{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:49:10Z","timestamp":1791539350187,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"23-24","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Statistics in Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with survivors frequently experiencing long\u2010term neurocognitive morbidities. Here, we utilize the TOTXVI clinical trial data to elucidate the mechanisms underlying treatment\u2010related neurocognitive side effects in pediatric ALL patients by incorporating brain connectivity network data. To enable such analysis, we propose a high\u2010dimensional mediation analysis method with a novel network mediation structural shrinkage (NMSS) prior, which is particularly suited for analyzing high\u2010dimensional brain structural connectivity network data that serve as mediators. Our method is capable of addressing the structural dependencies of brain connectivity networks including sparsity, effective degrees of nodes, and modularity, yielding accurate estimates of the high\u2010dimensional coefficients and mediation effects. We demonstrate the effectiveness and superiority of the proposed NMSS method through simulation studies and apply it to the TOTXVI data, revealing significant mediation effects of brain connectivity on visual processing speed directed by IT intensity. The findings shed light on the potential of targeted interventions to mitigate neurocognitive deficits in pediatric ALL survivors.<\/jats:p>","DOI":"10.1002\/sim.70756","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:33:59Z","timestamp":1790829239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010Dimensional Mediation Analysis With Network Mediators: Applications to Pediatric Acute Lymphoblastic Leukemia"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-0509","authenticated-orcid":false,"given":"Jade Xiaoqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Statistics Texas A&amp;M University  College Station Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Hua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Daiichi Sankyo  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-1201","authenticated-orcid":false,"given":"Wilburn E.","family":"Reddick","sequence":"additional","affiliation":[{"name":"Department of Radiology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Conklin","sequence":"additional","affiliation":[{"name":"Department of Psychology &amp; Biobehavioral Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-2054","authenticated-orcid":false,"given":"John O.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Radiology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2698-5816","authenticated-orcid":false,"given":"Lisa","family":"Jacola","sequence":"additional","affiliation":[{"name":"Department of Psychology &amp; Biobehavioral Sciences St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Onar\u2010Thomas","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2835-5869","authenticated-orcid":false,"given":"Sima","family":"Jeha","sequence":"additional","affiliation":[{"name":"Department of Global Pediatric Medicine St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-7599","authenticated-orcid":false,"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Statistics and Data Science Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0136-6"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21992"},{"issue":"3","key":"e_1_2_13_4_1","first-page":"346","article-title":"Chemotherapy\u2010Only Treatment Effects on Long\u2010Term Neurocognitive Functioning in Childhood ALL Survivors: A Review and Meta\u2010Analysis","volume":"126","author":"Iyer N. 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