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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 4. |
- Lee, Seung Won, et al.
(författare)
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Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 56:16, s. 901-912
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea. Methods Data regarding 212 768 Korean adults (age >= 20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020. Results Out of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500-1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses. Conclusion Adults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.
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| 5. |
- Baumann, Stefan, et al.
(författare)
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Gender differences in the diagnostic performance of machine learning coronary CT angiography-derived fractional flow reserve -results from the MACHINE registry
- 2019
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Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 119
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study investigated the impact of gender differences on the diagnostic performance of machine-learning based coronary CT angiography (cCTA)-derived fractional flow reserve (CT-FFR mL ) for the detection of lesion-specific ischemia. Method: Five centers enrolled 351 patients (73.5% male) with 525 vessels in the MACHINE (Machine leArning Based CT angiograpHy derIved FFR: a Multi-ceNtEr) registry. CT-FFRML and invasive FFR amp;lt;= 0.80 were considered hemodynamically significant, whereas cCTA luminal stenosis amp;gt;= 50% was considered obstructive. The diagnostic performance to assess lesion-specific ischemia in both men and women was assessed on a per-vessel basis. Results: In total, 398 vessels in men and 127 vessels in women were included. Compared to invasive FFR, CT-FFRML reached a sensitivity, specificity, positive predictive value, and negative predictive value of 78% (95%CI 72-84), 79% (95%CI 73-84), 75% (95%CI 69-79), and 82% (95%CI: 76-86) in men vs. 75% (95%CI 58-88), 81 (95%CI 72-89), 61% (95%CI 50-72) and 89% (95%CI 82-94) in women, respectively. CT-FFRML showed no statistically significant difference in the area under the receiver-operating characteristic curve (AUC) in men vs. women (AUC: 0.83 [95%CI 0.79-0.87] vs. 0.83 [95%CI 0.75-0.89], p = 0.89). CT-FFRML was not superior to cCTA alone [AUC: 0.83 (95%CI: 0.75-0.89) vs. 0.74 (95%CI: 0.65-0.81), p = 0.12] in women, but showed a statistically significant improvement in men [0.83 (95%CI: 0.79-0.87) vs. 0.76 (95%CI: 0.71-0.80), p = 0.007]. Conclusions: Machine-learning based CT-FFR performs equally in men and women with superior diagnostic performance over cCTA alone for the detection of lesion-specific ischemia.
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| 6. |
- Coenen, Adriaan, et al.
(författare)
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Diagnostic Accuracy of a Machine-Learning Approach to Coronary Computed Tomographic Angiography-Based Fractional Flow Reserve Result From the MACHINE Consortium
- 2018
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Ingår i: Circulation Cardiovascular Imaging. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-9651 .- 1942-0080. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coronary computed tomographic angiography (CTA) is a reliable modality to detect coronary artery disease. However, CTA generally overestimates stenosis severity compared with invasive angiography, and angiographic stenosis does not necessarily imply hemodynamic relevance when fractional flow reserve (FFR) is used as reference. CTA-based FFR (CT-FFR), using computational fluid dynamics (CFD), improves the correlation with invasive FFR results but is computationally demanding. More recently, a new machine-learning (ML) CT-FFR algorithm has been developed based on a deep learning model, which can be performed on a regular workstation. In this large multicenter cohort, the diagnostic performance ML-based CT-FFR was compared with CTA and CFD-based CT-FFR for detection of functionally obstructive coronary artery disease. Methods and Results: At 5 centers in Europe, Asia, and the United States, 351 patients, including 525 vessels with invasive FFR comparison, were included. ML-based and CFD-based CT-FFR were performed on the CTA data, and diagnostic performance was evaluated using invasive FFR as reference. Correlation between ML-based and CFD-based CT-FFR was excellent (R=0.997). ML-based (area under curve, 0.84) and CFD-based CT-FFR (0.84) outperformed visual CTA (0.69; Pamp;lt;0.0001). On a per-vessel basis, diagnostic accuracy improved from 58% (95% confidence interval, 54%-63%) by CTA to 78% (75%-82%) by ML-based CT-FFR. The per-patient accuracy improved from 71% (66%-76%) by CTA to 85% (81%-89%) by adding ML-based CT-FFR as 62 of 85 (73%) false-positive CTA results could be correctly reclassified by adding ML-based CT-FFR. Conclusions: On-site CT-FFR based on ML improves the performance of CTA by correctly reclassifying hemodynamically nonsignificant stenosis and performs equally well as CFD-based CT-FFR.
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| 7. |
- de Geer, Jakob, et al.
