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- Bahira, M., et al.
(författare)
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A ruthenium dimer complex with a flexible linker slowly threads between DNA bases in two distinct steps
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:18, s. 8856-8867
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Tidskriftsartikel (refereegranskat)abstract
- Several multi-component DNA intercalating small molecules have been designed around ruthenium-based intercalating monomers to optimize DNA binding properties for therapeutic use. Here we probe the DNA binding ligand [mu-C-4(cpdppz)(2)(phen)(4)Ru-2](4+), which consists of two Ru(phen)(2)dppz(2+) moieties joined by a flexible linker. To quantify ligand binding, double-stranded DNA is stretched with optical tweezers and exposed to ligand under constant applied force. In contrast to other bis-intercalators, we find that ligand association is described by a two-step process, which consists of fast bimolecular intercalation of the first dppz moiety followed by similar to 10-fold slower intercalation of the second dppz moiety. The second step is rate-limited by the requirement for a DNA-ligand conformational change that allows the flexible linker to pass through the DNA duplex. Based on our measured force-dependent binding rates and ligand-induced DNA elongation measurements, we are able to map out the energy landscape and structural dynamics for both ligand binding steps. In addition, we find that at zero force the overall binding process involves fast association (similar to 10 s), slow dissociation (similar to 300 s), and very high affinity (K-d similar to 10 nM). The methodology developed in this work will be useful for studying the mechanism of DNA binding by other multi-step intercalating ligands and proteins.
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| 5. |
- Simonato, Matheus, et al.
(författare)
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Minimum Core Data Elements for Evaluation of TAVR : A Scientific Statement by PASSION CV, HVC, and TVT Registry
- 2022
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Ingår i: Academic pediatrics. - : Elsevier. - 1876-2859 .- 1876-2867. ; 22:3, s. 685-697
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Tidskriftsartikel (refereegranskat)abstract
- Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.
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| 6. |
- Simonato, Matheus, et al.
(författare)
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Minimum Core Data Elements for Evaluation of TAVR : A Scientific Statement by PASSION CV, HVC, and TVT Registry
- 2022
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Ingår i: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 113:5, s. 1730-1742
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Tidskriftsartikel (refereegranskat)abstract
- Transcatheter aortic valve replacement (TAVR) is the standard of care for severe, symptomatic aortic stenosis. Real-world TAVR data collection contributes to benefit/risk assessment and safety evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, as well as clinical research and real-world implementation through appropriate use criteria. The essential minimum core dataset for these purposes has not previously been defined but is necessary to promote efficient, reusable real-world data collection supporting quality, regulatory, and clinical applications. The authors performed a systematic review of the published research for high-impact TAVR studies and U.S. multicenter, multidevice registries. Two expert task forces, one from the Predictable and Sustainable Implementation of National Cardiovascular Registries/Heart Valve Collaboratory and another from The Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry convened separately and then met to reconcile a final list of essential data elements. From 276 unique data elements considered, unanimous consensus agreement was achieved on 132 "core" data elements, with the most common reasons for exclusion from the minimum core dataset being burden or difficulty in accurate assessment (36.9%), duplicative information (33.3%), and low likelihood of affecting outcomes (10.7%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established 132 interoperable, reusable essential core data elements essential to supporting more efficient, consistent, and informative TAVR device evidence for regulatory submissions, safety surveillance, best practice, and hospital quality assessments.
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| 7. |
- Vemulapalli, Sreekanth, et al.
(författare)
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Minimum Core Data Elements for Transcatheter Mitral Therapies : Scientific Statement by PASSION CV, HVC, and TVTR
- 2023
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Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 16:12, s. 1437-1447
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Forskningsöversikt (refereegranskat)abstract
- Mitral regurgitation is the most common valvular disease and is estimated to affect over 5 million Americans. Real-world data collection contributes to safety and effectiveness evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, and clinical best practice research. We aimed to establish a minimum core data set in mitral interventions to promote efficient, reusable real-world data collection for all of these purposes. Two expert task forces separately evaluated and reconciled a list of candidate elements derived from: 1) 2 ongoing transcatheter mitral trials; and 2) a systemic literature review of high-impact mitral trials and U.S multicenter, multidevice registries. From 703 unique data elements considered, unanimous consensus agreement was achieved on 127 "core" data elements, with the most common reasons for exclusion from the minimum core data set being burden or difficulty in accurate assessment (41.2%), duplicative information (25.0%), and low likelihood of affecting outcomes (19.6%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established and implemented into the national Society of Thoracic Surgery/ American College of Cardiology Transcatheter Valve Therapies Registry 127 interoperable, reusable core data elements to support more efficient, consistent, and informative transcatheter mitral device evidence for regulatory submissions, safety surveillance, best practice development, and hospital quality assessments.
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