bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is comprehensive geriatric assessment hospital at home a cost-effective alternative to hospital admission for older people?
Authors: Singh Surya , Gray Alastair , Shepperd Sasha , Stott David J , Ellis Graham , Hemsley Anthony , Khanna Pradeep , Ramsay Scott , Schiff Rebekah , Tsiachristas Apostolos , Wilkinson Angela , Young John 
Published: October 2021

Abstract

Background
hospital level healthcare in the home guided by comprehensive geriatric assessment (CGA) might provide a less costly alternative to hospitalisation for older people.

Objective
to determine the cost-effectiveness of CGA admission avoidance hospital at home (HAH) compared with hospital admission.

Design/intervention
a cost-effectiveness study alongside a randomised trial of CGA in an admission avoidance HAH setting, compared with admission to hospital.

Participants/setting
older people considered for a hospital admission in nine locations across the UK were randomised using a 2:1 randomisation schedule to admission avoidance HAH with CGA (N = 700), or admission to hospital with CGA when available (N = 355).

Measurements
quality adjusted life years, resource use and costs at baseline and 6 months; incremental cost-effectiveness ratios were calculated. The main analysis used complete cases.

Results
adjusting for baseline covariates, HAH was less costly than admission to hospital from a health and social care perspective (mean −£2,265, 95% CI: −4,279 to −252), and remained less costly with the addition of informal care costs (mean difference −£2,840, 95% CI: −5,495 to −185). There was no difference in quality adjusted survival. Using multiple imputation for missing data, the mean difference in health and social care costs widened to −£2,458 (95% CI: −4,977 to 61) and societal costs remained significantly lower (−£3,083, 95% CI: −5,880 to −287). There was little change to quality adjusted survival.

Conclusions
CGA HAH is a cost-effective alternative to admission to hospital for selected older people.
EDCNN: identification of genome-wide RNA-binding proteins using evolutionary deep convolutional neural network
Authors: Wang Yawei , Yang Yuning , Ma Zhiqiang , Wong Ka-Chun , Li Xiangtao 
Published: October 2021

AbstractMotivationRNA-binding proteins (RBPs) are a group of proteins associated with RNA regulation and metabolism, and play an essential role in mediating the maturation, transport, localization and translation of RNA. Recently, Genome-wide RNA-binding event detection methods have been developed to predict RBPs. Unfortunately, the existing computational methods usually suffer some limitations, such as high-dimensionality, data sparsity and low model performance.ResultsDeep convolution neural network has a useful advantage for solving high-dimensional and sparse data. To improve further the performance of deep convolution neural network, we propose evolutionary deep convolutional neural network (EDCNN) to identify protein–RNA interactions by synergizing evolutionary optimization with gradient descent to enhance deep conventional neural network. In particular, EDCNN combines evolutionary algorithms and different gradient descent models in a complementary algorithm, where the gradient descent and evolution steps can alternately optimize the RNA-binding event search. To validate the performance of EDCNN, an experiment is conducted on two large-scale CLIP-seq datasets, and results reveal that EDCNN provides superior performance to other state-of-the-art methods. Furthermore, time complexity analysis, parameter analysis and motif analysis are conducted to demonstrate the effectiveness of our proposed algorithm from several perspectives.Availability and implementationThe EDCNN algorithm is available at GitHub: https://github.com/yaweiwang1232/EDCNN. Both the software and the supporting data can be downloaded from: https://figshare.com/articles/software/EDCNN/16803217.Supplementary informationSupplementary data are available at Bioinformatics online.
The phosphorylated retinoid X receptor-α promotes diethylnitrosamine-induced hepatocarcinogenesis in mice through the activation of β-catenin signaling pathway
Authors: Sakai Hiroyasu , Yamada Yasuhiro , Kubota Masaya , Imai Kenji , Shirakami Yohei , Tomita Hiroyuki , Hara Akira , Shimizu Masahito 
Published: October 2021

