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Abstract With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives to kidney replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine cell signaling. To build three-dimensional structures for implantation into the 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ scaffolds with PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z). The oxygen free radical scavenger EDV was incorporated to induce tubular regeneration. mEVs were engineered to serve regenerative activities with a combination of two EVs from SDF-1α overexpressed tonsil-derived mesenchymal stem cells (sEVs) and intermediate mesoderm (IM) cells during differentiation into kidney progenitor cells (dEVs). mEVs displayed beneficial effects on regeneration by facilitating migration and inducing differentiation of surrounding stem cells, and EDV improved kidney function by regulating the GDNF/RET pathway and their downstream genes. The promotion of MSC recruitment was confirmed with sEV particles number dependently, and the regulation of the GDNF/RET pathway by the effect of EDV and its enhanced effect by mEVs were elucidated using in vitro analysis. The regeneration of tubules was additionally demonstrated through the increased expression of aquaporin-1 (AQP-1) and cadherin-16 (CDH16) for proximal tubules, and calbindin and PAX2 for distal tubules in the renal defect model. With these, structural regeneration and functional recovery were achieved with kidney regeneration in the 5/6 nephrectomy mice model. Graphical abstract

Abstract Patients with diabetes mellitus (DM) are at a higher risk of infectious diseases, and exercise is an important treatment modality for DM. Despite their susceptibility to infection in diabetic patients, the association between the amount of physical activity and the incidence of infective endocarditis (IE) is unclear. We attempted to demonstrate risk reduction by physical activity in diabetic patients with IE. From the National Health Insurance database, patients with DM were verified, and the incidence of IE was investigated. The level of physical activity was categorized into

On 5 April 2024, an earthquake of magnitude 4.8 occurred in Tewksbury, New Jersey. It was the largest instrumentally recorded event since 1900 in New Jersey and southern New York. Millions of people around New York City, ∼65 km east-northeast of Tewksbury, felt the shaking from the mainshock, but the epicentral area experienced no known significant property damages. We determine the focal mechanism, which is oblique faulting, and retrieve the Lg-wave relative source time functions (RSTFs) from the stations at regional distances to understand rupture processes and ground motions. Our fault-slip models well explain azimuthal variations of the RSTFs. The models show the rupture propagating toward the east-northeast (∼50° to 60°), not along the fault strike. The slip distribution on the nodal plane striking north and dipping to the east shows a slip area of 1.1 km radius with the rupture propagating down-dip. The down-dip rupture may account for the observed lack of strong shaking in the epicentral area.

Abstract The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.

Abstract Background Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. Methods This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. Results We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21–63). There was a significant inverse correlation between age and Sab levels after the second dose (slope − 14.96, P = 0.032), and this was more pronounced after the third dose (slope − 208.9, P

Background/Aims Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P

Abstract Background Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. Methods The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. Results In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. Conclusion Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.

Objectives: We evaluated the vaccine effectiveness of monovalent XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and the need for oxygen therapy in South Korea. Design: This study employed a test-negative case-control design. COVID-19 test results in symptomatic subjects from six university hospitals across South Korea were collected (October 26–December 31, 2023). The adjusted absolute and relative vaccine effectiveness were assessed. Results: In total, 5516 subjects were enrolled: 4,824 were unvaccinated with XBB.1.5, and 692 were vaccinated with XBB.1.5 COVID-19 mRNA vaccines. The absolute vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 65.2% (95% CI, 36.1-81.0), 77.3% (95% CI, 51.1-89.5), and 85.3% (95% CI, 57.8-94.9), respectively. The relative vaccine effectiveness when comparing the odds between XBB.1.5 vaccination and no XBB.1.5 vaccination against symptomatic COVID-19 infection, hospitalization, and oxygen therapy was 57.7% (95% CI, 34.7-72.6), 64.3% (95% CI, 35.9-80.2), and 65.5% (95% CI, 27.0-83.7), respectively. Conclusion: The short-term effectiveness of the XBB.1.5 vaccine against symptomatic COVID-19 infection, hospitalization, and receipt of oxygen therapy in South Korea was significant. Long-term vaccine effectiveness warrants evaluation, and these assessments should be conducted regularly.

