Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Purpose: To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections. Materials and Methods: Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization. Results: In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/ Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling. Conclusions Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Many plant extracts have been recognized for their potential anti-cancer properties. Schoenoplectus triqueter (L.) Palla, commonly known as triangular rush (TAR) and part of the Cyperaceae family, predominantly thrives in the wetlands of the Huangpu Yangtze estuary. In this study, we explored the anti-cancer capabilities of TAR on lung cancer A549 cells. Our findings revealed that TAR was significantly more cytotoxic to A549 cells than to normal lung HEL 299 cells. TAR promoted apoptosis through enhanced caspase-3 activity and subsequent cleavage of poly ADP ribose polymerase (PARP). This apoptotic effect was associated with the downregulation of several STAT3-regulated genes, including Survivin, IAP-1, Cyclin D1, COX-2, and matrix metallopeptidase 9 (MMP-9). Moreover, TAR effectively reduced cell proliferation, invasion, and migration. The inhibition of STAT3 activation was achieved by blocking the upstream Janus activated kinases 1 and 2 (JAK1, JAK2), c-Src kinases, and the nuclear translocation of STAT3 in A549 cells. Additionally, TAR enhanced the effects of cisplatin through synergistic inhibition of STAT3 activation and increased apoptosis in A549 cells. Key compounds contributing to these biological activities were identified via LCHRMS analysis. Our results suggest that TAR blocks constitutive STAT3 activation, exhibiting anti-proliferative and pro-apoptotic effects in lung cancer A549 cells.

Background: and Purpose Excess or insufficient sleep, irregular sleep-wake patterns, and an extreme early or late chronotypes adversely impact physical and mental health. Changes in sleep characteristics should therefore be tracked, and factors that contribute to poor sleep should be identified. We investigated the changes in sleep patterns among South Korean adults during 2009–2018. Methods: Using data of a representative sample of South Korean adults from the 2009 (n= 2,658, 48.5% males; age=44.5±15.0 years old [mean±standard deviation], age range=19–86 years) and 2018 (n=2,389, 49.1% males; age=47.9±16.3 years, age range=19–92 years) Korean Headache-Sleep Study, we explored changes in sleep timing, sleep duration, chronotype, and social jetlag (SJL). Logistic regression analysis was used to examine the association between average sleep duration and depression. Results: From 2009 to 2018, bedtimes were advanced by 10 and 25 min on workdays and free days, respectively. Meanwhile, wake-up times were advanced by 13 min and delayed by 12 min on workdays and free days, respectively. The average sleep duration significantly decreased from 7.45 h to 7.13 h. The prevalence of short sleep duration (<7 h) increased, whereas that of long sleep duration (≥8 h) decreased. A circadian preference toward eveningness and SJL increased. The prevalence of depression increased from 4.6% to 8.4%, and there were significant reverse J-shaped and U-shaped associations between average sleep duration and depression in 2009 and 2018, respectively. Conclusions Changes in sleep patterns and the association between sleep duration and depressive mood were determined from a representative sample of the South Korean adult population. Interventions to modify sleep behaviors might improve public health.

Purpose: Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. Materials and Methods: We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). Results: We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l 1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. Conclusion We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.

Background/Aims: The optimal systolic blood pressure (SBP) goal for elderly patients with hypertension, especially to reduce cardiovascular disease (CVD) incidence and improve outcome, is unclear. This study aimed to evaluate the beneficial effects of intensive treatment for hypertension on the incidence of CVD in elderly Korean patients. Methods: The HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial is a multicenter, parallel-design, open-label, randomized controlled trial designed to evaluate whether intensive treatment (SBP ≤ 130 mmHg) will provide more benefits in lowering the incidence and mortality associated with CVD than standard treatment (SBP ≤ 140 mmHg) in elderly patients with hypertension aged ≥ 65 years. For this study, eleven university hospitals in Korea will enroll approximately 3,176 elderly patients with hypertension between 2019 and 2022. Patients will be requested to visit the clinic every 4 months for the first year and every 6 months thereafter for 36 months. Parameters, including clinic and home blood pressure, anthropometric and laboratory findings, and frailty assessments, will be collected according to the standardized protocol. The primary outcome is a composite of CVD (acute coronary syndrome, stroke, and heart failure) incidence and cardiovascular deaths. Results: As of December 2021, 1,655 participants had been enrolled in the study, including 831 patients in the standard group and 824 patients in the intensive group. Conclusions The HOWOLD-BP trial is the first study performed in Korea to evaluate the beneficial effects of intensive blood pressure treatment on CVD in elderly patients with hypertension. The results of this study will help clarify the appropriate target SBP for this population.