| 1. |
- Frigoli, Enrico, et al.
(författare)
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Design and rationale of the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen (MASTER DAPT) Study
- 2019
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 209, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background The optimal duration of antiplatelet therapy in high-bleeding risk (HBR) patients with coronary artery disease treated with newer-generation drug-eluting bioresorbable polymer-coated stents remains unclear. Design MASTER DAPT (clinicaltrial.gov NCT03023020) is an investigator-initiated, open-label, multicenter, randomized controlled trial comparing an abbreviated versus a standard duration of antiplatelet therapy after bioresorbable polymer-coated Ultimaster (TANSEI) sirolimus-eluting stent implantation in approximately 4,300 HBR patients recruited from >= 100 interventional cardiology centers globally. After a mandatory 30-day dual-antiplatelet therapy (DAPT) run-in phase, patients are randomized to (a) a single antiplatelet regimen until study completion or up to 5 months in patients with clinically indicated oral anticoagulation (experimental 1-month DAPT group) or (b) continue DAPT for at least 5 months in patients without or 2 in patients with concomitant indication to oral anticoagulation, followed by a single antiplatelet regimen (standard antipkitelet regimen). With a final sample size of 4,300 patients, this study is powered to assess the noninferiority of the abbreviated antiplatelet regimen with respect to the net adverse clinical and major adverse cardiac and cerebral events composite end points and if satisfied for the superiority of abbreviated as compared to standard antiplatelet therapy duration in terms of major or clinically relevant nonmajor bleeding. Study end points will be adjudicated by a blinded Clinical Events Committee. Conclusions The MASTER DAPT study is the first randomized controlled trial aiming at ascertaining the optimal duration of antiplatelet therapy in HBR patients treated with sirolimus-eluting bioresorbable polymer-coated stent implantation.
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| 2. |
- Hatos, Andras, et al.
(författare)
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DisProt : intrinsic protein disorder annotation in 2020
- 2020
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
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Tidskriftsartikel (refereegranskat)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
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| 3. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 4. |
- Calnan, Sonya, et al.
(författare)
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Development of Various Photovoltaic‐Driven Water Electrolysis Technologies for Green Solar Hydrogen Generation
- 2021
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Ingår i: Solar RRL. - : John Wiley & Sons. - 2367-198X. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Direct solar hydrogen generation via a combination of photovoltaics (PV) and water electrolysis can potentially ensure a sustainable energy supply while minimizing greenhouse emissions. The PECSYS project aims at demonstrating asolar-driven electrochemical hydrogen generation system with an area >10 m2 with high efficiency and at reasonable cost. Thermally integrated PV electrolyzers(ECs) using thin-film silicon, undoped, and silver-doped Cu(In,Ga)Se2 and silicon heterojunction PV combined with alkaline electrolysis to form one unit are developed on a prototype level with solar collection areas in the range from 64 to2600 cm2 with the solar-to-hydrogen (StH) efficiency ranging from 4 to 13%. Electrical direct coupling of PV modules to a proton exchange membrane EC test the effects of bifacially (730 cm2 solar collection area) and to study the long-term operation under outdoor conditions (10 m2 collection area) is also investigated. In both cases, StH efficiencies exceeding 10% can be maintained over the test periods used. All the StH efficiencies reported are based on measured gas outflow using mass flow meters.
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| 5. |
- Carraro, Marco, et al.
(författare)
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Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants in CAGI
- 2017
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 38:9, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome Interpretation (CAGI) experiment aims to test and define the state of the art of genotype-phenotype interpretation. Here, we present the assessment of the CAGI p16INK4a challenge. Participants were asked to predict the effect on cellular proliferation of 10 variants for the p16INK4a tumor suppressor, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene. Twenty-two pathogenicity predictors were assessed with a variety of accuracy measures for reliability in a medical context. Different assessment measures were combined in an overall ranking to provide more robust results. The R scripts used for assessment are publicly available from a GitHub repository for future use in similar assessment exercises. Despite a limited test-set size, our findings show a variety of results, with some methods performing significantly better. Methods combining different strategies frequently outperform simpler approaches. The best predictor, Yang&Zhou lab, uses a machine learning method combining an empirical energy function measuring protein stability with an evolutionary conservation term. The p16INK4a challenge highlights how subtle structural effects can neutralize otherwise deleterious variants.
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| 6. |
- Daneshjou, Roxana, et al.
(författare)
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Working toward precision medicine : Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges
- 2017
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 38:9, s. 1182-1192
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype-phenotype relationships.
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| 7. |
- Landi, Antonio, et al.
(författare)
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Antithrombotic therapy in patients with acute coronary syndrome : similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 13:1, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.
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| 8. |
- Landi, Antonio, et al.
(författare)
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Transient vs In-Hospital Persistent AcuteKidney Injury in Patients With Acute Coronary Syndrome.
- 2023
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Ingår i: JACC. Cardiovascular interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 16:2, s. 193-205
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ.The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS.In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding.Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95%CI: 1.48-3.64; P< 0.001; NACE: adjusted HR: 2.29; 95%CI: 1.48-3.52; P< 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95%CI: 2.03-5.82; P< 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria.Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627).
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| 9. |
- Leonardi, Sergio, et al.
(författare)
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Composition, structure, and function of heart teams: a joint position paper of the ACVC, EAPCI, EACTS, and EACTA focused on the management of patients with complex coronary artery disease requiring myocardial revascularization
- 2021
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Ingår i: EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 59:3, s. 522-531
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Tidskriftsartikel (refereegranskat)abstract
- Contemporary cardiovascular medicine is complex, dynamic, and interactive. Therefore, multidisciplinary dialogue between different specialists is required to deliver optimal and patient-centred care. This has led to the concept of explicit collaborations of different specialists caring for patients with complex cardiovascular diseases-that is 'heart teams'. These teams are particularly valuable to minimize referral bias and improve guideline adherence as so to be responsive to patient preferences, needs, and values but may be challenging to coordinate, especially in the acute setting. This position paper-jointly developed by four cardiovascular associations-is intended to provide conceptual and practical considerations for the composition, structure, and function of multidisciplinary teams. It focuses on patients with complex coronary artery diseases in both elective and urgent setting and provide guidance on how to implement the heart team both in chronic and in acute coronary syndromes patients, including cases with mechanical complications and haemodynamic instability; it also discusses strategies for clear and transparent patient communication and provision of a patient-centric approach. Finally, gaps in evidence and research perspectives in this context are discussed.
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| 10. |
- Navarese, Eliano Pio, et al.
(författare)
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Within and beyond 12-month efficacy and safety of antithrombotic strategies in patients with established coronary artery disease : two companion network meta-analyses of the 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute CardioVascular Care (ACVC), and European Association of Preventive Cardiology (EAPC)
- 2023
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 9:3, s. 271-290
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Tidskriftsartikel (refereegranskat)abstract
- Aims To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses. Methods and results Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49-0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76-0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51-0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR, 0.68; 95% CI, 0.55-0.85) or P2Y(12) inhibitor monotherapy (HR, 0.76; 95% CI: 0.61-0.95), especially ticagrelor 90 mg (HR, 0.54; 95% CI, 0.32-0.92), and of stroke with VKA (HR, 0.56; 95% CI, 0.44-0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95% CI, 0.44-0.76). All treatments increased bleeding except P2Y(12) monotherapy, compared with aspirin. Conclusion Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y(12) monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin. Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398. [GRAPHICS] .
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