Skip to Main Content
DownloadHi-Res Photo

Caroline Johnson, PhD

Assistant Professor of Epidemiology (Environmental Health Sciences)

Contact Information

Caroline Johnson, PhD

Office Location

Johnson-lab

Related Links

Extensive Research Description

Microbial metabolites and colon cancer

Colon cancers that present on the right versus the left side of the colon have significantly worse prognosis for the patient. A recent discovery revealed that right-sided colon cancers (RCCs) harbor mucosal bacterial biofilms, whereas left-sided colon cancers (LCC) are predominantly devoid of biofilms. These biofilms are associated with increased cellular proliferation and inflammation even in normal colon tissues. Using mass spectrometry-based metabolomics, we investigated the metabolism of colon cancers with and without biofilms, and observed a correlation between increased diacetylspermine production and biofilm presence on RCCs. Using antibiotic treatment, IHC, and stable isotope-assisted metabolomics we showed that diacetylspermine is an end product of polyamine metabolism produced by bacterial biofilms. We thus hypothesized that microbiota use host-derived polyamines to form biofilms. It is still not known why biofilms only form only on RCC, but it could be due to other factors such as diet and genetic predisposition.

Therefore, we aim are to examine the influence of these factors in LCC and RCC pathogenicity by investigating the roles of dietary metabolites, microbial communities and genetic predisposition.

Assessment of chemical exposures and adverse pregnancy outcomes

Preterm birth can cause serious life-long health problems for the child, importantly it is the greatest contributor to neonatal mortality. One of the major causes for preterm birth is preterm premature rupture of the membranes (PPROM). The mechanism for PPROM is unknown but hypothesized to be caused by placental inflammation which induces early labor. One potential mediator of placental inflammation is exposure to environmental toxins.

In the Johnson Lab we will be developing methods for measuring exposures during pregnancy and identify novel mechanisms for PPROM. We will be using samples collected locally from the Yale Pregnancy and prediction Outcome Study (YPOPS) http://ypops.yale.edu/


Coauthors

Research Interests

Environmental Exposure; Mass Spectrometry; Metabolomics; Biostatistics

Public Health Interests

Biomarkers; Cancer; Environmental Health; Genetics, Genomics, Epigenetics; Maternal & Child Health; Women's Health; Microbiome; Metabolomics; Perinatal/Prenatal Health

