bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated impact of the GST on tobacco products in India
Authors: John Rijo M , Dauchy Estelle , Goodchild Mark 
Published: September 2018

ObjectiveTo examine the potential impact of the goods and services tax (GST) on price, consumption and tax revenue from tobacco products in India and across states.MethodsData on prices, tax rates and tax revenue are used to estimate a benchmark scenario prior to the GST implementation in 2017–2018. Using own-price elasticity of demand for tobacco products, we estimate the impact of GST at the state level and the aggregate state-wise impact to obtain the national level impact.FindingsWe predict that the statutory GST rate of 28% plus compensation cess will increase the price of cigarettes,bidiand smokeless tobacco by 0.18%, 8.8% and 6%, respectively, and, as a result, it will reduce the weighted average consumption by 0.3%, 10% and 6% and increase tax revenue by 0.17%, 35% and 4.7%, respectively. Most states will experience a fall in tax revenue from tobacco products by more than 50% compared with the value-added tax revenue they collected pre-GST. The GST compensation cess will have to be used to compensate states’ revenue shortfalls.ConclusionsThe GST has increased the complexity of the tax system for tobacco products. In particular, for cigarettes, the specific cess constitutes the majority of tax revenue, and therefore, it must be revised regularly to protect revenue and keep real prices from falling. In addition, India should reintroduce excise taxation on all tobacco products, at least in part, on top of the GST, to make them less affordable and to smooth the transition after the expiration of the compensation cess.
BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase)
Authors: Descamps Betty , Saif Jaimy , Benest Andrew V. , Biglino Giovanni , Bates David O. , Chamorro-Jorganes Aranzazu , Emanueli Costanza 
Published: September 2018

Objective—
The NTs (neurotrophins), BDNF (brain-derived neurotrophic factor) and NT-3 promote vascular development and angiogenesis. This study investigated the contribution of endogenous NTs in embryonic stem cell (ESC) vascular differentiation and the potential of exogenous BDNF to improve the process of ESC differentiation to endothelial cells (ECs).

Approach and Results—

Mouse ESCs were differentiated into vascular cells using a 2-dimensional embryoid body (EB) model. Supplementation of either BDNF or NT-3 increased EC progenitors’ abundance at day 7 and enlarged the peripheral vascular plexus with ECs and SM22α
+
(smooth muscle 22 alpha-positive) smooth muscle cells by day 13. Conversely, inhibition of either BDNF or NT-3 receptor signaling reduced ECs, without affecting smooth muscle cells spread. This suggests that during vascular development, endogenous NTs are especially relevant for endothelial differentiation. At mechanistic level, we have identified that BDNF-driven ESC-endothelial differentiation is mediated by a pathway encompassing the transcriptional repressor EZH2 (enhancer of zeste homolog 2), microRNA-214 (miR-214), and eNOS (endothelial nitric oxide synthase). It was known that eNOS, which is needed for endothelial differentiation, can be transcriptionally repressed by EZH2. In turn, miR-214 targets EZH2 for inhibition. We newly found that in ESC-ECs, BDNF increases miR-214 expression, reduces EZH2 occupancy of the
eNOS
promoter, and increases eNOS expression. Moreover, we found that NRP-1 (neuropilin 1), KDR (kinase insert domain receptor), and pCas
130
(p130 Crk-associated substrate kinase), which reportedly induce definitive endothelial differentiation of pluripotent cells, were increased in BDNF-conditioned ESC-EC. Mechanistically, miR-214 mediated the BDNF-induced expressional changes, contributing to BDNF-driven endothelial differentiation. Finally, BDNF-conditioned ESC-ECs promoted angiogenesis in vitro and in vivo.

Conclusions—
BDNF promotes ESC-endothelial differentiation acting via miR-214.
Pharmacological Modulation of Right Ventricular Endocardial-Epicardial Gradients in Brugada Syndrome
Authors: Bhar-Amato Justine , Finlay Malcolm , Santos Diogo , Orini Michele , Chaubey Sanjay , Vyas Vishal , Taggart Peter , Grace Andrew A. , Huang Christopher L.-H. , Ben Simon Ron , Tinker Andrew , Lambiase Pier D. 
Published: September 2018

Background
We explored the hypothesis that increased cholinergic tone exerts its proarrhythmic effects in Brugada syndrome (BrS) through increasing dispersion of transmural repolarization in patients with spontaneous and drug-induced BrS.

