Transcriptomic and metabolomic analysis unveils nanoplastic-induced gut barrier dysfunction via STAT1/6 and ERK pathways.

The widespread prevalence of micro and nanoplastics in the environment raises concerns about their potential impact on human health. Recent evidence demonstrates the presence of nanoplastics in human blood and tissues following ingestion and inhalation, yet the specific risks and mechanisms of nanoplastic toxicity remain inadequately understood. In this study, we aimed to explore the molecular mechanisms underlying the toxicity of nanoplastics at both systemic and molecular levels by analyzing the transcriptomic/metabolomic responses and signaling pathways in the intestines of mice after oral administration of nanoplastics. Transcriptome analysis in nanoplastic-administered mice revealed a notable upregulation of genes involved in pro-inflammatory immune responses. In addition, nanoplastics substantially reduced the expression of tight junction proteins, including occludin, zonula occluden-1, and tricellulin, which are crucial for maintaining gut barrier integrity and function. Importantly, nanoplastic administration increased gut permeability and exacerbated dextran sulfate sodium-induced colitis. Further investigation into the underlying molecular mechanisms highlighted significant activation of signaling transsducer and activator of transcription (STAT)1 and STAT6 by nanoplastic administration, which was in line with the elevation of interferon and JAK-STAT pathway signatures identified through transcriptome enrichment analysis. Additionally, the consumption of nanoplastics specifically induced nuclear factor kappa-B (NF-κB) and extracellular signal-regulated kinase (ERK)1/2 signaling pathways in the intestines. Collectively, this study identifies molecular mechanisms contributing to adverse effects mediated by nanoplastics in the intestine, providing novel insights into the pathophysiological consequences of nanoplastic exposure.

Homeostasis effects of fermented Maillard reaction products by Lactobacillus gasseri 4M13 in dextran sulfate sodium-induced colitis mice.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase worldwide. Multiple factors, including diet, loss of the intestinal barrier function, and imbalance of the immune system can cause IBD. A balanced diet is important for maintaining a healthy bowel and preventing IBD from occurring. The effects of probiotic Lactobacillus gasseri-fermented Maillard reaction products (MRPs) prepared by reacting whey protein with galactose on anti-inflammation and intestinal homeostasis were investigated in this study, which compared MPRs and probiotics separately. RESULTS: In an animal colitis model induced by 2% dextran sulfate sodium (DSS), FWG administration alleviated colon length loss and maintained intestinal immune system homeostasis as reflected by down-regulated interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α output, and metallopeptidase-9, and epithelial barrier balance as reflected by up-regulated occludin, E-cadherin, and zonula occludens-1 production in the colon. Furthermore, the expression of splenic cytokines such as IL-6, TNF-α, and IL-10 was up-regulated in the FWG-treated mice in a comparable amount to the control group to ensure the balance of immune responses. CONCLUSION: This study showed that the use of FWG protects the intestines from colitis caused by DSS and maintains immune balance. FWG increased antioxidant enzyme activity, increased intestinal permeability, and regulated the balance of pro- and anti-inflammatory cytokines in the intestines and spleen. Continued intake of FWG can alleviate IBD symptoms through the preservation of mucosal immune responses, epithelial junction and homeostasis through the regulated splenic cytokines. © 2021 Society of Chemical Industry.

cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential.

Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed chromatin immunoprecipitation (ChIP) sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways, including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of the cyclic AMP (cAMP)/exchange proteins directly activated by cAMP (EPAC)/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that the cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential.

Modification of Pediatric Sequential Organ Failure Assessment Score Using Acute Kidney Injury Diagnostic Criteria.

OBJECTIVES: To develop a modified pediatric Sequential Organ Failure Assessment score using the acute kidney injury diagnostic criteria and evaluate its performance in predicting mortality. DESIGN: A single-center retrospective study. SETTING: Fourteen-bed PICU in a tertiary care academic children's hospital. PATIENTS: Critically ill children admitted to the PICU between January 2017 and September 2019 with at least more than two serum creatinine measurements-one for baseline and the other within the first 48 hours of PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 755 patients were included. Overall, 265 patients were diagnosed with acute kidney injury using the current acute kidney injury diagnostic criteria. The overall PICU mortality was 5.8%. Patients with acute kidney injury required more vasoactive-inotropic drugs and showed higher illness severity scores, including the Pediatric Risk of Mortality III, Pediatric Logistic Organ Dysfunction 2, pediatric Sequential Organ Failure Assessment, and modified pediatric Sequential Organ Failure Assessment scores, as well as higher PICU mortality than patients without acute kidney injury (p < 0.001). As acute kidney injury stages increase, PICU mortality also increased (p < 0.001). Based on multivariable logistic regression analysis adjusted for age and sex, the modified pediatric Sequential Organ Failure Assessment score was an independent prognostic factor of PICU mortality. The modified pediatric Sequential Organ Failure Assessment score showed better performance in predicting PICU mortality (area under the receiver operating characteristic curve, 0.821; 95% CI, 0.759-0.882) than other severity scores (area under the receiver operating characteristic curve [95% CI] of Pediatric Risk of Mortality III, Pediatric Logistic Organ Dysfunction 2, and pediatric Sequential Organ Failure Assessment scores: 0.788 [0.723-0.853], 0.735 [0.663-0.807], and 0.785 [0.718-0.853], respectively). CONCLUSIONS: Acute kidney injury is prevalent and associated with poor clinical outcomes in critically ill children. The modified pediatric Sequential Organ Failure Assessment score, based on the acute kidney injury diagnostic criteria, showed improved performance in predicting PICU mortality. The modified pediatric Sequential Organ Failure Assessment score could be a promising prognostic factor for critically ill children.

