bluuebunny/crossref_metadata_2025 huggingface dataset:
P544Evaluation of three-dimensional trajectory of pacing cathode pole in coronary sinus to predict long-term response to cardiac resynchronization therapy
Authors: Tomasi C , Severi S , Zanon F , Molon G , Corzani A , Rossillo A , Biffi M , Marcantoni L , Costa A , Dal Monte A , Santarelli G , Lanzoni L , Corsi C
Published: June 2020

Background

An automated method for 3D reconstruction of coronary sinus (CS) lead’s pacing cathode trajectory (3DTJ) was proposed  to acutely predict long term left ventricular (LV) mechanic response to  cardiac resynchronization therapy (CRT). Preliminary data showed that 3DTJ at biventricular pacing (BIV) start changed  in CRT responders (R) to be,  becoming less eccentric and more multi-directional, as described by the ratio between its two major axes (S1/S2).

Purpose

The TRAJECTORIES study (Trajectory Changes Of Coronary Sinus Lead Tip And Cardiac Resynchronization Therapy Outcome, NCT02340546) is an observational study by seven Italian centers about  the prediction of CRT-induced LV reverse remodeling by means of the acute 3DTJ changes at CRT implant.

Methods

In CRT implants with standard indications, stable CHF and regular ventricular rhythm,  a fluoroscopic sequence in two standard X-rays views of a few seconds was acquired immediately before (T-1) and after the start of BIV (T0). 3DTJ  of CS lead cathode pole throughout the cardiac cycle at T-1 and T0 were reconstructed and analyzed. Changes of the ratio between its two major axes (S1/S2) between T-1 and T0 (ΔS1/S2), were compared with the volumetric response at six-month f.u: the percent negative variation of S1/S2 (ΔS1/S2 < 0), marking a more multi-directional shape of 3DTJ, was assumed to predict the response to CRT. Volumetric response was adjudicated by a core-lab using a cut-off reduction ≥ 15% in echocardiographic LV end-systolic volume at f.u.. 

Results

  Out of 119 patients enrolled in 42 months, 74 pts ended f.u. (55 m; age 69 ± 10) and 30 dropped–out. Patients baseline features were: ischemic heart disease (IHD) 34 /74 pts; sinus rhythm 64/74 pts; upgrade from PM/ICD 13/74 pts; QRS morphology with LBBB 57/74, intraventricular aspecific delay 6 and  RV pace 11 pts;  LV ejection fraction (EF) 30 ± 9%; QRS duration 162 ± 25 ms. At f.u., volumetric R were 45/74 (60%). Concordance between ΔS1/S2 (as either ΔS1/S2 < 0 or ΔS1/S2 > 0) and volumetric response was 77% overall (57/74), 82% in R (37/45), 69% in non-R (20/29). Non-concordant patients were mostly non-R: 52% vs  35% of non-R in concordant group, but no other differences were found. The proposed 3DTJ metric showed sensitivity = 72%, specificity =80%;  positive predictive value = 69%, negative predictive value = 82%.

Conclusions

Metrics of 3DTJ can be useful to acutely predict CS pacing site-specific response to CRT in long-term, above all in R. 3DTJ assessment might highlight aspects of  CRT effects  on LV mechanics.
P471Experience with the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation and a high risk of hemorrhagic complications
Authors: Emelina E , Gendlin G , Nikitin I
Published: June 2020

Background. The use of NOACs in patients with chronic lymphocytic leukemia (CLL) is a difficult task due to the tendency to hemorrhage in these patients associated with CLL. The use of targeted ibrutinib (Ib) therapy in the treatment of CLL patients increases the risk of bleeding due to thrombocytopathy. A feature of targeted Ib therapy is the need for daily and lifelong use. One of the cardiotoxic effects of Ib is the development of atrial fibrillation (AF). Some patients receiving Ib have a history of AF. Warfarin is contraindicated in patients taking Ib, so all patients received NOACs.

Purpose. To evaluate the possibility of using NOACs in CLL patients receiving Ib, taking into account the frequency and severity of hemorrhagic manifestations, the need to cancel, reduce the dose and replace with another NOACs.

Methods. We examined and observed the dynamics of 224 patients with CLL receiving Ib from 5 to 56 months at a dose of 420 mg per day as 1, 2, 3, and 4 lines of CLL therapy. Patients with CLL aged 32 to 91 years (66.0 (59.0-72.0) years) were Included, of whom 82 are women aged 39 to 83 years (64.0 (54.0-71.0 ) years) and 142 men aged 32 to 91 years (66.0 (60.0-72.0) years). All hemorrhagic manifestations in patients receiving Ib and NOACs were evaluated, taking into account the glomerular filtration rate and platelet count.

