Bio

Honors & Awards


  • Travel award, World Molecular Imaging Conference (WMIC) (2013)
  • Trainee Research Prize, Radiological Society of North America (RSNA) (2012)
  • Travel award, World Molecular Imaging Conference (WMIC) (2012)
  • Travel award, International Cartilage Repair Society (ICRS) (2010)
  • Scholarship award, National University of Singapore School of Medicine (SoM) (2009 and 2010)
  • Travel award, International Cartilage Repair Society (ICRS) (2009)
  • Scholarship award, Agency for Science, Technology and Research (A*STAR) (2007 and 2008)

Professional Education


  • Postdoctoral fellowship, Stanford University, Radiology
  • PhD Scholar, National University of Singapore (2013)
  • Medical internship, Isfahan University of Medical Sciences, (transitional internship) (2005)
  • Doctor of Medicine, University Of Isfahan (2005)

Stanford Advisors


Community and International Work


  • member of Molecular Imaging Program at Stanford (MIPS)

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Member of International Society for Magnetic Resonance in Medicine (ISMRM)

    Location

    California

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Member of European Society for Magnetic Resonance in Medicine and Biology (ESMRMB)

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • member of International Cartilage Repair Society (ICRS)

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Research & Scholarship

Current Research and Scholarly Interests


Stem Cell Imaging: The ultimate goal of my research is to develop clinically applicable, non-invasive and repeatable imaging tools, which can be used for long-term tracking of transplanted stem cells in bone defects and osteochondral defects. I evaluate novel contrast agents for non-invasive in vivo detection of stem cells with MR imaging in mouse models of bone and cartilage repair, I test smart, activatable MR contrast agents, which can provide non-invasive information about the viability and in vivo differentiation of transplanted stem cells, and I evaluate specific nanoparticle-based labels for immune cells, which allow monitoring host responses to stem cell transplants. The new imaging tools are used to improve bone and cartilage regeneration outcomes of mesenchymal stem cells, adipose derived stem cells and induced pluripotent stem cells.

Publications

Journal Articles


  • Ferumoxytol: a new, clinically applicable label for stem-cell tracking in arthritic joints with MRI. Nanomedicine Khurana, A., Nejadnik, H., Chapelin, F., Lenkov, O., Gawande, R., Lee, S., Gupta, S. N., Aflakian, N., Derugin, N., Messing, S., Lin, G., Lue, T. F., Pisani, L., Daldrup-Link, H. E. 2013; 8 (12): 1969-1983

    Abstract

    Aim: To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol. Materials & methods: Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology. Results: An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time. Conclusion: Ferumoxytol can be used for in vivo tracking of stem cells with MRI. Original submitted 28 February 2012; Revised submitted 8 November 2012.

    View details for DOI 10.2217/nnm.12.198

    View details for PubMedID 23534832

  • Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation. Radiology Khurana, A., Chapelin, F., Beck, G., Lenkov, O. D., Donig, J., Nejadnik, H., Messing, S., Derugin, N., Chan, R. C., Gaur, A., Sennino, B., McDonald, D. M., Kempen, P. J., Tikhomirov, G. A., Rao, J., Daldrup-Link, H. E. 2013; 269 (1): 186-197

    Abstract

    Purpose:To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants.Materials and Methods:This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6-8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo-labeling procedures. The in vivo-labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo-labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results.Results:In vivo-labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo-labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo-labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling.Conclusion:Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo-labeling procedures.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130858/-/DC1.

    View details for DOI 10.1148/radiol.13130858

    View details for PubMedID 23850832

  • Enhancing in vivo survival of adipose-derived stromal cells through bcl-2 overexpression using a minicircle vector. Stem cells translational medicine Hyun, J., Grova, M., Nejadnik, H., Lo, D., Morrison, S., Montoro, D., Chung, M., Zimmermann, A., Walmsley, G. G., Lee, M., Daldrup-Link, H., Wan, D. C., Longaker, M. T. 2013; 2 (9): 690-702

