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To date, no clear conclusion on the relationships of gout with the occurrence of typical neurodegenerative diseases, Alzheimer’s disease (AD) and Parkinson’s disease (PD), has been reached. This study aimed to determine whether the patients with gout are at a lower or higher probability of developing AD or PD than those without gout. Longitudinal follow-up data of a representative sample of Korean adults were assessed. 18,079 individuals diagnosed with gout between 2003 and 2015 were enrolled in the gout group. The comparison group comprised 72,316 demographics-matched individuals not diagnosed with gout. Longitudinal associations of gout with AD or PD were estimated using Cox proportional hazard regression adjusting for potential confounders. The adjusted hazard ratios (HRs) of AD and PD in the gout group were 1.01 and 1.16 times higher than controls, but these differences were not statistically significant (95% confidence interval [CI] = 0.92–1.12 and 95% CI = 0.97–1.38, respectively). Although there was no significant association in the entire sample, AD and PD probabilities in patients with gout were significantly higher in participants

Vascular aging is well known to be associated with the breakdown of the neurovascular unit (NVU), which is essential for maintaining brain homeostasis and linked to higher cognitive dysfunction. Oxidative stress is believed to be a significant cause of the vascular aging process. Vitamin C is easily oxidized under physiological conditions, so it loses its potent antioxidant activity. We developed a DNA aptamer that enhances the function of vitamin C. NXP032 is the binding form of the aptamer and vitamin C. In this study, we investigated the effect of NXP032 on neurovascular stabilization through the changes of PECAM-1, PDGFR-β, ZO-1, laminin, and glial cells involved in maintaining the integrity of the blood–brain barrier (BBB) in aged mice. NXP032 was orally administered daily for 8 weeks. Compared to young mice and NXP032-treated mice, 20-month-old mice displayed cognitive impairments in Y-maze and passive avoidance tests. NXP032 treatment contributed to reducing the BBB damage by attenuating the fragmentation of microvessels and reducing PDGFR-β, ZO-1, and laminin expression, thereby mitigating astrocytes and microglia activation during normal aging. Based on the results, we suggest that NXP032 reduces vascular aging and may be a novel intervention for aging-induced cognitive impairment.

This study aimed to investigate the efficacy of a closed-cell self-expandable metallic stent (SEMS) with or without expanded-polytetrafluoroethylene (e-PTFE)-covering membrane in a porcine iliac artery model. Twelve Yorkshire domestic pigs were divided into a bare closed-cell SEMS (B-SEMS) group (n = 6) and covered closed-cell SEMS (C-SEMS) group (n = 6). Both closed-cell SEMSs were placed in the right or left iliac artery. Thrombogenicity score in the C-SEMS group was significantly higher than that in the B-SEMS group (p = 0.004) after 4 weeks. Angiographic findings of mean luminal diameters at 4 weeks follow-up did not differ significantly between B-SEMS and C-SEMS groups. Neointimal hyperplasia thickness as well as degree of inflammatory cell infiltration and collagen deposition in the C-SEMS group was significantly greater than that in the B-SEMS group (p

The management of patients with history or suspicion of difficult intubation can be challenging, especially in surgical procedures requiring one-lung ventilation. The ease of insertion of silicone double lumen tube (DLT) have previously been shown to be comparable to polyvinyl single lumen tube (SLT) in fiberoptic bronchoscope (FOB) tracheal intubation. Hence, in difficult airway situation, we hypothesized that the performance of insertion of silicone DLT would also be non-inferior to polyvinyl SLT in FOB intubation. We used a neck collar to mimic patients with difficult airway. 80 patients who required one-lung ventilation were enrolled in a prospective, randomized, non-inferiority trial. Patients were randomly allocated to the DLT or SLT groups (SLT with bronchial blocker). Neck collar was supplied to all patients before FOB intubation. The time of insertion for FOB, railroading, tracheal intubation, and total procedure were measured. The difficulty of railroading was evaluated in 4 grades. In the DLT group, the railroading was significantly shorter and easier comparing to the SLT group. The total procedure was also simpler and faster in the DLT group. While simulated difficult airways may not fully replicate actual difficult airways, we suggest that fiberoptic intubation with silicone DLT could be a feasible first-line option for patients with expected difficult airways requiring lung separation, unless the size of the DLT relative to the patient’s airway is problematic.Trial registration: NCT03392766.

Wearable assistive robotics has emerged as a promising technology to supplement or replace motor functions and to retrain people recovering from an injury or living with reduced mobility. We developed delayed output feedback control for a wearable hip-assistive robot, the EX1, to provide gait assistance. Our purpose in this study was to investigate the effects of long-term exercise with EX1 on gait, physical function, and cardiopulmonary metabolic energy efficiency in elderly people. This study used parallel experimental (exercise with EX1) and control groups (exercise without EX1). A total of 60 community-dwelling elderly persons participated in 18 exercise intervention sessions during 6 weeks, and all participants were assessed at 5 time points: before exercise, after 9 exercise sessions, after 18 sessions, and 1 month and 3 months after the last session. The spatiotemporal gait parameters, kinematics, kinetics, and muscle strength of the trunk and lower extremities improved more after exercise with EX1 than in that without EX1. Furthermore, the effort of muscles over the trunk and lower extremities throughout the total gait cycle (100%) significantly decreased after exercise with EX1. The net metabolic energy costs during walking significantly improved, and functional assessment scores improved more in the experimental group than in the control group. Our findings provide evidence supporting the application of EX1 in physical activity and gait exercise is effective to improve age-related declines in gait, physical function, and cardiopulmonary metabolic efficiency among older adults.

The genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P P = 0.006, HR 5.7). Our findings support the presence of genotype–phenotype correlation not only in male patients but also in female patients with XLAS.

