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Background: This study aimed to evaluate the predictive ability of two widely used early warning scoring systems, the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), for predicting stroke occurrence in hospitalized patients., Methods: The study enrolled 5,474 patients admitted to the intensive care unit from the general ward using data from the Smart Clinical Data Warehouse (CDW). MEWS and NEWS were calculated based on vital signs and clinical parameters within four hours of stroke onset. Stroke occurrence was categorized as ischemic or hemorrhagic. Logistic regression and receiver operating characteristic curve analyses were performed to assess the predictive abilities of the scoring systems., Results: Of the enrolled patients, 33.9% (n = 1853) experienced stroke, comprising 783 cases of ischemic stroke and 1,070 cases of hemorrhagic stroke. Both the MEWS and the NEWS were found to significantly predict overall stroke occurrence with a cutoff value of 4 (MEWS>4; OR [95% CI]: 13.90 [11.51-16.79], p<0.001; NEWS>4; OR [95% CI]: 6.71 [5.75-7.83], p<0.001). Parameters, such as prior malignancy, atrial fibrillation, AVPU response, heart rate, respiratory rate, and oxygen saturation, are also associated with stroke occurrence. The predictive ability of MEWS and NEWS was good for overall stroke occurrence. (AUC of MEWS: 0.92, 95% CI [0.91-0.93], p<0.001; AUC of NEWS: 0.85, 95% CI [0.84-0.86], p<0.001). The predictive ability was considered fair for ischemic stroke but good for hemorrhagic stroke., Conclusion: MEWS and NEWS demonstrated significant predictive abilities for overall stroke occurrence among hospitalized patients, with MEWS slightly outperforming NEWS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to identify radiotherapy dosimetric parameters related to local failure (LF)-free survival (LFFS) in patients with lung and liver oligometastases from colorectal cancer treated with stereotactic body radiotherapy (SBRT). We analyzed 75 oligometastatic lesions in 55 patients treated with SBRT between January 2014 and December 2021. There was no constraint or intentional increase in maximum dose. LF was defined as the progression of the treated lesion until the last follow-up or death. The dose distributions were recalculated using Monte Carlo-based algorithms. The significance of the planning target volume (PTV) biologically effective dose (BED) 10s (D2, D95, D98, Dmean) in LFFS was evaluated using Cox regression, considering sex, age, primary cancer, tumor site, oligometastatic status, multiplicity, and either tumor size or one of the volume parameters. LF occurred in 23.4% of the lesions. Lesions showing LF received significantly lower PTV D2 (146 ± 21 vs. 164 ± 23, p = 0.006). Multivariate analysis revealed that PTV D2 (< 159 Gy10 vs. ≥ 159 Gy10) was the sole dosimetric parameter associated with LFFS. Tumors equal to or larger than the median size/volume yet receiving < 159 Gy10 of PTV D2 showed the lowest LFFS following stratification by median PTV D2 combined with tumor size or volume parameters. The maximum dose (PTV D2) was significantly associated with LFFS after SBRT for lung and liver oligometastases from colorectal cancer. Increasing the maximum dose may be beneficial for managing larger tumors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Participants' satisfaction is an important factor in securing competitiveness in clinical trials. In many industries, such as healthcare, customer service quality has been analyzed to increase customer satisfaction. However, no study so far has attempted to measure participants' perceptions of service quality in the clinical trial area and identify its effect on participant satisfaction., Objective: This study examined the experiences and perceptions of clinical trial participants in terms of service quality and identified the factors that impact participant satisfaction in clinical trials., Methods: This study used a cross-sectional descriptive and explanatory research design. Data were collected from March 29 to May 26, 2023, via a survey. The survey was conducted with 206 adults participating in clinical trials at two hospitals in Korea. The collected data were analyzed using descriptive statistics, independent t-tests, one-way ANOVA, Pearson's correlation, and multiple linear regression analysis., Results: Participants' perceptions of the service quality and their satisfaction in clinical trials were generally positive. The variables that significantly predicted participant satisfaction in clinical trials included quality of interaction with researchers, physical environment, performance results in clinical trials, changes in health status after participating in the trial, and consideration of discontinuing the trial., Conclusions: Participants' perception of the service quality significantly affected their satisfaction in clinical trials. Thus, all components of service quality should be considered in the overall clinical trial process to increase participants' satisfaction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Symptomatic vestibulopathy impairs patients' lives. However, few studies have explored the lives of patients with compensated or asymptomatic vestibulopathy. This study investigated the quality of life (QOL), psychological health, and physical function of patients with vestibulopathy., Materials and Methods: Using the eighth Korea National Health and Nutrition Examination Survey database, we included individuals with data on demographic factors, diabetes, hypertension, dizziness experiences, pure-tone audiometry, video head impulse test (vHIT), Health-related Quality of Life Instrument with 8 Items, General Anxiety Disorder 7-item scale, stress, and walking and sitting times. Participants were classified into the following groups: an uncompensated group with abnormal vHIT result and chronic dizziness, a compensated group with abnormal vHIT result and a history of dizziness, an asymptomatic group with abnormal vHIT result and no history of dizziness, and a normal group without abnormal vHIT result or a history of dizziness., Results: Uncompensated vestibulopathy was more common in older individuals and women. The uncompensated group showed impairments in climbing stairs (P < 0.001), pain (P < 0.001), vitality (P = 0.001), working (P < 0.001), depression (P < 0.001), sleep (P = 0.001), happiness (P = 0.002), anxiety (P = 0.006), and stress (P = 0.003). The compensated group showed deficits in pain (P < 0.001), work (P = 0.006), sleep (P = 0.001), and happiness (P = 0.001). The asymptomatic group had no deficits in QOL, psychological health, or physical function. These tendencies were similar after controlling for age and gender., Conclusion: Vestibulopathy with a history of dizziness has a long-lasting impact on QOL and emotional status, even after compensation. Uncompensated vestibulopathy has a significant effect on QOL and mental health. Notably, though, the compensated group also showed a reduction in QOL. Appropriate interventions for each category of patients should be provided based on their impaired functions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study aimed to determine whether the olfactory bulb height (OBH) measured using magnetic resonance imaging (MRI) has clinical utility as an imaging biomarker in the evaluation of patients with idiopathic Parkinson's disease (iPD) through its correlation with movement impairment., Methods: This retrospective study included cognitively intact patients with suspected parkinsonism. All participants underwent T2-weighted imaging to measure OBH. Logistic regression was used to determine whether OBH was an independent risk factor for distinguishing iPD patients from disease controls, and its relation with clinical parameters related to motor impairment, including clinical laterality, modified Hoehn and Yahr (HY) stage, and Unified Parkinson's Disease Rating Scale (UPDRS) III score, was investigated., Results: Based on the final clinical diagnosis, 79 patients with iPD and 16 disease controls were included. The mean OBH was significantly smaller in iPD than in disease controls (p < 0.0001). OBH was a significant independent predictor of iPD, with a cutoff of 1.52 mm. In the comparison among the ipsilateral, contralateral side of iPD with clinical laterality, and disease control group, the OBH of the disease control group was significantly larger than both the ipsilateral and contralateral sides (P < 0.05). However, there was no significant difference in OBH between the ipsilateral and contralateral sides (p > 0.05). OBH according to HY stage was significantly smaller in HY stage 2-3 groups than in the disease control group (p < 0.001). The correlation analysis between UPDRS III and OBH showed a mild negative correlation (r = -0.32, p = 0.013)., Conclusions: MRI-measured OBH is decreased in iPD regardless of age and sex and may be correlated with the progression of motor symptoms in the iPD., Competing Interests: NO authors have competing interests, (Copyright: © 2024 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous studies have demonstrated geographical disparities regarding the quality of care for acute myocardial infarction (AMI). The aim of this study was two-fold: first, to calculate the proportion of patients with AMI who received primary percutaneous coronary interventions (pPCIs) by