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  1. Book: Genetic engineering of plants

    Boyle, Patrick M. / Burrill, Devin R.

    recent advances

    2016  

    Author's details contributors: Patrick M. Boyle, Devin R. Burrill et al
    Keywords Plant genetic engineering
    Subject code 631.5233
    Language English
    Size xv, 277 Seiten, Illustrationen, Diagramme, 26 cm
    Publisher Auris Reference Limited
    Publishing place London
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT019220227
    ISBN 978-1-78154-955-1 ; 1-78154-955-9
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

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  2. Article ; Online: Computational Modeling and Simulation of the Fibrotic Human Atria.

    Bifulco, Savannah F / Boyle, Patrick M

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2735, Page(s) 105–115

    Abstract: Patient-specific modeling of atrial electrical activity enables the execution of simulations that can provide mechanistic insights and provide novel solutions to vexing clinical problems. The geometry and fibrotic remodeling of the heart can be ... ...

    Abstract Patient-specific modeling of atrial electrical activity enables the execution of simulations that can provide mechanistic insights and provide novel solutions to vexing clinical problems. The geometry and fibrotic remodeling of the heart can be reconstructed from clinical-grade medical scans and used to inform personalized models with detail incorporated at the cell- and tissue-scale to represent changes in image-identified diseased regions. Here, we provide a rubric for the reconstruction of realistic atrial models from pre-segmented 3D renderings of the left atrium with fibrotic tissue regions delineated, which are the output from clinical-grade systems for quantifying fibrosis. We then provide a roadmap for using those models to carry out patient-specific characterization of the fibrotic substrate in terms of its potential to harbor reentrant drivers via cardiac electrophysiology simulations.
    MeSH term(s) Humans ; Atrial Fibrillation/pathology ; Atrial Remodeling ; Models, Cardiovascular ; Action Potentials ; Heart Atria/surgery ; Computer Simulation ; Fibrosis
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3527-8_6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Optogenetic Modulation of Arrhythmia Triggers: Proof-of-Concept from Computational Modeling.

    Ochs, Alexander R / Boyle, Patrick M

    Cellular and molecular bioengineering

    2023  Volume 16, Issue 4, Page(s) 243–259

    Abstract: Introduction: Early afterdepolarizations (EADs) are secondary voltage depolarizations associated with reduced repolarization reserve (RRR) that can trigger lethal arrhythmias. Relating EADs to triggered activity is difficult to study, so the ability to ... ...

    Abstract Introduction: Early afterdepolarizations (EADs) are secondary voltage depolarizations associated with reduced repolarization reserve (RRR) that can trigger lethal arrhythmias. Relating EADs to triggered activity is difficult to study, so the ability to suppress or provoke EADs would be experimentally useful. Here, we use computational simulations to assess the feasibility of subthreshold optogenetic stimulation modulating the propensity for EADs (cell-scale) and EAD-associated ectopic beats (organ-scale).
    Methods: We modified a ventricular ionic model by reducing rapid delayed rectifier potassium (0.25-0.1 × baseline) and increasing L-type calcium (1.0-3.5 × baseline) currents to create RRR conditions with varying severity. We ran simulations in models of single cardiomyocytes and left ventricles from post-myocardial infarction patient MRI scans. Optogenetic stimulation was simulated using either ChR2 (depolarizing) or GtACR1 (repolarizing) opsins.
    Results: In cell-scale simulations without illumination, EADs were seen for 164 of 416 RRR conditions. Subthreshold stimulation of GtACR1 reduced EAD incidence by up to 84.8% (25/416 RRR conditions; 0.1 μW/mm
    Conclusions: Our findings suggest that optogenetics could be used to silence or provoke both EADs and EAD-associated ectopic beats. Validation in animal models could lead to exciting new experimental regimes and potentially to novel anti-arrhythmia treatments.
    Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00781-z.
    Language English
    Publishing date 2023-08-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2416037-4
    ISSN 1865-5033 ; 1865-5025
    ISSN (online) 1865-5033
    ISSN 1865-5025
    DOI 10.1007/s12195-023-00781-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Leave the light on: chronic optogenetic tachypacing of human engineered cardiac tissue constructs.

