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Foundation","award":["1R01HL155523"],"award-info":[{"award-number":["1R01HL155523"]}]},{"name":"The Lipedema Foundation","award":["1R01HL157378"],"award-info":[{"award-number":["1R01HL157378"]}]},{"name":"The Lipedema Foundation","award":["R01 DK119497"],"award-info":[{"award-number":["R01 DK119497"]}]},{"name":"The Lipedema Foundation","award":["LF45_21_Rutkowski_COL"],"award-info":[{"award-number":["LF45_21_Rutkowski_COL"]}]},{"name":"The Lipedema Foundation","award":["LF30-B"],"award-info":[{"award-number":["LF30-B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.<\/jats:p>","DOI":"10.3390\/ijms23126621","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T23:50:14Z","timestamp":1655250614000},"page":"6621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-6565","authenticated-orcid":false,"given":"Bailey H.","family":"Duhon","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Texas A & M University College of Medicine, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3940-1613","authenticated-orcid":false,"given":"Thien T.","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Texas A & M University College of Medicine, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1143-267X","authenticated-orcid":false,"given":"Shannon L.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN 37232, USA"},{"name":"Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1008-4570","authenticated-orcid":false,"given":"Rachelle L.","family":"Crescenzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN 37232, USA"},{"name":"Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Texas A & M University College of Medicine, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1161\/CIRCRESAHA.121.318307","article-title":"Advances in Lymphedema","volume":"128","author":"Rockson","year":"2021","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1177\/02683555211015887","article-title":"Standard of care for lipedema in the United States","volume":"36","author":"Herbst","year":"2021","journal-title":"Phlebol. Phlebol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1097\/PRS.0000000000002136","article-title":"Lymphedema: Presentation, Diagnosis, and Treatment","volume":"137","author":"Kamali","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1056\/NEJMc1201684","article-title":"Lower-Extremity Lymphedema and Elevated Body-Mass Index","volume":"366","author":"Greene","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1177\/1358863X10364553","article-title":"Current concepts and future directions in the diagnosis and management of lymphatic vascular disease","volume":"15","author":"Rockson","year":"2010","journal-title":"Vasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1002\/cncr.25458","article-title":"Lymphedema beyond breast cancer: A systematic review and meta-analysis of cancer-related secondary lymphedema","volume":"116","author":"Cormier","year":"2010","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1188\/14.CJON.S3.68-79","article-title":"Putting Evidence into Practice: Cancer-Related Lymphedema","volume":"18","author":"Fu","year":"2014","journal-title":"Clin. J. Oncol. Nurs."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41572-019-0072-5","article-title":"Cancer-associated secondary lymphoedema","volume":"5","author":"Rockson","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1055\/s-0038-1635117","article-title":"Diagnosis and Staging of Lymphedema","volume":"32","author":"Goss","year":"2018","journal-title":"Semin. Plast. Surg."},{"key":"ref_10","first-page":"85","article-title":"Stemmer\u2019s sign\u2014Possibilities and limits of clinical diagnosis of lymphedema","volume":"149","author":"Stemmer","year":"1999","journal-title":"Wien. Med. Wochenschr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Suehiro, K., Mizumoto, Y., Morikage, N., Harada, T., Samura, M., Nagase, T., Takeuchi, Y., Mizoguchi, T., Suzuki, R., and Kurazumi, H. (2021). Hardness Sensed by Skin Palpation in Legs with Lymphedema Is Predominantly Correlated with Dermal Thickening. Lymphat. Res. Biol.","DOI":"10.1089\/lrb.2020.0133"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.jaad.2017.03.021","article-title":"Lymphedema: Diagnostic workup and management","volume":"77","author":"Grada","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, J., Hoffner, M., and Brorson, H. (2021). Adipocytes are larger in lymphedematous extremities than in controls. J. Plast. Surg. Hand Surg., 1\u20138.","DOI":"10.1080\/2000656X.2021.1953042"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10549-021-06419-w","article-title":"Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema","volume":"191","author":"Crescenzi","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1172\/JCI71608","article-title":"New developments in clinical aspects of lymphatic disease","volume":"124","author":"Mortimer","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1111\/j.1749-6632.2010.05804.x","article-title":"Causes