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Articles in E-pub version are posted online ahead of regular printed publication.

Original Article
Differences in Type 2 Fiber Composition in the Vastus Lateralis and Gluteus Maximus of Patients with Hip Fractures
Jingwen Tian, Minchul Song, Kyu Jeong Cho, Ho Yeop Lee, Sang Hyeon Ju, Jung Ryul Lim, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Jung-Mo Hwang, Hyon-Seung Yi
Received January 13, 2024  Accepted March 21, 2024  Published online June 11, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1935    [Epub ahead of print]
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  • 25 Download
AbstractAbstract PDF
Background
Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls.
Methods
A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type.
Results
In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters.
Conclusion
This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.
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Corrigendum: Text Correction
Effects of an Electronic Medical Records-Linked Diabetes Self-Management System on Treatment Targets in Real Clinical Practice: Retrospective, Observational Cohort Study
So Jung Yang, Sun-Young Lim, Yoon Hee Choi, Jin Hee Lee, Kun-Ho Yoon
Published online June 10, 2024  
DOI: https://doi.org/10.3803/EnM.2024.301    [Epub ahead of print]
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  • 3 Download
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Review Articles
Parathyroid Gland Generation from Pluripotent Stem Cells
Mayuko Kano
Received March 25, 2024  Accepted May 7, 2024  Published online June 10, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1989    [Epub ahead of print]
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  • 18 Download
AbstractAbstract PDF
Patients with permanent hypoparathyroidism require lifelong treatment. Current replacement therapies sometimes have adverse effects (e.g., hypercalciuria and chronic kidney disease). Generating parathyroid glands (PTGs) from the patient’s own induced pluripotent stem cells (PSCs), with transplantation of these PTGs, would be an effective treatment option. Multiple methods for generating PTGs from PSCs have been reported. One major trend is in vitro differentiation of PSCs into PTGs. Another is in vivo generation of PSC-derived PTGs by injecting PSCs into PTG-deficient embryos. This review discusses current achievements and challenges in present and future PTG regenerative medicine.
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Artificial Intelligence Applications in Diabetic Retinopathy: What We Have Now and What to Expect in the Future
Mingui Kong, Su Jeong Song
Received December 28, 2023  Accepted April 3, 2024  Published online June 10, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1913    [Epub ahead of print]
  • 143 View
  • 17 Download
AbstractAbstract PDF
Diabetic retinopathy (DR) is a major complication of diabetes mellitus and is a leading cause of vision loss globally. A prompt and accurate diagnosis is crucial for ensuring favorable visual outcomes, highlighting the need for increased access to medical care. The recent remarkable advancements in artificial intelligence (AI) have raised high expectations for its role in disease diagnosis and prognosis prediction across various medical fields. In addition to achieving high precision comparable to that of ophthalmologists, AI-based diagnosis of DR has the potential to improve medical accessibility, especially through telemedicine. In this review paper, we aim to examine the current role of AI in the diagnosis of DR and explore future directions.
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Metabolic Reprogramming in Thyroid Cancer
Sang-Hyeon Ju, Minchul Song, Joung Youl Lim, Yea Eun Kang, Hyon-Seung Yi, Minho Shong
Received August 15, 2023  Accepted March 12, 2024  Published online June 10, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1802    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Thyroid cancer is a common endocrine malignancy with increasing incidence globally. Although most cases can be treated effectively, some cases are more aggressive and have a higher risk of mortality. Inhibiting RET and BRAF kinases has emerged as a potential therapeutic strategy for the treatment of thyroid cancer, particularly in cases of advanced or aggressive disease. However, the development of resistance mechanisms may limit the efficacy of these kinase inhibitors. Therefore, developing precise strategies to target thyroid cancer cell metabolism and overcome resistance is a critical area of research for advancing thyroid cancer treatment. In the field of cancer therapeutics, researchers have explored combinatorial strategies involving dual metabolic inhibition and metabolic inhibitors in combination with targeted therapy, chemotherapy, and immunotherapy to overcome the challenge of metabolic plasticity. This review highlights the need for new therapeutic approaches for thyroid cancer and discusses promising metabolic inhibitors targeting thyroid cancer. It also discusses the challenges posed by metabolic plasticity in the development of effective strategies for targeting cancer cell metabolism and explores the potential advantages of combined metabolic targeting.
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Osteocalcin: Beyond Bones
Jakub Krzysztof Nowicki, Elżbieta Jakubowska-Pietkiewicz
