Association of a postoperative multigene-based grouping with ultrasonographic and pathological features in papillary thyroid carcinoma: a single-center retrospective study

Association of a postoperative multigene-based grouping with ultrasonographic and pathological features in papillary thyroid carcinoma: a single-center retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of a postoperative multigene-based grouping with ultrasonographic and pathological features in papillary thyroid carcinoma: a single-center retrospective study Dehao Wang, Hailin Sun, Zhong Zhuang, Lin Han, Zhaoqing Cui, Zhen Wu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9366720/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Most molecular association studies in papillary thyroid carcinoma (PTC) have focused on single-gene events or selected co-mutations. Whether a pragmatic multigene-based grouping is associated with preoperative ultrasonographic features and postoperative pathological features remains unclear. Methods We retrospectively included patients who underwent thyroidectomy for pathologically confirmed PTC at a single center between April and December 2025. Multigene testing was performed on postoperative FFPE specimens. Using a postoperative FFPE-based grouping approach defined by multigene results, patients with wild-type results or isolated BRAF V600E were grouped as Low-MRG, and all others as High-MRG. Univariable analyses used Fisher's exact test and the Wilcoxon rank-sum test. Size-adjusted models included maximum tumor diameter on preoperative ultrasonography and used Firth penalized-likelihood logistic regression or ordinary least-squares linear regression. Benjamini–Hochberg false discovery rate correction was applied. Results Seventy-nine patients were included (High-MRG, n = 15; Low-MRG, n = 64). In unadjusted analyses, High-MRG was associated with larger maximum tumor diameter on ultrasonography (median 2.50 vs. 1.30 cm; q value = 0.011), lower aspect ratio (0.74 vs. 1.01; q value = 0.031), suspicious cervical lymph nodes on ultrasonography (86.7% vs. 46.9%; OR = 7.37; q value = 0.034), aggressive histological subtypes (53.3% vs. 14.1%; OR = 6.98; q value = 0.027), and advanced T stage (60.0% vs. 20.3%; OR = 5.88; q value = 0.027). After adjustment for maximum tumor diameter, associations with suspicious cervical lymph nodes on ultrasonography, aggressive histological subtypes, and advanced T stage were attenuated. A greater total number of positive lymph nodes remained associated with High-MRG after size adjustment (β = 7.065; q value = 0.019). Conclusions In this exploratory postoperative FFPE-based grouping approach, High-MRG was associated with adverse preoperative ultrasonographic and postoperative pathological features, but most associations were attenuated after adjustment for tumor size. The most stable size-adjusted finding was a greater total number of positive lymph nodes. Further evaluation in larger multicenter cohorts, ideally using preoperative FNA specimens, is needed. papillary thyroid carcinoma multigene-based grouping ultrasonographic features pathological features thyroid molecular testing lymph node metastasis Figures Figure 1 Figure 2 Figure 3 1. Introduction Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy and generally has a favorable prognosis [ 1 , 2 ]. Nevertheless, a subset of tumors shows more aggressive behavior, including larger primary size, extrathyroidal extension, aggressive histological subtypes, and heavier nodal metastatic burden. Understanding how molecular abnormalities relate to preoperative ultrasonographic features and postoperative pathological features remains clinically relevant, particularly for hypothesis generation in risk-oriented diagnostic research. Molecular testing has expanded the characterization of PTC beyond conventional histopathology. Common driver events such as BRAF V600E, RAS-family mutations, and RET /NTRK fusions define biologically distinct subgroups [ 3 – 7 ]. Additional alterations, including TERT promoter mutations, co-occurring driver events, and abnormalities involving the TP53 /PI3K-AKT pathway, have been more frequently associated with tumor progression and dedifferentiation [ 8 – 12 ]. However, isolated molecular events may not fully capture the biological complexity of PTC, especially in clinical specimens with heterogeneous multigene profiles. Most previous clinicopathological association studies have evaluated single-gene alterations or selected two-gene combinations, such as BRAF V600E alone or BRAF - TERT co-mutation [ 8 – 10 , 13 , 14 ]. By contrast, the relationship between a pragmatic multigene-based grouping and preoperative ultrasonographic features or postoperative pathological features has been less systematically examined. An exploratory assessment of such a grouping may help identify clinically recognizable patterns while acknowledging that it is not a mature molecular stratification system. In this single-center retrospective study, we evaluated whether a postoperative multigene-based grouping (hereafter, the MRG grouping) was associated with preoperative ultrasonographic and postoperative pathological features in PTC. 2. Methods 2.1 Study design This single-center retrospective observational study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [ 15 ]. Ethical approval and the informed-consent waiver are described in the Declarations section. 2.2 Study population: inclusion and exclusion criteria We retrospectively screened all consecutive eligible patients who underwent thyroid surgery at Liaocheng People's Hospital, Affiliated to Shandong First Medical University between April and December 2025. No formal sample size calculation was performed because this was a retrospective study, and all eligible cases during the prespecified study period were included. The inclusion criteria were as follows: (1) preoperative fine-needle aspiration (FNA) cytology suggesting malignancy or suspicion for malignancy, with surgery planned; (2) postoperative pathological confirmation of papillary thyroid carcinoma (PTC); (3) multigene testing performed on postoperative formalin-fixed paraffin-embedded (FFPE) surgical specimens; (4) cervical ultrasonography performed at Liaocheng People's Hospital, Affiliated to Shandong First Medical University within 1 month before surgery, with complete reports and clear imaging records available; and (5) no prior history of thyroid surgery. The exclusion criteria were as follows: (1) other histological types of thyroid carcinoma; (2) reoperation cases; and (3) key variables missing and not retrievable from the electronic medical record, imaging archive, or pathology information system. A total of 92 patients were initially screened. After exclusion of patients with missing essential ultrasonographic reports (n = 7) and those with other pathological subtypes (n = 6), 79 patients were included in the final analytic cohort. 2.3 Surgical management and lymph node handling All patients underwent central neck lymph node dissection during the index operation, and all dissected nodes were submitted for pathological examination. Lateral neck dissection was performed selectively according to preoperative imaging findings or intraoperative assessment. Because this was a surgically treated cohort with postoperative molecular testing, its postoperative pathological profile may differ from that of the broader PTC population. Accordingly, lymph node burden-related variables, including the total number of positive lymph nodes and the lymph node ratio (LNR), were interpreted as postoperative pathological measures that may also reflect the extent of dissection and the number of submitted nodes. 2.4 Molecular testing and postoperative multigene-based grouping (MRG) MRG was determined from molecular testing results obtained from postoperative FFPE specimens. Preoperative FNA specimens were used only for cytological diagnosis and were not incorporated into the MRG grouping. Molecular testing was performed using real-time quantitative polymerase chain reaction (qPCR) on an ABI 7500 real-time PCR platform with assay kits supplied by Shanghai Ruijing Biotechnology Co., Ltd., including the BRAF/TERT/CCDC6-RET Mutation Detection Kit and the Thyroid Multigene Detection Kit. The panel covered BRAF V600E and TERT promoter C228T/C250T mutations; hotspot mutations in the RAS family ( NRAS , HRAS , and KRAS ), RET , TP53 , PIK3CA , and AKT1 ; and the fusion variants CCDC6 :: RET , NCOA4 :: RET , TPM3 :: NTRK1 , PAX8 :: PPARG , and ETV6 :: NTRK3 (12 genes and 16 loci in total, according to the manufacturer's instructions). Assay precision was defined as a coefficient of variation of ≤ 5% for Ct values, and the reported clinical sensitivity and specificity were 84.3% and 98.3%, respectively. Quality control procedures included positive and negative controls, internal reference gene detection, and dual-review verification. The binary MRG grouping used in this study was a pragmatic analytic approach rather than a mature clinical molecular classification system. BRAF V600E alone is the most common alteration in PTC and, when present in isolation, does not consistently distinguish a clearly higher-risk phenotype [ 8 – 12 ]. By contrast, TERT promoter mutations, BRAF - TERT co-mutations, RET /NTRK fusions, and alterations involving TP53 , PIK3CA , or AKT1 have more often been linked to aggressive biological behavior [ 8 – 12 ]. Patients with wild-type results (n = 3) or isolated BRAF V600E mutation (n = 61) were classified as Low-MRG, whereas all other detectable molecular alterations were classified as High-MRG (n = 15). This binary grouping was chosen because the cohort was small, the non-isolated BRAF subgroup was molecularly heterogeneous, and individual alteration categories were sparse. Pooling these alterations was intended to improve estimate stability and reduce sparse-data bias. Low-MRG should therefore be interpreted as a relatively lower molecular-risk background rather than as equivalent to clinically low-risk disease. The detailed molecular composition of the High-MRG group is shown in Additional file 1. 2.5 Clinical data and variable definitions Clinical, ultrasonographic, and pathological data were extracted from the electronic medical record and pathology information system, including age, sex, tumor size, number of tumor foci, bilateral involvement, Hashimoto’s thyroiditis, capsule/extrathyroidal extension-related information, central and lateral lymph node metastasis, and TNM stage. TNM staging was assigned according to the 8th edition of the AJCC staging system (2017). Aggressive histological subtypes were defined as pathologically confirmed tall cell, hobnail, columnar cell, diffuse sclerosing, or solid variants of PTC, whereas classical and follicular variants were classified as non-aggressive [ 2 , 16 ]. For interpretive clarity, the analysis focused on three main outcome features: (1) suspicious cervical lymph nodes on preoperative ultrasonography; (2) aggressive histological subtype; and (3) advanced T stage (defined as T3/T4). Extrathyroidal extension-related features and lymph node stage/burden-related features, such as preoperative suspicion of extrathyroidal extension, postoperative pathological extrathyroidal extension, N1b stage, total positive lymph nodes, and lymph node ratio, were analyzed as secondary outcomes because they may be influenced by the extent of dissection and the number of examined nodes. Maximum tumor diameter on preoperative ultrasonography was recorded as a continuous variable (cm), whereas pathological tumor size > 4 cm was treated as a binary postoperative pathological feature. Suspected extrathyroidal extension or capsule-related findings on preoperative ultrasonography were distinguished from pathologically confirmed extrathyroidal extension. For multifocal PTC, the target nodule was defined as the nodule with the highest TI-RADS category; if multiple nodules had the same TI-RADS category, the largest nodule was selected. All other preoperative ultrasonographic features were assigned on the basis of this target nodule. Aspect ratio and taller-than-wide status were both extracted directly from the original ultrasonographic report fields and recorded as separate variables; taller-than-wide status was not recalculated from the numerical aspect ratio. Suspicious cervical lymph nodes on ultrasonography were defined as suspicious lymph nodes in either the central or lateral neck compartment on the ultrasonographic report. TI-RADS classification was based on the original C-TI-RADS categories (3, 4a, 4b, 4c, 5, and 6). In the multi-level TI-RADS analysis, Unknown was retained as a separate category. For binary analysis, high-risk TI-RADS was defined as TI-RADS 4b or higher (4b-6); TI-RADS 4a or lower and Unknown were grouped as non-high-risk to preserve the full cohort, and the proportion of Unknown was reported separately in descriptive statistics. 2.6 Missing data handling Based on the routine reporting pattern of structured ultrasonographic reports at Liaocheng People's Hospital, Affiliated to Shandong First Medical University, in which some routine negative findings are often left undescribed, the following prespecified missing-data handling rules were applied: (1) structured-report convention-based coding, whereby binary ultrasonographic features not explicitly described in the structured report were coded as absent, consistent with the institutional reporting convention that positive findings are routinely documented whereas negative findings may be omitted; (2) conditional median imputation, whereby missing aspect ratio values (n = 14) were imputed according to taller-than-wide status using the corresponding subgroup medians (0.8 for nodules not taller-than-wide and 1.1 for nodules classified as taller-than-wide); (3) label-based imputation, whereby missing TI-RADS values were coded as "Unknown"; and (4) retrospective completion, whereby missing lymph node-related variables in the structured system were completed by case-by-case review of pathology reports, and derived indicators (e.g., lymph node ratio) were then generated in a standardized manner. If the pathology report explicitly indicated no lymph node metastasis, the variable was coded as a structural zero. After retrospective completion and uniform recoding, the main inferential analyses were performed on the full cohort (N = 79). 