secondary medical areas (SMAs), which provide general inpatient care, as a quality indicator (QI) of the process of AMI practice. Second, to identify patterns in their trajectories and to investigate the factors related to regional differences in their trajectories., Methods: We included patients hospitalized with AMI between April 2014 and March 2020 from the national health insurance claims database in Japan and calculated the proportion of pPCIs across 335 SMAs and fiscal years. Using these proportions, we conducted group-based trajectory modeling to identify groups that shared similar trajectories of the proportions. In addition, we investigated area-level factors that were associated with the different trajectories., Results: The median (interquartile range) proportions of pPCIs by SMAs were 63.5% (52.9% to 70.5%) in FY 2014 and 69.6% (63.3% to 74.2%) in FY 2020. Four groups, named low to low (LL; n = 48), low to middle (LM; n = 16), middle to middle (MM; n = 68), and high to high (HH; n = 208), were identified from our trajectory analysis. The HH and MM groups had higher population densities and higher numbers of physicians and cardiologists per capita than the LL and LM groups. The LL and LM groups had similar numbers of physicians per capita, but the number of cardiologists per capita in the LM group increased over the years of the study compared with the LL group., Conclusion: The trajectory of the proportion of pPCIs for AMI patients identified groups of SMAs. Among the four groups, the LM group showed an increasing trend in the proportions of pPCIs, whereas the three other groups showed relatively stable trends., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Itoshima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study reports the effects of changes in the waveform and frequency of radio frequency (RF) energy on the tissue ablation range. We developed a 70-watt RFA generator that provides sine and square waves and allows frequency control between 10 Hz and 500 kHz. The changes in the ablation range according to the waveform and frequency were observed using the developed generator. In the waveform variation test, the distance between the electrodes and the electrode type were changed for both waveforms with the frequency set to 500 kHz. In the frequency variation test, the waveform and electrode type were changed with the frequency set to 10, 100, and 500 kHz, while the distance between the electrodes was set to 20 mm. A fixed 45 voltage was applied using the bipolar method. RF energy was applied for 90 s in vitro. The temperature was regulated to not exceed 70°C. The ablation range was calculated using ImageJ software. The analysis results showed that the ablation range was larger with the square wave than with the sine wave and at 10 kHz than at 500 kHz. The developed generator can advance research on ablation area and depth in RF ablation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 An et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A 50:50 blend of two Bacillus subtilis strains positively impacted the productivity of finishing pigs. Given this observed effect, we hypothesized that each strain has distinct effects on weight gain and their influence on gut microbiota. In a 16-week test, 160 pigs were divided into four groups: basal diet, B. subtilis ps4100, B. subtilis ps4060, and 50:50 mixture supplemented. Subsequently, we compared body weight and fecal microbiota. Among the supplements, ps4100, ps4060, and the 50:50 mix yielded respective average daily weight gains (ADG) of 3.6%, 4.6%, and 3.9% by the 6th week. The weight difference was maintained through the 16th week. At the 11th week, the difference in α-diversity among the fecal microbiota was marginal, and 17 of 229 genera showed differential abundance between the control and either of the treatment groups. A total of 12 of the 17 genera, including Lactobacillus, showed differential abundance between the ps4100 and ps4060-fed groups, and only Eubacterium consistently decreased in abundance in both the ps4100 and ps4060 groups. In comparison, microbial diversity was significantly different at the 16th week (p < 0.05), with 96 out of 229 genera exhibiting differential abundance. A total of 42 of the 96 genera exhibited similar patterns in both the ps4100 and ps4060 groups compared to the control group. Additionally, 236 of 687 microbial enzymes with differential abundance deduced from 16S rRNA reads showed similar differential abundance in both groups compared to the control group. We concluded that the overall microbial balance, rather than the dominance or significant decrease of a few specific genera, likely caused the enhanced ADG until the 11th week. Substantial changes in microbiota manifested at the 16th week did not cause dramatically increased ADG but were a consequence of weight gain and could positively affect animal physiology and health afterward., Competing Interests: YC owns over 70% stocks of a startup company, ProxEnrem INC. This manuscript could facilitate the process of registering the strains described in the manuscript as animal diet supplement in the Republic of Korea. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML., Materials and Methods: BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples., Results: We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers., Conclusions: Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: We investigated the vertical implantation of a toric implantable collamer lens (ICL) and compared the rotational stability with that of horizontal implantation., Methods: This matched comparative study retrospectively reviewed and analyzed data from patients who underwent ICL implantation from 2003-2022 by 1:1 matching vertical and horizontal (V and H toric groups, respectively) implantation patients according to preoperative astigmatism, spherical equivalent, sulcus-to-sulcus, anterior chamber depth, and ICL size. Visual acuity, manifest refraction, vaulting, and rotation were measured 3 months postoperatively., Results: We included 646 eyes (323 each in the V and H toric groups). No statistically significant difference was observed between groups in postoperative visual acuity, refractive error, and astigmatism. Vaulting was lower in the V toric group. (P < 0.001). The mean lens rotation in the V toric group was less than that in the H toric group (1.11 ± 2.84° versus 3.02 ± 10.34°, P = 0.001). The proportion of eyes in the V and H toric groups showing ≥10° of rotation was 2.5% (8 eyes) and 6.5% (21 eyes), respectively (P = 0.014). Despite repositioning from rotation, three (0.9%) and eight (2.5%) eyes required removal owing to lens re-rotation in the V and H toric groups, respectively., Conclusion: Toric ICL vertical implantation showed good rotational stability, and appropriate visual acuity correction results with relatively low vaulting. This procedure therefore presents an effective novel method that could replace horizontal toric ICL implantation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To compare the efficacy of a 0.15% HA with that of 0.1% HA eye drops for DES after cataract surgery., Methods: This study was double blinded, randomized and prospective study, and conducted in 69 participants (70 eyes) from Pusan National University Yangsan Hospital and executed from February 1, 2022 to November 30, 2022. Participants were adult cataract patients with normal lid position, not suffering from any other ocular disease and not meet the exclusion cirteria of clinical trial. Participants were randomly divided into two groups: 35 participants (17 males and 18 females) in the 0.1% HA group and 34 participants (19 males and 15 females) in the 0.15% HA group, receiving treatment six times daily for 6 weeks following cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits, including ocular surface disease index score, tear break up time, corneal staining score, Schirmer's I test score, lipid layer thickness), meiboscore, and biochemical analysis of the eye drops., Results: Throughout the study, the postoperative ocular surface disease index score was significantly lower in the group receiving 0.15% hyaluronic acid than in the group receiving 0.1% hyaluronic acid. Additionally, the postoperative ocular surface disease index score showed a significant positive correlation with the postoperative use of 0.15% hyaluronic acid and the preoperative Schirmer's I test score. In multivariate analysis, treatment with 0.15% hyaluronic acid and the preoperative ocular surface disease index score were significant independent parameters affecting the postoperative ocular surface disease index score., Conclusion: The use of 0.15% hyaluronic acid is recommended for its potential advantages in alleviating symptoms following cataract surgery, making it a viable alternative to traditional 0.1% hyaluronic acid treatment., Trial Registration: ISRCTN95830348., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, we identified a new strain of the genus Neocypholaelaps from the beehives of Apis mellifera colonies in the Republic of Korea (ROK). The Neocypholaelap sp. KOR23 mites were collected from the hives of honeybee apiaries in Wonju, Gangwon-do, in May 2023. Morphological and molecular analyses based on 18S and 28S rRNA gene regions conclusively identified that these mites belong to the genus Neocypholaelaps, closely resembling Neocypholaelaps