Pulmonary contusion is an important risk factor for respiratory complications in trauma patients. Hence, we aimed to determine the relationship between the ratio of pulmonary contusion volume to the total lung volume and patient outcomes and the predictability of respiratory complications. We retrospectively included 73 patients with a pulmonary contusion on chest computed tomography (CT) from 800 patients with chest trauma admitted to our facility between January 2019 and January 2020. Chest injury severity was expressed as the ratio of pulmonary contusion volume to total lung volume by quantifying pulmonary contusion volume on chest CT. The cut-off value was 80%. Among the 73 patients with pulmonary contusion (77% males, mean age: 45.3 years), 28 patients had pneumonia, and five had acute respiratory distress syndrome. The number of patients in the severe risk group with > 20% of pulmonary contusion volume was 38, among whom 23 had pneumonia. For predicting pneumonia, the area under the receiver operating characteristic curves for the ratio of pulmonary contusion volume was 0.85 (95% confidence interval 0.76–0.95, p = 0.008); the optimal threshold was 70.4%. Quantifying pulmonary contusion volume using initial CT enables identifying patients with chest trauma at high risk of delayed respiratory complications.

This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P P P

We retrospectively analyzed National Health Insurance claims data (January 2002–December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

Desflurane is known to have a larger vasodilatory effect than that of sevoflurane. However, its generalizability and effect size in actual clinical practice are yet to be proven. Patients aged ≥ 18 years who underwent noncardiac surgery under general anesthesia using inhalation anesthetics (desflurane or sevoflurane) were matched 1:1 by propensity score. The mean intraoperative perfusion index (PI) of each patient were compared between the two groups. Propensity score matching of 1680 patients in the study cohort identified 230 pairs of patients. PI was significantly higher in the desflurane group (median of paired difference, 0.45; 95% CI 0.16 to 0.74, p = 0.002). PI durations below 1.0 and 1.5 were significantly longer in the sevoflurane group. Mean arterial pressure (MAP) and durations of low MAP did not differ significantly between the two groups. Generalized linear mixed models revealed that the use of sevoflurane, mean MAP, mean heart rate, age, and duration of anesthesia had significant negative effects (lower PI), whereas mean age-adjusted minimum alveolar concentration of inhalation agent had a positive effect on PI (higher value). Intraoperative PI was significantly higher in patients administered desflurane than sevoflurane. However, the impact of the choice between desflurane and sevoflurane on intraoperative PI in this clinical setting was minimal.

Human enteroviruses (EVs) are associated with a broad spectrum of diseases. To understand EV epidemiology, we present longitudinal data reflecting changing EV prevalence patterns in South Korea. We collected 7160 specimens from patients with suspected EV infections in ten hospitals in Gwangju, Korea during 2011–2020. RNA extraction and real-time reverse transcription polymerase chain reaction using EV-specific probes and primers were performed. EV genotyping and phylogenetic analysis were performed; EVs were detected in 3076 samples (43.0%), and the annual EV detection rate varied. EV infection rates did not differ with sex, and children aged ≤ 4 years were the most prone to EV infection; this trend did not change over time. Overall, 35 different EV types belonging to four distinctive species and rhinoviruses were identified. Although serotype distribution changed annually, the most frequently observed EVs were EV-A71 (13.1% of the cases), CVA6 (8.3%), CVB5 (7.6%), CVA16 (7.6%), CVA10 (7.5%), E18 (7.5%), E30 (7.0%), and E11 (5.0%) during 2011–2020. The predominant EV genotypes by clinical manifestation were CVB5 for aseptic meningitis; EV-A71 for hand, foot, and mouth disease cases; and CVA10 for herpangina. These results will aid the development of vaccines against EV infection and allow comprehensive disease control.

The Korean Intermittent Exotropia Multicenter Study (KIEMS) was a retrospective, cross-sectional and multicenter study for the investigation of intermittent exotropia involved 65 strabismus specialists from 53 institutions in Korea. Purpose of this study was to present ophthalmologic findings of intermittent exotropia from the KIEMS. Consecutive patients with intermittent exotropia of ≥ 8 prism diopters (PD) at distance or near fixation were included. Best-corrected visual acuity, cycloplegic refraction data, angles of deviation at several cardinal positions, ocular dominance, fusion control, oblique muscle function, and binocular sensory outcomes were collected. A total of 5385 participants (2793 females; age 8.2 years) were included. Non-dominant eye was more myopic than the dominant eye (− 0.60 vs. − 0.47 diopters, P

The CT syndesmophyte score (CTSS) can evaluate spinal progression more precisely than mSASSS in ankylosing spondylitis (AS); however, it is complex and time consuming. Here, we propose a simplified CTSS (sCTSS) for measuring spinal structural changes in AS. Patients with AS were recruited from a single tertiary hospital. Baseline and 2-year follow-up whole spine CT images were used to calculate CTSS and sCTSS. The sCTSS used the anterior and posterior vertebral corners, and ranged 0–184. Intraclass correlation coefficients (ICC) were calculated, as well as the smallest detectable changes. Fifty AS patients were included. For reader 1, the mean sCTSS at baseline and 2-year follow-up were 11.7 ± 14.6 and 15.8 ± 16.1, whereas those for reader 2 were 12.0 ± 12.5 and 15.8 ± 15.7, respectively. The ICCs for CTSS at baseline and at 2-year follow-up were 0.97 (95% confidence interval [CI] 0.96–0.99) and 0.98 (0.97–0.99), respectively, and that for changes over the 2 years was 0.48 (95% CI 0.23–0.67). For sCTSS, the ICCs were 0.96 (95% CI 0.92–0.97), 0.97 (95% CI 0.94–0.98), and 0.58 (95% CI 0.36–0.74), respectively. Detection rates for syndesmophyte progression were comparable between CTSS and sCTSS. The detection rate for syndesmophytes on only lateral side was 13.2 and 11.4%, and 11.4 and 15.2% at baseline and 2-year follow-up (reader 1 and 2). sCTSS and CTSS showed similar detection rates for syndesmophyte progression. sCTSS may be a reliable method for evaluating spinal structural damage in AS.

