{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T07:18:41Z","timestamp":1726211921138},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Cancer Institute (NCI) in Egypt"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Indian J Hematol Blood Transfus"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple myeloma (MM) is a malignant plasma cell neoplasm with complex biology and heterogenous course. Interferon regulatory factor 4 (IRF4) transcription factor, important key developmental stages of hematopoiesis, represents an excellent potential therapeutic target. The present work aimed to investigate the expression status of IRF4 in the diagnostic bone marrow biopsy (BMB) cores of MM patients. This prospective study included 62 newly diagnosed MM patients. The expression of IRF4 was assessed in the BMB by immunohistochemistry (IHC). The data were correlated to the patients\u2019 clinico-pathological features, response to treatment and survival rates. IRF4 expression was observed in 50% of MM patients (31\/62). IRF-4 positive patients were more frequently male patients (<jats:italic>P<\/jats:italic>\u2009=\u20090.018), have immunoglobulin heavy chain (IgH) translocations (<jats:italic>P<\/jats:italic>\u2009=\u20090.05) and tended to present with a higher platelets count (<jats:italic>P<\/jats:italic>\u2009=\u20090.07). Multiple myeloma patients presenting with urine M-protein had worse overall survival (OS) than negative cases (<jats:italic>P<\/jats:italic>\u2009=\u20090.012). Normocellular BM aspirate (BMA) was associated with better OS than hypercellular and hypocellular BMA (<jats:italic>P<\/jats:italic>\u2009=\u20090.006). Patchy distribution of plasma cells in BMB was associated with better disease-free survival (DFS) while diffuse infiltration had the worst (<jats:italic>P<\/jats:italic>\u2009=\u20090.019). Of note, after treatment, MM patients had significantly lower percentage of BMA plasma cells, platelet count, <jats:italic>\u03b22<\/jats:italic> microglobulin and creatinine levels (<jats:italic>P<\/jats:italic>\u2009=\u20090.037, &lt;\u20090.001, 0.022 and 0.026, respectively). Had higher albumin level (<jats:italic>P<\/jats:italic>\u2009=\u20090.007), compared to initial investigations. No significant association was found between IRF4 expression and the patients\u2019clinical outcomes. Patterns of plasma cells distribution in BMB, BMA cellularity and urine M-protein are prognostically relevant in MM.<\/jats:p>","DOI":"10.1007\/s12288-023-01628-3","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T18:02:52Z","timestamp":1673892172000},"page":"525-536","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Relevance of Interferon Regulatory Family-4 (IRF4) Expression in Newly Diagnosed Patients with Multiple Myeloma"],"prefix":"10.1007","volume":"39","author":[{"given":"May E.","family":"Abdelmonem","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hend A.","family":"Nooh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona S.","family":"El Ashry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"1628_CR1","unstructured":"Cancer Network (2021) Multiple myeloma: statistics. https:\/\/www.cancer.net\/cancer-types\/multiple-myeloma\/statistics"},{"key":"1628_CR2","unstructured":"National Cancer Institute (2021) Cancer stat facts: myeloma. https:\/\/seer.cancer.gov\/statfacts\/html\/mulmy.html"},{"key":"1628_CR3","doi-asserted-by":"publisher","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","volume":"3","author":"SK Kumar","year":"2017","unstructured":"Kumar SK, Rajkumar V, Kyle RA et al (2017) Multiple myeloma. Nat Rev Dis Primers 3:17046","journal-title":"Nat Rev Dis Primers"},{"key":"1628_CR4","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/j.1600-0609.2008.01127","volume":"81","author":"J Caers","year":"2008","unstructured":"Caers J, Vande Broek I, De Raeve H, Michaux L, Trullemans F, Schots R, Van Camp B, Vanderkerken K (2008) Multiple myeloma-an update on diagnosis and treatment. Eur J Haematol 