sp. APGD-2010 that was first isolated from the United States. The presence of 9 of 25 honeybee pathogens in these mite samples suggests that Neocypholaelaps sp. KOR23 mite may act as an intermediate vector and carrier of honeybee diseases. The identification of various honeybee pathogens within this mite highlights their significance in disease transmission among honeybee colonies. This comprehensive study provides valuable insights into the taxonomy and implications of these mites for bee health management and pathogen dissemination., Competing Interests: No authors have competing interests, (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients., Methods: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation., Results: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group., Conclusion: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Longitudinal research has provided systematic empirical data on the short- and long-term outcomes of admissions policies, curricular innovations, and complex decisions on students' academic progress. This study aimed to investigate the academic performance of medical students and related factors using cohort database collected from a medical school. The study participants included 134 medical students who graduated from Chonnam National University Medical School in 2022. The medical school's cohort database was used to collect data on demographics, admission, academic performance, extracurricular activities, and performance on the National Korean Medical Licensing Examination (KMLE). Participating in club activities had a significant association with medical students' academic advancement delay or leave of absence during the entire course of medical school (P = 0.007). Logistic regression analysis indicated that the nationwide clinical knowledge mock examination during the fourth year of medical school was significantly associated with passing the KMLE (adjusted odds ratio 1.12, 95% confidence interval 1.02-1.22; P = 0.014). Extracurricular school activities (a non-cognitive student attribute) and a wide range of cognitive student attributes captured from the cohort database were associated with medical students' academic performance. In conclusion, this study can reinforce a strong emphasis on the inclusion of cognitive and non-cognitive information in medical school curricula and assessments in order to improve medical education programs and future postgraduate performance., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recently, particulate matter (PM) has been shown to exacerbate atopic dermatitis (AD) by inducing an inflammatory response. Meanwhile, several studies revealed that exosomes derived from adipose tissue-derived mesenchymal stem cells promote wound healing and alleviate inflammation via their regenerative and immunomodulatory capacities. Our study aimed to investigate the effects of human adipose tissue-derived mesenchymal stem cell-derived (ASC)-exosomes in PM-induced AD. An AD-like triple-cell model was established by treating human keratinocytes, dermal fibroblasts, and mast cells with polyinosinic:polycytidylic acid (Poly I:C) and interleukin 1 alpha (IL-1α). The effects of PM and ASC-exosomes on the expression of pro-inflammatory cytokines and skin barrier proteins were examined using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. PM increased pro-inflammatory cytokines (IL-6, IL-1β, and IL-1α) and decreased the anti-inflammatory cytokine IL-10, while the mRNA expression of skin barrier proteins (loricrin and filaggrin) decreased. However, when the cells were treated with ASC-exosomes, the PM-induced effects on pro-inflammatory cytokines and skin barrier proteins were reversed. Our results confirmed that PM-induced inflammation and skin barrier damage were alleviated by ASC-exosomes in our AD-like triple-cell model. These data suggest that ASC-exosomes can serve as a therapeutic agent for PM-exacerbated AD., Competing Interests: Byong Seung Cho is founder and stockholder of ExoCoBio Inc. Jun Ho Lee and Yu Jin Won are employees of ExoCoBio Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Roh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: We aimed to investigate the association between smartphone use and adverse behavioral health outcomes using nationwide Korea Youth Risk Behavior Web-based Survey data for 2017 and 2020., Methods: The 2020 data (N = 54,809) were used to analyze the relationships between daily smartphone usage time (non-user, 0-2 h [hour], 2-4 h, 4-6 h, 6-8 h, and > 8 h), and adverse health outcomes (stress, sleep, depression, suicide, substance use, and smartphone overdependence). A 1:1 propensity score matching (PSM) was used to control for confounding variables., Results: A total of 40,998 adolescents with < 4 h/day and > 4 h/day of usage were included. Adolescents' mean smartphone usage time in 2020 increased compared to that in 2017 (weighted % of > 2 h/day; 64.3% vs. 85.7%). The curvilinear relationships between smartphone usage time and adverse health outcomes were prominent after > 4 h/day. Adolescents using smartphones 2-4 h/day showed no increased adverse health outcomes compared to non-users, except for smartphone overdependence. Using a smartphone > 4 h/day was significantly associated with stress perception (1.16; 1.11-1.22), suicidal ideation (1.22; 1.13-1.31), and substance use (alcohol, 1.66; 1.57-1.75) after PSM., Conclusions: Our study demonstrated the curvilinear relationship between smartphone usage time and adverse health outcomes in adolescents. Our findings can help establish smartphone usage guidelines for adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Type 2 diabetes is considered one of the top ten life-threatening diseases worldwide. Following economic growth, obesity and metabolic syndrome became the most common risk factor for type 2 diabetes. In this regard, high-fat diet-fed C57BL/6J mouse model is widely used for type 2 diabetes pathogenesis and novel therapeutics development. However, criteria for classifying type 2 diabetes progressive stages in this mouse model are yet to be determined, led to the difficulty in experimental end-point decision. In this study, we fed C57BL/6J male mice with 45% high-fat diet, which is physiologically close to human high-fat consumption, and evaluated the progression of type 2 diabetes. After consuming high-fat diet for 4 weeks, mice developed metabolic syndrome, including obesity, significant increase of fasting plasma cholesterol level, elevation of both C-peptide and fasting blood glucose levels. By combining both fasting blood glucose test and 2-hour-oral glucose tolerance test, our results illustrated clear progressive stages from metabolic syndrome into pre-diabetes before onset of type 2 diabetes in C57BL/6J mice given a 45% high-fat diet. Besides, among metabolic measurements, accumulating body weight gain > 16.23 g for 12 weeks could be utilized as a potential parameter to predict type 2 diabetes development in C57BL/6J mice. Thus, these results might support future investigations in term of selecting appropriate disease stage in high-fat diet-fed C57BL/6J mouse model for studying early prevention and treatment of type 2 diabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nguyen-Phuong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Skin photoaging induced by ultraviolet (UV) irradiation contributes to the formation of thick and coarse wrinkles. Humans are exposed to UV light throughout their lives. Therefore, it is crucial to determine the time-sequential effects of UV on the skin. In this study, we irradiated the mouse back skin with UV light for eight weeks and observed the changes in gene expressions via microarray analysis every week. There were more downregulated genes (514) than upregulated genes (123). The downregulated genes had more functional diversity than the upregulated genes. Additionally, the number of downregulated genes did not increase in a time-dependent manner. Instead, time-dependent kinetic patterns were observed. Interestingly, each kinetic cluster harbored functionally enriched gene sets. Since collagen changes in the dermis are considered to be a major cause of photoaging, we hypothesized that other gene sets contributing to photoaging would exhibit kinetics similar to those of the collagen-regulatory genes identified in this study. Accordingly, co-expression network analysis was conducted using 11 well-known collagen-regulatory seed genes to predict genes with similar kinetics. We ranked all downregulated genes from 1 to 504 based on their expression levels, and the top 50 genes were suggested to be involved in the photoaging process. Additionally, to validate and support our identified top 50 gene lists, we demonstrated that the genes (FN1, CCDC80, PRELP, and TGFBR3) we discovered are downregulated by UV irradiation in cultured human fibroblasts, leading to decreased collagen levels, which is indicative of photoaging processes. Overall, this study demonstrated the time-sequential genetic changes in chronically UV-irradiated skin and proposed 50 genes that are involved in the mechanisms of photoaging., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Acute myocardial infarction is an acute-stage disease that requires prompt diagnosis and treatment. Primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is a high-risk factor for post-contrast acute kidney injury (PC-AKI). This