Results. AF were revealed in 51 patients with CLL receiving Ib. AF was registered in 32 patients during the treatment with Ib, in 19 patients AF was before prescribing of Ib. The need for NOACs because of AF arose in 38 patients with CLL who were prescribed rivaroxaban (n = 11), dabigatran (n = 6), apixaban (n = 21). Hemorrhages were observed in 88.2% of patients receiving NOACs and Ib, represented by hematomas (n = 32), petechiae (n = 4), nosebleeds (n = 6), gingival bleeding (n = 7), hemorrhage in the anterior chamber of the eye (n = 1), hemorrhage in the sclera of the eye (n = 3) and macrohematuria (n = 4). A combination of several hemorrhagic manifestations (combined hemorrhages) was observed in 40.7% of CLL patients receiving NOACs. 10 patients were transferred to the minimum dose of apixaban 2.5 mg twice a day due to the development of recurring nosebleeds (n = 5), macrohematuria (n = 3), large, recurring hematomas with localization on the neck and face (n = 1 ), hemorrhages in the anterior chamber of the eye (n = 1). Cancellation of NOACs in 1 patient was associated with recurrent macrohematuria. Rivaroxaban 20 mg per day was canceled in 6 patients due to the development of persistent thrombocytopenia of less than 50 × 109/L. Conclusions. There were no life-threatening hemorrhages. The main reason for the withdrawal of NOACs was persistent thrombocytopenia. Due to hemorrhagic complication, NOACs was canceled only in 1 patient, 10 patients (26.3%) required a transfer to the minimum dose of apixaban. The arising hemorrhages did not require hospitalization of patients.
P1450Deep vein thrombosis after right sided catheter ablation; more common then previously thought?
Authors: Bruce C , Rogers S , Saraf K , Kirkwood G , Kirkland N , Wright M , Jamil-Copley S , Abozguia K , Fox D , Mccollum C , Morris G
Published: June 2020

Funding Acknowledgements

Bristol-Myers Squibb

Background

Right sided cardiac catheter ablation has become an indispensable tool to treat supraventricular cardiac dysrhythmias, with ablation of certain arrhythmias having cure rates over 90%. Due to this the frequency of these procedures is increasing annually and it is imperative we understand the incidence of all complication. One lesser studied complication is that of deep vein thrombosis (DVT), for which catheter ablation demonstrates all elements of Virchow"s triad.  As right sided ablations are carried out to treat troublesome palpitations, not to reduce mortality, it is important all risks are identified, especially those which are themselves potentially life threatening and can be modified.

Purpose

 

To determine the incidence of DVT after right sided cardiac catheter ablation.

Methods

 

We undertook a prospective multi-center study recruiting adult patients undergoing clinically indicated cardiac ablation for atrioventricular nodal re-entrant tachycardia and atrioventricular re-entrant tachycardia with right sided accessory pathway. Important exclusion criteria included patients on anticoagulation or antiplatelet therapy. Participants underwent bilateral compression venous duplex ultrasonography from the inferior vena cava to the popliteal vein to access for DVT at 24 hours and between 10 to 14 days post-procedure. The uncannulated contralateral leg acted as a control.

Result

 

At interim analysis 71 participants had completed the study with average age 47 year (+/- 14), procedure duration 67 minutes, and with a female predominance. Seven patients developed acute DVT in either the femoral or internal iliac vein in the access leg. No thrombus was seen in the control leg. This gives an incidence of 10% (95% CI 4-19%) with p value of 0.023 on Chi-square testing.

Conclusion

We found a statistically significant proportion of patients undergoing right sided cardiac catheter ablation developed acute proximal DVT on ultrasound. All patients were treated with 3 to 6 months of anticoagulation therapy in accordance with NICE guidelines. These results suggest that DVT may occur at a high frequency then previously thought in this cohort and supports the consideration of peri-procedural prophylactic anticoagulation.