81:329\u201343. https:\/\/doi.org\/10.1111\/j.1600-0609.2008.01127","journal-title":"Eur J Haematol"},{"key":"1628_CR5","doi-asserted-by":"publisher","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","volume":"15","author":"SV Rajkumar","year":"2014","unstructured":"Rajkumar SV, Dimopoulos MA, Palumbo A et al (2014) International Myeloma Working Group Updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15:e538\u2013e548","journal-title":"Lancet Oncol"},{"issue":"1","key":"1628_CR6","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70(1):7\u201330","journal-title":"CA Cancer J Clin"},{"key":"1628_CR7","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1016\/S0140-6736(14)60493-1","volume":"385","author":"C Rollig","year":"2015","unstructured":"Rollig C, Knop S, Bornhauser M (2015) Multiple myeloma. Lancet 385:2197\u20132208. https:\/\/doi.org\/10.1016\/S0140-6736(14)60493-1","journal-title":"Lancet"},{"key":"1628_CR8","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1001\/jamaoncol.2018.2128","volume":"4","author":"AJ Cowan","year":"2018","unstructured":"Cowan AJ, Allen C, Barac A et al (2018) Global burden of multiple myeloma: a systematic analysis for the Global Burden of Disease Study 2016. JAMA Oncol 4:1221\u20131227","journal-title":"JAMA Oncol"},{"issue":"1","key":"1628_CR9","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13045-019-0706-9","volume":"12","author":"W Liu","year":"2019","unstructured":"Liu W, Liu J, Song Y et al (2019) Union for China Leukemia Investigators of the Chinese Society of Clinical Oncology, Union for China Lymphoma Investigators of the Chinese Society of Clinical Oncology. Mortality of lymphoma and myeloma in China, 2004\u20132017: an observational study. J Hematol Oncol 12(1):22","journal-title":"J Hematol Oncol"},{"key":"1628_CR10","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41571-018-0018-y","volume":"15","author":"S Kumar","year":"2018","unstructured":"Kumar S, Rajkumar SV (2018) The multiple myelomas: current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol 15:409\u2013421","journal-title":"Nat Rev Clin Oncol"},{"key":"1628_CR11","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S0140-6736(16)30954-0","volume":"388","author":"P Moreau","year":"2016","unstructured":"Moreau P, Rajkumar SV (2016) Multiple myeloma\u2013translation of trial results into reality. Lancet 388:111\u2013113","journal-title":"Lancet"},{"key":"1628_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3016","author":"A Agnarelli","year":"2022","unstructured":"Agnarelli A, Mitchell S, Caalim G, Wood CD et al (2022) Dissecting the impact of bromodomain inhibitors on the Interferon Regulatory Factor 4-MYC oncogenic axis in multiple myeloma. Hematol Oncol. https:\/\/doi.org\/10.1002\/hon.3016","journal-title":"Hematol Oncol"},{"issue":"10272","key":"1628_CR13","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/S0140-6736(21)00135-5","volume":"397","author":"NWJ Van de Donk","year":"2021","unstructured":"Van de Donk NWJ, Pawlyn C, Yong KL (2021) Multiple myeloma. The Lancet 397(10272):410\u2013427","journal-title":"The Lancet"},{"key":"1628_CR14","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrc746","volume":"2","author":"WM Kuehl","year":"2002","unstructured":"Kuehl WM, Bergsagel PL (2002) Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2:175\u2013187","journal-title":"Nat Rev Cancer"},{"key":"1628_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41408-020-0284-7","volume":"10","author":"CR Marinac","year":"2020","unstructured":"Marinac CR, Ghobrial IM, Birmann BM, Soiffer J, Rebbeck TR (2020) Dissecting racial disparities in multiple myeloma. Blood Cancer J 10:1\u20138","journal-title":"Blood Cancer J"},{"key":"1628_CR16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/978-1-4939-6703-2_23","volume":"1541","author":"NC Chan","year":"2017","unstructured":"Chan NC, Chan NP (2017) Recurrent cytogenetic abnormalities in multiple myeloma. Methods Mol Biol 1541:295\u2013302","journal-title":"Methods