retrospective cohort study analyzed the data of 754 patients with STEMI who underwent pPCI and were integrated into the Fast Interrogation Rule for STEMI critical pathway program between 2015 and 2019. We aimed to determine the optimal cutoff baseline eGFR for identifying a high risk of PC-AKI after multivariable adjustment with statistically significant risk factors. We also compared the incidence rates of PC-AKI between the previous and current diagnostic criteria. The probability of PC-AKI increased when the baseline estimated glomerular filtration rate (eGFR) was ≤ 79mL/min/1.73 m2. The optimal cutoff baseline eGFR for high risk of PC-AKI was found to be an eGFR of ≤ 61 mL/min/1.73 m2 after multivariable adjustment. The current diagnostic criteria more accurately identified the patient group with impaired renal function. Our results have clinically significant implications for identifying patients at a high risk of developing PC-AKI, especially before and after the use of contrast agents in patients who require PCI for STEMI in the emergency department., Competing Interests: NO authors have competing interests Enter: The authors have declared that no competing interests exist., (Copyright: © 2023 You et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: We applied a radiomics approach to skin surface images to objectively assess acute radiation dermatitis in patients undergoing radiotherapy for breast cancer., Methods: A prospective cohort study of 20 patients was conducted. Skin surface images in normal, polarized, and ultraviolet (UV) modes were acquired using a skin analysis device before starting radiotherapy ('Before RT'), approximately 7 days after the first treatment ('RT D7'), on 'RT D14', and approximately 10 days after the radiotherapy ended ('After RT D10'). Eighteen types of radiomic feature ratios were calculated based on the values acquired 'Before RT'. We measured skin doses in ipsilateral breasts using optically stimulated luminescent dosimeters on the first day of radiotherapy. Clinical evaluation of acute radiation dermatitis was performed using the Radiation Therapy Oncology Group scoring criteria on 'RT D14' and 'After RT D10'. Several statistical analysis methods were used in this study to test the performance of radiomic features as indicators of radiodermatitis evaluation., Results: As the skin was damaged by radiation, the energy for normal mode and sum variance for polarized and UV modes decreased significantly for ipsilateral breasts, whereas contralateral breasts exhibited a smaller decrease with statistical significance. The radiomic feature ratios at 'RT D7' had strong correlations to skin doses and those at 'RT D14' and 'after RT D10' with statistical significance., Conclusions: The energy for normal mode and sum variance for polarized and UV modes demonstrated the potential to evaluate and predict acute radiation, which assists in its appropriate management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The most common cause of sensorineural hearing loss is damage of auditory hair cells. Tumor necrosis factor-alpha (TNF-α) is closely associated with sensorineural hearing loss. The present study examined the preconditioning effect of dexamethasone (DEX) on TNF-α-induced ototoxicity in mouse auditory hair cells (HEI-OC1) and cochlear explants. Treatment of HEI-OC1 with 10 ng/ml TNF-α for 24 h decreased cell viability, increased the accumulation of reactive oxygen species (ROS), and induced caspase-mediated apoptotic signaling pathways. Pretreatment with 10 nM DEX for 6 h before TNF-α exposure restored cell viability, decreased ROS accumulation, and attenuated apoptotic signaling activation induced by TNF-α. Incubation of cochlear explants with 20 ng/ml TNF-α for 24 h resulted in significant loss of both inner hair cells (IHCs) and outer hair cells (OHCs) and an increase in apoptotic activation accessed by annexin V staining. The cochlear explants pre-incubated with 10 nM DEX attenuated TNF-α ototoxicity in both IHCs and OHCs and apoptotic cell death. These results indicated that DEX plays a protective role in ototoxicity induced by TNF-α through attenuation of caspase-dependent apoptosis signaling pathway and ROS accumulation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Seongmoon Jung, Jong Min Park, Chang Heon Choi, Hong-Gyun Wu, and Jung-in Kim have financial relationships with Parprica Lab., LTD. to disclose., (Copyright: © 2023 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Insomnia and depression have been known to be risk factors of several diseases, including coronary heart disease. We hypothesized that insomnia affects the out-of-hospital cardiac arrest (OHCA) incidence, and these effects may vary depending on whether it is accompanied by depression. This study aimed to determine the association between insomnia and OHCA incidence and whether the effect of insomnia is influenced by depression., Methods: This prospective multicenter case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiology Surveillance (CAPTURES-II) project database for OHCA cases and community-based controls in Korea. The main exposure was history of insomnia. We conducted conditional logistic regression analysis to estimate the effect of insomnia on the risk of OHCA incidence and performed interaction analysis between insomnia and depression. Finally, subgroup analysis was conducted in the patients with insomnia., Results: Insomnia was not associated with increased OHCA risk (0.95 [0.64-1.40]). In the interaction analysis, insomnia interacted with depression on OHCA incidence in the young population. Insomnia was associated with significantly higher odds of OHCA incidence (3.65 [1.29-10.33]) in patients with depression than in those without depression (0.84 [0.59-1.17]). In the subgroup analysis, depression increased OHCA incidence only in patients who were not taking insomnia medication (3.66 [1.15-11.66])., Conclusion: Insomnia with depression is a risk factor for OHCA in the young population. This trend was maintained only in the population not consuming insomnia medication. Early and active medical intervention for patients with insomnia may contribute to lowering the risk of OHCA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Son et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to assess the safety and effectiveness of the highly cross-linked hyaluronic acid-LBSA0103-in patients with knee osteoarthritis (OA) as per the prescribing information (PI) in South Korea. A total of 3,140 subjects aged ≥19 years were enrolled in this post-marketing surveillance (PMS) study from 2013 to 2019. The subjects received one or two injections of LBSA0103. The median duration of follow-up was 308 days. Adverse events (AEs), adverse drug reactions (ADRs), and serious AEs (SAEs) were monitored. Effectiveness was evaluated based on an index of effectiveness in accordance with the guidelines established by the Ministry of Food and Drug Safety and using a 100-mm visual analog scale (VAS) for weight-bearing pain. Overall, 250 subjects (7.96%) experienced 292 AEs and of these, unexpected AEs occurred in 114 subjects (3.63% [95% CI: 3.00-4.35]). Injection site pain was the most frequent AE reported by 81 subjects (2.58% [95% confidence intervals (CI): 2.05-3.20]). One hundred subjects experienced 108 ADRs (3.18% [95% CI: 2.60, 3.86]) and 15 unexpected ADRs were experienced by 13 subjects (0.41% [95% CI: 0.22-0.71]). Seventeen subjects experienced 22 SAEs (0.54% [95% CI: 0.32-0.87]) during the entire PMS period, and all were considered "unlikely" related to the study drug. Most AEs were mild in terms of severity and resolved during the study period. LBSA0103 was also effective in relieving symptomatic pain in knee OA patients. The condition in more than 80% of the subjects was considered to be improved when assessed by the investigators. LBSA0103 resulted in a significant reduction in the mean VAS score at 12 weeks after the first and second injections (24.79 (± 20.55) mm and 17.63 (±12.31) mm, respectively; p<0.0001). In conclusion, LBSA0103, used for the treatment of knee OA in a real-world setting, was well tolerated, with an acceptable safety profile and consistent therapeutic effect., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Tenosynovial giant cell tumors (TSGCTs) of the knee differ in their clinical outcome according to disease subtypes and severity. The aim of this study was to determine the predictive MRI features related to local recurrence in TSGCT of the knee regarding disease subtypes and severity., Methods: This retrospective study included 20 patients with pathology-proven TSGCT of the knee who underwent preoperative MRI and surgery from Jan. 2007 to Jan. 2022. The anatomical point of the lesion was determined with a knee mapping. And then MRI features related to disease subtype including nodularity (single vs. multinodular); margin (circumscribed vs. infiltrative); peripheral hypointenseity (present vs. absent); internal hypointensity reflecting hemosiderin deposition (speckled vs. granular) were assessed. Third, MRI features related to disease severity including involvement of bone, cartilage, and tendon were evaluated. MRI features for predicting local recurrence of TSGCT were tested using chi-square test and logistic regression analysis., Results: Ten patients with diffuse-type TSGCT (D-TSGCT) and 10 patients with localized-type