There was a significant improvement in NYHA functional class in 63.6% pts and an average improvement of -26.1 (-45.1, -7.1) msec in QRS duration.

Conclusion
Despite a history of failed conventional CRT implantation, pts undergoing CRT upgrades with a WiSE-CRT have a high success rate and a complication rate similar to previously described. In addition endocardial LV pacing led to symptomatic improvements in 64% of patients reaching the 24 month of follow up.
Abstract Figure 1: Forest Plot NYHA Responder Rat
235Anatomic guided ablation of the right ganglionated plexus is enough for cardiac autonomic denervation in patients with significant bradyarrhythmias
Authors: Valbom Mesquita D , Parreira L , Carmo P , Amador P , Cavaco D , Marinheiro R , Costa F , Fonseca M , Farinha J , Esteves A , Pinheiro A , Lopes A , Scanavacca M , Adragao P 
Published: June 2020

Abstract

Background
In patients with significant bradyarrhytmias, cardiac denervation is an alternative therapeutic approach. Previous reports proposed different methods (as high frequency ednocardial stimulation of ganglionated plexus and specific atrial electrogram identification) and targets (right and left atrial ganglionated plexus) for adequate denervation. There is no consensus on the best way to perform these procedures, in spite the right atrial ganglia plexus (GP) ablation seeming to be the most contributive to its success.

Purpose
To assess the results of a purely anatomic approach for ablation of just the right atrial plexus in patients with severe vagal bradyarrhytmias.

Methods
We enrolled patients referred for ablation of cardiac parasympathetic ganglia, with or without atrial fibrillation ablation. We performed eletroanatomic mapping of the right and left atria and used an irrigated tip catheter for ablation, aiming at the anterior right GP at the right pulmonary veins antrum along with ablation at the superior vena cava junction and the inferior right GP at the posterior aspect of the right inferior pulmonary vein along with ablation of the right aspect of the interatrial septum, between the posterior wall and coronary sinus ostium (Figure 1). We assessed the PW and Wenckenback cycle lengths (CL) pre and post procedure in patients with sinus arrest or AV block, respectively, and the patients had new 24h holter readings at least 30 days from the index procedure.

Results
We enrolled 12 patients: 9 males (75%), median age of 49,5 years (IQR 36-61,75). All patients had structurally normal hearts. 7 patients had only ablation of the parasympathetic ganglia and 5 patients had simultaneous pulmonary vein isolation for previously documented atrial fibrillation. 7 patients (58,3%) had sinus bradycardia (2 patients had sinus arrest with pauses of 8 and 13 seconds), 2 patients with cardioinhibitory syncope (with pauses of 23 and 28 seconds) and 3 patients had transient high degree AV block. The ablation procedure led to a median sinus rate acceleration of 15 bpm (IQR 3-29), a median decrease of 320 ms in PW (IQR 23,75-609,5) in patients with sinus arrest and a decrease of 80 ms in wenckenback CL (IQR 60-200) in patients with AV block. With a median follow up of 133,50 days (IQR 36-61,75), no patient had recurrence of symptoms or conduction disturbances.

Conclusions
In selected patients with severe functional paroxysmal bradyarrhytmias, cardiac denervation using an ablation strategy purely based on anatomic aspects and targeting only the right GP, seems to be an effective therapeutic approach.
Abstract Figure 1: Abl of right ganglionated plex
P921Feasibility of multipoint, high-definition mapping with grid cathether of SVTs in patients with D-Transposition of the great arteries treated with atrial switch surgery
Authors: Llerena Butron S I , Francisco Pascual J , Perez Rodon J , Santos Ortega A , Benito B , Rodriguez Garcia J , Dos Subira L , Pijuan A , Subirana M T , Miranda B , Gonzalez V , Escalona Silva R , Ferreira Gonzalez I , Rivas Gandara N 
Published: June 2020

Abstract

Introduction
Patients with D-transposition of the great arteries (TGA) treated with Senning or Mustard surgery develop supraventricular tachycardias (SVTs) that require treatment with ablation. The use of multipoint, high-density, wavefront-activation-orientation independent mapping catheters hasn’t been reported in literature.