    Boyle, Patrick M / Trayanova, Natalia A

    Cardiovascular research

    2020  Volume 116, Issue 8, Page(s) 1405–1406

    MeSH term(s) Heart ; Humans ; Optogenetics ; Tissue Engineering
    Language English
    Publishing date 2020-02-27
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvaa029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Machine learning identifies esophageal luminal temperature patterns associated with thermal injury in catheter ablation for atrial fibrillation.

    Chahine, Yaacoub / Afroze, Tanzina / Bifulco, Savannah F / Tekmenzhi, Demyan V / Jafarvand, Mahbod / Boyle, Patrick M / Akoum, Nazem

    Journal of cardiovascular electrophysiology

    2024  Volume 35, Issue 4, Page(s) 737–746

    Abstract: Introduction: Luminal esophageal temperature (LET) monitoring during atrial fibrillation (AF) ablation is widely used to reduce the incidence of endoscopically detected esophageal lesion (EDEL). We sought to assess whether specific patterns of LET ... ...

    Abstract Introduction: Luminal esophageal temperature (LET) monitoring during atrial fibrillation (AF) ablation is widely used to reduce the incidence of endoscopically detected esophageal lesion (EDEL). We sought to assess whether specific patterns of LET variation are associated with EDEL.
    Methods: A high-fidelity multisensor probe was used to record LET in AF patients undergoing radiofrequency ablation (RFA) or cryoballoon ablation (CBA). Explainable machine learning and SHapley Additive exPlanations (SHAP) analysis were used to predict EDEL and assess feature importance.
    Results: A total of 94 patients (38.3% persistent AF, 71.3% male, 72 RFA, and 22 CBA) were included. EDEL was detected in 11 patients (10 RFA and one CBA). In the RFA group, the highest LET recorded was similar between patients with and without EDEL (40.6 [40.1-41]°C vs. 40.2 [39.1-40.9]°C; p = .313), however, the rate of LET rise for the highest recorded peak was higher (0.08 [0.03-0.12]°C/s vs. 0.02 [0.01-0.05]°C/s; p = .033), and the area under the curve (AUC) for the highest peak was smaller (412.5 [206.8-634.1] vs. 588.6 [380.4-861.1]; p = .047) in patients who had EDEL. In case of CBA, the patient with EDEL had a faster LET decline (0.12 vs. 0.07 [0.02-0.14]°C/s), and a smaller AUC for the lowest trough (2491.3 vs. 2629.3 [1712.6-5283.2]). SHAP analysis revealed that a rate of LET change higher than 0.05°C/s and an AUC less than 600 were more predictive of EDEL in RFA.
    Conclusion: The rate of LET change and AUC for the recorded temperature predicted EDEL, whereas absolute peak temperatures did not.
    MeSH term(s) Humans ; Male ; Female ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/surgery ; Atrial Fibrillation/epidemiology ; Esophagoscopy ; Temperature ; Esophagus/injuries ; Catheter Ablation/adverse effects ; Burns/epidemiology ; Pulmonary Veins/surgery
    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1025989-2
    ISSN 1540-8167 ; 1045-3873
    ISSN (online) 1540-8167
    ISSN 1045-3873
    DOI 10.1111/jce.16213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Proactive therapeutic drug monitoring and vedolizumab dose optimization in children with inflammatory bowel disease.

    Rowland, Patrick / McNicol, Megan / Kiel, Ashley / Maltz, Ross M / Donegan, Amy / Dotson, Jennifer L / Michel, Hilary K / Boyle, Brendan

    Journal of pediatric gastroenterology and nutrition

    2024  Volume 78, Issue 4, Page(s) 853–861

    Abstract: Objectives: Therapeutic drug monitoring (TDM) and dose optimization have been shown to improve clinical outcomes with antitumor necrosis factor and recent studies in adults suggest an exposure-response relationship with drug levels associated with ... ...