TSGCT (L-TSGCT) were included. There were six cases of local recurrence and all of them were D-TSGCT and none for L-TSGCT with statistical difference (P = 0.015). D-TSGCT that was direct risk factor for local recurrence showed more multinodular (80.0% vs. 10.0%; P = 0.007), infiltrative margin (90.0% vs. 10.0%; P = 0.002), and absent peripheral hypointensity (100.0% vs. 20.0%; P = 0.001) than L-TSGCT. Multivariate analysis showed infiltrative margin (odds ratio [OR], 81.0; P = 0.003) was independent MRI factor for D-TSGCT. Disease severity for risk of local recurrence included cartilage (66.7% vs. 7.1%; P = 0.024) and tendon (100.0% vs. 28.6%; P = 0.015) involvement compared to no local recurrence. Multivariate analysis showed tendon involvement (OR, 12.5; P = 0.042) was predictive MRI parameter for local recurrence. By combining tumor margin and tendon involvement, local recurrence was predicted sensitively on preoperative MRI (sensitivity, 100%; specificity, 50%; accuracy, 65%)., Conclusion: D-TSGCTs was associated with local recurrence and showed multinodularity infiltrative margin, and absent peripheral hypointensity. Disease severity including cartilage and tendon involvement was associated with local recurrence. Preoperative MRI evaluation by combining disease subtypes and severity can predict local recurrence sensitively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Prehospital advanced life support (ALS) has been offered in many countries for patients experiencing out-of-hospital cardiac arrest (OHCA); however, its effectiveness remains unclear. This study aimed to determine the impact of emergency medical service (EMS) with ALS training as a nationwide pilot project for adults with OHCA in the Republic of Korea. This retrospective multicenter observational study was conducted between July 2019 and December 2020 using the Korean Cardiac Arrest Research Consortium registry. The patients were categorized into an intervention group that received EMS with ALS training and a control group that did not receive EMS with ALS training. Conditional logistic regression analysis was performed using matched data to compare clinical outcomes between the two groups. Compared with the control group, the intervention group had a lower rate of supraglottic airway usage (60.5% vs. 75.6%) and a higher rate of undergoing endotracheal intubation (21.7% vs. 6.1%, P < 0.001). In addition, the intervention group was administered more intravenous epinephrine (59.8% vs. 14.2%, P < 0.001) and used mechanical chest compression devices more frequently in prehospital settings than the control group (59.0% vs. 23.8%, P < 0.001). Based on the results of multivariable conditional logistic regression analysis, survival to hospital discharge (odds ratio: 0.48, 95% confidence interval: 0.27-0.87) of the intervention group was significantly lower than that of the control group; however, good neurological outcome was not significantly different between the two groups. In this study, survival to hospital discharge was worse in patients with OHCA who received EMS with ALS training than in those who did not., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The coronavirus disease 2019 (COVID-19) pandemic and the corresponding lockdown have drastically changed our lives and led to high psychological distress and mental health problems. This study examined whether psychological factors such as loneliness, perfectionism, and health anxiety are associated with COVID-19 related anxiety and depression during the pandemic in young Korean adults, after controlling for various socio-demographic factors and early life stress., Methods: A total of 189 participants (58.2% women) completed a cross-sectional online survey including the Fear of COVID-19 Scale, Center for Epidemiologic Studies Depression Scale, 3-item Revised UCLA Loneliness Scale, Frost Multidimensional Perfectionism Scale, and Whiteley Index-6. Hierarchical linear regression analyses with three blocks were employed to identify the factors that contributed to COVID-19 related anxiety and depressive symptoms., Results: Hierarchical regression analyses showed that higher health anxiety was significantly associated with more severe COVID-19 related anxiety (standardized regression coefficient, β = 0.599, p < 0.001). Additionally, higher levels of loneliness (β = 0.482, p < 0.001), perfectionism (β = 0.124, p = 0.035), and health anxiety (β = 0.228, p < 0.001) were significantly associated with higher depression scores. The three psychological factors explained 32.8% of the total variance in depressive symptom scores, after taking all covariates into account., Conclusion: The results showed that health anxiety was a risk factor for both COVID-19 related anxiety and depression in young adults. Loneliness was the strongest predictor of depressive symptoms during the COVID-19 pandemic. These findings highlight the importance of identifying vulnerable individuals and encouraging psychological counselling and social connections to reduce the burden of psychiatric disorders during the pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tetra-O-methyl-nordihydroguaiaretic acid (terameprocol; M4N), a global transcription inhibitor, in combination with a second anticancer drug induces strong tumoricidal activity and has the ability to suppress energy metabolism in cultured cancer cells. In this study, we showed that after continuous oral consumption of high-fat (HF) diets containing M4N, the M4N concentration in most of the organs in mice reached ~1 μM (the M4N concentration in intestines and fat pads was as high as 20-40 μM) and treatment with the combination of M4N with temozolomide (TMZ) suppressed glycolysis and the tricarboxylic acid cycle in LN229 human glioblastoma implanted in xenograft mice. Combination treatment of M4N with TMZ also reduced the levels of lactate dehydrogenase A (LDHA), a key enzyme for glycolysis; lactate, a product of LDHA-mediated enzymatic activity; nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for nicotinamide adenine dinucleotide plus hydrogen (NADH)/NAD+ salvage pathway; and NAD+, a redox electron carrier essential for energy metabolism. It was also shown that M4N suppressed oxygen consumption in cultured LN229 cells, indicating that M4N inhibited oxidative phosphorylation. Treatment with M4N and TMZ also decreased the level of hypoxia-inducible factor 1A, a major regulator of LDHA, under hypoxic conditions. The ability of M4N to suppress energy metabolism resulted in induction of the stress-related proteins activating transcription factor 4 and cation transport regulator-like protein 1, and an increase in reactive oxygen species production. In addition, the combination treatment of M4N with TMZ reduced the levels of oncometabolites such as 2-hydroxyglutarate as well as the aforementioned lactate. M4N also induced methylidenesuccinic acid (itaconate), a macrophage-specific metabolite with anti-inflammatory activity, in tumor microenvironments. Meanwhile, the ability of M4N to suppress energy metabolism prevented obesity in mice consuming HF diets, indicating that M4N has beneficial effects on normal tissues. The dual ability of combination treatment with M4N to suppress both energy metabolism and oncometabolites shows that it is potentially an effective therapy for cancer., Competing Interests: The authors have declared that no competing interests exist. However, for full disclosure we acknowledge that Ru Chih C. Huang is a principal inventor and Jong Ho Chun, Tiffany L. B. Jackson, Yu-Ling Lin and Yu-Chuan Liang are inventors of a patent application "Formulations of Terameprocol and Temozolomide and Their Use in Stimulation of Humoral Immunity in Tumors" (PCT WO/2021/108601 - patent date June 3, 2021). Dr. Huang is also a principal inventor of several other JHU patents on M4N. This does not alter the authors’ adherence to policies on sharing data and materials., (Copyright: © 2023 Kimura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The number of people with dementia increases in an aging society; therefore, promoting policies for dementia throughout the community is crucial to creating a dementia-friendly society. Understanding the status of older adults with dementia in each region of Japan will be a helpful indicator. We calculated Dementia-free Life Expectancy and aimed to examine regional disparities and their associated factors., Methods: We calculated Dementia-free Life Expectancy and Life Expectancy with Dementia for each secondary medical area in Japan based on the Degree of Independence in Daily Living for the Demented Elderly, using data extracted from the Japanese long-term care insurance claims database. We then conducted a partial least squares regression analysis, the objective variables being Dementia-free Life Expectancy and Life Expectancy with Dementia for both sexes at age 65, and explanatory regional-level variables included demographic, socioeconomic, and healthcare resources variables., Results: The mean estimated regional-level Dementia-free Life Expectancy at age 65 was 17.33 years (95% confidence interval [CI] 17.27-17.38) for males and 20.05 years (95% CI 19.99-20.11) for females. Three latent components identified by partial least squares regression analysis represented urbanicity, socioeconomic conditions, and health services-related factors of the secondary medical areas. The second component explained