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M. Rita I Young, PhD
Professor of Otolaryngology
College of Medicine
MUSC

Email: youngmr@musc.edu
 
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M. Rita I Young, PhD

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Research Interest:

My research focus is in the area of oncology, with particular emphasis on immune regulation in patients with squamous cell carcinoma of the head and neck (HNSCC). Immunotherapy for cancer patients is a treatment approach that has been the thrust of my studies. However, stimulation of anti-cancer immune reactivity is hampered by the severe immune dysfunction in cancer patients. The studies in my laboratory have identified several mechanisms to overcome this immune dysfunction so that subsequent immune vaccines can be effective. Toward this goal, my basic science laboratory studies have progressed into several clinical trials with HNSCC patients. I have been an independent PI for more than 25 years with national, peer-reviewed funding from VA, NIH, DOD, and others.

Positions:
Associate Chief of Staff for Research, Ralph H. Johnson VA Medical Center

Selected Publications:

1.Johnson SD, De Costa AM, Young MR. Effect of the premalignant and tumor microenvironment on immune cell cytokine production in head and neck cancer. Cancers (Basel). .6(2):756-70, 2014. PMCID: PMC4074802
View in: PubMed

2.Vielma SA, Klein RL, Levingston CA, Young MR. Skewing of immune cell cytokine production by mediators from adipocytes and endothelial cells. Adipocyte. .3(2):126-31, 2014. PMCID: PMC3979877
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3.Young MR, Day TA. Immune regulatory activity of vitamin d3 in head and neck cancer. Cancers (Basel). .5(3):1072-85, 2013. PMCID: PMC3795379
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4.Vielma SA, Klein RL, Levingston CA, Young MR. Premalignant lesions skew spleen cell responses to immune modulation by adipocytes. Anticancer Res. .33(5):1809-18, 2013.
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5.Vielma SA, Klein RL, Levingston CA, Young MR. Adipocytes as immune regulatory cells. Int Immunopharmacol. .16(2):224-31, 2013. PMCID: PMC3752601
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6.Young MR. Endothelial cells in the eyes of an immunologist. Cancer Immunol Immunother. .61(10):1609-16, 2012. PMCID: PMC3448862
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7.De Costa AM, Justis DN, Schuyler CA, Young MR. Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response. Int Immunopharmacol. .13(3):322-30, 2012. PMCID: PMC3372686
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8.Walker DD, Reeves TD, de Costa AM, Schuyler C, Young MR. Immunological modulation by 1a,25-dihydroxyvitamin D3 in patients with squamous cell carcinoma of the head and neck. Cytokine. .58(3):448-54, 2012. PMCID: PMC3340440
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9.De Costa AM, Schuyler CA, Walker DD, Young MR. Characterization of the evolution of immune phenotype during the development and progression of squamous cell carcinoma of the head and neck. Cancer Immunol Immunother. .61(6):927-39, 2011.
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10.Walsh JE, Young MR. TGF-beta regulation of focal adhesion proteins and motility of premalignant oral lesions via protein phosphatase 1. Anticancer Res. .31(10):3159-64, 2011. PMCID: PMC3622218
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11.De Costa AM, Young MR. Immunotherapy for head and neck cancer: advances and deficiencies. Anticancer Drugs. .22(7):674-81, 2011. PMCID: PMC3124569
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12.Mailloux AW, Clark AM, Young MR. NK depletion results in increased CCL22 secretion and Treg levels in Lewis lung carcinoma via the accumulation of CCL22-secreting CD11b+CD11c+ cells. Int J Cancer. .127(11):2598-611, 2010. PMCID: PMC2947555
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13.Walsh JE, Young MR. Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells. Anticancer Res. .30(12):4861-6, 2010. PMCID: PMC3337686
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14.Walsh JE, Clark AM, Day TA, Gillespie MB, Young MR. Use of alpha,25-dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma. Hum Immunol. .71(7):659-65, 2010. PMCID: PMC3337687
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15.Mulligan JK, Young MR. Tumors induce the formation of suppressor endothelial cells in vivo. Cancer Immunol Immunother. .59(2):267-77, 2010. PMCID: PMC3337521
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16.Mulligan JK, Rosenzweig SA, Young MR. Tumor secretion of VEGF induces endothelial cells to suppress T cell functions through the production of PGE2. J Immunother. .33(2):126-35, 2010. PMCID: PMC3333835
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17.Mailloux AW, Young MR. Regulatory T-cell trafficking: from thymic development to tumor-induced immune suppression. Crit Rev Immunol. .30(5):435-47, 2010. PMCID: PMC3196532
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18.Clark JI, Eisner RM, Hofmeister C, Norton J, Thomas S, Choudhury A, Petruzzelli G, Lathers D, Young MR, Lau A, Emami B. Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer. Am J Clin Oncol. .32(4):396-400, 2009. PMCID: PMC4047115
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19.Mailloux AW, Young MR. NK-dependent increases in CCL22 secretion selectively recruits regulatory T cells to the tumor microenvironment. J Immunol. .182(5):2753-65, 2009. PMCID: PMC3337694
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20.Mulligan JK, Day TA, Gillespie MB, Rosenzweig SA, Young MR. Secretion of vascular endothelial growth factor by oral squamous cell carcinoma cells skews endothelial cells to suppress T-cell functions. Hum Immunol. .70(6):375-82, 2009. PMCID: PMC2746465
View in: PubMed