Mol Biol"},{"key":"1628_CR17","doi-asserted-by":"publisher","first-page":"e365","DOI":"10.1038\/bcj.2015.92","volume":"5","author":"AM Rajan","year":"2015","unstructured":"Rajan AM, Rajkumar SV (2015) Interpretation of cytogenetic results in multiple myeloma for clinical practice. Blood Cancer J 5:e365","journal-title":"Blood Cancer J"},{"key":"1628_CR18","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1002\/ajh.25791","volume":"95","author":"SV Rajkumar","year":"2020","unstructured":"Rajkumar SV (2020) Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol 95:548\u2013567","journal-title":"Am J Hematol"},{"key":"1628_CR19","doi-asserted-by":"publisher","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","volume":"33","author":"A Palumbo","year":"2015","unstructured":"Palumbo A et al (2015) Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol Off J Am Soc Clin Oncol 33:2863\u20132869","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"issue":"7","key":"1628_CR20","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/ni1357","volume":"7","author":"U Klein","year":"2006","unstructured":"Klein U, Casola S, Cattoretti G et al (2006) Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination. Nat Immunol 7(7):773\u2013782","journal-title":"Nat Immunol"},{"key":"1628_CR21","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.leukres.2018.07.025","volume":"72","author":"A Agnarelli","year":"2018","unstructured":"Agnarelli A, Chevassut T, Mancini EJ (2018) IRF4 in multiple myeloma: biology, disease and therapeutic target. Leuk Res 72:52\u201358","journal-title":"Leuk Res"},{"issue":"49","key":"1628_CR22","doi-asserted-by":"publisher","first-page":"85392","DOI":"10.18632\/oncotarget.19907","volume":"8","author":"H Bai","year":"2017","unstructured":"Bai H, Wu S, Wang R, Xu J, Chen L (2017) Bone marrow IRF4 level in multiple myeloma: an indicator of peripheral blood Th17 and disease. Oncotarget 8(49):85392\u201385400","journal-title":"Oncotarget"},{"issue":"9","key":"1628_CR23","doi-asserted-by":"publisher","first-page":"e106788","DOI":"10.1371\/journal.pone.0106788","volume":"9","author":"L Wang","year":"2014","unstructured":"Wang L, Yao ZQ, Moorman JP, Xu Y, Ning S (2014) Gene expression profiling identifies IRF4-associated molecular signatures in hematological malignancies. PLoS ONE 9(9):e106788","journal-title":"PLoS ONE"},{"issue":"2","key":"1628_CR24","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/ng1097-226","volume":"17","author":"S Iida","year":"1997","unstructured":"Iida S, Rao PH, Butler M et al (1997) Deregulation of MUM1\/IRF4 by chromosomal translocation in multiple myeloma. Nat Genet 17(2):226\u2013230","journal-title":"Nat Genet"},{"issue":"11","key":"1628_CR25","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1038\/sj.leu.2401563","volume":"13","author":"S Yoshida","year":"1999","unstructured":"Yoshida S, Nakazawa N, Iida S et al (1999) Detection of MUM1\/IRF4-IgH fusion in multiple myeloma. Leukemia 13(11):1812\u20131816","journal-title":"Leukemia"},{"issue":"7201","key":"1628_CR26","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature07064","volume":"454","author":"AL Shaffer","year":"2008","unstructured":"Shaffer AL, Emre NC, Lamy L et al (2008) IRF4 addiction in multiple myeloma. Nature 454(7201):226\u2013231","journal-title":"Nature"},{"key":"1628_CR27","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.stem.2020.12.017","volume":"28","author":"PK Mondala","year":"2021","unstructured":"Mondala PK, Vora AA, Zhou T, Lazzari E, Ladel L, Luo X, Kim Y et al (2021) Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption. Cell Stem Cell 28:623-636.e9","journal-title":"Cell Stem Cell"},{"key":"1628_CR28","doi-asserted-by":"crossref","unstructured":"McGowan-Jordan J, Simons A, Schmid M (2016) ISCN 2016: an international system for human cytogenomic nomenclature","DOI":"10.1159\/isbn.978-3-318-06861-0"},{"key":"1628_CR29","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41408-020-00359-2","volume":"10","author":"SV