RET alterations, including RET fusions and RET mutations, have been identified in thyroid cancer. RET fusions are predominantly found in papillary thyroid carcinoma, whereas RET mutations are primarily associated with medullary thyroid carcinoma. Consequently, RET has emerged as an attractive therapeutic target. Previously, multikinase inhibitors, such as vandetanib and cabozantinib, were primarily used for treatment; however, their efficacy was limited due to off-target effects. Recently, selective tyrosine kinase inhibitors, including selpercatinib and pralsetinib, have been introduced, demonstrating improved selectivity and clinical efficacy. Nevertheless, challenges such as gatekeeper and solvent-front mutations have emerged, contributing to acquired drug resistance. To address this issue, next-generation RET inhibitors, including zeteletinib and SYHA1815, are currently under investigation, reflecting an expanding therapeutic landscape. This article provides an overview of the molecular mechanisms of RET alterations in thyroid cancer, targeted therapies, and emerging resistance to targeted treatment.

BACKGROUND:To comprehensively investigate the relationship between common genetic alterations and tumor recurrence in patients with papillary thyroid cancer (PTC) and evaluate whether integrating genetic status could improve the performance of the 2025 American Thyroid Association (ATA) tumor recurrence risk stratification system (RSS). METHODS:This retrospective study included 2,056 patients (1,414 females and 642 males) with a median age of 39 years [interquartile range (IQR), 31-50 years] and a median follow-up time of 25 months (IQR, 13-35 months) who were treated for PTC at three medical centers in China between 2020 and 2024. RESULTS:Tumor recurrence rates were significantly higher in patients carrying RET fusions alone or genetic alteration combination, but not in patients carrying BRAF V600E alone, RAS mutations alone, or NTRK fusions alone, than that in patients without any genetic alteration, with an HR of 2.64 (95% CI, 1.31-5.32) and 3.37 (95% CI, 1.21-9.35) after adjusted for clinicopathological factors, respectively. RET fusions or genetic alteration combination were significantly associated with increased risk of tumor recurrence in all the ATA RSS categories, with an adjusted HR of 14.02 (95% CI, 3.75-52.48) in patients with ATA RSS low or low-intermediate categories, an HR of 3.01 (95% CI, 1.51-5.99) in the intermediate-high category, and an HR of 3.75 (95% CI, 2.17-6.48) in the high category, respectively. CONCLUSION:RET fusions and genetic alteration combination are independent prognostic markers for tumor recurrence of PTC, integrating tumors' genetic status into the 2025 ATA RSS system improves the accuracy of risk stratification for PTC.

BACKGROUND:Inflammation is an important pathogenic factor that leads to thyroid follicular epithelial cells injury after Hashimoto's thyroiditis (HT). Recent studies proposed relationships between pyroptosis and apolipoproteins in HT. However, the molecular signatures involved in the pathophysiological changes that occur during the course of HT remain ambiguous. METHODS:The current study obtained thyroid tissues from HT patients and investigated the genes and pathways involved in HT by transcriptome sequencing analysis. Besides, ELISA, immunohistochemical staining, western blot analysis, LDH release assay and RNA interference were conducted to validate the expression levels of dysregulated proteins and underlying pathways. RESULTS:Transcriptomic analysis demonstrated that HT was associated with the enrichment of genes related to the inflammatory response, pyroptosis, and regulation of the lipid metabolic process. The transcription level of APOC1 gene ranked highest among apolipoproteins, and genes associated with the interleukin (IL)-18 signaling pathway and the NLRP3 inflammasome were upregulated. The expression levels of IL-18, NLRP3, and APOC1 proteins were increased in HT patients. Furthermore, in vitro studies using LPS-treated Nthy-ori 3-1 thyroid cells confirmed that APOC1 induced pyroptosis through TLR10/MyD88/NF-κB p65 dependent pathway. CONCLUSIONS:APOC1 probably participated in the pathogenesis of HT by mediating TFCs pyroptosis through TLR10/MyD88/NF-κB pathway.

