bluuebunny/crossref_metadata_2025_split huggingface dataset:
DAmiRLocGNet: miRNA subcellular localization prediction by combining miRNA–disease associations and graph convolutional networks
Authors: Bai Tao , Yan Ke , Liu Bin 
Published: June 2023

AbstractMicroRNAs (miRNAs) are human post-transcriptional regulators in humans, which are involved in regulating various physiological processes by regulating the gene expression. The subcellular localization of miRNAs plays a crucial role in the discovery of their biological functions. Although several computational methods based on miRNA functional similarity networks have been presented to identify the subcellular localization of miRNAs, it remains difficult for these approaches to effectively extract well-referenced miRNA functional representations due to insufficient miRNA–disease association representation and disease semantic representation. Currently, there has been a significant amount of research on miRNA–disease associations, making it possible to address the issue of insufficient miRNA functional representation. In this work, a novel model is established, named DAmiRLocGNet, based on graph convolutional network (GCN) and autoencoder (AE) for identifying the subcellular localizations of miRNA. The DAmiRLocGNet constructs the features based on miRNA sequence information, miRNA–disease association information and disease semantic information. GCN is utilized to gather the information of neighboring nodes and capture the implicit information of network structures from miRNA–disease association information and disease semantic information. AE is employed to capture sequence semantics from sequence similarity networks. The evaluation demonstrates that the performance of DAmiRLocGNet is superior to other competing computational approaches, benefiting from implicit features captured by using GCNs. The DAmiRLocGNet has the potential to be applied to the identification of subcellular localization of other non-coding RNAs. Moreover, it can facilitate further investigation into the functional mechanisms underlying miRNA localization. The source code and datasets are accessed at http://bliulab.net/DAmiRLocGNet.
Robust sample weighting to facilitate individualized treatment rule learning for a target population
Authors: Chen Rui , Huling Jared D , Chen Guanhua , Yu Menggang 
Published: June 2023

Summary
Learning individualized treatment rules is an important topic in precision medicine. Current literature mainly focuses on deriving individualized treatment rules from a single source population. We consider the observational data setting when the source population differs from a target population of interest. Compared with causal generalization for the average treatment effect that is a scalar quantity, individualized treatment rule generalization poses new challenges due to the need to model and generalize the rules based on a prespecified class of functions that may not contain the unrestricted true optimal individualized treatment rule. The aim of this paper is to develop a weighting framework to mitigate the impact of such misspecification, and thus facilitate the generalizability of optimal individualized treatment rules from a source population to a target population. Our method seeks covariate balance over a nonparametric function class characterized by a reproducing kernel Hilbert space and can improve many individualized treatment rule learning methods that rely on weights. We show that the proposed method encompasses importance weights and overlap weights as two extreme cases, allowing for a better bias-variance trade-off in between. Numerical examples demonstrate that the use of our weighting method can greatly improve individualized treatment rule estimation for the target population compared with other weighting methods.
Theological and Ethical Problems with Medicalizing Risk
Authors: Curlin Farr , Scherz Paul 
Published: June 2023

AbstractWhile the COVID-19 pandemic riveted public attention on questions regarding how to respond reasonably to risk of illness, everyday medical care involves more mundane forms of pharmaceutical risk management for conditions like high blood pressure, prediabetes, or high cholesterol. This essay, and the collection it introduces, explore medicalization of risk as a theological problem, drawing on resources such as the Sermon on the Mount that caution us about the potential dangers of risk management to Christian discipleship. Medicalization of risk threatens to become an idol that promises immanent security at the cost of one’s relationship with God and others. It misleads contemporary society as to the true human end and medicine’s own capabilities to provide temporal salvation. The essays in this special issue illustrate these problems with respect to pharmaceutical risk management.
Eurasian otters prefer to prey on religious released non-native fish on the Qinghai-Tibetan Plateau
Authors: Wang Qiaoyun , Han Xuesong , Wang Zichen , Zheng Kaidan , Dong Zhengyi , Zhang Peng , Fan Pengfei , Zhang Lu 
Published: June 2023