Purpose
To describe the feasibility of using a specific mapping catheter in SVTs in this set of patients.

Methods
Prospective observational study in patients with history of SVT and atrial switch surgery, that underwent EP study and electroanatomic (EA) mapping with a new 8Fr deflectable, multipoint (16 equidistant electrodes along 4 splines), with magnetic sensor, wavefront-activation-orientation independent catheter, in a third level hospital since April 2018 until May 2019, with medium-term follow-up.

Results
A total of 8 EPS (electrophysiologic studies) were performed in 7 patients (clinical data in Table 1). One patient had a tachycardia recurrence, accounting for a second EPS. The pulmonary venous atrium (PVA) was mapped in all procedures, whereas the systemic venous atrium (SVA) was mapped only in 75% of them, A total of 15 EA maps were obtained, with a ratio of 1.9 maps/patient, and an average of 20 375 ± 13 045 total points per patient. In all cases, PVA mapping was performed via retrograde transaortic approach, without transbaffle puncture. Tachycardia was induced in 5 out of 8 procedures, obtaining 6 different tachycardias (4 CTI dependent macro-reentry: 3 w/anticlockwise activation; 1 localized re-entry in SVA; 1 focal AT in SVA). No arrhythmia was induced in the other 3 procedures, however, in a patient with a previous CTI ablation, evidence of a gap in the ablation line on the voltage map was found. Ablation was performed with an irrigated, contact force, 3.5 mm catheter in 6 of the 8 procedures (75%). A retrograde transaortic approach was used in 3 of CTI dependent macro-reentries (75%). In one patient (who underwent two procedures) ablation was performed through a baffle leak. We report an acute success rate of ablation of 100%, and a recurrence rate of 20% on medium-term follow up. There were no major complications; nonetheless, one patient with history of morbid obesity had a minor vascular complication on the femoral puncture site treated medically.

Conclusions
it’s feasible and safe to use this new mapping catheter in patients with history of atrial switch surgery, both via retrograde and anterograde approach on the PVA and SVA respectively. The most frequent tachycardia observed in this study was anticlockwise CTI-dependent atrial flutter.
Abstract Figure. Patient characteristics
P1169Cardiac resynchronization theraphy. Long term benefit
Authors: Galizio N , Peltzer M , Tronconi A , Carnero G , Mysuta M , Bozza A , Gavilan L , Labin B , Gonzalez J L 
Published: June 2020

Abstract

Introduction
The benefit of cardiac resynchronization therapy (CRT) in patients (pts) with left ventricular dysfunction is mainly evaluated in multicenter studies with a follow up of 6, 12 or 24 months (m).

Objectives
To describe the response of pts implanted with a CRT-D/P, from a single center prospective registry, at 12, 24, 36 and 48 m.

Methods
Between june 2009 and june 2018, 381 pts implanted with CRT-D/P were followed at 12, 24, 36 and 48 m. Indications were performed according to international guidelines. Primary prevention: 335 pts (88%). The A-V and V-V delay were programmed according the results of Cardiac Doppler after implantation and when it was necesary. All pts had an out patient control and 10% remote monitoring control. The pts were considered Responders: decrease ≥ 1 FC NYHA or increase LVEF ≥ 5% (absolute), Super-Responders: increase LVEF ≥ 10% (absolute) and with LVEF normalization: LVEF ≥ 50%. Baseline characteristics: Age 64 ± 11 years, men 268 p (70%), ischemic cardiomyopathy 144 pts (38%), nonischemic cardiomyopathy 237 (62%), FC II-III NYHA 341 p (90%), LBBB 246 p (72%), mean QRSd 165 ± 27ms, mean LVDD 68 ± 10mm, mean LVSD 56 ± 12mm, and mean LVEF 24 ± 9%. Pts were on β-blockers (93%), ACEi/ARBs (90%), mineral receptor blockers (83%) and diuretics (73%).

