Role of Peroxiredoxin 1 Induced by Epstein-Barr Virus Infection in Nasopharyngeal Carcinoma.

BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC), a common cancer in Southern China, is associated with Epstein-Barr Virus (EBV) infection. Although many therapies for NPC have been established, the definite role of EBV in NPC remains unclear. Therefore, this work focuses on LMP2A, a latent EBV gene, and investigates whether LMP2A is related to peroxiredoxin 1 (PRDX1) in EBV-positive NPC. MATERIALS AND METHODS: The mRNA and protein expression levels of LMP2A, PRDX1, and beta-catenin were compared in patient samples. To identify molecular mechanisms, EBV-negative NP69 and EBV-positive C666-1 NPC cell lines were used. After making an agar cell block for cell slides, the intensity of LMP2A expression was observed visually. To measure the level of reactive oxygen species, both fluorescence microscope and flow cytometry were used. To investigate the intracellular signaling molecular mechanisms with and without the LMP2A gene, reverse transcription polymerase chain reaction and western blotting were used. RESULTS: Both patient samples and cells of nasopharyngeal carcinoma infected with EBV had increased expression of LMP2A compared with controls, and high ROS levels were identified. Cell viability assay showed that LMP2A promoted cell growth by regulating gene expression. Furthermore, LMP2A induced the expression of PRDX1 and beta-catenin. LMP2A also increased the expression of both cyclin B1 and cyclin D1. CONCLUSION: In NPC cells, PRDX1 and beta-catenin were regulated through LMP2A expression, which reduced cell growth through cell cycle-related gene expression. This study suggests that LMP2A could be a target molecule for inhibiting cancer progression in NPC cells infected with EBV.

Examining the moderating effect of perceived risk from particulate matter on outdoor sports participants: a theory of planned behavior perspective.

Purpose: This study, drawing from the theoretical framework of the Theory of Planned Behavior (TPB), examines the structural relationship among attitudes, subjective norms, perceived behavioral control (PBC), and behavioral intention. The study focuses on investigating how the perceived risk associated with particulate matter moderates the relationships between "attitudes and behavioral intention," "subjective norms and behavioral intention," and "PBC and behavioral intention" within the context of individuals engaged in outdoor sports. Design/methodology/approach: The data were collected from outdoor sports gatherings facilitated through a popular South Korean sports meetup application. Confirmatory factor analysis was employed to establish the construct validity of the measurement scale, assess factor loadings, averaged variance extracted (AVE), and construct reliability (CR). We also ensured the reliability of the measurement scale through Cronbach's α analysis. To achieve our research objectives, we utilized structural equation modeling with maximum likelihood estimation to examine the positive relationships under investigation. Additionally, we performed moderation analysis using the statistical software Jamovi. Findings: The findings demonstrate the significant impacts of attitudes, subjective norms, and PBC on behavioral intention and reveal that perceived risk acts as a moderator, influencing the relationship between PBC and behavioral intention.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Imidazole-carbazole conjugate for two-photon-excited photodynamic therapy and fluorescence bioimaging.

A heavy-atom-free photosensitizer (CI) based on an imidazole-carbazole conjugate exhibited strong fluorescence emission and ROS generation via both type I and II mechanisms. In particular, CI showed efficient photodynamic therapy and fluorescence bioimaging under two-photon (TP) excitation (740 nm) toward HeLa cells with negligible dark toxicity.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Management of talar lesions with cement augmentation and autologous bone graft.

BACKGROUND: Treatment of bone lesions involved with the articular cartilage at the talus is challenging. We report the management of talus lesions, particularly tumors and avascular necrosis (AVN), at the articular surface through treatment with cement augmentation and autologous bone graft. METHODS: Eight benign bone tumors and three cases of AVN were reviewed retrospectively at a mean follow-up of 56 months (range, 12-162). The mean age of all patients was 36.1 years old (range, 15-73) when assessed between February 2005 and November 2021. Curettage of tumorous and necrotic lesions resulted in significant bone defects filled with bone cement augmentation. Cartilage defects of the talar dome were supported with autologous cancellous bone graft. Tolerable weight-bearing ambulation was permitted immediately after surgery. Radiological and functional evaluations were recorded. RESULTS: We observed an increase in the average The American Orthopaedic Foot and Ankle Score (AOFAS) (p = .003) and a decrease in the average Visual Analogue Scale pain score (p = .003). There was no statistically significant decrease in ROM before or after surgery (p = .114). Additionally, no talus collapse of the ankle joint occurred. Talar dome status did not aggravate before or after surgery, except for one patient. Despite no radiographic osteoarthritis exacerbation before or after surgery in six patients, five patients had osteoarthritic change. CONCLUSION: Cement implantation and autologous bone graft performed simultaneously for benign bone tumors with joint cartilage damage and AVN are technically simple, have good outcomes, and may be a suitable alternative to standard treatments.