    Abstract Objectives: Therapeutic drug monitoring (TDM) and dose optimization have been shown to improve clinical outcomes with antitumor necrosis factor and recent studies in adults suggest an exposure-response relationship with drug levels associated with improved clinical outcomes. However, these levels are not universally recognized as therapeutic targets for vedolizumab dosing. We aimed to assess the impact of a TDM quality improvement (QI) initiative on 52-week clinical outcomes and describe proactively obtained vedolizumab levels during the induction period in children with inflammatory bowel disease (IBD).
    Methods: A QI initiative to proactively obtain TDM levels at Week 6 was implemented in 2019. A retrospective review of pediatric patients with IBD treated with vedolizumab from 2018 to 2022 was performed. Baseline demographic data, medication dosing details, disease characteristics, lab results, and 12-month clinical outcomes were recorded. For this study, we defined therapeutic target levels (>20 μg/mL at Week 6 and >12 μg/mL during maintenance) based on existing data correlating these levels with improved clinical outcomes.
    Results: Fifty-nine patients (31 Crohn disease [CD], 28 ulcerative colitis [UC]/indeterminate colitis [IC]) were included in the study. In total, 68% (40/59) of patients had vedolizumab levels at Week 6 and 90% (53/59) had levels drawn at Week 6 or 14. Thirty-five percent of Week 6 trough levels were below our defined target of 20 μg/mL. Fifty-two of 59 patients had available data at 52 weeks. Over 80% (42/52) of patients remained on vedolizumab 52 weeks after initiation (CD 79% [23/29], UC/IC 83% [19/23]). Sixty-two percent (26/42) of patients that remained on vedolizumab at 52 weeks were treated with an intensified dosing interval of <8 weeks. Thirty-one of these 42 (74%) were in clinical remission (CR) rate at 52 weeks with 29/42 (69%) in corticosteroid-free remission. The CR rate for the entire cohort including those who discontinued therapy due to a lack of efficacy before 52 weeks was 60% (31/52).
    Conclusion: Proactive TDM and early dose optimization with vedolizumab may improve drug durability and clinical outcomes in pediatric patients with IBD.
    MeSH term(s) Adult ; Humans ; Child ; Drug Monitoring/methods ; Gastrointestinal Agents/therapeutic use ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/pathology ; Antibodies, Monoclonal, Humanized ; Colitis, Ulcerative/drug therapy ; Crohn Disease/drug therapy ; Treatment Outcome
    Chemical Substances vedolizumab (9RV78Q2002) ; Gastrointestinal Agents ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2024-01-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1002/jpn3.12132
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Explainable Machine Learning to Predict Anchored Reentry Substrate Created by Persistent Atrial Fibrillation Ablation in Computational Models.

    Bifulco, Savannah F / Macheret, Fima / Scott, Griffin D / Akoum, Nazem / Boyle, Patrick M

    Journal of the American Heart Association

    2023  Volume 12, Issue 16, Page(s) e030500

    Abstract: Background Postablation arrhythmia recurrence occurs in ~40% of patients with persistent atrial fibrillation. Fibrotic remodeling exacerbates arrhythmic activity in persistent atrial fibrillation and can play a key role in reentrant arrhythmia, but ... ...