AbstractPrevious studies have shown that phosphorylation of the retinoid X receptor-α (RXRα) is associated with the development of hepatocellular carcinoma (HCC). However, these findings were revealed using HCC cell lines that express phosphorylated-RXRα (p-RXRα) proteins; therefore, it remains unclear whether p-RXRα affects hepatocarcinogenesis in vivo. Therefore, to investigate the biological function of p-RXRα in vivo, we developed a doxycycline-inducible ES cell line and transgenic mouse, both of which overexpress the phosphomimetic mutant form of RXRα, T82D/S260D, in a doxycycline-dependent manner. We found that the development of liver tumors, especially high-grade adenoma and HCC, was enhanced in diethylnitrosamine (DEN)-treated T82D/S260D-inducible mice. Moreover, the increased incidence of liver tumors in the transgenic mice was attributable to the promotion of cell cycle progression. Interestingly, the expression of β-catenin protein and its target gene cyclin D1 was elevated in the liver tumors of DEN-treated T82D/S260D-inducible mice, concurrent with increased cytoplasmic and nuclear β-catenin protein expression, indicating its stabilization and transcriptional activation. These results indicate that p-RXRα promotes DEN-induced hepatocarcinogenesis in mice through the activation of the β-catenin signaling pathway, suggesting that p-RXRα may serve as a possible therapeutic target for HCC.
Prognostic values of exercise echocardiography and cardiopulmonary exercise testing in patients with primary mitral regurgitation
Authors: Coisne Augustin , Aghezzaf Samy , Galli Elena , Mouton Stéphanie , Richardson Marjorie , Dubois Denis , Delsart Pascal , Domanski Olivia , Bauters Christophe , Charton Marion , L'Official Guillaume , Modine Thomas , Vincentelli André , Juthier Francis , Lancellotti Patrizio , Donal Erwan , Montaigne David 
Published: October 2021

Abstract

Aims
To compare the clinical significance of exercise echocardiography (ExE) and cardiopulmonary exercise testing (CPX) in patients with ≥moderate primary mitral regurgitation (MR) and discrepancy between symptoms and MR severity.

Methods and results
Patients consulting for ≥moderate discordant primary MR prospectively underwent low (25 W) ExE, peak ExE, and CPX within 2 months in Lille and Rennes University Hospital. Patients with Class I recommendation for surgical MR correction were excluded. Changes in MR severity, systolic pulmonary artery pressure (SPAP), left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion were evaluated during ExE. Patients were followed for major events (ME): cardiovascular death, acute heart failure, or mitral valve surgery. Among 128 patients included, 22 presented mild-to-moderate, 61 moderate-to-severe, and 45 severe MR. Unlike MR variation, SPAP and LVEF were successfully assessed during ExE in most patients. Forty-one patients (32%) displayed reduced aerobic capacity (peak VO2 &lt; 80% of predicted value) with cardiac limitation in 28 (68%) and muscular or respiratory limitation in the 13 others (32%). ME occurred in 61 patients (47.7%) during a mean follow-up of 27 ± 21 months. Twenty-five Watts SPAP [hazard ratio (HR) (95% confidence interval, CI) = 1.03 (1.01–1.06), P = 0.003] and reduced aerobic capacity [HR (95% CI) = 1.74 (1.03–2.95), P = 0.04] were independently predictive of ME, even after adjustment for MR severity. The cut-off of 55 mmHg for 25 W SPAP showed the best accuracy to predict ME (area under the curve = 0.60, P = 0.05).

Conclusion
In patients with ≥moderate primary MR and discordant symptoms, 25 W exercise pulmonary hypertension, defined as an SPAP ≥55 mmHg, and poor aerobic capacity during CPX are independently associated with adverse events.
From trivial to severe arrhythmias: the diagnostic role of multimodality imaging in inflammatory cardiomyopathy through a case series
Authors: Haddad Christelle , Herrera-Siklody Claudia , Porretta Alessandra Pia , Carroz Patrice , Pascale Patrizio , Pruvot Etienne 
Published: October 2021

Abstract

Background
The diagnosis of inflammatory cardiomyopathy remains challenging in cases presenting with arrhythmia as sole manifestation. An early diagnosis is critical as it may prevent life-threatening complications such as sudden cardiac death and atrioventricular block (AVB). The diagnostic workup of suspected cases includes multimodality imaging that requires an adequate interpretation in order to limit the risk of overdiagnosis.