Research Image

Diacetylspermine and its role in biofilm-associated colon cancer

Selected Publications

  • Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics.Johnson CH, Slanař O, Krausz KW, Kang DW, Patterson AD, Kim JH, Luecke H, Gonzalez FJ, Idle JR. Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics. The American Journal Of Clinical Nutrition 2012, 96: 818-30. PMID: 22952181, PMCID: PMC3441109, DOI: 10.3945/ajcn.112.042929.
  • Xenobiotic metabolomics: major impact on the metabolome.Johnson CH, Patterson AD, Idle JR, Gonzalez FJ. Xenobiotic metabolomics: major impact on the metabolome. Annual Review Of Pharmacology And Toxicology 2012, 52: 37-56. PMID: 21819238, PMCID: PMC6300990, DOI: 10.1146/annurev-pharmtox-010611-134748.
  • Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database.Zhu ZJ, Schultz AW, Wang J, Johnson CH, Yannone SM, Patti GJ, Siuzdak G. Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database. Nature Protocols 2013, 8: 451-60. PMID: 23391889, PMCID: PMC3666335, DOI: 10.1038/nprot.2013.004.
  • Metabolomic data streaming for biology-dependent data acquisition.Rinehart D, Johnson CH, Nguyen T, Ivanisevic J, Benton HP, Lloyd J, Arkin AP, Deutschbauer AM, Patti GJ, Siuzdak G. Metabolomic data streaming for biology-dependent data acquisition. Nature Biotechnology 2014, 32: 524-7. PMID: 24911492, PMCID: PMC4112958, DOI: 10.1038/nbt.2927.
  • Metabolism links bacterial biofilms and colon carcinogenesis.Johnson CH, Dejea CM, Edler D, Hoang LT, Santidrian AF, Felding BH, Ivanisevic J, Cho K, Wick EC, Hechenbleikner EM, Uritboonthai W, Goetz L, Casero RA, Pardoll DM, White JR, Patti GJ, Sears CL, Siuzdak G. Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metabolism 2015, 21: 891-7. PMID: 25959674, PMCID: PMC4456201, DOI: 10.1016/j.cmet.2015.04.011.
  • Bioinformatics: the next frontier of metabolomics.Johnson CH, Ivanisevic J, Benton HP, Siuzdak G. Bioinformatics: the next frontier of metabolomics. Analytical Chemistry 2015, 87: 147-56. PMID: 25389922, PMCID: PMC4287838, DOI: 10.1021/ac5040693.
  • Autonomous metabolomics for rapid metabolite identification in global profiling.Benton HP, Ivanisevic J, Mahieu NG, Kurczy ME, Johnson CH, Franco L, Rinehart D, Valentine E, Gowda H, Ubhi BK, Tautenhahn R, Gieschen A, Fields MW, Patti GJ, Siuzdak G. Autonomous metabolomics for rapid metabolite identification in global profiling. Analytical Chemistry 2015, 87: 884-91. PMID: 25496351, PMCID: PMC4303330, DOI: 10.1021/ac5025649.
  • Comprehensive bioimaging with fluorinated nanoparticles using breathable liquids.Kurczy ME, Zhu ZJ, Ivanisevic J, Schuyler AM, Lalwani K, Santidrian AF, David JM, Giddabasappa A, Roberts AJ, Olivos HJ, O'Brien PJ, Franco L, Fields MW, Paris LP, Friedlander M, Johnson CH, Epstein AA, Gendelman HE, Wood MR, Felding BH, Patti GJ, Spilker ME, Siuzdak G. Comprehensive bioimaging with fluorinated nanoparticles using breathable liquids. Nature Communications 2015, 6: 5998. PMID: 25601659, PMCID: PMC4454288, DOI: 10.1038/ncomms6998.
  • Metabolite and Microbiome Interplay in Cancer Immunotherapy.Johnson CH, Spilker ME, Goetz L, Peterson SN, Siuzdak G. Metabolite and Microbiome Interplay in Cancer Immunotherapy. Cancer Research 2016, 76: 6146-6152. PMID: 27729325, PMCID: PMC5093024, DOI: 10.1158/0008-5472.CAN-16-0309.
  • Metabolomics: beyond biomarkers and towards mechanisms.Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nature Reviews. Molecular Cell Biology 2016, 17: 451-9. PMID: 26979502, PMCID: PMC5729912, DOI: 10.1038/nrm.2016.25.
  • Environmental influences in the etiology of colorectal cancer: the premise of metabolomics.Rattray NJW, Charkoftaki G, Rattray Z, Hansen JE, Vasiliou V, Johnson CH. Environmental influences in the etiology of colorectal cancer: the premise of metabolomics. Current Pharmacology Reports 2017, 3: 114-125. PMID: 28642837, PMCID: PMC5475285, DOI: 10.1007/s40495-017-0088-z.