Tranilast, an anti-allergic drug used in the treatment of bronchial asthma, was identified as an inhibitor of the transcription factor Forkhead box O-1 (FoxO-1) by high throughput chemical library screening in the present study. Based on FoxO-1’s role in apoptotic cell death and differentiation, we examined the effect of tranilast on palmitic acid (PA)-induced cell damage in INS-1 cells. Tranilast substantially inhibited lipoapoptosis and restored glucose-stimulated insulin secretion under high PA exposure. Moreover, PA-mediated downregulation of PDX-1, MafA, and insulin expression was attenuated by tranilast. PA-induced oxidative and ER stress were also reduced in the presence of tranilast. These protective effects were accompanied by increased phosphorylation and decreased nuclear translocation of FoxO-1. Conversely, the effects of tranilast were diminished when treated in transfected cells with FoxO-1 phosphorylation mutant (S256A), suggesting that the tranilast-mediated effects are associated with inactivation of FoxO-1. Examination of the in vivo effects of tranilast using wild type and diabetic db/db mice showed improved glucose tolerance along with FoxO-1 inactivation in the pancreas of the tranilast-treated groups. Thus, we report here that tranilast has protective effects against PA-induced lipotoxic stress in INS-1 cells, at least partly, via FoxO-1 inactivation, which results in improved glucose tolerance in vivo.

As a non-thermal ablation method, irreversible electroporation (IRE) has been widely investigated in the treatment of prostate cancer. However, no consensus has been achieved on the optimal parameters of IRE for prostate cancer. Since high voltage is known to carry risks of muscle contraction and patient discomfort, it is crucial to identify the minimum but effective and safer applied voltage to inhibit tumor growth. In this study, the effect of different applied voltages of IRE on prostate cancer was evaluated in BALB/c nude mice. Mathematical simulation and measurement of the actual ablation area revealed a larger ablation area at a higher voltage. In in vivo experiment, except for the three different voltages applied, all groups received identical electrical conditions: pulse number, 180 (20 groups × 9 pulses/group); pulse width, 100 µs; pulse interval, 2 ms; distance between the electrodes, 5 mm; and electrode exposure length, 15 mm. Whilst the tumor volume initially decreased in the 500 V (1000 V/cm) and 700 V (1400 V/cm) groups and subsequently increased, only a transient increase followed by a continuous decrease until the sacrifice was observed in the 900 V (1800 V/cm) group. This result demonstrated a lasting effect of a higher applied voltage on tumor growth inhibition. The histological, immunohistochemical, and western blot findings all confirmed IRE-induced apoptosis in the treatment groups. Taken together, 900 V seemed to be the minimum applied voltage required to reduce tumor growth, though subsequent studies are anticipated to further narrow the voltage intervals and lower the minimum voltage required for tumor inhibition.

We investigated the thermographic findings of carpal tunnel syndrome (CTS). We enrolled 304 hands with electrodiagnostically identified CTS and 88 control hands. CTS hands were assigned to duration groups (D1, P = 0.003, 0.001, 0.001, and P = 0.005 and 0.04, respectively) were noted. Thermal anisometry was higher in the S4 group than in the S1, S2, and S3 groups (P = 0.009

We aimed to investigate the associations of previous influenza/URI with the susceptibility of COVID-19 patients compared to that of non-COVID-19 participants. A nationwide COVID-19 cohort database was collected by the Korea National Health Insurance Corporation. A total of 8,070 COVID-19 patients (1 January 2020 through 4 June 2020) were matched with 32,280 control participants. Severe COVID-19 morbidity was defined based on the treatment histories of the intensive care unit, invasive ventilation, and extracorporeal membrane oxygenation and death. The susceptibility/morbidity/mortality associated with prior histories of 1–14, 1–30, 1–90, 15–45, 15–90, and 31–90 days before COVID-19 onset were analyzed using conditional/unconditional logistic regression. Prior influenza infection was related to increased susceptibility to COVID-19 (adjusted odds ratio [95% confidence interval] = 3.07 [1.61–5.85] for 1–14 days and 1.91 [1.54–2.37] for 1–90 days). Prior URI was also associated with increased susceptibility to COVID-19 (6.95 [6.38–7.58] for 1–14 days, 4.99 [4.64–5.37] for 1–30 days, and 2.70 [2.55–2.86] for 1–90 days). COVID-19 morbidity was positively associated with influenza (3.64 [1.55–9.21] and 3.59 [1.42–9.05]) and URI (1.40 [1.11–1.78] and 1.28 [1.02–1.61]) at 1–14 days and 1–30 days, respectively. Overall, previous influenza/URI did not show an association with COVID-19 mortality. Previous influenza/URI histories were associated with increased COVID-19 susceptibility and morbidity. Our findings indicate why controlling influenza/URI is important during the COVID-19 pandemic.

Purpose: Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue. This epithelial tumor can be categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with histopathological and genetic differences. Genomic and transcriptomic profiles of craniopharyngiomas have been investigated; however, the proteomic profile has yet to be elucidated and added to these profiles. Recent improvements in high-throughput quantitative proteomic approaches have introduced new opportunities for a better understanding of these diseases and the efficient discovery of biomarkers. We aimed to confirm subtype-associated proteomic changes between ACP and PCP specimens.Methods: We performed a system-level proteomic study using an integrated approach that combines mass spectrometry-based quantitative proteomic, statistical, and bioinformatics analyses.Results: The bioinformatics analysis showed that differentially expressed proteins between ACP and PCP were significantly involved in mitochondrial organization, fatty acid metabolic processes, exocytosis, the inflammatory response, the cell cycle, RNA splicing, cell migration, and neuron development. Furthermore, using network analysis, we identified hub proteins that were positively correlated with ACP and PCP phenotypes.Conclusions: Our findings improve our understanding of the pathogenesis of craniopharyngiomas and provide novel insights that may ultimately translate to the development of craniopharyngioma subtype-specific therapeutics.