Case summary
Herein, we report three cases presenting with various new-onset arrhythmias. The first patient was admitted for a third-degree AVB. The second patient suffered from a supraventricular tachycardia which degenerated into ventricular fibrillation. The third case was investigated for symptomatic premature ventricular complexes. No apparent heart disease was observed on standard exams (clinical, biological examinations, and echocardiography). However, cardiac magnetic resonance imaging (MRI) and nuclear imaging (68Ga-DOTATOC and/or 18F-FDG PET/CT) suggested an inflammatory substrate that seemed to correlate with the arrhythmic phenotype. Cardiac inflammation disappeared on immunotherapy for the first case and spontaneously for the third case.

Discussion
These cases emphasize the incremental diagnostic yield of multimodality imaging to highlight myocardial inflammation. Nuclear imaging modalities may complement MRI by enabling the detection of active inflammation. The 18F-FDG PET/CT is well established for the diagnosis of cardiac sarcoidosis but its role remains to be clarified for the diagnosis of myocarditis. An alternative radiotracer, 68Ga-DOTATOC, appears promising by overcoming the main limitation of 18F-FDG but its specificity is not yet well established. The role of functional investigations is discussed as well as the benefit of immunosuppressive treatments.
Mechanoenergetic coupling in heart failure with preserved, mid-range and reduced left ventricular ejection fraction
Authors: Hansen K B , Sorensen J , Hansson N H , Nielsen R , Larsen A H , Frokiaer J , Tolbod L P , Gormsen L C , Harms H J , Wiggers H 
Published: October 2021

Abstract

Background
Heart failure (HF) classification based on left ventricular ejection fraction (LVEF) can vary because of changes in filling pressures, afterload, and contractile function. 11C-acetate positron emission tomography (PET) provides a load-independent measure of myocardial external efficiency (MEE) by simultaneous assessment of myocardial oxygen consumption (MVO2), cardiac work, left ventricular mass (LVM), end-systolic wall stress (ESWS), and myocardial blood flow (MBF).

Purpose
We aimed to characterize mechanoenergetic derangements in patients with HF and to study its interrelation with age, sex and obesity.

Methods
MEE was measured in 121 participants with 11C-acetate PET, and LVEF was acquired with echocardiography. We investigated healthy controls (n=20) and patients with HF and reduced LVEF &lt;40% (HFrEF; n=25), mid-range LVEF 40–49% (HFmrEF; n=23), as well as patients with asymptomatic aortic valve stenosis (AS) and LVEF ≥50% (AS-asymp; n=38), and symptomatic AS and LVEF ≥50% (defined as HF with preserved LVEF (HFpEF); n=15).

Results
MEE declined in tandem with reduced LVEF from HFpEF and HFmrEF to HFrEF (p=0.041, p&lt;0.001, and p&lt;0.001 versus control, respectively; Figure 1). Impaired MEE was aggravated with increasing LVM (p=0.001) due to a disproportionate increase in overall left ventricular MVO2. In a multivariate analysis, female sex (p&lt;0.001), a lower body mass index (p&lt;0.001), and advanced age (p=0.01) were associated with a lower MEE (Figure 2). HFpEF, HFmrEF, and HFrEF patients had distinct energetic profiles involving MEE, MVO2, MBF, ESWS, and LVM (Figure 2).