the most variation in Dementia-free Life Expectancy of the three, indicating that higher socioeconomic status was associated with longer Dementia-free Life Expectancy., Conclusions: There were regional disparities in secondary medical area level Dementia-free Life Expectancy. Our results suggest that socioeconomic conditions are more related to Dementia-free Life Expectancy than urbanicity and health services-related factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yoshikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Osteochondral allograft (OCA) is an important surgical procedure used to repair extensive articular cartilage damage. It is known that chondrocyte viability is crucial for maintaining the biochemical and biomechanical properties of OCA, which is directly related to the clinical success of the operation and is the only standard for preoperative evaluation of OCA. However, there is a lack of systematic research on the effect of the content of cellular matrix in OCA cartilage tissue on the efficacy of transplantation. Therefore, we evaluated the effect of different GAG contents on the success of OCA transplantation in a rabbit animal model. Each rabbit OCA was treated with chondroitinase to regulate glycosaminoglycan (GAG) content in the tissue. Due to the different action times of chondroitinase, they were divided into 4 experimental groups (including control group, 2h, 4h, and 8h groups). The treated OCAs of each group were used for transplantation. In this study, transplant surgery effects were assessed using micro-computed tomography (μCT) and histological analysis. Our results showed that tissue integration at the graft site was poorer in the 4h and 8h groups compared to the control group at 4 and 12 weeks in vivo, as were the compressive modulus, GAG content, and cell density reduced. In conclusion, we evaluated the biochemical composition of OCAs before and after surgery using μCT analysis and demonstrated that the GAG content of the graft decreased, it also decreased during implantation; this resulted in decreased chondrocyte viability after transplantation and ultimately affected the functional success of OCAs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clinical benefits of the meso-jejunal lymph node (MJLN) dissection in remnant gastric cancer (RGC) patients have not been fully established. Hence, in this retrospective study, we evaluated the survival benefit of MJLN dissection and prognostic significance of MJLN metastasis in RGC patients who underwent gastrojejunostomy reconstruction after their initial gastrectomy., Methods: We retrospectively reviewed 391 patients who underwent surgery for RGC at our institution between 1996 and 2019. Among them, 60 patients had MJLN dissection. The index value of the survival benefit gained by dissection of the MJLN was calculated by multiplying the frequency of metastasis at the MJLN station and the 5-year overall survival rate (5YOS) of patients with metastasis at that station. When the metastatic rate or 5YOS exceeded 10%, dissection was recommended. An index value of dissection greater than 1.0 was considered significant., Results: Total metastatic rate of MJLN was 35% (n = 21/60). Patients with MJLN metastasis had advanced pathologic stage compared to patients in the no-metastasis group (p < 0.001). In T2-T4 RGC patients, the metastatic rate of MJLN was 48.6% (n = 17/35), and their 5YOS was 28.4%. The calculated index value was 13.8. Also, patients with MJLN metastasis had a poorer overall survival than those without metastasis. MJLN metastasis was an independent prognostic factor of overall survival in multivariate analysis (HR 6.77, 95%CI 2.21-20.79, p = 0.001)., Conclusion: MJLN dissection should be considered for advanced RGC patients who underwent gastrojejunostomy after distal gastrectomy during their initial surgery according to the index value., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Oh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The rate of preterm birth is increasing worldwide and preterm infants are susceptible to oral health problems. Hence, this study aimed to investigate the effect of premature birth on dietary and oral characteristics as well as dental treatment experiences of preterm infants using a nationwide cohort study. Data was retrospectively analyzed from National Health Screening Program for Infants and Children (NHSIC) of the National Health Insurance Service of Korea. 5% sample of children born between 2008 and 2012 who completed first or second infant health screening were included and divided into full-term and preterm-birth groups. Clinical data variables such as dietary habits, oral characteristics, and dental treatment experiences were investigated and comparatively analyzed. Preterm infants showed significantly lower rates of breastfeeding at 4-6 months (p<0.001), delayed start of weaning food at 9-12 months (p<0.001), higher rates of bottle feeding at 18-24 months (p<0.001), poor appetite at 30-36 months (p<0.001) and higher rates of improper swallowing and chewing function at 42-53 months (p = 0.023) than full-term infants. Preterm infants also had eating habits leading to poor oral conditions and higher percentage of absence of dental visit compared to full-term infants (p = 0.036). However, dental treatments including 1-visit pulpectomy (p = 0.007) and 2-visit pulpectomy (p = 0.042) significantly decreased when oral health screening was completed at least once. The NHSIC can be an effective policy for oral health management in preterm infants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Herr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Discharge planning enhances the safe and timely transfer of inpatients between facilities. Predicting the discharge destination of inpatients with aspiration pneumonia is important for discharge planning. We aimed to develop and validate prediction models for the discharge destination of elderly patients with aspiration pneumonia., Methods: Using a nationwide inpatient database, we identified aspiration pneumonia cases for patients aged ≥65 years who had been admitted to hospital from their home or from a nursing home between April 2020 and March 2021. We divided the cases into derivation and validation cohorts according to the location of the admitting hospital. We developed two prediction models by dividing the cases based on the patient's place of residence prior to admission, one model to predict the home discharge of cases admitted from home and the other to predict the home or to a nursing home discharge of cases admitted from a nursing home. The models were internally validated with bootstrapping and internal-externally validated using a validation cohort. Nomograms that could be used easily in clinical practice were also created., Results: The derivation cohort included 19,746 cases admitted from home and 14,359 cases admitted from a nursing home. Of the former, 10,760 (54.5%) cases were discharged home; from the latter, 7,071 (49.2%) were discharged to either home or a nursing home. The validation cohort included 6,262 cases admitted from home and 6,352 cases admitted from a nursing home. In the internal-external validation, the C-statistics of the final model for the cases admitted from home and the cases admitted from a nursing home were 0.71 and 0.67, respectively., Conclusions: We developed and validated new prediction models for the discharge of elderly patients with aspiration pneumonia either to home or to a nursing home. Our models and nomograms could facilitate the early implementation of discharge planning., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hirota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic emaciating disease of ruminants that causes enormous economic losses to the bovine industry, globally. However, there are still remaining clues to be solved in the pathogenesis and diagnosis of the disease. Therefore, an in vivo murine experimental model was tried to understand responses in early stage of MAP infection by oral and intraperitoneal (IP) routes. In the MAP infection size, and weight of spleen and liver were increased in the IP group compared with oral groups. Severe histopathological changes were also observed in the spleen and liver of IP infected mice at 12 weeks post-infection (PI). Acid-fast bacterial burden in the organs was closely related to histopathological lesions. In the cytokine production from splenocytes of MAP-infected mice, higher amounts of in TNF-α, IL-10, and IFN-γ were produced at early stage of IP-infected mice while IL-17 production was different at time and infected groups. This phenomenon may indicate the immune shift from Th1 to Th17 through the time course of MAP infection. Systemic and local responses in the MAP-infection were analyzed by using transcriptomic analysis in the spleens and mesenteric lymph nodes (MLN). Based on the analysis of biological processes at 6 weeks PI in spleen and MLN in each infection group, canonical pathways were analyzed with ingenuity pathway analysis in the immune responses and metabolism especially lipid metabolism. Infected host cells with MAP increased in the production of proinflammatory cytokines and reduced the availability of glucose at early stage of infection (p < 0.05). Also, host cells secreted cholesterol through cholesterol efflux to disturb energy source of MAP. These results reveal