Abstract Figure. Acute thrombus in the femoral vein
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

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

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

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

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

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

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

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 < 0.12 min). There were 493 pairs of pesticides with a mass-to-charge difference of <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

In 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

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

The 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, <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 >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

Putnam’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.
Impact of proton radiotherapy on treatment timing in pediatric and adult patients with CNS tumors
Authors: Jin Michael C , Shi Siyu , Wu Adela , Sandhu Navjot , Xiang Michael , Soltys Scott G , Hiniker Susan , Li Gordon , Pollom Erqi L
Published: June 2020

Background

Despite putative benefits associated with proton radiotherapy in the setting of CNS tumors, numerous barriers limit treatment accessibility. Given these challenges, we explored the association of proton use with variations in treatment timing.

Methods

Pediatric and adult patients with histologically confirmed CNS tumors were identified from the National Cancer Database (2004-2015). Univariable and multivariable regression models were constructed to assess factors impacting radiation timing. Multivariable Cox regression was used to evaluate the effect of treatment delay on survival.

Results

A total of 76 157 patients received photon or proton radiotherapy. Compared to photons, time to proton administration was longer in multiple pediatric (embryonal, ependymal, nonependymal glial, and other) and adult (ependymal, nonependymal glial, meningeal, other) tumor histologies. On adjusted analysis, proton radiotherapy was associated with longer delays in radiotherapy administration in pediatric embryonal tumors (+3.00 weeks, P = .024) and in all adult tumors (embryonal [+1.36 weeks, P = .018], ependymal [+3.15 weeks, P < .001], germ cell [+2.65 weeks, P = .024], glial [+2.15 weeks, P < .001], meningeal [+5.05 weeks, P < .001], and other [+3.06 weeks, P < .001]). In patients with high-risk tumors receiving protons, delays in adjuvant radiotherapy were independently associated with poorer survival (continuous [weeks], adjusted hazard ratio = 1.09, 95% CI = 1.02-1.16).

Conclusions

Proton radiotherapy is associated with later radiation initiation in pediatric and adult patients with CNS tumors. In patients with high-risk CNS malignancies receiving protons, delayed adjuvant radiotherapy is associated with poorer survival. Further studies are needed to understand this discrepancy to maximize the potential of proton radiotherapy for CNS malignancies.
The Quest for Pure Language
Authors: Brown Samuel Morris
Published: June 2020

Modern philosophical positions have restricted or eliminated the power and scope of the “language beyond language” once thought to have existed at the origins of the world. In this view, mortal language is the only language—either there is no primordial sacred language, or it exists but humans have no access to it. Joseph Smith saw these postures as capitulation to the curse of language at Babel (Genesis 11), which haunted him. The quest for pure language was a central aspect of his religious career and is a direct rejection of modernist assumptions about the potential of language. This quest for pure language—focused especially on the power of the hieroglyph—extended across Smith’s career, including extensive explorations of the Edenic language and traditions about powerful, nonordinary language.
The Transcendent Immanent Temple
Authors: Brown Samuel Morris
Published: June 2020

Smith culminated his metaphysics of translation in the rites of the Nauvoo temple in the early 1840s. The temple rites were a striking combination of Smith’s targums, the Hebrew and Christian Bibles, Freemasonry, ancient mystery religions, and his sense about the connections of humans and texts. This liturgy was Smith’s final rereading of the Hebrew Bible’s primeval history, and it pulled his followers to Eden and thence to heaven as transformed, divine beings. These rites were an apotheosis not just of Smith’s followers but also of his metaphysics of translation. In the temple, Smith worked to define space and time in terms of human beings. In an echo of Hebrew genealogies, Smith measured time in parental bonds effected by a force he called priesthood. These bonds at the base of time tied God to humanity and humans to each other.
Pastoral Power
Authors: Evans Richard Kent
Published: June 2020

From 1977 to 1978, the Philadelphia Police Department established a blockade around the MOVE house. Eventually, this blockade became a starvation blockade, when the mayor, Frank Rizzo, determined that the best way to end the standoff was to starve MOVE people into surrendering. During this standoff, respected religious leaders representing various faith traditions negotiated between MOVE and the city. These religious leaders initially came to MOVE’s defense. Some of them believed that MOVE was a religion, and that the city’s actions threatened religious freedom in the city. As the negotiations wore on, however, MOVE lost their initial support. The religious leaders who previously defended MOVE decided that MOVE was not, in fact, a religion and sided with the city. In so doing, these religious leaders articulated a series of claims about the nature of “true religion” to explain why MOVE was not, in their view, a religion.
Religion on Trial
Authors: Evans Richard Kent
Published: June 2020

