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In vitro model of perimenopausal depression implicates steroid metabolic and proinflammatory genes

Molecular Psychiatry volume 26, pages 3266–3276 (2021)Cite this article

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Abstract

The estimated 20–30% of women who develop perimenopausal depression (PMD) are at an increased risk of cardiovascular and all-cause mortality. The therapeutic benefits of estradiol (E2) and symptom-provoking effects of E2-withdrawal (E2-WD) suggest that a greater sensitivity to changes in E2 at the cellular level contribute to PMD. We developed an in vitro model of PMD with lymphoblastoid cell lines (LCLs) derived from participants of a prior E2-WD clinical study. LCLs from women with past PMD (n = 8) or control women (n = 9) were cultured in three experimental conditions: at vehicle baseline, during E2 treatment, and following E2-WD. Transcriptome analysis revealed significant differences in transcript expression in PMD in all experimental conditions, and significant overlap in genes that were changed in PMD regardless of experimental condition. Of these, chemokine CXCL10, previously linked to cardiovascular disease, was upregulated in women with PMD, but most so after E2-WD (p < 1.55 × 10−5). CYP7B1, an enzyme intrinsic to DHEA metabolism, was upregulated in PMD across experimental conditions (F(1,45) = 19.93, p < 0.0001). These transcripts were further validated via qRT-PCR. Gene networks dysregulated in PMD included inflammatory response, early/late E2-response, and cholesterol homeostasis. Our results provide evidence that differential behavioral responsivity to E2-WD in PMD reflects intrinsic differences in cellular gene expression. Genes such as CXCL10, CYP7B1, and corresponding proinflammatory and steroid biosynthetic gene networks, may represent biomarkers and molecular targets for intervention in PMD. Finally, this in vitro model allows for future investigations into the mechanisms of genes and gene networks involved in the vulnerability to, and consequences of, PMD.

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Fig. 1: PMD vs. Control LCLs: in vitro estradiol (E2) exposures.
Fig. 2: Significant overlap between DEGs in all experimental treatment groups.
Fig. 3: CXCL10, a proinflammatory chemokine, is significantly increased in LCLs from women with PMD, particularly after E2-Withdrawal.
Fig. 4: CYP7B1, the gene encoding the enzyme involved in DHEA metabolism, is significantly increased in LCLs from women with PMD, and significantly correlates to decreased plasma DHEA levels.

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References

  1. Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63:375–82.

    Article  CAS  PubMed  Google Scholar 

  2. Freeman EW, Sammel MD, Liu L, Gracia CR, Nelson DB, Hollander L. Hormones and menopausal status as predictors of depression in womenin transition to menopause. Arch Gen Psychiatry. 2004;61:62–70.

    Article  CAS  PubMed  Google Scholar 

  3. Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition. Arch Gen Psychiatry. 2006;63:385–90.

    Article  PubMed  Google Scholar 

  4. Bromberger JT, Kravitz HM, Chang YF, Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of Women’s Health Across the Nation (SWAN). Psychological Med. 2011;41:1879–88.

    Article  CAS  Google Scholar 

  5. Bromberger JT, Matthews KA, Schott LL, Brockwell S, Avis NE, Kravitz HM, et al. Depressive symptoms during the menopausal transition: The Study of Women’s Health Across the Nation (SWAN). J Affect Disord. 2007;103:267–72.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wariso BA, Guerrieri GM, Thompson K, Koziol DE, Haq N, Martinez PE, et al. Depression during the menopause transition: impact on quality of life, social adjustment, and disability. Arch Women’s Ment Health. 2017;20:273–82.

    Article  Google Scholar 

  7. Terauchi M, Hiramitsu S, Akiyoshi M, Owa Y, Kato K, Obayashi S, et al. Associations among depression, anxiety and somatic symptoms in peri- and postmenopausal women. J Obstet Gynaecol Res. 2013;39:1007–13.