Methods

BrS and supraventricular tachycardia patients were studied after deploying an Ensite Array in the right ventricular outflow tract and a Cardima catheter in the great cardiac vein to record endo and epicardial signals, respectively. S
1
-S
2
restitution curves from the right ventricular apex were conducted at baseline and after edrophonium challenge to promote increased cholinergic tone. The local unipolar electrograms were then analyzed to study transmural conduction and repolarization dynamics.

Results

The study included 8 BrS patients (5 men:3 women; mean age, 56 years) and 8 controls patients with supraventricular tachycardia (5 men:3 women; mean age, 48 years). Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times (mean difference: 26 ms;
P
<0.001). In contrast, patients with BrS showed longer endocardial than epicardial activation time (mean difference: −15 ms;
P
=0.001). BrS hearts, compared with controls, showed significantly larger transmural gradients in their activation recovery intervals (mean intervals, 20.5 versus 3.5 ms;
P
<0.01), with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased such gradients in both controls (to a mean of 16 ms [
P
<0.001]) and BrS (to 29.7 ms;
P
<0.001). However, these were attributable to epicardial and endocardial activation recovery interval prolongations in control and BrS hearts, respectively. Dynamic changes in repolarization gradients were also observed across the BrS right ventricular wall in BrS.

Conclusions
Differential contributions of conduction and repolarization were identified in BrS which critically modulated transmural dispersion of repolarization with significant cholinergic effects only identified in the patients with BrS. This has important implications for explaining the proarrhythmic effects of increased vagal tone in BrS, as well as evaluating autonomic modulation and epicardial ablation as therapeutic strategies.
Permanent His Bundle Pacing for Cardiac Resynchronization Therapy in Patients With Heart Failure and Right Bundle Branch Block
Authors: Sharma Parikshit S. , Naperkowski Angela , Bauch Terry D. , Chan Joseph Y.S. , Arnold Ahran D. , Whinnett Zachary I. , Ellenbogen Kenneth A. , Vijayaraman Pugazhendhi 
Published: September 2018

Background
Cardiac resynchronization therapy utilizing biventricular pacing is an effective therapy for patients with left ventricular (LV) systolic dysfunction, left bundle branch block, and heart failure. Benefits of biventricular pacing may be limited in patients with right bundle branch block (RBBB). Permanent His bundle pacing (HBP) has recently been reported as an option for cardiac resynchronization therapy. The aim of the study was to assess the feasibility and outcomes of HBP in patients with RBBB and heart failure.

Methods
HBP was attempted as a primary or rescue (failed LV lead implant) strategy in patients with reduced LV ejection fraction, RBBB, QRS duration ≥120 ms, and New York Heart Association class II to IV heart failure. Implant characteristics, New York Heart Association functional class, and echocardiographic data were assessed in follow-up.

Results

Mean age was 72±10 years, female 15%, with an average LV ejection fraction of 31±10%. HBP was successful in 37 of 39 patients (95%) with narrowing of RBBB in 78% cases. His capture and bundle branch block correction thresholds were 1.1±0.6 V and 1.4±0.7 V at 1 ms, respectively. During a mean follow-up of 15±23 months, there was a significant narrowing of QRS from 158±24 to 127±17 ms (
P
=0.0001), increase in LV ejection fraction from 31±10% to 39±13% (
P
=0.004), and improvement in New York Heart Association functional class from 2.8±0.6 to 2±0.7 (
P
=0.0001) with HBP. Increase in capture threshold occurred in 3 patients.

Conclusions
Permanent HBP was associated with significant narrowing of QRS duration and improvement in LV function in patients with RBBB and reduced LV ejection fraction. Permanent HBP is a promising option for cardiac resynchronization therapy in patients with RBBB and reduced LV ejection fraction.
Clinical and In Vitro Evidence That Left Ventricular Assist Device–Induced von Willebrand Factor Degradation Alters Angiogenesis
Authors: Bartoli Carlo R. , Zhang David M. , Hennessy-Strahs Samson , Kang Jooeun , Restle David J. , Bermudez Christian , Atluri Pavan , Acker Michael A. 
Published: September 2018

Background
Gastrointestinal bleeding from angiodysplasia is a major problem in continuous-flow left ventricular assist device (LVAD) patients. LVAD shear stress causes pathologic degradation of VWF (von Willebrand factor). A mechanistic relationship between VWF degradation and angiodysplasia has not been explored. We tested 2 novel hypotheses: (1) clinical hypothesis: VWF fragments are elevated in LVAD patients that develop angiodysplasia and (2) in vitro hypothesis: VWF fragments generated during LVAD support alter angiogenesis, which may contribute to angiodysplasia.

