Enhancing intracellular cholesterol efflux in chondrocytes alleviates osteoarthritis progression.

OBJECTIVES: Osteoarthritis (OA) is the most common degenerative disease worldwide with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol-lowering drugs in suppressing OA development in mice, and uncover the cholesterol-lowering mechanisms that effectively impede OA progression. METHODS: Five clinically approved cholesterol-lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to DMM-induced OA mice fed a 2% high-cholesterol diet. Gene expression linked to cholesterol metabolism were determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra-articular injection of either its inhibitor or adenovirus. RESULTS: Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol-lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high-density lipoprotein cholesterol that is crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via downregulation of apolipoprotein A1 binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression. CONCLUSIONS: Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for OA.

Thyroid Carcinoma With NSD3::NUTM1 Fusion and Secondary TERT Promoter Mutation: A Case Report and Literature Review.

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive tumor characterized by translocation of the NUTM1 gene. To date, only about 20 NUT carcinomas arising from the thyroid have been reported in the literature, with the majority showing immunohistochemical markers indicative of squamous differentiation. We present a 29-year-old man with NUT carcinoma arising from thyroid follicular cells. Notably, the tumor cells expressed markers characteristic of thyroid follicular cells such as thyroglobulin, TTF1 and PAX8, without obvious histological and immunohistochemical features of squamous differentiation. Molecular analysis revealed a concurrent TERT promoter mutation (C228T) together with the NSD3::NUTM1 fusion, a combination not previously documented in NUT carcinoma. The tumor highlights the need to include NUT carcinoma in the differential diagnosis of thyroid cancer, especially when it presents with unconventional histopathological features, even in the absence of signs of squamous differentiation.

Effect of Inter-Hospital Transfer on Mortality in Patients Admitted through the Emergency Department.

Background: Despite advancements in emergency medical systems, inter-hospital transfer (IHT) remains a critical component. Several studies have analyzed the impact of IHT on patient outcomes. Some studies have reported positive effects, indicating that transfers can improve patient prognosis. However, other studies have suggested that transfers may worsen outcomes. We investigated whether IHT is associated with in-hospital mortality. Methods: This retrospective observational study utilized data on patient outcomes from the National Emergency Department Information System (NEDIS) from 2016 to 2018, focusing on patients admitted to hospitals after visiting the emergency department (ED). The primary outcome was the in-hospital mortality rate. Results: This study included 2,955,476 adult patients admitted to emergency medical centers, with 832,598 (28.2%) undergoing IHT. The in-hospital mortality rate was significantly higher in the transfer group (6.9%) than in the non-transfer group (4.8%). Multiple logistic regression analysis revealed that IHT was an independent predictor of in-hospital mortality (adjusted odds ratio [aOR] 1.114, 95% confidence interval [CI] 1.101-1.128) after adjusting for variables. Sub-analysis indicated that higher severity scores, shorter symptom onset-to-arrival duration, and diagnoses of infectious or respiratory diseases were significantly associated with increased in-hospital mortality among transferred patients. Conclusions: This study identifies IHT as a significant factor associated with increased in-hospital mortality. Additionally, it suggested the need for policies to mitigate the risks associated with IHT, particularly in critically ill patients, those with the acute phase response, and those with infectious, genitourinary, and respiratory diseases.

Gamma-Irradiation-Induced Electrical Characteristic Variations in MoS2 Field-Effect Transistors with Buried Local Back-Gate Structure.

The impact of radiation on MoS2-based devices is an important factor in the utilization of two-dimensional semiconductor-based technology in radiation-sensitive environments. In this study, the effects of gamma irradiation on the electrical variations in MoS2 field-effect transistors with buried local back-gate structures were investigated, and their related effects on Al2O3 gate dielectrics and MoS2/Al2O3 interfaces were also analyzed. The transfer and output characteristics were analyzed before and after irradiation. The current levels decreased by 15.7% under an exposure of 3 kGy. Additionally, positive shifts in the threshold voltages of 0.50, 0.99, and 1.15 V were observed under irradiations of 1, 2, and 3 kGy, respectively, compared to the non-irradiated devices. This behavior is attributable to the comprehensive effects of hole accumulation in the Al2O3 dielectric interface near the MoS2 side and the formation of electron trapping sites at the interface, which increased the electron tunneling at the MoS2 channel/dielectric interface.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.