    Article  PubMed  Google Scholar 

  8. Wassertheil-Smoller S, Shumaker S, Ockene J, Talavera GA, Greenland P, Cochrane B, et al. Depression and cardiovascular sequelae in postmenopausal women. Arch Intern Med. 2004;164:289–98.

    Article  PubMed  Google Scholar 

  9. Burger HG. The endocrinology of the menopause. Maturitas. 1996;23:129–36.

    Article  CAS  PubMed  Google Scholar 

  10. Freeman EW. Depression in the menopause transition: risks in the changing hormone milieu as observed in the general population. Women’s Midlife Health. 2015;1:2.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Daly, R. C., Danaceau, M. A., Rubinow, D. R., and Schmidt, P. J.: Concordant restoration of ovarian function and mood in perimenopausal depression. Am. J. Psychiatry. 2003 160:1842–6.

    Article  PubMed  Google Scholar 

  12. Tepper PG, Randolph JF, McConnell DS, Crawford SL, El Khoudary SR, Joffe H, et al. Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women’s Health Across the Nation (SWAN). J Clin Endocrinol Metab. 2012;97:2872–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Santoro N, Brown JR, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81:1495–501.

    CAS  PubMed  Google Scholar 

  14. Schmidt PJ, Nieman L, Danaceau MA, Tobin MB, Roca CA, Murphy JH, et al. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol. 2000;183:414–20.

    Article  CAS  PubMed  Google Scholar 

  15. De Novaes Soares C, Almeida OP, Joffe H, Cohen LS. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women. Arch Gen Psychiatry. 2001;58:529–34.

    Article  Google Scholar 

  16. Gordon JL, Rubinow DR, Eisenlohr-Moul TA, Xia K, Schmidt PJ, Girdler SS. Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition. JAMA Psychiatry. 2018;75:149–57.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ockene JK. Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 2005;294:183–93.

    Article  CAS  PubMed  Google Scholar 

  18. Ness J, Aronow WS, Beck G. Menopausal symptoms after cessation of hormone replacement therapy. Maturitas. 2006;53:356–61.

    Article  CAS  PubMed  Google Scholar 

  19. Schmidt PJ, Murphy JH, Haq N, Danaceau MA, St. Clair LS. Basal plasma hormone levels in depressed perimenopausal women. Psychoneuroendocrinology. 2002;27:907–20.

    Article  CAS  PubMed  Google Scholar 

  20. Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, et al. Effects of estradiol withdrawal on mood in women with past perimenopausal depression: A randomized clinical trial. JAMA Psychiatry. 2015;72:714–26.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Dubey N, Hoffman JF, Schuebel K, Yuan Q, Martinez PE, Nieman LK et al. The ESC/E(Z) complex, an effector of response to ovarian steroids, manifests an intrinsic difference in cells from women with premenstrual dysphoric disorder. Mol Psychiatry. 2017;22:1172–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Steinberg EM, Rubinow DR, Bartko JJ, Fortinsky PM, Haq N, Thompson K et al. A cross-sectional evaluation of perimenopausal depression. J Clin Psychiatry. 2008;69:973–80.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Oh HM, Oh JM, Choi SC, Kim SW, Han WC, Kim TH, et al. An efficient method for the rapid establishment of Epstein-Barr virus immortalization of human B lymphocytes. Cell Prolif. 2003;36:191–7.

    Article  PubMed  Google Scholar 

  24. Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS. Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci. 1986;83:2496–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Welshons WV, Wolf MF, Murphy CS, Jordan VC. Estrogenic activity of phenol red. Mol Cell Endocrinol. 1988;57:169–78.

    Article  CAS  PubMed  Google Scholar 

  26. Milo GE MW, Powell JE, Blakeslee JR, Yohn DS. Effects of steroid hormones in fetal bovine serum on plating and cloning of human cells in vitro. In Vitro 1976;12:23–30.