Transplantation of PSA-NCAM-Positive Neural Precursors from Human Embryonic Stem Cells Promotes Functional Recovery in an Animal Model of Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) results in permanent impairment of motor and sensory functions at and below the lesion site. There is no therapeutic option to the functional recovery of SCI involving diverse injury responses of different cell types in the lesion that limit endogenous nerve regeneration. In this regard, cell replacement therapy utilizing stem cells or their derivatives has become a highly promising approach to promote locomotor recovery. For this reason, the demand for a safe and efficient multipotent cell source that can differentiate into various neural cells is increasing. In this study, we evaluated the efficacy and safety of human polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (hNPCsPSA-NCAM+) as a treatment for SCI. METHODS: One hundred thousand hNPCsPSA-NCAM+ isolated from human embryonic stem cell-derived NPCs were transplanted into the lesion site by microinjection 7 days after contusive SCI at the thoracic level. We examined the histological characteristics of the graft and behavioral improvement in the SCI rats 10 weeks after transplantation. RESULTS: Locomotor activity improvement was estimated by the Basso-Beattie-Bresnahan locomotor rating scale. Behavioral tests revealed that the transplantation of the hNPCsPSA-NCAM+ into the injured spinal cords of rats significantly improved locomotor function. Histological examination showed that hNPCsPSA-NCAM+ had differentiated into neural cells and successfully integrated into the host tissue with no evidence of tumor formation. We investigated cytokine expressions, which led to the early therapeutic effect of hNPCsPSA-NCAM+, and found that some undifferentiated NPCs still expressed midkine, a well-known neurotrophic factor involved in neural development and inflammatory responses, 10 weeks after transplantation. CONCLUSION: Our results demonstrate that hNPCsPSA-NCAM+ serve as a safe and efficient cell source which has the potential to improve impaired motor function following SCI.

Conditioned Medium of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Exerts Neurorestorative Effects against Ischemic Stroke Model.

Previous studies have shown that early therapeutic events of neural precursor cells (NPCs) transplantation to animals with acute ischemic stroke readily protected neuronal cell damage and improved behavioral recovery through paracrine mechanisms. In this study, we tested the hypothesis that administration of conditioned medium from NPCs (NPC-CMs) could recapitulate the beneficial effects of cell transplantation. Rats with permanent middle cerebral artery occlusion (pMCAO) were randomly assigned to one of the following groups: PBS control, Vehicle (medium) controls, single (NPC-CM(S)) or multiple injections of NPC-CM(NPC-CM(M)) groups. A single intravenous injection of NPC-CM exhibited strong neuroregenerative potential to induce behavioral recovery, and multiple injections enhanced this activity further by suppressing inflammatory damage and inducing endogenous neurogenesis leading to histopathological and functional recovery. Proteome analysis of NPC-CM identified a number of proteins that are known to be associated with nervous system development, neurogenesis, and angiogenesis. In addition, transcriptome analysis revealed the importance of the inflammatory response during stroke recovery and some of the key hub genes in the interaction network were validated. Thus, our findings demonstrated that NPC-CM promoted functional recovery and reduced cerebral infarct and inflammation with enhanced endogenous neurogenesis, and the results highlighted the potency of NPC-CM in stroke therapy.

Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy.