Here, we present the outcomes of four patients with COVID-19 who underwent hematopoietic stem cell transplantation (HSCT) at the National Cancer Center in South Korea. Despite concerns about the unfavorable course of COVID-19 in HSCT recipients, none of our patients experienced severe COVID-19. Moreover, extended viral shedding in case 1, lasting over 100 days, was resolved after successful engraftment. Contracting the virus when the host could not mount enough of an immune reaction might result in a paradoxically favorable course. Vaccination, monoclonal antibodies, and antiviral agent usage against COVID-19 might also be effective. We suggest, if necessary, HSCT should not be deferred in COVID-19 patients.

Abstract Right-sided infective endocarditis (RSIE) is less common than left-sided infective endocarditis (LSIE) and exhibits distinct epidemiological, clinical, and microbiological characteristics. Previous studies have focused primarily on RSIE in patients with intravenous drug use. We investigated the characteristics and risk factors for RSIE in an area where intravenous drug use is uncommon. A retrospective cohort study was conducted at a tertiary hospital in South Korea. Patients diagnosed with infective endocarditis between November 2005 and August 2017 were categorized into LSIE and RSIE groups. Of the 406 patients, 365 (89.9%) had LSIE and 41 (10.1%) had RSIE. The mortality rates were 31.7% in the RSIE group and 31.5% in the LSIE group (P = 0.860). Patients with RSIE had a higher prevalence of infection with Staphylococcus aureus (29.3% vs. 13.7%, P = 0.016), coagulase-negative staphylococci (17.1% vs. 6.0%, P = 0.022), and gram-negative bacilli other than HACEK (12.2% vs. 2.2%, P = 0.003). Younger age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.95–0.99, P = 0.006), implanted cardiac devices (aOR 37.75, 95% CI 11.63–141.64, P ≤ 0.001), and central venous catheterization (aOR 4.25, 95% CI 1.14–15.55, P = 0.029) were independent risk factors for RSIE. Treatment strategies that consider the epidemiologic and microbiologic characteristics of RSIE are warranted.

Abstract Background Supraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt treatment can significantly improve survival rates. The main focus of treatment is to maintain optimal laryngeal function. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, we conducted univariate and multivariate Cox regression analyses to identify independent prognostic factors for T1–T2 SGSCC. We also enrolled 109 patients with T1–T2 SGSCC from the First Affiliated Hospital of Xinjiang Medical University as an external validation set. In addition, we developed a nomogram to predict the prognosis of T1–T2 SGSCC, assessed the predictive accuracy and discriminatory ability of the nomogram using the area under the curve (AUC), C-index, receiver operating characteristic (ROC) curve and calibration curve, and confirmed the clinical validity of the nomogram using decision curve analysis (DCA). Results Our investigation identified nine prognostic indicators for T1–T2 SGSCC: age (≥ 65 years), marital status, American Joint Committee on Cancer (AJCC) stage (II–IV), grade (III–IV), M stage (M1), radiotherapy, chemotherapy, sex (female), and surgery. These variables were used to create accurate nomograms that predict overall and specific survival rates at 1, 3, and 5 years. The nomograms demonstrated superior prognostic value and accuracy compared to AJCC staging. Laryngectomy with partial laryngectomy is the preferred treatment option for T1–T2 SGSCC cases, providing superior overall survival (OS) and cancer-specific survival (CSS). Radiotherapy also improves OS and CSS. Our results were based on a comprehensive analysis of various indicators, including the C-index, ROC curve, calibration curve, and DCA curve. Conclusion Nomograms provide significant advantages in treatment decision making and diagnosis. Laryngectomy with partial laryngectomy is the most appropriate method for T1–T2 SGSCC cases. However, radiotherapy can also be used. Thus, patients with T1–T2 SGSCC should be evaluated to determine if combination therapy is the optimal treatment approach. Nevertheless, further research is needed to understand the role of chemotherapy. Overall, this study identified nine key predictors of future outcomes, aiding healthcare professionals in assessing risks and making treatment decisions for T1–T2 SGSCC patients.

Abstract Background The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months. Methods In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered. Results At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase. Conclusion A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period. Trial registration The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.

Abstract The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs. However, oral supplementation of drug is relatively less efficient in terms of transmissibility to RGCs compared to direct delivery methods such as intraocular injection or delivery using subconjunctival depots. Neither method is ideal, given the risks of infection and subconjunctival scarring without novel techniques. By contrast, extracellular vesicles (EVs) have advantages as a drug delivery system with low immunogeneity and tissue interactions. We have evaluated the EV delivery of NAM as an RGC protective agent using a quantitative assessment of dendritic integrity using DiOlistics, which is confirmed to be a more sensitive measure of neuronal health in our mouse glaucoma model than the evaluation of somatic loss via the immunostaining method. NAM or NAM-loaded EVs showed a significant neuroprotective effect in the mouse retinal explant model. Furthermore, NAM-loaded EVs can penetrate the sclera once deployed in the subconjunctival space. These results confirm the feasibility of using subconjunctival injection of EVs to deliver NAM to intraocular targets.

