Predicting central cervical lymph node metastasis in papillary thyroid microcarcinoma using deep learning.

Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F1 score. Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63). Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions.

Nanoclay Drug-Delivery System Loading Potassium Iodide Promotes Endocytosis and Targeted Therapy in Anaplastic Thyroid Cancer.

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.

Age-based factors modulating the required thyroxine dose to achieve thyrotropin suppression in intermediate-and high-risk papillary thyroid cancer.

Background: Guidelines widely recommend thyrotropin suppression to reduce the risk of recurrence in intermediate- and high-risk papillary thyroid cancer (PTC) after total thyroidectomy. However, an insufficient or excessive dosage may result in a number of symptoms/complications especially in older patients. Patients and methods: We constructed a retrospective cohort including 551 PTC patient encounters. Using propensity score matching and logistic regression models, we determined the independent risk factors affecting levothyroxine therapy at different ages. Our outcomes included: expected TSH level and an unexpected TSH level, which was based on the initial thyroid-stimulating hormone (TSH) goal< 0.1 mIU/L with usual dosage of L-T4 (1.6 µg/kg/day). Results: From our analysis, more than 70% of patients undergoing total thyroidectomy did not achieve the expected TSH level using an empirical medication regimen, and the effect of the drug was affected by age (odds ratio [OR], 1.063; 95% CI, 1.032-1.094), preoperative TSH level (OR, 0.554; 95% CI, 0.436-0.704) and preoperative fT3 level (OR, 0.820; 95% CI, 0.727-0.925). In patients with age < 55 years old, preoperative TSH level (OR, 0.588; 95% CI, 0.459-0.753), and preoperative fT3 level (OR, 0.859; 95% CI, 0.746-0.990) were two independent protective factors, while, in patients with age ≥ 55 years old, only preoperative TSH level (OR, 0.490; 95% CI, 0.278-0.861) was the independent protective factors to achieve expected TSH level. Conclusion: Our retrospective analysis suggested the following significant risk factors of getting TSH suppression in PTC patients: age (≥55 years), lower preoperative TSH and fT3 levels.

Zonotopic set-membership state estimation for multirate systems with dynamic event-triggered mechanisms.

This paper is concerned with the dynamic event-triggered set-membership state estimation issue for a class of multirate networked systems subject to unknown but bounded disturbance and noise. To economize the limited communication resource when performing the desired networked estimation task, a dynamic event-triggered transmission mechanism is proposed to significantly reduce the frequency of sensor data transmissions. A key issue of the addressed problem is to construct a zonotopic outer approximation set to bound the set of states that are consistent with the disturbed system model and the noisy measured outputs. With the help of a prediction-update-correction method, we design a zonotope that is guaranteed to enclose all possible system states due to the unknown disturbance and noise. Then, the size of such a zonotope is minimized by properly designing an introduced correlation matrix at each iteration. Subsequently, the estimation performance is analyzed under the developed zonotopic estimation method. A sufficient condition is further established to ensure the boundedness of the size of the obtained zonotope. Finally, an illustrative example is provided to demonstrate the effectiveness of the proposed method.

Association of Ozone Exposures with the risk of thyroid nodules in Hunan Province: a population-based cohort study.

BACKGROUND: Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear. METHODS: This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants' residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors. RESULTS: In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3-8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels. CONCLUSIONS: High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.

A Prognostic Model of Differentiated Thyroid Cancer Based on Up-Regulated Glycolysis-Related Genes.

Objective: This study aims to identify reliable prognostic biomarkers for differentiated thyroid cancer (DTC) based on glycolysis-related genes (GRGs), and to construct a glycolysis-related gene model for predicting the prognosis of DTC patients. Methods: We retrospectively analyzed the transcriptomic profiles and clinical parameters of 838 thyroid cancer patients from 6 public datasets. Single factor Cox proportional risk regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) were applied to screen genes related to prognosis based on 2528 GRGs. Then, an optimal prognostic model was developed as well as evaluated by Kaplan-Meier and ROC curves. In addition, the underlying molecular mechanisms in different risk subgroups were also explored via The Cancer Genome Atlas (TCGA) Pan-Cancer study. Results: The glycolysis risk score (GRS) outperformed conventional clinicopathological features for recurrence-free survival prediction. The GRS model identified four candidate genes (ADM, MKI67, CD44 and TYMS), and an accurate predictive model of relapse in DTC patients was established that was highly correlated with prognosis (AUC of 0.767). In vitro assays revealed that high expression of those genes increased DTC cancer cell viability and invasion. Functional enrichment analysis indicated that these signature GRGs are involved in remodelling the tumour microenvironment, which has been demonstrated in pan-cancers. Finally, we generated an integrated decision tree and nomogram based on the GRS model and clinicopathological features to optimize risk stratification (AUC of the composite model was 0.815). Conclusions: The GRG signature-based predictive model may help clinicians provide a prognosis for DTC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.

