| 1. |
- Bachi, Lorenzo, et al.
(författare)
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ECG Modeling for Simulation of Arrhythmias in Time-Varying Conditions
- 2023
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Ingår i: IEEE Transactions on Biomedical Engineering. - 0018-9294. ; 70:12, s. 3449-3460
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Tidskriftsartikel (refereegranskat)abstract
- The present paper proposes an ECG simulator that advances modeling of arrhythmias and noise by introducing time-varying signal characteristics. The simulator is built around a discrete-time Markov chain model for simulating atrial and ventricular arrhythmias of particular relevance when analyzing atrial fibrillation (AF). Each state is associated with statistical information on episode duration and heartbeat characteristics. Statistical, time-varying modeling of muscle noise, motion artifacts, and the influence of respiration is introduced to increase the complexity of simulated ECGs, making the simulator well suited for data augmentation in machine learning. Modeling of how the PQ and QT intervals depend on heart rate is also introduced. The realism of simulated ECGs is assessed by three experienced doctors, showing that simulated ECGs are difficult to distinguish from real ECGs. Simulator usefulness is illustrated in terms of AF detection performance when either simulated or real ECGs are used to train a neural network for signal quality control. The results show that both types of training lead to similar performance.
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| 2. |
- Perez, Cristina, et al.
(författare)
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Evaluation of a QT Adaptation Time Estimator for ECG Exercise Stress Test in Controlled Simulation
- 2023
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Ingår i: Computing in Cardiology, CinC 2023. - 2325-8861 .- 2325-887X. - 9798350382525
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Konferensbidrag (refereegranskat)abstract
- Slowed adaptation of the QT interval to sudden abrupt heart rate (HR) changes has been identified as a marker of ventricular arrhythmic risk. However, abrupt HR changes are difficult to induce in patients. Quantifying the QT adaptation time in gradual HR changes, as observed in ECGs recording during an exercise stress test, has been recently proposed. The time lag between the QT series and an instantaneous memoryless HR-dependent QT series along stress test was computed as QT memory. Here, this method was evaluated in a control scenario using simulated exercise stress test ECG signals presenting different QT adaptation times. The method robustness was studied by contaminating the ECGs with muscular noise (MN) signals with different Signal-to-Noise ratio (SNR) values, either synthetic or extracted from real recordings. We found that delineation of the T-wave end point in the first transformed lead from Periodic Component Analysis offers the best performance for low SNR. Moreover, we confirmed that the estimator provides an unbiased estimate of the QT memory introduced in the simulations for the studied range of SNR values (25 to 50 dB).
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| 3. |
- Wilkes, Mark C., et al.
(författare)
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The active component of ginseng, ginsenoside Rb1, improves erythropoiesis in models of Diamond–Blackfan anemia by targeting Nemo-like kinase
- 2021
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258. ; 297:3
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Tidskriftsartikel (refereegranskat)abstract
- Nemo-like kinase (NLK) is a member of the mitogen-activated protein kinase family of kinases and shares a highly conserved kinase domain with other mitogen-activated protein kinase family members. The activation of NLK contributes to the pathogenesis of Diamond–Blackfan anemia (DBA), reducing c-myb expression and mechanistic target of rapamycin activity, and is therefore a potential therapeutic target. Unlike other anemias, the hematopoietic effects of DBA are largely restricted to the erythroid lineage. Mutations in ribosomal genes induce ribosomal insufficiency and reduced protein translation, dramatically impacting early erythropoiesis in the bone marrow of patients with DBA. We sought to identify compounds that suppress NLK and increases erythropoiesis in ribosomal insufficiency. We report that the active component of ginseng, ginsenoside Rb1, suppresses NLK expression and improves erythropoiesis in in vitro models of DBA. Ginsenoside Rb1–mediated suppression of NLK occurs through the upregulation of miR-208, which binds to the 30-UTR of NLK mRNA and targets it for degradation. We also compare ginsenoside Rb1–mediated upregulation of miR-208 with metformin-mediated upregulation of miR-26. We conclude that targeting NLK expression through miRNA binding of the unique 30-UTR is a viable alternative to the challenges of developing small-molecule inhibitors to target the highly conserved kinase domain of this specific kinase.
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| 4. |
- Wilkes, Mark C., et al.
(författare)
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Metformin-induced suppression of Nemo-like kinase improves erythropoiesis in preclinical models of Diamond–Blackfan anemia through induction of miR-26a
- 2020
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Ingår i: Experimental Hematology. - : Elsevier BV. - 0301-472X. ; 91, s. 65-77
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Tidskriftsartikel (refereegranskat)abstract
- Diamond–Blackfan anemia (DBA) results from haploinsufficiency of ribosomal protein subunits in hematopoietic progenitors in the earliest stages of committed erythropoiesis. Nemo-like kinase (NLK) is chronically hyperactivated in committed erythroid progenitors and precursors in multiple human and murine models of DBA. Inhibition of NLK activity and suppression of NLK expression both improve erythroid expansion in these models. Metformin is a well-tolerated drug for type 2 diabetes with multiple cellular targets. Here we demonstrate that metformin improves erythropoiesis in human and zebrafish models of DBA. Our data indicate that the effects of metformin on erythroid proliferation and differentiation are mediated by suppression of NLK expression through induction of miR-26a, which recognizes a binding site within the NLK 3′ untranslated region (3′UTR) to facilitate transcript degradation. We propose that induction of miR-26a is a potentially novel approach to treatment of DBA and could improve anemia in DBA patients without the potentially adverse side effects of metformin in a DBA patient population.
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| 5. |
- Cederfeldt, Marie, 1957, et al.
(författare)
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Recovery in personal care related to cognitive impairment before and after stroke - a one-year follow-up
- 2010
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 122:6, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective: To examine whether there were any differences in the recovery in performance of personal activities of daily living (P-ADL) in elderly persons in relation to cognitive impairments pre- and poststroke from discharge to 6 and 12 months in elderly persons. Methods: Forty-five elderly persons after stroke were assessed at discharge from hospital and at 6 and at 12 months after stroke onset. A questionnaire posed to the next of kin was used to evaluate the person´s pre- and poststroke cognitive status. P-ADL was assessed with the Barthel Index. The Mini Mental State Examination and neuropsychological tests were used to measure cognitive functions after stroke. The National Institute of Health Stroke Scale was used to measure neurological deficits. Results: Persons with cognitive impairments before and after stroke did not improve in P-ADL from the acute phase until 6 and 12 months, while persons with intact cognition pre- and post stroke did. Conclusion: Since cognitive problems pre- and poststroke hinder recovery in P-ADL, it is important to understand the connection between cognitive impairment and activity limitations when planning the optimal rehabilitation, which could include special compensation strategies, learnt by the patients, cognitive assistive devices and/or appropriate personal support trained in meaningful activities in daily life in their natural environment.
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