scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Author(s):  
Dagmara Winiarczyk ◽  
Katarzyna Michalak ◽  
Łukasz Adaszek ◽  
Mateusz Winiarczyk ◽  
Stanisław Winiarczyk
Keyword(s):  
Metabolic Pathways ◽  
Protein Identification ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Urine Samples ◽  
Control Group ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs ◽  
Potential Biomarkers

Abstract This study aimed to identify proteins in the urine of dogs with renal dysfunction during the natural course of babesiosis (n=10) and to compare them with proteins in a control group (n=10) to reveal any potential biomarkers of renal damage. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common to both groups. Characteristic analysis of the 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. Furthermore, it was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins and TGF-β (transforming growth factor β) pathways. These pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and FER tyrosine kinase, which are potential biomarkers of damage during babesiosis in dogs that might indicate early renal injury.

scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Author(s):  
Dagmara Winiarczyk ◽  
Katarzyna Michalak ◽  
Łukasz Adaszek ◽  
Mateusz Winiarczyk ◽  
Stanisław Winiarczyk
Keyword(s):  
Metabolic Pathways ◽  
Protein Identification ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Urine Samples ◽  
Control Group ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs ◽  
Potential Biomarkers

Abstract This study aimed to identify proteins in the urine of dogs with renal dysfunction during the natural course of babesiosis (n=10) and to compare them with proteins in a control group (n=10) to reveal any potential biomarkers of renal damage. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common to both groups. Characteristic analysis of the 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. Furthermore, it was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins and TGF-β (transforming growth factor β) pathways. These pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and FER tyrosine kinase, which are potential biomarkers of damage during babesiosis in dogs that might indicate early renal injury.

scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Author(s):  
D. Winiarczyk ◽  
K. Michalak ◽  
L. Adaszek ◽  
M. Winiarczyk ◽  
J. Madany ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Urine Samples ◽  
Acute Injury ◽  
Control Group ◽  
2D Electrophoresis ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs

AbstractThis study aimed to identify proteins found in the urine of dogs with renal dysfunction leading to acute injury during the natural course of babesiosis (n=10) and to compare them with proteins of a control group (n=10) to reveal any potential biomarkers of renal damage. Pooled urine samples of both groups were separated by 2D electrophoresis (two dimensional electrophoresis), followed by the identification of all proteins using MALDI-TOF mass spectrometry (matrix assisted laser desorption ionization-time of flight). In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common to both groups. Characteristic analysis of the 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways that were attributed to immune and inflammatory response development. Furthermore, it was hypothesized that the epithelial-mesenchymal transition might play an important role in mechanisms underlying pathological renal tissue changes during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways and 4 of the 8 proteins associated with these pathways. These included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukin and TGF-β (transforming growth factor β) pathways. These pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and FER tyrosine kinase, which are potential damage biomarkers during babesiosis in dogs that might be assigned to early renal injury.

scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
D. Winiarczyk ◽  
K. Michalak ◽  
L. Adaszek ◽  
M. Winiarczyk ◽  
S. Winiarczyk
Keyword(s):  
Renal Injury ◽  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Urine Samples ◽  
Control Group ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs ◽  
Potential Biomarkers

Abstract Background Acute kidney injury is the most frequent complication of babesiosis in dogs and may provide a natural model for identifying early and specific markers of kidney injury in this species. There are limited data on urine proteomics in dogs, and none of the effect of babesiosis on the urine proteome. This study aimed to identify urinary proteins of dogs with kidney injury during the natural course of babesiosis caused by Babesia canis, and to compare them with proteins in a control group to reveal any potential biomarkers predicting renal injury before the presence of azotemia. Urine samples were collected from 10 dogs of various breeds and sex with naturally occurring babesiosis, and 10 healthy dogs. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. Results In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common for both groups. Characteristic analysis of 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. Conclusions It was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways, and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins, and TGF-β (transforming growth factor β) pathways. Those pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and tyrosine protein kinase Fer, which are potential biomarkers of damage during babesiosis in dogs, that might indicate early renal injury.

scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Author(s):  
Dagmara Winiarczyk ◽  
Katarzyna Michalak ◽  
Łukasz Adaszek ◽  
Mateusz Winiarczyk ◽  
Stanisław Winiarczyk
Keyword(s):  
Renal Injury ◽  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Urine Samples ◽  
Control Group ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs ◽  
Potential Biomarkers

Abstract BackgroundAcute kidney injury is the most frequent complication of babesiosis in dogs and may provide a natural model for identifying early and specific markers of kidney injury in this species. There are limited data on urine proteomics in dogs, and none of the effect of babesiosis on the urine proteome. This study aimed to identify urinary proteins of dogs with kidney injury during the natural course of babesiosis caused by Babesia canis, and to compare them with proteins in a control group to reveal any potential biomarkers predicting renal injury before the presence of azotemia.Urine samples were collected from 10 dogs of various breeds and sex with naturally occurring babesiosis, and 10 healthy dogs. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. ResultsIn total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common for both groups. Characteristic analysis of 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. ConclusionsIt was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways, and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins, and TGF-β (transforming growth factor β) pathways. Those pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and tyrosine protein kinase Fer, which are potential biomarkers of damage during babesiosis in dogs, that might indicate early renal injury.

scholarly journals Urinary proteome of dogs with kidney injury during babesiosis

2019 ◽  
Author(s):  
Dagmara Winiarczyk ◽  
Katarzyna Michalak ◽  
Łukasz Adaszek ◽  
Mateusz Winiarczyk ◽  
Stanisław Winiarczyk
Keyword(s):  
Acute Kidney Injury ◽  
Renal Injury ◽  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Urine Samples ◽  
Characteristic Analysis ◽  
Mesenchymal Transition ◽  
Healthy Dogs ◽  
Potential Biomarkers

Abstract Background Acute kidney injury is the most frequent complication of babesiosis in dogs and may provide a natural model for identifying early and specific markers of kidney injury in this species. There are limited data on urine proteomics in dogs, and none of the effect of babesiosis on the urine proteome. This study aimed to identify urinary proteins of dogs with kidney injury during the natural course of babesiosis caused by Babesia canis, and to compare them with proteins in a control group to reveal any potential biomarkers predicting renal injury before the presence of azotemia. Urine samples were collected from 10 dogs of various breeds and sex with naturally occurring babesiosis, and 10 healthy dogs. Pooled urine samples from both groups were separated by 2D (two-dimensional) electrophoresis, followed by protein identification using MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry. Results In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common for both groups. Characteristic analysis of 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways involved in immune and inflammatory responses. Conclusions It was hypothesized that epithelial-mesenchymal transition might play an important role in the mechanisms underlying pathological changes in renal tissue during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways, and 4 of the 8 proteins associated with these pathways; this network included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukins, and TGF-β (transforming growth factor β) pathways. Those pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and tyrosine protein kinase Fer, which are potential biomarkers of damage during babesiosis in dogs, that might indicate early renal injury. Keywords: Acute kidney injury, Babesiosis, Dog, Proteomics, Urine

scholarly journals Clinical Significance of Hepatocyte Growth Factor and Transforming Growth Factor-Beta-1 Levels in Assessing Disease Activity in Inflammatory Bowel Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Rania Naguib ◽  
Wafaa Mohamed El-Shikh
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Disease Activity ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Control Group ◽  
Inflammatory Bowel ◽  
Growth Factor Beta ◽  
Hepatocyte Growth