Objective Parameters for Evaluating Internal Nasal Valve Compromise: Beyond the Angle Perspective.

OBJECTIVES: Nasal valve surgery for internal nasal valve (INV) compromise has become increasingly popular. However, this rise in popularity has sparked debates regarding its indications and disputes over insurance coverage, primarily due to the lack of a gold-standard evaluation method. Therefore, we aimed to identify objective parameters for the INV compromise. METHODS: We analyzed 186 INVs in 93 patients who underwent nasal valve surgery. The data comprised facial computed tomography (CT) images, acoustic rhinometry, the modified Cottle test, and symptom scores. Patients were categorized based on their symptoms and the. RESULTS: of the modified Cottle test. We measured the INV angle, area, volume, lateral wall thickness, septal angle, and nasal bone area using CT. RESULTS: The compromised INV group, characterized by nasal obstruction with a positive modified Cottle test, exhibited smaller INV areas in both coronal and axial views, reduced INV volume in the axial view, and a thinner lateral wall in the coronal view (all P<0.05). Acoustic rhinometry indicated a smaller minimal cross-sectional area and volume in the compromised INV group (both P<0.001). Regression analysis demonstrated significant associations between a compromised INV and reduced INV area on the axial view, as well as the minimal cross-sectional area measured by acoustic rhinometry. CONCLUSION: Relying solely on the INV angle in CT scans has limitations in assessing compromised INV. Alternatively, the INV area on axial CT scans and the minimal cross-sectional area measured by acoustic rhinometry may serve as objective parameters for evaluating INV compromise.

Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis.

Bone is a highly dynamic tissue undergoing continuous formation and resorption. Here, we investigated differential but complementary roles of hypoxia-inducible factor (HIF)-1α and HIF-2α in regulating bone remodeling. Using RNA-seq analysis, we identified that specific genes involved in regulating osteoblast differentiation were similarly but slightly differently governed by HIF-1α and HIF-2α. We found that increased HIF-1α expression inhibited osteoblast differentiation via inhibiting RUNX2 function by upregulation of Twist2, confirmed using Hif1a conditional knockout (KO) mouse. Ectopic expression of HIF-1α via adenovirus transduction resulted in the increased expression and activity of RANKL, while knockdown of Hif1a expression via siRNA or osteoblast-specific depletion of Hif1a in conditional KO mice had no discernible effect on osteoblast-mediated osteoclast activation. The unexpected outcome was elucidated by the upregulation of HIF-2α upon Hif1a overexpression, providing evidence that Hif2a is a transcriptional target of HIF-1α in regulating RANKL expression, verified through an experiment of HIF-2α knockdown after HIF-1α overexpression. The above results were validated in an ovariectomized- and aging-induced osteoporosis model using Hif1a conditional KO mice. Our findings conclude that HIF-1α plays an important role in regulating bone homeostasis by controlling osteoblast differentiation, and in influencing osteoclast formation through the regulation of RANKL secretion via HIF-2α modulation.

Machine learning-based prediction of cerebral oxygen saturation based on multi-modal cerebral oximetry data.

This study develops machine learning-based algorithms that facilitate accurate prediction of cerebral oxygen saturation using waveform data in the near-infrared range from a multi-modal oxygen saturation sensor. Data were obtained from 150,000 observations of a popular cerebral oximeter, Masimo O3™ regional oximetry (Co., United States) and a multi-modal cerebral oximeter, Votem (Inc., Korea). Among these observations, 112,500 (75%) and 37,500 (25%) were used for training and test sets, respectively. The dependent variable was the cerebral oxygen saturation value from the Masimo O3™ (0-100%). The independent variables were the time of measurement (0-300,000 ms) and the 16-bit decimal amplitudes values (infrared and red) from Votem (0-65,535). For the right part of the forehead, the root mean square error of the random forest (0.06) was much smaller than those of linear regression (1.22) and the artificial neural network with one, two or three hidden layers (2.58). The result was similar for the left part of forehead, that is, random forest (0.05) vs logistic regression (1.22) and the artificial neural network with one, two or three hidden layers (2.97). Machine learning aids in accurately predicting of cerebral oxygen saturation, employing the data from a multi-modal cerebral oximeter.

Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats.

Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.

Saikosaponin D Inhibits Lung Metastasis of Colorectal Cancer Cells by Inducing Autophagy and Apoptosis.

Saikosaponin D (SSD), derived from Bupleurum falcatum L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.

Narrative Review of the Safety of Using Pigs for Xenotransplantation: Characteristics and Diagnostic Methods of Vertical Transmissible Viruses.

Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplantation can be a practical alternative because it makes an unlimited supply of organs possible. However, to perform xenotransplantation on patients, the source animals to be used must be free from infectious agents. This requires the breeding of animals using assisted reproductive techniques, such as somatic cell nuclear transfer, embryo transfer, and cesarean section, without colostrum derived in designated pathogen-free (DPF) facilities. Most infectious agents can be removed from animals produced via these methods, but several viruses known to pass through the placenta are not easy to remove, even with these methods. Therefore, in this narrative review, we examine the characteristics of several viruses that are important to consider in xenotransplantation due to their ability to cross the placenta, and investigate how these viruses can be detected. This review is intended to help maintain DPF facilities by preventing animals infected with the virus from entering DPF facilities and to help select pigs suitable for xenotransplantation.

Vitamin D deficiency as a risk factor for sudden cardiac arrest: A multicenter case-control study.

BACKGROUND AND AIMS: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. METHODS AND RESULTS: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20). CONCLUSION: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR.

Automated Information Extraction from Thyroid Operation Narrative: A Comparative Study of GPT-4 and Fine-tuned KoELECTRA.

In the rapidly evolving field of healthcare, the integration of artificial intelligence (AI) has become a pivotal component in the automation of clinical workflows, ushering in a new era of efficiency and accuracy. This study focuses on the transformative capabilities of the fine-tuned KoELECTRA model in comparison to the GPT-4 model, aiming to facilitate automated information extraction from thyroid operation narratives. The current research landscape is dominated by traditional methods heavily reliant on regular expressions, which often face challenges in processing free-style text formats containing critical details of operation records, including frozen biopsy reports. Addressing this, the study leverages advanced natural language processing (NLP) techniques to foster a paradigm shift towards more sophisticated data processing systems. Through this comparative study, we aspire to unveil a more streamlined, precise, and efficient approach to document processing in the healthcare domain, potentially revolutionizing the way medical data is handled and analyzed.

Case report: Development of central precocious puberty in a girl with late-diagnosed simple virilizing congenital adrenal hyperplasia complicated with Williams syndrome.

Congenital adrenal hyperplasia (CAH) and Williams Syndrome (WS; MIM # 194050) are distinct genetic conditions characterized by unique clinical features. 21-Hydroxylase deficiency (21-OHD; MIM #201910), the most common form of CAH, arises from mutations in the CYP21A2 gene, resulting in virilization of the external genitalia in affected females, early puberty in males, and short stature. Williams syndrome, caused by a microdeletion of 7q11.23, presents with distinctive facial features, intellectual disability, unique personality traits, early puberty, and short stature. This case report describe the clinical features of a 4-year-old girl referred due to progressive virilization and developmental delay. Genetic analysis confirmed concurrent CAH and WS, identifying a novel mutation in the CYP21A2 gene (c.1442T>C). Following corticosteroid therapy initiation, the patient developed central precocious puberty. This case report delves into the pubertal change patterns in a patient affected by overlapping genetic conditions, providing valuable insights in to the intricate clinical manifestation and management of these rare complex disorders.

Enhancing automated strabismus classification with limited data: Data augmentation using StyleGAN2-ADA.

In this study, we propose a generative data augmentation technique to overcome the challenges of severely limited data when designing a deep learning-based automated strabismus diagnosis system. We implement a generative model based on the StyleGAN2-ADA model for system design and assess strabismus classification performance using two classifiers. We evaluate the capability of our proposed method against traditional data augmentation techniques and confirm a substantial enhancement in performance. Furthermore, we conduct experiments to explore the relationship between the diagnosis agreement among ophthalmologists and the generation performance of the generative model. Beyond FID, we validate the generative samples on the classifier to establish their practicality. Through these experiments, we demonstrate that the generative model-based data augmentation improves overall quantitative performance in scenarios of extreme data scarcity and effectively mitigates overfitting issues during deep learning model training.