Comprehensive analysis of the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in papillary thyroid cancer.

Purpose: Hashimoto's thyroiditis often leads to reactive hyperplasia of the central compartment lymph nodes in papillary thyroid carcinoma (PTC) patients. However, the effect and clinical significance of Hashimoto's thyroiditis (HT) on ultrasonography evaluation for cervical lymph node (LN) lesions remain unknown. This study aims to investigate the effect of Hashimoto's thyroiditis on the diagnostic efficacy of preoperative ultrasonography on cervical lymph node lesions in PTC patients. Patients and methods: This study consecutively enrolled 1,874 PTC patients who underwent total thyroidectomy and radical cervical lymph node dissection between January 2010 and December 2021. Eligible patients were categorized as with HT and without HT. The diagnostic performance of preoperative ultrasonography for cervical LN lesions (including central LNs and lateral LNs) was evaluated between PTC patients with HT and those without HT, respectively. Results: Among the 1,874 PTC patients, 790 (42.1%) had central cN+ and 1,610 (85.9%) had lateral cN+. Compared with PTC patients without HT, the preoperative US for central LNs displays a higher false-positive rate (27.9% vs. 12.2%, p <0.001) and a lower specificity (72.1% vs. 87.8%, p < 0.001) in PTC patients with HT. Moreover, in PTC patients with HT, the ratio of the absence of fatty hilum in central LNs without metastasis was higher than in PTC patients without HT (13.02% vs. 7.46%, p = 0.013). However, no such differences were observed in lateral LNs. Conclusion: HT will interfere with the preoperative US evaluation for central LNs and increase the incidence of the absence of fatty hilum in central benign LNs. When PTC patients have concomitant HT, clinicians should thoroughly evaluate the central LNs, thereby decreasing the incidence of misdiagnosis and unnecessary surgery.

Effects of marital status on survival of medullary thyroid cancer stratified by age.

PURPOSE: Marital status has emerged as an important influence on several cancer outcomes, but its role in medullary thyroid cancer (MTC) remains unclear. This study was to explore the effects of marital status on the prognosis of MTC patients and to determine whether its effects vary by age. PATIENTS AND METHODS: We retrospectively extracted 1344 eligible patients diagnosed with MTC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the marital status, we divided those patients into married and unmarried groups. We compared the difference in overall survival (OS) and cancer-specific survival (CSS) between married and unmarried via the Kaplan-Meier analysis. Univariate and multivariate Cox proportional models were performed to identify the prognostic factors of OS and CSS. RESULTS: There were 1344 MTC eligible patients in a total of which 883 (65.7%) were married and 461 (34.3%) were unmarried. The comparison observed between married and unmarried patients was as follows: male (45.2% vs. 28.0%), age (≥52 years) (55.9% vs. 44.6%), White (86.7% vs. 78.7%), and undergo surgery (97.7% vs. 93.3%). Multivariate analysis revealed unmarried status as a risk factor independently associated with worse OS (HR: 2.15, 95% CI: 1.59-2.92) rate and CSS (HR: 1.70, 95% CI: 1.17-2.47) rate. In a further analysis stratified by age, there was no significant difference in OS and CSS between married and unmarried patients younger than 52 years. For the remaining group with 52 years old and higher, unmarried patients showed significantly higher risk of OS and CSS than married patients at all stages of the pathology except M1 stage. CONCLUSION: Married patients with MTC have a better prognosis than unmarried ones. Age can affect the association between marital status and the survival of MTC, and married elders may benefit more than youngers.

Recent advancements in peripheral nerve-specific fluorescent compounds.

Nerve injury is a common complication of surgery. Accidental nerve damage or transection can lead to severe clinical symptoms including pain, numbness, paralysis and even expiratory dyspnoea. In recent years, with the rise of the field of fluorescence-guided surgery, researchers have discovered that nerve-specific fluorescent agents can serve as nerve markers in animals and can be used to guide surgical procedures and reduce the incidence of intraoperative nerve damage. Currently, researchers have begun to focus on biochemistry, materials chemistry and other fields to produce more neuro-specific fluorescent agents with physiological relevance and they are expected to have clinical applications. This review discusses the agents with potential to be used in fluorescence-guided nerve imaging during surgery.