21.Kulbersh JS, Day TA, Gillespie MB, Young MR. 1alpha,25-Dihydroxyvitamin D(3) to skew intratumoral levels of immune inhibitory CD34(+) progenitor cells into dendritic cells. Otolaryngol Head Neck Surg. .140(2):235-40, 2009. PMCID: PMC3337726
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22.Mulligan JK, Lathers DM, Young MR. Tumors skew endothelial cells to disrupt NK cell, T-cell and macrophage functions. Cancer Immunol Immunother. .57(7):951-61, 2008. PMCID: PMC3333838
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23.Young MR. Use of carcinogen-induced premalignant oral lesions in a dendritic cell-based vaccine to stimulate immune reactivity against both premalignant oral lesions and oral cancer. J Immunother. .31(2):148-56, 2008.
View in: PubMed

24.Walsh JE, Lathers DM, Chi AC, Gillespie MB, Day TA, Young MR. Mechanisms of tumor growth and metastasis in head and neck squamous cell carcinoma. Curr Treat Options Oncol. .8(3):227-38, 2007.
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25.Matthews CP, Colburn NH, Young MR. AP-1 a target for cancer prevention. Curr Cancer Drug Targets. .7(4):317-24, 2007.
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26.Young MR, Neville BW, Chi AC, Lathers DM, Gillespie MB, Day TA. Autocrine motility-stimulatory pathways of oral premalignant lesion cells. Clin Exp Metastasis. .24(2):131-9, 2007.
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27.Kanabrocki EL, Ryan MD, Lathers D, Achille N, Young MR, Cauteren JV, Foley S, Johnson MC, Friedman NC, Siegel G, Nemchausky BA. Circadian distribution of serum cytokines in multiple sclerosis. Clin Ter. .158(2):157-62, 2007.
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28.Gillespie MB, Moody MW, Lee FS, Poole LJ, Hornig JD, Lathers D, Young MR, Day TA. Head and neck cancer recurrence and mortality in nonselective cyclooxygenase inhibitor users. Arch Otolaryngol Head Neck Surg. .133(1):28-31, 2007.
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29.Rashid RM, Lee JM, Fareed J, Young MR. In vitro heparan sulfate modulates the immune responses of normal and tumor-bearing mice. Immunol Invest. .36(2):183-201, 2007.
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30.Young MR, Neville BW, Chi AC, Lathers DM, Boyd Gillespie M, Day TA. Oral premalignant lesions induce immune reactivity to both premalignant oral lesions and head and neck squamous cell carcinoma. Cancer Immunol Immunother. .56(7):1077-86, 2006.
View in: PubMed