Abstract
Religious wildlife release is prevalent worldwide, especially in Asia countries. It is one of the anthropogenic pathways to cause biological invasions. Religious fish release is common on the Qinghai-Tibetan Plateau, yet few studies have assessed the influences of religious fish release on local species. In Yushu, a city on the Qinghai-Tibetan Plateau, we interviewed local people, conducted fish trap surveys in local rivers, and examined the diet of Eurasian otters Lutra lutra using a fecal DNA metabarcoding approach. We found that fish release started at least in 1980–1990s in Yushu. Tibetan residents released fish in large amounts and released fish were usually exotic commercial fish purchased from market. Despite such long-term and intensive fish release activities, released fish were few in local rivers. On the other hand, Eurasian otters mainly prey on fish and released fish accounted for ~20% of relative read abundance of prey DNA in otters’ diet, indicating their high preference on released fish. Our study suggested that religious fish release may provide additional food resources for otters, whereas otters, as a top predator in local rivers, may deplete non-native fish once they were released and, therefore, reduce the probability of colonization of released fish, although further studies are required to assess otters’ impact. Our study revealed otters’ diet in Yushu, providing basic information for local otter management and conservation. Furthermore, it represents a case showing that native predators prey on religious released animals, implying a probable direction for controlling invasive species through native predator conservation.
MPO activity determined by molecular MRI is associated with ruptured and destabilised human atherosclerotic plaques
Authors: Nadel J , Bongers A , Tumanov S , Giannotti N , Chen W , Jabbour A , Stocker R 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): National Health & Medical Research Council - Postgraduate Scholarship
National Heart Foundation - PhD Scholarship
University of New South Wales - RTP Scholarship

Introduction
Intraplaque MPO activity is associated with unstable atherosclerosis and elevated following acute cardiovascular events. Imaging probes for the detection of MPO exist, including MPO-Gd, a gadolinium-based probe activated and retained in the presence of MPO-specific chlorinating species. To date, the utility of MPO activity in plaque rupture has not been examined. We sought to assess the association between intraplaque MPO activity and ruptured human plaques.

Method
Carotid endarterectomy specimens (CEA) were collected from 30 patients undergoing surgery. Following pre-surgical in vivo MRI for plaque characterisation, ex vivo plaques were activated using MPO-Gd. MPO-Gd retention was then correlated to AHA plaque grading both histologically and by in vivo MRI as well as liquid chromatography mass spectrometry (LC-MS/MS) through the addition of hydroethidine tissue sections and it’s conversion to the MPO-specific adduct 2-chloroethidium (2-Cl-E+).

Results
MPO-Gd retention in CEA was greater in both histologically and MRI-graded ruptured and destabilised AHA type VI plaques compared to types III-V (T1 percentage recovery from baseline: VI: 52% ± 5.7 vs. V: 77% ± 7.8, IV: 83% ± 8.2 and III: 84% ± 6.8; p &lt; 0.0001). This association was confirmed by comparing histological AHA grade to MPO activity determined by LC-MS/MS (2-Cl-E+ corrected to internal standard per mgp: VI: 0.2 ± 0.2 vs. V: 0.00 ± 0.01, IV: 0.01 ± 0.01, and III: 0.03 ± 0.03; p = 0.005).

Discussion
We demonstrate that MPO activity determined by MPO-Gd and compared to histology is increased in ruptured human plaques. These results highlight the unique and specific role of intraplaque MPO activity and its potential application as a molecular probe in the detection of vulnerable atherosclerosis.
Prognostic value of myocardial strain on cardiac magnetic resonance imaging in patients with non-ischemic cardiomyopathy
Authors: Tao M , Despotidis G , Ghosalkar D , Tam E , Goldschmidt M , Mann N 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Myocardial strain measurements using feature tracking imaging (FTI) on cardiac magnetic resonance (CMR) has emerged as a reliable method for evaluating myocardial function. However, the prognostic value of left ventricular strain measurements on CMR remains unclear in patients with nonischemic cardiomyopathy (NICM).

Purpose
The purpose of this meta-analysis is to evaluate the association of myocardial strain measurements with adverse outcomes in patients with NICM.

Methods
A literature search was conducted for studies reporting on the association of left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), and left ventricular global radial strain (LVGRS) using FTI on CMR with cardiovascular outcomes on long term follow-up in patients with NICM. The primary endpoint was major adverse cardiac events (MACE). The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status.

Results
A total of 6 studies with 1004 participants (251 with MACE and 753 without MACE) met inclusion criteria. Mean follow-up duration was 39 months. Mean ejection fraction was 27%. Baseline LVGLS, LVGCS, and LVGRS were significantly lower in NICM patients who subsequently experienced MACE on follow-up compared to patients without MACE (SMD −0.58, 95% CI −1.01, −0.15; p&lt;0.01; SMD −0.58, 95% CI −0.96, −0.21; p&lt;0.01; SMD −0.43, 95% CI −0.81, −0.05; p = 0.03).

