13 results on '"Jackson, Isabel"'
Search Results
2. BIO 300, a Nanosuspension of Genistein, Mitigates Radiation-Induced Erectile Dysfunction and Sensitizes Human Prostate Cancer Xenografts to Radiation Therapy.
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Jackson, Isabel L., Pavlovic, Rada, Alexander, Allen A., Connors, Caroline Q., Newman, Diana, Mahmood, Javed, Eley, John, Harvey, Adam J., Kaytor, Michael D., and Vujaskovic, Zeljko
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GENISTEIN , *RADIOTHERAPY , *PROSTATE cancer , *RADIATION injuries , *RADIATION carcinogenesis , *IMPOTENCE , *XENOGRAFTS , *ANIMALS , *BIOLOGICAL models , *BLOOD circulation , *BLOOD pressure , *MICE , *NANOPARTICLES , *PENIS , *PROSTATE , *RADIATION-protective agents , *RATS , *RESEARCH funding , *STATISTICAL sampling , *SUSPENSIONS (Chemistry) , *FIBROSIS , *PENILE erection , *INVESTIGATIONAL drugs , *DISEASE complications , *PHYSIOLOGICAL effects of radiation - Abstract
Purpose: To assess whether BIO 300, a synthetic genistein nanosuspension, improves the therapeutic index in prostate cancer treatment by preventing radiation-induced erectile dysfunction (ED) without reducing tumor radiosensitivity.Methods and Materials: Male Sprague-Dawley rats were exposed to 25 Gy of 220-kV prostate-confined x-rays. Animals were randomized to receive sham radiation therapy (RT), RT alone, RT with daily BIO 300 at 2 experimental dosing regimens, or RT with daily genistein. Erectile response was evaluated over time. Penile shaft tissue was harvested for histologic analyses. Murine xenograft studies using prostate cancer cell lines determined the effects of BIO 300 dosing on RT efficacy.Results: Prostate-confined RT significantly decreased apomorphine-induced erectile response (P < .05 vs sham RT). Erection frequency in animals receiving prophylactic treatment with BIO 300 starting 3 days before RT was similar to sham controls after RT. Treatment with synthetic genistein did not mitigate loss in erectile frequency. At week 14, post-RT treatment with BIO 300 resulted in significantly higher quality of erectile function compared with both the RT arm and the RT arm receiving genistein starting 3 days before irradiation (P < .05). In hormone-sensitive and insensitive prostate tumor-bearing mice, BIO 300 administration did not negatively affect radiation-induced tumor growth delay.Conclusions: BIO 300 prevents radiation-induced ED, measured by erection frequency, erectile function, and erection quality, when administered 3 days before RT and continued daily for up to 14 weeks. Data also suggest that BIO 300 administered starting 2 hours after RT mitigates radiation-induced ED. Data provide strong nonclinical evidence to support clinical translation of BIO 300 for mitigation of ED while maintaining treatment response to RT. [ABSTRACT FROM AUTHOR]- Published
- 2019
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3. A survey of changing trends in modelling radiation lung injury in mice: bringing out the good, the bad, and the uncertain.
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Dabjan, Mohamad B, Buck, Carolyn MS, Jackson, Isabel L, Vujaskovic, Zeljko, Marples, Brian, and Down, Julian D
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- 2016
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4. Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoin.
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Kelsey, Chris R, Jackson, Isabel L, Langdon, Scott, Owzar, Kouros, Hubbs, Jessica, Vujaskovic, Zeljko, Das, Shiva, and Marks, Lawrence B
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- 2013
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5. Using Biological Markers to Predict Risk of Radiation Injury.
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Fleckenstein, Katharina, Gauter-Fleckenstein, Benjamin, Jackson, Isabel L., Rabbani, Zahid, Anscher, Mitchell, and Vujaskovic, Zeljko
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Recent advances in our understanding of the molecular events leading to the development of normal tissue complications after radiotherapy has led to an effort to identify biological markers that could identify patients at increased or decreased risk for treatment related injury. The goal of this effort is to improve the therapeutic ratio and enable physicians to optimize therapy for individual patients. In radiotherapy of the thoracic region, the lung is one of the most critical dose-limiting organs. This review briefly introduces the mechanisms of radiation-induced lung injury and gives a summary of clinical research focused on evaluating changes in biological markers before, during, and after radiation therapy of the thorax. [Copyright &y& Elsevier]
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- 2007
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6. Psychological stress enhances tumor growth and diminishes radiation response in preclinical model of lung cancer.