Background: Identifying parathyroid glands during surgery is challenging. Recent studies suggest that near-infrared autofluorescence (NIRAF) detection can improve their recognition. However, the correlation between positive NIRAF detection and clinical features in parathyroidectomy remains unclear. This study aimed to explore correlation between positive NIRAF detection and clinical features in parathyroid surgery, aiming to improve the application of this technology. Methods: Prospective data were collected from patients undergoing parathyroidectomy using handheld NIRAF devices. Data included the ratio of parathyroid NIRAF to baseline, and clinical features such as age, gender, body mass index (BMI), parathyroid gland size, preoperative blood calcium, parathyroid hormone levels, and pathological properties. Factors influencing parathyroid autofluorescence intensity were evaluated. Results: From June 2023 to June 2024, 20 primary and 19 secondary hyperparathyroidism patients with 98 parathyroid lesions were analyzed. NIRAF probe detection showed no significant correlation with age, gender, or preoperative serum calcium. However, it was significantly correlated with parathyroid volume, BMI, and pathological properties. Smaller glands, lower BMI, and diffuse parathyroid hyperplasia were more easily detected by near-infrared probes (P<0.01). Conclusions: NIRAF probes improve the accuracy and safety of parathyroidectomy. Positive NIRAF detection is significantly correlated with parathyroid volume, BMI, and pathology, making it particularly useful for patients with smaller BMI, smaller gland volume, and diffuse hyperplasia.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder primarily driven by T cell. The apoptosis of the follicular thyroid cells plays an important role in HT apart from the lymphocyte-mediated cytotoxicity. Advanced oxidation protein products (AOPPs), resulting from oxidative stress, are known to be involved in various inflammatory diseases. However, their role in HT development has not been explored. Here, we discovered that AOPP levels were significantly elevated in thyroid tissues of both HT patients (Ctrl 4.12 +/- 0.56, HT 30.00 +/- 2.78; p < 0.0001) and experimental autoimmune thyroiditis (EAT) mice (Ctrl 8.37 +/- 1.43, HT 55.82 +/- 2.87; p < 0.0001), accompanied by extensive thyroid follicular epithelial cell apoptosis in HT patients (Ctrl 32.16 +/- 1.79, HT 147.10 +/- 13.32; p < 0.0001) and EAT mice (Ctrl 66.78 +/- 6.72, HT 249.10 +/- 9.77; p < 0.0001). In vitro study showed that AOPPs induced reactive oxygen species (ROS) production via nicotinamide adenine dinucleotide phosphate oxidase (NOX), leading to apoptosis in human thyroid follicular epithelial cell (Nthy-ori 3-1). Treatment with apocynin, a NOX inhibitor, reduced AOPP-induced ROS production and apoptosis in Nthy-ori 3-1 cells, and in turn alleviated thyroid follicular epithelial cell apoptosis and autoimmune thyroiditis symptoms in mice. Mechanistically, AOPP treatment activated JNK pathway, leading to the downregulation of Bcl-2, upregulation of Bax, the mitochondrial membrane potential depolarization and consequently triggered the activation of mitochondria-dependent intrinsic apoptosis pathway. Collectively, our findings highlight the promotive roles of AOPP in HT and provide an attractive therapeutic target for HT therapy.

BackgroundThe impact of pectoralis major fascia (PMF) preservation during endoscopic thyroidectomy (ET) via axillary approach on postoperative recovery remains poorly understood. This study aimed to compare the quality of life (QoL) and shoulder function between patients with and without PMF preservation intraoperatively.MethodsA total of 77 patients were enrolled, including 39 cases with the PMF preservation (Group A) and 38 cases without (Group B). Postoperatively QoL and shoulder joint function were assessed at 1month, 3 months, and 6 months using Thyroid Cancer-Specific Quality of Life (THYCA-QoL) questionnaire and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) questionnaire, respectively.ResultsThe median follow-up time was 7.55 ± 1.36 months across all cases. Intraoperatively, Group A exhibited significantly lower total drainage volume than Group B (p <0.001). During postoperative follow-up, while THYCA-QoL scores were comparable at 1 and 6 months, Group A demonstrated superior neuromuscular (p = 0.03), sympathetic (p = 0.01), and sensory (p = 0.01) recovery at 6 months. ASES scores revealed no differences at 1 month, however, by 3 months, Group A achieved higher total scores (p = 0.02). At 6 months, Group A outperformed Group B in total ASES score (p < 0.001), pain (p = 0.04), and function (p < 0.001).ConclusionPreserving the PMF during ET via an axillary approach can improve QoL, reduce bleeding, enhance long-term sensory and shoulder functional recovery, suggesting that the protection of PMF might have a positive impact on the postoperative patient recovery.