    Abstract

    Tissue regeneration using progenitor cell-based therapy has the potential to aid in the healing of a diverse range of pathologies, ranging from short-gut syndrome to spinal cord lesions. However, there are numerous hurdles to be overcome prior to the widespread application of these cells in the clinical setting. One of the primary barriers to effective stem cell therapy is the hostile environment that progenitor cells encounter in the clinical injury wound setting. In order to promote cellular survival, stem cell differentiation, and participation in tissue regeneration, relevant cells and delivery scaffolds must be paired with strategies to prevent cell death to ensure that these cells can survive to form de novo tissue. The Bcl-2 protein is a prosurvival member of a family of proteins that regulate the mitochondrial pathway of apoptosis. Using several strategies to overexpress the Bcl-2 protein, we demonstrated a decrease in the mediators of apoptosis in vitro and in vivo. This was shown through the use of two different clinical tissue repair models. Cells overexpressing Bcl-2 not only survived within the wound environment at a statistically significantly higher rate than control cells, but also increased tissue regeneration. Finally, we used a nonintegrating minicircle technology to achieve this in a potentially clinically applicable strategy for stem cell therapy.

    View details for DOI 10.5966/sctm.2013-0035

    View details for PubMedID 23934910

  • Magnetic resonance imaging and tracking of stem cells. Methods in molecular biology (Clifton, N.J.) Nejadnik, H., Castillo, R., Daldrup-Link, H. E. 2013; 1052: 1-10

    Abstract

    To date, several stem cell labeling protocols have been developed, contributing to a fast growing and promising field of stem cell imaging by MRI (magnetic resonance imaging). Most of these methods utilize iron oxide nanoparticles (MION, SPIO, USPIO, VSIOP) for cell labeling, which provide negative (dark) signal effects on T2-weighted MR images. The following protocol describes stem cell labeling techniques with commercially available gadolinium chelates, which provide positive contrast on T1-weighted MR images, which can be advantageous for specific applications.

    View details for DOI 10.1007/7651_2013_16

    View details for PubMedID 23743862

  • MR Imaging Features of Gadofluorine-Labeled Matrix-Associated Stem Cell Implants in Cartilage Defects PLOS ONE Nejadnik, H., Henning, T. D., Thuy Do, T., Sutton, E. J., Baehner, F., Horvai, A., Sennino, B., McDonald, D., Meier, R., Misselwitz, B., Link, T. M., Daldrup-Link, H. E. 2012; 7 (12)
  • Intravenous Ferumoxytol Allows Noninvasive MR Imaging Monitoring of Macrophage Migration into Stem Cell Transplants RADIOLOGY Khurana, A., Nejadnik, H., Gawande, R., Lin, G., Lee, S., Messing, S., Castaneda, R., Derugin, N., Pisani, L., Lue, T. F., Daldrup-Link, H. E. 2012; 264 (3): 803-811

    Abstract

    To develop a clinically applicable imaging technique for monitoring differential migration of macrophages into viable and apoptotic matrix-associated stem cell implants (MASIs) in arthritic knee joints.With institutional animal care and use committee approval, six athymic rats were injected with intravenous ferumoxytol (0.5 mmol iron per kilogram of body weight) to preload macrophages of the reticuloendothelial system with iron oxide nanoparticles. Forty-eight hours later, all animals received MASIs of viable adipose-derived stem cells (ADSCs) in an osteochondral defect of the right femur and mitomycin-pretreated apoptotic ADSCs in an osteochondral defect of the left femur. One additional control animal each received intravenous ferumoxytol and bilateral scaffold-only implants (without cells) or bilateral MASIs without prior ferumoxytol injection. All knees were imaged with a 7.0-T magnetic resonance (MR) imaging unit with T2-weighted fast spin-echo sequences immediately after, as well as 2 and 4 weeks after, matrix-associated stem cell implantation. Signal-to-noise ratios (SNRs) of viable and apoptotic MASIs were compared by using a linear mixed-effects model. MR imaging data were correlated with histopathologic findings.All ADSC implants showed a slowly decreasing T2 signal over 4 weeks after matrix-associated stem cell implantation. SNRs decreased significantly over time for the apoptotic implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 16.9, 10.9, and 6.7, respectively; P = .0004) but not for the viable implants (SNRs on the day of matrix-associated stem cell implantation, 2 weeks after the procedure, and 4 weeks after the procedure were 17.7, 16.2, and 15.7, respectively; P = .2218). At 4 weeks after matrix-associated stem cell implantation, SNRs of apoptotic ADSCs were significantly lower than those of viable ADSCs (mean, 6.7 vs 15.7; P = .0013). This corresponded to differential migration of iron-loaded macrophages into MASIs.Iron oxide loading of macrophages in the reticuloendothelial system by means of intravenous ferumoxytol injection can be utilized to monitor differential migration of bone marrow macrophages into viable and apoptotic MASIs in a rat model.