Methods and Results

Clinical study: Paired blood samples were collected from continuous-flow LVAD patients (n=35). VWF was quantified with immunoblotting. In vitro experiments: (1) To investigate whether LVAD support alters angiogenesis, human endothelial cells were cultured with LVAD patient plasma (n=11). To investigate mechanism, endothelial cells were cultured with VWF fragments produced by exposing human VWF and ADAMTS-13 (VWF protease) to LVAD-like shear stress (175 dyne/cm
2
, n=8). Clinical study results: in all patients (n=35, mean support 666±430 days), LVAD support degraded high-molecular-weight VWF multimers (
P
<0.0001) into low-molecular-weight VWF multimers (
P
<0.0001) and VWF fragments (
P
<0.0001). In patients with gastrointestinal bleeding from angiodysplasia (n=7), VWF fragments were elevated (
P
=0.02) versus nonbleeders. In contrast, in patients with gastrointestinal bleeding without angiodysplasia, VWF fragments were not elevated versus nonbleeders (
P
=0.96). In vitro experiments results: LVAD patient plasma caused abnormal angiogenesis with reduced tubule length (
P
=0.04) and migration (
P
=0.05). Similarly, endothelial cells grown with VWF degradation fragments exhibited reduced tubule length (
P
<0.001) and migration (
P
=0.01).

Conclusions
LVAD patients who bled from angiodysplasia had higher levels of VWF fragments than nonbleeders and gastrointestinal bleeders without angiodysplasia. VWF fragments caused abnormal angiogenesis in vitro. These findings suggest that VWF fragments may be a mechanistic link between LVAD support, abnormal angiogenesis, angiodysplasia, and gastrointestinal bleeding.
Early Natural History of Spontaneous Coronary Artery Dissection
Authors: Waterbury Thomas M. , Tweet Marysia S. , Hayes Sharonne N. , Eleid Mackram F. , Bell Malcolm R. , Lerman Amir , Singh Mandeep , Best Patricia J.M. , Lewis Bradley R. , Rihal Charanjit S. , Gersh Bernard J. , Gulati Rajiv 
Published: September 2018

Background:
Risks and mechanisms of extension of conservatively managed spontaneous coronary artery dissection (SCAD) remain incompletely understood. Study objectives were to (1) evaluate mechanisms of early SCAD evolution through serial angiographic analysis, and (2) determine predictors of early SCAD progression.

Methods and Results:

Retrospective registry study of patients with SCAD managed with an initial conservative strategy (n=240). Patients who experienced significant SCAD progression within 14 days, defined as clinical worsening plus new critical coronary obstruction on repeat angiography, were compared with remaining controls. A total of 42 of 240 (17.5%) experienced significant SCAD progression after index conservative approach; 91% by day 6. Isolated intramural hematoma (IMH) at baseline (no intimal dissection) was observed more frequently in those experiencing progression compared with controls (69.1% versus 44.4%;
P
=0.004). Multivariable predictors of SCAD progression included lesion severity, multivessel involvement, and isolated IMH. To investigate mechanisms of SCAD evolution, all repeat angiograms ≤14 days were compared with corresponding baselines (n=82 patient angiogram pairs). Of those with isolated IMH at baseline, 20% developed intimal dissection at repeat study. IMH was associated with greater longitudinal lesion extension (11.5 versus 2.8 mm;
P
=0.01), worsening Thrombolysis in Myocardial Infarction flow (−0.8 versus 0.1;
P
=0.003), and a nonsignificant lower rate of angiographic improvement (20.0% versus 31.3%;
P
=0.16) compared with the group with baseline intimal dissection. Optical coherence tomography subgroup analysis (n=17) indicated intimo-medial thickness to be lowest at the midpoint of IMH.