Background:Tumor deposits (TDs), nodules in the peritumoral adipose tissue with no architectural residue of lymph node, have previously been described in colorectal adenocarcinomas with poor prognosis. However, the significance of TD has not been fully investigated in patients with papillary thyroid carcinoma (PTC). Method:We retrospectively enrolled 541 patients undergoing surgery between 2015 and 2021. The patients were classified into two groups according to TD status (TD vs non-TD), and the clinicopathologic characteristics and disease-free survival (DFS) were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the primary cohort's prognostic factors for DFS. A nomogram was constructed for clinicians as a quantitative tool for estimating DFS. Result:In our cohort, TD were identified in 16.1% of patients and had higher rate of aggressive features, including microscopic and gross extrathyroidal extension, invasion of the recurrent laryngeal nerve and esophagus, prevertebral fascia involvement or encasement of the carotid artery/internal jugular vein, extranodal extension, advanced clinical stage, tumor recurrence and distant metastasis (all P < 0.05). Univariate and multivariate Cox regression analyses confirmed TD as an independent prognostic factor for DFS, with a 2.501-fold increased risk of recurrence (P < 0.001). The nomogram, incorporating TD and other significant factors, demonstrated good discrimination and calibration (C-index = 0.79). Conclusion:The presence of TD was significantly associated with poor prognosis in PTC patients. TD showed promising efficacy as a potential prognostic indicator for PTC patients.

In a previous study, we proposed a modified technique for gasless transaxillary endoscopic total thyroidectomy (ETT) for patients with bilateral papillary thyroid carcinoma (PTC) using a single incision. Whether this method shows non-inferiority to the conventional open approach (COT) remains unclear. This study aims to investigate the safety and feasibility of ETT compared to COT in patients with PTC. We retrospectively analyzed the medical records of cT1-2 PTC patients who underwent total thyroidectomy between April 2020 and December 2022. All patients were diagnosed with bilateral PTC and categorized into ETT and COT groups based on the type of surgery. Propensity score matching (PSM) using nine clinicopathological characteristics was employed to compare the technical safety and short-term oncologic outcomes of ETT and COT, generating 45 pairs of matched patients to reduce potential selection bias. This study was followed by STROBE guideline. After PSM, 90 patients who underwent ETT (n = 45) or COT (n = 45) were included. Age, sex, tumor size, BMI, Hashimoto’s thyroiditis, multifocality, extrathyroidal extension, T-stage, and central compartment lymph node metastasis were not different between both groups. Both groups showed similar surgical outcomes, including lymph node yield, complications, and total medical costs. A few patients in each group experienced transient complications, all of which resolved within 6 months. No patients had permanent complications. Compared to COT, ETT with a modified technique offers excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with bilateral papillary thyroid carcinoma. ETT is a safe and feasible alternative to COT.