Conclusions
Mechanoenergetic uncoupling was evident in every clinical state within the HF syndrome and associated with left ventricular hypertrophy and progressive systolic dysfunction. Sex, age, and obesity impacted myocardial energetics. To date, the present study is the largest investigation of mechanoenergetic coupling across several categories of patients with heart failure. 11C-acetate PET extends our pathophysiological comprehension of the HF syndrome beyond LVEF.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Lundbeck Foundation Relationship between LVEF and MEEMyocardial energetics in heart failure
Left atrial strain evaluation and prognostic value in constrictive pericarditis patients undergoing pericardiectomy
Authors: Lo Presti S , Chan N , Saijo Y , Wang T , Klein A 
Published: October 2021

Abstract

Background
Left Atrial (LA) phasic volumes analyses is flawed with geometrical assumption requiring high endocardial border definition. LA strain analysis is an emergent technique that overcome some of these technical limitations. Prior studies of LA mechanics in pericardiectomy patients found improvement in LA strain at follow-up and manifested as symptomatic improvement, however their relationships with survival have not been investigated.

Purpose
We assessed LA strain before and after pericardiectomy and its association with all- cause mortality.

Methods
Consecutive patients with constrictive pericarditis who underwent pericardiectomy from 2000–2017 were retrospectively analyzed, analyzing pre-operative and post-operative (at 12 months) echocardiography. Exclusion criteria included atrial fibrillation, previous left sided valve surgery, concomitant valvular surgery at the index pericardiectomy, more than mild left sided valvulopathy and poor echocardiographic windows. Strain analyses was performed with Vector velocity imaging independent software. Univariate and multivariable analyses were utilized to identify factors associated with reduced survival.

Results
Amongst 190 patients included in the analyses, mean age was 58.5±12.7 years and 37 (19.5%) were female. The etiology of constriction was deemed idiopathic in 61.6% of the cases, median time interval surgery-postoperative echo was 67 days (IQR 6, 312 days). During median follow up of 3.3 years (IQR 0.73, 5.9 years) there were 37 deaths. After surgery, there was a significant decrease in LA reservoir, conduit and regional wall strains. (Table 1). Multivariable analysis demonstrated that postoperative 4C AL strain reservoir was independently associated with all-cause mortality (Table 2).

Conclusions
In pericardiectomy patients, postoperative 4C LA strain reservoir is independently associated with all-cause mortality. Perhaps, compensatory changes of septal and antero-posterior walls during constriction explain why after surgery these walls become less dynamic, negatively impacting the overall function. Overall, LA quantification and strains may become a useful clinical tool for risk stratification in pericardiectomy patients

Funding Acknowledgement
Type of funding sources: None. Table 1. Left atrial variables.Table 2. All-cause mortality predictors
Association between atrial high rate episode burden and autonomic and vascular function in patients with implanted cardiac device
Authors: Khan A A , Junejo R T , Thomas G N , Fisher J P , Lip G Y H 
Published: October 2021

Abstract

Background
Patients who experience frequent atrial high rate episodes (AHREs), recorded on implantable cardiac devices, are at an increased risk of stroke and systemic embolism. Increased duration of AHRE is related to higher risk of thromboembolic event. The underlying pathophysiology is unclear; however, autonomic and/or endothelial dysfunction may contribute.

Purpose
We tested the hypothesis that patients with high AHRE burden have worse autonomic and vascular function compared to patients with low AHRE burden.

Design
We studied 44 patients split in two groups: high AHRE burden (longest AHRE ≥24 hours; n=22) and low AHRE burden (longest AHRE &lt;24 hours; n=22). Resting time- and frequency-domain measures of HRV were determined to index cardiac autonomic function. High-resolution ultrasound was used to measure brachial artery diameter at rest and during reactive hyperaemia (endothelium-dependent flow mediated dilation (FMD)).

Results
FMD was higher in the low AHRE burden group compared to high AHRE group (5.5% [95% confidence interval (CI):3.4–7.6] vs 3.1% [95% CI: 1.9–6.2]; p=0.04) (table 1). Mean heart rate (p&lt;0.001) and AHRE burden (p=0.02) were independent predictors of FMD on multivariate analysis. Time-domain, frequency-domain and non-linear indices of HRV were not significantly different between the groups. A slower heart rate (Spearman's rho 0.369; p=0.01) and high AHRE burden (Spearman's rho −0.315; p=0.04) were independently associated with changes seen on FMD following adjustment for multiple variables (p=0.001 and p=0.03 respectively).