and consequences of lymphatic disease","volume":"1207","author":"Rockson","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Executive Committee of the International Society of Lymphology (2020). The diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology. Lymphology, 53, 3\u201319.","DOI":"10.2458\/lymph.4649"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/aps.2011.153","article-title":"Rare adipose disorders (RADs) masquerading as obesity","volume":"33","author":"Herbst","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1205","DOI":"10.1097\/GOX.0000000000001205","article-title":"Lymphaticovenous Anastomosis Releases the Lower Extremity Lymphedema-associated Pain","volume":"5","author":"Mihara","year":"2017","journal-title":"Plast. Reconstr. Surg. Glob. Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1007\/s00520-017-3671-2","article-title":"Immediate effects of active exercise with compression therapy on lower-limb lymphedema","volume":"25","author":"Fukushima","year":"2017","journal-title":"Support. Care Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/rnj.171","article-title":"Factors Associated with Reported Infection and Lymphedema Symptoms among Individuals with Extremity Lymphedema","volume":"40","author":"Deng","year":"2015","journal-title":"Rehabil. Nurs."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bowman, C., Piedalue, K.-A., Baydoun, M., and Carlson, L.E. (2020). The Quality of Life and Psychosocial Implications of Cancer-Related Lower-Extremity Lymphedema: A Systematic Review of the Literature. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103200"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1177\/0268355516639421","article-title":"First Dutch guidelines on lipedema using the international classification of functioning, disability and health","volume":"32","author":"Halk","year":"2016","journal-title":"Phlebol. J. Venous Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.jacc.2020.09.579","article-title":"ACC\/AHA\/SVM\/ACP Advanced Training Statement on Vascular Medicine (Revision of the 2004 ACC\/ACP\/SCAI\/SVMB\/SVS Clinical Competence Statement on Vascular Medicine and Catheter-Based Peripheral Vascular Interventions) A Report of the ACC Competency Management Committee","volume":"77","author":"Creager","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/ddg.13036","article-title":"S1 guidelines: Lipedema","volume":"15","author":"Schmeller","year":"2017","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1748-1716.2006.01531_1.x","article-title":"Convincing evidence for the pumping activity of lymphatics","volume":"186","year":"2006","journal-title":"Acta Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaad.2006.09.023","article-title":"Lipedema, a frequently unrecognized problem","volume":"57","author":"Fonder","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_28","unstructured":"Crescenzi, R., Donahue, P., Petersen, K., Garza, M., Guerreso, K., Luo, Y., Beckman, J., and Donahue, M. (2020, January 8\u201313). Lymphatic insufficiency observed by noninvasive MR lymphangiography and multi-nuclear 23Na-MRI in patients with lymphedema and lipedema. Proceedings of the 28th Annual Meeting of the International Society for Magnetic Resonance in Medicine (ISMRM), Oral Presentation at Scientific Sessions, Paris, France."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1046\/j.1439-0353.2004.04051.x","article-title":"Lipoedema\u2014Current status, new perspectives","volume":"2","author":"Schmeller","year":"2004","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_30","first-page":"10","article-title":"Lipedema fat and signs and symptoms of illness, increase with advancing stage","volume":"7","author":"Herbst","year":"2015","journal-title":"Arch. Med."},{"key":"ref_31","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dhatariya, K., Dungan, K., Grossman, A., Hershman, J.M., and Hofland, J. (2000). Subcutaneous Adipose Tissue Diseases: Dercum Disease, Lipedema, Familial Multiple Lipomatosis, and Madelung Disease, Endotext."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s13555-018-0241-6","article-title":"Exploration of Patient Characteristics and Quality of Life in Patients with Lipoedema Using a Survey","volume":"8","author":"Romeijn","year":"2018","journal-title":"Dermatol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/ijo.2016.205","article-title":"Differentiating lipedema and Dercum\u2019s disease","volume":"41","author":"Beltran","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_34","first-page":"1075","article-title":"Pressure-Volume relationships in the interstitial spaces","volume":"4","author":"Guyton","year":"1965","journal-title":"Investig. