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During T cell development in mice, thymic negative selection deletes cells with the potential to recognize and react to self-antigens. In human T cell-dependent autoimmune diseases such as Type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, T cells reactive to autoantigens are thought to escape negative selection, traffic to the periphery and attack self-tissues. However, physiological thymic negative selection of autoreactive human T cells has not been previously studied. We now describe a human T-cell receptor-transgenic humanized mouse model that permits the study of autoreactive T-cell development in a human thymus. Our studies demonstrate that thymocytes expressing the autoreactive Clone 5 TCR, which recognizes insulin B:9–23 presented by HLA-DQ8, are efficiently negatively selected at the double and single positive stage in human immune systems derived from HLA-DQ8+ HSCs. In the absence of hematopoietic expression of the HLA restriction element, negative selection of Clone 5 is less efficient and restricted to the single positive stage. To our knowledge, these data provide the first demonstration of negative selection of human T cells recognizing a naturally-expressed tissue-restricted antigen. Intrathymic antigen presenting cells are required to delete less mature thymocytes, while presentation by medullary thymic epithelial cells may be sufficient to delete more mature single positive cells. These observations set the stage for investigation of putative defects in negative selection in human autoimmune diseases.

Coronary artery disease (CAD) is one of the top ten leading causes of death in countries worldwide. There are several methods used by physicians to diagnose CAD. One common method is the use of X-ray angiogram (XRA) images. When employing a computer-aided automatic analysis method to locate blood vessels in XRA images, problems such as complex background noise, low contrast, and difficulty in separating blood vessels from the background are encountered, especially for blood vessels with a low contrast to the background noise. In this study, we used various image preprocessing methods to highlight blood vessels from complex backgrounds and different types of blood vessel, followed by the employment of four superpixel segmentation methods to partition an image into multiple segments, and finally the utilization of Weighted Voting to determine the best superpixel algorithm. A genetic algorithm was used to identify the best weights by which to determine the locations of blood vessels in images of cardiac catheterization. Our proposed method achieved an average F1-score of 73.4% in the analysis of five patients, which was better than the other superpixel algorithms tested. The results of this research will be helpful for future SYNTAX score analysis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To investigate whether arterial infundibular widening is a preaneurysmal lesion or not., Methods: Two hundred and nine patients with cerebral angiography were enrolled. The morphology, size and location of infundibula and cerebral aneurysms were studied in two-dimensional angiography and three-dimensional software space. Computational fluid dynamics (CFD) analysis was performed., Results: 234 infundibula and 129 infundibulum-like aneurysms (IFAs) were detected. In two-dimensional space, the typical morphology of an infundibulum was a symmetric dilatation at the arterial branch origin with a small vessel branch emanating from the tip and a wide base connecting the parent artery. In three-dimensional space, the infundibulum was dissymmetric with always one side longer than the other side. Furthermore, the infundibulum tilted upstream rather than downstream, with the longer side located downstream and the shorter side upstream in all cases. All the 129 IFAs occurred on the distal wall of the vessel branch origin, and no IFAs grew from the proximal wall of the branch origin. The possible development process of an infundibulum to an IFA was described in four development stages. The CFD analysis revealed that these lesions were associated with direct flow impingement in all cases. All the hemodynamic parameters on the distal wall of infundibula and IFAs were significantly (P<0.0001 or P<0.05) decreased compared with on the distal wall after virtual lesion removal., Conclusion: The infundibulum is a preaneurysmal lesion associated with high total pressure and high wall shear stress resulted from direct flow impingement and will progress to an aneurysm with time., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To investigate hemodynamic stresses on anterior cerebral artery bifurcation apex and possible mechanism of the optimality principle in protecting bifurcation wall from supercharged hemodynamic stresses., Methods: Three-dimensional angiographic datasets of 122 patients with anterior communicating artery (Acom) aneurysms, 21 patients with non-Acom aneurysms, and 220 control subjects with no aneurysms were used. Radii of parent (r 0 ) and daughter branches (r 1 and r 2 ) were measured, and bifurcations obeying the optimality principle required optimal caliber control of r 0 n  = r 1 n  + r 2 n , with the junction exponent n approximating 3. Radius ratio = r 0 3 /(r 1 3  + r 2 3 ) and n were compared between aneurysmal and control bifurcations. Blood flow was simulated for analysis of hemodynamic stresses., Results: Acom bifurcations in subjects without Acom aneurysms displayed optimal caliber radius, with mean radius ratio of 0.99 and n of 3.25, whereas Acom aneurysmal bifurcations had significantly lower radius ratio, 0.62 (P < 0.05), but higher n, 4.23 (P < 0.05). Peak wall shear stress and corresponding total pressure were significantly smaller for bifurcations obeying than disobeying the optimality principle (P < 0.001 and P < 0.05, respectively). Total pressures in the direct impinging center, peak wall shear stress distance, and anterior cerebral artery bifurcation angle all were significantly smaller for bifurcations obeying than disobeying the optimality principle (P < 0.05 and P < 0.001, respectively)., Conclusions: Normal anterior cerebral artery bifurcations obey the optimality principle whereas bifurcations with Acom aneurysms do not. Disobeying the optimality principle presents significantly enhanced hemodynamic stresses to possibly damage the bifurcation wall for aneurysm initiation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship of anterior cerebral artery (ACA) bifurcation angles with hemodynamic stresses for aneurysm initiation., Methods: Forty patients with or without anterior communicating artery aneurysms were enrolled, and 3 patients with ACA bifurcation angles of 169.0°, 136.9°, and 73.2°, respectively, were entered into computational fluid dynamics analysis for hemodynamic stresses., Results: Larger bifurcation angles had a larger direct flow impinging zone and larger peak pressure area. In the direct flow impinging center, the total pressure was the highest, whereas the other stresses were the lowest. As blood flowed distally, the total pressure decreased rapidly, whereas all other parameters increased quickly to their peaks. The hemodynamic peak distance was decreased as the bifurcation angle became narrower. The total pressure summit and the peak hemodynamic stresses all decreased with the decrease of bifurcation angles. The distance between the hemodynamic peaks was the smallest at 73.2° compared with larger angles. A significant (P < 0.01) positive linear correlation existed in the ACA bifurcation angle with the distance between hemodynamic stress peaks or in the ACA branch diameter with the distance from the direct impinging center to the ipsilateral hemodynamic stress peak. The hemodynamic stresses on the aneurysm dome were significantly (P < 0.001) smaller than at the aneurysm initiation site., Conclusions: Larger bifurcation angles may lead to abnormally enhanced hemodynamic stresses, enlarged zones of direct flow impingement, and increased distance between hemodynamic stress peaks to damage the vascular wall for aneurysm initiation on the bifurcation apex wall., (Copyright © 2018 Elsevier Inc. All rights reserved.)