A Prediction Model for Contralateral Central Neck Lymph Node Metastases in Unilateral Papillary Thyroid Cancer.

The health problems caused by the frequent relapse of papillary thyroid carcinoma (PTC) remain a worldwide concern since the morbidity rate of PTC ranks the highest among thyroid cancers. Residues from contralateral central lymph node metastases (con-CLNM) are the key reason for persistence or recurrence of unilateral papillary thyroid carcinoma (uni-PTC); however, the ability to assess the status of con-CLNM in uni-PTC patients is limited. To clarify the risk factors of con-CLNM, a total of 250 patients with uni-PTC who underwent total thyroidectomy and bilateral central lymph node dissection were recruited in this study. We compared the clinical, sonographic, and pathological characteristics of patients with con-CLNM to those without con-CLNM and established a nomogram for con-CLNM in uni-PTC. We found that male sex, without Hashimoto's thyroiditis, present capsular invasion, with ipsilateral lateral lymph node metastases, and the ratio of ipsilateral central lymph node metastases ≥0.16 were independent con-CLNM predictors of uni-PTC (ORs: 2.797, 0.430, 2.538, 2.202, and 26.588; 95% CIs: 1.182-6.617, 0.211-0.876, 1.223-5.267, 1.064-4.557, and 7.596-93.069, respectively). Additionally, a preoperative nomogram for the prediction of con-CLNM based on these risk factors showed good discrimination (C-index 0.881; 95% CI: 0.840-0.923; sensitivity 85.3%; specificity 76.0%) and good agreement via the calibration plot. Our study provided a way to quantitatively and accurately predict whether con-CLNM occurred in patients with uni-PTC, which may guide surgeons to evaluate the nodal status and perform tailored therapeutic central lymph node dissection.

Kinase gene fusions: roles and therapeutic value in progressive and refractory papillary thyroid cancer.

The incidence of papillary thyroid cancer (PTC), the major type of thyroid cancer, is increasing rapidly around the world, and its pathogenesis is still unclear. There is poor prognosis for PTC involved in rapidly progressive tumors and resistance to radioiodine therapy. Kinase gene fusions have been discovered to be present in a wide variety of malignant tumors, and an increasing number of novel types have been detected in PTC, especially progressive tumors. As a tumor-driving event, kinase fusions are constitutively activated or overexpress their kinase function, conferring oncogenic potential, and their frequency is second only to BRAFV600E mutation in PTC. Diverse forms of kinase fusions have been observed and are associated with specific pathological features of PTC (usually at an advanced stage), and clinical trials of therapeutic strategies targeting kinase gene fusions are feasible for radioiodine-resistant PTC. This review summarizes the roles of kinase gene fusions in PTC and the value of clinical therapy of targeting fusions in progressive or refractory PTC, and discusses the future perspectives and challenges related to kinase gene fusions in PTC patients.

Criminal of Adverse Pregnant Outcomes: A Perspective From Thyroid Hormone Disturbance Caused by SARS-CoV-2.

Nowadays, emerging evidence has shown adverse pregnancy outcomes, including preterm birth, preeclampsia, cesarean, and perinatal death, occurring in pregnant women after getting infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the underlying mechanisms remain elusive. Thyroid hormone disturbance has been unveiled consistently in various studies. As commonly known, thyroid hormone is vital for promoting pregnancy and optimal fetal growth and development. Even mild thyroid dysfunction can cause adverse pregnancy outcomes. We explored and summarized possible mechanisms of thyroid hormone abnormality in pregnant women after coronavirus disease 2019 (COVID-19) infection and made a scientific thypothesis that adverse pregnancy outcomes can be the result of thyroid hormone disorder during COVID-19. In which case, we accentuate the importance of thyroid hormone surveillance for COVID-19-infected pregnant women.

Predictive Factors for Level V Lymph Node Metastases in Papillary Thyroid Carcinoma with BRAFV600E Mutation and Clinicopathological Features.