    View details for DOI 10.1148/radiol.12112393

    View details for Web of Science ID 000308645500022

    View details for PubMedID 22820731

  • Engineering stem cells for treatment of osteochondral defects SKELETAL RADIOLOGY Nejadnik, H., Daldrup-Link, H. E. 2012; 41 (1): 1-4

    View details for DOI 10.1007/s00256-011-1272-6

    View details for Web of Science ID 000297543700001

    View details for PubMedID 22072236

  • Somatic Differentiation and MR Imaging of Magnetically Labeled Human Embryonic Stem Cells CELL TRANSPLANTATION Nejadnik, H., Henning, T. D., Castaneda, R. T., Boddington, S., Taubert, S., Jha, P., Tavri, S., Golovko, D., Ackerman, L., Meier, R., Daldrup-Link, H. E. 2012; 21 (12): 2555-2567

    Abstract

    Magnetic resonance (MR) imaging of superparamagnetic iron oxide (SPIO)-labeled stem cells offers a noninvasive evaluation of stem cell engraftment in host organs. Excessive cellular iron load from SPIO labeling, however, impairs stem cell differentiation. The purpose of this study was to magnetically label human embryonic stem cells (hESCs) via a reduced exposure protocol that maintains a significant MR signal and no significant impairment to cellular pluripotency or differentiation potential. hESCs were labeled by simple incubation with Food and Drug Administration-approved ferumoxides, using concentrations of 50- 200 µg Fe/ml and incubation times of 3-24 h. The most reduced exposure labeling protocol that still provided a significant MR signal comparable to accepted labeling protocols was selected for subsequent studies. Labeled hESCs were compared to unlabeled controls for differences in pluripotency as studied by fluorescence staining for SSEA-1, SSEA-4, TRA-60, and TRA-81 and in differentiation capacity as studied by quantitative real-time PCR for hOCT4, hACTC1, hSOX1, and hAFP after differentiation into embryoid bodies (EBs). Subsequent MR and microscopy imaging were performed to evaluate for cellular iron distribution and long-term persistence of the label. An incubation concentration of 50 µg Fe/ml and incubation time of 3 h demonstrated a significantly reduced exposure protocol that yielded an intracellular iron uptake of 4.50 ± 0.27 pg, an iron content comparable to currently accepted SPIO labeling protocols. Labeled and unlabeled hESCs showed no difference in pluripotency or differentiation capacity. Ferumoxide-labeled hESCs demonstrated persistent MR contrast effects as embryoid bodies for 21 days. Electron microscopy confirmed persistent lysosomal storage of iron oxide particles in EBs up to 9 days, while additional microscopy visualization confirmed the iron distribution within single and multiple EBs. Labeling hESCs with ferumoxides by this tailored protocol reduces exposure of cells to the labeling agent while allowing for long-term visualization with MR imaging and the retention of cellular pluripotency and differentiation potential.

    View details for DOI 10.3727/096368912X653156

    View details for Web of Science ID 000315001400002

    View details for PubMedID 22862886

  • MR imaging features of gadofluorine-labeled matrix-associated stem cell implants in cartilage defects. PloS one Nejadnik, H., Henning, T. D., Do, T., Sutton, E. J., Baehner, F., Horvai, A., Sennino, B., McDonald, D., Meier, R., Misselwitz, B., Link, T. M., Daldrup-Link, H. E. 2012; 7 (12)