Background: Although one of the characteristics of COVID-19 is accompanied by acute pneumonia immediately after infection, large-scale cohort studies focused on this issue are lacking. In addition, there is interest in how COVID-19 vaccinations reduce the incidence of acute pneumonia for people infected with different strains of SARS-CoV-2. Thus, we assess the short-term incidence of pneumonia after COVID-19 with the vaccination and SARS-CoV-2 variants. Methods: As data for 2136,751 COVID-19 patients between January 01, 2020 and February 28, 2022 was collected, they were observed for one month from the day of infection. Patients in retrospective cohort study were classified according to doses of the received vaccine and the epidemic phase when SARS-CoV-2 variants prevailed. Multivariable logistic regression analysis calculated adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for the pneumonia risk. Results: In B.1.1.7-B.1.351, B.1.617.2, and B.1.617.2 variants, the aORs (95% CIs; p-value) for incidence of pneumonia were 0.93 (0.89–0.98;

Background/Aims: Increased prevalence of nonalcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) has been reported. However, the effects of NAFLD on the outcome of IBD remains unclear. We investigated whether the presence of NAFLD could influence the outcomes of patients with IBD. Methods : We recruited 3,356 eligible patients with IBD into our study between November 2005 and November 2020. Hepatic steatosis and fibrosis were diagnosed using hepatic steatosis index of ≥30 and fibrosis-4 of ≥1.45, respectively. The primary outcome was clinical relapse, defined based on the following: IBD-related admission, surgery, or first use of corticosteroids, immunomodulators, or biologic agents for IBD. Results : The prevalence of NAFLD in patients with IBD was 16.7%. Patients with hepatic steatosis and advanced fibrosis were older, had a higher body mass index, and were more likely to have diabetes (all p

Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.

BackgroundPlasmodium vivax malaria has been one of the most troublesome diseases in the Democratic People’s Republic of Korea (DPRK). Given that a majority of malaria cases are concentrated near the demilitarized zone, concerted elimination efforts from both the Republic of Korea (ROK) and DPRK are essential for a malaria-free Korean Peninsula. This study assessed the impact of rapid diagnostic tests (RDTs) and tafenoquine on malaria incidence in DPRK.MethodsWe patterned the current model structure from the previously developed Plasmodium vivax malaria dynamic transmission model for ROK. Model parameters were adjusted using demographic and climate data from malaria-risk areas in DPRK, and the model was calibrated to annual malaria incidences from 2014 to 2018 in DPRK, as reported by the World Health Organization. Subsequently, we estimated the preventable malaria cases over a decade after introducing RDTs and tafenoquine compared to using microscopy alone and primaquine, respectively. Sensitivity analysis was performed to account for uncertainty in model parameters.ResultsWhen comparing RDTs to microscopy, a one-day reduction in diagnostic time due to the introduction of RDTs led to a reduction in malaria incidence by 26,235 cases (65.6%) over the next decade. With a two-day reduction, incidences decreased by 33,635 (84.1%). When comparing a single dose of tafenoquine with a 14-day primaquine regimen, the former prevented 1,222 (77.5%) relapse cases and 4,530 (11.3%) total cases over the years.ConclusionThe continuous and simultaneous implementation of RDTs and tafenoquine emerges as a potent strategy to considerably reduce malaria in DPRK.