Conclusions:
Conservatively managed SCAD carries a 1:6 hazard for serious deterioration within 6 days. The risk was higher in those with isolated IMH at baseline. IMH often precedes development of intimal dissection, which has implications for mechanisms of SCAD.
Long-Term Outcomes After Transcatheter Aortic Valve-in-Valve Replacement
Authors: de Freitas Campos Guimarães Leonardo , Urena Marina , Wijeysundera Harindra C. , Munoz-Garcia Antonio , Serra Vicenç , Benitez Luis M. , Auffret Vincent , Cheema Asim N. , Amat-Santos Ignacio J. , Fisher Quentin , Himbert Dominique , Garcia del Blanco Bruno , Dager Antonio , Le Breton Hervé , Paradis Jean-Michel , Dumont Eric , Pibarot Philippe , Rodés-Cabau Josep 
Published: September 2018

Background:
Data on long-term outcomes after valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) are scarce. The objective of this study was to determine the long-term clinical outcomes and structural valve degeneration (SVD) over time in patients undergoing ViV-TAVR.

Methods and Results:

Consecutive patients undergoing ViV-TAVR in 9 centers between 2009 and 2015 were included. Patients were followed yearly, and clinical and echocardiography data were collected prospectively. SVD was defined as subclinical (increase >10 mm Hg in mean transvalvular gradient+decrease >0.3 cm
2
in valve area or new-onset mild or moderate aortic regurgitation) and clinically relevant (increase >20 mm Hg in mean transvalvular gradient+decrease >0.6 cm
2
in valve area or new-onset moderate-to-severe aortic regurgitation). A total of 116 patients (mean age, 76±11 years; 64.7% male; mean Society of Thoracic Surgeons score, 8.0±5.1%) were included. Balloon- and self-expandable valves were used in 47.9% and 52.1% of patients, respectively, and 30-day mortality was 6.9%. At a median follow-up of 3 years (range, 2–7 years), 30 patients (25.9%) had died, 20 of them (17.2%) from cardiovascular causes. Average mean transvalvular gradients remained stable up to 5-year follow-up (
P
=0.92), but clinically relevant SVD occurred in 3/99 patients (3.0%), and 15/99 patients (15.1%) had subclinical SVD. One patient with SVD had redo ViV-TAVR.

Conclusions:
About one-fourth of ViV-TAVR recipients had died after a median follow-up of 3 years. Overall valve hemodynamics remained stable over time and clinically relevant SVD was infrequent, but 1 out of 10 patients exhibited some degree of SVD.
Fall Risk and Outcomes Among Patients Hospitalized With Cardiovascular Disease in the Community
Authors: Manemann Sheila M. , Chamberlain Alanna M. , Boyd Cynthia M. , Miller Donna M. , Poe Kimberly L. , Cheville Andrea , Weston Susan A. , Koepsell Ellen E. , Jiang Ruoxiang , Roger Véronique L. 
Published: September 2018

Background
As the population with cardiovascular disease ages, geriatric conditions are of increasing relevance. A possible geriatric prognostic indicator may be a fall risk score, which is mandated by The Joint Commission to be measured on all hospitalized patients. The prognostic value of a fall risk score on outcomes after dismissal is not well known. Thus, we aimed to determine whether a fall risk score is associated with death and hospital readmissions in patients with a recent incident cardiovascular disease event.

Methods and Results
In this retrospective cohort study, Olmsted County, MN patients with incident heart failure, myocardial infarction, or atrial fibrillation between August 1, 2005, and December 31, 2011, who were hospitalized within 180 days after the event were studied. Fall risk was measured by the Hendrich II fall risk model. Patients were followed for death or readmission within 30 days or 1 year. Among 2456 hospitalized patients with recent incident cardiovascular disease (549 heart failure, 784 myocardial infarction, 1123 atrial fibrillation; mean [SD] age, 71 [15] years; 55% men), the fall risk score was high in 22% of patients and moderate in 38%. The risk of death was increased if the fall risk score was increased, independent of age and comorbidities (moderate hazard ratio, 1.51; 95% CI, 1.09–2.08; high hazard ratio, 3.49; 95% CI, 2.52–4.85). Similarly, the risk of 30-day readmissions was substantially increased with a greater fall risk score (moderate hazard ratio, 1.29; 95% CI, 1.03–1.62; high hazard ratio, 1.63; 95% CI, 1.23–2.15). Results were similar for readmissions within 1 year.