    Article  PubMed  Google Scholar 

  27. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol). 1995;57:289–300.

    Google Scholar 

  28. Wang M, Zhao Y, Zhang B. Efficient test and visualization of multi-set intersections. Sci Rep. 2015;5:16923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Turner SD. qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots. bioRxiv 2014:005165.

  30. Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst 2015;1:417–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinforma. 2013;14:128.

    Article  Google Scholar 

  32. Duan Q, Flynn C, Niepel M, Hafner M, Muhlich JL, Fernandez NF, et al. LINCS canvas browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures. Nucleic Acids Res. 2014;42:W449–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ménard C, Hodes GE, Russo SJ. Pathogenesis of depression: insights from human and rodent studies. Neuroscience. 2016;321:138–62.

    Article  PubMed  CAS  Google Scholar 

  34. Hodes GE, Kana V, Menard C, Merad M, Russo SJ. Neuroimmune mechanisms of depression. Nat Neurosci. 2015;18:1386–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Altara R, Mallat Z, Booz GW, Zouein FA. The CXCL10/CXCR3 axis and cardiac inflammation: implications for immunotherapy to treat infectious and noninfectious diseases of the heart. J Immunol Res. 2016;2016:4396368.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Altara R, Manca M, Hessel MH, Gu Y, Van Vark LC, Akkerhuis KM, et al. CXCL10 is a circulating inflammatory marker in patients with advanced heart failure: a pilot study. J Cardiovascular Transl Res. 2016;9:302–14.

    Article  Google Scholar 

  37. van den Borne P, Quax PH, Hoefer IE, Pasterkamp G. The multifaceted functions of CXCL10 in cardiovascular disease. Biomed Res Int. 2014;2014:893106.

    PubMed  PubMed Central  Google Scholar 

  38. Le Thuc O, Stobbe K, Cansell C, Nahon JL, Blondeau N, Rovere C. Hypothalamic inflammation and energy balance disruptions: spotlight on chemokines. Front Endocrinol (Lausanne). 2017;8:197.

    Article  Google Scholar 

  39. Rotondi M, Chiovato L, Romagnani S, Serio M, Romagnani P. Role of chemokines in endocrine autoimmune diseases. Endocr Rev. 2007;28:492–520.

    Article  CAS  PubMed  Google Scholar 

  40. Bronger H, Kraeft S, Schwarz-Boeger U, Cerny C, Stockel A, Avril S, et al. Modulation of CXCR3 ligand secretion by prostaglandin E2 and cyclooxygenase inhibitors in human breast cancer. Breast Cancer Res. 2012;14:R30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Koten K, Hirohata S, Miyoshi T, Ogawa H, Usui S, Shinohata R, et al. Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size. Clin Biochem. 2008;41:30–7.

    Article  CAS  PubMed  Google Scholar 

  42. Xanthou G, Duchesnes CE, Williams TJ, Pease JE. CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11. Eur J Immunol. 2003;33:2241–50.

    Article  CAS  PubMed  Google Scholar 

  43. Evans J, Salamonsen LA. Decidualized human endometrial stromal cells are sensors of hormone withdrawal in the menstrual inflammatory cascade. Biol Reprod. 2014;14:1–12.

    Article  Google Scholar 

  44. Kanda N, Watanabe S. 17beta-estradiol inhibits the production of interferon-induced protein of 10 kDa by human keratinocytes. J Invest Dermatol. 2003;120:411–9.

    Article  CAS  PubMed  Google Scholar 

  45. Cerciat M, Unkila M, Garcia-Segura LM, Arevalo MA. Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-gamma-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro. Glia. 2010;58:93–102.

    Article  CAS  PubMed  Google Scholar 

  46. Sentman CL, Meadows SK, Wira CR, Eriksson M. Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. J Immunol. 2004;173:6760–6.