    Abstract

    The purpose of our study was to assess the chondrogenic potential and the MR signal effects of GadofluorineM-Cy labeled matrix associated stem cell implants (MASI) in pig knee specimen.Human mesenchymal stem cells (hMSCs) were labeled with the micelle-based contrast agent GadofluorineM-Cy. Ferucarbotran-labeled hMSCs, non-labeled hMSCs and scaffold only served as controls. Chondrogenic differentiation was induced and gene expression and histologic evaluation were performed. The proportions of spindle-shaped vs. round cells of chondrogenic pellets were compared between experimental groups using the Fisher's exact test. Labeled and unlabeled hMSCs and chondrocytes in scaffolds were implanted into cartilage defects of porcine femoral condyles and underwent MR imaging with T1- and T2-weighted SE and GE sequences. Contrast-to-noise ratios (CNR) between implants and adjacent cartilage were determined and analyzed for significant differences between different experimental groups using the Kruskal-Wallis test. Significance was assigned for p<0.017, considering a Bonferroni correction for multiple comparisons.Collagen type II gene expression levels were not significantly different between different groups (p>0.017). However, hMSC differentiation into chondrocytes was superior for unlabeled and GadofluorineM-Cy-labeled cells compared with Ferucarbotran-labeled cells, as evidenced by a significantly higher proportion of spindle cells in chondrogenic pellets (p<0.05). GadofluorineM-Cy-labeled hMSCs and chondrocytes showed a positive signal effect on T1-weighted images and a negative signal effect on T2-weighted images while Ferucarbotran-labeled cells provided a negative signal effect on all sequences. CNR data for both GadofluorineM-Cy-labeled and Ferucarbotran-labeled hMSCs were significantly different compared to unlabeled control cells on T1-weighted SE and T2*-weighted MR images (p<0.017).hMSCs can be labeled by simple incubation with GadofluorineM-Cy. The labeled cells provide significant MR signal effects and less impaired chondrogenesis compared to Ferucarbotran-labeled hMSCs. Thus, GadoflurineM-Cy might represent an alternative MR cell marker to Ferucarbotran, which is not distributed any more in Europe or North America.

    View details for DOI 10.1371/journal.pone.0049971

    View details for PubMedID 23251354

  • MR tracking of macrophage migration into matrix assosciated stem cell transplants via an indirect clinically applicable labeling technique Investigative Radiology Khurana A, Nejadnik H, Castaneda R, Gawande R, Derugin N, Pisani L, Daldrup-Link HE. 2011; 46 (11): 740
  • Vitamin D status of 6- to 7-year-old children living in Isfahan, Iran. Endokrynologia Polska Ardestani, P. M., Salek, M., Keshteli, A. H., Nejadnik, H., Amini, M., Hosseini, S. M., Rafati, H., Kelishadi, R., Hashemipour, M. 2010; 61 (4): 377-382

    Abstract

    Vitamin D is essential for the maintenance of good health, and vitamin D deficiency has been reported from many countries, including those with a lot of sunshine. This study was conducted to evaluate the vitamin D status in healthy 6- to 7-year-old children in Isfahan, Iran.Five hundred and thirteen healthy children were enrolled. Serum PTH and 25-hydroxyvitamin D (25-OHD) were measured. Dietary vitamin D intake, duration of daily sunlight exposure, and percentage of exposed body surface area were determined. 25-OHD levels < 20 ng/mL and < 10 ng/mL were defined as mild and severe vitamin D deficiency, respectively. The ROC curve was utilized to obtain a local cut-off point of vitamin D deficiency.25-OHD was < 20 ng/mL in 3% and < 33 ng/mL (local cut-off point of vitamin D deficiency) in 26% of subjects. Duration of sunlight exposure and daily intake of vitamin D had significant effects on serum level of vitamin D.A high prevalence of vitamin D deficiency in Isfahan children was observed in this study. Improvements in duration of sunlight exposure and daily intake of vitamin D can prevent vitamin D deficiency in these children.

    View details for PubMedID 20806182

  • Autologous Bone Marrow-Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation An Observational Cohort Study AMERICAN JOURNAL OF SPORTS MEDICINE Nejadnik, H., Hui, J. H., Choong, E. P., Tai, B., Lee, E. H. 2010; 38 (6): 1110-1116

    Abstract

    First-generation autologous chondrocyte implantation has limitations, and introducing new effective cell sources can improve cartilage repair.This study was conducted to compare the clinical outcomes of patients treated with first-generation autologous chondrocyte implantation to patients treated with autologous bone marrow-derived mesenchymal stem cells (BMSCs).Cohort study; Level of evidence, 3.Seventy-two matched (lesion site and age) patients underwent cartilage repair using chondrocytes (n = 36) or BMSCs (n = 36). Clinical outcomes were measured before operation and 3, 6, 9, 12, 18, and 24 months after operation using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale.There was significant improvement in the patients' quality of life (physical and mental components of the Short Form-36 questionnaire included in the ICRS package) after cartilage repair in both groups (autologous chondrocyte implantation and BMSCs). However, there was no difference between the BMSC and the autologous chondrocyte implantation group in terms of clinical outcomes except for Physical Role Functioning, with a greater improvement over time in the BMSC group (P = .044 for interaction effect). The IKDC subjective knee evaluation (P = .861), Lysholm (P = .627), and Tegner (P = .200) scores did not show any significant difference between groups over time. However, in general, men showed significantly better improvements than women. Patients younger than 45 years of age scored significantly better than patients older than 45 years in the autologous chondrocyte implantation group, but age did not make a difference in outcomes in the BMSC group.Using BMSCs in cartilage repair is as effective as chondrocytes for articular cartilage repair. In addition, it required 1 less knee surgery, reduced costs, and minimized donor-site morbidity.