    Abstract Background Postablation arrhythmia recurrence occurs in ~40% of patients with persistent atrial fibrillation. Fibrotic remodeling exacerbates arrhythmic activity in persistent atrial fibrillation and can play a key role in reentrant arrhythmia, but emergent interaction between nonconductive ablation-induced scar and native fibrosis (ie, residual fibrosis) is poorly understood. Methods and Results We conducted computational simulations in pre- and postablation left atrial models reconstructed from late gadolinium enhanced magnetic resonance imaging scans to test the hypothesis that ablation in patients with persistent atrial fibrillation creates new substrate conducive to recurrent arrhythmia mediated by anchored reentry. We trained a random forest machine learning classifier to accurately pinpoint specific nonconductive tissue regions (ie, areas of ablation-delivered scar or vein/valve boundaries) with the capacity to serve as substrate for anchored reentry-driven recurrent arrhythmia (area under the curve: 0.91±0.03). Our analysis suggests there is a distinctive nonconductive tissue pattern prone to serving as arrhythmogenic substrate in postablation models, defined by a specific size and proximity to residual fibrosis. Conclusions Overall, this suggests persistent atrial fibrillation ablation transforms substrate that favors functional reentry (ie, rotors meandering in excitable tissue) into an arrhythmogenic milieu more conducive to anchored reentry. Our work also indicates that explainable machine learning and computational simulations can be combined to effectively probe mechanisms of recurrent arrhythmia.
    MeSH term(s) Humans ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/surgery ; Atrial Fibrillation/pathology ; Cicatrix ; Heart Atria/diagnostic imaging ; Heart Atria/surgery ; Heart Atria/pathology ; Fibrosis ; Computer Simulation ; Machine Learning ; Catheter Ablation/adverse effects ; Catheter Ablation/methods ; Recurrence ; Treatment Outcome
    Language English
    Publishing date 2023-08-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.123.030500
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Personalized biomechanical insights in atrial fibrillation: opportunities & challenges.

    Telle, Åshild / Bargellini, Clarissa / Chahine, Yaacoub / Del Álamo, Juan C / Akoum, Nazem / Boyle, Patrick M

    Expert review of cardiovascular therapy

    2023  Volume 21, Issue 11, Page(s) 817–837

    Abstract: Introduction: Atrial fibrillation (AF) is an increasingly prevalent and significant worldwide health problem. Manifested as an irregular atrial electrophysiological activation, it is associated with many serious health complications. AF affects the ... ...

    Abstract Introduction: Atrial fibrillation (AF) is an increasingly prevalent and significant worldwide health problem. Manifested as an irregular atrial electrophysiological activation, it is associated with many serious health complications. AF affects the biomechanical function of the heart as contraction follows the electrical activation, subsequently leading to reduced blood flow. The underlying mechanisms behind AF are not fully understood, but it is known that AF is highly correlated with the presence of atrial fibrosis, and with a manifold increase in risk of stroke.
    Areas covered: In this review, we focus on biomechanical aspects in atrial fibrillation, current and emerging use of clinical images, and personalized computational models. We also discuss how these can be used to provide patient-specific care.
    Expert opinion: Understanding the connection betweenatrial fibrillation and atrial remodeling might lead to valuable understanding of stroke and heart failure pathophysiology. Established and emerging imaging modalities can bring us closer to this understanding, especially with continued advancements in processing accuracy, reproducibility, and clinical relevance of the associated technologies. Computational models of cardiac electromechanics can be used to glean additional insights on the roles of AF and remodeling in heart function.
    MeSH term(s) Humans ; Atrial Fibrillation ; Reproducibility of Results ; Heart Atria ; Fibrosis ; Stroke/etiology ; Stroke/prevention & control
    Language English
    Publishing date 2023-12-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2192343-7
    ISSN 1744-8344 ; 1477-9072
    ISSN (online) 1744-8344
    ISSN 1477-9072
    DOI 10.1080/14779072.2023.2273896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Graft-host coupling changes can lead to engraftment arrhythmia: a computational study.

    Gibbs, Chelsea E / Marchianó, Silvia / Zhang, Kelly / Yang, Xiulan / Murry, Charles E / Boyle, Patrick M

    The Journal of physiology

    2023  Volume 601, Issue 13, Page(s) 2733–2749

    Abstract: After myocardial infarction (MI), a significant portion of heart muscle is replaced with scar tissue, progressively leading to heart failure. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) offer a promising option for improving cardiac ... ...

