| 1. |
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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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| 10. |
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| 11. |
- Insulander Björk, Klara L, 1982, et al.
(författare)
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Irradiation testing of enhanced uranium oxide fuels
- 2019
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 125, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced uranium oxide fuel types are being tested in the Halden Research Reactor in Norway with the aim is to assess the effect that these enhancements have on fuel performance. Fuel temperatures, rod pressures and dimensional changes are being monitored online and an extensive post-irradiation examination programme is planned. Preliminary data show that fuel centerline temperatures can be lowered by addition of ThO2 to the fuel matrix, or by incorporating Cr or SiO2-TiO2 as a network structure within the fuel. In parallel, two types of cladding coatings are tested in order to investigate their in-core properties. No abnormal behaviour has been noted during the first 100 days of irradiation.
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| 12. |
- Kirchhoff, Tomas, et al.
(författare)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 13. |
- Nous, Fay M. A., et al.
(författare)
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Comparison of the Diagnostic Performance of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve in Patients With Versus Without Diabetes Mellitus (from the MACHINE Consortium)
- 2019
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Ingår i: American Journal of Cardiology. - : EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. - 0002-9149 .- 1879-1913. ; 123:4, s. 537-543
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Tidskriftsartikel (refereegranskat)abstract
- Coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) is a noninvasive application to evaluate the hemodynamic impact of coronary artery disease by simulating invasively measured FFR based on CT data. CT-FFR is based on the assumption of a normal coronary microvascular response. We assessed the diagnostic performance of a machine-learning based application for on-site computation of CT-FFR in patients with and without diabetes mellitus with suspected coronary artery disease. The study population included 75 diabetic and 276 nondiabetic patients who were enrolled in the MACHINE consortium. The overall diagnostic performance of coronary CT angiography alone and in combination with CT-FFR were analyzed with direct invasive FFR comparison in 110 coronary vessels of the diabetic group and in 415 coronary vessels of the nondiabetic group. Per-vessel discrimination of lesion-specific ischemia by CT-FFR was assessed by the area under the receiver operating characteristic curves. The overall diagnostic accuracy of CT-FFR in diabetic patients was 83% and in nondiabetic patients 75% (p = 0.088), showing improvement over the diagnostic accuracy of coronary CT angiography, which was 58% and 65% (p = 0.223), respectively. In addition, the diagnostic accuracy of CT-FFR was similar between diabetic and nondiabetic patients per stratified CT-FFR group (CT-FFR amp;lt; 0.6, 0.6 to 0.69, 0.7 to 0.79, 0.8 to 0.89, amp;gt;= 0.9). The area under the curves for diabetic and nondiabetic patients were also comparable, 0.88 and 0.82 (p = 0.113), respectively. In conclusion, on-site machine-learning CT-FFR analysis improved the diagnostic performance of coronary CT angiography and accurately discriminated lesion-specific ischemia in both diabetic and nondiabetic patients suspected of coronary artery disease. (C) 2018 Elsevier Inc. All rights reserved.
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| 14. |
- Park, Seung Hyun, et al.
(författare)
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Nonpharmaceutical interventions reduce the incidence and mortality of COVID-19: A study based on the survey from the International COVID-19 Research Network (ICRN)
- 2023
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Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 95:2
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Tidskriftsartikel (refereegranskat)abstract
- The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the worlds most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19.
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| 15. |
- Renker, Matthias, et al.
(författare)
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Influence of coronary stenosis location on diagnostic performance of machine learning-based fractional flow reserve from CT angiography
- 2021
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Ingår i: JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY. - : ELSEVIER SCIENCE INC. - 1934-5925. ; 15:6, s. 492-498
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Tidskriftsartikel (refereegranskat)abstract
- Background: Compared with invasive fractional flow reserve (FFR), coronary CT angiography (cCTA) is limited in detecting hemodynamically relevant lesions. cCTA-based FFR (CT-FFR) is an approach to overcome this insufficiency by use of computational fluid dynamics. Applying recent innovations in computer science, a machine learning (ML) method for CT-FFR derivation was introduced and showed improved diagnostic performance compared to cCTA alone. We sought to investigate the influence of stenosis location in the coronary artery system on the performance of ML-CT-FFR in a large, multicenter cohort. Methods: Three hundred and thirty patients (75.2% male, median age 63 years) with 502 coronary artery stenoses were included in this substudy of the MACHINE (Machine Learning Based CT Angiography Derived FFR: A MultiCenter Registry) registry. Correlation of ML-CT-FFR with the invasive reference standard FFR was assessed and pooled diagnostic performance of ML-CT-FFR and cCTA was determined separately for the following stenosis locations: RCA, LAD, LCX, proximal, middle, and distal vessel segments. Results: ML-CT-FFR correlated well with invasive FFR across the different stenosis locations. Per-lesion analysis revealed improved diagnostic accuracy of ML-CT-FFR compared with conventional cCTA for stenoses in the RCA (71.8% [95% confidence interval, 63.0%-79.5%] vs. 54.8% [45.7%-63.8%]), LAD (79.3 [73.9-84.0] vs. 59.6 [53.5-65.6]), LCX (84.1 [76.0-90.3] vs. 63.7 [54.1-72.6]), proximal (81.5 [74.6-87.1] vs. 63.8 [55.9-71.2]), middle (81.2 [75.7-85.9] vs. 59.4 [53.0-65.6]) and distal stenosis location (67.4 [57.0-76.6] vs. 51.6 [41.1-62.0]). Conclusion: In a multicenter cohort with high disease prevalence, ML-CT-FFR offered improved diagnostic performance over cCTA for detecting hemodynamically relevant stenoses regardless of their location.
