bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Alcohol-Induced Golgi Fragmentation for Androgen Receptor Signaling in Prostate Cancer
Authors: Manca Sonia , Frisbie Cole P. , LaGrange Chad A. , Casey Carol A. , Riethoven Jean-Jack M. , Petrosyan Armen 
Published: September 2018

Abstract

Multiple epidemiologic observations and meta-analysis clearly indicate the link between alcohol abuse and the incidence and progression of prostate cancer; however, the mechanism remains enigmatic. Recently, it was found that ethanol (EtOH) induces disorganization of the Golgi complex caused by impaired function of the largest Golgi matrix protein, giantin (GOLGB1), which, in turn, alters the Golgi docking of resident Golgi proteins. Here, it is determined that in normal prostate cells, histone deacetylase 6 (HDAC6), the known regulator of androgen receptor (AR) signaling, localizes in the cytoplasm and nucleus, while its kinase, glycogen synthase kinase β (GSK3β), primarily resides in the Golgi. Progression of prostate cancer is accompanied by Golgi scattering, translocation of GSK3β from the Golgi to the cytoplasm, and the cytoplasmic shift in HDAC6 localization. Alcohol dehydrogenase–generated metabolites induces Golgi disorganization in androgen-responsive LNCaP and 22Rv1 cells, facilitates tumor growth in a mouse xenograft model and activates anchorage-independent proliferation, migration, and cell adhesion. EtOH-treated cells demonstrate reduced giantin and subsequent cytoplasmic GSK3β; this phenomenon was validated in giantin-depleted cells. Redistribution of GSK3β to the cytoplasm results in phosphorylation of HDAC6 and its retention in the cytoplasm, which, in turn, stimulates deacetylation of HSP90, AR import into the nucleus, and secretion of prostate-specific antigen (PSA). Finally, the relationship between Golgi morphology, HDAC6 cytoplasmic content, and clinicopathologic features was assessed in human prostate cancer patient specimens with and without a history of alcohol dependence.

Implications:
This study demonstrates the importance of alcohol-induced Golgi fragmentation in the activation of AR-mediated proliferation.
Right Ventricular Strain and Dyssynchrony Assessment in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Prati Giulio , Vitrella Giancarlo , Allocca Giuseppe , Muser Daniele , Buttignoni Sonja Cukon , Piccoli Gianluca , Morocutti Giorgio , Delise Pietro , Pinamonti Bruno , Proclemer Alessandro , Sinagra Gianfranco , Nucifora Gaetano 
Published: September 2018

Background—
Analysis of right ventricular (RV) regional dysfunction by cardiac magnetic resonance (CMR) imaging in arrhythmogenic RV cardiomyopathy (ARVC) may be inadequate because of the complex contraction pattern of the RV. Aim of this study was to determine the use of RV strain and dyssynchrony assessment in ARVC using feature-tracking CMR analysis.

Methods and Results—

Thirty-two consecutive patients with ARVC referred to CMR imaging were included. Thirty-two patients with idiopathic RV outflow tract arrhythmias and 32 control subjects, matched for age and sex to the ARVC group, were included for comparison purpose. CMR imaging was performed to assess biventricular function; feature-tracking analysis was applied to the cine CMR images to assess regional and global longitudinal, circumferential, and radial RV strains and RV dyssynchrony (defined as the SD of the time-to-peak strain of the RV segments). RV global longitudinal strain (−17±5% versus −26±6% versus −29±6%;
P
<0.001), global circumferential strain (−9±4% versus −12±4% versus −13±5%;
P
=0.001), and global radial strain (18 [12–26]% versus 22 [15–32]% versus 27 [20–39]%;
P
=0.015) were significantly lower and SD of the time-to-peak RV strain in all 3 directions were significantly higher among patients with ARVC compared with patients with RV outflow tract arrhythmias and controls. RV global longitudinal strain >−23.2%, SD of the time-to-peak RV longitudinal strain >113.1 ms, and SD of the time-to-peak RV circumferential strain >177.1 ms allowed correct identification of 88%, 75%, and 63% of ARVC patients with no or only minor CMR criteria for ARVC diagnosis.