For pheochromocytoma and sympathetic paraganglioma (PPGL), surgery can be used as a curative treatment; however, the life-threatening risk of perioperative hemodynamic instability (HI) presents challenges. This study aimed to analyze the incidence and predictive factors of perioperative HI. The electronic medical records of 114 consecutive patients who underwent surgery for PPGLs at our institution were retrospectively reviewed. HI was defined as one or more episodes of systolic blood pressure > 200 mmHg or mean blood pressure

The use of cellular structures has led to unprecedented outcomes in various fields involving optical and mechanical cloaking, negative thermal expansion, and a negative Poisson’s ratio. The unique characteristics of periodic cellular structures primarily originate from the interconnectivity, periodicity, and unique design of the unit cells. However, the periodicity often induces unfavorable mechanical behaviors such as a “post-yielding collapse”, and the mechanical performance is often limited by the design of the unit cells. Therefore, we propose a novel structure called a meta grain structure (MGS), which is inspired by a polycrystalline structure, to enhance flexibility in design and mechanical reliability. A total of 138 different MGSs were built and tested numerically, and the correlations between the design parameters (e.g., the relative density) and mechanical properties of the MGSs were rigorously analyzed. A systematic design methodology was developed to obtain the optimal design of the MGS with the target Young’s modulus. This methodology makes it possible to build a unique structure that offers various design options and overcomes the current limitations of cellular structures. Furthermore, a systematic inverse design methodology makes it possible to produce an MGS that satisfies the required mechanical performance.

Central serous chorioretinopathy (CSC), characterized by serous detachment of the macular retina, can cause permanent vision loss in the chronic course. Chronic CSC is generally treated with photodynamic therapy (PDT), which is costly and quite invasive, and the results are unpredictable. In a retrospective case–control study design, we developed a two-stage deep learning model to predict 1-year outcome of PDT using initial multimodal clinical data. The training dataset included 166 eyes with chronic CSC and an additional learning dataset containing 745 healthy control eyes. A pre-trained ResNet50-based convolutional neural network was first trained with normal fundus photographs (FPs) to detect CSC and then adapted to predict CSC treatability through transfer learning. The domain-specific ResNet50 successfully predicted treatable and refractory CSC (accuracy, 83.9%). Then other multimodal clinical data were integrated with the FP deep features using XGBoost.The final combined model (DeepPDT-Net) outperformed the domain-specific ResNet50 (accuracy, 88.0%). The FP deep features had the greatest impact on DeepPDT-Net performance, followed by central foveal thickness and age. In conclusion, DeepPDT-Net could solve the PDT outcome prediction task challenging even to retinal specialists. This two-stage strategy, adopting transfer learning and concatenating multimodal data, can overcome the clinical prediction obstacles arising from insufficient datasets.

Monitoring nicotinamide adenine dinucleotide (NADH) is important because NADH is involved in cellular redox reactions and cellular energy production. Currently, few biosensors quantify NADH in whole blood. However, they still have limitations due to several defects, including poor repeatability, long analysis time, and their requirement of extra sample pretreatment. In this study, we developed electrocatalytic sensors using screen-printed electrodes with a redox-active monolayer 4′-mercapto-N-phenylquinone diamine formed by a self-assembled monolayer of a 4-aminothiophenol (4-ATP). We exhibited their behavior as electrocatalysts toward the oxidation of NADH in whole blood. Finally, the electrocatalytic sensors maintained stability and exhibited 3.5 µM limit of detection, with 0.0076 ± 0.0006 µM/µA sensitivity in a mouse’s whole blood. As proof of concept, a polyhexamethylene guanidine phosphate–treated mouse model was used to induce inflammatory and fibrotic responses, and NADH level was measured for 45 days. This work demonstrates the potential of electrocatalytic sensors to analyze NADH in whole blood and to be developed for extensive applications.

Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P P = 0.002, − 27.2%). Three months postoperative copeptin level

Identifying the severity of carpal tunnel syndrome (CTS) is essential to providing appropriate therapeutic interventions. We developed and validated machine-learning (ML) models for classifying CTS severity. Here, 1037 CTS hands with 11 variables each were retrospectively analyzed. CTS was confirmed using electrodiagnosis, and its severity was classified into three grades: mild, moderate, and severe. The dataset was randomly split into a training (70%) and test (30%) set. A total of 507 mild, 276 moderate, and 254 severe CTS hands were included. Extreme gradient boosting (XGB) showed the highest external validation accuracy in the multi-class classification at 76.6% (95% confidence interval [CI] 71.2–81.5). XGB also had an optimal model training accuracy of 76.1%. Random forest (RF) and k-nearest neighbors had the second-highest external validation accuracy of 75.6% (95% CI 70.0–80.5). For the RF and XGB models, the numeric rating scale of pain was the most important variable, and body mass index was the second most important. The one-versus-rest classification yielded improved external validation accuracies for each severity grade compared with the multi-class classification (mild, 83.6%; moderate, 78.8%; severe, 90.9%). The CTS severity classification based on the ML model was validated and is readily applicable to aiding clinical evaluations.

The association between weather-related variables or seasons and the development of Bell’s palsy (BP) is controversial. This study aimed to evaluate the incidence and clinical characteristics of BP and assess the effects of meteorological factors on seasonal and monthly incidence. This retrospective population-based study used data from the Korean Health Insurance claims database (NHICD) from 2010 to 2018, in which annual, seasonal, and monthly incidence rates and age and sex distributions were calculated. A multivariate linear regression and autoregressive integrated moving average (ARIMA) model was used to determine the association between the seasonal and monthly incidence of BP and meteorological factors, including average wind speed, temperature, relative humidity, and atmospheric pressure. We also conducted a scoping review of the literature on epidemiological and seasonality studies of BP in the past 30 years and summarized them in a table for easy comparison with other studies. In this study, the incidence rate of BP increased over 9 years (from 12.86 to 19.92 per 100,000 persons) and was the highest in patients in their 60s (31.6/100,000 persons). The seasonal incidence of BP was the highest in autumn and showed a significant difference compared with spring (coefficient − 0.318, p = 0.003) and summer (coefficient − 0.463, p p = 0.002), high atmospheric pressure (p = 0.034), and low relative humidity (p

Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein35–55 (MOG35–55)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood–brain barrier (BBB) integrity. In MOG35–55-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-γ and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4+ T cells and CD4−CD11b+CD45+ macrophage/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.