Conclusion
Endothelium-dependent FMD is impaired in patients with high AHRE burden, while HRV derived indices of autonomic function were not affected by AHRE burden. Endothelial dysfunction may play an important role in the adverse outcomes seen in patients who experience frequent AHRE.

Funding Acknowledgement
Type of funding sources: None.
Higher incidence of stroke in severe COVID-19 is not associated with a higher burden of arrhythmias: comparison to other types of severe pneumonia
Authors: Jirak P , Shomanova Z , Larbig R , Dankl D , Frank N , Seelmaier C , Butkiene D , Lichtenauer M , Strohmer B , Sackarnd J , Hoppe U , Sindermann J , Reinecke H , Pistulli R , Motloch L 
Published: October 2021

Abstract

Background
Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias, and stroke during rhythm monitoring in critically ill COVID-19, compared to severe pneumonias of other origin.

Methods
Recruited were 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n=60 COVID-19, matched according to risk factors for occurrence of arrhythmias to n=60 patients from a retrospective consecutive cohort of severe pneumonias of other origin.

Results
Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared to nonCOVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4%, p=ns and asystole 5.0 vs. 3.3%, p=ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0% p=ns). AF was even more common in nonCOVID-19 (AF 18.3 vs. 43.3%, p=0.003; newly onset AF 10.0 vs. 30.0%, p=0.006) which resulted in higher need for electrical cardioversion (6.7 vs. 20.0%, p=0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p=0.042). These events happened also in absence of AF (50%) and with TAC (50%).

Conclusion
Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonias of other origin. A contrasting higher incidence of stroke independent of arrhythmias observed also with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Comparative effectiveness and safety of edoxaban vs warfarin in patients with atrial fibrillation: a nationwide cohort study
Authors: Nielsen P B , Soegaard M , Jensen M , Ording A G , Lip G Y H 
Published: October 2021

Abstract

Background and purpose
The effectiveness and safety of edoxaban 60 mg and 30 mg for stroke prevention compared with warfarin in patients with atrial fibrillation (AF) has not been well-described in a nationwide cohort of Caucasian patients treated in standard clinical practice.

Methods
We used Danish nationwide registries to identify patients with AF during June 2016 and November 2018 who were treated with edoxaban or warfarin and computed rates per 100 person-years of thromboembolic, all-cause mortality, and bleeding events using an inverse probability of treatment weighting approach to account for baseline confounding. We used weighted pooled logistic regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing events between edoxaban 60 mg and warfarin users; edoxaban 30 mg was not included in formal comparisons.

Results
We identified 6451 AF patients, mean age was 72 years and 40% were females. A total of 1772 patients were treated with edoxaban 60 mg, 537 with edoxaban 30 mg, and 4142 with warfarin. The median CHA2DS2-VASc score was similar between warfarin and edoxaban 60 mg with a score of 3 (interquartile range [IQR] 2–4). In the inverse probability of treatment-weighted pseudo-population, the thromboembolic event rate for edoxaban 60 mg was 0.95 and 1.0 for warfarin, corresponding weighted HR of 1.00 (95% confidence intervals [CI] 0.59, 1.71); see Figure. Edoxaban 60 mg users were associated with lower rates of all-cause mortality (3.93) compared to warfarin (6.04), with a HR of 0.64 (95% CI 0.47 to 0.88). The event rates for bleeding were 3.36 and 3.14, respectively; HR 1.09 (95% CI 0.77, 1.57)

Conclusion
Edoxaban 60 mg is a safe and effective treatment compared with warfarin for stroke prevention in routine clinical care for white European patients with AF, with non-significantly different risks for stroke and clinically relevant bleeding, but lower all-cause mortality.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Daiichi-Sankyo Europe GmbH. This funding source had no role in the design of this study, its execution, analyses, interpretation of the data, or decision to submit results.