Conclusions
Myocardial strain measurement using FTI on CMR may represent a useful clinical tool for risk stratification of NICM patients at risk for adverse cardiac events.
Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk
Authors: Bohbot Y , Tordjman L , Dreyfus J , Le Tourneau T , Lavie Badie Y , Selto C , Elegamandji B , L'official G , Fraix A , Aghezzaf S , Turgeon P Y , Enriquez Sarano M , Coisne A , Donal E , Tribouilloy C 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Various definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes.

Purpose
To compare EROA and TCG for outcome prediction in patients with severe TR

Methods
In this French multicentre retrospective study, we included 606 patients with ≥ moderate-to-severe isolated TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm²) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality.

Results
The relationship between the EROA and TCG was poor (R²=0.21), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA &lt;60 mm² vs. ≥ 60 mm² (67±3% vs. 64±4%, p = 0.64), even after adjustment, for all-cause (p = 0.72) and cardiovascular mortality (p = 0.18). A TCG ≥10 mm was associated with lower four-year survival than a TCG &lt;10 mm (53±7% vs. 69±3%, p&lt;0.001). After adjustment for covariates, including age, comorbidity, right heart failure, dose of diuretics, and right ventricular dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95%CI]=1.46[1.15–2.18], p = 0.015) and cardiovascular mortality (adjusted HR[95%CI]=1.95[1.22–3.14], p &lt;0.001), whereas an EROA ≥60 mm² was not associated with all-cause or cardiovascular mortality (adjusted HR[95%CI]:1.07[0.75–1.51], p = 0.720, and adjusted HR[95%CI]:1.35[0.87–2.09], p = 0.176, respectively)

Conclusion
The correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated TR.
Assessment of left atrial appendage flow velocities to unmask atrial fibrillation in cryptogenic stroke
Authors: Dhont S , Wouters F , Deferm S , Bekelaar K , Nuyens D , Verhaert D , Vandervoort P , Bertrand P B 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Hemostasis in the left atrial (LA) appendage (LAA) is a common cause of stroke, particularly in atrial fibrillation (AF). LAA flow have been determined to quantify LAA function.

Objectives
To investigate whether LAA peak flow velocities early after cryptogenic stroke have a predictive value for AF occurrence and to determine the determinants of impaired flow.

Methods
Consecutive cryptogenic stroke patients (139) were enrolled. LAA flow velocities during sinus rhythm were assessed early post-stroke with transesophageal echocardiography. All patients received rhythm monitoring using 7-day Holter and if negative, an implantable cardiac monitor.

Results
47 Patients (34%) developed AF during a median follow-up of 554 days, median time to AF diagnosis was 93 days. Both, LAA filling (LAAfv) and emptying (LAAev) velocities were lower in stroke patients who developed AF (resp. 44.3±14.2 cm/s and 50.7±13.3 cm/s) compared with those who didn’t (resp. 59.8±14.0 cm/s and 76.8±17.3 cm/s). LAAev was the strongest predictor of AF with an AUC of 0.878 in ROC curve analysis and with optimal cut-off value of 55 cm/s. Age and mitral regurgitation were independent determinants of reduced LAAev.

Conclusions
Reduced LAA flow velocities can identify cryptogenic stroke patients at high risk of occult AF, and who may benefit from intensive rhythm monitoring or anticoagulation strategies.
Prospective cascade screening for transthyretin amyloid cardiomyopathy in patients undergoing spinal stenosis surgery: results of the CASS (Cardiac Amyloidosis in Spinal Stenosis) study
Authors: Debonnaire P , Claeys M , Trenson S , De Paepe P , Lycke M , Geerts B , De Geeter F , Hoste D , Van Meirhaeghe J , Van Droogenbroeck J , Verhoeven K , Janssens A , De Muynck S , Vantomme N , Tavernier R 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Ligamentum flavum hypertrophy due to transthyretin amyloid (ATTR) deposition is common in patients with symptomatic spinal stenosis, although prospective data on systematic screening for coinciding ATTR-cardiomyopathy (CM) are lacking.

Purpose
To evaluate a prospective screening strategy to identify de novo ATTR-CM in all-comers undergoing spinal stenosis surgery.

Methods
Patients undergoing symptomatic spinal stenosis surgery were prospectively screened for potential increased ATTR-CM risk, based on predefined criteria on electrocardiography, laboratory (hs-troponin, NT-proBNP), echocardiography and peroperative ligamentum flavum histology. ≥1 Positive criteria mandated ATTR-CM exclusion by HMDP-bonescintigraphy.