Rajkumar","year":"2020","unstructured":"Rajkumar SV, Kumar S (2020) Multiple myeloma current treatment algorithms. Blood Cancer J 10:94","journal-title":"Blood Cancer J"},{"key":"1628_CR30","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/ni.3348","volume":"17","author":"J Tellier","year":"2016","unstructured":"Tellier J, Shi W, Minnich M, Liao Y, Crawford S et al (2016) Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response. Nat Immunol 17:323\u2013330","journal-title":"Nat Immunol"},{"key":"1628_CR31","doi-asserted-by":"publisher","first-page":"3200","DOI":"10.4049\/jimmunol.1303216","volume":"192","author":"SN Willis","year":"2014","unstructured":"Willis SN, Good-Jacobson KL, Curtis J, Light A, Tellier J et al (2014) Transcription factor IRF4 regulates germinal center cell formation through a B cell-intrinsic mechanism. J. Immunol 192:3200\u20133206","journal-title":"J. Immunol"},{"key":"1628_CR32","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1016\/j.celrep.2019.10.097","volume":"29","author":"MSY Low","year":"2019","unstructured":"Low MSY, Brodie EJ, Fedele PL, Liao Y, Grigoriadis G, Strasser A et al (2019) IRF4 activity is required in established plasma cells to regulate gene transcription and mitochondrial homeostasis. Cell Rep 29:2634\u20132645","journal-title":"Cell Rep"},{"key":"1628_CR33","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41408-022-00638-0","volume":"12","author":"S Atrash","year":"2022","unstructured":"Atrash S, Flahavan EM, Xu T, Ma E et al (2022) Treatment patterns and outcomes according to cytogenetic risk stratification in patients with multiple myeloma: a real-world analysis. Blood Cancer J 12:46","journal-title":"Blood Cancer J"},{"issue":"12","key":"1628_CR34","doi-asserted-by":"publisher","first-page":"2683","DOI":"10.3390\/jcm10122683","volume":"10","author":"J Barankiewicz","year":"2021","unstructured":"Barankiewicz J, Salomon A, Perzy\u0144ski A et al (2021) The CRBN, CUL4A and DDB1 expression predicts the response to immunomodulatory drugs and survival of multiple myeloma patients. J Clin Med 10(12):2683","journal-title":"J Clin Med"},{"key":"1628_CR35","doi-asserted-by":"publisher","first-page":"110248","DOI":"10.1016\/j.cellsig.2022.110248","volume":"92","author":"S Fakhari","year":"2022","unstructured":"Fakhari S, Jalili A, Nikkhoo B, Ghaderi B et al (2022) MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression. Cell Signal 92:110248","journal-title":"Cell Signal"},{"key":"1628_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13039-017-0327-3","volume":"10","author":"T Smol","year":"2017","unstructured":"Smol T, Dufour A, Tricot S, Wemeau M et al (2017) Combination of t(4;14), del(17p13), del(1p32) and 1q21 gain FISH probes identifies clonal heterogeneity and enhances the detection of adverse cytogenetic profiles in 233 newly diagnosed multiple myeloma. Mol Cytogenet 10:1\u20136","journal-title":"Mol Cytogenet"},{"issue":"10","key":"1628_CR37","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1182\/bloodadvances.2019001275","volume":"4","author":"PW Mellors","year":"2020","unstructured":"Mellors PW, Binder M, Ketterling RP, Greipp PT et al (2020) Metaphase cytogenetics and plasma cell proliferation index for risk stratification in newly diagnosed multiple myeloma. Blood Adv 4(10):2236\u20132242","journal-title":"Blood Adv"},{"key":"1628_CR38","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1111\/j.1365-2141.2011.08689.x","volume":"154","author":"A Lopez-Girona","year":"2011","unstructured":"Lopez-Girona A, Heintel D, Zhang LH, Mendy D, Gaidarova S, Brady H et al (2011) Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol 154:325\u2013336","journal-title":"Br J Haematol"},{"issue":"23","key":"1628_CR39","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1182\/blood.V126.23.2965.2965","volume":"126","author":"A Belotti","year":"2015","unstructured":"Belotti A, Malagola M, Crippa C, Prezioso I, Schieppati F, Ribolla R et al (2015) Urinary