31.Yen KL, Horner MJ, Reed SG, Daguise VG, Bolick-Aldrich SW, Young MR, Day TA, Wood PA, Hebert JR. Head and neck cancer disparities in South Carolina: descriptive epidemiology, early detection, and special programs. J S C Med Assoc. .102(7):192-200, 2006.
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32.Young MR. Cytokine-containing gelfoam implants at a postsurgical tumor excision site to stimulate local immune reactivity. Int J Cancer. .119(1):133-8, 2006.
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33.Woodworth BA, Lathers D, Neal JG, Skinner M, Richardson M, Young MR, Schlosser RJ. Immunolocalization of surfactant protein A and D in sinonasal mucosa. Am J Rhinol. .20(4):461-5, 2006.
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34.Young MR. Protective mechanisms of head and neck squamous cell carcinomas from immune assault. Head Neck. .28(5):462-70, 2006.
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35.Rashid RM, Lee JM, Fareed J, Young MR. In vivo heparan sulfate treatment alters the immune response of normal and LLC-bearing mice. Immunopharmacol Immunotoxicol. .28(1):67-79, 2006.
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36.Young MR, Lathers DM. Combination docetaxel plus vitamin D(3) as an immune therapy in animals bearing squamous cell carcinomas. Otolaryngol Head Neck Surg. .133(4):611-8, 2005.
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37.Young MR, Cigal M. Tumor skewing of CD34+ cell differentiation from a dendritic cell pathway into endothelial cells. Cancer Immunol Immunother. .55(5):558-68, 2005.
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38.Rashid RM, Achille NJ, Lee JM, Lathers DM, Young MR. Decreased T-cell proliferation and skewed immune responses in LLC-bearing mice. J Environ Pathol Toxicol Oncol. .24(3):175-92, 2005.
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39.Sparano A, Lathers DM, Achille N, Petruzzelli GJ, Young MR. Modulation of Th1 and Th2 cytokine profiles and their association with advanced head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. .131(5):573-6, 2004.
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40.Young MR. Tumor skewing of CD34+ progenitor cell differentiation into endothelial cells. Int J Cancer. .109(4):516-24, 2004.
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41.Lathers DM, Young MR. Increased aberrance of cytokine expression in plasma of patients with more advanced squamous cell carcinoma of the head and neck. Cytokine. .25(5):220-8, 2004.
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42.Romashko AA, Young MR. Protein phosphatase-2A maintains focal adhesion complexes in keratinocytes and the loss of this regulation in squamous cell carcinomas. Clin Exp Metastasis. .21(4):371-9, 2004.
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43.Young MR. Tumor-derived prostaglandin E2 and transforming growth factor-beta stimulate endothelial cell motility through inhibition of protein phosphatase-2A and involvement of PTEN and phosphatidylinositide 3-kinase. Angiogenesis. .7(2):123-31, 2004.
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44.Lathers DM, Achille NJ, Young MR. Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck. Hum Immunol. .64(12):1160-6, 2003.
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45.Lathers DM, Clark JI, Achille NJ, Young MR. Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother. .53(5):422-30, 2003.
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46.Young MR. Trials and tribulations of immunotherapy as a treatment option for patients with squamous cell carcinoma of the head and neck. Cancer Immunol Immunother. .53(5):375-82, 2003.
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47.Brockenbrough JM, Marzo S, Wurster R, Young MR. Bone wax prevents nystagmus after labyrinthine fenestration in guinea pigs. Otolaryngol Head Neck Surg. .128(5):726-31, 2003.
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48.Lathers DM, Achille N, Young MR. Dendritic cell development from mobilized peripheral blood CD34+ cells. Methods Mol Biol. .215:409-15, 2003.
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49.Banich JC, Kolesiak K, Young MR. Chemoattraction of CD34+ progenitor cells and dendritic cells to the site of tumor excision as the first step of an immunotherapeutic approach to target residual tumor cells. J Immunother. .26(1):31-40, 2003.
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50.Jackson JL, Young MR. Protein phosphatase-2A regulates protein tyrosine phosphatase activity in Lewis lung carcinoma tumor variants. Clin Exp Metastasis. .20(4):357-64, 2003.
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51.Young MR, Liu SW, Meisinger J. Protein phosphatase-2A restricts migration of Lewis lung carcinoma cells by modulating the phosphorylation of focal adhesion proteins. Int J Cancer. .103(1):38-44, 2003.
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52.Young MR, Kolesiak K, Meisinger J. Protein phosphatase-2A regulates endothelial cell motility and both the phosphorylation and the stability of focal adhesion complexes. Int J Cancer. .100(3):276-82, 2002.
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53.Wachter BG, Leonetti JP, Lee JM, Wurster RD, Young MR. Silver nitrate injury in the rat sciatic nerve: a model of facial nerve injury. Otolaryngol Head Neck Surg. .127(1):48-54, 2002.
