Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Objectives: Excessive sedentary behavior in youth is a major global issue, contributing to the rise in childhood obesity and metabolic diseases. International public health authorities have issued guidelines recommending that children and adolescents limit their daily sedentary time, including screen time. However, to date, no studies have explored the relationship between sedentary behavior as an exposure factor and skeletal muscle strength and mass as outcomes in this population. The present study investigated the association of sedentary behavior with handgrip strength (HGS) and appendicular lean mass (ALM) among United States adolescents. Methods: A total of 1449 adolescent participants from the National Health and Nutrition Examination Survey (2011-2014) were included. Information on sedentary behavior, specifically daily sedentary time, was obtained through a self-reported questionnaire. Muscular parameters, including HGS and ALM, were measured. To adjust for differences in body size, these parameters were divided by body mass index (BMI) and weight. Linear regression analyses were performed to evaluate the associations between daily sedentary time and each muscular parameter, adjusting for age, sex, ethnicity, annual family income, and moderate-to-vigorous physical activity (MVPA). Results: The linear regression analyses revealed negative associations between daily sedentary time and all muscular parameters, apart from absolute ALM. These included HGS (β, -0.265; standard error [SE], 0.074; p=0.001), HGS/BMI (β, -0.021; SE, 0.004; p<0.001), HGS/weight (β, -0.008; SE, 0.002; p<0.001), ALM/BMI (β, -0.008; SE, 0.003; p=0.010), and ALM/weight (β, -0.003; SE, 0.001; p=0.005). Conclusions After adjusting for MVPA, daily sedentary time was inversely associated with HGS, HGS/BMI, HGS/weight, ALM/BMI, and ALM/weight in United States adolescents.

Background and Objectives: Among various emerging catheter-based treatments for severe tricuspid regurgitation (TR), the spacer device can reduce the regurgitation orifice without manipulating the valve leaflet. However, its clinical application has been hampered by traumatic anchoring to the myocardium and the coaxial alignment of the balloon resulting in insufficient TR reduction. This study aimed to evaluate the early-stage safety, technical feasibility, and preliminary efficacy of the novel atraumatic vertical spacer in patients with isolated severe TR. Methods: All procedures were guided by fluoroscopy and transthoracic echocardiography.The maximum device placement time with an inflated balloon was 24 hours. Changes in the amount of TR, right ventricular function, and patient hemodynamics were measured during balloon deployment. Results: A total of 7 patients (median age 74), underwent successful device implantation without procedure-related complications. During balloon inflation (median 25 minutes), there were no symptoms or signs indicative of TR intolerance. TR was reduced by 1 grade or greater in all patients, with 2 patients exhibiting a reduction of 3 grades, from torrential TR to a moderate degree. Mild TR after balloon inflation was achieved in 3 patients with baseline severe TR. The TR reduction observed during initial balloon deployment was sustained during the subsequent balloon maintenance period. Conclusions The Pivot-balloon procedure was safe, technically feasible, and effective in reducing TR in patients with severe TR. No periprocedural complications or adverse cardiovascular events were reported during device placement with TR reduction observed in all patients. However, longer-term follow-up is needed to confirm safety and treatment effect.

Background: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments. Materials and Methods: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19. Results: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis. Conclusion Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a devastating and growing global threat, calling for new antibiotic treatments. In Korea, the challenge of treating CRAB is compounded by high nosocomial acquisition rates and limited availability of novel antibiotics. Minocycline, a semisynthetic tetracycline derivative, has been proposed as a therapeutic option for CRAB infections. Nonsusceptibility to minocycline may occur through the efflux pump, TetB. The prevalence of tetB in A. baumannii has increased, along with higher minocycline minimum inhibitory concentrations (MICs). We aimed to evaluate minocycline susceptibility rates in clinical strains of CRAB, and the association between tetB carriage and minocycline susceptibility across different genotypes. Materials and Methods: Representative CRAB blood isolates were collected from Asan Medical Center, Seoul.Minocycline susceptibility was assessed using the Clinical and Laboratory Standards Institute (CLSI) breakpoint (≤4 mg/L) and the proposed pharmacokinetics (PK)/pharmacodynamics (PD) breakpoint (≤1 mg/L). Tigecycline was used as a comparator, and its susceptibility breakpoint for Enterobacterales defined by EUCAST was applied (≤0.5 mg/L).The presence of tetB was detected by PCR, and multilocus sequence typing (MLST) was performed using seven housekeeping genes. Results: Of the 160 CRAB blood isolates, 83.8% were susceptible to minocycline by the CLSI criteria, and 50.6% were PK-PD susceptible by the PK-PD criteria. The minocycline minimum inhibitory concentration (MIC)50 /MIC90 was 1/8 mg/L. tetB was present in 49% of isolates and was associated with a higher minocycline MIC (MIC50/90 2/8 mg/L vs. 1/2 mg/L). No clear correlation was observed between tetB positivity and tigecycline MIC. Nine MLSTs were identified, with significant differences in tetB carriage rates between the major sequence types. Notably, ST191, associated with non-tetB carriage and greater susceptibility to minocycline, declined over the study period (P=0.004), while ST451, associated with tetB carriage, increased. Conclusion tetB was present in 49% of CRAB isolates and was associated with higher MICs and non-susceptibility by both CLSI and PK-PD criteria. However, absence of tetB was not a reliable predictor of minocycline PK-PD susceptibility. Additionally, shifts over time towards genotypes with reduced minocycline susceptibility were observed. Further research is needed to correlate these findings with clinical outcomes and identify additional resistance mechanisms.

Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

Background: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia and obesity by inhibiting renal glucose reabsorption. This post hoc study evaluated clinical factors influencing patient response to dapagliflozin. Methods: The analysis focused on patients treated with dapagliflozin (10 mg/day for 52 weeks) within the randomized, double-blind, parallel-group BEYOND trial. Adequate glycemic control (GC) was defined as a reduction in glycated hemoglobin (HbA1c) of ≥ 1.0% or the achievement of an HbA1c level <7.0% at week 52. Significant weight loss (WL) referred to a reduction in body weight of ≥3.0% at week 52. Participants were classified into four groups based on their GC and WL responses: GC+/WL+, GC+/WL−, GC−/WL+, and GC−/WL−. Results: Among dapagliflozin recipients (n=56), at 52 weeks, HbA1c had decreased by 1.0%±0.8% from baseline, while body weight had declined by 2.4±3.1 kg. Overall, 69.6% of participants achieved GC+, and 57.1% achieved WL+. Male sex and shorter diabetes duration were significantly associated with achieving GC+. Conversely, higher estimated glomerular filtration rate was significantly linked to WL+. The only factor significantly associated with both GC+ and WL+ was shorter diabetes duration (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97; P=0.023). The GC+ and WL+ groups exhibited favorable responses beginning soon after dapagliflozin therapy was initiated. Furthermore, HbA1c decline was more strongly associated with reduction in visceral fat than with WL. Conclusion A short duration of diabetes and early response to treatment appear to represent key factors in maximizing the benefits of dapagliflozin for blood glucose and weight management.

Background: This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules. Methods: This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images. Results: Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity. Conclusion CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.