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/oby.22597","article-title":"Lipedema: A Call to Action!","volume":"27","author":"Buso","year":"2019","journal-title":"Obesity"},{"key":"ref_36","first-page":"e14364","article-title":"Cause and management of lipedema-associated pain","volume":"34","author":"Aksoy","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/ard.32.5.413","article-title":"Articular mobility in an African population","volume":"32","author":"Beighton","year":"1973","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1742-1241.2003.tb10455.x","article-title":"A simple questionnaire to detect hypermobility: An adjunct to the assessment of patients with diffuse musculoskeletal pain","volume":"57","author":"Hakim","year":"2003","journal-title":"Int. J. Clin. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Katzer, K., Hill, J.L., McIver, K.B., and Foster, M.T. (2021). Lipedema and the Potential Role of Estrogen in Excessive Adipose Tissue Accumulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111720"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/ajmg.a.33313","article-title":"Lipedema: An inherited condition","volume":"152A","author":"Child","year":"2010","journal-title":"Am. J. Med Genet. Part A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0002-9343(00)00727-0","article-title":"Lymphedema","volume":"110","author":"Rockson","year":"2001","journal-title":"Am. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"H1097","DOI":"10.1152\/ajpheart.1990.259.4.H1097","article-title":"Hyaluronan in prenodal lymph from skin: Changes with lymph flow","volume":"259","author":"Reed","year":"1990","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_43","first-page":"322","article-title":"The Pathophysiology of Lymphedema\u20142012","volume":"44","author":"Olszewski","year":"2012","journal-title":"Handchir. Mikrochir. Plast. Chir."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/lrb.2013.1132","article-title":"The Lymphatics and the Inflammatory Response: Lessons Learned from Human Lymphedema","volume":"11","author":"Rockson","year":"2013","journal-title":"Lymphat. Res. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.jaad.2017.03.022","article-title":"Lymphedema: Pathophysiology and clinical manifestations","volume":"77","author":"Grada","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1113\/jphysiol.2006.108308","article-title":"Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedema","volume":"574","author":"Karlsen","year":"2006","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/cs0850737","article-title":"Change in macromolecular composition of interstitial fluid from swollen arms after breast cancer treatment, and its implications","volume":"85","author":"Bates","year":"1993","journal-title":"Clin. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1097\/PRS.0b013e3182450b2d","article-title":"Regulation of adipogenesis by lymphatic fluid stasis: Part I. Adipogenesis, fibrosis, and inflammation","volume":"129","author":"Zampell","year":"2012","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mehrara, B.J., Park, H.J., Kataru, R.P., Bromberg, J., Coriddi, M., Baik, J.E., Shin, J., Li, C., Cavalli, M.R., and Encarnacion, E.M. (2021). Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema. Biology, 10.","DOI":"10.3390\/biology10090934"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1096\/fj.12-222695","article-title":"Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema","volume":"27","author":"Avraham","year":"2012","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Savetsky, I.L., Ghanta, S., Gardenier, J.C., Torrisi, J.S., Nores, G.D.G., Hespe, G.E., Nitti, M.D., Kataru, R.P., and Mehrara, B.J. (2015). Data from: Th2 cytokines inhibit lymphangiogenesis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126908"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e89081","DOI":"10.1172\/jci.insight.89081","article-title":"Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function","volume":"1","author":"Gousopoulos","year":"2016","journal-title":"JCI Insight"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14345","DOI":"10.1038\/ncomms14345","article-title":"Topical tacrolimus for the treatment of secondary lymphedema","volume":"8","author":"Gardenier","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jid.2015.12.001","article-title":"Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4+ T Cells Drives the Pathogenesis of Lymphedema","volume":"136","author":"Ogata","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.ajpath.2016.04.006","article-title":"Prominent Lymphatic Vessel Hyperplasia with Progressive Dysfunction and Distinct Immune Cell Infiltration in Lymphedema","volume":"186","author":"Gousopoulos","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1038\/s41598-021-87494-3","article-title":"Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: A hypothesis-generating study in breast cancer survivors","volume":"11","author":"Koc","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sedger, L.M., Tull, D., McConville, M.J., DE Souza, D., Rupasinghe, T.W.T., Williams, S., Dayalan, S., Lanzer, D., Mackie, H., and Lam, T.C. (2016). Lipidomic Profiling of Adipose Tissue Reveals an Inflammatory Signature in Cancer-Related and Primary Lymphedema. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0154650"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-physiol-022516-034008","article-title":"Lymphatic Dysfunction, Leukotrienes, and Lymphedema","volume":"80","author":"Jiang","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lin, S., Kim, J., Lee, M.-J., Roche, L., Yang, N.L., Tsao, P.S., and Rockson, S.G. (2012). Prospective Transcriptomic Pathway Analysis of Human Lymphatic Vascular Insufficiency: Identification and Validation of a Circulating Biomarker Panel. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052021"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1089\/lrb.2013.0024","article-title":"Cytokine Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery","volume":"12","author":"Leung","year":"2014","journal-title":"Lymphat. Res. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e135109","DOI":"10.1172\/jci.insight.135109","article-title":"Platelet factor 4 is a biomarker for lymphatic-promoted disorders","volume":"5","author":"Ma","year":"2020","journal-title":"JCI Insight"},{"key":"ref_62","first-page":"19","article-title":"Effect of complex decongestive physiotherapy on gene expression for the inflammatory response in peripheral lymphedema","volume":"33","author":"Sauerwald","year":"2000","journal-title":"Lymphology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"eaal3920","DOI":"10.1126\/scitranslmed.aal3920","article-title":"Leukotriene B4 antagonism ameliorates experimental lymphedema","volume":"9","author":"Tian","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e123775","DOI":"10.1172\/jci.insight.123775","article-title":"Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema","volume":"3","author":"Rockson","year":"2018","journal-title":"JCI Insight"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1001\/jama.1962.03050400016004","article-title":"Idiopathic Lymphedema","volume":"182","author":"Schirger","year":"1962","journal-title":"JAMA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"C709","DOI":"10.1152\/ajpcell.00284.2011","article-title":"Toll-like receptor deficiency worsens inflammation and lymphedema after lymphatic injury","volume":"302","author":"Zampell","year":"2012","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zampell, J.C., Yan, A., Elhadad, S., Avraham, T., Weitman, E., and Mehrara, B.J. (2012). CD4(+) cells regulate fibrosis and lymphangiogenesis in response to lymphatic fluid stasis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049940"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1097\/01.prs.0000277995.25009.3e","article-title":"Changes in the Lymph Structure of the Upper Limb after Axillary Dissection: Radiographic and Anatomical Study in a Human Cadaver","volume":"120","author":"Suami","year":"2007","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_69","first-page":"G723","article-title":"Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages","volume":"300","author":"Barron","year":"2011","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1089\/lrb.2017.0074","article-title":"Biomarkers Associated with Lymphedema and Fibrosis in Patients with Cancer of the Head and Neck","volume":"16","author":"Ridner","year":"2018","journal-title":"Lymphat. Res. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1089\/lrb.2016.0010","article-title":"Pathological Changes of Lymphedematous Skin: Increased Mast Cells, Related Proteases, and Activated Transforming Growth Factor-\u03b21","volume":"14","author":"Di","year":"2016","journal-title":"Lymphat. Res. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/j.metabol.2005.05.024","article-title":"Transforming growth factor beta1 release by human adipose tissue is enhanced in obesity","volume":"54","author":"Fain","year":"2005","journal-title":"Metabolism"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.2353\/ajpath.2010.100594","article-title":"Blockade of transforming growth factor-beta1 accelerates lymphatic regeneration during wound repair","volume":"177","author":"Avraham","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"H2113","DOI":"10.1152\/ajpheart.00879.2008","article-title":"TGF-beta1 is a negative regulator of lymphatic regeneration during wound repair","volume":"295","author":"Clavin","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/lrb.2006.4404","article-title":"Adipose Tissue Dominates Chronic Arm Lymphedema Following Breast Cancer: An Analysis Using Volume Rendered CT Images","volume":"4","author":"Brorson","year":"2006","journal-title":"Lymphat. Res. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1089\/lrb.2018.0027","article-title":"Assessment of Subfascial Muscle\/Water and Fat Accumulation in Lymphedema Patients Using Magnetic Resonance Imaging","volume":"17","author":"Trinh","year":"2019","journal-title":"Lymphat. Res. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/RLI.0000000000000386","article-title":"Magnetic Resonance Imaging\u2013Based Assessment of Breast Cancer\u2013Related Lymphoedema Tissue Composition","volume":"52","author":"Borri","year":"2017","journal-title":"Investig. Radiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1089\/lrb.2016.0047","article-title":"Breast Cancer-Related Lymphedema: Differentiating Fat from Fluid Using Magnetic Resonance Imaging Segmentation","volume":"16","author":"Sen","year":"2018","journal-title":"Lymphat. Res. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000461579","article-title":"High-Fat Diet in the Absence of Obesity Does Not Aggravate Surgically Induced Lymphoedema in Mice","volume":"58","author":"Gousopoulos","year":"2017","journal-title":"Eur. Surg. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/ijo.2016.96","article-title":"Obesity but not high-fat diet impairs lymphatic function","volume":"40","author":"Cuzzone","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.2353\/ajpath.2010.090733","article-title":"Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema","volume":"176","author":"Rutkowski","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e85096","DOI":"10.1172\/jci.insight.85096","article-title":"Restoration of lymphatic function rescues obesity in Prox1-haploinsufficient mice","volume":"1","author":"Escobedo","year":"2016","journal-title":"JCI Insight"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5738","DOI":"10.1111\/j.1742-4658.2009.07303.x","article-title":"Mechanisms of obesity and related pathologies: The macro- and microcirculation of adipose tissue","volume":"276","author":"Rutkowski","year":"2009","journal-title":"FEBS J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.addr.2020.08.013","article-title":"Imaging technology of the lymphatic system","volume":"170","author":"Polomska","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/cob.12239","article-title":"Lipoedema in patients after bariatric surgery: Report of two cases and review of literature","volume":"8","author":"Pouwels","year":"2018","journal-title":"Clin. Obes."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/01.ASW.0000363503.92360.91","article-title":"Lipedema: A frequently misdiagnosed and misunderstood fatty deposition syndrome","volume":"23","author":"Fife","year":"2010","journal-title":"Adv. Ski. Wound Care"},{"key":"ref_87","first-page":"8747461","article-title":"Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue","volume":"2019","author":"Cromer","year":"2019","journal-title":"J. Obes."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jss.2020.03.055","article-title":"Adipose Tissue Hypertrophy, An Aberrant Biochemical Profile and Distinct Gene Expression in Lipedema","volume":"253","author":"Felmerer","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1111\/j.1600-0560.2009.01256.x","article-title":"Adipose tissue remodeling in lipedema: Adipocyte death and concurrent regeneration","volume":"36","author":"Suga","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Al-Ghadban, S., Pursell, I., Diaz, Z., Herbst, K., and Bunnell, B. (2020). 3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218350"},{"key":"ref_91","first-page":"480","article-title":"Interstitial Fluid in Lipedema and Control Skin","volume":"1","author":"Allen","year":"2020","journal-title":"Womens Health Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cmet.2013.06.016","article-title":"Fibrosis and Adipose Tissue Dysfunction","volume":"18","author":"Sun","year":"2013","journal-title":"Cell Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1038\/ncomms4485","article-title":"Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction","volume":"5","author":"Sun","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e00564-19","DOI":"10.1128\/MCB.00564-19","article-title":"Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity","volume":"40","author":"Li","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/oby.22090","article-title":"Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema","volume":"26","author":"Crescenzi","year":"2017","journal-title":"Obesity"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/oby.22778","article-title":"Upper and Lower Extremity Measurement of Tissue Sodium and Fat Content in Patients with Lipedema","volume":"28","author":"Crescenzi","year":"2020","journal-title":"Obesity"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41574-020-0395-z","article-title":"The MMP14\u2013caveolin axis and its potential relevance for lipoedema","volume":"16","author":"Kruglikov","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_98","first-page":"315","article-title":"Measurements of skin elasticity in patients with lipedema of the Moncorps \u201crusticanus\u201d type","volume":"37","author":"Jagtman","year":"1984","journal-title":"Phlebologie"},{"key":"ref_99","first-page":"71","article-title":"Lipedema is associated with increased aortic stiffness","volume":"45","author":"Szolnoky","year":"2012","journal-title":"Lymphology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"104298","DOI":"10.1016\/j.mvr.2021.104298","article-title":"Indocyanine green lymphography as novel tool to assess lymphatics in patients with lipedema","volume":"140","author":"Buso","year":"2021","journal-title":"Microvasc. Res."