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54.Ziroli NE, Na H, Chow JM, Stankiewicz JA, Samter M, Young MR. Aspirin-sensitive versus non-aspirin-sensitive nasal polyp patients: analysis of leukotrienes/Fas and Fas-ligand expression. Otolaryngol Head Neck Surg. .126(2):141-6, 2002.
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55.Shafer LL, McNulty JA, Young MR. Brain activation of monocyte lineage cells: brain-derived soluble factors differentially regulate BV2 microglia and peripheral macrophage immune functions. Neuroimmunomodulation. .10(5):283-94, 2002.
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56.Shafer LL, McNulty JA, Young MR. Brain activation of monocyte-lineage cells: involvement of interleukin-6. Neuroimmunomodulation. .10(5):295-304, 2002.
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57.Jackson JL, Young MR. Protein phosphatase-2A modulates the serine and tyrosine phosphorylation of paxillin in Lewis lung carcinoma tumor variants. Clin Exp Metastasis. .19(5):409-15, 2002.
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58.Lathers DM, Clark JI, Achille NJ, Young MR. Phase IB study of 25-hydroxyvitamin D(3) treatment to diminish suppressor cells in head and neck cancer patients. Hum Immunol. .62(11):1282-93, 2001.
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59.Shafer LL, McNulty JA, Young MR. Assessment of melatonin's ability to regulate cytokine production by macrophage and microglia cell types. J Neuroimmunol. .120(1-2):84-93, 2001.
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60.Lathers DM, Achille N, Kolesiak K, Hulett K, Sparano A, Petruzzelli GJ, Young MR. Increased levels of immune inhibitory CD34+ progenitor cells in the peripheral blood of patients with node positive head and neck squamous cell carcinomas and the ability of these CD34+ cells to differentiate into immune stimulatory dendritic cells. Otolaryngol Head Neck Surg. .125(3):205-12, 2001.
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61.Young MR, Kolesiak K, Achille NJ, Meisinger J, Gonzalez E, Liu SW, Wrone-Smith T, Lathers DM. Impact of aging on immune modulation by tumor. Cancer Immunol Immunother. .50(6):315-20, 2001.
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62.Fowler SS, Leonetti JP, Banich JC, Lee JM, Wurster R, Young MR. Duration of neuronal stretch correlates with functional loss. Otolaryngol Head Neck Surg. .124(6):641-4, 2001.
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63.Young MR, Petruzzelli GJ, Kolesiak K, Achille N, Lathers DM, Gabrilovich DI. Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34(+) progenitor cells. Hum Immunol. .62(4):332-41, 2001.
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64.Pandit R, Lathers DM, Beal NM, Garrity T, Young MR. CD34+ immune suppressive cells in the peripheral blood of patients with head and neck cancer. Ann Otol Rhinol Laryngol. .109(8 Pt 1):749-54, 2000.
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65.Witt CJ, Gabel SP, Meisinger J, Werra G, Liu SW, Young MR. Interrelationship between protein phosphatase-2A and cytoskeletal architecture during the endothelial cell response to soluble products produced by human head and neck cancer. Otolaryngol Head Neck Surg. .122(5):721-7, 2000.
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66.Young MR. Chemokines and cancer Arch Pathol Lab Med. .124(4):642, 2000.
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67.Prechel MM, Ding C, Washington RL, Kolodziej MS, Young MR. In vivo indomethacin treatment causes microglial activation in adult mice. Neurochem Res. .25(3):357-62, 2000.
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68.Donzelli J, Leonetti JP, Wurster RD, Lee JM, Young MR. Neuroprotection due to irrigation during bipolar cautery. Arch Otolaryngol Head Neck Surg. .126(2):149-53, 2000.
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69.Young MR, Liu SW, Meisinger J. Differences in association of the serine/threonine protein phosphatase PP-2A with microtubules of metastatic and nonmetastatic tumor cells. Clin Exp Metastasis. .18(5):407-13, 2000.
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70.Wiers KM, Lathers DM, Wright MA, Young MR. Vitamin D3 treatment to diminish the levels of immune suppressive CD34+ cells increases the effectiveness of adoptive immunotherapy. J Immunother. .23(1):115-24, 2000.
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71.Lathers DM, Lubbers E, Beal NM, Wright MA, Young MR. Cultures derived from peripheral blood CD34+ progenitor cells of head and neck cancer patients and from cord blood are functionally different. Hum Immunol. .60(12):1207-15, 1999.
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72.Young MR, Wright MA, Vellody K, Lathers DM. Skewed differentiation of bone marrow CD34+ cells of tumor bearers from dendritic toward monocytic cells, and the redirection of differentiation toward dendritic cells by 1alpha,25-dihydroxyvitamin D3. Int J Immunopharmacol. .21(10):675-88, 1999.
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73.Young MR, Kolesiak K, Wright MA, Gabrilovich DI. Chemoattraction of femoral CD34+ progenitor cells by tumor-derived vascular endothelial cell growth factor. Clin Exp Metastasis. .17(10):881-8, 1999.
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