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Zhang, Yi, Zanos, Panos, Jackson, Isabel L., Zhang, Xiuwu, Zhu, Xiongzhao, Gould, Todd, and Vujaskovic, Zeljko
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PSYCHOLOGICAL stress , *TUMOR growth , *ANIMAL models in research , *LUNG cancer , *EPITHELIAL-mesenchymal transition , *IMMOBILIZATION stress - Abstract
• Psychological stress-induced depression increased tumor growth and radioresistance. • Psychological stress activates epithelial-mesenchymal transition associated with resistance. • Psychological stress increased tumor growth and radioresistance via adrenergic receptors. Patients with life-threatening illnesses, such as cancer, experience emotional distress. This study was to investigate the molecular and cellular mechanisms of relevant psychological stressor on tumor growth and therapeutic resistance. Stress was induced in C57BL/6J mice bearing LLC lung tumors by exposure to a conspecific mice receiving inescapable foot shocks. Mice were irradiated at 7 Gy for 3 consecutive days. Behaviors were monitored by open field test (OFT), elevated plus maze (EPM), sucrose preference test (SPT), and learned helplessness (LH) test. Protein expression in tissues and cultured cells were measured by Western blot. This study in animals showed that observing a conspecific mouse receiving foot shocks induced depression like behaviors with increased plasma corticosterone and adrenaline levels which increased tumor growth and radioresistance. Stress increased Wnt1, Drosha, and vimentin expression and decreased E-cadherin expression in tumor tissues. The combination of stress and irradiation enhanced radioresistance along with the increase in vimentin expression. The in vitro study showed that a β 2 -adrenergic receptor (β2-AR) agonist blocked irradiation-induced cell apoptosis and decreased cell viability, while silencing β2-AR expression reduced the protective effects of β2-AR agonist. β2-AR agonist obviously increased Wnt1 and Drosha expression in LLC-1 cells. Psychological stress increased tumor growth and enhanced radioresistance associated with the activation of epithelial-mesenchymal transition by stress hormone-stimulated adrenergic receptors. [ABSTRACT FROM AUTHOR]
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- 2020
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7. Radioprotective Effects of Amifostine on Acute and Chronic Esophageal Injury in Rodents
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Vujaskovic, Zeljko, Thrasher, Bradley A., Jackson, Isabel L., Brizel, Marla B., and Brizel, David M.
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ESOPHAGEAL injuries , *GROWTH factors , *EXTRACELLULAR matrix proteins , *LABORATORY rodents - Abstract
Purpose: This study was performed to evaluate the protective benefit of amifostine against esophageal injury from fractionated radiation in a rodent model. Methods: Fractionated or sham esophageal irradiation was administered to Fisher-344 rats for 5 consecutive daily fractions of 9 Gy using 150 kV X-rays. Animals received an intraperitoneal injection of amifostine or placebo 30 min before each fraction. Histopathologic analyses for mucosal thickness, submucosal collagen deposition, activation of macrophages, oxidative stress and expression/activation of integrinαvβ6 and transforming growth factor (TGF)–β were performed 5 days and 10 weeks after irradiation. Results: Pre-RT mean mucosal thickness was 35 μm in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 μm in the placebo group versus 37 μm in the amifostine group (p = 0.024). At 10 weeks post-RT, the group receiving amifostine experienced a significant decrease in tunica muscularis damage (p = 0.002), submucosal collagen deposition (p = 0.027), and macrophage accumulation (p = 0.026) when compared with the placebo group. The levels of immunoreactivity for oxidative stress, TGF-β, and integrinαvβ6 were significantly decreased 10 weeks post-RT in the group receiving amifostine treatment compared with placebo group. Conclusions: This study demonstrates that amifostine given before each radiation fraction protects against acute and chronic esophageal injury in a rodent model. Protection of the mucosal epithelium integrity by amifostine prevents integrinαvβ6 expression which reduces TGF-β activation and subsequent development of chronic esophageal injury in this model. Further investigation is necessary to determine the clinical relevance of these findings. [Copyright &y& Elsevier]
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- 2007
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8. A Dose of Reality: How 20 Years of Incomplete Physics and Dosimetry Reporting in Radiobiology Studies May Have Contributed to the Reproducibility Crisis.
