An accurate and time-efficient deep learning-based system for automated segmentation and reporting of cardiac magnetic resonance-detected ischemic scar

Background and objectives: Myocardial infarction scar (MIS) assessment by cardiac magnetic resonance provides prognostic information and guides patients' clinical management. However, MIS segmentation is time-consuming and not performed routinely. This study presents a deep-learning-based computational workflow for the segmentation of left ventricular (LV) MIS, for the first time performed on state-of-the-art dark-blood late gadolinium enhancement (DB-LGE) images, and the computation of MIS transmurality and extent.Methods: DB-LGE short-axis images of consecutive patients with myocardial infarction were acquired at 1.5T in two centres between Jan 1, 2019, and June 1, 2021. Two convolutional neural network (CNN) mod-els based on the U-Net architecture were trained to sequentially segment the LV and MIS, by processing an incoming series of DB-LGE images. A 5-fold cross-validation was performed to assess the performance of the models. Model outputs were compared respectively with manual (LV endo-and epicardial border) and semi-automated (MIS, 4-Standard Deviation technique) ground truth to assess the accuracy of the segmentation. An automated post-processing and reporting tool was developed, computing MIS extent (expressed as relative infarcted mass) and transmurality.Results: The dataset included 1355 DB-LGE short-axis images from 144 patients (MIS in 942 images). High performance (> 0.85) as measured by the Intersection over Union metric was obtained for both the LV and MIS segmentations on the training sets. The performance for both LV and MIS segmentations was 0.83 on the test sets.Compared to the 4-Standard Deviation segmentation technique, our system was five times quicker ( <1 min versus 7 +/- 3 min), and required minimal user interaction. Conclusions: Our solution successfully addresses different issues related to automatic MIS segmentation, including accuracy, time-effectiveness, and the automatic generation of a clinical report.(c) 2022 Elsevier B.V. All rights reserved

A Characterization of Scale Invariant Responses in Enzymatic Networks

An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of enzymatic networks. Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Isolation and propagation of glomerular mesangial cells.

Cultures of glomerular mesangial cells (MC) of rodent or human origin have been extensively employed in renal research laboratories since the early 1980s. Cultured MC retain extensive analogies with the fairly undifferentiated in vivo phenotype of an intercapillary mesenchymal cell population, i.e., a myofibroblast. MC proliferating in response to mitogens and growth factors can be growth-arrested by withdrawal of serum or 3D culture in collagen gels. They synthesize an extracellular matrix that includes interstitial collagens and has analogies with the glomerular basement membrane; a prominent cytoskeleton acts as a functional contractile apparatus. Cultured MC have been extensively employed as a tool for studying pathophysiological events such as mesangial expansion, scarring, and glomerulosclerosis. Current technology for MC isolation and culture is reviewed, with emphasis on methodological issues relevant to characterization, propagation, and long-term maintenance of homogeneous clones