  • Exposome-Scale Investigations Guided by Global Metabolomics, Pathway Analysis, and Cognitive Computing.Warth B, Spangler S, Fang M, Johnson CH, Forsberg EM, Granados A, Martin RL, Domingo-Almenara X, Huan T, Rinehart D, Montenegro-Burke JR, Hilmers B, Aisporna A, Hoang LT, Uritboonthai W, Benton HP, Richardson SD, Williams AJ, Siuzdak G. Exposome-Scale Investigations Guided by Global Metabolomics, Pathway Analysis, and Cognitive Computing. Analytical Chemistry 2017, 89: 11505-11513. PMID: 28945073, DOI: 10.1021/acs.analchem.7b02759.
  • Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections.Johnson CH, Athersuch TJ, Collman GW, Dhungana S, Grant DF, Jones DP, Patel CJ, Vasiliou V. Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections. Human Genomics 2017, 11: 32. PMID: 29221465, PMCID: PMC5723043, DOI: 10.1186/s40246-017-0128-0.
  • Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids.Johnson CH, Santidrian AF, LeBoeuf SE, Kurczy ME, Rattray NJW, Rattray Z, Warth B, Ritland M, Hoang LT, Loriot C, Higa J, Hansen JE, Felding BH, Siuzdak G. Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids. Cancer & Metabolism 2017, 5: 9. PMID: 29093815, PMCID: PMC5663111, DOI: 10.1186/s40170-017-0171-2.
  • Systems biology guided by XCMS Online metabolomics.Huan T, Forsberg EM, Rinehart D, Johnson CH, Ivanisevic J, Benton HP, Fang M, Aisporna A, Hilmers B, Poole FL, Thorgersen MP, Adams MWW, Krantz G, Fields MW, Robbins PD, Niedernhofer LJ, Ideker T, Majumder EL, Wall JD, Rattray NJW, Goodacre R, Lairson LL, Siuzdak G. Systems biology guided by XCMS Online metabolomics. Nature Methods 2017, 14: 461-462. PMID: 28448069, PMCID: PMC5933448, DOI: 10.1038/nmeth.4260.
  • Metabolomics Reveals that Dietary Xenoestrogens Alter Cellular Metabolism Induced by Palbociclib/Letrozole Combination Cancer Therapy.Warth B, Raffeiner P, Granados A, Huan T, Fang M, Forsberg EM, Benton HP, Goetz L, Johnson CH, Siuzdak G. Metabolomics Reveals that Dietary Xenoestrogens Alter Cellular Metabolism Induced by Palbociclib/Letrozole Combination Cancer Therapy. Cell Chemical Biology 2018, 25: 291-300.e3. PMID: 29337187, PMCID: PMC5856613, DOI: 10.1016/j.chembiol.2017.12.010.
  • Beyond genomics: understanding exposotypes through metabolomics.Rattray NJW, Deziel NC, Wallach JD, Khan SA, Vasiliou V, Ioannidis JPA, Johnson CH. Beyond genomics: understanding exposotypes through metabolomics. Human Genomics 2018, 12: 4. PMID: 29373992, PMCID: PMC5787293, DOI: 10.1186/s40246-018-0134-x.
  • Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum.Zhu R, Liu F, Grisotti G, Pérez-Irizarry J, Cha CH, Johnson CH, Boffa DJ, Han D, Johung KL, Zhang Y, Khan SA. Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum. Journal Of Gastrointestinal Oncology 2018, 9: 231-240. PMID: 29755761, PMCID: PMC5934147, DOI: 10.21037/jgo.2017.11.12.
  • Defining Early-Onset Colon and Rectal Cancers.Jacobs D, Zhu R, Luo J, Grisotti G, Heller DR, Kurbatov V, Johnson CH, Zhang Y, Khan SA. Defining Early-Onset Colon and Rectal Cancers. Frontiers In Oncology 2018, 8: 504. PMID: 30460196, PMCID: PMC6232522, DOI: 10.3389/fonc.2018.00504.
  • Evaluation of potential carcinogenicity of organic chemicals in synthetic turf crumb rubber.Perkins AN, Inayat-Hussain SH, Deziel NC, Johnson CH, Ferguson SS, Garcia-Milian R, Thompson DC, Vasiliou V. Evaluation of potential carcinogenicity of organic chemicals in synthetic turf crumb rubber. Environmental Research 2019, 169: 163-172. PMID: 30458352, PMCID: PMC6396308, DOI: 10.1016/j.envres.2018.10.018.
  • Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells.Warth B, Palermo A, Rattray NJW, Lee NV, Zhu Z, Hoang LT, Cai Y, Mazurek A, Dann S, VanArsdale T, Fantin VR, Shields D, Siuzdak G, Johnson CH. Palbociclib and Fulvestrant Act in Synergy to Modulate Central Carbon Metabolism in Breast Cancer Cells. Metabolites 2019, 9 PMID: 30609717, PMCID: PMC6359333, DOI: 10.3390/metabo9010007.