BackgroundCurrent clinicopathological risk factors lack the precision necessary for accurate prediction of central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). Structural remodeling of the tumor microenvironment (TME), particularly collagen organization, may play a pivotal role in metastatic dissemination.ObjectiveThe objective of this study was to develop a collagen signature within the TME to predict CLNM in PTC and validate that the new model incorporating it into the assessment alongside clinicopathological risk factors would enhance the predictive accuracy.MethodsIn this retrospective study, we included 350 patients with classic PTC, all of whom underwent thyroidectomy with prophylactic central lymph node dissection. The cases were randomly assigned to a training cohort and a testing cohort with a 6:4 ratio. A total of 142 collagen features in the TME were extracted from second harmonic generation images of tumor specimens. We constructed a collagen signature using a least absolute shrinkage and selection operator (LASSO) regression model. Multivariate logistic regression was used to integrate the signature with clinicopathological variables and construct a nomogram.ResultsThe predictive ability of collagen signature was also validated by AUC of 0.821 in training cohort and AUC of 0.793 in testing cohort. The collagen signature remained an independent predictor after adjustment for tumor size, capsular invasion, and tumor location in the multivariate analysis. Furthermore, the integrated model showed superior predictive performance compared to the clinicopathological model alone (0.842 vs. 0.679, p < 0.001). Decision curve analysis confirmed higher net clinical benefit across a wide range of thresholds.ConclusionsThe collagen signature within the TME represents a promising new biomarker that can effectively predict CLNM in PTC patients, potentially improving clinical decision-making and patient management.

Figure S1: Thyroglobulin concentrations changes for individual patients with negative thyroglobulin antibody from baseline to the end of cycle 2.

Interdisciplinary MedicineVolume 2, Issue 3 e12116 COVEROpen Access PDE5 Inhibitors Against Cancer Via Mediating Immune Cells in Tumor Microenvironment: AI-Based Approach for Future Drug Repurposing Exploration (3/2024) Zhenzhan Zhang, Zhenzhan ZhangSearch for more papers by this authorDonghua Huang, Donghua HuangSearch for more papers by this authorJunjie Feng, Junjie FengSearch for more papers by this authorWangji Li, Wangji LiSearch for more papers by this authorZhe Wang, Zhe WangSearch for more papers by this authorMengting Lu, Mengting LuSearch for more papers by this authorYangyang Luo, Yangyang LuoSearch for more papers by this authorWeihao Yang, Weihao YangSearch for more papers by this authorZhou Xu, Zhou XuSearch for more papers by this authorQingfeng Xie, Qingfeng XieSearch for more papers by this authorWenfu Ding, Wenfu DingSearch for more papers by this authorXin Tan, Xin TanSearch for more papers by this authorWenjun He, Wenjun HeSearch for more papers by this authorGuoxin Li, Guoxin LiSearch for more papers by this authorHao Liu, Hao LiuSearch for more papers by this authorShangtong Lei, Shangtong LeiSearch for more papers by this author Zhenzhan Zhang, Zhenzhan ZhangSearch for more papers by this authorDonghua Huang, Donghua HuangSearch for more papers by this authorJunjie Feng, Junjie FengSearch for more papers by this authorWangji Li, Wangji LiSearch for more papers by this authorZhe Wang, Zhe WangSearch for more papers by this authorMengting Lu, Mengting LuSearch for more papers by this authorYangyang Luo, Yangyang LuoSearch for more papers by this authorWeihao Yang, Weihao YangSearch for more papers by this authorZhou Xu, Zhou XuSearch for more papers by this authorQingfeng Xie, Qingfeng XieSearch for more papers by this authorWenfu Ding, Wenfu DingSearch for more papers by this authorXin Tan, Xin TanSearch for more papers by this authorWenjun He, Wenjun HeSearch for more papers by this authorGuoxin Li, Guoxin LiSearch for more papers by this authorHao Liu, Hao LiuSearch for more papers by this authorShangtong Lei, Shangtong LeiSearch for more papers by this author First published: 31 July 2024 https://doi.org/10.1002/inmd.12116AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract This review summarized the effects of PDE5 inhibitors on immune cells in the tumor microenvironment (TME). By combining new methods of artificial intelligence (AI), it proposes that AI can explore the drug targets of PDE5 inhibitors on immune cells in the TME and predict pharmacodynamic targets and responses, has significant scientific implications. Volume2, Issue3July 2024e12116 RelatedInformation