2.7 Statistical analysis All tests were two-sided. In unadjusted analyses, binary outcomes were compared using Fisher’s exact test and reported as ORs with 95% confidence intervals (CIs). If a zero cell occurred in a 2 × 2 table, the Haldane–Anscombe continuity correction (0.5 added to each cell) was used to obtain finite OR estimates [ 17 , 18 ], whereas P values were still derived from Fisher’s exact test. Continuous outcomes were compared using the Wilcoxon rank-sum test [ 19 ], and effect sizes were reported as HL shifts (High-MRG minus Low-MRG) with 95% CIs [ 20 ]. Multi-level categorical variables were analyzed using the chi-square test or Fisher’s exact test, with Cramer’s V reported as the effect size. Raw P values from the univariable analyses were adjusted for multiple comparisons using the Benjamini–Hochberg false discovery rate (BH-FDR) procedure [ 21 ], yielding q values. BH-FDR correction was applied separately within the preoperative ultrasonographic feature domain (15 binary and 2 continuous outcomes; 17 tests) and the postoperative pathological feature domain (12 binary and 2 continuous outcomes; 14 tests). Statistical significance was prespecified at q value < 0.05, and figure and table annotations were based on q values. To assess whether observed associations were materially influenced by tumor size, multivariable models included maximum tumor diameter on preoperative ultrasonography as a covariate. Binary outcomes were analyzed using Firth penalized-likelihood logistic regression [ 22 ], with aORs, profile-likelihood 95% CIs, and P values reported. Continuous outcomes were analyzed using ordinary least-squares linear regression, with β estimates, 95% CIs, and P values reported. Ordinary least-squares models were used to provide interpretable adjusted mean-difference estimates in this small exploratory cohort, in which more complex count-based models were considered potentially unstable. Outcomes conceptually overlapping with the covariate, including maximum tumor diameter itself and pathological tumor size > 4 cm, were not entered into the adjusted models to avoid collinearity. For advanced T stage, because tumor size is itself a defining component of the outcome, adjustment for maximum diameter may constitute part-whole adjustment; the size-adjusted result for this outcome was therefore interpreted cautiously. P values from the multivariable model set were again adjusted using the BH-FDR procedure, applied separately within the size-adjusted preoperative ultrasonographic model set (13 binary and 1 continuous outcome; 14 tests) and the size-adjusted postoperative pathological model set (11 binary and 2 continuous outcomes; 13 tests). The resulting q values were interpreted only within their respective analytic pools rather than mixed across univariable and multivariable analyses. Results with raw P value < 0.05 but q value ≥ 0.05 were described as nominally significant and exploratory rather than as meeting the prespecified threshold. As a sensitivity analysis, the primary univariable associations that reached q value < 0.05 were re-examined using multivariable models additionally adjusted for age and sex, without adjustment for tumor size, to assess potential demographic confounding. BH-FDR correction was applied within each sensitivity-analysis domain (3 tests for preoperative ultrasonographic outcomes and 2 tests for postoperative pathological outcomes). These models were supplementary and did not replace the primary size-adjusted analyses. Given the modest sample size and limited number of High-MRG events, no further covariates were added to these supplementary models in order to preserve model stability in this exploratory setting. 2.8 Visualization and software Binary outcomes were visualized using forest plots on a logarithmic scale, displaying ORs or aORs with 95% CIs. Continuous outcomes were visualized using violin plots overlaid with boxplots to illustrate between-group distributional differences. All statistical analyses and figures were generated in R software (version 4.5.3). 3. Results 3.1 Study population and baseline characteristics A total of 92 patients were screened, and 79 patients with PTC were included in the analytic cohort (High-MRG, n = 15; Low-MRG, n = 64; Fig. 1 and Table 1 ). Table 1 summarizes the descriptive baseline characteristics of the analytic cohort. Compared with the Low-MRG group, the High-MRG group showed larger preoperative maximum tumor diameter, lower aspect ratio, more suspicious cervical lymph nodes on ultrasonography, higher frequencies of aggressive histological subtype and advanced T stage, and a greater total number of positive lymph nodes. Molecular alterations within the High-MRG group were heterogeneous, as summarized in Supplementary Table S1. Table 1 Baseline characteristics by MRG group. Variable Level High-MRG Low-MRG Age, years 56.00 (32.00–65.00) 46.50 (37.00–55.25) Male sex 1 (Yes) 3 (20.0%) 13 (20.3%) Maximum tumor diameter on ultrasonography, cm 2.50 (1.71–3.95) 1.30 (0.90–2.00) Aspect ratio (AP/TR) 0.74 (0.66–0.87) 1.01 (0.82–1.14) Irregular margin on ultrasonography 1 (Yes) 12 (80.0%) 47 (73.4%) Microcalcifications on ultrasonography 1 (Yes) 9 (60.0%) 40 (62.5%) Taller-than-wide on ultrasonography 1 (Yes) 4 (26.7%) 40 (62.5%) Hypoechogenicity on ultrasonography 1 (Yes) 12 (80.0%) 55 (85.9%) Heterogeneous echotexture on ultrasonography 1 (Yes) 12 (80.0%) 42 (65.6%) Intranodular blood flow on ultrasonography 1 (Yes) 9 (60.0%) 32 (50.0%) High-risk TI-RADS (≥ 4b) 1 (Yes) 11 (73.3%) 42 (65.6%) TI-RADS category 3 1 (6.7%) 0 (0.0%) TI-RADS category 4a 1 (6.7%) 17 (26.6%) TI-RADS category 4b 1 (6.7%) 21 (32.8%) TI-RADS category 4c 3 (20.0%) 11 (17.2%) TI-RADS category 5 7 (46.7%) 7 (10.9%) TI-RADS category 6 0 (0.0%) 3 (4.7%) TI-RADS category Unknown 2 (13.3%) 5 (7.8%) Suspicious cervical lymph nodes on ultrasonography 1 (Yes) 13 (86.7%) 30 (46.9%) Suspected extrathyroidal extension/capsule-related finding on ultrasonography 1 (Yes) 1 (6.7%) 10 (15.6%) Tumor location on ultrasonography Bilateral 4 (26.7%) 18 (28.1%) Tumor location on ultrasonography Isthmus 1 (6.7%) 4 (6.2%) Tumor location on ultrasonography Left 5 (33.3%) 24 (37.5%) Tumor location on ultrasonography Right 5 (33.3%) 18 (28.1%) Bilateral involvement on ultrasonography 1 (Yes) 4 (26.7%) 18 (28.1%) Isthmus location on ultrasonography 1 (Yes) 1 (6.7%) 6 (9.4%) Upper pole location on ultrasonography 1 (Yes) 0 (0.0%) 10 (15.6%) Lower pole location on ultrasonography 1 (Yes) 0 (0.0%) 7 (10.9%) Intrathyroidal spread (pathology) 1 (Yes) 4 (26.7%) 10 (15.6%) Aggressive histological subtype 1 (Yes) 8 (53.3%) 9 (14.1%) Capsular invasion (pathology) 1 (Yes) 14 (93.3%) 60 (93.8%) Vascular invasion (pathology) 1 (Yes) 2 (13.3%) 6 (9.4%) Nerve invasion (pathology) 1 (Yes) 5 (33.3%) 10 (15.6%) Pathological extrathyroidal extension 1 (Yes) 3 (20.0%) 10 (15.6%) Lymph node metastasis (pathology) 1 (Yes) 14 (93.3%) 60 (93.8%) N1b stage 1 (Yes) 9 (60.0%) 29 (45.3%) Multifocality (pathology) 1 (Yes) 9 (60.0%) 33 (51.6%) Advanced T stage (T3/T4) 1 (Yes) 9 (60.0%) 13 (20.3%) Pathological tumor size > 4 cm 1 (Yes) 2 (13.3%) 2 (3.1%) Lymph node ratio > 0.2 1 (Yes) 13 (86.7%) 51 (79.7%) Total positive lymph nodes 14.00 (5.00–16.50) 4.00 (2.00–10.25) Lymph node ratio 0.50 (0.44–0.64) 0.39 (0.25–0.62) Note: Continuous variables are presented as median (IQR) and categorical variables as n (%). All available cases from the analytic cohort were used for this descriptive table unless otherwise indicated. Inferential comparisons are reported in the subsequent association tables. 3.2 Univariable analysis of preoperative ultrasonographic features Univariable associations between MRG and preoperative ultrasonographic features are presented in Table 2 . High-MRG was associated with larger maximum tumor diameter on preoperative ultrasonography (HL shift = 1.14 cm, 95% CI 0.50 to 1.90; P value < 0.001; q value = 0.011) and lower aspect ratio (HL shift = -0.24, 95% CI -0.38 to -0.08; P value = 0.005; q value = 0.031). Among binary features, suspicious cervical lymph nodes on ultrasonography were more common in the High-MRG group (OR = 7.37, 95% CI 1.54 to 35.32; P value = 0.008; q value = 0.034). The overall TI-RADS category distribution was also associated with High-MRG (Cramer's V = 0.494; P value = 0.003; q value = 0.024). This was not necessarily inconsistent with the nonsignificant binary high-risk TI-RADS result, because the multicategory comparison captures finer shifts across category distributions that may be obscured when TI-RADS is dichotomized as 4b or higher versus <4b. Taller-than-wide morphology reached nominal significance at the raw P value threshold (OR = 0.22, 95% CI 0.06 to 0.76; P value = 0.019) but did not meet the prespecified BH-FDR threshold (q value = 0.066). No other preoperative ultrasonographic feature met q value < 0.05. Figure 2 A. Forest plot showing unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for binary preoperative ultrasonographic features in the High-MRG group relative to the Low-MRG group. The dashed vertical line indicates OR = 1, and the x-axis is shown on a logarithmic scale. Values greater than 1 indicate that the feature was more common in the High-MRG group. An asterisk (*) indicates q value < 0.05 after BH-FDR correction. Table 2 Univariable associations between MRG and preoperative ultrasonographic features. Variable Measure High-MRG Low-MRG Effect size (95% CI) P value q value Maximum tumor diameter on ultrasonography, cm HL shift (95% CI) 2.50 (1.71–3.95) 1.30 (0.90–2.00) 1.14 (0.5, 1.9) < 0.001 0.011 TI-RADS category Cramer's V levels = 7 levels = 7 0.494 0.003 0.024 Aspect ratio (AP/TR) HL shift (95% CI) 0.74 (0.66–0.87) 1.01 (0.82–1.14) -0.24 (-0.38, -0.08) 0.005 0.031 Suspicious cervical lymph nodes on ultrasonography OR (95% CI) 13 (86.7%) 30 (46.9%) 7.37 (1.54, 35.32) 0.008 0.034 Taller-than-wide on ultrasonography OR (95% CI) 4 (26.7%) 40 (62.5%) 0.22 (0.06, 0.76) 0.019 0.066 Upper pole location on ultrasonography OR (95% CI) 0 (0.0%) 10 (15.6%) 0.17 (0.01, 3.02) 0.194 0.551 Lower pole location on ultrasonography OR (95% CI) 0 (0.0%) 7 (10.9%) 0.25 (0.01, 4.57) 0.336 0.775 Heterogeneous echotexture on ultrasonography OR (95% CI) 12 (80.0%) 42 (65.6%) 2.1 (0.53, 8.21) 0.365 0.775 Intranodular blood flow on ultrasonography OR (95% CI) 9 (60.0%) 32 (50.0%) 1.5 (0.48, 4.71) 0.572 0.997 Suspected extrathyroidal extension/capsule-related finding on ultrasonography OR (95% CI) 1 (6.7%) 10 (15.6%) 0.39 (0.05, 3.27) 0.680 0.997 Hypoechogenicity on ultrasonography OR (95% CI) 12 (80.0%) 55 (85.9%) 0.65 (0.15, 2.79) 0.689 0.997 Irregular margin on ultrasonography OR (95% CI) 12 (80.0%) 47 (73.4%) 1.45 (0.36, 5.76) 0.749 0.997 High-risk TI-RADS (≥ 4b) OR (95% CI) 11 (73.3%) 42 (65.6%) 1.44 (0.41, 5.05) 0.762 0.997 Tumor location on ultrasonography Cramer's V levels = 4 levels = 4 0.048 0.972 1 Microcalcifications on ultrasonography OR (95% CI) 9 (60.0%) 40 (62.5%) 0.9 (0.28, 2.84) 1.000 1 Bilateral involvement on ultrasonography OR (95% CI) 4 (26.7%) 18 (28.1%) 0.93 (0.26, 3.3) 1.000 1 Isthmus location on ultrasonography OR (95% CI) 1 (6.7%) 6 (9.4%) 0.69 (0.08, 6.21) 1.000 1 Note: This table presents univariable associations between High-MRG and preoperative ultrasonographic features. Binary outcomes are reported as ORs with 95% CIs, and continuous outcomes are presented as median (IQR) in the group columns. When a zero cell occurred in a 2 × 2 contingency table, the Haldane–Anscombe continuity correction (0.5 added to each cell) was applied to obtain finite OR and CI estimates; P values were derived from Fisher’s exact test. Continuous outcomes were analyzed using the Wilcoxon rank-sum test, and effect sizes are presented as HL shifts (High-MRG minus Low-MRG) with 95% CIs. q values were obtained using BH-FDR correction within the preoperative ultrasonographic feature domain (15 binary and 2 continuous outcomes; 17 tests in total). Statistical significance was defined as q value < 0.05. Abbreviations: OR, odds ratio; CI, confidence interval; HL, Hodges-Lehmann; BH-FDR, Benjamini–Hochberg false discovery rate. 3.3 Univariable analysis of postoperative pathological features Univariable associations between MRG and postoperative pathological features are presented in Table 3 . High-MRG was associated with aggressive histological subtype (OR = 6.98, 95% CI 2.03 to 24.02; P value = 0.003; q value = 0.027) and advanced T stage (OR = 5.88, 95% CI 1.77 to 19.52; P value = 0.004; q value = 0.027). The total number of positive lymph nodes was higher in the High-MRG group in the unadjusted analysis (HL shift = 6.00, 95% CI 1 to 12; P value = 0.014), but this did not meet the prespecified BH-FDR threshold and therefore remained nominally significant (q value = 0.066). No other postoperative pathological feature met q value < 0.05. Table 3 Univariable associations between MRG and postoperative pathological features. Variable Measure High-MRG Low-MRG Effect size (95% CI) P value q value Aggressive histological subtype OR (95% CI) 8 (53.3%) 9 (14.1%) 6.98 (2.03, 24.02) 0.003 0.027 Advanced T stage (T3/T4) OR (95% CI) 9 (60.0%) 13 (20.3%) 5.88 (1.77, 19.52) 0.004 0.027 Total positive lymph nodes HL shift (95% CI) 14.00 (5.00–16.50) 4.00 (2.00–10.25) 6 (1, 12) 0.014 0.066 Nerve invasion (pathology) OR (95% CI) 5 (33.3%) 10 (15.6%) 2.7 (0.76, 9.59) 0.146 0.376 Lymph node ratio HL shift (95% CI) 0.50 (0.44–0.64) 0.39 (0.25–0.62) 0.12 (-0.06, 0.26) 0.15 0.376 Pathological tumor size > 4 cm OR (95% CI) 2 (13.3%) 2 (3.1%) 4.77 (0.61, 37.02) 0.161 0.376 N1b stage OR (95% CI) 9 (60.0%) 29 (45.3%) 1.81 (0.58, 5.68) 0.393 0.786 Intrathyroidal spread (pathology) OR (95% CI) 4 (26.7%) 10 (15.6%) 1.96 (0.52, 7.41) 0.451 0.789 Multifocality (pathology) OR (95% CI) 9 (60.0%) 33 (51.6%) 1.41 (0.45, 4.42) 0.581 0.843 Vascular invasion (pathology) OR (95% CI) 2 (13.3%) 6 (9.4%) 1.49 (0.27, 8.22) 0.643 0.843 Pathological extrathyroidal extension OR (95% CI) 3 (20.0%) 10 (15.6%) 1.35 (0.32, 5.66) 0.704 0.843 Lymph node ratio > 0.2 OR (95% CI) 13 (86.7%) 51 (79.7%) 1.66 (0.33, 8.28) 0.723 0.843 Capsular invasion (pathology) OR (95% CI) 14 (93.3%) 60 (93.8%) 0.93 (0.1, 9.01) 1 1 Lymph node metastasis (pathology) OR (95% CI) 14 (93.3%) 60 (93.8%) 0.93 (0.1, 9.01) 1 1 Note: This table presents univariable associations between High-MRG and postoperative pathological features. Statistical methods were the same as those used in Table 2 . Continuous outcomes are presented as median (IQR) in the group columns. q values were obtained using BH-FDR correction within the postoperative pathological feature domain (12 binary and 2 continuous outcomes; 14 tests in total). Statistical significance was defined as q value < 0.05. Abbreviations are the same as in Table 2 . 