The accurate diagnosis of papillary urothelial carcinoma (PUC) is frequently challenging due to benign mimickers. Other than morphology-based diagnostic criteria, reliable biomarkers for differentiating benign and malignant papillary urothelial neoplasms remain elusive, so we sought to discover new markers to address this challenge. We first performed tandem mass spectrometry-based quantitative proteomics using diverse papillary urothelial lesions, including PUC, urothelial papilloma (UP), inverted urothelial papilloma, and cystitis cystica. We prioritized potential diagnostic biomarkers using machine learning, and subsequently validated through immunohistochemistry (IHC) in two independent cohorts. Metabolism, transport, cell cycle, development, and immune response functions were differentially enriched between malignant and benign papillary neoplasms. RhoB and NT5DC2 were shortlisted as optimal candidate markers for PUC diagnosis. In our pilot study using IHC, NT5DC2 was subsequently selected as its expression consistently differed in PUC (p = 0.007). Further validation of NT5DC2 using 49 low-grade (LG) urothelial lesions, including 15 LG-PUCs and 17 UPs, which are the most common mimickers, concordantly revealed lower IHC expression levels in LG-PUC (p = 0.0298). Independent external validation with eight LG-PUCs and eight UPs confirmed the significant downregulation of NT5DC2 in LG-PUC (p = 0.0104). We suggest that NT5DC2 is a potential IHC biomarker for differentiating LG-PUC from its benign mimickers, especially UP.

Background: Data on antimicrobial use at the national level is crucial to establish domestic antimicrobial stewardship policies and enable medical institutions to benchmark against each other. This study aimed to analyze antimicrobial use in Korean hospitals. Methods: We investigated the antimicrobials prescribed in Korean hospitals between 2018 and 2021, using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. Results: Out of more than 1,900 hospitals, PCHs and TCHs represented the largest and lowest percentage of hospitals, respectively. The most frequently prescribed antimicrobial in 2021 was piperacillin/β-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial class according to the KONAS classification was ‘broad-spectrum antibacterial agents predominantly used for community-acquired infections’ in TCHs and SCHs, and 'narrow spectrum beta-lactam agents' in PCH. Total consumption of antimicrobials has decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and from 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period, but not in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, while use of reserve antimicrobials has decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs, it has increased from 0.7 to 0.8 DOT/1,000 patient-days in PCHs. Conclusion: This study confirms that antimicrobial use differs by hospital type in Korea. Recent increases of use of antimicrobials, including reserve antimicrobials, in PCHs reflect the challenges that must be addressed.

Privacy must be preserved when working with client data in machine learning. Federated learning (FL) provides a way to preserve user data privacy by aggregating locally trained models without sharing the user data. Still, the privacy of user identity is not preserved. Secure aggregation is a popular technique in FL for aggregating gradients without disclosing individual data. However, it is costly and inaccurate. Therefore, we propose a novel, scalable, cost-effective group signature-based secure aggregation algorithm in FL, called GSFedSec, where secure aggregation helps conceal the user’s update while the group signature helps conceal their identity. Our algorithm preserves the data and their source. Our simulation results show that the proposed algorithm does not suffer from a loss of accuracy, handles increases in network size competently, offers computational and communication efficiency, and is secure against various security attacks. We have compared the results of efficiency and security against existing algorithms in FL. Also, the security of the algorithm is verified using Burrows–Abadi–Needham (BAN) logic and simulated via the Automated Validation of Internet Security Protocols and Applications (AVISPA) protocol.

Abstract Lactobacillus is a probiotic with therapeutic potential for several diseases, including liver disease. However, the therapeutic effect of L. plantarum against nonalcoholic steatohepatitis (NASH) and its underlying mechanisms remain unelucidated. Therefore, we delineated the L. plantarum-mediated NASH regulation in a mouse model to understand its therapeutic effect. We used a choline-deficient high-fat diet (CD-HFD)-induced murine model that recapitulated the critical features of human metabolic syndrome and investigated the effect of L. plantarum on NASH pathogenesis using transcriptomic, metagenomic, and immunohistochemistry analyses. Validation experiments were performed using liver organoids and a murine model fed a methionine-choline-deficient (MCD) diet. L. plantarum treatment in mice significantly decreased liver inflammation and improved metabolic phenotypes, such as insulin tolerance and the hepatic lipid content, compared with those in the vehicle group. RNA-sequencing analysis revealed that L. plantarum treatment significantly downregulated inflammation-related pathways. Shotgun metagenomic analysis revealed that L-arginine biosynthesis-related microbial genes were significantly upregulated in the L. plantarum group. We also confirmed the elevated arginine levels in the serum of the L. plantarum group. We further used liver organoids and mice fed an MCD diet to demonstrate that L-arginine alone was sufficient to alleviate liver inflammation. Our data revealed a novel and counterintuitive therapeutic effect of L. plantarum on alleviating NASH-related liver inflammation by increasing circulating L-arginine.