BACKGROUND:Anaplastic thyroid cancer (ATC) is the most aggressive thyroid malignancy and has an extremely poor prognosis, necessitating novel therapeutic strategies. This study investigated the role of anillin (ANLN) in ATC, focusing on its impact on tumor growth and metastasis through the RhoA/PI3K/AKT signaling pathway. METHODS:TCGA and GEO datasets were analyzed to identify key molecular alterations in thyroid cancer. ANLN expression was assessed in clinical samples. Functional assays, including CCK-8, colony formation, scratch, and Transwell invasion assays, and mouse xenograft models, were conducted to evaluate the biological role of ANLN. Coimmunoprecipitation, immunofluorescence, and active Rho GTPase pull-down assays, as well as phosphorylation antibody arrays, were used to explore the underlying mechanisms. RESULTS:Analysis of TCGA and GEO datasets revealed that ANLN is upregulated in thyroid cancers, including ATC and PTC, with higher ANLN expression correlating with worse survival outcomes. Functional studies demonstrated that ANLN promoted ATC cell proliferation, migration, and invasion. In vivo, ANLN knockdown inhibited tumor growth in xenograft models. Mechanistically, ANLN directly interacted with RhoA, facilitating its activation and subsequent stimulation of the PI3K/AKT signaling pathway. The tumorigenic effects of ANLN were suppressed by AKT inhibition with afuresertib or RhoA silencing. CONCLUSION:ANLN plays a crucial role in ATC progression by activating the RhoA/PI3K/AKT pathway, suggesting its potential as a therapeutic target in ATC.

Purpose Inflammation is recognized as a hallmark of Hashimoto’s thyroiditis (HT). Although inflammation is an important pathogenic factor that leads to thyroid follicular epithelial cell injury after HT, anti-inflammatory treatments remain controversial in the management of HT. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of HT remain ambiguous.Methods The current study investigated the genes and pathways involved in HT by transcriptome sequencing analysis. Furthermore, western blot assays, ELISA and immunohistochemical staining were conducted to validate the expression levels of dysregulated proteins.Results HT was found to be associated with the enrichment of genes related to the inflammatory response, pyroptosis, and regulation of the lipid metabolic process. Further analysis revealed that genes associated with the interleukin (IL)-18 signaling pathway and the NLRP3 inflammasome were upregulated, and the expression levels of the IL-18, NLRP3, and APOC1 proteins were increased.Conclusion The transcriptome data obtained from HT patient samples revealed notable genes and pathways that may be novel therapeutic targets for the treatment of HT.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients’ clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85–160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3–4.5) days. The median hospitalization expense for these patients was 3848 (3781–4145) USD. The median number of lymph node yielded was 10.5 (8–15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

To develop a nomogram model for predicting contralateral patent processus vaginalis in children with unilateral inguinal hernia or hydrocele. A retrospective analysis was conducted on 259 children with unilateral inguinal hernia or hydrocele who underwent laparoscopic surgery at the Southern Hospital of Southern Medical University from January 2021 to December 2023. The patients were randomly divided into a training set (n = 207) and a validation set (n = 52) in an 8:2 ratio to analyze the characteristics of CPPV. Multivariate logistic regression analysis was used to screen for independent risk factors for CPPV, and a nomogram prediction model was constructed. The predictive ability, calibration, and clinical net benefit of the model were evaluated by plotting receiver operating characteristic (ROC) curves, calibration curves (HL), and clinical decision curves (DCA). Among children under 1 year old, the laparoscopic exploration revealed a CPPV incidence rate of 55.17

Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher’s exact test. A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8

Phosphodiesterase-5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti-cancer agents for cancer management to enhance the anti-tumor immune response by mediating various immune cells, which included the myeloid-derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI-based approach for future drug repurposing exploration.

Objective: To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach. Methods: A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data. Results: All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%). Conclusion: The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients.

Objective To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). Methods This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. Results The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74–27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27–18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. Conclusion Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.

Figure S1: Thyroglobulin concentrations changes for individual patients with negative thyroglobulin antibody from baseline to the end of cycle 2.