This chapter highlights the social actors who have perhaps the most outsized influence on religious classification in the modern United States: judges. In 1981, MOVE’s claims to religious legitimacy received their day in court. A MOVE person, Frank Africa, who was then incarcerated in a Pennsylvania state prison, requested from the prison a religious accommodation for his MOVE diet. The prison denied his request, and Frank appealed to the Third Circuit Court of Appeals. Before the court could decide on Frank’s request, the judges had to first determine whether or not MOVE was a religion.
Innocence
Authors: Evans Richard Kent
Published: June 2020

This chapter tells the story of the MOVE Bombing. In the thirty-three years since the MOVE Bombing, writers, artists, and filmmakers have struggled to make sense of what happened on May 13, 1985. Overall, they have failed to do so. This author does not expect to succeed. His main contribution to an understanding of the MOVE Bombing is this: it is not exceptional and it is not inexplicable. Such acts of state violence have happened many times before, and there is no reason to suspect that that they will not happen again. Rather than looking at the MOVE Bombing as an inexplicable event, one should look at it as a perfectly normal behavior of the secular state. The MOVE Bombing, the author argues, makes sense only when one sees it as a logical extension of secularism; as the secular state preempting “illegitimate” religious violence with “legitimate” state violence.
Precursors to the Priestly Creation Account (Gen 1:1–2:3)
Authors: Carr David M.
Published: June 2020

This chapter looks at potential precursors to the Priestly creation account, both within the Bible and outside it. It starts by building a case that Genesis 1 shows a particular engagement with the Mesopotamian Enuma Elish epic, claiming a dominance of the Israelite God superior to that which is claimed for Marduk in that epic. It then turns to signs that Genesis 1 also seems to reflect knowledge of the cosmological tradition reflected in Psalm 104, which in turn reflects nonbiblical traditions about origins from Canaan and (perhaps earlier) Egypt. In addition, despite the arguments of some recent studies that Genesis 1 preceded Genesis 2–3, select parts of Genesis 1 appear to be incompletely adapted elements (“blind motifs”) that originated in the non-Priestly story of creation in the Garden of Eden (Gen 2:4b–3:24). This suggests that this non-Priestly creation story likely also stands among the texts that preceded and were engaged by the author of Genesis 1. The chapter concludes with brief consideration of the possibility that the Priestly creation account may also preserve, embedded within itself, an earlier literary precursor. The most likely possibility in this case is that the day-structure and final Sabbath focus now found in Gen 1:1–2:3 was a later addition to it, possibly by an author-redactor associated with what is often termed the “Holiness School.”
Pole Dancing for Jesus
Authors: Jones Alisha Lola
Published: June 2020

Chapter 3 dissects the sociocultural sensitivity about the extent to which men’s dance or gesture in worship registers as queer by analyzing a case study of a man who worships God through pole fitness. Derived from ethnographic research of widely circulated Jungle Cat’s amateur “pole dancing for Jesus” performance footage, chapter 3 teases out innumerable creative processes through which men’s situating of identity takes place. Jungle Cat worships God to recorded gospel music with ritual components of private dancing and contemplation that absolve him from ecclesial, denominational, and organizational restrictions and surveillance. While anxieties about black male identity also apply to more conventional forms of men’s praise dance such as mime and step, pole dancing cultivates especially passionate responses from gospel music observers.
Promises to Keep
Authors: Nieman Donald G.
Published: June 2020

This book examines the influence of race in the development of the US Constitution and argues that African Americans have had a powerful influence creating constitutional rights. It examines the debate over slavery in the Revolutionary era and at the Constitutional Convention and how antislavery advocates, black and white, created constitutional ideas that promoted equality, and their role in ending slavery, securing adoption of the Thirteenth, Fourteenth, and Fifteenth Amendments, and establishing civil rights protections during Reconstruction. By 1900, southern whites had reversed most of these changes through disfranchisement, segregation, and sharecropping, but African Americans continued to resist. Through organizations like the National Association for the Advancement for Colored People, they challenged segregation, discriminatory criminal justice, lynching, and disfranchisement. After World War II, the civil rights movement triumphed through legal victories (e.g., Brown v. Board of Education), legislation (the Civil Rights Act of 1964 and the Voting Rights Act), and mass protest. Civil rights advocates won victories in the 1970s and 1980s challenging institutionalized racism, even though conservative political strength grew. However, from the 1980s to the 2010s, a conservative Supreme Court invoked color-blind constitutional principles to weaken civil rights protections. Continued economic disparities between blacks and whites as well as the war of drugs and mass incarceration undermined gains made by the civil rights movement, although new social movements like Black Lives Matter continued the quest for equal justice.
The Age of Segregation, 1900–1950
Authors: Nieman Donald G.
Published: June 2020