3.4 Multivariable analysis with adjustment for tumor size To assess whether the observed associations were attenuated after accounting for tumor size, size-adjusted models were fitted with maximum tumor diameter on preoperative ultrasonography as a covariate (see Methods 2.7). For preoperative ultrasonographic features (Tables 4 A and 4 B; Fig. 3 A), none of the associations met the prespecified BH-FDR threshold after size adjustment. The association between High-MRG and suspicious cervical lymph nodes on ultrasonography remained nominally significant (aOR = 5.37, 95% CI 1.38 to 30.15; P value = 0.014; q value = 0.197), whereas the remaining adjusted ultrasonographic associations were further attenuated. For postoperative pathological features (Tables 5 A and 5 B; Fig. 3 B), a greater total number of positive lymph nodes remained associated with High-MRG after size adjustment (β = 7.065, 95% CI 2.872 to 11.257; P value = 0.001; q value = 0.019). The association with aggressive histological subtype remained nominally significant (aOR = 5.25, 95% CI 1.49 to 19.39; P value = 0.010; q value = 0.065), whereas the association with advanced T stage was attenuated after adjustment (aOR = 2.69, 95% CI 0.68 to 10.38; P value = 0.156; q value = 0.506). Figure 3 A. Comparison of unadjusted ORs from Fisher's exact test and adjusted ORs from size-adjusted Firth penalized-likelihood logistic regression for binary preoperative ultrasonographic features. Triangles represent unadjusted ORs from Fisher's exact test, circles represent adjusted ORs from Firth penalized-likelihood logistic regression, and horizontal lines indicate 95% confidence intervals. The dashed vertical line indicates OR = 1, and the x-axis is shown on a logarithmic scale. Table 4 A. Size-adjusted preoperative ultrasonographic features (binary outcomes). Variable High-MRG (n = 15), n (%) Low-MRG (n = 64), n (%) Adjusted OR (95% CI) P value q value Suspicious cervical lymph nodes on ultrasonography 13 (86.7%) 30 (46.9%) 5.37 (1.38, 30.15) 0.014 0.197 Lower pole location on ultrasonography 0 (0.0%) 7 (10.9%) 0.16 (0, 1.63) 0.14 0.656 Upper pole location on ultrasonography 0 (0.0%) 10 (15.6%) 0.21 (0, 2.11) 0.216 0.755 Heterogeneous echotexture on ultrasonography 12 (80.0%) 42 (65.6%) 2.05 (0.56, 9.27) 0.288 0.806 Suspected extrathyroidal extension/capsule-related finding on ultrasonography 1 (6.7%) 10 (15.6%) 0.43 (0.04, 2.36) 0.36 0.839 Irregular margin on ultrasonography 12 (80.0%) 47 (73.4%) 1.65 (0.44, 7.67) 0.473 0.843 High-risk TI-RADS (≥ 4b) 11 (73.3%) 42 (65.6%) 1.57 (0.46, 6.29) 0.482 0.843 Taller-than-wide on ultrasonography 4 (26.7%) 40 (62.5%) 0.65 (0.15, 2.88) 0.563 0.875 Bilateral involvement on ultrasonography 4 (26.7%) 18 (28.1%) 0.87 (0.22, 3.06) 0.831 0.94 Isthmus location on ultrasonography 1 (6.7%) 6 (9.4%) 1.25 (0.11, 8.79) 0.838 0.94 Intranodular blood flow on ultrasonography 9 (60.0%) 32 (50.0%) 1.09 (0.32, 3.71) 0.89 0.94 Microcalcifications on ultrasonography 9 (60.0%) 40 (62.5%) 0.95 (0.29, 3.28) 0.937 0.94 Hypoechogenicity on ultrasonography 12 (80.0%) 55 (85.9%) 1.06 (0.25, 5.46) 0.94 0.94 Table 4 B. Size-adjusted preoperative ultrasonographic features (continuous outcomes). Variable High-MRG (n = 15), median (IQR) Low-MRG (n = 64), median (IQR) Adjusted β (95% CI) P value q value Aspect ratio (AP/TR) 0.74 (0.66–0.87) 1.01 (0.82–1.14) -0.115 (-0.256, 0.026) 0.114 0.656 Note: These models were used to assess whether the observed associations were attenuated after adjustment for tumor size. All models were adjusted for maximum tumor diameter on preoperative ultrasonography. Binary outcomes were analyzed using Firth penalized-likelihood logistic regression with profile-likelihood 95% CIs, and continuous outcomes were analyzed using ordinary least-squares linear regression. q values were obtained using BH-FDR correction within the size-adjusted preoperative ultrasonographic model set (13 binary and 1 continuous outcome; 14 tests in total). Statistical significance was defined as q value < 0.05. Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; BH-FDR, Benjamini–Hochberg false discovery rate. Table 5 A. Size-adjusted postoperative pathological features (binary outcomes). Variable High-MRG (n = 15), n (%) Low-MRG (n = 64), n (%) Adjusted OR (95% CI) P value q value Aggressive histological subtype 8 (53.3%) 9 (14.1%) 5.25 (1.49, 19.39) 0.01 0.065 Advanced T stage (T3/T4) 9 (60.0%) 13 (20.3%) 2.69 (0.68, 10.38) 0.156 0.506 Nerve invasion (pathology) 5 (33.3%) 10 (15.6%) 1.87 (0.47, 6.79) 0.36 0.779 Intrathyroidal spread (pathology) 4 (26.7%) 10 (15.6%) 1.79 (0.42, 6.98) 0.414 0.779 Multifocality (pathology) 9 (60.0%) 33 (51.6%) 1.56 (0.48, 5.43) 0.46 0.779 Lymph node ratio > 0.2 13 (86.7%) 51 (79.7%) 1.64 (0.38, 9.75) 0.526 0.779 Pathological extrathyroidal extension 3 (20.0%) 10 (15.6%) 0.63 (0.11, 2.78) 0.561 0.779 Vascular invasion (pathology) 2 (13.3%) 6 (9.4%) 1.6 (0.24, 8.74) 0.599 0.779 N1b stage 9 (60.0%) 29 (45.3%) 1.21 (0.35, 4.15) 0.758 0.839 Capsular invasion (pathology) 14 (93.3%) 60 (93.8%) 0.73 (0.09, 8.72) 0.774 0.839 Lymph node metastasis (pathology) 14 (93.3%) 60 (93.8%) 1.11 (0.16, 12.68) 0.918 0.918 Table 5 B. Size-adjusted postoperative pathological features (continuous outcomes). Variable High-MRG (n = 15), median (IQR) Low-MRG (n = 64), median (IQR) Adjusted β (95% CI) P value q value Total positive lymph nodes 14.00 (5.00–16.50) 4.00 (2.00–10.25) 7.065 (2.872, 11.257) 0.001 0.019 Lymph node ratio 0.50 (0.44–0.64) 0.39 (0.25–0.62) 0.133 (-0.038, 0.304) 0.131 0.506 Note: As in Tables 4 A and 4 B, all models were adjusted for maximum tumor diameter on preoperative ultrasonography; binary outcomes were analyzed using Firth penalized-likelihood logistic regression and continuous outcomes using ordinary least-squares linear regression. For advanced T stage, adjustment for maximum diameter should be interpreted cautiously because tumor size contributes to the stage definition. For continuous postoperative pathological outcomes derived from counts or ratios, the ordinary least-squares estimates should be interpreted as adjusted mean-difference summaries in this exploratory setting rather than as count-model parameters. q values were obtained using BH-FDR correction within the size-adjusted postoperative pathological model set (11 binary and 2 continuous outcomes; 13 tests in total). Statistical significance was defined as q value < 0.05. Abbreviations are the same as in Table 4 . 3.5 Sensitivity analysis with adjustment for age and sex In the age- and sex-adjusted sensitivity analysis, the direction of the main associations was broadly consistent with the unadjusted analyses. Larger maximum tumor diameter, lower aspect ratio, suspicious cervical lymph nodes on ultrasonography, aggressive histological subtype, and advanced T stage remained associated with High-MRG (all q values < 0.05; Tables 6 A and 6 B). These supplementary models assessed potential demographic confounding and did not alter the interpretation of the primary size-adjusted analyses. Table 6 A. Age- and sex-adjusted sensitivity analysis of preoperative ultrasonographic features. Variable Adjusted effect (95% CI) P value q value N Maximum tumor diameter on ultrasonography, cm 1.161 (0.516, 1.807) < 0.001 0.002 79 Aspect ratio (AP/TR) -0.235 (-0.375, -0.096) 0.001 0.002 79 Suspicious cervical lymph nodes on ultrasonography 6.33 (1.69, 35.49) 0.005 0.005 79 Note: All models were additionally adjusted for age and sex. q values were calculated using the Benjamini–Hochberg false discovery rate procedure within the preoperative ultrasonographic sensitivity-analysis domain (3 tests). Table 6 B. Age- and sex-adjusted sensitivity analysis of postoperative pathological features. Variable Adjusted effect (95% CI) P value q value N Aggressive histological subtype 6.08 (1.87, 20.49) 0.003 0.004 79 Advanced T stage (T3/T4) 5.33 (1.71, 17.65) 0.004 0.004 79 Note: All models were additionally adjusted for age and sex. q values were calculated using the Benjamini–Hochberg false discovery rate procedure within the postoperative pathological sensitivity-analysis domain (2 tests). 4. Discussion High-MRG was associated with several adverse preoperative ultrasonographic and postoperative pathological features in unadjusted analyses. After adjustment for tumor size, however, the three main outcome features of suspicious cervical lymph nodes on ultrasonography, aggressive histological subtype, and advanced T stage were attenuated and no longer met the prespecified BH-FDR threshold, suggesting that tumor size may partly explain these associations. The association that persisted after size adjustment involved a greater total number of positive lymph nodes (β = 7.065; q value = 0.019), a postoperative pathological measure reflecting metastatic lymph node burden. This direction is consistent with prior literature linking higher-risk molecular alterations, particularly BRAF - TERT co-mutation and selected fusion or pathway alterations, with more aggressive clinicopathological behavior [ 9 , 10 ]. Because the total number of positive lymph nodes can also be influenced by surgical extent and the number of examined nodes, this finding should be interpreted within the context of this surgically treated cohort. In the present cohort, the High-MRG group was composed predominantly of cases with concurrent BRAF V600E and TERT promoter alterations. The observed associations may therefore largely reflect the clinicopathological behavior of this subgroup rather than a uniform effect across all higher-risk molecular events pooled into the binary MRG grouping. Because individual non-isolated BRAF alteration categories were sparse, separate subgroup analyses were not considered sufficiently stable. Accordingly, the current findings support the analytic utility of this pragmatic grouping while not implying equivalent effects across all component alterations. The attenuation of associations with suspicious cervical lymph nodes and aggressive histological subtype after size adjustment is clinically relevant. Rather than supporting a strong size-independent effect, the data suggest that High-MRG may cluster with a broader aggressive presentation in which tumor size is an important component. The lower aspect ratio in the High-MRG group, together with the concordant direction of the taller-than-wide analysis, may likewise reflect tumor size, because larger tumors may expand more in the transverse plane. The discordance between the significant overall TI-RADS category distribution and the nonsignificant binary high-risk TI-RADS result may similarly reflect information loss from dichotomization. For advanced T stage, interpretation after size adjustment remains particularly cautious because maximum diameter contributes to the stage definition. This study extends prior work that mainly evaluated single-gene events or selected two-gene combinations by examining a multigene grouping in relation to both preoperative ultrasonographic and postoperative pathological features. This framework may aid pattern recognition, but it reduces molecular resolution and cannot identify which specific alterations drive the observed associations. Several limitations should be considered. This was a single-center retrospective study with a small, imbalanced cohort and no independent validation set. Molecular testing was performed on postoperative FFPE specimens rather than preoperative FNA samples, limiting direct inference about preoperative decision-making. The binary High-MRG/Low-MRG grouping reduced sparse-data bias but sacrificed molecular granularity by pooling heterogeneous alterations. Because the cohort was surgically treated and had a high prevalence of nodal disease, lymph node burden-related outcomes may also reflect the extent of central and especially lateral neck dissection and the number of examined nodes. Missing ultrasonographic variables were handled using prespecified recoding and conditional imputation rules, which may have introduced misclassification and reduced variability in some derived ultrasonographic measures, particularly aspect ratio. Continuous postoperative pathological outcomes derived from counts or ratios were summarized using ordinary least-squares models for interpretive simplicity; alternative count-based modeling may be preferable in larger validation cohorts. Overall, the size-adjusted analyses suggest that tumor size accounts for part of the association between High-MRG and adverse clinicopathological features, whereas the residual association with the total number of positive lymph nodes warrants further study. 5. Conclusion High-MRG was associated with adverse preoperative ultrasonographic and postoperative pathological features, but many associations weakened after adjustment for tumor size. The most consistent size-adjusted finding was a greater total number of positive lymph nodes. Confirmation in larger multicenter cohorts is needed. Abbreviations AJCC American Joint Committee on Cancer aOR adjusted odds ratio BH-FDR Benjamini–Hochberg false discovery rate CI confidence interval FFPE formalin-fixed paraffin-embedded FNA fine-needle aspiration HL Hodges-Lehmann LNR lymph node ratio MRG postoperative multigene-based grouping OR odds ratio PTC papillary thyroid carcinoma qPCR quantitative polymerase chain reaction STROBE Strengthening the Reporting of Observational Studies in Epidemiology TI-RADS Thyroid Imaging Reporting and Data System WT wild type. Declarations Ethics approval and consent to participate The study protocol was approved by the Ethics Committee of Liaocheng People's Hospital, Affiliated to Shandong First Medical University (Approval No. 2025148). Because this retrospective study used de-identified data generated during routine clinical care and involved no additional intervention, the requirement for informed consent was waived by the Ethics Committee. Clinical trial number: not applicable. Consent for publication Not applicable. Availability of data and materials The datasets analyzed during the current study are not publicly available because they contain potentially identifiable clinical information. De-identified data may be available from the corresponding author on reasonable request, subject to institutional approval and applicable ethical and privacy requirements. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Key Medical and Health Science and Technology Program of Shandong Province (Grant No. 202404011050) and the Liaocheng Key Research and Development Program (Policy-Guided Category) (Project No. 2024YD16). Authors’ contributions DW conceived the study, performed the formal analysis, and drafted the manuscript. HS and ZZ collected and curated the data. LH contributed to pathological assessment and data interpretation. ZC and ZW supervised the study and critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript. Acknowledgements Not applicable. References Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388(10061):2783–95. 10.1016/S0140-6736(16)30172-6 . Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1–133. 10.1089/thy.2015.0020 . Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28(7):742–62. 10.1210/er.2007-0007 . Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569–80. 10.1038/nrendo.2011.142 . Santoro M, Melillo RM, Fusco A. RET/PTC activation in papillary thyroid carcinoma: european journal of endocrinology prize lecture. Eur J Endocrinol. 2006;155(5):645–53. 10.1530/eje.1.02289 . Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731–47. 10.1038/s41571-018-0113-0 . Agrawal N, Akbani R, Aksoy BA, Ally A, Arachchi H, Asa SL, et al. Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell. 2014;159(3):676–90. 10.1016/j.cell.2014.09.050 . Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer. 2016;23(3):R143–55. 10.1530/ERC-15-0533 . Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014;32(25):2718–26. 10.1200/JCO.2014.55.5094 . Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, et al. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab. 2014;99(6):E1130–6. 10.1210/jc.2013-4048 . Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016;126(3):1052–66. 10.1172/JCI85271 . Hou P, Liu D, Shan Y, Hu S, Studeman K, Condouris S, et al. Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer. Clin Cancer Res. 2007;13(4):1161–70. 