Results
Responders: 227/276 pts (82%) at 12 m, 184/224 pts (82%) at 24 m, 141/180 p (78%) at 36 m and 112/137 (82%) at 48 m. Super-Responders: 92/186 pts (49%) at 12 m, 92/172 pts (53%) at 24 m, 71/128 (55%) at 36 m and 66/116 (57%) at 48 m. LVEF normalization: 22/186 pts (12%) at 12 m, 31/172 pts (18%) at 24 m, 24/128 pts (19%) at 36 m and 23/116 pts (20%) at 48 m.

Conclusion
In our study population, pts with CRT-D/P implanted according an appropriate indication, programming and follow up, with in-office and/or remote monitoring control, showed an elevated percentage of Responders, Super-Responders and LVEF normalization. The benefit was sustained or even incresed over time.
Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine
Authors: Michlmayr Daniela , Andrade Paulina , Nascimento Eduardo J M , Parker Allan , Narvekar Parnal , Dean Hansi J , Harris Eva 
Published: June 2020

Abstract

Background
Dengue is caused by 4 antigenically distinct serotypes of dengue virus (DENV1–4). Takeda’s live attenuated tetravalent dengue vaccine (TAK-003) candidate is composed of an attenuated DENV2 and chimeric viruses containing prM/E of DENV1, 3 and 4 on the DENV2 backbone. The multicolor FluoroSpot (MCF) assay enables quantitation of serotype-specific and cross-reactive individual memory B cells (MBCs) secreting DENV-specific antibodies in a polyclonal mixture.

Methods
Using the MCF assay, we determined the type-specific and cross-reactive MBC response in peripheral blood mononuclear cells collected pre- and postvaccination from 7 macaques and 15 randomly selected individuals who received TAK-003 (8 DENV seronegative and 7 DENV seropositive) in a phase 2 clinical trial in Singapore (DEN-205 study).

Results
Preexisting DENV-specific MBC responses were detected only in seropositive vaccine recipients at day 0. Following vaccination, both type-specific and cross-reactive MBCs to all 4 DENV serotypes were observed in all macaques and clinical trial participants. The proportion of type-specific MBCs was higher than cross-reactive MBCs and remained stable between day 30 and 360 post vaccination.

Conclusions
These results demonstrate that, unlike primary or secondary natural DENV infection, tetravalent vaccination elicits tetravalent type-specific MBCs, and thus all 4 components of TAK-003 contribute to the DENV-specific MBC response following vaccination.

Clinical Trials Registration
NCT02425098.
Connecting secretome to hematopoietic stem cell phenotype shifts in an engineered bone marrow niche
Authors: Gilchrist Aidan E , Harley Brendan A C 
Published: June 2020

Abstract
Hematopoietic stem cells (HSCs) primarily reside in the bone marrow, where they receive external cues from their local microenvironment. The complex milieu of biophysical cues, cellular components and cell-secreted factors regulates the process by which HSC produce the blood and immune system. We previously showed direct coculture of primary murine hematopoietic stem and progenitor cells with a population of marrow-derived mesenchymal stromal and progenitor cells (MSPCs) in a methacrylamide-functionalized gelatin (GelMA) hydrogel improves hematopoietic progenitor maintenance. However, the mechanism by which MSPCs influenced HSC fate decisions remained unknown. Herein, we report the use of proteomic analysis to correlate HSC phenotype to a broad candidate pool of 200 soluble factors produced by combined mesenchymal and hematopoietic progeny. Partial least squares regression (PLSR), along with an iterative filter method, identified TGFβ-1, MMP-3, c-RP and TROY as positively correlated with HSC maintenance. Experimentally, we then observe exogenous stimulation of HSC monocultures in GelMA hydrogels with these combined cytokines increases the ratio of hematopoietic progenitors to committed progeny after a 7-day culture 7.52 ± 3.65-fold compared to non-stimulated monocultures. Findings suggest a cocktail of the downselected cytokines amplifies hematopoietic maintenance potential of HSCs beyond that of MSPC-secreted factors alone. This work integrates empirical and computation methods to identify cytokine combinations to improve HSC maintenance within an engineered HSC niche, suggesting a route toward identifying feeder-free culture platforms for HSC expansion. Insight Hematopoietic stem cells within an artificial niche receive maintenance cues in the form of soluble factors from hematopoietic and mesenchymal progeny. Applying a proteomic regression analysis, we identify a reduced set of soluble factors correlated to maintenance of a hematopoietic phenotype during culture in a biomaterial model of the bone marrow niche. We identify a minimum factor cocktail that promotes hematopoietic maintenance potential in a gelatin-based culture, regardless of the presence of mesenchymal feeder cells. By combining empirical and computational methods, we report an experimentally feasible number of factors from a large dataset, enabling exogenous integration of soluble factors into an engineered hematopoietic stem cell for enhanced maintenance potential of a quiescent stem cell population.
UHPLC/ESI Q-Orbitrap Quantitation of 655 Pesticide Residues in Fruits and Vegetables—A Companion to an nDATA Working Flow
Authors: Wang Jian , Leung Daniel , Chow Willis , Wong Jon W , Chang James 
Published: June 2020