Asymptomatic hematuria in children: Korean Society of Pediatric Nephrology recommendations for diagnosis and management.

Hematuria is a relatively common condition among school-aged children. Because international guidelines for asymptomatic hematuria in children are unavailable, developing practical guidelines for the diagnosis and management of asymptomatic hematuria based on scientific evidence while considering real-world practice settings, values, and patient and physician preferences is essential. The Korean Society of Pediatric Nephrology developed clinical guidelines to address key questions regarding the diagnosis and management of asymptomatic hematuria in children.

Surgical outcomes of robotic thyroidectomy for thyroid tumors over 4 cm via the bilateral axillo-breast approach.

The study investigated the feasibility of robotic bilateral axillo-breast approach (BABA) thyroidectomy for patients with thyroid tumors larger than 4 cm. BABA thyroidectomy has previously shown safety and effectiveness for thyroid surgeries but lacked extensive data on its application to larger tumors. Between October 2008 and August 2022, there were 74 patients underwent robotic BABA thyroidectomy due to thyroid nodules exceeding 4 cm in size. The mean patient age was 40.3 years. Fine needle aspiration results classified the tumors as benign (50.0%), atypia of undetermined significance (27.0%), follicular neoplasm (16.2%), suspicious for malignancy/malignancy (5.4%), or lymphoma (1.4%). The average tumor size was 4.9 cm, with the majority (85.1%) undergoing thyroid lobectomy, and the rest (14.9%) receiving total thyroidectomy. The mean total operation time was 178.4 min for lobectomy and 207.3 min for total thyroidectomy. Transient vocal cord palsy (VCP) was found in 3 patients (4.1%), and there was no permanent VCP. Among patients who underwent total thyroidectomy, transient hypoparathyroidism was observed in three (27.2%), and permanent hypoparathyroidism was observed in one (9.1%). There were no cases of open conversion, tumor spillage, bleeding, flap injury, or tumor recurrence. In conclusion, robotic BABA thyroidectomy may be a safe treatment option for large-sized thyroid tumors that carries no significant increase in complication rates.

Comparison of Helicobacter pylori eradication rates between 7 and 14 days of tailored therapy according to clarithromycin resistance test: A randomized, multicenter, non-inferiority study.

BACKGROUND: Recently, a simple tailored therapy based on clarithromycin resistance has been implemented as Helicobacter pylori (H. pylori) eradication therapy. Nonetheless, despite the tailored therapy and frequent adverse events, studies on treatment period are lacking. This study aimed to compare the H. pylori eradication rates of 7-day and 14-day tailored therapy regimens according to clarithromycin resistance. MATERIALS AND METHODS: This multicenter, prospective, randomized, noninferiority trial enrolled H. pylori-positive patients who were randomly assigned to 7-day and 14-day regimen groups, depending on the presence or absence of clarithromycin resistance by 23S rRNA gene point mutations. Standard triple therapy (STT) (20 mg rabeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily) or bismuth quadruple therapy (BQT) (20 mg rabeprazole twice daily, 500 mg metronidazole thrice daily, 120 mg bismuth four times daily, and 500 mg tetracycline four times daily) was assigned by clarithromycin resistance. Eradication rates and adverse events were evaluated. RESULTS: A total of 314 and 278 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively; however, 31 patients were lost to follow-up, whereas five patients violated the protocol. Both the 7-day and 14-day regimens showed similar eradication rates in the ITT (7-day vs. 14-day: 78.3% vs. 78.3%, p > 0.99) and PP (87.9% vs. 89.1%, p = 0.851) analyses. Non-inferiority was confirmed (p < 0.025). A subgroup analysis according to clarithromycin resistance (clarithromycin resistance rate: 28.7%) revealed no significant difference in eradication rates between the 7-day and 14-day STT (90.0% vs. 90.1%, p > 0.99) and BQT (82.5% vs. 86.5%, p = 0.757). Furthermore, adverse events did not significantly differ between the two groups. CONCLUSIONS: The 7-day triple and quadruple therapy according to clarithromycin resistance showed similar eradication rates, as compared to the 14-day therapy.