10.1158/1078-0432.CCR-06-1125 . Kabaker AS, Tublin ME, Nikiforov YE, Armstrong MJ, Hodak SP, Stang MT, et al. Suspicious ultrasound characteristics predict BRAF V600E -positive papillary thyroid carcinoma. Thyroid. 2012;22(6):585–9. 10.1089/thy.2011.0274 . Kwak JY, Kim EK, Chung WY, Moon HJ, Kim MJ, Choi JR. Association of BRAF V600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology. 2009;253(3):854–60. 10.1148/radiol.2533090471 . Elm EV, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335(7624):806–8. 10.1136/bmj.39335.541782.AD . Coca-Pelaz A, Shah JP, Hernandez-Prera JC, Ghossein RA, Rodrigo JP, Hartl DM, et al. Papillary Thyroid Cancer—Aggressive Variants and Impact on Management: A Narrative Review. Adv Ther. 2020;37(7):3112–28. 10.1007/s12325-020-01391-1 . Haldane JBS. The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956;20(4):309–11. 10.1111/j.1469-1809.1955.tb01285.x . Anscombe FJ. On estimating binomial response relations. Biometrika. 1956;43(3–4):461–4. 10.1093/biomet/43.3-4.461 . Wilcoxon F. Individual comparisons by ranking methods. Biom Bull. 1945;1(6):80–3. 10.2307/3001968 . Hodges JL, Lehmann EL. Estimates of location based on rank tests. Ann Math Stat. 1963;34(2):598–611. 10.1214/aoms/1177704172 . Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol. 1995;57(1):289–300. 10.1111/j.2517-6161.1995.tb02031.x . Firth D. Bias reduction of maximum likelihood estimates. Biometrika. 1993;80(1):27–38. 10.1093/biomet/80.1.27 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 09 May, 2026 Reviewers invited by journal 14 Apr, 2026 Editor assigned by journal 11 Apr, 2026 Submission checks completed at journal 11 Apr, 2026 First submitted to journal 09 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9366720","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625448184,"identity":"a6da8487-96f4-4722-853f-ebaeb803f614","order_by":0,"name":"Dehao Wang","email":"","orcid":"","institution":"School of Medicine, Shandong First Medical University, Jinan, Shandong, China","correspondingAuthor":false,"prefix":"","firstName":"Dehao","middleName":"","lastName":"Wang","suffix":""},{"id":625448185,"identity":"ed5271fa-177d-4b4e-b989-6158b343fb58","order_by":1,"name":"Hailin Sun","email":"","orcid":"","institution":"Department of Thyroid, Breast and Hernia Surgery, Liaocheng People's Hospital, Affiliated to Shandong First Medical University, Liaocheng, Shandong, China","correspondingAuthor":false,"prefix":"","firstName":"Hailin","middleName":"","lastName":"Sun","suffix":""},{"id":625448187,"identity":"de17728b-f890-42b7-ba84-e26cb2ae7324","order_by":2,"name":"Zhong Zhuang","email":"","orcid":"","institution":"School of Medicine, Shandong First Medical University, Jinan, Shandong, China","correspondingAuthor":false,"prefix":"","firstName":"Zhong","middleName":"","lastName":"Zhuang","suffix":""},{"id":625448188,"identity":"4146d5c5-6469-45ec-8dda-47bd5231bbad","order_by":3,"name":"Lin Han","email":"","orcid":"","institution":"Department of Pathology, Liaocheng People's Hospital, Affiliated to Shandong First Medical University, Liaocheng, Shandong, China","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Han","suffix":""},{"id":625448189,"identity":"c12ee382-fe4b-474e-98cd-996b9068250f","order_by":4,"name":"Zhaoqing Cui","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYFACxgZmEMUGZD1I+GHDw8/fQLwWZoOPPWkykjMOELaHGUqzSc5gO2xj0JCAXzn/jOTmzwU1NrJ90u0XpHl4zvMYMBxg/PAxB7cWiRuJDcYzjqUZt8mcKTDmsbjNY87cwCw5cxtuLQYSiQ3JPGyHE9skchKSeXhu81g2HGBj5iWg5TDPP4iWwzxs53gMDiQQ1NLYzNsG0pJ+sHEG2wHCWiTOPGxm5u0D+kUih5nhY08yj+SMg814/cLfnv74M883G9n5M9Kf/0j4YWfPz9988MNHPFpggLGBARi8cDYxAKiM/QFRKkfBKBgFo2DkAQD5/VJaWGC5aAAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Thyroid, Breast and Hernia Surgery, Liaocheng People's Hospital, Affiliated to Shandong First Medical University, Liaocheng, Shandong, China","correspondingAuthor":true,"prefix":"","firstName":"Zhaoqing","middleName":"","lastName":"Cui","suffix":""},{"id":625448190,"identity":"0a1c4756-1768-46d3-ad6e-ca83d2c2344d","order_by":5,"name":"Zhen Wu","email":"","orcid":"","institution":"Department of Thyroid, Breast and Hernia Surgery, Liaocheng People's Hospital, Affiliated to Shandong First Medical University, Liaocheng, Shandong, China","correspondingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2026-04-09 09:57:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9366720/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9366720/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107616418,"identity":"3b18d8db-18d3-4458-a30c-14962abf67f4","added_by":"auto","created_at":"2026-04-23 09:13:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":90371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSTROBE flowchart of patient selection.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9366720/v1/e67e1eb3cf68df765bfd667c.png"},{"id":107616420,"identity":"5804862c-a81d-43cb-b732-7a401ff67124","added_by":"auto","created_at":"2026-04-23 09:13:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":553678,"visible":true,"origin":"","legend":"\u003cp\u003eA. Forest plot showing unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for binary preoperative ultrasonographic features in the High-MRG group relative to the Low-MRG group. The dashed vertical line indicates OR = 1, and the x-axis is shown on a logarithmic scale. Values greater than 1 indicate that the feature was more common in the High-MRG group. An asterisk (*) indicates q value \u0026lt; 0.05 after BH-FDR correction.\u003c/p\u003e\n\u003cp\u003eB. Violin plots comparing the distributions of the two continuous preoperative ultrasonographic features shown in this study. Embedded boxplots indicate the median and interquartile range for each group.\u003c/p\u003e\n\u003cp\u003eC. Forest plot showing unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for binary postoperative pathological features in the High-MRG group relative to the Low-MRG group. The dashed vertical line indicates OR = 1, and the x-axis is shown on a logarithmic scale. Values greater than 1 indicate that the feature was more common in the High-MRG group. An asterisk (*) indicates q value \u0026lt; 0.05 after BH-FDR correction.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9366720/v1/f4f49ad66ec8788a0c3b7418.png"},{"id":107616419,"identity":"c976d584-9fc7-4a2c-a7d3-96da780a748f","added_by":"auto","created_at":"2026-04-23 09:13:17","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":232445,"visible":true,"origin":"","legend":"\u003cp\u003eA. Comparison of unadjusted ORs from Fisher's exact test and adjusted ORs from size-adjusted Firth penalized-likelihood logistic regression for binary preoperative ultrasonographic features. Triangles represent unadjusted ORs from Fisher's exact test, circles represent adjusted ORs from Firth penalized-likelihood logistic regression, and horizontal lines indicate 95% confidence intervals. The dashed vertical line indicates OR = 1, and the x-axis is shown on a logarithmic scale.\u003c/p\u003e\n\u003cp\u003eB. Comparison of unadjusted ORs from Fisher's exact test and adjusted ORs from size-adjusted Firth penalized-likelihood logistic regression for binary postoperative pathological features. Triangles represent unadjusted ORs from Fisher's exact test, circles represent adjusted ORs from Firth penalized-likelihood logistic regression, and horizontal lines indicate 95% confidence intervals. The dashed vertical line indicates OR = 1, and the x-axis is shown on a logarithmic scale.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9366720/v1/bca6e5ff20e3815843d3a37d.png"},{"id":107707187,"identity":"b147277c-9530-477e-aa15-8a55ae12340d","added_by":"auto","created_at":"2026-04-24 09:19:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1354411,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9366720/v1/72c16e55-9e28-494b-b2b8-23a1abb2a91a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of a postoperative multigene-based grouping with ultrasonographic and pathological features in papillary thyroid carcinoma: a single-center retrospective study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePapillary thyroid carcinoma (PTC) is the most common thyroid malignancy and generally has a favorable prognosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Nevertheless, a subset of tumors shows more aggressive behavior, including larger primary size, extrathyroidal extension, aggressive histological subtypes, and heavier nodal metastatic burden. Understanding how molecular abnormalities relate to preoperative ultrasonographic features and postoperative pathological features remains clinically relevant, particularly for hypothesis generation in risk-oriented diagnostic research.\u003c/p\u003e \u003cp\u003eMolecular testing has expanded the characterization of PTC beyond conventional histopathology. Common driver events such as \u003cem\u003eBRAF\u003c/em\u003e V600E, RAS-family mutations, and \u003cem\u003eRET\u003c/em\u003e/NTRK fusions define biologically distinct subgroups [\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Additional alterations, including \u003cem\u003eTERT\u003c/em\u003e promoter mutations, co-occurring driver events, and abnormalities involving the \u003cem\u003eTP53\u003c/em\u003e/PI3K-AKT pathway, have been more frequently associated with tumor progression and dedifferentiation [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, isolated molecular events may not fully capture the biological complexity of PTC, especially in clinical specimens with heterogeneous multigene profiles.\u003c/p\u003e \u003cp\u003eMost previous clinicopathological association studies have evaluated single-gene alterations or selected two-gene combinations, such as \u003cem\u003eBRAF\u003c/em\u003e V600E alone or \u003cem\u003eBRAF\u003c/em\u003e-\u003cem\u003eTERT\u003c/em\u003e co-mutation [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. By contrast, the relationship between a pragmatic multigene-based grouping and preoperative ultrasonographic features or postoperative pathological features has been less systematically examined. An exploratory assessment of such a grouping may help identify clinically recognizable patterns while acknowledging that it is not a mature molecular stratification system.\u003c/p\u003e \u003cp\u003eIn this single-center retrospective study, we evaluated whether a postoperative multigene-based grouping (hereafter, the MRG grouping) was associated with preoperative ultrasonographic and postoperative pathological features in PTC.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design\u003c/h2\u003e \u003cp\u003eThis single-center retrospective observational study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Ethical approval and the informed-consent waiver are described in the Declarations section.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study population: inclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eWe retrospectively screened all consecutive eligible patients who underwent thyroid surgery at Liaocheng People's Hospital, Affiliated to Shandong First Medical University between April and December 2025. No formal sample size calculation was performed because this was a retrospective study, and all eligible cases during the prespecified study period were included.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were as follows:\u003c/p\u003e \u003cp\u003e(1) preoperative fine-needle aspiration (FNA) cytology suggesting malignancy or suspicion for malignancy, with surgery planned;\u003c/p\u003e \u003cp\u003e(2) postoperative pathological confirmation of papillary thyroid carcinoma (PTC);\u003c/p\u003e \u003cp\u003e(3) multigene testing performed on postoperative formalin-fixed paraffin-embedded (FFPE) surgical specimens;\u003c/p\u003e \u003cp\u003e(4) cervical ultrasonography performed at Liaocheng People's Hospital, Affiliated to Shandong First Medical University within 1 month before surgery, with complete reports and clear imaging records available; and\u003c/p\u003e \u003cp\u003e(5) no prior history of thyroid surgery.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows:\u003c/p\u003e \u003cp\u003e(1) other histological types of thyroid carcinoma;\u003c/p\u003e \u003cp\u003e(2) reoperation cases; and\u003c/p\u003e \u003cp\u003e(3) key variables missing and not retrievable from the electronic medical record, imaging archive, or pathology information system.\u003c/p\u003e \u003cp\u003eA total of 92 patients were initially screened. After exclusion of patients with missing essential ultrasonographic reports (n\u0026thinsp;=\u0026thinsp;7) and those with other pathological subtypes (n\u0026thinsp;=\u0026thinsp;6), 79 patients were included in the final analytic cohort.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Surgical management and lymph node handling\u003c/h2\u003e \u003cp\u003eAll patients underwent central neck lymph node dissection during the index operation, and all dissected nodes were submitted for pathological examination. Lateral neck dissection was performed selectively according to preoperative imaging findings or intraoperative assessment. Because this was a surgically treated cohort with postoperative molecular testing, its postoperative pathological profile may differ from that of the broader PTC population. Accordingly, lymph node burden-related variables, including the total number of positive lymph nodes and the lymph node ratio (LNR), were interpreted as postoperative pathological measures that may also reflect the extent of dissection and the number of submitted nodes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Molecular testing and postoperative multigene-based grouping (MRG)\u003c/h2\u003e \u003cp\u003eMRG was determined from molecular testing results obtained from postoperative FFPE specimens. Preoperative FNA specimens were used only for cytological diagnosis and were not incorporated into the MRG grouping. Molecular testing was performed using real-time quantitative polymerase chain reaction (qPCR) on an ABI 7500 real-time PCR platform with assay kits supplied by Shanghai Ruijing Biotechnology Co., Ltd., including the BRAF/TERT/CCDC6-RET Mutation Detection Kit and the Thyroid Multigene Detection Kit. The panel covered \u003cem\u003eBRAF\u003c/em\u003e V600E and \u003cem\u003eTERT\u003c/em\u003e promoter C228T/C250T mutations; hotspot mutations in the RAS family (\u003cem\u003eNRAS\u003c/em\u003e, \u003cem\u003eHRAS\u003c/em\u003e, and \u003cem\u003eKRAS\u003c/em\u003e), \u003cem\u003eRET\u003c/em\u003e, \u003cem\u003eTP53\u003c/em\u003e, \u003cem\u003ePIK3CA\u003c/em\u003e, and \u003cem\u003eAKT1\u003c/em\u003e; and the fusion variants \u003cem\u003eCCDC6\u003c/em\u003e::\u003cem\u003eRET\u003c/em\u003e, \u003cem\u003eNCOA4\u003c/em\u003e::\u003cem\u003eRET\u003c/em\u003e, \u003cem\u003eTPM3\u003c/em\u003e::\u003cem\u003eNTRK1\u003c/em\u003e, \u003cem\u003ePAX8\u003c/em\u003e::\u003cem\u003ePPARG\u003c/em\u003e, and \u003cem\u003eETV6\u003c/em\u003e::\u003cem\u003eNTRK3\u003c/em\u003e (12 genes and 16 loci in total, according to the manufacturer's instructions). Assay precision was defined as a coefficient of variation of \u0026le;\u0026thinsp;5% for Ct values, and the reported clinical sensitivity and specificity were 84.3% and 98.3%, respectively. Quality control procedures included positive and negative controls, internal reference gene detection, and dual-review verification.