Abstract

Background
Effective and expansive methods for multiresidue pesticide analysis are desired for routine monitoring programs. These methods are complex, especially when several hundred pesticides are involved.

Objective
Two approaches to sort data and identify isomers and isobaric ions in pesticide mixtures were evaluated to determine whether they could be differentiated by mass resolving power and/or chromatographic resolution.

Method
This study presents an application of ultra-high performance liquid chromatography electrospray Q-Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap) along with QuEChERS for the quantitation of 655 pesticide residues in fruits and vegetables.

Results
From the developed method, 94.7% of the 655 pesticides in fruits and 93.9% of those in vegetables had recoveries between 81% and 110%; 98.3% in both fruits and vegetables had an intermediate precision of ≤20%; and 97.7% in fruits or 97.4% in vegetables showed measurement uncertainty of ≤50%. When the retention time difference (ΔtR) of two isomers was ≥0.12 min, they were chromatographically resolved. Twenty five out of 35 pairs or groups of isomers were chromatographically separated (ΔtR ≥ 0.12 min), but 14 pairs were not resolved (ΔtR &lt; 0.12 min). There were 493 pairs of pesticides with a mass-to-charge difference of &lt;1 Da. Only one pair of isobaric ions could not be separated by mass and chromatographic resolution.

Highlights
UHPLC/ESI Q-Orbitrap along with QuEChERS sample preparation offers a practical quantitative companion method to a non-target data acquisition for target analysis workflow for pesticide residue analysis in routine monitoring programs for food safety.
A second hybrid-binding domain modulates the activity of Drosophila ribonuclease H1
Authors: González de Cózar Jose M , Carretero-Junquera Maria , Ciesielski Grzegorz L , Miettinen Sini M , Varjosalo Markku , Kaguni Laurie S , Dufour Eric , Jacobs Howard T 
Published: June 2020

AbstractIn eukaryotes, ribonuclease H1 (RNase H1) is involved in the processing and removal of RNA/DNA hybrids in both nuclear and mitochondrial DNA. The enzyme comprises a C-terminal catalytic domain and an N-terminal hybrid-binding domain (HBD), separated by a linker of variable length, 115 amino acids in Drosophila melanogaster (Dm). Molecular modelling predicted this extended linker to fold into a structure similar to the conserved HBD. Based on a deletion series, both the catalytic domain and the conserved HBD were required for high-affinity binding to heteroduplex substrates, while loss of the novel HBD led to an ∼90% drop in Kcat with a decreased KM, and a large increase in the stability of the RNA/DNA hybrid-enzyme complex, supporting a bipartite-binding model in which the second HBD facilitates processivity. Shotgun proteomics following in vivo cross-linking identified single-stranded DNA-binding proteins from both nuclear and mitochondrial compartments, respectively RpA-70 and mtSSB, as prominent interaction partners of Dm RNase H1. However, we were not able to document direct and stable interactions with mtSSB when the proteins were co-overexpressed in S2 cells, and functional interactions between them in vitro were minor.
The use of Kepler solver in numerical integrations of quasi-Keplerian orbits
Authors: Deng Chen , Wu Xin , Liang Enwei 
Published: June 2020