    Article  CAS  PubMed  Google Scholar 

  47. Muller C, Hennebert O, Morfin R. The native anti-glucocorticoid paradigm. J Steroid Biochem Mol Biol. 2006;100:95–105.

    Article  CAS  PubMed  Google Scholar 

  48. Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, et al. Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7 -hydroxy dehydroepiandrosterone and 7 -hydroxy pregnenolone. Proc Natl Acad Sci. 1997;94:4925–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pak TR, Chung WC, Hinds LR, Handa RJ. Estrogen receptor-beta mediates dihydrotestosterone-induced stimulation of the arginine vasopressin promoter in neuronal cells. Endocrinology. 2007;148:3371–82.

    Article  CAS  PubMed  Google Scholar 

  50. Handa RJ, Pak TR, Kudwa AE, Lund TD, Hinds L. An alternate pathway for androgen regulation of brain function: activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5alpha-androstane-3beta,17beta-diol. Horm Behav. 2008;53:741–52.

    Article  CAS  PubMed  Google Scholar 

  51. Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009;30:65–91.

    Article  CAS  PubMed  Google Scholar 

  52. Schmidt PJ, Daly RC, Bloch M, Smith MJ, Danaceau MA, Simpson St. Clair L, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005;62:154–62.

    Article  CAS  PubMed  Google Scholar 

  53. Dor RB, Marx CE, Shampine LJ, Rubinow DR, Schmidt PJ. DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA’s antidepressant action. Psychopharmacology. 2015;232:3375–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Tang W, Eggertsen G, Chiang JY, Norlin M. Estrogen-mediated regulation of CYP7B1: a possible role for controlling DHEA levels in human tissues. J Steroid Biochem Mol Biol. 2006;100:42–51.

    Article  CAS  PubMed  Google Scholar 

  55. Morrison MF, Freeman EW, Lin H, Sammel MD. Higher DHEA-S (dehydroepiandrosterone sulfate) levels are associated with depressive symptoms during the menopausal transition: results from the PENN Ovarian Aging Study. Arch Women’s Ment Health. 2011;14:375–82.

    Article  Google Scholar 

  56. Martin C, Bean R, Rose K, Habib F, Seckl J. cyp7b1 catalyses the 7alpha-hydroxylation of dehydroepiandrosterone and 25-hydroxycholesterol in rat prostate. Biochemical J. 2001;355:509–15.

    Article  CAS  Google Scholar 

  57. Martin C, Ross M, Chapman KE, Andrew R, Bollina P, Seckl JR, et al. CYP7B generates a selective estrogen receptor β agonist in human prostate. J Clin Endocrinol Metab. 2004;89:2928–35.

    Article  CAS  PubMed  Google Scholar 

  58. Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019;22:343–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nagel M, Jansen PR, Stringer S, Watanabe K, de Leeuw CA, Bryois J, et al. Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways. Nat Genet. 2018;50:920–7.

    Article  CAS  PubMed  Google Scholar 

  60. Baselmans BML, Jansen R, Ip HF, van Dongen J, Abdellaoui A, van de Weijer MP, et al. Multivariate genome-wide analyses of the well-being spectrum. Nat Genet. 2019;51:445–51.

    Article  CAS  PubMed  Google Scholar 

  61. Slowik A, Lammerding L, Hoffmann S, Beyer C. Brain inflammasomes in stroke and depressive disorders: Regulation by oestrogen. J Neuroendocrinol. 2018;30. https://doi.org/10.1111/jne.12482.

  62. Pfeilschifter J, Köditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr Rev. 2002;23:90–119.

    Article  CAS  PubMed  Google Scholar 

  63. Dulos J, Verbraak E, Bagchus WM, Boots AM, Kaptein A. Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta. Arthritis Rheum 2004;50:3346–53.

    Article  CAS  PubMed  Google Scholar 

  64. Zare N, Khalifeh S, Khodagholi F, Shahamati SZ, Motamedi F, Maghsoudi N. Geldanamycin Reduces Abeta-Associated Anxiety and Depression, Concurrent with Autophagy Provocation. J Mol Neurosci 2015;57:317–24.