Conclusions—
Strain analysis by feature-tracking CMR helps to objectively quantify global and regional RV dysfunction and RV dyssynchrony in patients with ARVC and provides incremental value over conventional cine CMR imaging.
Absence of Myocardial Fibrosis Predicts Favorable Long-Term Survival in New-Onset Heart Failure
Authors: Gulati Ankur , Japp Alan G. , Raza Sadaf , Halliday Brian P. , Jones Daniel A. , Newsome Simon , Ismail Nizar A. , Morarji Kishen , Khwaja Jahanzaib , Spath Nick , Shakespeare Carl , Kalra Paul R. , Lloyd Guy , Mathur Anthony , Cleland John G.F. , Cowie Martin R. , Assomull Ravi G. , Pennell Dudley J. , Ismail Tevfik F. , Prasad Sanjay K. 
Published: September 2018

Background:
Myocardial fibrosis, identified by late gadolinium enhancement cardiovascular magnetic resonance, predicts outcomes in chronic heart failure (HF). Its prognostic significance in new-onset HF and reduced left ventricular ejection fraction (LVEF) is unclear. We investigated whether the pattern and extent of fibrosis predict survival in new-onset HF and reduced LVEF of initially uncertain pathogenesis.

Methods and Results:

Of 120 consecutive patients with new-onset (<6 months) HF and reduced LVEF, 31 (26%) had infarct fibrosis, 25 (21%) had midwall fibrosis, and 64 (53%) had no fibrosis. During median follow-up of 8.9 years, 33 (28%) patients died. Patients with infarct fibrosis (hazard ratios [HR], 3.32; 95% CI, 1.46–7.58;
P
=0.004) or midwall fibrosis (HR, 2.99; 95% CI, 1.24–7.19;
P
=0.014) were more likely to die compared with those without fibrosis. On multivariable analysis, the pattern and extent of fibrosis were both associated with all-cause mortality (by fibrosis pattern: infarct: HR, 2.60; 95% CI, 1.08–6.27;
P
=0.033; midwall: HR, 2.64; 95% CI, 1.08–6.47;
P
=0.034; by fibrosis extent per 1%: HR, 1.07; 95% CI, 1.03–1.12;
P
<0.001). Fibrosis pattern also predicted composites of cardiovascular mortality or aborted sudden cardiac death (infarct: HR, 3.45; 95% CI, 1.20–9.90;
P
=0.022; midwall: HR, 6.59; 95% CI, 2.26–19.22;
P
<0.001), and all-cause mortality, HF hospitalization, or aborted sudden cardiac death (infarct: HR, 2.69; 95% CI, 1.26–5.76;
P
=0.011; midwall fibrosis: HR, 2.97; 95% CI, 1.37–6.45;
P
=0.006). Addition of fibrosis pattern to LVEF improved risk prediction for all-cause mortality (LVEF versus LVEF+fibrosis C statistic: 0.66 versus 0.71;
P
=0.033). Importantly, the absence of fibrosis heralded a favorable prognosis with an 85% survival rate over the duration of follow-up.

Conclusions:
The pattern and extent of myocardial fibrosis predict adverse outcomes in new-onset HF and reduced LVEF. In contrast, the absence of fibrosis portends a durable warranty period with a low incidence of adverse events. These findings support a role for late gadolinium enhancement cardiovascular magnetic resonance in the early risk stratification of patients with HF of uncertain pathogenesis.
Unselected Use of Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Coronary Revascularization
Authors: Yamaji Kyohei , Zanchin Thomas , Zanchin Christian , Stortecky Stefan , Koskinas Konstantinos C. , Hunziker Lukas , Praz Fabien , Blöchlinger Stefan , Moro Christina , Moschovitis Aris , Seiler Christian , Valgimigli Marco , Billinger Michael , Pilgrim Thomas , Heg Dik , Windecker Stephan , Räber Lorenz 
Published: September 2018

Background:
Biodegradable polymer sirolimus-eluting stents (BP-SESs) have been reported to be noninferior compared with durable polymer everolimus-eluting stents (DP-EES) in a randomized clinical trial. We sought to compare the efficacy and safety of an ultrathin strut BP-SES with a DP-EES in an all-comers population.

Methods and Results:

Among 7640 consecutive patients who underwent percutaneous coronary intervention between March 2011 and June 2015, 4638 patients were exclusively treated with BP-SES (N=1896; 3137 lesions) or DP-EES (N=2742; 4468 lesions). After propensity score matching within strata of clinical indications, the final study population consisted of 2902 matched patients (BP-SES 2406 lesions and DP-EES 2368 lesions). The primary device-oriented composite end point (DOCE) included cardiac death, target vessel myocardial infarction, and target lesion revascularization at 1 year. BP-SES (6.9%) was noninferior to DP-EES (8.0%) with respect to device-oriented composite end point (hazard ratio [HR], 0.85; 95% CI, 0.65–1.11;
P
for noninferiority <0.001;
P
for superiority=0.24). No differences in cardiac death (BP-SES, 2.3% versus DP-EES, 3.0%; HR, 0.76; 95% CI, 0.49–1.20;
P
=0.25), myocardial infarction (BP-SES, 4.6% versus DP-EES, 4.6%; HR, 1.00; 95% CI, 0.71–1.40;
P
=0.99), or target lesion revascularization (BP-SES, 2.8% versus DP-EES, 2.5%; HR, 1.11; 95% CI, 0.71–1.74;
P
=0.65) were observed. The rate of periprocedural myocardial infarction was comparable between the 2 groups (2.1% versus 2.2%; HR, 0.97; 95% CI, 0.59–1.58;
P
=0.89). The rate of definite stent thrombosis was similarly low throughout 1 year (BP-SES, 0.8% versus DP-EES, 0.8%; HR, 1.00; 95% CI, 0.45–2.22;
P
=1.00).