\u003c/p\u003e \u003cp\u003eThe binary MRG grouping used in this study was a pragmatic analytic approach rather than a mature clinical molecular classification system. \u003cem\u003eBRAF\u003c/em\u003e V600E alone is the most common alteration in PTC and, when present in isolation, does not consistently distinguish a clearly higher-risk phenotype [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. By contrast, \u003cem\u003eTERT\u003c/em\u003e promoter mutations, \u003cem\u003eBRAF\u003c/em\u003e-\u003cem\u003eTERT\u003c/em\u003e co-mutations, \u003cem\u003eRET\u003c/em\u003e/NTRK fusions, and alterations involving \u003cem\u003eTP53\u003c/em\u003e, \u003cem\u003ePIK3CA\u003c/em\u003e, or \u003cem\u003eAKT1\u003c/em\u003e have more often been linked to aggressive biological behavior [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients with wild-type results (n\u0026thinsp;=\u0026thinsp;3) or isolated \u003cem\u003eBRAF\u003c/em\u003e V600E mutation (n\u0026thinsp;=\u0026thinsp;61) were classified as Low-MRG, whereas all other detectable molecular alterations were classified as High-MRG (n\u0026thinsp;=\u0026thinsp;15). This binary grouping was chosen because the cohort was small, the non-isolated \u003cem\u003eBRAF\u003c/em\u003e subgroup was molecularly heterogeneous, and individual alteration categories were sparse. Pooling these alterations was intended to improve estimate stability and reduce sparse-data bias. Low-MRG should therefore be interpreted as a relatively lower molecular-risk background rather than as equivalent to clinically low-risk disease. The detailed molecular composition of the High-MRG group is shown in Additional file 1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Clinical data and variable definitions\u003c/h2\u003e \u003cp\u003eClinical, ultrasonographic, and pathological data were extracted from the electronic medical record and pathology information system, including age, sex, tumor size, number of tumor foci, bilateral involvement, Hashimoto\u0026rsquo;s thyroiditis, capsule/extrathyroidal extension-related information, central and lateral lymph node metastasis, and TNM stage. TNM staging was assigned according to the 8th edition of the AJCC staging system (2017).\u003c/p\u003e \u003cp\u003eAggressive histological subtypes were defined as pathologically confirmed tall cell, hobnail, columnar cell, diffuse sclerosing, or solid variants of PTC, whereas classical and follicular variants were classified as non-aggressive [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor interpretive clarity, the analysis focused on three main outcome features: (1) suspicious cervical lymph nodes on preoperative ultrasonography; (2) aggressive histological subtype; and (3) advanced T stage (defined as T3/T4). Extrathyroidal extension-related features and lymph node stage/burden-related features, such as preoperative suspicion of extrathyroidal extension, postoperative pathological extrathyroidal extension, N1b stage, total positive lymph nodes, and lymph node ratio, were analyzed as secondary outcomes because they may be influenced by the extent of dissection and the number of examined nodes.\u003c/p\u003e \u003cp\u003eMaximum tumor diameter on preoperative ultrasonography was recorded as a continuous variable (cm), whereas pathological tumor size\u0026thinsp;\u0026gt;\u0026thinsp;4 cm was treated as a binary postoperative pathological feature. Suspected extrathyroidal extension or capsule-related findings on preoperative ultrasonography were distinguished from pathologically confirmed extrathyroidal extension. For multifocal PTC, the target nodule was defined as the nodule with the highest TI-RADS category; if multiple nodules had the same TI-RADS category, the largest nodule was selected. All other preoperative ultrasonographic features were assigned on the basis of this target nodule. Aspect ratio and taller-than-wide status were both extracted directly from the original ultrasonographic report fields and recorded as separate variables; taller-than-wide status was not recalculated from the numerical aspect ratio. Suspicious cervical lymph nodes on ultrasonography were defined as suspicious lymph nodes in either the central or lateral neck compartment on the ultrasonographic report. TI-RADS classification was based on the original C-TI-RADS categories (3, 4a, 4b, 4c, 5, and 6). In the multi-level TI-RADS analysis, Unknown was retained as a separate category. For binary analysis, high-risk TI-RADS was defined as TI-RADS 4b or higher (4b-6); TI-RADS 4a or lower and Unknown were grouped as non-high-risk to preserve the full cohort, and the proportion of Unknown was reported separately in descriptive statistics.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Missing data handling\u003c/h2\u003e \u003cp\u003eBased on the routine reporting pattern of structured ultrasonographic reports at Liaocheng People's Hospital, Affiliated to Shandong First Medical University, in which some routine negative findings are often left undescribed, the following prespecified missing-data handling rules were applied: (1) structured-report convention-based coding, whereby binary ultrasonographic features not explicitly described in the structured report were coded as absent, consistent with the institutional reporting convention that positive findings are routinely documented whereas negative findings may be omitted; (2) conditional median imputation, whereby missing aspect ratio values (n\u0026thinsp;=\u0026thinsp;14) were imputed according to taller-than-wide status using the corresponding subgroup medians (0.8 for nodules not taller-than-wide and 1.1 for nodules classified as taller-than-wide); (3) label-based imputation, whereby missing TI-RADS values were coded as \"Unknown\"; and (4) retrospective completion, whereby missing lymph node-related variables in the structured system were completed by case-by-case review of pathology reports, and derived indicators (e.g., lymph node ratio) were then generated in a standardized manner. If the pathology report explicitly indicated no lymph node metastasis, the variable was coded as a structural zero. After retrospective completion and uniform recoding, the main inferential analyses were performed on the full cohort (N\u0026thinsp;=\u0026thinsp;79).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Statistical analysis\u003c/h2\u003e \u003cp\u003eAll tests were two-sided. In unadjusted analyses, binary outcomes were compared using Fisher\u0026rsquo;s exact test and reported as ORs with 95% confidence intervals (CIs). If a zero cell occurred in a 2 \u0026times; 2 table, the Haldane\u0026ndash;Anscombe continuity correction (0.5 added to each cell) was used to obtain finite OR estimates [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], whereas P values were still derived from Fisher\u0026rsquo;s exact test. Continuous outcomes were compared using the Wilcoxon rank-sum test [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and effect sizes were reported as HL shifts (High-MRG minus Low-MRG) with 95% CIs [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Multi-level categorical variables were analyzed using the chi-square test or Fisher\u0026rsquo;s exact test, with Cramer\u0026rsquo;s V reported as the effect size.\u003c/p\u003e \u003cp\u003eRaw P values from the univariable analyses were adjusted for multiple comparisons using the Benjamini\u0026ndash;Hochberg false discovery rate (BH-FDR) procedure [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], yielding q values. BH-FDR correction was applied separately within the preoperative ultrasonographic feature domain (15 binary and 2 continuous outcomes; 17 tests) and the postoperative pathological feature domain (12 binary and 2 continuous outcomes; 14 tests). Statistical significance was prespecified at q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05, and figure and table annotations were based on q values. To assess whether observed associations were materially influenced by tumor size, multivariable models included maximum tumor diameter on preoperative ultrasonography as a covariate. Binary outcomes were analyzed using Firth penalized-likelihood logistic regression [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], with aORs, profile-likelihood 95% CIs, and P values reported. Continuous outcomes were analyzed using ordinary least-squares linear regression, with β estimates, 95% CIs, and P values reported. Ordinary least-squares models were used to provide interpretable adjusted mean-difference estimates in this small exploratory cohort, in which more complex count-based models were considered potentially unstable. Outcomes conceptually overlapping with the covariate, including maximum tumor diameter itself and pathological tumor size\u0026thinsp;\u0026gt;\u0026thinsp;4 cm, were not entered into the adjusted models to avoid collinearity. For advanced T stage, because tumor size is itself a defining component of the outcome, adjustment for maximum diameter may constitute part-whole adjustment; the size-adjusted result for this outcome was therefore interpreted cautiously. P values from the multivariable model set were again adjusted using the BH-FDR procedure, applied separately within the size-adjusted preoperative ultrasonographic model set (13 binary and 1 continuous outcome; 14 tests) and the size-adjusted postoperative pathological model set (11 binary and 2 continuous outcomes; 13 tests). The resulting q values were interpreted only within their respective analytic pools rather than mixed across univariable and multivariable analyses. Results with raw P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 but q value\u0026thinsp;\u0026ge;\u0026thinsp;0.05 were described as nominally significant and exploratory rather than as meeting the prespecified threshold. As a sensitivity analysis, the primary univariable associations that reached q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were re-examined using multivariable models additionally adjusted for age and sex, without adjustment for tumor size, to assess potential demographic confounding. BH-FDR correction was applied within each sensitivity-analysis domain (3 tests for preoperative ultrasonographic outcomes and 2 tests for postoperative pathological outcomes). These models were supplementary and did not replace the primary size-adjusted analyses. Given the modest sample size and limited number of High-MRG events, no further covariates were added to these supplementary models in order to preserve model stability in this exploratory setting.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8 Visualization and software\u003c/h2\u003e \u003cp\u003eBinary outcomes were visualized using forest plots on a logarithmic scale, displaying ORs or aORs with 95% CIs. Continuous outcomes were visualized using violin plots overlaid with boxplots to illustrate between-group distributional differences. All statistical analyses and figures were generated in R software (version 4.5.3).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Study population and baseline characteristics\u003c/h2\u003e \u003cp\u003eA total of 92 patients were screened, and 79 patients with PTC were included in the analytic cohort (High-MRG, n\u0026thinsp;=\u0026thinsp;15; Low-MRG, n\u0026thinsp;=\u0026thinsp;64; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the descriptive baseline characteristics of the analytic cohort. Compared with the Low-MRG group, the High-MRG group showed larger preoperative maximum tumor diameter, lower aspect ratio, more suspicious cervical lymph nodes on ultrasonography, higher frequencies of aggressive histological subtype and advanced T stage, and a greater total number of positive lymph nodes. Molecular alterations within the High-MRG group were heterogeneous, as summarized in Supplementary Table S1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics by MRG group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-MRG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow-MRG\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56.00 (32.00\u0026ndash;65.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46.50 (37.00\u0026ndash;55.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum tumor diameter on ultrasonography, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.50 (1.71\u0026ndash;3.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.30 (0.90\u0026ndash;2.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspect ratio (AP/TR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.74 (0.66\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.01 (0.82\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrregular margin on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47 (73.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrocalcifications on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaller-than-wide on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoechogenicity on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e55 (85.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeterogeneous echotexture on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntranodular blood flow on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-risk TI-RADS (\u0026ge;\u0026thinsp;4b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (73.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17 (26.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4b\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21 (32.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (46.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspicious cervical lymph nodes on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspected extrathyroidal extension/capsule-related finding on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBilateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIsthmus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral involvement on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsthmus location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper pole location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower pole location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrathyroidal spread (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAggressive histological subtype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCapsular invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60 (93.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNerve invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological extrathyroidal extension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node metastasis (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60 (93.