Background. Transforming growth factor-beta (TGF-β) and hepatocyte growth factor (HGF) are inflammatory cytokines which function as key regulators of immunological homeostasis and inflammatory responses. They have been linked to inflammatory bowel diseases (IBD). In this study, we aim to assess the levels of TGF-β and HGF and other inflammatory markers in patients with IBD and correlate them with the disease activity. Study Design. A cross-sectional study involving 100 patients with ulcerative colitis (UC) and 100 patients with Crohn’s disease (CD) and 50 control subjects. TGF-β and HGF levels were measured and correlated with disease activity. Results and Conclusion. Serum levels of TGF-β and HGF were significantly higher in IBD patients compared with the control group. In the UC group, the levels of HGF and TGF-β were significantly higher than in the CD group. Levels of TGF-β and HGF correlate with the activity of IBD.

scholarly journals Ketoprofen as an Add-on Treatment to Sertraline for Drug-Naïve Major Depressed Patients: Normalization of Plasma Levels of Indoleamine-2,3-Dioxygenase in Association with Pro-Inflammatory and Immune Regulatory Cytokines

2018 ◽  
Author(s):  
Hussein Al-Hakeim ◽  
Ahmed Jasim Twayej ◽  
Arafat Hussein Al-Dujaili ◽  
Michael Maes
Keyword(s):  
Clinical Efficacy ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Future Research ◽  
Control Group ◽  
Clinical Effects ◽  
Indoleamine 2,3 Dioxygenase ◽  
Anti Inflammatory ◽  
Normal Controls

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

Circulating Micro RNA 181A as Biomarker in Breast Cancer, Its Possible Association with Metastasis & Epithelial Mesenchymal Transformation

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
LA Rashed ◽  
SH Faiz ◽  
MA Hassan ◽  
MM Elsebaie ◽  
AE Saad
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Metastatic Disease ◽  
Transforming Growth Factor ◽  
Metastatic Breast ◽  
Micro Rna ◽  
Control Group ◽  
Tgf Beta ◽  
Mesenchymal Transition ◽  
Mesenchymal Transformation

Background: Recent studies have reported the involvement of micro RNA 181a in diverse cellular functions. Though some studies have shown that miR-181a expression is downregulated in several human solid tumors, others have demonstrated that upregulation of miR-181a may promote metastasis and invasion of human cancers. Aim of the Study: The aim of this work is to detect the level of circulating miRNA-181a in breast cancer cases at different stages and to study its role in metastasis & epithelial mesenchymal transformation (EMT) through the possible association between miRNA 181a and transforming growth factor beta (TGFβ) signaling pathway. Subjects and Methods: The present work included 70 female patients, with breast cancer at different stages 30 patients with metastatic disease and 40 patients with non-metastatic disease 20 healthy subjects were taken as a control group. We detected miRNA-181a expression in peripheral blood with qRT PCR, and TGF-beta, SMAD-4, SNAIL-1 and Bim expression by quantitative PCR. Results: miRNA-181a, TGF-beta, SNAIL-1 and SMAD-4 were significantly upregulated in patients with metastatic breast cancer compared to patients with non-metastatic disease while Bim is significantly downregulated in metastatic versus non-metastatic group. Also, miRNA-181a was a prognostic marker for disease progression and overall survival. Conclusion: signaling pathway of TGFβ-SMAD, regulate miRNA-181a which in turn play role in stabilizing SNAIL transcription factor that promote tumor aggressiveness and metastasis through epithelial mesenchymal transition, as well as down-regulation of Bim.

scholarly journals Cytokine Gene Polymorphisms in Autoimmune Thyroid Disease

2000 ◽  
Vol 85 (5) ◽  
pp. 1984-1988 ◽  
Author(s):  
P. J. Hunt ◽  
S. E. Marshall ◽  
A. P. Weetman ◽  
J. I. Bell ◽  
J. A. H. Wass ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Thyroid Disease ◽  
Odds Ratio ◽  
Autoimmune Thyroid Disease ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
The Other ◽  
Control Group ◽  
Potential Candidate ◽  
Autoimmune Thyroid