Conclusions:
In a consecutively enrolled percutaneous coronary intervention population reflecting routine clinical practice, BP-SES was noninferior to DP-EES for device-oriented composite end point at 1 year.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02241291.
Concomitant Intra-Aortic Balloon Pump Use in Cardiogenic Shock Requiring Veno-Arterial Extracorporeal Membrane Oxygenation
Authors: Vallabhajosyula Saraschandra , O’Horo John C. , Antharam Phanindra , Ananthaneni Sindhura , Vallabhajosyula Saarwaani , Stulak John M. , Eleid Mackram F. , Dunlay Shannon M. , Gersh Bernard J. , Rihal Charanjit S. , Barsness Gregory W. 
Published: September 2018

Background:
There are contrasting reports on the effectiveness of a concomitant intra-aortic balloon pump (IABP) in cardiogenic shock patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). This study sought to compare short-term mortality in patients with cardiogenic shock treated with VA-ECMO with and without IABP.

Methods and Results:

We reviewed the published literature from 2000 to 2018 for studies evaluating adult patients requiring VA-ECMO for cardiogenic shock with concomitant IABP. Studies reporting short-term mortality were included. Meta-analysis of the association of IABP with mortality was performed using Mantel-Haenszel models. Subgroup analyses were performed in patients with cardiogenic shock complicating acute myocardial infarction (AMI) and postcardiotomy cardiogenic shock. Twenty-two observational studies with 4653 patients were included. These studies showed high heterogeneity for the total and postcardiotomy cardiogenic shock cohorts and low heterogeneity for the AMI cohort. Short-term mortality was not significantly different in patients with and without IABP 42.1% versus 57.8%; risk ratio, 0.80; 95% CI, 0.52–1.22;
P
=0.30. However, concomitant IABP with VA-ECMO was associated with lower mortality in patients with AMI (50.8% versus 62.4%; risk ratio, 0.56; 95% CI, 0.46–0.67;
P
<0.001). There was no difference in mortality in postcardiotomy cardiogenic shock and mixed causes for cardiogenic shock.

Conclusions:
In cardiogenic shock patients requiring VA-ECMO support, the use of IABP did not influence mortality in the total cohort. In patients with AMI, use of IABP with VA-ECMO was associated with 18.5% lower mortality in comparison to patients on VA-ECMO alone. Further randomized studies are warranted to corroborate these observational data.
Rate, Timing, Correlates, and Outcomes of Hemodynamic Valve Deterioration After Bioprosthetic Surgical Aortic Valve Replacement
Authors: Salaun Erwan , Mahjoub Haïfa , Girerd Nicolas , Dagenais François , Voisine Pierre , Mohammadi Siamak , Yanagawa Bobby , Kalavrouziotis Dimitri , Juni Peter , Verma Subodh , Puri Rishi , Coté Nancy , Rodés-Cabau Josep , Mathieu Patrick , Clavel Marie-Annick , Pibarot Philippe 
Published: September 2018

Background:
The incidence of structural valve deterioration after bioprosthesis (BP) aortic valve replacement (AVR) established on the basis of reoperation may substantially underestimate the true incidence. The objective is to determine the rate, timing, correlates, and association between hemodynamic valve deterioration (HVD) and outcomes assessed by Doppler echocardiography after surgical BP AVR.

Methods:
A total of 1387 patients (62.2% male, 70.5±7.8 years of age) who underwent BP AVR were included in this retrospective study. Baseline echocardiography was performed at a median time of 4.1 (1.3–6.5) months after AVR. All patients had an echocardiographic follow-up ≥2 years after AVR (926 at least 5 years and 385 at least 10 years). HVD was defined by Doppler assessment as a ≥10 mm Hg increase in mean gradient or worsening of transprosthetic regurgitation ≥1/3 class. HVD was classified according to the timing after AVR: “very early,” during the first 2-years; “early,” between 2 and 5 years; “midterm,” between 5 and 10 years; and “long-term,” >10 years.