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1b stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultifocality (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdvanced T stage (T3/T4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological tumor size\u0026thinsp;\u0026gt;\u0026thinsp;4 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node ratio\u0026thinsp;\u0026gt;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (Yes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51 (79.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal positive lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.00 (5.00\u0026ndash;16.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.00 (2.00\u0026ndash;10.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.50 (0.44\u0026ndash;0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.39 (0.25\u0026ndash;0.62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Continuous variables are presented as median (IQR) and categorical variables as n (%). All available cases from the analytic cohort were used for this descriptive table unless otherwise indicated. Inferential comparisons are reported in the subsequent association tables.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Univariable analysis of preoperative ultrasonographic features\u003c/h2\u003e \u003cp\u003eUnivariable associations between MRG and preoperative ultrasonographic features are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. High-MRG was associated with larger maximum tumor diameter on preoperative ultrasonography (HL shift\u0026thinsp;=\u0026thinsp;1.14 cm, 95% CI 0.50 to 1.90; P value\u0026thinsp;\u0026lt;\u0026thinsp;0.001; q value\u0026thinsp;=\u0026thinsp;0.011) and lower aspect ratio (HL shift = -0.24, 95% CI -0.38 to -0.08; P value\u0026thinsp;=\u0026thinsp;0.005; q value\u0026thinsp;=\u0026thinsp;0.031). Among binary features, suspicious cervical lymph nodes on ultrasonography were more common in the High-MRG group (OR\u0026thinsp;=\u0026thinsp;7.37, 95% CI 1.54 to 35.32; P value\u0026thinsp;=\u0026thinsp;0.008; q value\u0026thinsp;=\u0026thinsp;0.034). The overall TI-RADS category distribution was also associated with High-MRG (Cramer's V\u0026thinsp;=\u0026thinsp;0.494; P value\u0026thinsp;=\u0026thinsp;0.003; q value\u0026thinsp;=\u0026thinsp;0.024). This was not necessarily inconsistent with the nonsignificant binary high-risk TI-RADS result, because the multicategory comparison captures finer shifts across category distributions that may be obscured when TI-RADS is dichotomized as 4b or higher versus \u0026lt;4b. Taller-than-wide morphology reached nominal significance at the raw P value threshold (OR\u0026thinsp;=\u0026thinsp;0.22, 95% CI 0.06 to 0.76; P value\u0026thinsp;=\u0026thinsp;0.019) but did not meet the prespecified BH-FDR threshold (q value\u0026thinsp;=\u0026thinsp;0.066). No other preoperative ultrasonographic feature met q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003eA. Forest plot showing unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) for binary preoperative ultrasonographic features in the High-MRG group relative to the Low-MRG group. The dashed vertical line indicates OR\u0026thinsp;=\u0026thinsp;1, and the x-axis is shown on a logarithmic scale. Values greater than 1 indicate that the feature was more common in the High-MRG group. An asterisk (*) indicates q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 after BH-FDR correction.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariable associations between MRG and preoperative ultrasonographic features.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeasure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-MRG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow-MRG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEffect size (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum tumor diameter on ultrasonography, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHL shift (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.50 (1.71\u0026ndash;3.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.30 (0.90\u0026ndash;2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.14 (0.5, 1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS category\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCramer's V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003elevels\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003elevels\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.494\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspect ratio (AP/TR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHL shift (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.74 (0.66\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.01 (0.82\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.24 (-0.38, -0.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspicious cervical lymph nodes on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.37 (1.54, 35.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaller-than-wide on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.22 (0.06, 0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper pole location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.17 (0.01, 3.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower pole location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.25 (0.01, 4.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.775\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeterogeneous echotexture on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.1 (0.53, 8.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.365\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.775\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntranodular blood flow on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.5 (0.48, 4.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.572\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspected extrathyroidal extension/capsule-related finding on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.39 (0.05, 3.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoechogenicity on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (85.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.65 (0.15, 2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrregular margin on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (73.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.45 (0.36, 5.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-risk TI-RADS (\u0026ge;\u0026thinsp;4b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (73.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.44 (0.41, 5.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.762\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCramer's V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003elevels\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003elevels\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrocalcifications on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.9 (0.28, 2.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral involvement on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.93 (0.26, 3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsthmus location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.69 (0.08, 6.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote: This table presents univariable associations between High-MRG and preoperative ultrasonographic features. Binary outcomes are reported as ORs with 95% CIs, and continuous outcomes are presented as median (IQR) in the group columns. When a zero cell occurred in a 2 \u0026times; 2 contingency table, the Haldane\u0026ndash;Anscombe continuity correction (0.5 added to each cell) was applied to obtain finite OR and CI estimates; P values were derived from Fisher\u0026rsquo;s exact test. Continuous outcomes were analyzed using the Wilcoxon rank-sum test, and effect sizes are presented as HL shifts (High-MRG minus Low-MRG) with 95% CIs. q values were obtained using BH-FDR correction within the preoperative ultrasonographic feature domain (15 binary and 2 continuous outcomes; 17 tests in total). Statistical significance was defined as q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Abbreviations: OR, odds ratio; CI, confidence interval; HL, Hodges-Lehmann; BH-FDR, Benjamini\u0026ndash;Hochberg false discovery rate.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Univariable analysis of postoperative pathological features\u003c/h2\u003e \u003cp\u003eUnivariable associations between MRG and postoperative pathological features are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. High-MRG was associated with aggressive histological subtype (OR\u0026thinsp;=\u0026thinsp;6.98, 95% CI 2.03 to 24.02; P value\u0026thinsp;=\u0026thinsp;0.003; q value\u0026thinsp;=\u0026thinsp;0.027) and advanced T stage (OR\u0026thinsp;=\u0026thinsp;5.88, 95% CI 1.77 to 19.52; P value\u0026thinsp;=\u0026thinsp;0.004; q value\u0026thinsp;=\u0026thinsp;0.027). The total number of positive lymph nodes was higher in the High-MRG group in the unadjusted analysis (HL shift\u0026thinsp;=\u0026thinsp;6.00, 95% CI 1 to 12; P value\u0026thinsp;=\u0026thinsp;0.014), but this did not meet the prespecified BH-FDR threshold and therefore remained nominally significant (q value\u0026thinsp;=\u0026thinsp;0.066). No other postoperative pathological feature met q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariable associations between MRG and postoperative pathological features.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeasure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh-MRG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow-MRG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEffect size (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAggressive histological subtype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.98 (2.03, 24.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdvanced T stage (T3/T4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.88 (1.77, 19.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal positive lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHL shift (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.00 (5.00\u0026ndash;16.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.00 (2.00\u0026ndash;10.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (1, 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNerve invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7 (0.76, 9.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHL shift (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.50 (0.44\u0026ndash;0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.39 (0.25\u0026ndash;0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.12 (-0.06, 0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological tumor size\u0026thinsp;\u0026gt;\u0026thinsp;4 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.77 (0.61, 37.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1b stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e29 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.81 (0.58, 5.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.786\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrathyroidal spread (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.96 (0.52, 7.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.451\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.789\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultifocality (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.41 (0.45, 4.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.581\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.49 (0.27, 8.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological extrathyroidal extension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.35 (0.32, 5.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node ratio\u0026thinsp;\u0026gt;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51 (79.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.66 (0.33, 8.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCapsular invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60 (93.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93 (0.1, 9.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node metastasis (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60 (93.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93 (0.1, 9.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote: This table presents univariable associations between High-MRG and postoperative pathological features. Statistical methods were the same as those used in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Continuous outcomes are presented as median (IQR) in the group columns. q values were obtained using BH-FDR correction within the postoperative pathological feature domain (12 binary and 2 continuous outcomes; 14 tests in total). Statistical significance was defined as q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Abbreviations are the same as in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Multivariable analysis with adjustment for tumor size\u003c/h2\u003e \u003cp\u003eTo assess whether the observed associations were attenuated after accounting for tumor size, size-adjusted models were fitted with maximum tumor diameter on preoperative ultrasonography as a covariate (see Methods 2.7). For preoperative ultrasonographic features (Tables\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003eA and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003eB; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003eA), none of the associations met the prespecified BH-FDR threshold after size adjustment. The association between High-MRG and suspicious cervical lymph nodes on ultrasonography remained nominally significant (aOR\u0026thinsp;=\u0026thinsp;5.37, 95% CI 1.38 to 30.15; P value\u0026thinsp;=\u0026thinsp;0.014; q value\u0026thinsp;=\u0026thinsp;0.197), whereas the remaining adjusted ultrasonographic associations were further attenuated.\u003c/p\u003e \u003cp\u003eFor postoperative pathological features (Tables\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e5\u003c/span\u003eA and \u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e5\u003c/span\u003eB; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003eB), a greater total number of positive lymph nodes remained associated with High-MRG after size adjustment (β\u0026thinsp;=\u0026thinsp;7.065, 95% CI 2.872 to 11.257; P value\u0026thinsp;=\u0026thinsp;0.001; q value\u0026thinsp;=\u0026thinsp;0.019). The association with aggressive histological subtype remained nominally significant (aOR\u0026thinsp;=\u0026thinsp;5.25, 95% CI 1.49 to 19.39; P value\u0026thinsp;=\u0026thinsp;0.010; q value\u0026thinsp;=\u0026thinsp;0.065), whereas the association with advanced T stage was attenuated after adjustment (aOR\u0026thinsp;=\u0026thinsp;2.69, 95% CI 0.68 to 10.38; P value\u0026thinsp;=\u0026thinsp;0.156; q value\u0026thinsp;=\u0026thinsp;0.506).