},{"key":"ref_101","first-page":"386","article-title":"Imaging for treatment planning in lipo-and lymphedema","volume":"50","author":"Zetzmann","year":"2018","journal-title":"Search Life Sci. Literature."},{"key":"ref_102","first-page":"341","article-title":"Lymphoscintigraphic findings in patients with lipedema","volume":"37","year":"2018","journal-title":"Rev. Esp. Med. Nucl. Imagen Mol. (Engl. Ed.)"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1177\/000331979504600408","article-title":"Functional Lymphatic Alterations in Patients Suffering from Lipedema","volume":"46","author":"Bilancini","year":"1995","journal-title":"Angiology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0398-0499(04)96770-4","article-title":"Comparative analysis of lymphoscintigraphy between lipedema and lower limb lymphedema","volume":"29","author":"Boursier","year":"2004","journal-title":"J. Mal. Vasc."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"10947","DOI":"10.1038\/s41598-020-67987-3","article-title":"Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology","volume":"10","author":"Felmerer","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.mvr.2009.01.005","article-title":"MR imaging of the lymphatic system in patients with lipedema and lipo-lymphedema","volume":"77","author":"Lohrmann","year":"2009","journal-title":"Microvasc. Res."},{"key":"ref_107","first-page":"161","article-title":"Complex decongestive physiotherapy decreases capillary fragility in lipedema","volume":"41","author":"Szolnoky","year":"2008","journal-title":"Lymphology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"srep46476","DOI":"10.1038\/srep46476","article-title":"Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation","volume":"7","author":"Schierke","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1083\/jcb.201409063","article-title":"The cell biology of fat expansion","volume":"208","author":"Rutkowski","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41572-021-00309-7","article-title":"Primary lymphoedema","volume":"7","author":"Brouillard","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1152\/physrev.00006.2020","article-title":"Development and physiological functions of the lymphatic system: Insights from human genetic studies of primary lymphedema","volume":"101","author":"Mortimer","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1172\/JCI71609","article-title":"Development of the mammalian lymphatic vasculature","volume":"124","author":"Yang","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/emboj\/21.7.1505","article-title":"An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype","volume":"21","author":"Wigle","year":"2002","journal-title":"EMBO J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1086\/375614","article-title":"Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia","volume":"72","author":"Irrthum","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1086\/316915","article-title":"Mutations in FOXC2 (MFH-1), a Forkhead Family Transcription Factor, Are Responsible for the Hereditary Lymphedema-Distichiasis Syndrome","volume":"67","author":"Fang","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1086\/303019","article-title":"Congenital Hereditary Lymphedema Caused by a Mutation That Inactivates VEGFR3 Tyrosine Kinase","volume":"67","author":"Irrthum","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1093\/hmg\/7.13.2073","article-title":"Hereditary lymphedema: Evidence for linkage and genetic heterogeneity","volume":"7","author":"Ferrell","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.ctm.2017.01.001","article-title":"Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction","volume":"79","author":"Alper","year":"2017","journal-title":"Curr. Top. Membr."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"12","DOI":"10.2458\/lymph.4678","article-title":"SVEP1 is important for morphogenesis of lymphatic system: Possible implications in lymphedema","volume":"54","author":"Michelini","year":"2021","journal-title":"Lymphology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/ajmg.a.61269","article-title":"Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of-function variants","volume":"179","author":"Maltese","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"eaax8013","DOI":"10.1126\/scitranslmed.aax8013","article-title":"Characterization of ANGPT2 mutations associated with primary lymphedema","volume":"12","author":"Brouillard","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1038\/sj.emboj.7600763","article-title":"Hepatocyte