Results:

A total of 428 patients (30.9%) developed HVD. Among these patients, 52 (12.0%) were classified as “very early,” 129 (30.1%) as “early,” 158 (36.9%) as “midterm,” and 89 (20.8%) as “long-term” HVD. Factors independently associated with HVD occurring within the first 5 years after AVR were diabetes mellitus (
P
=0.01), active smoking (
P
=0.01), renal insufficiency (
P
=0.01), baseline postoperative mean gradient ≥15 mm Hg (
P
=0.04) or transprosthetic regurgitation ≥mild (
P
=0.04), and type of BP (stented versus stentless,
P
=0.003). Factors associated with HVD occurring after the fifth year after AVR were female sex (
P
=0.03), warfarin use (
P
=0.007), and BP type (
P
<0.001). HVD was independently associated with mortality (hazard ratio, 2.18; 95% CI, 1.86–2.57;
P
<0.001).

Conclusions:
HVD as identified by Doppler echocardiography occurred in one third of patients and was associated with a 2.2-fold higher adjusted mortality. Diabetes mellitus and renal insufficiency were associated with early HVD, whereas female sex, warfarin use, and stented BPs (versus stentless) were associated with late HVD.
ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK‐AKT Signaling
Authors: Xiang Mei , Luo Hongbo , Wu Jia , Ren Lingyun , Ding Xiangchao , Wu Chuangyan , Chen Jiuling , Chen Shanshan , Zhang Hao , Yu Lu , Zou Yanqiang , Xu Heng , Ye Ping , Chen Manhua , Xia Jiahong 
Published: September 2018

Background
Cardiac hypertrophy has been recognized as an important independent risk factor for the development of heart failure and increases the risk of cardiac morbidity and mortality. A disintegrin and metalloprotease 23 (ADAM23), a member of ADAM family, is involved in cancer and neuronal differentiation. Although ADAM23 is expressed in the heart, the role of ADAM23 in the heart and in cardiac diseases remains unknown.

Methods and Results

We observed that ADAM23 expression is decreased in both failing human hearts and hypertrophic mice hearts. Cardiac‐specific conditional ADAM23‐knockout mice significantly exhibited exacerbated cardiac hypertrophy, fibrosis, and dysfunction, whereas transgenic mice overexpressing ADAM23 in the heart exhibited reduced cardiac hypertrophy in response to pressure overload. Consistent results were also observed in angiotensin
II
‐induced neonatal rat cardiomyocyte hypertrophy. Mechanistically, ADAM23 exerts anti‐hypertrophic effects by specifically targeting the focal adhesion kinase‐protein kinase B (FAK‐AKT) signaling cascade. Focal adhesion kinase inactivation by inhibitor (
PF
‐562271) greatly reversed the detrimental effects in ADAM23‐knockout mice subjected to aortic banding.

Conclusion
Altogether, we identified ADAM23 as a negative regulator of cardiac hypertrophy through inhibiting focal adhesion kinase‐protein kinase B signaling pathway, which could be a promising therapeutic target for this malady.
Breastfeeding History and Risk of Stroke Among Parous Postmenopausal Women in the Women's Health Initiative
Authors: Jacobson Lisette T. , Hade Erinn M. , Collins Tracie C. , Margolis Karen L. , Waring Molly E. , Van Horn Linda V. , Silver Brian , Sattari Maryam , Bird Chloe E. , Kimminau Kim , Wambach Karen , Stefanick Marcia L. 
Published: September 2018

Background
Stroke is the third leading cause of death among US Hispanic and non‐Hispanic black women aged 65 and older. One factor that may protect against stroke is breastfeeding. Few studies have assessed the association between breastfeeding and stroke and whether this association differs by race and ethnicity.

Methods and Results

Data were taken from the Women's Health Initiative Observational Study with follow‐up through 2010; adjusted hazard ratios for stroke subsequent to childbirth were estimated with Cox regression models accounting for left and right censoring, overall and stratified by race/ethnicity. Of the 80 191 parous women in the Women's Health Initiative Observational Study, 2699 (3.4%) had experienced a stroke within a follow‐up period of 12.6 years. The average age was 63.7 years at baseline. Fifty‐eight percent (n=46 699) reported ever breastfeeding; 83% were non‐Hispanic white, 8% were non‐Hispanic black, 4% were Hispanic, and 5% were of other race/ethnicity. After adjustment for nonmodifiable potential confounders, compared with women who had never breastfed, women who reported ever breastfeeding had a 23% lower risk of stroke (adjusted hazard ratio=0.77; 95% confidence interval 0.70‐0.83). This association was strongest for non‐Hispanic black women (adjusted hazard ratio=0.52; 95% confidence interval 0.37‐0.71). Further, breastfeeding for a relatively short duration (1‐6 months) was associated with a 19% lower risk of stroke (adjusted hazard ratios=0.81; 95% confidence interval 0.74‐0.89). This association appeared stronger with longer breastfeeding duration and among non‐Hispanic white and non‐Hispanic black women (test for trend
P<
0.01).