BACKGROUND: Aptamer has been called "chemical antibody" which displays the specific affinity to target molecules compared to that of antibodies and possesses several therapeutic advantages over antibodies in terms of size, accessibility to synthesis, and modification. Based on the attractive properties, aptamers have been interested in many directions and now are emerged as new target-designed cancer drug. MAIN BODY: Currently, new types of aptamers have been reported and attracted many scientists' interesting. Due to simplicity of chemical modification and ready-made molecular engineering, scientists have developed newly designed aptamers conjugated with a wide range of therapeutics, aptamer-drug conjugates; ApDCs, from chemotherapy to phototherapy, gene therapy, and vaccines. ApDCs display synergistic therapeutic effects in cancer treatment. CONCLUSION: In this paper, we reviewed various kinds of ApDCs, i.e., ApDC nucleotide analogs, ApDC by drug intercalation, and ApDC by using chemical linker. Current data prove these ApDCs have sufficient potential to complete clinical development soon. Advanced technology of cancer drug delivery and combination treatment of cancers enables aptamer and conjugated drug (ApDCs) efficient means for targeted cancer treatment that reduces potential toxicity and increases therapeutic efficacy.

Near-Infrared Autofluorescence Imaging May Reduce Temporary Hypoparathyroidism in Patients Undergoing Total Thyroidectomy and Central Neck Dissection.

Background: Near-infrared autofluorescence (NIRAF) imaging is known to reduce the incidence of post-thyroidectomy hypocalcemia. However, there are no studies on how much NIRAF imaging affects the serum parathyroid hormone (PTH) level after surgery. We investigated the changes of the serum PTH level and ionized calcium (iCa.) in patients undergoing total thyroidectomy with central neck dissection (CND). Materials and Methods: This retrospective study with historical control enrolled 542 patients who underwent total thyroidectomy with CND. Patients were divided into two groups: the NIRAF group (261 patients) and the control group (281 patients). PTH and iCa. levels were measured at the hospital stay, 1, 3, and 6 months after surgery. In addition, the number of identified parathyroid glands (PGs), autotransplanted PGs, and the inadvertent resection rate of PGs was evaluated. Results: The incidence of postoperative hypoparathyroidism (PTH <15 pg/mL) was significantly lower in the NIRAF group during the hospitalization (88 patients: 33.7% vs. 131 patients: 46.6%; p = 0.002) and at 1 month postoperatively (23 patients: 8.8% vs. 53 patients: 18.9%; p = 0.001). There was no difference in the permanent hypoparathyroidism rate (6 months after surgery) between the NIRAF group and the control group (4.2% vs. 4.6%; p = 0.816). There was no difference in the incidence of hypocalcemia (iCa. <1.09 mmol/L) (during hospitalization: 6.5% vs. 10.0%; 1 month: 2.3% vs. 2.5%; 3 months: 0.8% vs. 0.7%; 6 months after surgery: 1.1% vs. 1.1%) between the two groups. The number of inadvertently resected PGs was significantly lower in the NIRAF group (18:6.9% vs. 36:12.8%; p = 0.021). Conclusions: These results suggest that NIRAF imaging may reduce temporary hypoparathyroidism and the risk of inadvertent resection of PGs in patients undergoing total thyroidectomy with CND.

Improved effect of a mitochondria-targeted antioxidant on hydrogen peroxide-induced oxidative stress in human retinal pigment epithelium cells.

BACKGROUND: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. METHODS: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR). RESULTS: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1). CONCLUSION: We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.

Generation of a human induced pluripotent stem cell line, YCMi002-A, from a Factor VII deficiency patient carrying F7 mutations.

Factor VII (FVII) deficiency is the most common among the rare bleeding disorders, which is caused by mutations in coagulation factor VII. Clinical features caused by FVII deficiency vary from mild or asymptomatic to fatal cerebral hemorrhage. We generated an induced pluripotent stem cell (iPSC) line, YCMi002-A, from FVII deficiency patient-derived fibroblasts. YCMi002-A cells are characterized by novel compound heterozygous mutations. The c.345C > A; p.C115X is well known and the second one, c.1276C > T; p.Q426X, remains novel. YCMi002-A cells may help researchers to understand correlation between these mutations and the symptoms of FVII deficiency.

Comparison of Ultrasonography Features and K-TIRADS for Isthmic and Lobar Papillary Thyroid Carcinomas: A Single-Center Study.