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Draeger, Emily, Sawant, Amit, Johnstone, Christopher, Koger, Brandon, Becker, Stewart, Vujaskovic, Zeljko, Jackson, Isabel-Lauren, and Poirier, Yannick
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RADIOBIOLOGY , *RADIATION dosimetry , *SCIENTIFIC literature , *PHYSICS , *RADIATION exposure , *RADIATION measurements , *WEIGHTS & measures , *TIME , *BIBLIOMETRICS , *CONFERENCES & conventions , *RADIATION doses , *PERIODICAL articles , *MEDICAL research , *IMPACT factor (Citation analysis) ,RESEARCH evaluation - Abstract
Purpose: A large proportion of preclinical or translational studies using radiation have poor replicability. For a study involving radiation exposure to be replicable, interpretable, and comparable, its experimental methodology must be well reported, particularly in terms of irradiation protocol, including the amount, rate, quality, and geometry of radiation delivery. Here we perform the first large-scale literature review of the current state of reporting of essential experimental physics and dosimetry details in the scientific literature.Methods and Materials: For 1758 peer-reviewed articles from 469 journals, we evaluated the reporting of basic experimental physics and dosimetry details recommended by the authoritative National Institute of Standards and Technology symposium.Results: We demonstrate that although some physics and dosimetry parameters, such as dose, source type, and energy, are well reported, the majority are not. Furthermore, highly cited journals and articles are systematically more likely to be lacking experimental details related to the irradiation protocol.Conclusions: These findings show a crucial deficiency in the reporting of basic experimental details and severely affect the reproducibility and translatability of a large proportion of radiation biology studies. [ABSTRACT FROM AUTHOR]- Published
- 2020
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9. Cavernous Nerve Injury by Radiation Therapy May Potentiate Erectile Dysfunction in Rats.
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Mahmood, Javed, Connors, Caroline Q., Alexander, Allen A., Pavlovic, Radmila, Samanta, Santanu, Soman, Sandrine, Eley, John, Sawant, Amit, Jackson, Isabel L., Vujaskovic, Zeljko, Matsui, Hotaka, Sopko, Nikolai A., Bivalacqua, Trinity J., Weinreich, Daniel, and Ho, Cheng-Ying
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ANIMAL models in research , *IMPOTENCE , *RADIOTHERAPY , *QUALITY of life , *CANCER patients , *ANIMAL experimentation , *BIOLOGICAL models , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *NEURAL conduction , *PENIS , *PROSTATE , *RADIATION injuries , *RATS , *RESEARCH , *STATISTICAL sampling , *STAINS & staining (Microscopy) , *EVALUATION research , *PENILE erection , *DISEASE complications , *PHYSIOLOGICAL effects of radiation , *INNERVATION - Abstract
Purpose/objectives: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established. The cavernous nerves (CN) are postganglionic parasympathetic nerves located beside the prostate gland that assist in penile erection. This study was designed to investigate the role of CN injury, tissue damage, and altered signaling pathways in an RiED rat model.Methods and Materials: Male rats were exposed to a single dose of 25 Gy prostate-confined RT. Erectile function was evaluated by intracavernous pressure (ICP) measurements conducted both 9 and 14 weeks after RT. Neuronal injury was evaluated in the CN using quantitative polymerase chain reaction, conduction studies, transmission electron microscopy, and immunoblotting. Masson trichrome staining was performed to elucidate fibrosis level in penile tissues.Results: There were significant alterations in the ICP (P<.0001) of RT rats versus non-RT rats. TEM analysis showed decreased myelination, increased microvascular damage, and progressive axonal atrophy of the CN fibers after RT. Electrophysiologic analysis showed significant impairment of the CN conduction velocity after RT. RT also significantly increased RhoA/Rho-associated protein kinase 1 (ROCK1) mRNA and protein expression. In addition, penile tissue showed increased apoptosis and fibrosis 14 weeks after RT.Conclusions: RT-induced CN injury may contribute to RiED; this is therefore a rationale for developing novel therapeutic strategies to mitigate CN and tissue damage. Moreover, further investigation of the RhoA/ROCK pathway's role in mitigating RiED is necessary. [ABSTRACT FROM AUTHOR]- Published
- 2017
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10. Oxidative Stress Mediates Radiation Lung Injury by Inducing Apoptosis
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Zhang, Yu, Zhang, Xiuwu, Rabbani, Zahid N., Jackson, Isabel L., and Vujaskovic, Zeljko
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OXIDATIVE stress , *LUNG injuries , *APOPTOSIS , *TISSUES , *RADIOTHERAPY , *TRANSFORMING growth factors , *LABORATORY mice - Abstract
Purpose: Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown. Methods and Materials: C57BL/6J mice were irradiated with 15 Gy to the whole thorax. Pro-apoptotic signaling was evaluated 6 weeks after radiation with or without administration of AEOL10150, a potent catalytic scavenger of reactive oxygen and nitrogen species. Results: Apoptosis was observed primarily in type I and type II pneumocytes and endothelium. Apoptosis correlated with increased PTEN expression, inhibition of downstream PI3K/AKT signaling, and increased p53 and Bax protein levels. Transforming growth factor-β1, Nox4, and oxidative stress were also increased 6 weeks after radiation. Therapeutic administration of AEOL10150 suppressed pro-apoptotic signaling and dramatically reduced the number of apoptotic cells. Conclusion: Increased PTEN signaling after radiation results in apoptosis of lung parenchymal cells. We hypothesize that upregulation of PTEN is influenced by Nox4-derived oxidative stress. To our knowledge, this is the first study to highlight the role of PTEN in radiation-induced pulmonary toxicity. [ABSTRACT FROM AUTHOR]
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- 2012
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11. Proteomic analysis of radiation-induced changes in rat lung: Modulation by the superoxide dismutase mimetic MnTE-2-PyP(5+).