Conclusions
More than half of hospitalized patients with recent incident cardiovascular disease have an elevated fall risk score, which is associated with an increased risk in readmissions and death. These results delineate an approach for risk stratification and management that may prevent readmissions and improve survival.
Association Between Postoperative Pneumonia and 90-Day Episode Payments and Outcomes Among Medicare Beneficiaries Undergoing Cardiac Surgery
Authors: Thompson Michael P. , Cabrera Lourdes , Strobel Raymond J. , Harrington Steven D. , Zhang Min , Wu Xiaoting , Prager Richard L. , Likosky Donald S. 
Published: September 2018

Background
Postoperative pneumonia is the most common healthcare-associated infection in cardiac surgical patients, yet their impact across a 90-day episode of care remains unknown. Our objective was to examine the relationship between pneumonia and 90-day episode payments and outcomes among Medicare beneficiaries undergoing cardiac surgery.

Methods and Results

Medicare claims were used to identify beneficiaries with episodes of coronary artery bypass grafting (CABG; n=56 728) and valve surgery (n=56 377) across 1045 centers between April 2014 and March 2015. Using a published diagnosis code-based algorithm, we identified pneumonia in 6.4% CABG episodes and 6.6% of valve surgery episodes. We compared price-standardized 90-day episode payments and outcome measures (postoperative length of stay, discharge to postacute care, mortality, and readmission) between beneficiaries with and without pneumonia using hierarchical regression models, adjusting for patient factors and hospital random effects. Pneumonia was associated with 24.5% higher episode payments for CABG ($46 723 versus $37 496;
P
<0.001) and 26.5% higher episode payments for valve surgery ($61 544 versus $48 549;
P
<0.001). For both cohorts, pneumonia was significantly associated with longer postoperative length of stay (CABG: +4.1 days, valve: +5.6 days), more frequent discharge to postacute care (CABG: odds ratio [OR]=1.99, valve: OR=2.17), and higher rates of 30-day mortality (CABG: OR=2.42, valve: OR=2.57) and 90-day readmission (CABG: OR=1.20, valve: OR=1.25), all
P
<0.001. We compared episode payments and outcomes across terciles of pneumonia rates and found that high pneumonia rate hospitals had higher episode payments and poorer outcomes compared with episodes at low pneumonia rate hospitals in both CABG and valve surgery cohorts.

Conclusions
Postoperative pneumonia was associated with significantly higher 90-day episode payments and inferior outcomes at the patient and hospital level. Future work should examine whether reducing pneumonia after cardiac surgery reduces episode spending and improves outcomes, which could facilitate hospital success in value-based reimbursement programs.
Physiological and Molecular Responses to Altered Sodium Intake in Rat Pregnancy
Authors: Eisele Nicole , Klossner Rahel , Escher Geneviève , Rudloff Stefan , Larionov Alexey , Theilig Franziska , Mohaupt Markus G. , Mistry Hiten D. , Gennari‐Moser Carine 
Published: September 2018

Background

In pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure (
BP
). Reducing
BP
by increasing Na
+
intake via plasma volume expansion appears contra‐intuitive. We hypothesize that an appropriate Na
+
intake in pregnancy reduces maternal
BP
and adapts the renin‐angiotensin system in a pregnancy‐specific manner.

Methods and Results

BP
was measured by implanted telemetry in Sprague‐Dawley rats before and throughout pregnancy. Pregnant and nonpregnant animals received either a normal‐salt (0.4%;
NS
), high‐salt (8%;
HS
), or low‐salt (0.01%;
LS
) diet, or
HS
(days 1–14) followed by
LS
(days 14–20) diet (
HS
/
LS
). Before delivery (day 20), animals were euthanized and organs collected. Food, water, and Na
+
intake were monitored in metabolic cages, and urinary creatinine and Na
+
were analyzed. Na
+
intake and retention increased in pregnancy (
NS
,
LS
), leading to a positive Na
+
balance (
NS
,
LS
).
BP
was stable during
LS
, but reduced in
HS
conditions in pregnancy. The renin‐angiotensin system was adapted as expected. Activating cleavage of α‐ and γ‐subunits of the renal epithelial Na
+
channel and expression of‐full length medullary β‐subunits, accentuated further in all
LS
conditions, were upregulated in pregnancy.

Conclusions

Pregnancy led to Na
+
retention adapted to dietary changes.
HS
exposure paradoxically reduced
BP
. Na
+
uptake while only modestly linked to the renin‐angiotensin system is enhanced in the presence of posttranslational renal epithelial Na
+
channel modifications. This suggests (1) storage of Na
+
in pregnancy upon
HS
exposure, bridging periods of
LS
availability; and (2) that potentially non–renin‐angiotensin–related mechanisms participate in
EN
aC activation and consecutive Na
+
retention.