Abstract Background Sorafenib improves the overall survival in patients with advanced hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) is commonly overexpressed in HCC. In this study, we investigated whether the inhibition of DKK1 enhances the anti-tumor efficacy of sorafenib in HCC. Methods HCC cells were treated with sorafenib and WAY-262611, which is an inhibitor of DKK1. Transgenic mouse models were also developed using hydrodynamic tail vein injection. Mice were orally administered with sorafenib (32 mg/kg), WAY-262611 (16 mg/kg), or sorafenib + WAY-262611 for 10 days. Mechanisms of sorafenib and WAY-262611 were explored via western blotting, immunostaining, and RNA sequencing. Results DKK1 was significantly overexpressed in patients with HCC than in the healthy controls and patients with liver diseases except HCC (all P

Background and Objectives Laryngopharyngeal reflux (LPR) is an increasingly common disease, characterized by stomach acid reflux reaching the upper airways. Postnasal drip (PND) is a known consequence of LPR, defined as mucus accumulation perceived in the posterior areas of the nose and throat. PND is among the most common causes of persistent cough, hoarseness, sore throat, and other symptoms, affecting the quality of life. This study aimed to evaluate the effects of a proton-pump inhibitor (PPI) on PND symptoms in patients with LPR. Methods We prospectively enrolled patients diagnosed with LPR at our institution between September 2019 and June 2020. The patients were randomly assigned to either the treatment group (20 mg of ilaprazole daily for 8 weeks) or the control group. The scores for the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and Sino-Nasal Outcome Test (SNOT)-20 were evaluated at baseline and at the end of treatment, focusing on PND symptoms. Results Eighty patients (28 men and 52 women; mean age, 48.8 years, range, 22–78 years) were enrolled, with 43 in the treatment group and 37 in the control group. The initial RSI, RFS, and SNOT-20 scores were similar between the two groups, and they decreased significantly only in the treatment group (p=0.002, p

Abstract Background Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. Methods We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. Results A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. Conclusion A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

Background: Despite the low measles antibody positivity rate among young healthcare workers (HCWs) who have previously received two doses of a measles-containing vaccine (MCV), whether an additional dose of MCV acts as a booster remains unknown. Thus, we aimed to evaluate the immune responses to a third dose of MCV in young HCWs. Methods: Hospital-wide measles seroprevalence was assessed using enzyme-linked immunosorbent assay (ELISA). The immunogenicity of a third dose of MCV was determined in young seronegative HCWs (born between 1986 and 1997) who had previously received a two-dose measles vaccination. Results: A total of 3033 (92.6%) HCWs had anti-measles immunoglobulin G. The lowest seropositivity rate was observed in HCWs aged 20–24 years (87.7%). In this group, HCWs who received a third dose of MCV had higher seropositivity than those who received a second dose (89.5% vs. 75.4%). A third dose of MCV was administered to 18 HCWs who did not have anti-measles IgG despite two doses. Neutralizing antibody titers increased significantly 4 weeks after the third vaccination. Although neutralizing antibody titers decreased 1 year post vaccination, 17 (94.4%) HCWs had medium (121–900 mIU/mL) or high (>900 mIU/mL) levels. Furthermore, the third dose of MCV increased the measles virus-specific T-cell effector function. Conclusions: The third dose of MCV induced a strong immune response against measles in young seronegative HCWs who had previously received a two-dose measles vaccination.

Background/Aims: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC. The loss of ARID1A expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables. Methods: We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns. Results: Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)-deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p

Objective This study aimed to evaluate the treatment of spinal stenosis with spondylolisthesis using bilateral-contralateral unilateral biportal endoscopic (UBE) decompression to minimize facet joint damage. Methods We retrospectively evaluated 42 patients with grade 1 spondylolisthesis who underwent bilateral-contralateral UBE decompression between July 2018 and September 2019. To identify segmental instability, static and dynamic images from preoperative and postoperative procedures and final follow-up radiographs were reviewed. Lateral radiograph slippage ratio, sagittal motion, and facet joint preservation were evaluated. Clinical assessments were conducted using the visual analogue scale (VAS), Oswestry Disability Index (ODI), and modified MacNab criteria. Results The average final follow-up period was 26.5 ± 1.3 months. The average preoperative slip percentage was 15.70% ± 5.25%, which worsened to 18.80% ± 5.41% at the final follow-up (p < 0.005). The facet joint preservation rate was 95.6% ± 4.1% on the contralateral side. Improvements in the VAS scores (leg pain: from 7.9 ± 2.2 to 3.1 ± 0.7; p < 0.005; back pain: from 7.2 ± 3.0 to 2.8 ± 1.0; p < 0.005) were observed at the final follow-up. The mean preoperative ODI was 26.19 ± 3.42, which improved to 9.6 ± 1.0 (p < 0.005). Thirteen patients exhibited delayed focal segmental instability following decompression. Despite the absence of symptoms or improvement with conservative treatment in the majority of patients with delayed instability, two patients required fusion surgery to address the instability. Additionally, 2 patients developed facet synovial cysts, while 2 experienced spinous process fractures. Conclusion Bilateral decompression with a contralateral UBE approach could be an effective and alternative treatment method to reduce instability in spinal stenosis with grade 1 spondylolisthesis.