  • 1,4-Dioxane as an emerging water contaminant: State of the science and evaluation of research needs.Godri Pollitt KJ, Kim JH, Peccia J, Elimelech M, Zhang Y, Charkoftaki G, Hodges B, Zucker I, Huang H, Deziel NC, Murphy K, Ishii M, Johnson CH, Boissevain A, O'Keefe E, Anastas PT, Orlicky D, Thompson DC, Vasiliou V. 1,4-Dioxane as an emerging water contaminant: State of the science and evaluation of research needs. The Science Of The Total Environment 2019, 690: 853-866. PMID: 31302550, DOI: 10.1016/j.scitotenv.2019.06.443.
  • Normalizing Untargeted Periconceptional Urinary Metabolomics Data: A Comparison of Approaches.Rosen Vollmar AK, Rattray NJW, Cai Y, Santos-Neto ÁJ, Deziel NC, Jukic AMZ, Johnson CH. Normalizing Untargeted Periconceptional Urinary Metabolomics Data: A Comparison of Approaches. Metabolites 2019, 9 PMID: 31546636, PMCID: PMC6835889, DOI: 10.3390/metabo9100198.
  • Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty.Rattray NJW, Trivedi DK, Xu Y, Chandola T, Johnson CH, Marshall AD, Mekli K, Rattray Z, Tampubolon G, Vanhoutte B, White IR, Wu FCW, Pendleton N, Nazroo J, Goodacre R. Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. Nature Communications 2019, 10: 5027. PMID: 31690722, PMCID: PMC6831565, DOI: 10.1038/s41467-019-12716-2.
  • Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer.Sun Y, Mironova V, Chen Y, Lundh EPF, Zhang Q, Cai Y, Vasiliou V, Zhang Y, Garcia-Milian R, Khan SA, Johnson CH. Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer. Translational Oncology 2020, 13: 42-56. PMID: 31760268, PMCID: PMC6883319, DOI: 10.1016/j.tranon.2019.09.004.
  • Analyzing Metabolomics Data for Environmental Health and Exposome Research.Cai Y, Rosen Vollmar AK, Johnson CH. Analyzing Metabolomics Data for Environmental Health and Exposome Research. Methods In Molecular Biology (Clifton, N.J.) 2020, 2104: 447-467. PMID: 31953830, DOI: 10.1007/978-1-0716-0239-3_22.
  • Sex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype.Cai Y, Rattray NJW, Zhang Q, Mironova V, Santos-Neto A, Hsu KS, Rattray Z, Cross JR, Zhang Y, Paty PB, Khan SA, Johnson CH. Sex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype. Scientific Reports 2020, 10: 4905. PMID: 32184446, PMCID: PMC7078199, DOI: 10.1038/s41598-020-61851-0.
  • Joint effect of pre-operative anemia and perioperative blood transfusion on outcomes of colon-cancer patients undergoing colectomy.Liu Z, Luo JJ, Pei KY, Khan SA, Wang XX, Zhao ZX, Yang M, Johnson CH, Wang XS, Zhang Y. Joint effect of pre-operative anemia and perioperative blood transfusion on outcomes of colon-cancer patients undergoing colectomy. Gastroenterology Report 2020, 8: 151-157. PMID: 32280475, PMCID: PMC7136710, DOI: 10.1093/gastro/goz033.
  • Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling.Rosen Vollmar AK, Johnson CH, Weinberg CR, Deziel NC, Baird DD, Wilcox AJ, Jukic AMZ. Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling. Journal Of Exposure Science & Environmental Epidemiology 2021, 31: 356-365. PMID: 32424331, PMCID: PMC7671945, DOI: 10.1038/s41370-020-0227-1.
  • Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage.Cai Y, Rattray NJW, Zhang Q, Mironova V, Santos-Neto A, Muca E, Vollmar AKR, Hsu KS, Rattray Z, Cross JR, Zhang Y, Paty PB, Khan SA, Johnson CH. Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage. Metabolites 2020, 10 PMID: 32575361, PMCID: PMC7345993, DOI: 10.3390/metabo10060257.
  • Kynurenic acid underlies sex-specific immune responses to COVID-19.Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh J, Silva J, Wong P, Ko AJ, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid underlies sex-specific immune responses to COVID-19. MedRxiv : The Preprint Server For Health Sciences 2020 PMID: 32935119, PMCID: PMC7491534, DOI: 10.1101/2020.09.06.20189159.
  • Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients.Liu J, Huang X, Liu H, Wei C, Ru H, Qin H, Lai H, Meng Y, Wu G, Xie W, Mo X, Johnson CH, Zhang Y, Tang W. Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients. Journal Of Translational Medicine 2021, 19: 27. PMID: 33413474, PMCID: PMC7789428, DOI: 10.1186/s12967-020-02638-9.
  • Use of Untargeted Metabolomics to Explore the Air Pollution-Related Disease Continuum.Jin L, Godri Pollitt KJ, Liew Z, Rosen Vollmar AK, Vasiliou V, Johnson CH, Zhang Y. Use of Untargeted Metabolomics to Explore the Air Pollution-Related Disease Continuum. Current Environmental Health Reports 2021, 8: 7-22. PMID: 33420964, DOI: 10.1007/s40572-020-00298-x.
  • Gene Alterations of N6-Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study.Zhang Q, Cai Y, Kurbatov V, Khan SA, Lu L, Zhang Y, Johnson CH. Gene Alterations of N6-Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study. BioMed Research International 2020, 2020: 8826456. PMID: 33415160, PMCID: PMC7769650, DOI: 10.1155/2020/8826456.
  • Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach.Charkoftaki G, Golla JP, Santos-Neto A, Orlicky DJ, Garcia-Milian R, Chen Y, Rattray NJW, Cai Y, Wang Y, Shearn CT, Mironova V, Wang Y, Johnson CH, Thompson DC, Vasiliou V. Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach. Toxicological Sciences : An Official Journal Of The Society Of Toxicology 2021, 183: 338-351. PMID: 33693819, PMCID: PMC8921626, DOI: 10.1093/toxsci/kfab030.
  • Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma.Zhu G, Su H, Johnson CH, Khan SA, Kluger H, Lu L. Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma. European Journal Of Cancer (Oxford, England : 1990) 2021, 151: 25-34. PMID: 33962358, PMCID: PMC8184628, DOI: 10.1016/j.ejca.2021.03.053.
  • ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody.Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray NJ, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6 PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.
  • YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment.Yang X, Lam W, Jiang Z, Guan F, Han X, Hu R, Cai W, Cheng W, Liu SH, Cheng P, Cai Y, Rattray NJW, Johnson CH, Chen L, Cheng YC. YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment. Scientific Reports 2021, 11: 13482. PMID: 34188068, PMCID: PMC8242098, DOI: 10.1038/s41598-021-91623-3.
  • Kynurenic acid may underlie sex-specific immune responses to COVID-19.Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14 PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.
  • Molecular Mechanisms of Alcohol-Induced Colorectal Carcinogenesis.Johnson CH, Golla JP, Dioletis E, Singh S, Ishii M, Charkoftaki G, Thompson DC, Vasiliou V. Molecular Mechanisms of Alcohol-Induced Colorectal Carcinogenesis. Cancers 2021, 13 PMID: 34503214, PMCID: PMC8431530, DOI: 10.3390/cancers13174404.
  • Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study.Shen X, Cai Y, Lu L, Huang H, Yan H, Paty PB, Muca E, Ahuja N, Zhang Y, Johnson CH, Khan SA. Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study. Metabolites 2022, 12 PMID: 35208238, PMCID: PMC8875032, DOI: 10.3390/metabo12020164.
  • Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review.Guo P, Furnary T, Vasiliou V, Yan Q, Nyhan K, Jones DP, Johnson CH, Liew Z. Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review. Environment International 2022, 162: 107159. PMID: 35231839, PMCID: PMC8969205, DOI: 10.1016/j.envint.2022.107159.
  • Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery.Bakkila BF, Kerekes D, Nunez-Smith M, Billingsley KG, Ahuja N, Wang K, Oladele C, Johnson CH, Khan SA. Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery. JAMA Network Open 2022, 5: e225664. PMID: 35377425, PMCID: PMC8980937, DOI: 10.1001/jamanetworkopen.2022.5664.
Edit Profile