Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes.

Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60.

Combined Area of Left and Right Atria May Outperform Atrial Volumes as a Predictor of Recurrences after Ablation in Patients with Persistent Atrial Fibrillation-A Pilot Study.

: Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. : This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.

Functional analysis of structural variants in single cells using Strand-seq.

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones.

Progressive and Simultaneous Right and Left Atrial Remodeling Uncovered by a Comprehensive Magnetic Resonance Assessment in Atrial Fibrillation.

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.

Quantification of right atrial fibrosis by cardiac magnetic resonance: verification of the method to standardize thresholds.

Introduction And Objectives: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) allows noninvasive detection of left atrial fibrosis in patients with atrial fibrillation (AF). However, whether the same methodology can be used in the right atrium (RA) remains unknown. Our aim was to define a standardized threshold to characterize RA fibrosis in LGE-CMR.

Recurrent inversion polymorphisms in humans associate with genetic instability and genomic disorders.

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs.

Influence of PACE score and conduction disturbances in the incidence of early new onset atrial fibrillation after typical atrial flutter ablation.

Purpose: Patients undergoing cavotricuspid isthmus (CTI) ablation for typical flutter (AFL) have a high incidence of new onset atrial fibrillation (AF). We aimed to analyze the influence of PACE score to predict new onset AF in this subset of patients to stratify thromboembolic risk.

Methods: Between 2017 and 2019, patients undergoing CTI ablation for AFL and without history of AF were prospectively included.

A microRNA signature that correlates with cognition and is a target against cognitive decline.

While some individuals age without pathological memory impairments, others develop age-associated cognitive diseases. Since changes in cognitive function develop slowly over time in these patients, they are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for the identification of inexpensive and minimal invasive approaches that could be used for screening with the aim to identify individuals at risk for cognitive decline that can then undergo further diagnostics and eventually stratified therapies.

Merged two-way mapping technique: an alternative 3D electroanatomical mapping approach to guide challenging ablation procedures of accessory pathways with bidirectional conduction properties.

Background: Catheter ablation of accessory pathways (AP) with bidirectional conduction may be challenging due to issues related to anatomical course or location.

Objective: We describe an alternative electro-anatomical mapping technique which aims at depicting the entire anatomic course of the AP from the atrial toward the ventricular insertion in order to guide catheter ablation.

Methods: Twenty consecutive patients with confirmed bidirectional AP conduction and at least one previous ablation procedure or para-Hisian location were included.

Proximity to the descending aorta predicts regional fibrosis in the adjacent left atrial wall: aetiopathogenic and prognostic implications.

Aims: Left atrial (LA) fibrosis is present in patients with atrial fibrillation (AF) and can be visualized by magnetic resonance imaging with late gadolinium enhancement (LGE-MRI). Previous studies have shown that LA fibrosis is not randomly distributed, being more frequent in the area adjacent to the descending aorta (DAo). The objective of this study is to analyse the relationship between fibrosis in the atrial area adjacent to the DAo and the distance to it, as well as the prognostic implications of this fibrosis.

Reduction in new cardiac electronic device implantations in Catalonia during COVID-19.

Aims: During the COVID-19 pandemic, concern regarding its effect on the management of non-communicable diseases has been raised. However, there are no data on the impact on cardiac implantable electronic devices (CIED) implantation rates. We aimed to determine the impact of SARS-CoV2 on the monthly incidence rates and type of pacemaker (PM) and implantable cardiac defibrillator (ICD) implantations in Catalonia before and after the declaration of the state of alarm in Spain on 14 March 2020.

Accuracy of left atrial fibrosis detection with cardiac magnetic resonance: correlation of late gadolinium enhancement with endocardial voltage and conduction velocity.

Aims: Myocardial fibrosis is a hallmark of atrial fibrillation (AF) and its characterization could be used to guide ablation procedures. Late gadolinium enhanced-magnetic resonance imaging (LGE-MRI) detects areas of atrial fibrosis. However, its accuracy remains controversial.

Magnetic resonance-guided re-ablation for atrial fibrillation is associated with a lower recurrence rate: a case-control study.

Aims: Our aim was to analyse whether using delayed enhancement cardiac magnetic resonance imaging (DE-CMR) to localize veno-atrial gaps in atrial fibrillation (AF) redo ablation procedures improves outcomes during follow-up.

Methods And Results: We conducted a case-control study with 35 consecutive patients undergoing a DE-CMR-guided Repeat-pulmonary vein isolation (Re-PVI) procedure. Those with more extensive ablations (e.