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(−) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.

Abstract Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.

Background/Aims This study aimed to evaluate the characteristics of endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography (EUS)-related adverse events (AEs) that eventually lead to medical disputes or claims on medical professional liability. Methods Medical disputes for ERCP/EUS-related AEs filed in the Korea Medical Dispute Mediation and Arbitration Agency between April 2012 and August 2020 were evaluated using corresponding medical records. AEs were categorized into three sections: procedure-related, sedation-related, and safety-related AEs. Results Among a total of 34 cases, procedure-related AEs were 26 (76.5%; 12 duodenal perforations, 7 post-ERCP pancreatitis, 5 bleedings, 2 perforations combined with post-ERCP pancreatitis); sedation-related AEs were 5 (14.7%; 4 cardiac arrests, 1 desaturation), and safety-related AEs were 5 (8.8%; 1 follow-up loss for stent removal, 1 asphyxia, 1 fall). Regarding clinical outcomes, 20 (58.8%) were fatal and eventually succumbed to AEs. For the types of medical institutions, 21 cases (61.8%) occurred at tertiary or academic hospitals, and 13 (38.2%) occurred at community hospitals. Conclusions The ERCP/EUS-related AEs filed in Korea Medical Dispute Mediation and Arbitration Agency showed distinct features: duodenal perforation was the most frequent AE, and clinical outcomes were fatal, resulting in at least more than permanent physical impairment.

Abstract Replication Protein A (RPA) is a broadly conserved complex comprised of the RPA1, 2 and 3 subunits. RPA protects the exposed single-stranded DNA (ssDNA) during DNA replication and repair. Using structural modeling, we discover an inhibitor, JC-229, that targets RPA1 in Trypanosoma brucei, the causative parasite of African trypanosomiasis. The inhibitor is highly toxic to T. brucei cells, while mildly toxic to human cells. JC-229 treatment mimics the effects of TbRPA1 depletion, including DNA replication inhibition and DNA damage accumulation. In-vitro ssDNA-binding assays demonstrate that JC-229 inhibits the activity of TbRPA1, but not the human ortholog. Indeed, despite the high sequence identity with T. cruzi and Leishmania RPA1, JC-229 only impacts the ssDNA-binding activity of TbRPA1. Site-directed mutagenesis confirms that the DNA-Binding Domain A (DBD-A) in TbRPA1 contains a JC-229 binding pocket. Residue Serine 105 determines specific binding and inhibition of TbRPA1 but not T. cruzi and Leishmania RPA1. Our data suggest a path toward developing and testing highly specific inhibitors for the treatment of African trypanosomiasis.

Abstract We used local P and S waves, and regional Lg waves to investigate the Mw 4.9 Offshore Jeju Island earthquake, whose records show evidence of a complex rupture. This earthquake provides a rare window to understand the seismogenesis of moderate‐sized earthquakes on the southern Korea–East China Sea continental shelf. We computed the relative source time functions (RSTFs) by aligning the signals on the origin time of the main and its empirical Green's function (EGF) events, allowing us to use them as differential times of the EGF pair. We determined subevent locations using direct‐wave RSTFs, and captured the rupture variability of the two large subevents using waveform inversion of stacked Lg‐wave RSTFs. The first subevent rupture started by two weak nucleation phases and propagated slowly and bilaterally. Then the second subevent ruptured westward. Our analysis demonstrates that the Lg‐wave train observed at regional distances is useful in investigating detailed slip history.