Three-dimensional visualization of cellular and subcellular-structures in histological-tissues is essential for understanding the complexities of biological-phenomena, especially with regards structural and spatial relationships and pathologlical-diagnosis. Recent advancements in tissue-clearing technology, such as Magnified Analysis of Proteome (MAP), have significantly improved our ability to study biological-structures in three-dimensional space; however, their wide applicability to a variety of tissues is limited by long incubation-times and a need for advanced imaging-systems that are not readily available in most-laboratories. Here, we present optimized MAP-based method for paper-thin samples, Paper-MAP, which allow for rapid clearing and subsequent imaging of three-dimensional sections derived from various tissues using conventional confocal-microscopy. Paper-MAP successfully clear tissues within 1-day, compared to the original-MAP, without significant differences in achieved optical-transparency. As a proof-of-concept, we investigated the vasculature and neuronal-networks of a variety of human and rodent tissues processed via Paper-MAP, in both healthy and diseased contexts, including Alzheimer’s disease and glioma.

In cellular experiments, radiation-induced DNA damage can be quantified by counting the number of γ-H2AX foci in cell nucleus by using an immunofluorescence microscope. Quantification of DNA damage carries uncertainty, not only due to lack of full understanding the biological processes but also limitations in measurement techniques. The causes of limited certainty include the possibility of expressing foci in varying sizes responding individual DSBs and the overlapping of foci on the two-dimensional (2D) immunofluorescence microscopy image of γ-H2AX foci, especially when produced due to high-LET radiation exposure. There have been discussions on those limitations, but no successful studies to overcome them. In this paper, a practical modelling has been developed to simulate the occurrences of double-strand breaks (DSBs) and the formations of γ-H2AX foci in response to individual DSB formations, in cell nucleus due to exposure to alpha particles. Cell irradiation and DSB production were simulated using a user-written code that utilizes Geant4-DNA physics models. A C + + code was used to simulate the formation γ-H2AX foci, which were spatially correlated to the loci of DBSs, and to calculate the number of individual foci from the observed 2D image of the cell nucleus containing the overlapping γ-H2AX foci. The average size of focal images was larger from alpha particle exposure than that from X-ray exposure, whereas the number of separate focal images were comparable except at doses up to 0.5 Gy. About 40% of separate focal images consisted of overlapping γ-H2AX foci at 1 Gy of alpha particle exposure. The foci overlapping ratios were obtained by simulation for individual size groups of focal images at varying doses. The size distributions of foci at varying doses were determined with experimentally obtained separate focal images. The correction factor for foci number was calculated using the foci overlapping ratio and foci size distribution, which are specific to dose from alpha particle exposure. The number of individual foci formations induced by applying the correction factor to the experimentally observed number of focal images better reflected the quality of alpha particles in causing DNA damage. Consequently, the conventional γ-H2AX assay can be better implemented by employing this computational modelling of γ-H2AX foci formation.

Dysbiosis of the oral microbiota plays an important role in the progression of periodontitis, which is characterized by chronic inflammation and alveolar bone loss, and associated with systemic diseases. Bacterial extracellular vesicles (EVs) contain various bioactive molecules and show diverse effects on host environments depending on the bacterial species. Recently, we reported that EVs derived from Filifactor alocis, a Gram-positive periodontal pathogen, had osteoclastogenic activity. In the present study, we analysed the osteoclastogenic potency and immunostimulatory activity of EVs derived from the Gram-negative periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia, the oral commensal bacterium Streptococcus oralis, and the gut probiotic strain Lactobacillus reuteri. Bacterial EVs were purified by density gradient ultracentrifugation using OptiPrep (iodixanol) reagent. EVs from P. gingivalis, T. forsythia, and S. oralis increased osteoclast differentiation and osteoclstogenic cytokine expression in osteoclast precursors, whereas EVs from L. reuteri did not. EVs from P. gingivalis, T. forsythia, and S. oralis preferentially activated Toll-like receptor 2 (TLR2) rather than TLR4 or TLR9, and induced osteoclastogenesis mainly through TLR2. The osteoclastogenic effects of EVs from P. gingivalis and T. forsythia were reduced by both lipoprotein lipase and polymyxin B, an inhibitor of lipopolysaccharide (LPS), while the osteoclastogenic effects of EVs from S. oralis were reduced by lipoprotein lipase alone. These results demonstrate that EVs from periodontal pathogens and oral commensal have osteoclastogenic activity through TLR2 activation by lipoproteins and/or LPS.

The present study evaluated the predictive role of baseline radiographic change and disease activity on drug retention and clinical response in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor inhibitor (TNFi). Korean Observational Study Network for Arthritis (KORONA) registry was evaluated to identify RA patients treated with a TNFi. Disease activity score-28 (DAS28) was evaluated at baseline and 1 year after TNFi initiation or at termination of TNFi due to inefficacy (within 1 year). The retention rate of TNFi was compared in patients with and without bony erosions. The hazard ratio (HR) for drug retention was evaluated by Cox regression analysis, as was the odds ratio (OR) for achieving remission (DAS28 p = 0.04). Factors significantly associated with drug discontinuation included the presence of erosions (HR = 2.45, 95% CI 1.08–5.51) and higher time-averaged DAS28 (HR = 2.17, 95% CI 1.47–3.20), whereas concomitant methotrexate was associated with lack of drug discontinuation (HR = 0.40, 95% CI 0.17–0.95). The presence of erosions and high time-averaged disease activity could predict poor retention of TNFi by RA patients. Higher baseline DAS28 was associated with a reduced clinical response in patients with RA.Trial registration Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.