Magnetic Resonance Imaging-Guided Fibrosis Ablation for the Treatment of Atrial Fibrillation: The ALICIA Trial.

Background: Myocardial fibrosis is key for atrial fibrillation maintenance. We aimed to test the efficacy of ablating cardiac magnetic resonance (CMR)-detected atrial fibrosis plus pulmonary vein isolation (PVI).

Methods: This was an open-label, parallel-group, randomized, controlled trial.

Microglial Corpse Clearance: Lessons From Macrophages.

From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we will first summarize the differences in the origin, lineage and population maintenance of microglia and macrophages.

Impact of cryoballoon applications on lesion gaps detected by magnetic resonance after pulmonary vein isolation.

Introduction: Ablation with second-generation cryoballoon technology evolves as an effective and safe alternative to radiofrequency for atrial fibrillation ablation procedures. Nevertheless, the optimal freezing strategy remains unknown. Our objective was to identify the procedural cryoablation parameters predicting successful peri-pulmonary vein (PV) lesions by directly analyzing Postablation gaps in late-gadolinium-enhanced cardiac magnetic resonance (LGE-CMR).

Cryoballoon vs. radiofrequency lesions as detected by late-enhancement cardiac magnetic resonance after ablation of paroxysmal atrial fibrillation: a case-control study.

Aims: Cryoballoon (CB) ablation has emerged as a reliable modality to isolate pulmonary veins (PVs) in atrial fibrillation. Ablation lesions and the long-term effects of energy delivery can be assessed by delayed-enhancement cardiac magnetic resonance (DE-CMR). The aim of the study was to compare the number, extension, and localization of gaps in CB and radiofrequency (RF) techniques in pulmonary vein isolation (PVI).

Verification of threshold for image intensity ratio analyses of late gadolinium enhancement magnetic resonance imaging of left atrial fibrosis in 1.5T scans.

The use of cardiovascular magnetic resonance imaging left atrial late gadolinium enhancement (LA LGE) is increasing for fibrosis evaluation though the use is still limited to specialized centres due to complex image acquisition and lack of consensus on image analyses. Analysis of LA LGE with image intensity ratio (IIR) (pixel intensity of atrial wall normalized by blood pool intensity) provides an objective method to obtain quantitative data on atrial fibrosis. A threshold between healthy myocardium and fibrosis of 1.

Diagnosis-to-ablation time in atrial fibrillation: A modifiable factor relevant to clinical outcome.

Introduction: Recurrences after atrial fibrillation (AF) ablation are still common. Among the reported clinical and imaging predictors of recurrences, diagnosis-to-ablation time (DAT) has been defined as a predictor of ablation outcome in single-center studies. We aimed to validate DAT in a multicenter real-life cohort.

Translocator Protein Ligand Protects against Neurodegeneration in the MPTP Mouse Model of Parkinsonism.

Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease. Parkinson's disease is a movement disorder with characteristic motor features that arise due to the loss of dopaminergic neurons from the substantia nigra. Although symptomatic treatment by the dopamine precursor levodopa and dopamine agonists can improve motor symptoms, no disease-modifying therapy exists yet.

Reproducibility and accuracy of late gadolinium enhancement cardiac magnetic resonance measurements for the detection of left atrial fibrosis in patients undergoing atrial fibrillation ablation procedures.

Aims: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) may define left atrial (LA) anatomy and structural remodelling, and facilitate atrial fibrillation (AF) ablation. We aimed to assess the intra- and inter-observer reproducibility and agreement of LGE-CMR parameters with direct application to AF ablation techniques.

Methods And Results: One experienced and one non-experienced observer performed complete LGE-CMR data analysis twice, on different days, in 40 randomly selected LGE-CMR examinations [20 performed before ablation (pre-ablation) and 20 performed 3 months after ablation (post-ablation)].

Delayed Gadolinium Enhancement Magnetic Resonance Imaging Detected Anatomic Gap Length in Wide Circumferential Pulmonary Vein Ablation Lesions Is Associated With Recurrence of Atrial Fibrillation.

Background: There is limited knowledge about the impact of anatomic gaps as assessed by delayed gadolinium enhancement cardiac magnetic resonance on atrial fibrillation (AF) recurrence after first pulmonary vein (PV) isolation.

Methods: Consecutive patients underwent delayed gadolinium enhancement cardiac magnetic resonance 3 months after radiofrequency circumferential PV isolation. Delayed gadolinium enhancement cardiac magnetic resonance images were assessed from 360 PV resulting in 2880 segments in the 2×8-segment model from 94 patients (52±11 years, 62% paroxysmal AF).