Results
In total 82 consecutive patients (mean age 68±9 years, 48% males) underwent prospective cascade screening. In 90% ≥1 positive risk criterium was noted and 4.1% of patients (n=3/74, 67% male) were identified with de novo ATTR-CM. Importantly, 59% (n=48/82) had ATTR deposition on ligamentum flavum biopsy, of which 21% (n=10/48) being &lt;60 years old. ATTR burden on histology increased with age, the sole independent predictor of ATTR presence (HR 1.15, 95%CI 1.07–1.22, p&lt;0.001). High ATTR burden (Westermark grade 4, ≥10% amyloid on ligamentum flavum histology) was noted in 12% (n=10/82). All 3 de novo ATTR-CM patients had high ATTR burden, translating into a prevalence and positive predictive value (PPV) of 30% (n=3/10) and 85% accuracy for ATTR-CM in Westermark grade 4 patients. Other increased risk markers with PPV&gt;5% are hs-troponin, left ventricular wall thickness ≥12mm, global longitudinal strain &gt;-20% and relative apical sparing.

Conclusions
High ATTR burden on ligamentum flavum histology during spinal stenosis surgery relates to high risk of coincident ATTR-CM.
Is myocardial fibrosis appropriately assessed by 2D strain derived integrated backscatter?
Authors: Lima M , Abecasis J , Reis Santos R , Maltes S , Guerreiro S , Campino Padrao C , Freitas P , Ferreira A , Ribeiras R , Andrade M J , Cardim N , Madeira M , Ramos S , Mendes M 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Calibrated integrated backscatter (cIBS) may be obtained from bidimensional (2D) strain echocardiography as a quantification measurement of myocardial ultrasound reflectivity. Increased collagen content of the myocardium modifies tissue reflectivity and cIBS is suggested as a marker of left ventricular (LV) fibrosis. However, its diagnostic accuracy is not established.

Aim
To assess the correlation between cIBS by 2D strain and LV myocardial fibrosis (MF), as evaluated by non-invasive imaging and histopathology.

Methods
Correlation study from a cohort of 157 patients with severe symptomatic aortic stenosis (AS) referred for surgical aortic valve replacement (AVR). Patients with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of AVR were selected. Two groups of 30 patients were evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak in decibels (dB) from both parasternal long axis (PLAX) and apical three chamber (A3C) cine clips at Qanalysis (Figure 1A). cIBS was calculated by subtracting the pericardial intensity from the average of the anteroseptal and basal inferolateral wall values. Correlation analysis was performed for the whole group of patients with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) from Masson´s Trichrome staining. IBS values were compared in both group of patients.

Results
60 patients (73 [68–74] years, 45% male) with high gradient (mean gradient: 64±20mmHg), normal flow (45±10mL/m2), preserved ejection fraction (60±9%) AS. Basal septal cIBS was −9.2±9.5dB and −16.3±7.9dB from A3C and PLAX views, respectively. These indexes did not correlate with basal septum thickness or global LV mass. Absolute and cIBS did not correlate neither with global and regional T1 and ECV values, nor with CVF at EMB (Figure 1B). These were not significantly different in both groups of patients and there was no correlation between cIBS values and mass of replacement MF in patients with LGE.

Conclusion
In these cohort of patients with classical severe AS, there was no correlation of cIBS with imaging markers of both replacement and diffuse MF. cIBS also didn´t correlate with CVF at histopathology. These findings suggest that reflectivity indexes are not suitable for myocardial tissue characterization in this setting.
Impact of myocardial inflammation on quantitative myocardial perfusion at long-term follow-up - a descriptive hybrid PET/MR myocarditis study
Authors: Buechel R , Ciancone D , Bakula A , Schmidt G A , Patriki D , Benz D C , Giannopoulos A A , Kaufmann P A 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF).

Background
Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown.

Objectives
To assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis.

Methods
Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n=469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n=118), and scarred (LGE at follow-up, n=72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n=18).

Results
Compared to remote segments, healed segments showed higher stress MBF (2.71mL*min-1*g-1 [IQR 2.18–3.08] vs. 2.20 mL*min-1*g-1 [1.75–2.68], p&lt;0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p&lt;0.0001) and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ∼30% (p&lt;0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with myocardial scar but without corresponding LGE.

Conclusions
In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.