Herein, we investigated the effect of DJ-1 on helper T cell differentiation, fibroblast-like synoviocyte (FLS) activation, and osteoclastogenesis in rheumatoid arthritis (RA). Serum and synovial fluid (SF) of RA and osteoarthritis (OA) patients were collected, and DJ-1 and H2O2 levels were investigated. CD4+ cells from peripheral blood mononuclear cells (PBMCs) were cultured under type 17 helper T cell (Th17) polarization conditions, and CD4+ T cell differentiation, pro-inflammatory cytokine levels, and soluble receptor activator of nuclear factor kappa-Β ligand (RANKL) were assessed. RA-FLSs were stimulated with 50 μM H2O2, and DJ-1 (10, 50, 100 ng/mL) to evaluate MMP-9, VEGF, TNF-α, and sRANKL production, while RANKL+ FLSs were assessed using flow cytometry. Monocytes were cultured with RANKL or IL-17A with or without DJ-1 and H2O2-pretreated RA-FLS, and tartrate-resistant acid phosphatase (TRAP) staining and RT-qPCR of osteoclast-related genes were performed. The levels of DJ-1 and H2O2 in serum and SF of RA patients were higher than those of OA patients. Under Th17-polarizing conditions, CD4+RANKL+ and CD4+CCR4+CCR6+CXCR3- T cells decreased, whereas CD4+CD25highFoxp3+ T cell increased after DJ-1 administration. Additionally, IL-17A, TNF-α, and sRANKL levels decreased in DJ-1-treated groups. DJ-1 lowered MMP-9, VEGF, TNF-α, and sRANKL levels, and RANKL+ FLS in ROS-stimulated RA-FLS. Both RANKL and IL-17A stimulated osteoclast differentiation, DJ-1 decreased TRAP+ cell count, and the expression levels of TRAP, ATP6v0d2, NFATc1, and CTSK. These findings were also observed in in vitro osteoclastogenesis with DJ-1 pretreated RA-FLS. As DJ-1 regulates Th17/Treg imbalance, pro-inflammatory cytokine production, RA-FLS activation, and osteoclastogenesis, it holds potential for RA therapy.

Several investigations on the feasibility of stent placement into the Eustachian tube (ET) are being conducted. However, stents optimized for the anatomical structure of the ET have not yet been developed. In this study, the efficacy and safety of a self-expandable metallic stent (SEMS) optimized for porcine ET morphology was investigated. Silicone was injected into a cadaveric porcine ET to analyze the ET morphology. The three-dimensional-reconstructed porcine ET phantom images obtained after a computed tomography scan were measured to determine the dimensions of the porcine ET. The SEMS was designed as a tapered structure on the basis of the morphological findings of the porcine ET. The tapered SEMS (T-SEMS) and conventional SEMS (C-SEMS) were placed into the porcine ET to compare the safety and efficacy of the two types of SEMSs. Stent-induced tissue hyperplasia in the T-SEMS group was significantly lower than that in the C-SEMS group (p

This study aims to investigate the difference in physiological loading on the spine in three different motions (flexion–extension, lateral bending, and axial rotation) between osteoporotic and normal spines, using finite element modelling. A three-dimensional finite element (FE) model centered on the lumbar spine was constructed. We applied two different material properties of osteoporotic and normal spines. For the FE analysis, three loading conditions (flexion–extension, lateral bending, and axial rotation) were applied. The von Mises stress was higher on the nucleus pulposus at all vertebral levels in all movements, in the osteoporosis group than in the normal group. On the annulus fibrosus, the von Mises stress increased at the level of L3–L4, L4–L5, and L5–S in the flexion–extension group and at L4–L5 and L5–S levels in the lateral bending group. The values of two motions, flexion–extension and lateral bending, increased in the L4 and L5 cortical bones. In axial rotation, the von Mises stress increased at the level of L5 of cortical bone. Additionally, the von Mises stress increased in the lower endplate of L5–S and L4–L5 in all movements, especially lateral bending. Even in the group with no increase, there was a part that received increased von Mises stress locally for each element in the three-dimensional reconstructed view of the pressure distribution in color. The von Mises stress on the lumbar region in the three loading conditions, was greater in most components of osteoporotic vertebrae than in normal vertebrae and the value was highest in the nucleus pulposus. Considering the increase in the measured von Mises stress and the local increase in the pressure distribution, we believe that these results can contribute to explaining discogenic pain and degeneration.

This study analyzed the effect of parental supervision of infants at age 4 to 6 months on injuries at age 4 to 12 months. Among all Korean children born during 2008–2009, 464,326 (50.6%) infant had parents who responded to a questionnaire that surveyed their safety and supervision when infant were 4 to 6 months-old. Based on questionnaire score, infant were divided into “safe” or “unsafe” group. 1:1 propensity score matching was used to balance the groups, and injury diagnosis and treatments were analyzed. After matching, we examined the records of 405,862 infant. The unsafe group had significantly increased risk ratios (RRs) for injury of head/neck (RR: 1.06), trunk/abdominopelvic region (RR: 1.12), upper extremities (RR: 1.04), and from burn and frostbite (RR: 1.10). The risks of a wound and fracture and foreign body injury were significantly greater in infant whose parents sometimes left them alone (RR: 1.15 and 1.06, respectively), and whose parents did not always keep their eyes on them (RR: 1.04 and 1.13, respectively). Infant whose parents had a hot drink when carrying them had an increased risk of burn injuries (RR: 1.21). Injuries were less common in infant whose parents provided more supervision.