Conclusions
Study results show an association and dose‐response relationship between breastfeeding and lower risk of stroke among postmenopausal women after adjustment for multiple stroke risk factors and lifestyle variables. Further investigation is warranted.
Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris
Authors: Dhar Indu , Svingen Gard F.T. , Ueland Per M. , Lysne Vegard , Svenningsson Mads M. , Tell Grethe S. , Nygård Ottar K. 
Published: September 2018

Background
Cystathionine is an intermediate product in the transsulfuration pathway and formed during the B6‐dependent conversion of methionine to cysteine. Elevated plasma cystathionine has been related to atherosclerosis, which is a major etiological factor for ischemic stroke. However, the role of cystathionine in stroke development is unknown. Therefore, we prospectively assessed the association of circulating levels of cystathionine with risk of total and ischemic stroke.

Methods and Results
Two‐thousand thirty‐six patients (64% men; median age, 62 years) undergoing coronary angiography for suspected stable angina pectoris were included. Stroke cases were identified by linkage to the CVDNOR (Cardiovascular Disease in Norway) project. Hazard ratios with confidence intervals (95% confidence interval) were estimated by using Cox‐regression analyses. During 7.3 years of median follow‐up, 124 (6.1%) incident strokes were ascertained, which comprised 100 cases of ischemic stroke. There was a positive association of plasma cystathionine with risk of total stroke and ischemic stroke. Comparing the fourth versus the first cystathionine quartiles, age‐ and sex‐adjusted hazard ratios (95% confidence interval) were 2.11 (1.19–3.75) and 2.56 (1.31–4.99) for total and ischemic stroke, respectively. Additional adjustment for major stroke risk factors only slightly attenuated the associations, which tended to be stronger in patients without previous or existing atrial fibrillation at baseline (hazard ratio [95% confidence interval], 2.43 [1.27–4.65] and 2.88 [1.39–5.98] for total and ischemic stroke, respectively).

Conclusions
In patients with suspected stable angina pectoris, plasma cystathionine was independently related to increased risk of total stroke and, in particular, ischemic stroke.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00354081.
INCA (Peru) Study: Impact of Non‐Invasive Cardiac Magnetic Resonance Assessment in the Developing World
Authors: Menacho Katia , Ramirez Sara , Segura Pedro , Nordin Sabrina , Abdel‐Gadir Amna , Illatopa Violeta , Bhuva Anish , Benedetti Giulia , Boubertakh Redha , Abad Pedro , Rodriguez Bertha , Medina Felix , Treibel Thomas , Westwood Mark , Fernandes Juliano , Walker John Malcolm , Litt Harold , Moon James C. 
Published: September 2018

Background

Advanced cardiac imaging permits optimal targeting of cardiac treatment but needs to be faster, cheaper, and easier for global delivery. We aimed to pilot rapid cardiac magnetic resonance (
CMR
) with contrast in a developing nation, embedding it within clinical care along with training and mentoring.

Methods and Results

A cross‐sectional study of
CMR
delivery and clinical impact assessment performed 2016–2017 in an upper middle‐income country. An International partnership (clinicians in Peru and collaborators from the United Kingdom, United States, Brazil, and Colombia) developed and tested a 15‐minute
CMR
protocol in the United Kingdom, for cardiac volumes, function and scar, and delivered it with reporting combined with training, education and mentoring in 2 centers in the capital city, Lima, Peru, 100 patients referred by local doctors from 6 centers. Management changes related to the
CMR
were reviewed at 12 months. One‐hundred scans were conducted in 98 patients with no complications. Final diagnoses were cardiomyopathy (hypertrophic, 26%; dilated, 22%; ischemic, 15%) and 12 other pathologies including tumors, congenital heart disease, iron overload, amyloidosis, genetic syndromes, vasculitis, thrombi, and valve disease. Scan cost was $150 USD, and the average scan duration was 18±7 minutes. Findings impacted management in 56% of patients, including previously unsuspected diagnoses in 19% and therapeutic management changes in 37%.

Conclusions

Advanced cardiac diagnostics, here
CMR
with contrast, is possible using existing infrastructure in the developing world in 18 minutes for $150, resulting in important changes in patient care.