Objective: This study aimed to compare ultrasonography (US) features and the Korean-Thyroid Imaging Reporting and Data System (K-TIRADS) categories for diagnosing isthmic and lobar papillary thyroid carcinomas (PTC). Methods: From January 2009 to December 2012, 163 patients who underwent thyroid surgery and were confirmed with a post-operative histopathological diagnosis of isthmic PTC were retrospectively included. Fifty-nine patients were excluded because their tumor size was <0.5 cm or because of other reasons. The control group comprised of 145 patients who underwent thyroid surgery from January to April 2013 for a classic type of PTC, with the largest diameter being ≥ 0.5 cm and located in the thyroid lobe. A single radiologist retrospectively reviewed the US features and K-TIRADS categories of each nodule using a picture archiving and communication system. Results: Among 104 patients with isthmic PTC, 95 and 9 had primary and secondary cancers, respectively. On the other hand, all 145 patients with lobar PTC had primary cancers. Isthmic PTC showed a lower prevalence of non-parallel orientation than lobar PTC (23.1 and 71%). Nodule orientation was the only US feature statistically different between the two groups (p < 0.0001). However, there was no significant difference in patient age, sex, nodule size, composition, echogenicity, microcalcification, spiculated/microlobulated margin, and K-TIRADS category between the two groups (p > 0.05). Conclusions: K-TIRADS may be useful in the diagnosis of both isthmic and lobar PTC.

Flexible Graphite/PPG Hybrid Composite-Based Resistive Sensor for Sensing Organic Compounds.

Our objective in this study was to investigate a sensor for volatile organic compounds based on a graphite (G)/polypropylene glycol (PPG) hybrid composite (HC) for sensing hybrid elements. The G/PPG HC sensor films for organic-matter detection were successfully fabricated on polyethylene terephthalate (PET) film with a simple blade-coating method. The sensing paste based on G/PPG (1:2) HC showed good dispersibility and stability. In addition, G/PPG HC sensor films with organic compounds showed different thickness changes as a function of the G/PPG ratio because of the swelling effect of the polymer. The observed differences in resistance of the G/PPG HC films corresponded to those of common organic compounds, suggesting that the disconnection of graphite caused by the swollen PPG matrix caused explosive resistance change. Moreover, we evaluated the sensitivity of typical hydrocarbon materials, such as benzene and toluene, in the sensor film as well as petroleum materials without moisture-induced malfunctions. This study could provoke knowledge about superior sensing with cost-effective and easily scalable materials using polymer/graphite composite-based sensors to improve the sensitivity, selectivity, and stability of chemical sensor applications.

Prevalence and Features of Thyroglossal Duct Cyst on Ultrasonography, According to Radioactive Iodine Therapy: A Single-Center Study.

Objective: The relationship between radioactive iodine therapy (RIT) and prevalence of thyroglossal duct cysts (TGDC) on ultrasonography (US) has not been reported. We assessed the prevalence and US features of TGDC according to RIT. Methods: From July 2017 to June 2018, 3,146 subjects underwent thyroid or neck US at our center. The presence or absence of TGDCs was prospectively investigated based on real-time US examination. Among the 3,146 subjects, 261 subjects were excluded because of <18 years of age, unclear information of RIT, or the presence of a radiation therapy history to the neck. Eventually, 2,885 subjects were included in this study. Results: Of the 2,885 subjects finally included, 126 (4.4%) showed a TGDC on US. Those with RIT history showed a higher prevalence of TGDCs than those without (no statistical difference, p = 0.062). In 697 male subjects, there were statistical differences in type of surgery, RIT history, and session number of RIT between those with or without TGDCs (p < 0.0001). In 126 subjects with TGDCs, only sex showed a significant difference between those with or without RIT history (p = 0.015). However, there were no significant differences in the location, size, and shape of TGDCs (p > 0.05). The common US features of TGDC were suprahyoid location, ~1 centimeter, and flat-to-ovoid or round shape. Conclusions: RIT may increase the prevalence of TGDCs, particularly in men.

Comparison of Prevalence and Ultrasonography Features of Thyroglossal Duct Cyst in Adults According to Radioactive Iodine Ablation.