This chapter argues that segregation generated organized opposition from African Americans and a small group of whites that challenged the system. Segregation was rigid, capricious, and designed to demonstrate white power. While it kept most blacks in menial positions, a small black middle class emerged that produced leaders who attacked Jim Crow. The organization leading the charge was the NAACP, which developed publicity, lobbying, and litigation campaigns. The effort gained steam in the 1930s, as a cadre of black lawyers challenged segregated education, the CIO and the Communist party championed civil rights, and the New Deal gave blacks a voice in federal policy. It further accelerated during World War II as the federal government challenged workplace discrimination, membership in civil rights organizations swelled, black veterans demanded their rights, and the Supreme Court became more aggressive on civil rights.
GWOT
Authors: Devji Faisal
Published: June 2020

The emergence of Al-Qaeda resulted in the deterritorialization of the war waged against it. Neither an old-fashioned enemy operating through institutions like states and armies, nor a civilian and purely criminal enterprise, its networked form of militancy ended up fragmenting and disrupting the hierarchies of Western military force from the inside. This became evident in juridical enclaves like Guantanamo Bay as well as in the culture of torture and abuse at Abu Ghraib.
Dithering
Authors: Toohey Peter
Published: June 2020

Unlike the pausing that takes place in music, the hesitant pause, such as in dithering or procrastination, can be, if not debilitating, at least a problem. But there can be some advantages to dithering. One is that it slows down time, allowing us more time to contemplate what is about to or liable to happen, and to make a decision at the appropriate time. That’s probably the very latest minute. This is Frank Partnoy’s conclusion as it relates to decision-making and as it relates to being effective in business. This version of dithering, a process rather than an emotional experience, is almost a competitive strategy—that’s a very good reason for thinking of dithering as being alarming.
Cuban Music Is African Music
Authors: Whitmore Aleysia K.
Published: June 2020

Part II examines how AfroCubism and Orchestra Baobab musicians negotiate geographic, cultural, and linguistic boundaries as they mix musics across the black Atlantic and bring their music into the word music industry. In so doing, this section shows how musicians’ experiences are intertwined with the commodities they create, and that many of us consume (and critique). This chapter explores how musicians creatively combine African and Cuban musics. In bringing these musics together, musicians (re)negotiate and (re)imagine cultural, historical, political, and economic ties between Africans, Cubans, Europeans, and Americans. Their ideas conflict, diverge, and intersect as they strategically combine musics and social meanings, idealistically connect peoples and musics across the Atlantic, and pragmatically address the limits of musical mixing and collaboration.
Experiencing Pleasure
Authors: Whitmore Aleysia K.
Published: June 2020

This chapter explores how audiences experience these musics and why they are drawn to them. The chapter shows how politics and pleasure intertwine for audiences at performances. Audiences find pleasure in “exotic” sounds and in the politics these musics allow them to express and experience. Festivals and concert halls offer fleeting spaces in which audiences express and experience their aesthetic and political imaginations in pleasurable ways. They create new dance moves, meet Greenpeace volunteers, and listen to musicians promote African children’s charities. Audiences’ experiences of pleasure, unconstrained by (yet made possible by) Western culture and politics, is paramount as they develop a particular kind of connoisseurship and love of world music in which the depth of their fandom does not emerge from profound knowledge of a band but rather from a commitment to the cultural and political world they see on stage and experience off stage.
Introduction
Authors: Raghavan Pallavi
Published: June 2020

The bilateral relationship between India and Pakistan occupies a strange place at the heart of the process of state-making in the subcontinent in the years that followed the partition. The introduction details what topics each chapter will cover.
Conclusion
Authors: Raghavan Pallavi
Published: June 2020

1950, then, was an interesting year: it had all the makings of the sets of causes that bring about both war and peace between India and Pakistan. Nehru and Liaquat Ali Khan had fulminated to their constituent assemblies over each other’s duplicity over the refugee question; but they had also gone ahead with the shaping of a correspondence on the No War Pact. No ‘permanent’ solution—war, peace, or any of the intervening shades in between—was put into place, but a series of ad hoc, interim measures that could be countenanced by both states were devised in the meanwhile to patch things over. What was acknowledged on both sides was that the way to a lasting stability lay in finding answers that could lay the ghosts of partition to rest once and for all. And, to some extent at least, both governments made concerted efforts to bring this about....