Abstract Susceptibility to the autoimmune thyroid diseases, Graves’ disease (GD) and autoimmune hypothyroidism (AIH), depends on a complex interaction between environmental and genetic factors. The human leukocyte antigen and cytotoxic T lymphocyte-associated-4 regions appear to influence susceptibility to disease, but the effect is not major, and the other genes remain unknown. Cytokines are crucial in the regulation of immune and inflammatory responses and therefore are potential candidate genes for autoimmune thyroid disease. In a case-control study, using a unified method of genotyping, we have examined 15 polymorphisms in 9 cytokine genes in 215 patients with autoimmune thyroid disease (GD, 138; AIH, 77) and 101 normal controls. Polymorphisms in the genes for interleukin-1α (IL-1α), IL-1β, IL-1 receptor antagonist, IL-1 receptor 1, IL-4, IL-4 receptor, IL-6, IL-10, and transforming growth factor-β were investigated. Genotyping was performed using the PCR and sequence-specific primers. Analysis showed a reduced frequency of the variant t allele in the IL-4 promoter polymorphism (position −590) in patients with GD and in the entire patient group (GD and AIH) compared with the control group [corrected P (Pc) = 0.00004 and Pc < 0.00001 for GD and all patients, respectively]. This was reflected in a reduction in the heterozygote genotype in the patient groups compared to the controls [c/t heterozygotes GD, 12%; Pc = 0.06, odds ratio, 0.4 (95% confidence interval, 0.2–0.7); all patients, 11%; Pc = 0.008; odds ratio, 0.4 (95% confidence interval, 0.2–0.7); control subjects, 23%]. There were no significant differences between the study groups for the other polymorphisms examined, and subgroup analysis revealed no association with clinical parameters of disease. These results suggest that an IL-4 variant or a closely linked gene has a modest protective effect against the development of autoimmune thyroid disease, particularly GD. This variation in the IL-4 gene may provide further clues to the pathogenesis of autoimmune thyroid disease and other organ-specific autoimmune diseases. Furthermore, these results suggest that subtle variation in immunoregulatory genes may be associated with autoimmune disease states.

scholarly journals Topically Applied Cross-Linked Hyaluronan Attenuates the Formation of Spinal Epidural Fibrosis in a Swine Model of Laminectomy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Cheng-Li Lin ◽  
I-Ming Jou ◽  
Cheng-Yi Wu ◽  
Yuh-Ruey Kuo ◽  
Shih-Chieh Yang ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Healing Process ◽  
Scar Tissue ◽  
Control Group ◽  
Swine Model ◽  
Epidural Fibrosis ◽  
Mesenchymal Transition ◽  
Failed Back Surgery ◽  
Anti Inflammatory ◽  
Spinal Epidural

Abstract Epidural fibrosis is an inevitable aspect of the postoperative healing process which is one of the causes of failed back surgery syndrome following spinal surgery. The aim of the present study was to examine the inhibitory effect of 1,4-butanediol diglycidyl ether-crosslinked hyaluronan (cHA) on spinal epidural fibrosis in a swine model. Epidural fibrosis was induced through conduction of hemi-laminotomy (L2 and L3) or laminectomy (L4 and L5), while L1 was assigned as the control group in six pigs. The cHA was applied to L3 and L5 surgical sites. MRI evaluation, histologic examination, expressions of matrix metalloproteinases (MMPs), and cytokines in scar tissue were assessed four months after surgery. cHA treatment significantly decreased the scar formation in both hemi-laminotomy and laminectomy sites. cHA also significantly increased MMP-3 and MMP-9 expression in scar tissue. Further, the epithelial-mesenchymal transition -related factors (transforming growth factor-β and vimentin) were suppressed and the anti-inflammatory cytokines (CD44 and interleukin-6) were increasingly expressed in cHA-treated sites. The current study demonstrated that cHA may attenuate spinal epidural fibrosis formation after laminectomy surgery by enhancing the expression of MMPs and anti-inflammatory pathways.

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