immunopathological and metabolic responses in the early stage of MAP infection through the development of a murine model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The purpose of this study was to examine the relationship between the lobar emphysema ratio (LER) and tumor recurrence and survival in patients with stage I non-small cell lung cancer (NSCLC)., Methods: We enrolled 258 patients with surgically proven stage I NSCLC. These patients underwent noncontrast chest CT, and pulmonary lobe segmentation and lobar emphysema quantification were performed using commercially available software. We assessed the LER in the lobe with lung cancer. We divided the patients into two groups according to the LER, and the cut-off value was 1. Furthermore, we analyzed the disease-free survival of high LER and other clinical factors after surgical resection., Results: The 258 patients were divided into two groups: low LER (n = 195) and high LER (n = 63). The right upper lobe was the most frequent location in lung cancer and the most severe location in emphysema. In the Kaplan‒Meier curve, high LER showed a significantly lower disease-free survival (8.21 ± 0.27 years vs 6.53 ± 0.60 years, p = 0.005) and overall survival (9.56 ± 0.15 years vs. 8.51 ± 0.49 years, p = 0.011) than low LER. Stage Ib (2.812 [1.661-4.762], p<0.001) and high LER (2.062 [1.191-3.571], p = 0.010) were poor predictors for disease-free survival in multivariate Cox regression analysis. Stage Ib (4.729 [1.674-13.356], p = 0.003) and high LER (3.346 [1.208-9.269], p = 0.020) were significant predictors for overall survival in multivariate Cox regression analysis., Conclusion: A LER of more than 1% in the lobe with lung cancer is a poor predictor for cancer recurrence and overall survival in patients with stage I NSCLC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Some cerebral arterial silicone phantoms have been used in preclinical evaluations. However, typical silicone-based phantoms are limited in their capacity to reproduce real contrast filling dynamics of the human cerebral artery. This study aimed to develop a cerebral arterial silicone phantom to analyze the feasibility of real contrast filling dynamics. The fluid circulation phantom system consisted of a cerebral arterial silicone phantom without or with additional devices, a pump, an injection system, a pressure-monitoring system, a constant-temperature bath, and a venous drainage container. Vascular resistance was reproduced with a plastic cistern only or a plastic cistern filled with a sponge pad. Three phantom groups were constructed as follows: a) the cerebral arterial silicone phantom used as the control group (type A), b) phantom with the incorporated plastic cistern (type B), and c) phantom with the incorporated plastic cistern filled with a sponge pad (type C). The contrast concentration-time curve patterns of the three groups obtained from digital subtraction angiography (DSA) were compared. Consequently, the DSA pattern of the type C phantom was the most similar to that obtained from the control group as the reference data, which showed the broadest full-width-at-half-maximum and the area under the curve values and the highest maximum contrast concentration. In conclusion, we could emulate the arterial contrast filling dynamics of clinical cerebral angiography by applying a small cistern filled with a sponge pad at the drainage side of the phantom., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/purpose: The benefit of neuromuscular blockades (NMBs) in critically ill patients receiving mechanical ventilation remains uncertain. Therefore, we aimed to investigate whether NMB use is associated with improved survival of mechanically ventilated pneumonia patients with moderate to severe hypoxemia., Methods: This retrospective multicenter study was conducted at five university-affiliated hospitals. Data of pneumonia patients aged 18 years and older who received mechanical ventilation between January 1, 2011, and December 31, 2020, were analyzed., Results: In a total of 1,130 patients, the mean patient age was 73.1 years (SD±12.6), and the overall mortality rate at 30 d was 29.5% (n = 333). NMB users had a higher 30 d mortality rate than NMB nonusers (33.9% vs. 26.8%, P = 0.014). After PS matching, the 30 d mortality rate was not significantly different between NMB users and nonusers (33.4% vs. 27.8%, p = 0.089). However, 90 d mortality rate was significantly increased in NMB users (39.7% vs. 31.9%, p = 0.021). Univariable Cox proportional hazard regression analyses showed that NMB use ≥ 3 d was significant risk factor for the 90 d mortality than those with < 3 d use (90 d mortality HR 1.39 [95% CI: 1.01-1.91], P = 0.045)., Conclusions: NMB use was not associated with lower 30 d mortality among mechanically ventilated pneumonia patients with moderate to severe hypoxemia. Rather, NMB users had higher 90 d mortality, furthermore, and NMB use ≥ 3 d was associated with a higher risk of long-term mortality compared to NMB use < 3 d. Therefore, care should be taken to avoid extended use of NMB in critically ill pneumonia patients during mechanical ventilation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Baek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent studies regarding deep vein thrombosis (DVT) after anterior cruciate ligament (ACL) reconstruction investigated only symptomatic complications. The purpose of this study was to assess the true incidence of DVT after ACL reconstruction, regardless of symptom manifestation., Materials and Methods: Medical records of 260 patients who underwent isolated ACL reconstruction between January 2014 and December 2019 were retrospectively reviewed. Regardless of symptom manifestation, DVT was examined for all patients at 1 week postoperatively using ultrasonography. Demographics, injury mechanism (high energy direct injury and low energy indirect injury), soft tissue injury, preoperative anterior laxity, tourniquet time, and surgical technique (transtibial, anteromedial portal, and outside-in techniques) were investigated. Soft tissue injury was evaluated on magnetic resonance imaging (MRI) scans, based on the Tscherne classification. Risk factors for proximal DVT were identified using logistic regression analyses., Results: A total of 21 (8.1%) patients showed DVT. 5 (1.9%) patients had thrombosis at the popliteal vein; however, none of them exhibited symptoms. The other 16 patients had thrombosis at the distal veins: 1 patient at the anterior tibial vein, 5 patients at the posterior tibial vein, 3 patients at the peroneal vein, 6 patients at the soleal vein, and 1 patient at the muscular branch vein. The risk factors for proximal DVT included high energy direct injury (p = 0.013, odds ratio = 10.62) and grade 2 soft tissue injury (p = 0.039, odds ratio = 6.78)., Conclusions: The true incidence of DVT, including symptomatic and asymptomatic complications, were 8.1% after ACL reconstruction. This rate is higher than the previously known incidence which has been investigated only for symptomatic patients. Injury mechanism and soft tissue injury should be assessed when considering thromboprophylaxis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Joo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the technical success rate and complications associated with percutaneous nephrostomy (PCN) via percutaneous renal access behind the stone and renal calyx dilation in patients with complex renal stones., Materials and Methods: From January 2010 to February 2021, we identified 69 patients with 70 complex renal stones who underwent PCN. Complex renal stones were classified as simple (renal pelvis only) (27.1%, 19/70), borderline staghorn (8.6%, 6/70), partial staghorn (51.4%, 36/70), or complete staghorn (12.9%, 9/70). All PCNs were performed under ultrasound and fluoroscopic guidance using one of two renal-entry techniques: puncture behind the stone (56%, 39/70) or renal calyx dilation (44%, 31/70). Then, we retrospectively evaluated the technical success rates and complications associated with each renal entry access technique., Results: The overall technical success rate was 100%, and the complication rate was 20.0% (14/70). For those who underwent renal access behind the stone, the complication rate was 15.4% (6/39), and six patients (six PCNs) had transient gross hematuria. For those who underwent dilated renal calyx entry, the complication rate was 25.8% (8/31), and one patient had significant bleeding complications requiring transfusion. Furthermore, seven patients (seven PCNs) had transient gross hematuria. Overall, the complication rates did not differ between the technique groups (p = 0.279)., Conclusion: PCN for complex renal stones has a high technical success rate and an acceptable complication rate regardless of the specific technique. Renal entry behind the stone is as safe and feasible as approaching via a dilated renal calyx., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Ahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although some human studies have reported gut microbiome changes in individuals with Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI), gut microbiome alterations in preclinical AD, i.e., cerebral amyloidosis without cognitive impairment, is largely unknown., Objective: We aimed to identify gut microbial alterations associated with preclinical AD by comparing