Received November 28, 2023  Accepted January 31, 2024  Published online May 28, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1895    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Apart from basic roles such as supporting the body, protecting internal organs, and storing calcium, the skeletal system also performs hormonal functions. In recent years, several reports have been published on proteins secreted by bones and their impact on the homeostasis of the entire body. These proteins include fibroblast growth factor 23, sclerostin, lipocalin 2, and osteocalcin. Osteocalcin, the most abundant non-collagenous protein in bone tissue, is routinely measured as a clinical marker for diagnosing bone metabolism disorders. Its molecule undergoes numerous transformations, with decarboxylation being the critical process. Decarboxylation occurs in the acidic environment typical of bone resorption, facilitating the release of the molecule into the bloodstream and enabling its hormonal action. Decarboxylated osteocalcin promotes insulin secretion and stimulates the proliferation of pancreatic islet β-cells. It also plays a role in reducing the accumulation of visceral fat and decreasing fat storage in the liver. Furthermore, decarboxylated osteocalcin levels are inversely correlated with fasting serum glucose levels, total body fat, visceral fat area, and body mass index. Apart from its role in energy metabolism, osteocalcin affects testosterone production and the synthesis of glucagon-like peptide-1. It is also actively involved in muscle-bone crosstalk and influences cognitive function.
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Letter
Potential of Calcilytics as a Novel Treatment for Post-Surgical Hypoparathyroidism
Han Seok Choi
Received May 10, 2024  Accepted May 16, 2024  Published online May 27, 2024  
DOI: https://doi.org/10.3803/EnM.2024.2035    [Epub ahead of print]
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  • 19 Download
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Original Article
Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes
Ying Li, Seul Ki Kwon, Hoonsung Choi, Yoo Hyung Kim, Sunyoung Kang, Kyeong Cheon Jung, Jae-Kyung Won, Do Joon Park, Young Joo Park, Sun Wook Cho
Received October 31, 2023  Accepted February 2, 2024  Published online May 27, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1872    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups.
Methods
In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed.
Results
The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery.
Conclusion
Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.
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Editorial
Insights from Decades of Supplementing Calcium and Vitamin D
Sung Hye Kong
Received April 19, 2024  Accepted May 2, 2024  Published online May 23, 2024  
DOI: https://doi.org/10.3803/EnM.2024.2016    [Epub ahead of print]
  • 513 View
  • 32 Download
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Original Articles
Dynamic Risk Model for the Medical Treatment of Graves’ Hyperthyroidism according to Treatment Duration
Meihua Jin, Chae A Kim, Min Ji Jeon, Won Bae Kim, Tae Yong Kim, Won Gu Kim
Received December 27, 2023  Accepted March 26, 2024  Published online May 23, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1918    [Epub ahead of print]
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  • 28 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves’ hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established.
Methods
In this retrospective cohort study, 1,235 patients with Graves’ hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12–24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared.
Results
The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1.
Conclusion
The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves’ hyperthyroidism who underwent longer ATD treatment duration.
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Utilizing Immunoglobulin IgG4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis
Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung
Received January 2, 2024  Accepted February 28, 2024  Published online May 20, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1923    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Background
Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished.
Methods
This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery.
Results
Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT.
Conclusion
This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.
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Letter
Beyond Bone: Embracing Osteosarcopenia for Comprehensive Fracture Prevention
Beom-Jun Kim
Received April 5, 2024  Accepted April 15, 2024  Published online May 16, 2024  
DOI: https://doi.org/10.3803/EnM.2024.2002    [Epub ahead of print]
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Review Article
Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease
Yosuke Nakagawa, Hirotaka Komaba
Received March 11, 2024  Accepted March 29, 2024  Published online May 16, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1978    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
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Brief Report
Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment
Hyun Ah Kim, Han Na Jang, Sung Hye Kong, Young Lee, Sung Hee Choi, Young Min Cho, Hak Chul Jang, Tae Jung Oh
Received December 27, 2023  Accepted March 26, 2024  Published online May 16, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1919    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, –0.02 mL/min/1.73 m2 [95% confidence interval (CI), –3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications’ substantial renoprotective effects in individuals with ketonuria.
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Original Article
Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress
Marie Rhee, Joonyub Lee, Eun Young Lee, Kun-Ho Yoon, Seung-Hwan Lee
Received December 22, 2023  Accepted March 14, 2024  Published online May 16, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1915    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.
Methods
Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay.
Results
Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression.
Conclusion
Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

Citations

Citations to this article as recorded by  
  • Can Daily Dietary Choices Have a Cardioprotective Effect? Food Compounds in the Prevention and Treatment of Cardiometabolic Diseases
    Elżbieta Szczepańska, Barbara Janota, Marika Wlazło, Magdalena Gacal
    Metabolites.2024; 14(6): 296.     CrossRef
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