Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function. While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago, the mechanisms underlying these phenomena (e.g., heterogenous cellular responses to nerve injury and the signaling pathways involved) remain poorly understood. Here, using mouse genetics, nerve injury models, pharmacologic manipulation, and taste bud organoid models, we identify a specific subpopulation of taste cells, predominantly c-Kit-expressing sweet cells, that exhibit superior resistance to nerve injury. We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2, subsequently attenuating the re-emergence of other type II cells by post-operation week 4. In taste bud organoids, c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib, while other taste cell types showed the opposite behavior. We also observed a distinct population of residual taste cells that acquired stem-like properties, generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling. Together, our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.
Animals ; Taste Buds/metabolism* ; Proto-Oncogene Proteins c-kit/metabolism* ; Mice ; Signal Transduction ; Imatinib Mesylate/pharmacology* ; Mice, Inbred C57BL

Background: Despite advances in systemic targeted therapies, topical agents remain the primary treatment for localized psoriasis. However, their therapeutic effects are often delayed and unsatisfactory. The dissolving microneedle (DMN) patch, a novel transdermal drug delivery system, enhances the absorption of topical agents through micro-channels. Objective: To evaluate the efficacy of DMN patches in enhancing drug delivery and improving clinical outcomes in psoriatic plaques. Methods: A prospective, randomized, split-body study was conducted to verify the efficacy of additional use of DMN patches after topical agent application in psoriasis treatment. Patients with mild psoriasis were enrolled and 6 paired lesions per patient were randomized into 3 groups: ointment-only, ointment-with-no needle patch, and ointment-with-DMN patch. Lesions were treated with a topical agent (betamethasone and calcipotriol) once daily for 2 weeks. Modified psoriasis area and severity index (mPASI) scores were measured weekly. In vitro and ex vivo experiments were performed to confirm micro-channel formation, microneedle dissolution, and drug penetration enhancement. Results: A total of 132 paired lesions from 22 patients were analyzed. The ointment-with-DMN patch group showed significantly improved mPASI scores (80.4%±20.5%; 5.42→1.06) compared to the ointment-with-no needle patch (64.6%±33.0%; 4.94→1.68) (p<0.05) and ointment-only groups (55.5%±31.4%; 5.00→2.15) (p<0.001). In vitro studies demonstrated 2.1-fold enhanced drug delivery with DMN patches, while ex vivo histological analysis confirmed micro-channel formation. No adverse events, including infection or psoriasis exacerbation, were observed. Conclusion The DMN patch is an effective adjunctive tool that enhances transdermal drug delivery and improves therapeutic outcomes in psoriatic plaques, particularly those refractory to topical agents.

Background: Liver transplantation (LT) is the standard treatment for end-stage liver disease; however, it can lead to biliary strictures in 25%–30% of cases. We aimed to develop a biodegradable stent loaded with paclitaxel that could be inserted during surgery without requiring removal. We evaluated the safety and efficacy of this stent using a porcine model. Methods: Fourteen pigs underwent simulated ischemic injury during LT, and a biodegradable paclitaxel-eluting stent was inserted after duct-to-duct anastomosis.Pigs were divided into four groups: no stent (n=3), bare stent (n=3), 300 µg paclitaxel stent (n=4), and 900 µg paclitaxel stent (n=4). After 3 months of follow-up, autopsies were conducted to obtain common bile duct tissue samples, and inflammation and fibrosis thicknesses were assessed under a microscope. Results: Most tissues had resolved the inflammatory reactions by the 3-month mark. The thinnest fibrosis thickness was observed in the 900 µg group (359.08±167.23 µm); however, no statistical significance was observed. Conclusion This study demonstrated the safety of paclitaxel-eluting biodegradable biliary stents and their positive effects on fibrosis in an ischemic bile duct porcine model. This biodegradable stent represents a potential approach for overcoming the complications associated with biliary strictures after LT.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Background/Aims: The incidence of steatotic liver disease (SLD) is increasing across all age groups as the incidence of obesity increases worldwide. The existing noninvasive prediction models for SLD require laboratory tests or imaging and perform poorly in the early diagnosis of infrequently screened populations such as young adults and individuals with healthcare disparities. We developed a machine learning-based point-of-care prediction model for SLD that is readily available to the broader population with the aim of facilitating early detection and timely intervention and ultimately reducing the burden of SLD. Methods: We retrospectively analyzed the clinical data of 28,506 adults who had routine health check-ups in South Korea from January to December 2022. A total of 229,162 individuals were included in the external validation study. Data were analyzed and predictions were made using a logistic regression model with machine learning algorithms. Results: A total of 20,094 individuals were categorized into SLD and non-SLD groups on the basis of the presence of fatty liver disease. We developed three prediction models: SLD model 1, which included age and body mass index (BMI); SLD model 2, which included BMI and body fat per muscle mass; and SLD model 3, which included BMI and visceral fat per muscle mass. In the derivation cohort, the area under the receiver operating characteristic curve (AUROC) was 0.817 for model 1, 0.821 for model 2, and 0.820 for model 3. In the internal validation cohort, 86.9% of individuals were correctly classified by the SLD models. The external validation study revealed an AUROC above 0.84 for all the models. Conclusions As our three novel SLD prediction models are cost-effective, noninvasive, and accessible, they could serve as validated clinical tools for mass screening of SLD.

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.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection commonly observed in immunocompromised patients, necessitating prompt diagnosis and treatment. This review evaluates the diagnostic performance of various tests used for PJP diagnosis through a comprehensive literature review. Additionally, we propose a diagnostic algorithm tailored to non-human immunodeficiency virus immunocompromised patients, considering the specific characteristics of current medical resources in Korea.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: and Purpose The pain lateralization in cluster headache (CH) may be related to the asymmetry in the functions of the brain hemispheres. The right-sided dominance of pain in CH has been found inconsistently across studies, and so we aimed to characterize this and identify the factors influencing pain lateralization during current and previous bouts. Methods: This study enrolled 227 patients from the Korean Cluster Headache Registry between October 2018 and December 2020. We evaluated the side of pain during current and previous bouts, demographic features, and clinical characteristics, including handedness. Multivariable logistic regression analyses were performed to identify factors associated with the side of pain. Results: The 227 patients with CH included 131 (57.7%) with right-sided pain and 86 (37.9%) with left-sided pain during the current bout (p<0.001). The 189 patients with previous bouts of CH included 86.8% who consistently reported the same side of pain throughout multiple bouts (side-locked pain), with a higher prevalence of pain on the right than the left side (55.0% vs. 31.7%, p<0.001). Multivariable analyses revealed that higher age at diagnosis (odds ratio [OR]=1.045, p=0.031) and shorter CH attacks (OR=0.992, p=0.017) were associated with left-side-locked pain. However, handedness was not associated with the lateralization of leftside-locked pain. Conclusions This study has confirmed the predominance of right-sided pain throughout multiple CH bouts. We found that higher age at diagnosis and shorter CH attacks were associated with left-side-locked pain, suggesting that certain clinical factors are associated with the pain laterality. However, the underlying mechanisms linking these factors to lateralized pain remain unclear and therefore require further investigation.