cognitively normal (CN) older adults with cerebral Aβ deposition (Aβ+ CN) and those without cerebral Aβ deposition (Aβ- CN)., Methods: Seventy-eight CN older participants (18 Aβ+ CN and 60 Aβ- CN) were included, and all participants underwent clinical assessment and Pittsburg compound B-positron emission tomography. The V3-V4 region of the 16S rRNA gene of genomic DNA extracted from feces was amplified and sequenced to establish the microbial community., Results: Generalized linear model analysis revealed that the genera Megamonas (B = 3.399, q<0.001), Serratia (B = 3.044, q = 0.005), Leptotrichia (B = 5.862, q = 0.024) and Clostridium (family Clostridiaceae) (B = 0.788, q = 0.034) were more abundant in the Aβ+ CN group than the Aβ- CN group. In contrast, genera CF231 (B = -3.237, q< 0.001), Victivallis (B = -3.447, q = 0.004) Enterococcus (B = -2.044, q = 0.042), Mitsuokella (B = -2.119, q = 0.042) and Clostridium (family Erysipelotrichaceae) (B = -2.222, q = 0.043) were decreased in Aβ+ CN compared to Aβ- CN. Notably, the classification model including the differently abundant genera could effectively distinguish Aβ+ CN from Aβ- CN (AUC = 0.823)., Conclusion: Our findings suggest that specific alterations of gut bacterial taxa are related to preclinical AD, which means these changes may precede cognitive decline. Therefore, examining changes in the microbiome may be helpful in preclinical AD screening., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the introduction of combination antiretroviral therapy (cART), the prevalence of human immunodeficiency virus (HIV)-associated nontuberculous mycobacteria (NTM) disease has declined. However, NTM diseases still occur in people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHA). We analysed the clinical and microbiological features of NTM diseases in PLWHA in South Korea. PLWHA who were diagnosed with NTM diseases between January 2000 and March 2021 were retrospectively enrolled from five different hospitals in South Korea. Data on baseline demographics, HIV status, CD4+ T cell counts, viral load, past and current cART regimens, isolated NTM species, results of antimicrobial susceptibility tests, treatment regimens, and outcomes were collected by reviewing medical records. A total of 34 cases of NTM in PLWHA were included. Pulmonary and extrapulmonary NTM diseases accounted for 58.8% (n = 20) and 41.2% (n = 14), respectively. The lymph node was the most common site of extrapulmonary NTM disease (64.3%). The age at the time of NTM disease diagnosis was younger in the extrapulmonary NTM group than in the pulmonary NTM group (37.0 vs. 49.0 years). Mean CD4+ T cell counts at the time of NTM disease diagnosis was 186.6 cells/μL (range: 1-1394). Nine patients (26.5%) had fully suppressed viral loads at the time of NTM disease diagnosis. Mycobacterium avium complex (MAC) was the most common species found, followed by M. intracellulare and M. kansasii. MAC isolates were all susceptible to clarithromycin, but the rates of non-susceptibility to moxifloxacin, linezolid, ethambutol, and rifampin were 75%, 37.5%, 12.5%, and 12.5%, respectively. The average duration of treatment was 17 months and the mortality rate was 8.8%. NTM diseases may occur in PLWHA, even with completely suppressed viral loads. The identified clinical features of NTM diseases are essential for its clinical management in South Korea., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Percutaneous transhepatic biliary drainage (PTBD) has been an effective treatment to access the biliary tree, especially in case of endoscopically inaccessible biliary tree. In general, PTBD techniques are divided into two methods: fluoroscopy-guided PTBD and ultrasound (US)-guided PTBD. This study aimed to evaluate the effectiveness of US-guided PTBD, focusing on radiation exposure according to intrahepatic duct (IHD) dilatation degree, differences between right- and left-sided approaches and differences between benign and malignant biliary stenosis/obstruction. We evaluated technical success, clinical success, procedural data (the number of liver capsule punctures, procedural time, fluoroscopy time and radiation dose), and procedure-related complications. During the study period, a total of 123 patients with biliary stenosis/obstruction or bile leakage were initially eligible. We excluded 76 patients treated with only ERCP or initially treated with ERCP followed underwent PTBD insertion. Finally, a total of 50 procedures were performed in 47 patients. Of the 47 patients, 8 patients had anatomical alteration due to previous surgery, 6 patients refused ERCP, and 3 patients failed ERCP. For the remaining 30 patients, PTBD was performed on weekend or at night, 11 of whom had poor general condition, 10 patients underwent ERCP 3 to 4 days later after PTBD insertion, 6 patients improved after PTBD insertion without ERCP, 1 patient died, and 1 patient was referred to other hospital. Remaining 1 patient underwent surgery due to Mirizzi syndrome. All procedures were performed by two interventional radiologists. Technical success rate was 100%, clinical success was 94%, and the complication rate was 10%. Fluoroscopy time and the reported radiation dose were significantly lower in patients with dilated bile ducts than in those with non-dilated bile ducts, when biliary puncture under US guidance was performed initially. However, even in patients with non-dilated bile ducts undergoing initial trials of biliary puncture under US guidance, the fluoroscopy time and the reported radiation dose were low, based on current studies. No statistical significant differences were observed in terms of technical and dosimetry results according to right-sided and left-sided procedures and benign and malignant biliary stenosis/obstruction. Thus, US-guided PTBD was found to be a safe and effective technique that significantly reduced fluoroscopy time and radiation doses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The 2021 World Health Organization classification includes telomerase reverse transcriptase promoter (TERTp) mutation status as a factor for differentiating meningioma grades. Therefore, preoperative prediction of TERTp mutation may assist in clinical decision making. However, no previous study has applied fractal analysis for TERTp mutation status prediction in meningiomas. The purpose of this study was to assess the utility of three-dimensional (3D) fractal analysis for predicting the TERTp mutation status in grade 2 meningiomas., Methods: Forty-eight patients with surgically confirmed grade 2 meningiomas (41 TERTp-wildtype and 7 TERTp-mutant) were included. 3D fractal dimension (FD) and lacunarity values were extracted from the fractal analysis. A predictive model combining clinical, conventional, and fractal parameters was built using logistic regression analysis. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict TERTp mutation status., Results: Patients with TERTp-mutant grade 2 meningiomas were older (P = 0.029) and had higher 3D FD (P = 0.026) and lacunarity (P = 0.004) values than patients with TERTp-wildtype grade 2 meningiomas. On multivariable logistic analysis, higher 3D FD values (odds ratio = 32.50, P = 0.039) and higher 3D lacunarity values (odds ratio = 20.54, P = 0.014) were significant predictors of TERTp mutation status. The area under the curve, accuracy, sensitivity, and specificity of the multivariable model were 0.84 (95% confidence interval 0.71-0.93), 83.3%, 71.4%, and 85.4%, respectively., Conclusion: 3D FD and lacunarity may be useful imaging biomarkers for predicting TERTp mutation status in grade 2 meningiomas., Competing Interests: The authors have declared that no competing interests exist.

Backgrounds and Objective: Evaluating the tympanic membrane (TM) using an otoendoscope is the first and most important step in various clinical fields. Unfortunately, most lesions of TM have more than one diagnostic name. Therefore, we built a database of otoendoscopic images with multiple diseases and investigated the impact of concurrent diseases on the classification performance of deep learning networks., Study Design: This retrospective study investigated the impact of concurrent diseases in the tympanic membrane on diagnostic performance using multi-class classification. A customized architecture of EfficientNet-B4 was introduced to predict the primary class (otitis media with effusion (OME), chronic otitis media (COM), and 'None' without OME and COM) and secondary classes (attic cholesteatoma, myringitis, otomycosis, and ventilating tube)., Results: Deep-learning classifications accurately predicted the primary class with dice similarity coefficient (DSC) of 95.19%, while misidentification between COM and OME rarely occurred. Among the secondary classes, the diagnosis of attic cholesteatoma and myringitis achieved a DSC of 88.37% and 88.28%, respectively. Although concurrent diseases hampered the prediction performance, there was only a 0.44% probability of inaccurately predicting two or more secondary classes (29/6,630). The inference time per image was 2.594 ms on average., Conclusion: Deep-learning classification can be used to support clinical decision-making by accurately and reproducibly predicting tympanic membrane changes in real time, even in the presence of multiple concurrent diseases., Competing Interests: The authors have declared that no competing interests exist.