    Article  CAS  PubMed  Google Scholar 

  65. Binder EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology. 2009;34:S186–95.

    Article  CAS  PubMed  Google Scholar 

  66. Criado-Marrero M, Rein T, Binder EB, Porter JT, Koren J, 3rd., Blair LJ. Hsp90 and FKBP51: complex regulators of psychiatric diseases. Philos Trans R Soc Lond B Biol Sci 2018;373.

  67. Tsai YC, Leu SY, Chen SY, Kung CW, Lee YM, Liu YP, et al. 17-DMAG, an Hsp90 inhibitor, ameliorates ovariectomy-induced obesity in rats. Life Sci. 2019;232:116672.

  68. Dome P, Tombor L, Lazary J, Gonda X, Rihmer Z. Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review. Brain Res Bull. 2019;146:51–78.

    Article  CAS  PubMed  Google Scholar 

  69. Abd-Rabo MM, Georgy GS, Saied NM, Hassan WA. Involvement of the serotonergic system and neuroplasticity in the antidepressant effect of curcumin in ovariectomized rats: Comparison with oestradiol and fluoxetine. Phytother Res. 2019;33:387–96.

    Article  CAS  PubMed  Google Scholar 

  70. Bhat A, Mahalakshmi AM, Ray B, Tuladhar S, Hediyal TA, Manthiannem E et al. Benefits of curcumin in brain disorders. Biofactors 2019;45:666–89.

    Article  CAS  PubMed  Google Scholar 

  71. Miodownik C, Lerner V, Kudkaeva N, Lerner PP, Pashinian A, Bersudsky Y, et al. Curcumin as add-on to antipsychotic treatment in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2019;42:117–22.

    Article  PubMed  Google Scholar 

  72. Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc. 2017;18:503–8.

    Article  PubMed  Google Scholar 

  73. Caliskan M, Cusanovich DA, Ober C, Gilad Y. The effects of EBV transformation on gene expression levels and methylation profiles. Hum Mol Genet. 2011;20:1643–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Richards M, Rubinow DR, Daly RC, Schmidt PJ. Premenstrual symptoms and perimenopausal depression. Am J Psychiatry. 2006;163:133–7.

    Article  PubMed  Google Scholar 

  75. Honigberg MC, Zekavat SM, Aragam K, et al. Association of Premature Natural and Surgical Menopause With Incident Cardiovascular Disease. JAMA. 2019; https://doi.org/10.1001/jama.2019.19191. Online ahead of print.

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Acknowledgements

We would like to thank Alan Meyers, Cheryl Marietta, Longina Akhtar, Allison Goff, and Maria Mazzu of NIH/NIAAA for their technical assistance and expertise in conducting this study. We would also like to thank Karla Thompson, Kai Shi, and Linda Schenkel of NIH/NIMH for their clinical support and data management. This research was supported by the Intramural Research Program of the NIMH and NIAAA NIH; NIMH Protocols 03-M-0175 (NCT00060736), 88-M-0131 (NCT00001231); NIMH Project ZIA MH002537; NIAAA Project ZIA AA000301.

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  1. Behavioral Endocrinology Branch, NIMH, Bethesda, MD, USA

    Sarah Rudzinskas, Jessica F. Hoffman, Pedro Martinez & Peter J. Schmidt

  2. Laboratory of Neurogenetics, NIAAA, Rockville, MD, USA

    Sarah Rudzinskas, Jessica F. Hoffman & David Goldman

  3. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    David R. Rubinow

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Rudzinskas, S., Hoffman, J.F., Martinez, P. et al. In vitro model of perimenopausal depression implicates steroid metabolic and proinflammatory genes. Mol Psychiatry 26, 3266–3276 (2021). https://doi.org/10.1038/s41380-020-00860-x

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