(författare)
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Effect of Tube Voltage on Diagnostic Performance of Fractional Flow Reserve Derived From Coronary CT Angiography With Machine Learning: Results From the MACHINE Registry
- 2019
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Ingår i: American Journal of Roentgenology. - : AMER ROENTGEN RAY SOC. - 0361-803X .- 1546-3141. ; 213:2, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE. Coronary CT angiography (CCTA)-based methods allow noninvasive estimation of fractional flow reserve (cFFR), recently through use of a machine learning (ML) algorithm (cFFR(ML)). However, attenuation values vary according to the tube voltage used, and it has not been shown whether this significantly affects the diagnostic performance of cFFR and cFFR(ML). Therefore, the purpose of this study is to retrospectively evaluate the effect of tube voltage on the diagnostic performance of cFFR(ML). MATERIALS AND METHODS. A total of 525 coronary vessels in 351 patients identified in the MACHINE consortium registry were evaluated in terms of invasively measured FFR and cFFR(ML). CCTA examinations were performed with a tube voltage of 80, 100, or 120 kVp. For each tube voltage value, correlation (assessed by Spearman rank correlation coefficient), agreement (evaluated by intraclass correlation coefficient and Bland-Altman plot analysis), and diagnostic performance (based on ROC AUC value, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the cFFR(ML) in terms of detection of significant stenosis were calculated. RESULTS. For tube voltages of 80, 100, and 120 kVp, the Spearman correlation coefficient for cFFR(ML) in relation to the invasively measured FFR value was rho = 0.684, rho = 0.622, and rho = 0.669, respectively (p amp;lt; 0.001 for all). The corresponding intraclass correlation coefficient was 0.78, 0.76, and 0.77, respectively (p amp;lt; 0.001 for all). Sensitivity was 100.0%, 73.5%, and 85.0%, and specificity was 76.2%, 79.0%, and 72.8% for tube voltages of 80, 100, and 120 kVp, respectively. The ROC AUC value was 0.90, 0.82, and 0.80 for 80, 100, and 120 kVp, respectively (p amp;lt; 0.001 for all). CONCLUSION. CCTA-derived cFFR(ML) is a robust method, and its performance does not vary significantly between examinations performed using tube voltages of 100 kVp and 120 kVp. However, because of rapid advancements in CT and postprocessing technology, further research is needed.
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| 8. |
- Ha, Hojin, et al.
(författare)
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In-vitro and In-Vivo Assessment of 4D Flow MRI Reynolds Stress Mapping for Pulsatile Blood Flow
- 2021
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Imaging hemodynamics play an important role in the diagnosis of abnormal blood flow due to vascular and valvular diseases as well as in monitoring the recovery of normal blood flow after surgical or interventional treatment. Recently, characterization of turbulent blood flow using 4D flow magnetic resonance imaging (MRI) has been demonstrated by utilizing the changes in signal magnitude depending on intravoxel spin distribution. The imaging sequence was extended with a six-directional icosahedral (ICOSA6) flow-encoding to characterize all elements of the Reynolds stress tensor (RST) in turbulent blood flow. In the present study, we aimed to demonstrate the feasibility of full RST analysis using ICOSA6 4D flow MRI under physiological conditions. First, the turbulence analysis was performed through in vitro experiments with a physiological pulsatile flow condition. Second, a total of 12 normal subjects and one patient with severe aortic stenosis were analyzed using the same sequence. The in-vitro study showed that total turbulent kinetic energy (TKE) was less affected by the signal-to-noise ratio (SNR), however, maximum principal turbulence shear stress (MPTSS) and total turbulence production (TP) had a noise-induced bias. Smaller degree of the bias was observed for TP compared to MPTSS. In-vivo study showed that the subject-variability on turbulence quantification was relatively low for the consistent scan protocol. The in vivo demonstration of the stenosis patient showed that the turbulence analysis could clearly distinguish the difference in all turbulence parameters as they were at least an order of magnitude larger than those from the normal subjects.
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| 9. |
- Ha, Hojin, et al.
(författare)
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In vitro experiments on ICOSA6 4D flow MRI measurement for the quantification of velocity and turbulence parameters
- 2020
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Ingår i: Magnetic Resonance Imaging. - : ELSEVIER SCIENCE INC. - 0730-725X .- 1873-5894. ; 72, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To perform comprehensive in vitro experiments using six-directional icosahedral flow encoding (ICOSA6) 4D flow magnetic resonance imaging (MRI) under various scan conditions to analyze the robustness of velocity and turbulence quantification. Materials and methods: In vitro flow phantoms with steady flow rates of 10 and 20 L/min were scanned using both conventional 4D flow MRI and ICOSA6. Experiments focused on comparisons between ICOSA6 and conventional four point (4P) methods, and the effects of contrast agents, velocity encoding range (Venc), and scan direction on velocity and turbulence quantification. Results: The results demonstrated that 1) ICOSA6 improves the velocity-to-noise ratio (VNR) of velocity estimation by 33% (on average) and results in similar turbulent kinetic energy (TKE) estimation as the 4P method. 2) Measurements with a contrast agent resulted in more than a 2.5 fold increase in average VNR. However, the improvement of total TKE quantification was not obvious. 3) TKE estimation was less affected by Venc and the scan direction, whereas turbulence production (TP) estimation was largely affected by these measurement conditions. The effects of Venc and scan direction accounted for less than 11.63% of TKE estimation, but up to 33.89% of TP estimation. Conclusion: The ICOSA6 scheme is compatible with conventional 4D flow MRI for velocity and TKE measurement. Contrast agents are effective at increasing VNR, but not signal-to-noise ratio for TKE quantification. The effects of Venc and scan direction influence total TP more than total TKE.
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