protein levels in Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) predict severe disease related complications at myeloma progression. Blood 126(23):2965","journal-title":"Blood"},{"key":"1628_CR40","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/ajh.10003","volume":"68","author":"SV Rajkumar","year":"2001","unstructured":"Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Witzig TE et al (2001) Methods for estimation of bone marrow plasma cell involvement in myeloma: predictive value for response and survival in patients undergoing autologous stem cell transplantation. Am J Hematol 68:269\u2013275","journal-title":"Am J Hematol"},{"issue":"7","key":"1628_CR41","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1182\/blood-2005-05-1858","volume":"106","author":"GS Nowakowski","year":"2005","unstructured":"Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ et al (2005) Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 106(7):2276\u20132279","journal-title":"Blood"},{"key":"1628_CR42","first-page":"1147","volume":"90","author":"A Wei","year":"2005","unstructured":"Wei A, Westerman D, Feleppa F (2005) Bone marrow plasma cell microaggregates detected by immunohistology predict earlier relapse in patients with minimal disease after high-dose therapy for myeloma. Haematologica 90:1147\u20131149","journal-title":"Haematologica"},{"issue":"5","key":"1628_CR43","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1182\/bloodadvances.2018022806","volume":"3","author":"N Tandon","year":"2019","unstructured":"Tandon N, Sidana S, Rajkumar SV, Gertz MA, Buadi FK, Lacy MQ, Kumar SK et al (2019) Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma. Blood Adv 3(5):744\u2013750","journal-title":"Blood Adv"},{"issue":"11","key":"1628_CR44","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1182\/blood-2010-09-307645","volume":"117","author":"F Gay","year":"2011","unstructured":"Gay F, Larocca A, Wijermans P et al (2011) Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood 117(11):3025\u20133031","journal-title":"Blood"},{"issue":"3","key":"1628_CR45","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1111\/ejh.12829","volume":"98","author":"H Van de Velde","year":"2017","unstructured":"Van de Velde H, Londhe A, Ataman O et al (2017) Association between complete response and outcomes in transplant-eligible myeloma patients in the era of novel agents. Eur J Haematol 98(3):269\u2013279","journal-title":"Eur J Haematol"},{"issue":"35","key":"1628_CR46","doi-asserted-by":"publisher","first-page":"5775","DOI":"10.1200\/JCO.2008.17.9721","volume":"26","author":"JJ Lahuerta","year":"2008","unstructured":"Lahuerta JJ, Mateos MV, Mart\u00ednez-L\u00f3pez J et al (2008) Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol 26(35):5775\u20135782","journal-title":"J Clin Oncol"}],"container-title":["Indian Journal of Hematology and Blood Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12288-023-01628-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12288-023-01628-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12288-023-01628-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T01:04:58Z","timestamp":1696122298000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12288-023-01628-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,16]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["1628"],"URL":"https:\/\/doi.org\/10.1007\/s12288-023-01628-3","relation":{},"ISSN":["0971-4502","0974-0449"],"issn-type":[{"value":"0971-4502","type":"print"},{"value":"0974-0449","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,16]]},"assertion":[{"value":"6 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare that there is no possible conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All patients provided informed consent. The study was performed following the 2011 declaration of Helsinki and was approved by the internal review board of the National Cancer Institute.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}