    View details for DOI 10.1177/0363546509359067

    View details for Web of Science ID 000278062200004

    View details for PubMedID 20392971

  • Vitamin D status of 6-to 7-year-old children living in Isfahan, Iran ENDOKRYNOLOGIA POLSKA Ardestani, P. M., Salek, M., Keshteli, A. H., Nejadnik, H., Amini, M., Hosseini, S. M., Rafati, H., Kelishadi, R., Hashemipour, M. 2010; 61 (4): 377-381
  • Cavernous angioma: a clinical study of 35 cases with review of the literature NEUROLOGICAL RESEARCH Ebrahimi, A., Etemadifar, M., Ardestani, P. M., Maghzi, A. H., Jaffe, S., Nejadnik, H. 2009; 31 (8): 785-793

    Abstract

    Cavernous angioma is a vascular malformation which can be found in any region within the central nervous system.There are few clinical and demographic cavernous angioma studies with large sample sizes. Therefore, the present study was designed to provide further information on the clinical and demographic characteristics of cavernous angioma using a relatively large sample of Persian patients.Patients with cavernous angioma were recruited from the outpatient neurology clinics in Isfahan, Iran, from October 2003 to October 2006.In all cases, the diagnosis of cavernous angioma was based on brain magnetic resonance imaging. There were 35 patients (female/male: 17 : 18) identified with cavernous angioma. The mean age at presentation was 28.8 years. Initial manifestations included seizures in 16, headache in 11 and intracranial hemorrhage in eight patients. During follow-up, all patients experienced seizures and 19 developed headaches. Depression, vertigo, nausea, vomiting, disequilibrium, loss of consciousness and sensorimotor symptoms were also observed.Some of the findings of the present study were in accordance with previous studies. However, more of our patients with positive family history had solitary rather than multiple lesions, and more of our patients had generalized tonic-clonic seizures rather than partial seizures. Moreover, our data demonstrated that if there is a history of cavernous angioma with intracranial hemorrhage in family members, the presenting cavernous angioma patient is more prone to intracranial hemorrhage.

    View details for DOI 10.1179/016164109X12445505689445

    View details for Web of Science ID 000269131700003

    View details for PubMedID 19723446

  • Vitamin D deficiency among pregnant women and their newborns in Isfahan, Iran EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES Salek, M., Hashemipour, M., Aminorroaya, A., Gheiratmand, A., Kelishadi, R., Ardestani, P. M., Nejadnik, H., Amini, M., Zolfaghari, B. 2008; 116 (6): 352-356

    Abstract

    Vitamin D deficiency is one of the major health problems and unexpectedly has a high prevalence in sunny countries (e.g. Middle East). In this study we determined the prevalence of vitamin D deficiency in pregnant women and their newborns in Isfahan, a sunny city in Iran.In a cross-sectional study, 88 newborns born in Beheshty hospital, affiliated to Isfahan University of Medical Sciences (August-September, 2005) and their mothers were studied. Their data were collected by questionnaires and blood sampling was done to measure serum alkaline phosphatase (ALP), calcium, phosphorus, 25 (OH) vitamin D and parathormone (PTH). Vitamin D deficiency defined as levels of 25 (OH) D < 20 and < 12.5 ng/ml for mothers and newborns, respectively and local cut-offs defined as levels in which mean serum PTH started to increase.The prevalence of vitamin D deficiency according to 25 (OH) D < 20 ng/ml in mothers and < 12.5 ng/ml in newborns was 5.7% and 4.5%, respectively. According to local cut-offs (35 ng/ml for mothers and 26 ng/ml for newborns) 26.1% of mothers and 53.4% of newborns were vitamin D deficient.According to local definition, vitamin D deficiency is a health problem in pregnant women and their newborns in this sunny city.

    View details for DOI 10.1055/s-2008-1042403

    View details for Web of Science ID 000257245900008

    View details for PubMedID 18700279

  • Effect of lime juice consumption on urine pH value SAUDI MEDICAL JOURNAL Mazdak, H., Ardestani, P. M., Nejadnik, H. 2006; 27 (12): 1923-1924

    View details for Web of Science ID 000244073200030

    View details for PubMedID 17143381

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