growth factor promotes lymphatic vessel formation and function","volume":"24","author":"Kajiya","year":"2005","journal-title":"EMBO J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/s41467-018-03959-6","article-title":"Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program","volume":"9","author":"Frye","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1101\/gad.330105","article-title":"PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature","volume":"19","author":"Adams","year":"2005","journal-title":"Genes Dev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e1529","DOI":"10.1002\/mgg3.1529","article-title":"NOTCH1: Review of its role in lymphatic development and study of seven families with rare pathogenic variants","volume":"9","author":"Michelini","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1089\/lrb.2011.0024","article-title":"Possible Genetic Predisposition to Lymphedema after Breast Cancer","volume":"10","author":"Newman","year":"2012","journal-title":"Lymphat. Res. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Miaskowski, C., Dodd, M., Paul, S.M., West, C., Hamolsky, D., Abrams, G., Cooper, B.A., Elboim, C., Neuhaus, J., and Schmidt, B.L. (2013). Lymphatic and Angiogenic Candidate Genes Predict the Development of Secondary Lymphedema following Breast Cancer Surgery. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060164"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1364\/BOE.3.001256","article-title":"Lymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging","volume":"3","author":"Aldrich","year":"2012","journal-title":"Biomed. Opt. Express"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1161\/ATVBAHA.118.310997","article-title":"Lymphatic Vasculature Requires Estrogen Receptor-\u03b1 Signaling to Protect from Lymphedema","volume":"38","author":"Morfoisse","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1097\/PRS.0b013e318213a218","article-title":"Primary Lymphedema: Clinical Features and Management in 138 Pediatric Patients","volume":"127","author":"Schook","year":"2011","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/sj.ijo.0802987","article-title":"Angiogenic factors are elevated in overweight and obese individuals","volume":"29","author":"Silha","year":"2005","journal-title":"Int. J. Obes."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1021\/acsptsci.9b00051","article-title":"Lymphatic Function and Dysfunction in the Context of Sex Differences","volume":"2","author":"Trincot","year":"2019","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Michelini, S., Chiurazzi, P., Marino, V., Dell\u2019Orco, D., Manara, E., Baglivo, M., Fiorentino, A., Maltese, P.E., Pinelli, M., and Herbst, K.L. (2020). Aldo-Keto Reductase 1C1 (AKR1C1) as the First Mutated Gene in a Family with Nonsyndromic Primary Lipedema. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176264"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1055\/s-0029-1224154","article-title":"Pit-1 Mutation and Lipoedema in a Family","volume":"118","author":"Bano","year":"2009","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/84651","article-title":"Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3","volume":"7","author":"Makinen","year":"2001","journal-title":"Nat. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ejmg.2017.02.007","article-title":"Altered body composition, lipedema, and decreased bone density in individuals with Williams syndrome: A preliminary report","volume":"60","author":"Waxler","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41572-021-00276-z","article-title":"Williams syndrome","volume":"7","author":"Kozel","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/MED.0000000000000588","article-title":"Growth, body composition, and endocrine issues in Williams syndrome","volume":"28","author":"Stanley","year":"2020","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers-Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Michelini, S., Herbst, K.L., Precone, V., Manara, E., Marceddu, G., Dautaj, A., Maltese, P.E., Paolacci, S., Ceccarini, M.R., and Beccari, T. (2022). A Multi-Gene Panel to Identify Lipedema-Predisposing Genetic Variants by a Next-Generation Sequencing Strategy. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020268"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Grigoriadis, D., Sackey, E., Riches, K., van Zanten, M., Brice, G., England, R., Mills, M., Dobbins, S.E., Consortium, L., and Consortium, G.E.R. (2021). Investigation of clinical characteristics and genome associations in the \u2018UK Lipoedema\u2019 cohort. medRxiv.","DOI":"10.1101\/2021.06.15.21258988"},{"key":"ref_142","first-page":"5581","article-title":"Genetics of lipedema: New perspectives on genetic research and molecular diagnoses","volume":"23","author":"Paolacci","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. 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