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Yakovlev VA, Rabender CS, Sankala H, Gauter-Fleckenstein B, Fleckenstein K, Batinic-Haberle I, Jackson I, Vujaskovic Z, Anscher MS, Mikkelsen RB, Graves PR, Yakovlev, Vasily A, Rabender, Christopher S, Sankala, Heidi, Gauter-Fleckenstein, Ben, Fleckenstein, Katharina, Batinic-Haberle, Ines, Jackson, Isabel, Vujaskovic, Zeljko, and Anscher, Mitchell S
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Purpose: To identify temporal changes in protein expression in the irradiated rat lung and generate putative mechanisms underlying the radioprotective effect of the manganese superoxide dismutase mimetic MnTE-2-PyP(5+).Methods and Materials: Female Fischer 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy and killed from day 1 to 20 weeks after irradiation. Proteomic profiling was performed to identify proteins that underwent significant changes in abundance. Some irradiated rats were administered MnTE-2-PyP(5+) and changes in protein expression and phosphorylation determined at 6 weeks after irradiation.Results: Radiation induced a biphasic stress response in the lung, as shown by the induction of heme oxygenase 1 at 1-3 days and at 6-8 weeks after irradiation. At 6-8 weeks after irradiation, the down-regulation of proteins involved in cytoskeletal architecture (filamin A and talin), antioxidant defense (biliverdin reductase and peroxiredoxin II), and cell signaling (β-catenin, annexin II, and Rho-guanosine diphosphate dissociation inhibitor) was observed. Treatment with MnTE-2-PyP(5+) partially prevented the apparent degradation of filamin and talin, reduced the level of cleaved caspases 3 and 9, and promoted Akt phosphorylation as well as β-catenin expression.Conclusion: A significant down-regulation of proteins and an increase in protein markers of apoptosis were observed at the onset of lung injury in the irradiated rat lung. Treatment with MnTE-2-PyP(5+), which has been demonstrated to reduce lung injury from radiation, reduced apparent protein degradation and apoptosis indicators, suggesting that preservation of lung structural integrity and prevention of cell loss may underlie the radioprotective effect of this compound. [ABSTRACT FROM AUTHOR]- Published
- 2010
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12. Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation
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Fleckenstein, Katharina, Zgonjanin, Larisa, Chen, Liguang, Rabbani, Zahid, Jackson, Isabel L., Thrasher, Bradley, Kirkpatrick, John, Foster, W. Michael, and Vujaskovic, Zeljko
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IRRADIATION , *CEREBRAL anoxia , *RADIATION , *OXIDATIVE stress - Abstract
Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury.Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-beta [TGF-beta]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines.Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-beta expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation.Conclusions: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury. [ABSTRACT FROM AUTHOR]- Published
- 2007
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13. Pilot Study Evaluating a Rat Model of Radiation-induced Erectile Dysfunction Using an Image-guided Microirradiator.
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Kimura, Masaki, Zodda, Andrew R., Mahmood, Javed, Das, Shiva K., Nguyen, Giao B., Jackson, Isabel L., and Vujaskovic, Zeljko
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PILOT projects , *LABORATORY rats , *RADIATION-induced abnormalities , *IMPOTENCE , *IMAGE-guided radiation therapy , *QUALITY assurance , *DIAGNOSIS - Abstract
Objective To establish a feasible rat model of radiation-induced erectile dysfunction after targeted prostate irradiation using an image-guided irradiation unit specially designed for small-animal radiation research. Methods The X-RAD 225Cx research platform was used in the present study. We first performed quality assurance testing using a rat cadaver. After confirming dosimetry, 24 age-matched, young, adult, male rats were assigned to sham radiation or radiation to the prostate with doses of 15, 20, or 25 Gy. To confirm appropriate prostate irradiation, physiological erectile function was evaluated using intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation at 9 weeks after radiotherapy. Each animal was weighed at the time of ICP measurement. In addition, we investigated the cyclic guanosine monophosphate level in the penile cavernosa using a commercial enzyme-linked immunosorbent assay kit. Results Quality assurance results confirmed the accuracy of the irradiation technique. Dose-dependent decreases in ICP in irradiated rats were observed without major toxicity. No difference in body weight was noted among the experimental groups. Cyclic guanosine monophosphate levels were significantly decreased in the group that received 25 Gy compared with the age-matched sham-irradiated group. Conclusion High-precision imaging and targeting capabilities provided by the micro-IGRT platform enable us to develop a reproducible animal model of radiation-induced erectile dysfunction in prostate cancer research. [ABSTRACT FROM AUTHOR]
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- 2015
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