In this cross-sectional study, we investigated choroidal thickness (CT) and scleral thickness (ST) in highly myopic eyes and their associations with ocular factors. Patients underwent widefield swept-source optical coherence tomography (OCT) to measure the CT and ST at the subfovea and 3000 μm superior, inferior, temporal, and nasal to the fovea and macular curvature. A total of 237 eyes (154 patients) were included. At all five measurement points, thinner CTs and STs were associated with longer axial lengths (r = − 0.548 to − 0.357, all P r = − 0.542 to − 0.305, all P P ≤ 0.006) but did not differ between eyes with the wide macular and narrow macular type of staphyloma. Eyes with myopic maculopathy of category ≥ 3 according to the International Meta-Analysis for Pathologic Myopia classification had significantly thinner CTs and STs than those with category ≤ 2 (all P ≤ 0.005). In highly myopic eyes, a decrease in the CT and ST was more pronounced in eyes with more structural changes, such as longer axial length, steeper macular curvature, and the presence of posterior staphyloma.

Since a potential link between statins and the risk of adverse chronic periodontitis (CP) has been raised, we aimed to validate the association between statin use and the incidence of CP using nationwide cohort data. This longitudinal follow-up study included 169,381 patients prescribed statins who were matched with an equal number of controls using propensity scores from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2015). A Cox proportional hazard model was used to assess the occurrence of CP following statin use after adjusting for multiple covariates. The occurrence of CP was significantly higher in patients who had long-term use (1–3 years, 3–5 years, or > 5 years) than with short-term use (≤ 1 year) of statins. After adjustment, statin users exhibited an occurrence of CP 1.32-fold higher (95% confidence interval 1.30–1.33) than that of the matched nonusers (incidence: 25.0 and 22.0 per 100 person-years, respectively). Subgroup analyses supported the adverse impact of statins on CP independent of age and gender. Statin user odds ratios for developing CP were higher compared to those of nonusers. This was consistent in individuals aged > 40 years in both genders, especially with long-term use.

This study was aimed at investigating the clinical efficacy of probiotics in pneumonia patients. To this end, we enrolled 80 participants diagnosed with pneumonia at Naval Pohang Hospital, Pohang, Korea, from May 2016 to January 2017. The participants were randomly assigned to the control and probiotic groups depending on whether they received probiotics. All participants clinically improved but 22.6% of the participants complained of abnormal stool habits after pneumonia treatment. In comparison, fever duration was significantly shorter in the probiotic group, and the group exhibited an improved general condition. The probiotic group also showed better stool characteristics according to the Bristol stool scale (P = 0.009). Notably, the serum hs-CRP levels were significantly lower in the probiotic group at 2 weeks of treatment (P = 0.015), and all participants in the probiotic group achieved their levels within the normal range. Flow cytometry was used to analyze T-helper 17 (Th17) cells and regulatory T cells (Tregs). Tregs were promoted and the Th17 cell/Treg ratio was suppressed after 2 weeks of treatment in the probiotic group (P = 0.007 and 0.037, respectively). This study demonstrated that probiotics improved clinical symptoms and normalized inflammatory biomarker levels in patients with pneumonia. Early infection and inflammation recovery may be due to the immunomodulatory effects of probiotics by facilitating the subset of Tregs and suppressing the Th17 cell/Treg ratio.

Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have been attracted as candidate treatments for Alzheimer's disease (AD). Fifteen khellactone-type coumarins from the roots of Peucedanum japonicum Thunberg were tested for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and MAO inhibitory activities. Compound 3′-angeloyl-4′-(2-methylbutyryl)khellactone (PJ13) most potently inhibited AChE (IC50 = 9.28 µM), followed by 3′-isovaleryl-4′-(2-methylbutyroyl)khellactone (PJ15) (IC50 = 10.0 μM). Compound senecioyl-4′-angeloyl-khellactone (PJ5) most potently inhibited BChE (IC50 = 7.22 μM) and had the highest selectivity index (> 5.54), followed by 3′-senecioyl-4′-(2-methylbutyryl)khellactone (PJ10) and 3′,4′-disenecioylkhellactone (PJ4) (IC50 = 10.2 and 10.7 μM, respectively). Compounds PJ13, PJ15, and PJ5 showed reversible and mixed-types of inhibition with Ki values of 5.98, 10.4 (for AChE), and 4.16 µM (for BChE), respectively. However, all 15 compounds weakly inhibited MAO-A and MAO-B. Molecular docking simulation revealed that PJ13 had a higher binding affinity (− 9.3 kcal/mol) with AChE than PJ15 (− 7.8 kcal/mol) or PJ5 (− 5.4 kcal/mol), due to the formation of a hydrogen bond with Tyr121 (distance: 2.52 Å). On the other hand, the binding affinity of PJ5 (− 10.0 kcal/mol) with BChE was higher than for PJ13 (− 7.7 kcal/mol) or PJ15 (− 8.1 kcal/mol), due to the formation of a hydrogen bond with Ser198 (distance: 2.05 Å). These results suggest that PJ13 and PJ5 are potential reversible selective inhibitors of AChE and BChE, respectively, for the treatment of AD.

Stent-grafts composed of expanded polytetrafluoroethylene (e-PTFE), polyethylene terephthalate (PET) and polyurethane (PU) are characterized by poor endothelialization, high modulus, and low compliance, leading to thrombosis and intimal hyperplasia. A composite synthetic/natural matrix is considered a promising alternative to conventional synthetic stent-grafts. This study aimed to investigate the efficacy of thermoplastic polyurethane (TPU) and gelatin (GL) blended nanofibers (NFs) covered stent-graft in the porcine iliac artery. Twelve pigs were randomly sacrificed 7 days (n = 6) and 28 days (n = 6) after stent-graft placement. The thrombogenicity score at 28 days was significantly increased compared at 7 days (p p

To facilitate rapid determination of cellular viability caused by the inhibitory effect of drugs, numerical deep learning algorithms was used for unlabeled cell culture images captured by a light microscope as input. In this study, A549, HEK293, and NCI-H1975 cells were cultured, each of which have different molecular shapes and levels of drug responsiveness to doxorubicin (DOX). The microscopic images of these cells following exposure to various concentrations of DOX were trained with the measured value of cell viability using a colorimetric cell proliferation assay. Convolutional neural network (CNN) models for the study cells were constructed using augmented image data; the predicted cell viability using CNN models was compared to the cell viability measured by colorimetric assay. The linear relationship coefficient (r2) between measured and predicted cell viability was determined as 0.94–0.95 for the three cell types. In addition, the measured and predicted IC50 values were not statistically different. When drug responsiveness was estimated using allogenic models that were trained with a different cell type, the correlation coefficient decreased to 0.004085–0.8643. Our models could be applied to label-free cells to conduct rapid and large-scale tests while minimizing cost and labor, such as high-throughput screening for drug responsiveness.

