{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:08:56Z","timestamp":1789711736853,"version":"4.0.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Central lymph node metastasis in clinically node-negative papillary thyroid carcinoma is regulated by the tumor immune microenvironment, yet existing studies have addressed molecular, systemic immune, and local imaging signals in isolation without examining their cross-scale associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort of 1,000 cN0 PTC patients was enrolled. BRAF V600E mutation status, six peripheral blood immune-inflammatory indices, and an ultrasound radiomics deep learning score were integrated into four progressive LightGBM models. Cross-scale Spearman correlations, BRAF-stratified Fisher z-transformation tests, and TCGA-THCA immune deconvolution analysis were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The three-scale integrated model achieved a validation AUC of 0.824, with all DeLong incremental comparisons reaching statistical significance. The DLR-score was significantly correlated with all six immune-inflammatory indices after Bonferroni correction. BRAF-positive subgroup exhibited significantly stronger imaging-immune coupling for NLR and SII, and this enhanced coupling persisted after adjustment for age, tumor size, multifocality, and Hashimoto\u2019s thyroiditis in partial correlation analyses. TCGA tissue immune infiltration patterns were directionally consistent with peripheral observations. Calibration assessment confirmed probability accuracy across the predicted range, and decision curve analysis demonstrated sustained net benefit superiority of the integrated model over single-scale alternatives within the clinically relevant 10% to 50% threshold interval.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Three-scale noninvasive immune signals provide complementary CLNM prediction and exhibit directionally consistent cross-scale statistical associations at the correlation level, suggesting that they may serve as noninvasive surrogates reflecting partially overlapping aspects of the same tumor immune dysregulation process, although confirmation of the underlying biological mechanisms requires prospective studies incorporating direct tissue-level immune profiling.<\/jats:p>\n                  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