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003eA. Comparison of unadjusted ORs from Fisher's exact test and adjusted ORs from size-adjusted Firth penalized-likelihood logistic regression for binary preoperative ultrasonographic features. Triangles represent unadjusted ORs from Fisher's exact test, circles represent adjusted ORs from Firth penalized-likelihood logistic regression, and horizontal lines indicate 95% confidence intervals. The dashed vertical line indicates OR\u0026thinsp;=\u0026thinsp;1, and the x-axis is shown on a logarithmic scale.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eA. Size-adjusted preoperative ultrasonographic features (binary outcomes).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh-MRG (n\u0026thinsp;=\u0026thinsp;15), n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-MRG (n\u0026thinsp;=\u0026thinsp;64), n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspicious cervical lymph nodes on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.37 (1.38, 30.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.197\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower pole location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.16 (0, 1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.656\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper pole location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.21 (0, 2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.216\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeterogeneous echotexture on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.05 (0.56, 9.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspected extrathyroidal extension/capsule-related finding on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.43 (0.04, 2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrregular margin on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (73.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.65 (0.44, 7.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-risk TI-RADS (\u0026ge;\u0026thinsp;4b)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (73.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42 (65.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.57 (0.46, 6.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaller-than-wide on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.65 (0.15, 2.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.563\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.875\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral involvement on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.87 (0.22, 3.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsthmus location on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.25 (0.11, 8.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.838\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntranodular blood flow on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.09 (0.32, 3.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrocalcifications on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.95 (0.29, 3.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.937\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoechogenicity on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55 (85.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.06 (0.25, 5.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eB. Size-adjusted preoperative ultrasonographic features (continuous outcomes).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh-MRG (n\u0026thinsp;=\u0026thinsp;15), median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-MRG (n\u0026thinsp;=\u0026thinsp;64), median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted β (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspect ratio (AP/TR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.74 (0.66\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.82\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.115 (-0.256, 0.026)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.656\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: These models were used to assess whether the observed associations were attenuated after adjustment for tumor size. All models were adjusted for maximum tumor diameter on preoperative ultrasonography. Binary outcomes were analyzed using Firth penalized-likelihood logistic regression with profile-likelihood 95% CIs, and continuous outcomes were analyzed using ordinary least-squares linear regression. q values were obtained using BH-FDR correction within the size-adjusted preoperative ultrasonographic model set (13 binary and 1 continuous outcome; 14 tests in total). Statistical significance was defined as q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; BH-FDR, Benjamini\u0026ndash;Hochberg false discovery rate.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eA. Size-adjusted postoperative pathological features (binary outcomes).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh-MRG (n\u0026thinsp;=\u0026thinsp;15), n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-MRG (n\u0026thinsp;=\u0026thinsp;64), n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAggressive histological subtype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.25 (1.49, 19.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdvanced T stage (T3/T4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.69 (0.68, 10.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNerve invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.87 (0.47, 6.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrathyroidal spread (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.79 (0.42, 6.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultifocality (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.56 (0.48, 5.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node ratio\u0026thinsp;\u0026gt;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51 (79.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.64 (0.38, 9.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological extrathyroidal extension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63 (0.11, 2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.6 (0.24, 8.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.599\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN1b stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.21 (0.35, 4.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.758\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCapsular invasion (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (93.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.73 (0.09, 8.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.774\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node metastasis (pathology)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (93.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.11 (0.16, 12.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.918\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.918\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eB. Size-adjusted postoperative pathological features (continuous outcomes).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh-MRG (n\u0026thinsp;=\u0026thinsp;15), median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow-MRG (n\u0026thinsp;=\u0026thinsp;64), median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted β (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal positive lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.00 (5.00\u0026ndash;16.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.00 (2.00\u0026ndash;10.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.065 (2.872, 11.257)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.50 (0.44\u0026ndash;0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.39 (0.25\u0026ndash;0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.133 (-0.038, 0.304)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: As in Tables\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003eA and \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003eB, all models were adjusted for maximum tumor diameter on preoperative ultrasonography; binary outcomes were analyzed using Firth penalized-likelihood logistic regression and continuous outcomes using ordinary least-squares linear regression. For advanced T stage, adjustment for maximum diameter should be interpreted cautiously because tumor size contributes to the stage definition. For continuous postoperative pathological outcomes derived from counts or ratios, the ordinary least-squares estimates should be interpreted as adjusted mean-difference summaries in this exploratory setting rather than as count-model parameters. q values were obtained using BH-FDR correction within the size-adjusted postoperative pathological model set (11 binary and 2 continuous outcomes; 13 tests in total). Statistical significance was defined as q value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Abbreviations are the same as in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Sensitivity analysis with adjustment for age and sex\u003c/h2\u003e \u003cp\u003eIn the age- and sex-adjusted sensitivity analysis, the direction of the main associations was broadly consistent with the unadjusted analyses. Larger maximum tumor diameter, lower aspect ratio, suspicious cervical lymph nodes on ultrasonography, aggressive histological subtype, and advanced T stage remained associated with High-MRG (all q values\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Tables\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e6\u003c/span\u003eA and \u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). These supplementary models assessed potential demographic confounding and did not alter the interpretation of the primary size-adjusted analyses.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eA. Age- and sex-adjusted sensitivity analysis of preoperative ultrasonographic features.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted effect (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaximum tumor diameter on ultrasonography, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.161 (0.516, 1.807)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspect ratio (AP/TR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.235 (-0.375, -0.096)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuspicious cervical lymph nodes on ultrasonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.33 (1.69, 35.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: All models were additionally adjusted for age and sex. q values were calculated using the Benjamini\u0026ndash;Hochberg false discovery rate procedure within the preoperative ultrasonographic sensitivity-analysis domain (3 tests).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eB. Age- and sex-adjusted sensitivity analysis of postoperative pathological features.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted effect (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eq value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAggressive histological subtype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.08 (1.87, 20.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdvanced T stage (T3/T4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.33 (1.71, 17.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: All models were additionally adjusted for age and sex. q values were calculated using the Benjamini\u0026ndash;Hochberg false discovery rate procedure within the postoperative pathological sensitivity-analysis domain (2 tests).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eHigh-MRG was associated with several adverse preoperative ultrasonographic and postoperative pathological features in unadjusted analyses. After adjustment for tumor size, however, the three main outcome features of suspicious cervical lymph nodes on ultrasonography, aggressive histological subtype, and advanced T stage were attenuated and no longer met the prespecified BH-FDR threshold, suggesting that tumor size may partly explain these associations.\u003c/p\u003e \u003cp\u003eThe association that persisted after size adjustment involved a greater total number of positive lymph nodes (β\u0026thinsp;=\u0026thinsp;7.065; q value\u0026thinsp;=\u0026thinsp;0.019), a postoperative pathological measure reflecting metastatic lymph node burden. This direction is consistent with prior literature linking higher-risk molecular alterations, particularly \u003cem\u003eBRAF\u003c/em\u003e-\u003cem\u003eTERT\u003c/em\u003e co-mutation and selected fusion or pathway alterations, with more aggressive clinicopathological behavior [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Because the total number of positive lymph nodes can also be influenced by surgical extent and the number of examined nodes, this finding should be interpreted within the context of this surgically treated cohort.\u003c/p\u003e \u003cp\u003eIn the present cohort, the High-MRG group was composed predominantly of cases with concurrent BRAF V600E and TERT promoter alterations. The observed associations may therefore largely reflect the clinicopathological behavior of this subgroup rather than a uniform effect across all higher-risk molecular events pooled into the binary MRG grouping. Because individual non-isolated BRAF alteration categories were sparse, separate subgroup analyses were not considered sufficiently stable. Accordingly, the current findings support the analytic utility of this pragmatic grouping while not implying equivalent effects across all component alterations.\u003c/p\u003e \u003cp\u003eThe attenuation of associations with suspicious cervical lymph nodes and aggressive histological subtype after size adjustment is clinically relevant. Rather than supporting a strong size-independent effect, the data suggest that High-MRG may cluster with a broader aggressive presentation in which tumor size is an important component. The lower aspect ratio in the High-MRG group, together with the concordant direction of the taller-than-wide analysis, may likewise reflect tumor size, because larger tumors may expand more in the transverse plane. The discordance between the significant overall TI-RADS category distribution and the nonsignificant binary high-risk TI-RADS result may similarly reflect information loss from dichotomization. For advanced T stage, interpretation after size adjustment remains particularly cautious because maximum diameter contributes to the stage definition.\u003c/p\u003e \u003cp\u003eThis study extends prior work that mainly evaluated single-gene events or selected two-gene combinations by examining a multigene grouping in relation to both preoperative ultrasonographic and postoperative pathological features. This framework may aid pattern recognition, but it reduces molecular resolution and cannot identify which specific alterations drive the observed associations.