17 research outputs found
Automated Cardiac Resting Phase Detection Targeted on the Right Coronary Artery
Static cardiac imaging such as late gadolinium enhancement, mapping, or 3-D
coronary angiography require prior information, e.g., the phase during a
cardiac cycle with least motion, called resting phase (RP). The purpose of this
work is to propose a fully automated framework that allows the detection of the
right coronary artery (RCA) RP within CINE series. The proposed prototype
system consists of three main steps. First, the localization of the regions of
interest (ROI) is performed. Second, the cropped ROI series are taken for
tracking motions over all time points. Third, the output motion values are used
to classify RPs. In this work, we focused on the detection of the area with the
outer edge of the cross-section of the RCA as our target. The proposed
framework was evaluated on 102 clinically acquired dataset at 1.5T and 3T. The
automatically classified RPs were compared with the reference RPs annotated
manually by a expert for testing the robustness and feasibility of the
framework. The predicted RCA RPs showed high agreement with the experts
annotated RPs with 92.7% accuracy, 90.5% sensitivity and 95.0% specificity for
the unseen study dataset. The mean absolute difference of the start and end RP
was 13.6 18.6 ms for the validation study dataset (n=102). In this work,
automated RP detection has been introduced by the proposed framework and
demonstrated feasibility, robustness, and applicability for static imaging
acquisitions.Comment: Accepted for publication at the Journal of Machine Learning for
Biomedical Imaging (MELBA) https://melba-journal.org/2023:00
Involvement of cyclic guanosine monophosphate-dependent protein kinase I in renal antifibrotic effects of serelaxin
Introduction: Kidney fibrosis has shown to be ameliorated through the involvement of cyclic guanosine monophosphate (cGMP) and its dependent protein kinase I (cGKI). Serelaxin, the recombinant form of human relaxin-II, increases cGMP levels and has shown beneficial effects on kidney function in acute heart failure patients. Antifibrotic properties of serelaxin are supposed to be mediated via relaxin family peptide receptor 1 and subsequently enhanced nitric oxide/ cGMP to inhibit transforming growth factor 1)) (TGFI)) signaling. This study examines the involvement of cGKI in the antifibrotic signaling of serelaxin. Methods and Results: Kidney fibrosis was induced by unilateral ureteral obstruction in wildtype (WT) and cGKI knock-out (KO) mice. After 7 days, renal antifibrotic effects of serelaxin were assessed. Serelaxin treatment for 7 days significantly increased cGMP in the kidney of WT and cGKI-KO. In WT, renal fibrosis was reduced through decreased accumulation of collagenl A1, total collagen, and fibronectin. The profibrotic connective tissue growth factor as well as myofibroblast differentiation were reduced and matrix metalloproteinases-2 and-9 were positively modulated after treatment. Moreover, Smad2 as well as extracellular signal-regulated kinase 1 (ERK1) phosphorylation were decreased, whereas phosphodiesterase (PDE) 5a phosphorylation was increased. However, these effects were not observed in cGKI-KO. Conclusion: Antifibrotic renal effects of serelaxin are mediated via cGMP/cGKI to inhibit Smad2- and ERK1-dependent TGF-13 signaling and increased PDE5a phosphorylation
The Landscape of Parallel Computing Research Multi-core architectures and programming The Berkeley View "The Landscape of Parallel Computing Research" Report published by a multidisciplinary group at Berkeley Based on 7 questions
Cyclic Nucleotide Signalling in Kidney Fibrosis
Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure
Fully automated background phase correction using M‐estimate SAmple consensus (MSAC)—Application to 2D and 4D flow
Involvement of cyclic guanosine monophosphate-dependent protein kinase I in renal antifibrotic effects of serelaxin
Introduction: Kidney fibrosis has shown to be ameliorated through the involvement of cyclic guanosine monophosphate (cGMP) and its dependent protein kinase I (cGKI). Serelaxin, the recombinant form of human relaxin-II, increases cGMP levels and has shown beneficial effects on kidney function in acute heart failure patients. Antifibrotic properties of serelaxin are supposed to be mediated via relaxin family peptide receptor 1 and subsequently enhanced nitric oxide/ cGMP to inhibit TGF-β signaling. This study examines the involvement of cGKI in the antifibrotic signaling of serelaxin. Methods and Results: Kidney fibrosis was induced by unilateral ureter obstruction in wildtype (WT) and cGKI knock-out (KO) mice. After 7 days, renal antifibrotic effects of serelaxin were assessed. Serelaxin treatment for 7 days significantly increased cGMP in the kidney of WT and cGKI-KO. In WT, renal fibrosis was reduced through decreased accumulation of collagen1A1, total collagen and fibronectin. The profibrotic CTGF as well as myofibroblast differentiation were reduced and matrix metalloproteinases-2 and -9 were positively modulated after treatment. Moreover, Smad2 as well as extracellular signal-regulated kinase 1 (ERK1) phosphorylation were decreased, whereas phosphodiesterase (PDE) 5a phosphorylation was increased. However, these effects were not observed in cGKI-KO. Conclusion: Antifibrotic renal effects of serelaxin are mediated via cGMP/cGKI to inhibit Smad2- and ERK1 -dependent TGF-β signaling and increased PDE5a phosphorylation
Differences in the renal antifibrotic cGMP/cGKI-dependent signaling of serelaxin, zaprinast, and their combination
Renal fibrosis is an important factor for end-stage renal failure. However, only few therapeutic options for its treatment are established. Zaprinast, a phosphodiesterase 5 inhibitor, and serelaxin, the recombinant form of the naturally occurring hormone relaxin, are differently acting modulators of cyclic guanosine monophosphate (cGMP) signaling. Both agents enhance cGMP availability in kidney tissue. These substances alone or in combination might interfere with the development of kidney fibrosis. Therefore, we compared the effects of combination therapy with the effects of monotherapy on renal fibrosis. Renal fibrosis was induced by unilateral ureteral obstruction (UUO) for 7 days in wild-type (WT) and cGKI knockout (KO) mice. Renal antifibrotic effects were assessed after 7 days. In WT, zaprinast and the combination of zaprinast and serelaxin significantly reduced renal interstitial fibrosis assessed by alpha-SMA, fibronectin, collagen1A1, and gelatinases (MMP2 and MMP9). Intriguingly in cGKI-KO, mRNA and protein expression of fibronectin and collagen1A1 were reduced by zaprinast, in contrast to serelaxin. Gelatinases are not regulated by zaprinast. Although both substances showed similar antifibrotic properties in WT, they distinguished in their effect mechanisms. In contrast to serelaxin which acts both on Smad2 and Erk1, zaprinast did not significantly diminish Erk1/2 phosphorylation. Interestingly, the combination of serelaxin/zaprinast achieved no additive antifibrotic effects compared to the monotherapy. Due to antifibrotic effects of zaprinast in cGKI-KO, we hypothesize that additional cGKI-independent mechanisms are supposed for antifibrotic signaling of zaprinast