Abstract Compared with monofacial solar cells, the development of bifacial solar cells has garnered considerable attention for achieving higher power output by simultaneously harvesting direct and diffused light while incurring fewer additional manufacturing costs. Perovskite light absorbers, given their outstanding optoelectronic properties, present great opportunities for fabricating bifacial solar cells. However, one of the challenges in designing bifacial perovskite solar cells (PSCs) is that they suffer from optical and electrical losses due to insufficient light absorption in the perovskite layer. In this respect, in this work, a hot‐pressing transfer process is developed to fabricate a diffraction‐grating (DG) perovskite layer to form a bifacial PSC. The constructed DG structure on the perovskite layer improved its light‐harvesting efficiency, reduced its charge recombination, and enhanced its charge extraction properties. The bifacial DG PSC achieved power conversion efficiencies of 14.01% and 10.04% for the bottom and top illuminations, respectively, resulting in a bifaciality factor of 0.71. Therefore, the newly developed hot‐pressing transfer process for fabricating DG structures on perovskite layers is a promising technique for fabricating high‐efficiency bifacial PSCs with high bifaciality factors.

[This corrects the article DOI: 10.1371/journal.pone.0266610.].

Abstract Background Serogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana’s meningitis belt. Methods Polymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran–Armitage trend test. Results Of the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P

Abstract The beginning of human immunodeficiency virus (HIV) infection treatment depends on various factors, which are significantly correlated with the initial CD4 cell number. However, a covariate correlation between these factors may not reflect the correct outcome variable. Thus, we evaluated the effects of a combination of fixed factors (reduced dimensions), which determine when to start treatment for the first time, on short-term outcome, long-term outcome, and survival, considering correlations between factors. Multiple correspondence analysis was performed on variables obtained from 925 patients who participated in a Korean HIV/acquired immunodeficiency syndrome cohort study (2006–2017). Five reduced dimension groups were derived according to clinical data, viral load, CD4 cell count at diagnosis, initial antiretroviral therapy, and others. The dimension group with high initial viral loads (55,000 copies/mL) and low CD4 cell counts ( 350 cells/mm3) that did not require immediate treatment according to previous guidelines had a higher failure rate for long-term relative CD4 recovery. Our results highlight the importance of early diagnosis and treatment to positively influence long-term disease outcomes, even if the initial immune status is poor, given the patient’s combination of early diagnostic symptoms.

Abstract Bone marrow mesenchymal stromal/stem cells (MSCs) are a heterogeneous population that can self-renew and generate stroma, cartilage, fat, and bone. Although a significant progress has been made toward recognizing about the phenotypic characteristics of MSCs, the true identity and properties of MSCs in bone marrow remain unclear. Here, we report the expression landscape of human fetal BM nucleated cells (BMNCs) based on the single-cell transcriptomic analysis. Unexpectedly, while the common cell surface markers such as CD146, CD271, and PDGFRa used for isolating MSCs were not detected, LIFR+PDGFRB+ were identified to be specific markers of MSCs as the early progenitors. In vivo transplantation demonstrated that LIFR+PDGFRB+CD45-CD31-CD235a- MSCs could form bone tissues and reconstitute the hematopoietic microenvironment (HME) effectively in vivo. Interestingly, we also identified a subpopulation of bone unipotent progenitor expressing TM4SF1+CD44+CD73+CD45-CD31-CD235a-, which had osteogenic potentials, but could not reconstitute HME. MSCs expressed a set of different transcription factors at the different stages of human fetal bone marrow, indicating that the stemness properties of MSCs might change during development. Moreover, transcriptional characteristics of cultured MSCs were significantly changed compared with freshly isolated primary MSCs. Our cellular profiling provides a general landscape of heterogeneity, development, hierarchy, microenvironment of the human fetal BM-derived stem cells at single-cell resolution.

Abstract Background During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case–control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. Methods This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1–2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. Results 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72–0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006–1.293; P = 0.041). Conclusions Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

OBJECTIVES To assess the risk of lymphadenopathy following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1-day to 42-day risk interval after coronavirus disease 2019 (COVID-19) vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval. RESULTS The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% confidence interval [CI], 1.17 to 1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44 to 1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson’s comorbidity index BNT162b2). Within the 1-day to 42-day post-dose risk period, the relative risk was highest during the 1-day to 7-day post-dose period (1.59; 95% CI, 1.57 to 1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI. CONCLUSIONS SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.

There is still need for representative models of intrahepatic cholangiocarcinoma (ICC) subtypes. Here, the authors develop organoids for two recently suggested ICC subtypes and identify distinct transcriptional profiles and potential therapeutic targets.