    Abstract After myocardial infarction (MI), a significant portion of heart muscle is replaced with scar tissue, progressively leading to heart failure. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) offer a promising option for improving cardiac function after MI. However, hPSC-CM transplantation can lead to engraftment arrhythmia (EA). EA is a transient phenomenon arising shortly after transplantation then spontaneously resolving after a few weeks. The underlying mechanism of EA is unknown. We hypothesize that EA may be explained partially by time-varying, spatially heterogeneous, graft-host electrical coupling. Here, we created computational slice models derived from histological images that reflect different configuration of grafts in the infarcted ventricle. We ran simulations with varying degrees of connection imposed upon the graft-host perimeter to assess how heterogeneous electrical coupling affected EA with non-conductive scar, slow-conducting scar and scar replaced by host myocardium. We also quantified the effect of variation in intrinsic graft conductivity. Susceptibility to EA initially increased and subsequently decreased with increasing graft-host coupling, suggesting the waxing and waning of EA is regulated by progressive increases in graft-host coupling. Different spatial distributions of graft, host and scar yielded markedly different susceptibility curves. Computationally replacing non-conductive scar with host myocardium or slow-conducting scar, and increasing intrinsic graft conductivity both demonstrated potential means to blunt EA vulnerability. These data show how graft location, especially relative to scar, along with its dynamic electrical coupling to host, can influence EA burden; moreover, they offer a rational base for further studies aimed to define the optimal delivery of hPSC-CM injection. KEY POINTS: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) hold great cardiac regenerative potential but can also cause engraftment arrhythmias (EA). Spatiotemporal evolution in the pattern of electrical coupling between injected hPSC-CMs and surrounding host myocardium may explain the dynamics of EA observed in large animal models. We conducted simulations in histology-derived 2D slice computational models to assess the effects of heterogeneous graft-host electrical coupling on EA propensity, with or without scar tissue. Our findings suggest spatiotemporally heterogeneous graft-host coupling can create an electrophysiological milieu that favours graft-initiated host excitation, a surrogate metric of EA susceptibility. Removing scar from our models reduced but did not abolish the propensity for this phenomenon. Conversely, reduced intra-graft electrical connectedness increased the incidence of graft-initiated host excitation. The computational framework created for this study can be used to generate new hypotheses, targeted delivery of hPSC-CMs.
    MeSH term(s) Animals ; Humans ; Cicatrix/pathology ; Myocardium/pathology ; Myocytes, Cardiac/pathology ; Myocardial Infarction/pathology ; Arrhythmias, Cardiac ; Cell Differentiation
    Language English
    Publishing date 2023-04-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP284244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Optogenetic Stimulation Using Anion Channelrhodopsin (GtACR1) Facilitates Termination of Reentrant Arrhythmias With Low Light Energy Requirements: A Computational Study.

    Ochs, Alexander R / Karathanos, Thomas V / Trayanova, Natalia A / Boyle, Patrick M

    Frontiers in physiology

    2021  Volume 12, Page(s) 718622

    Abstract: Optogenetic defibrillation of hearts expressing light-sensitive cation channels (e.g., ChR2) has been proposed as an alternative to conventional electrotherapy. Past modeling work has shown that ChR2 stimulation can depolarize enough myocardium to ... ...

    Abstract Optogenetic defibrillation of hearts expressing light-sensitive cation channels (e.g., ChR2) has been proposed as an alternative to conventional electrotherapy. Past modeling work has shown that ChR2 stimulation can depolarize enough myocardium to interrupt arrhythmia, but its efficacy is limited by light attenuation and high energy needs. These shortcomings may be mitigated by using new optogenetic proteins like
    Language English
    Publishing date 2021-08-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2021.718622
    Database MEDical Literature Analysis and Retrieval System OnLINE

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