BACKGROUND: Therapeutic lateral neck dissection (LND) is recommended in papillary thyroid carcinoma (PTC) patients with clinically lateral lymph node metastasis (LLNM), whether underwent level V LND remains controversial for lacking of sensitive predicting system. BRAFV600E mutation is associated with aggressive tumor behavior, recurrence, and disease-specific mortality of PTC. However, the relationship between BRAFV600E mutation and level V LNM is unclear. METHODS: Univariate and multivariate analyses were retrospectively conducted on the potential predictive factors of 252 PTC patients who underwent initial treatment of neck lymph node dissection from September 2015 to October 2018 in our institute. BRAFV600E mutation and the clinicopathological characteristics of the two groups were compared. RESULTS: LLNM was presented in 208 (82.5%) patients and level II-V LNM was present in 42.8%, 71.2%, 85.1%, 17.8% patients, respectively. BRAFV600E mutation was observed in 188 (74.6%) patients and was significantly associated with patients' age, lymphocytic thyroiditis, capsule invasion, bilateral central lymph node metastasis (CLNM) and level V LNM in PTC. Univariate analysis revealed that lymphocytic thyroiditis, tumor size, number of CLNM, Level II LNM, Level III LNM, simultaneous Level II+III, simultaneous Level III+IV and simultaneous Level II+III+IV were significantly correlated with Level V LNM. In addition, multivariate analysis revealed that tumor size ≥2.5 cm, number of CLNM≥3, level II metastases and BRAFV600E mutation were independent Level V LNM predictors (odds ratio 3.910, 3.660, 8.410, 0.439; 95% CI 1.737-10.135, 1.054-12.713, 1.233-57.355, 0.280-0.827, respectively). CONCLUSION: In summary, we presented several independent predictive factors for level V LNM in PTC patients. We constructed a risk prediction model consisting of tumor size ≥2.5 cm, number of CLNM≥3 and level II metastases and BRAFV600E mutation that may guide surgeons to evaluate the nodal status in PTC and perform tailored therapeutic LND.

Preoperative Sonographic and Clinicopathological Predictors for Solitary Lateral Neck Node Metastasis in Papillary Thyroid Carcinoma: A Retrospective Study.

BACKGROUND: Cervical lymph node metastasis (LNM) is an independent risk factor for poor prognosis of papillary thyroid carcinoma (PTC), but the scope of PTC lateral neck dissection (LND) is controversial. Solitary lateral lymph node metastasis (SLNM) is a special type of PTC with lateral LNM. Currently, study on the preoperative clinical characteristics of SLNM has been seldomly reported. This study evaluated the preoperative characteristics for predicting the SLNM of PTC. METHODS: We included 391 patients diagnosed with PTC between May 2011 and July 2017. Among those patients, 44 had SLNM and 347 had multiple lateral neck node metastasis (MLNM). The clinicopathologic characteristics and other central lymph node metastasis risk factors were retrospectively analyzed. RESULTS: Univariate analysis revealed that age and tumor size (≤1 cm) were significantly correlated with SLNM. In ROC curve analysis, the optimal cutoff age of preoperative predictors for the prediction of SLNM was 46.5 years (AUC=0.623, 0.536-0.710). Besides, the frequency and mean number of CLNM was significantly less in the SLNM than MLNM group. The oval and round tumor shape and well-defined margin of the tumor were more common in the SLNM group (p =0.001; p=0.024, respectively). In addition, multivariate analysis revealed that age ≥47, capsular invasion, no extrathyroidal extension, with central lymph node metastases and irregular shape were independent SLNM predictors of PTCs (odds ratio 2.386, 0.173, 0.284, 0.239, 0.188; 95% CI 1.07-5.140, 0.058-0.840, 0.066-0.926, 0.091-0.437, 0.167-0.864, respectively). CONCLUSION: This study supported that SLNM is more likely to happen in PTC patients with age ≥47 years, capsular invasion, no extrathyroidal extension, with central lymph node metastases and irregular shape. That denotes, selective single level neck dissection can be considered as an alternative to systemic lateral neck dissection in those patients.

A novel ratiometric and reversible fluorescence probe with a large Stokes shift for Cu2+ based on a new clamp-on unit.

A novel ratiometric and reversible chemosensor 4-((2-(Benzo[d]thiazol-2-yl)phenyl)ethynyl)-N,N-diethylaniline (BT-1) based on ortho-arylethynyl benzothiazole with large Stokes shift (Δλ≈190 nm) was designed and synthesized to recognize Cu2+. Copper ion induces a remarkable fluorescence enhancement and causes formation of a BT-1-Cu complex. The clamp-on coordination mode of BT-1 to Cu2+ was demonstrated using Job's plot, mass spectrum (MS) and DFT calculations. The calculations also indicate that Cu2+ was chelated to BT-1 through N and alkyne instead of S and alkyne. The probe could quantify Cu2+ with the detection limit of 3.2 × 10-9 M. The in vitro imaging results indicated that the probe BT-1 was membrane-permeable and could be applied into the recognition of Cu2+ ions in living cells.