Background The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear. Methods We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation. Results We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This “UC-like signature” was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG. Conclusions Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

Abstract The breasts in women pectus excavatum patients frequently appear to be slanting medially along the inclination of the distorted ribs. This study aims to evaluate changes in the distance between the nipples and to find out whether medially slanting breasts are corrected in women pectus excavatum patients following modified Nuss procedure. This case series analysis enrolled 22 young women patients with pectus excavatum between October 2011 and September 2020. We measured all the patients’ distances from the sternal midline to the right and left nipples, based on chest computerized tomography. We calculated the distances between nipples as being the sum of the right and left distances. The mean age of patients was 16.50 ± 4.73 years, and the follow-up periods were 35.59 ± 20.23 months. The postoperative Haller indices (2.89 ± 0.43) were significantly lower than the preoperative Haller indices (5.14 ± 1.96) (p = 0.000). The distances between the nipples before and after Nuss procedure were 145.17 ± 17.73 mm and 172.29 ± 19.11 mm, which is a significant increase following surgery. (p = 0.000). Our results demonstrated that skeletal correction with modified Nuss procedure in pectus excavatum increased the distance between nipples, indicating that medially slanting breasts had been corrected.

Abstract Human mesenchymal stem cells (hMSCs)-derived extracellular vesicles (EVs) have been known to possess the features of the origin cell with nano size and have shown therapeutic potentials for regenerative medicine in recent studies as alternatives for cell-based therapies. However, extremely low production yield, unknown effects derived from serum impurities, and relatively low bioactivities on doses must be overcome for translational applications. As several reports have demonstrated the tunability of secretion and bioactivities of EVs, herein, we introduced three-dimensional (3D) culture and cell priming approaches for MSCs in serum-free chemically defined media to exclude side effects from serum-derived impurities. Aggregates (spheroids) with 3D culture dramatically enhanced secretion of EVs about 6.7 times more than cells with two-dimensional (2D) culture, and altered surface compositions. Further modulation with cell priming with the combination of TNF-α and IFN-γ (TI) facilitated the production of EVs about 1.4 times more than cells without priming (9.4 times more than cells with 2D culture without priming), and bioactivities of EVs related to tissue regenerations. Interestingly, unlike changing 2D to 3D culture, TI priming altered internal cytokines of MSC-derived EVs. Through simulating characteristics of EVs with bioinformatics analysis, the regeneration-relative properties such as angiogenesis, wound healing, anti-inflammation, anti-apoptosis, and anti-fibrosis, for three different types of EVs were comparatively analyzed using cell-based assays. The present study demonstrated that a combinatory strategy, 3D cultures and priming MSCs in chemically defined media, provided the optimum environments to maximize secretion and regeneration-related bioactivities of MSC-derived EVs without impurities for future translational applications.

Abstract People living with human immunodeficiency virus (PLWH) in Korea demonstrate insufficient self-management behaviors. Especially during pandemics such as COVID-19, technology-based self-management programs are needed to overcome time and space limitations. The purpose of this study was to evaluate the effects of a self-management program using a mobile app (Health Manager) on self-management outcomes among PLWH in Korea. A randomized controlled pilot trial was performed and participants were enrolled in the infectious outpatient clinic of a single hospital. The intervention group used the mobile app for 4 weeks, while the control group received self-management education materials in a portable document format. The online self-report questionnaire assessed primary outcomes including self-efficacy for self-management, self-management behaviors, and medication adherence, and secondary outcomes including perceived health status, depression, and perceived stigma. Thirty-three participants were randomly assigned to the intervention (n = 17) or the control group (n = 16). In the intention-to-treat analysis, self-efficacy for self-management and self-management behaviors increased, while perceived stigma decreased. The app-based self-management program could be considered a helpful strategy to improve self-management outcomes among PLWH and reduce their perceived stigma during the pandemic. Further studies with larger samples and longer follow-ups are needed. Trial registration: Clinical Research Information Service, KCT0004696 [04/02/2020].

Background/Aims: Metabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD. Methods: We recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011). Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD. Results: The prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend

Background/Aim The profile of patients with hepatocellular carcinoma (HCC) has changed globally; the role of etiology in predicting prognosis of HCC patients remains unclear. We aimed to analyze the characteristics and prognosis of Korean patients with HCC according to disease etiology. Methods This retrospective observational study included patients diagnosed with HCC between 2010 and 2014 in a single center in Korea. Patients with HCC aged

Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.