ABSTRACT
A Kepler solver is an analytical method used to solve a two-body problem. In this paper, we propose a new correction method by slightly modifying the Kepler solver. The only change to the analytical solutions is that the obtainment of the eccentric anomaly relies on the true anomaly that is associated with a unit radial vector calculated by an integrator. This scheme rigorously conserves all integrals and orbital elements except the mean longitude. However, the Kepler energy, angular momentum vector, and Laplace–Runge–Lenz vector for perturbed Kepler problems are slowly varying quantities. However, their integral invariant relations give the quantities high-precision values that directly govern five slowly varying orbital elements. These elements combined with the eccentric anomaly determine the desired numerical solutions. The newly proposed method can considerably reduce various errors for a post-Newtonian two-body problem compared with an uncorrected integrator, making it suitable for a dissipative two-body problem. Spurious secular changes of some elements or quasi-integrals in the outer Solar system may be caused by short integration times of the fourth-order Runge–Kutta algorithm. However, they can be eliminated in a long integration time of 108 yr by the proposed method, similar to Wisdom–Holman second-order symplectic integrator. The proposed method has an advantage over the symplectic algorithm in the accuracy but gives a larger slope to the phase error growth.
Recent Common Origin, Reduced Population Size, and Marked Admixture Have Shaped European Roma Genomes
Authors: Bianco Erica , Laval Guillaume , Font-Porterias Neus , García-Fernández Carla , Dobon Begoña , Sabido-Vera Rubén , Sukarova Stefanovska Emilija , Kučinskas Vaidutis , Makukh Halyna , Pamjav Horolma , Quintana-Murci Lluis , Netea Mihai G , Bertranpetit Jaume , Calafell Francesc , Comas David 
Published: June 2020

AbstractThe Roma Diaspora—traditionally known as Gypsies—remains among the least explored population migratory events in historical times. It involved the migration of Roma ancestors out-of-India through the plateaus of Western Asia ultimately reaching Europe. The demographic effects of the Diaspora—bottlenecks, endogamy, and gene flow—might have left marked molecular traces in the Roma genomes. Here, we analyze the whole-genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. Our analyses revealed a strong, early founder effect followed by a drastic reduction of ∼44% in effective population size. The Roma common ancestors split from the Punjabi population, from Northwest India, some generations before the Diaspora started, &lt;2,000 years ago. The initial bottleneck and subsequent endogamy are revealed by the occurrence of extensive runs of homozygosity and identity-by-descent segments in all Roma populations. Furthermore, we provide evidence of gene flow from Armenian and Anatolian groups in present-day Roma, although the primary contribution to Roma gene pool comes from non-Roma Europeans, which accounts for &gt;50% of their genomes. The linguistic and historical differentiation of Roma in migrant groups is confirmed by the differential proportion, but not a differential source, of European admixture in the Roma groups, which shows a westward cline. In the present study, we found that despite the strong admixture Roma had in their diaspora, the signature of the initial bottleneck and the subsequent endogamy is still present in Roma genomes.
Descriptivism about the Reference of Set-Theoretic Expressions: Revisiting Putnam’s Model-Theoretic Arguments
Authors: Soysal Zeynep 
Published: June 2020

AbstractPutnam’s model-theoretic arguments for the indeterminacy of reference have been taken to pose a special problem for mathematical languages. In this paper, I argue that if one accepts that there are theory-external constraints on the reference of at least some expressions of ordinary language, then Putnam’s model-theoretic arguments for mathematical languages don’t go through. In particular, I argue for a kind of descriptivism about mathematical expressions according to which their reference is “anchored” in the reference of expressions of ordinary language. These anchors add enough to the content of mathematical expressions to forestall the radical kind of indeterminacy that model-theoretic arguments are purported to show, while still leaving room for a plausible, moderate kind of indeterminacy.