\u003c/p\u003e \u003cp\u003eSeveral limitations should be considered. This was a single-center retrospective study with a small, imbalanced cohort and no independent validation set. Molecular testing was performed on postoperative FFPE specimens rather than preoperative FNA samples, limiting direct inference about preoperative decision-making. The binary High-MRG/Low-MRG grouping reduced sparse-data bias but sacrificed molecular granularity by pooling heterogeneous alterations. Because the cohort was surgically treated and had a high prevalence of nodal disease, lymph node burden-related outcomes may also reflect the extent of central and especially lateral neck dissection and the number of examined nodes. Missing ultrasonographic variables were handled using prespecified recoding and conditional imputation rules, which may have introduced misclassification and reduced variability in some derived ultrasonographic measures, particularly aspect ratio. Continuous postoperative pathological outcomes derived from counts or ratios were summarized using ordinary least-squares models for interpretive simplicity; alternative count-based modeling may be preferable in larger validation cohorts.\u003c/p\u003e \u003cp\u003eOverall, the size-adjusted analyses suggest that tumor size accounts for part of the association between High-MRG and adverse clinicopathological features, whereas the residual association with the total number of positive lymph nodes warrants further study.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eHigh-MRG was associated with adverse preoperative ultrasonographic and postoperative pathological features, but many associations weakened after adjustment for tumor size. The most consistent size-adjusted finding was a greater total number of positive lymph nodes. Confirmation in larger multicenter cohorts is needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAJCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican Joint Committee on Cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eadjusted odds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBH-FDR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBenjamini\u0026ndash;Hochberg false discovery rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFFPE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eformalin-fixed paraffin-embedded\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFNA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efine-needle aspiration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHodges-Lehmann\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLNR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elymph node ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epostoperative multigene-based grouping\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epapillary thyroid carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eqPCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003equantitative polymerase chain reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTROBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTI-RADS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThyroid Imaging Reporting and Data System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewild type.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eThe study protocol was approved by the Ethics Committee of Liaocheng People\u0026apos;s Hospital, Affiliated to Shandong First Medical University (Approval No. 2025148). Because this retrospective study used de-identified data generated during routine clinical care and involved no additional intervention, the requirement for informed consent was waived by the Ethics Committee. Clinical trial number: not applicable.\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch3\u003eAvailability of data and materials\u003c/h3\u003e\n\u003cp\u003eThe datasets analyzed during the current study are not publicly available because they contain potentially identifiable clinical information. De-identified data may be available from the corresponding author on reasonable request, subject to institutional approval and applicable ethical and privacy requirements.\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis work was supported by the Key Medical and Health Science and Technology Program of Shandong Province (Grant No. 202404011050) and the Liaocheng Key Research and Development Program (Policy-Guided Category) (Project No. 2024YD16).\u003c/p\u003e\n\u003ch3\u003eAuthors\u0026rsquo; contributions\u003c/h3\u003e\n\u003cp\u003eDW conceived the study, performed the formal analysis, and drafted the manuscript. HS and ZZ collected and curated the data. LH contributed to pathological assessment and data interpretation. ZC and ZW supervised the study and critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet. 2016;388(10061):2783\u0026ndash;95. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(16)30172-6\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(16)30172-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1\u0026ndash;133. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/thy.2015.0020\u003c/span\u003e\u003cspan address=\"10.1089/thy.2015.0020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007;28(7):742\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/er.2007-0007\u003c/span\u003e\u003cspan address=\"10.1210/er.2007-0007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrendo.2011.142\u003c/span\u003e\u003cspan address=\"10.1038/nrendo.2011.142\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSantoro M, Melillo RM, Fusco A. RET/PTC activation in papillary thyroid carcinoma: european journal of endocrinology prize lecture. Eur J Endocrinol. 2006;155(5):645\u0026ndash;53. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1530/eje.1.02289\u003c/span\u003e\u003cspan address=\"10.1530/eje.1.02289\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731\u0026ndash;47. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41571-018-0113-0\u003c/span\u003e\u003cspan address=\"10.1038/s41571-018-0113-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgrawal N, Akbani R, Aksoy BA, Ally A, Arachchi H, Asa SL, et al. Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell. 2014;159(3):676\u0026ndash;90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cell.2014.09.050\u003c/span\u003e\u003cspan address=\"10.1016/j.cell.2014.09.050\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer. 2016;23(3):R143\u0026ndash;55. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1530/ERC-15-0533\u003c/span\u003e\u003cspan address=\"10.1530/ERC-15-0533\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, et al. \u003cem\u003eBRAF\u003c/em\u003e V600E and \u003cem\u003eTERT\u003c/em\u003e promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014;32(25):2718\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.2014.55.5094\u003c/span\u003e\u003cspan address=\"10.1200/JCO.2014.55.5094\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, et al. \u003cem\u003eTERT\u003c/em\u003e promoter mutations and their association with \u003cem\u003eBRAF\u003c/em\u003e V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab. 2014;99(6):E1130\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/jc.2013-4048\u003c/span\u003e\u003cspan address=\"10.1210/jc.2013-4048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLanda I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016;126(3):1052\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/JCI85271\u003c/span\u003e\u003cspan address=\"10.1172/JCI85271\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHou P, Liu D, Shan Y, Hu S, Studeman K, Condouris S, et al. Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer. Clin Cancer Res. 2007;13(4):1161\u0026ndash;70. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1158/1078-0432.CCR-06-1125\u003c/span\u003e\u003cspan address=\"10.1158/1078-0432.CCR-06-1125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKabaker AS, Tublin ME, Nikiforov YE, Armstrong MJ, Hodak SP, Stang MT, et al. Suspicious ultrasound characteristics predict \u003cem\u003eBRAF\u003c/em\u003e \u003csup\u003eV600E\u003c/sup\u003e-positive papillary thyroid carcinoma. Thyroid. 2012;22(6):585\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1089/thy.2011.0274\u003c/span\u003e\u003cspan address=\"10.1089/thy.2011.0274\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwak JY, Kim EK, Chung WY, Moon HJ, Kim MJ, Choi JR. Association of BRAF\u003csup\u003eV600E\u003c/sup\u003e mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma. Radiology. 2009;253(3):854\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1148/radiol.2533090471\u003c/span\u003e\u003cspan address=\"10.1148/radiol.2533090471\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElm EV, Altman DG, Egger M, Pocock SJ, G\u0026oslash;tzsche PC, Vandenbroucke JP. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335(7624):806\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.39335.541782.AD\u003c/span\u003e\u003cspan address=\"10.1136/bmj.39335.541782.AD\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoca-Pelaz A, Shah JP, Hernandez-Prera JC, Ghossein RA, Rodrigo JP, Hartl DM, et al. Papillary Thyroid Cancer\u0026mdash;Aggressive Variants and Impact on Management: A Narrative Review. Adv Ther. 2020;37(7):3112\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12325-020-01391-1\u003c/span\u003e\u003cspan address=\"10.1007/s12325-020-01391-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaldane JBS. The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956;20(4):309\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1469-1809.1955.tb01285.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1469-1809.1955.tb01285.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnscombe FJ. On estimating binomial response relations. Biometrika. 1956;43(3\u0026ndash;4):461\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/biomet/43.3-4.461\u003c/span\u003e\u003cspan address=\"10.1093/biomet/43.3-4.461\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilcoxon F. Individual comparisons by ranking methods. Biom Bull. 1945;1(6):80\u0026ndash;3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2307/3001968\u003c/span\u003e\u003cspan address=\"10.2307/3001968\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHodges JL, Lehmann EL. Estimates of location based on rank tests. Ann Math Stat. 1963;34(2):598\u0026ndash;611. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1214/aoms/1177704172\u003c/span\u003e\u003cspan address=\"10.1214/aoms/1177704172\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol. 1995;57(1):289\u0026ndash;300. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.2517-6161.1995.tb02031.x\u003c/span\u003e\u003cspan address=\"10.1111/j.2517-6161.1995.tb02031.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFirth D. Bias reduction of maximum likelihood estimates. Biometrika. 1993;80(1):27\u0026ndash;38. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/biomet/80.1.27\u003c/span\u003e\u003cspan address=\"10.1093/biomet/80.1.27\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"papillary thyroid carcinoma, multigene-based grouping, ultrasonographic features, pathological features, thyroid molecular testing, lymph node metastasis","lastPublishedDoi":"10.21203/rs.3.rs-9366720/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9366720/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMost molecular association studies in papillary thyroid carcinoma (PTC) have focused on single-gene events or selected co-mutations. Whether a pragmatic multigene-based grouping is associated with preoperative ultrasonographic features and postoperative pathological features remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively included patients who underwent thyroidectomy for pathologically confirmed PTC at a single center between April and December 2025. Multigene testing was performed on postoperative FFPE specimens. Using a postoperative FFPE-based grouping approach defined by multigene results, patients with wild-type results or isolated BRAF V600E were grouped as Low-MRG, and all others as High-MRG. Univariable analyses used Fisher's exact test and the Wilcoxon rank-sum test. Size-adjusted models included maximum tumor diameter on preoperative ultrasonography and used Firth penalized-likelihood logistic regression or ordinary least-squares linear regression. Benjamini\u0026ndash;Hochberg false discovery rate correction was applied.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSeventy-nine patients were included (High-MRG, n\u0026thinsp;=\u0026thinsp;15; Low-MRG, n\u0026thinsp;=\u0026thinsp;64). In unadjusted analyses, High-MRG was associated with larger maximum tumor diameter on ultrasonography (median 2.50 vs. 1.30 cm; q value\u0026thinsp;=\u0026thinsp;0.011), lower aspect ratio (0.74 vs. 1.01; q value\u0026thinsp;=\u0026thinsp;0.031), suspicious cervical lymph nodes on ultrasonography (86.7% vs. 46.9%; OR\u0026thinsp;=\u0026thinsp;7.37; q value\u0026thinsp;=\u0026thinsp;0.034), aggressive histological subtypes (53.3% vs. 14.1%; OR\u0026thinsp;=\u0026thinsp;6.98; q value\u0026thinsp;=\u0026thinsp;0.027), and advanced T stage (60.0% vs. 20.3%; OR\u0026thinsp;=\u0026thinsp;5.88; q value\u0026thinsp;=\u0026thinsp;0.027). After adjustment for maximum tumor diameter, associations with suspicious cervical lymph nodes on ultrasonography, aggressive histological subtypes, and advanced T stage were attenuated. A greater total number of positive lymph nodes remained associated with High-MRG after size adjustment (β\u0026thinsp;=\u0026thinsp;7.065; q value\u0026thinsp;=\u0026thinsp;0.019).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this exploratory postoperative FFPE-based grouping approach, High-MRG was associated with adverse preoperative ultrasonographic and postoperative pathological features, but most associations were attenuated after adjustment for tumor size. The most stable size-adjusted finding was a greater total number of positive lymph nodes. Further evaluation in larger multicenter cohorts, ideally using preoperative FNA specimens, is needed.\u003c/p\u003e","manuscriptTitle":"Association of a postoperative multigene-based grouping with ultrasonographic and pathological features in papillary thyroid carcinoma: a single-center retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 09:13:10","doi":"10.21203/rs.3.rs-9366720/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"109069249386762328568462960712847125743","date":"2026-05-09T04:41:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T17:24:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-11T05:28:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-11T05:28:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2026-04-09T09:40:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e78270a3-a439-4d7b-97f8-865bd9fb9f21","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"109069249386762328568462960712847125743","date":"2026-05-09T04:41:16+00:00","index":140,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T09:13:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 09:13:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9366720","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9366720","identity":"rs-9366720","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}