BACKGROUND This study aimed to evaluate the prevalence of thyroglossal duct cysts (TGDCs) on ultrasonography (US) and US features of TGDCs in adults, and to assess whether the prevalence or size of TGDCs increases after radioactive iodine ablation (RIA). MATERIAL AND METHODS Between July and December 2018, 2820 patients underwent thyroid or neck US examination, performed by 2 radiologists, at our center. On the basis of real-time US, the presence or absence of TGDCs was prospectively investigated by 2 radiologists. Among the 2820 patients, 54 patients who were <19 years of age or had a radiation therapy history to the neck were excluded. Eventually, 2766 patients were included. RESULTS Of the 2766 patients, 160 (5.8%) showed a TGDC on US. The mean size of TGDCs in RIA history (+) (n=36) and RIA history (-) (n=124) groups was 0.92±0.41 cm and 0.86±0.45 cm, respectively. There was no significant difference in size of TGDCs between RIA history (+) and RIA history (-) groups (p=0.684). Between the TGDC (+) and TGDC (-) groups, there was no significant difference in patient age, gender, reason for thyroid/neck US, type of thyroid surgery, and session number and application/no application of RIA (p>0.05). The prevalence rate of TGDCs in radiologist A and B was 4.9% (70/1427) and 6.7% (90/1339), respectively. TGDCs were more common in the suprahyoid neck, and the common shapes of TGDCs were flat-to-ovoid and round. CONCLUSIONS RIA may not be associated with the prevalence or enlargement of TGDCs.

Thyroid Imaging Reporting and Data System for Detecting Diffuse Thyroid Disease on Ultrasonography: A Single-Center Study.

Objective: This study aimed to compare the ultrasonography (US) features of diffuse thyroid disease (DTD) and normal thyroid parenchyma (NTP), and to propose a structured imaging reporting system for detecting DTD. Methods: This retrospective study assessed the findings for 270 consecutive patients who underwent thyroid US before thyroid surgery. The following US data were analyzed: DTD-specific features, parenchymal echotexture and echogenicity, anteroposterior diameter, glandular margin, and parenchymal vascularity. Univariate and multivariate analyses with generalized estimating equations were performed to investigate the relationship between US features and DTD. The fitted probability of DTD was analyzed by using a regression equation. Results: Of the 270 patients, there were NTP (n = 193), Hashimoto thyroiditis (n = 24), non-Hashimoto lymphocytic thyroiditis (n = 51), Graves' disease (n = 1), and diffuse hyperplasia (n = 1). The following US features were significantly associated with DTD: decreased or increased parenchymal echogenicity, coarse parenchymal echotexture, increased anteroposterior diameter, lobulated glandular margin, and increased parenchymal vascularity. Of these, coarse parenchymal echotexture was the most significant independent predictor of DTD. The numbers of abnormal US features were positively correlated with the fitted probability and risk of DTD. The diagnostic indices were highest when the chosen cut-off criterion was category III with the largest Az value (0.867, 95% confidence interval: 0.820-0.905), yielding a sensitivity of 68.8%, specificity of 92.2%, positive predictive value of 77.9%, negative predictive value of 88.1%, and accuracy of 85.6% (p < 0.001). Conclusions: Our sonographic reporting and data system may be useful for detecting DTD.

Unexpected Lung and Brain Metastases 9 Years After Thyroid Lobectomy for Follicular Adenoma: A Case Report.

Background: Benign thyroid follicular tumors without histological evidence of carcinoma can metastasize. However, the pathogenesis of metastasis remains unclear. Here, the new proposed terminology, "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" should be considered. We present a case of an encapsulated type of follicular variant of papillary thyroid carcinoma (FVPTC) that exhibited distant lung and brain metastases and was initially diagnosed as follicular adenoma. Case Report: In December 2006, a 64-year-old woman underwent ultrasonography-guided fine-needle aspiration of the right thyroid nodule at our hospital because of a palpable right neck mass. Right lobectomy was performed, and a follicular adenoma was diagnosed. In October 2015, she visited our hospital owing to dry cough and mild dyspnea and underwent computed tomography-guided transthoracic core needle biopsy for the lung nodule owing to probably multiple lung metastasis on chest X-ray and computed tomography. Based on retrospective analysis of the primary thyroid tumor and lung nodule specimen, an encapsulated follicular variant of papillary thyroid carcinoma with lung metastasis was confirmed. Conclusion: We report a case of an encapsulated follicular variant of papillary thyroid carcinoma with unexpected metastasis to the lung 9 years after thyroid surgery in a patient who was initially diagnosed as follicular adenoma. A careful close follow-up with re-examination of the histopathology specimen may be needed in patients who were diagnosed with benign thyroid follicular tumors.