Beta-4 (β4)-spectrin, encoded by the gene Sptbn4, is a cytoskeleton protein found at nodes and the axon initial segments (AIS). Sptbn4 mutations are associated with myopathy, neuropathy, and auditory deficits in humans. Related to auditory dysfunction, however, the expression and roles of β4-spectrin at axon segments along the myelinated axon in the developing auditory brain are not well explored. We found during postnatal development, β4-spectrin is critical for voltage-gated sodium channel (Nav) clustering at the heminode along the nerve terminal, but not for the formation of nodal and AIS structures in the auditory brainstem. Presynaptic terminal recordings in Sptbn4geo mice, β4-spectrin null mice, showed an elevated threshold of action potential and increased failures during action potential train at high-frequency. Sptbn4geo mice exhibited a slower central conduction and showed no startle responses, but had normal cochlear function. Taken together, the lack of β4-spectrin impairs Nav clustering at the heminode along the nerve terminal and the temporal fidelity and reliability of presynaptic spikes, leading to central auditory processing deficits during postnatal development.

Northeast Asia has been suffering from dramatic increases of particulate matter (PM) since the late 1990s, and it still continues to undergo haze despite various abating regulations. In this study, we investigated aerosol-cloud-precipitation (ACP) interactions with the varied PM, and the impact of long-range transport (LRT) process on ACP in springtime was assessed in Northeast Asia. Our long-term (1995–2019) analysis of PM10 exhibited the correlation with decreases of both sunshine duration and drizzle occurrences that can be interpreted as direct and indirect aerosol effects, while cloud cover induced by the varied PM10 was found only in more than 90% cloud cover (9/10–10/10 category). The online WRF-Chem with wind-blown dust simulation indicated that cloud water was affected by secondary inorganic aerosol (SIA) formation near the surface in upwind areas dominantly, whereas, along the LRT pathway, cloud water perturbation altitudes were increased quasi-linearly toward downward between 1 and 3 km. The gas-to-particle conversion ratios of sulfur ([SO42−]/[SO2 + SO42−]) and nitrogen ([NO3−]/[NO2 + NO3−]) both remain aloft long at the same vertical levels of most perturbed cloud altitude enough to be transported over long distance in springtime. Formations of sulfate and nitrate showed different ACP interaction timing; distinctive shifts in the ratios observed at the exit (Shanghai-Yellow Sea) by nitrate, and entrance areas (Seoul-Tokyo) by sulfate along the LRT pathway, respectively, with higher ratios of 0.8 or more in springtime. Our results indicate that ACP processes have been enhanced at a LRT-related altitude with different SIA production timings that can be considered in species-specific springtime PM abatements over Northeast Asia.

Although large exciton binding energies of typically 0.6–1.0 eV are observed for monolayer transition metal dichalcogenides (TMDs) owing to strong Coulomb interaction, multilayered TMDs yield relatively low exciton binding energies owing to increased dielectric screening. Recently, the ideal carrier-multiplication threshold energy of twice the bandgap has been realized in multilayered semiconducting 2H-MoTe2 with a conversion efficiency of 99%, which suggests strong Coulomb interaction. However, the origin of strong Coulomb interaction in multilayered 2H-MoTe2, including the exciton binding energy, has not been elucidated to date. In this study, unusually large exciton binding energy is observed through optical spectroscopy conducted on CVD-grown 2H-MoTe2. To extract exciton binding energy, the optical conductivity is fitted using the Lorentz model to describe the exciton peaks and the Tauc–Lorentz model to describe the indirect and direct bandgaps. The exciton binding energy of 4 nm thick multilayered 2H-MoTe2 is approximately 300 meV, which is unusually large by one order of magnitude when compared with other multilayered TMD semiconductors such as 2H-MoS2 or 2H-MoSe2. This finding is interpreted in terms of small exciton radius based on the 2D Rydberg model. The exciton radius of multilayered 2H-MoTe2 resembles that of monolayer 2H-MoTe2, whereas those of multilayered 2H-MoS2 and 2H-MoSe2 are large when compared with monolayer 2H-MoS2 and 2H-MoSe2. From the large exciton binding energy in multilayered 2H-MoTe2, it is expected to realize the future applications such as room-temperature and high-temperature polariton lasing.

DNA double-strand break (DSB) induction is one of the phenotypes of cellular damage from radiation exposure and is commonly quantified by γ-H2AX assay with the number of excess fluorescent foci per cell as the main component. However, the number of foci alone may not fully characterize the state of DNA damage following exposures to different radiation qualities. This study investigated the feasibility of utilizing the focus size distribution and dephosphorylation rate of γ-H2AX to identify the type of causative radiation and dose. Human lung epithelial cells and mouse vascular endothelial cells were used to observe the expression changes of γ-H2AX foci due to alpha particle and X-ray exposures. Results showed that the average number of excess foci per cell linearly increased with the dose. The focus size distribution showed a consistent pattern depending on the causative radiation type. Three criteria for the identification of causative radiation type were derived from experimental focus size distributions and were validated in blind testing with correct identification of 27 out of 32 samples. The dose could be estimated based on the proportionality constant specific to the identified radiation type with a difference of less than 15% from the actual value. The different dephosphorylation rates of γ-H2AX produced from alpha particle and X-ray exposures were effectively utilized to determine the individual dose contributions of alpha particles and X-rays under mixed beam exposure. Individual doses were estimated to have differences of less than ~ 12% from actual values.