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| 16. |
- Shu, Xiang, et al.
(författare)
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Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:6, s. 1216-1226
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Tidskriftsartikel (refereegranskat)abstract
- Background: The etiology of colorectal cancer is not fully understood.Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 > 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis.Results: Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini-Hochberg FDR (BH-FDR) < 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10-8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR < 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60−2.36, P = 2.6 × 10-11; OREUR: 1.01, 95% CI, 0.99−1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het < 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer.Conclusions: This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data.Impact: The identified metabolites could be developed into new tools for risk assessment of colorectal cancer in both European and EA populations.
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| 17. |
- Tesche, Christian, et al.
(författare)
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Influence of Coronary Calcium on Diagnostic Performance of Machine Learning CT-FFR Results From MACHINE Registry
- 2020
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Ingår i: JACC Cardiovascular Imaging. - : ELSEVIER SCIENCE INC. - 1936-878X .- 1876-7591. ; 13:3, s. 760-770
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESThis study was conducted to investigate the influence of coronary artery calcium (CAC) score on the diagnostic performance of machine-learning-based coronary computed tomography (CT) angiography (cCTA)-derived fractional flow reserve (CT-FFR).BACKGROUNDCT-FFR is used reliably to detect lesion-specific ischemia. Novel CT-FFR algorithms using machine-learning artificial intelligence techniques perform fast and require less complex computational fluid dynamics. Yet, influence of CAC score on diagnostic performance of the machine-learning approach has not been investigated.METHODSA total of 482 vessels from 314 patients (age 62.3 +/- 9.3 years, 77% male) who underwent cCTA followed by invasive FFR were investigated from the MACHINE (Machine Learning based CT Angiography derived FFR: a Multi-center Registry) registry data. CAC scores were quantified using the Agatston convention. The diagnostic performance of CT-FFR to detect lesion-specific ischemia was assessed across all Agatston score categories (CAC 0, >0 to <100, 100 to <400, and >=$400) on a per-vessel level with invasive FFR as the reference standard.RESULTSThe diagnostic accuracy of CT-FFR versus invasive FFR was superior to cCTA alone on a per-vessel level (78% vs. 60%) and per patient level (83% vs. 73%) across all Agatston score categories. No statistically significant differences in the diagnostic accuracy, sensitivity, or specificity of CT-FFR were observed across the categories. CT-FFR showed good discriminatory power in vessels with high Agatston scores (CAC >= 400) and high performance in low-to-intermediate Agatston scores (CAC >0 to <400) with a statistically significant difference in the area under the receiver-operating characteristic curve (AUC) (AUC: 0.71 [95% confidence interval (CI): 0.57 to 0.85] vs. 0.85 [95% CI: 0.82 to 0.89], p = 0.04). CT-FFR showed superior diagnostic value over cCTA in vessels with high Agatston scores (CAC >= 400: AUC 0.71 vs. 0.55, p = 0.04) and low-to-intermediate Agatston scores (CAC >0 to <400: AUC 0.86 vs. 0.63, p < 0.001).CONCLUSIONSMachine-learning-based CT-FFR showed superior diagnostic performance over cCTA alone in CAC with a significant difference in the performance of CT-FFR as calcium burden/Agatston calcium score increased. (Machine Learning Based CT Angiography Derived FFR: a Multicenter, Registry [MACHINE] NCT02805621). (C) 2020 by the American College of Cardiology Foundation.
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- Wang, Yong, et al.
(författare)
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Inclusion Engineering in Medium Mn Steels : Effect of Hot-Rolling Process on the Deformation Behaviors of Oxide and Sulfide Inclusions
- 2022
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Ingår i: Metallurgical and materials transactions. B, process metallurgy and materials processing science. - : Springer Nature. - 1073-5615 .- 1543-1916. ; 53:4, s. 2182-2197
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Tidskriftsartikel (refereegranskat)abstract
- Medium Mn steel (MMS) is a new category of the third-generation advanced high strength steel (3rd AHSS) which is developed in the recent 1-2 decades due to a unique trade-off of strength and ductility. Thus, this steel grade has a wide application potential in different fields of industry. The current work provides a fundamental study of the effect of hot-rolling on the inclusion deformation inMMSincluding a varied 7 to 9 mass pctMn. Specifically, the deformation behavior of different types of inclusions (i.e., Mn(S,Se), liquid oxide (MnSiO3), MnAl2O4, and complex oxy-sulfide) was investigated. The results show that both MnSiO3 and Mn(S,Se) are soft inclusions which are able to be deformed during the hot-rolling process but MnAl2O4 does not. The aspect ratio of soft inclusions increases significantly from as-cast to hot-rolling conditions. When the maximum size of different inclusions is similar, Mn(S,Se) deforms more than MnSiO3 does. This is due to a joint influence of physical parameters including Young's modulus, coefficient of thermal expansion (α), etc. However, when the maximum size of one type of inclusion (e.g., MnSiO3) is much larger than another one (e.g., Mn(S,Se)), this maximum size of soft inclusions plays a dominant role than other factors. In addition, the deformation behavior of dual-phase inclusion depends on the major phase, i.e., either oxide or sulfide. Last but not least, empirical correlations between the reduction ratio of the thickness of plate, grain size, and aspect ratio of oxide and sulfide inclusions after hot-rolling are provided quantitatively. This work aims to contribute to the 'inclusion engineering' concept in the manufacturing of new generation AHSS.
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