Placental Pathologic Changes Associated with Fetal Growth Restriction and Consequent Neonatal Outcomes.

OBJECTIVE: To evaluate the pathological changes of the placenta to determine the mechanism underlying placenta-derived fetal growth restriction (FGR) and investigate its influence on neonatal outcomes. Study design: This retrospective case-control study included 120 singleton pregnancies with FGR as well as 120 gestational age-matched controls. We compared the placental pathological findings and neonatal outcomes according to the presence of placental malperfusion. Results: The FGR group demonstrated lower placental weight (350.8 ± 118.8 vs. 436.1 ± 109.7g, P < .0001), smaller chorionic plate area (157.7 ± 48.0 vs. 201.5 ± 53.4 cm2, P < .0001), and higher rate of villous change lesions (84.2% vs. 52.5%, P < .0001) than the control group. FGR neonates with placental malperfusion had a higher rate of adverse neonatal outcomes (87.1% vs. 63.2%, P = .0175). Conclusion: Small placentas and placental malperfusion reflected in villous changes are associated with FGR. FGR neonates with placental malperfusion are more susceptible to adverse neonatal outcomes.

Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells.

Background: Arsenic compounds (As2O3 and As4O6) have demonstrated anticancer effects in various malignancies. In this study, the cytotoxicity of arsenic compounds on ovarian cancer cell lines and the anticancer activity of the combination of arsenic compounds and cisplatin IN chemoresistant ovarian cancer cells were investigated.Methods: We investigated the cytotoxicity of As2O3 and As4O6 and their combinations with cisplatin in the paclitaxel-sensitive ovarian cancer cell lines SKOV3ip1 and HeyA8 and paclitaxel-resistant ovarian cancer cell lines SKOV3TRip2 and HeyA8-MDR. Growth and apoptosis were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. For detection of apoptotic cells, immunofluorescence was performed using a cleaved caspase-3 antibody. Cell-cycle distribution was determined by propidium iodide staining and flow cytometry.Results: Treatment of each cell line with As2O3 or As4O6 led to a marked dose-dependent inhibition of cell growth. As2O3 and As4O6 treatment induced caspase-3-dependent apoptosis in all cell lines compared to the respective control groups (p < .05). As2O3 and As4O6 induced apoptosis of paclitaxel-sensitive and -resistant cancer cell lines following G2/M cell cycle arrest (p < .05). A synergistic effect was achieved by combining cisplatin with As2O3 or As4O6 in the paclitaxel-resistant ovarian cancer cell lines.Conclusions: As2O3 and As4O6 can inhibit cell growth and induce apoptosis in paclitaxel-sensitive and -resistant ovarian cancer cell lines. Their combination with cisplatin resulted in a synergistic effect in paclitaxel-resistant cancer cell lines. These results suggest that arsenic compounds may be given in monotherapy or combination therapy with cisplatin for treating paclitaxel-resistant ovarian cancer.

Coronary artery involvement in chronic graft-versus-host disease presenting as sudden cardiac arrest.

Graft-versus-host disease (GVHD) is related to considerable morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Cardiac complications associated with GVHD are uncommon, and coronary artery involvement is even more unusual. We report on a male pediatric patient with chronic GVHD who developed a fatal ventricular arrhythmia caused by coronary artery obstruction after HSCT. At 30 months after HSCT, he suddenly collapsed with ventricular fibrillation. After resuscitation, electrocardiography showed abnormal q-wave and ST changes in the inferior leads, suggesting a coronary event. Coronary angiography revealed complete obstruction of the proximal left anterior descending artery, subtotal obstruction of the mid left circumflex artery, and mild narrowing at the right coronary artery. This boy had none of the risk factors for coronary artery disease, and the only possible explanation for the cardiac event is GVHD. Coronary artery disease only rarely occurs as a cardiac event in children. However, coronary artery involvement should be recognized as one of the important manifestations of chronic GVHD in children.

Anti-inflammatory activities of Maillard reaction products from whey protein isolate fermented by Lactobacillus gasseri 4M13 in lipopolysaccharide-stimulated RAW264.7 cells.

Maillard reaction products formed from whey protein isolate (WPI) and sugar have been shown to have an anti-inflammatory effect in vitro. Here, we incubated WPI and galactose (GWA) in an aqueous solution at 65°C for 24 h to produce a glycated conjugate, which was then fermented using Lactobacillus gasseri 4M13 to obtain the fermented product (F-GWA). We demonstrated that F-GWA had an anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. It reduced both LPS-stimulated nitric oxide production and LPS-stimulated increases in the gene expression levels of tumor necrosis factor-α and cyclooxygenase-2 in a dose-dependent manner. Furthermore, F-GWA inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, members of the mitogen-activated protein kinase family. The glycation process was evaluated by measuring fluorescence intensity and the furosine concentration during the Maillard reaction to form GWA. The protein modifications of WPI were analyzed using MALDI-TOF tandem mass spectrometry. We found that the combination of the Maillard reaction and L. gasseri 4M13 fermentation increased the prebiotic properties of GWA as well as organic acid production, compared with the nonreacted WPI and galactose.

Risk factors for persistent hyperparathyroidism in children with stable renal function after kidney transplantation.

This study aimed to investigate the risk factors for PHPT in children with stable renal function who received KT. We retrospectively analyzed the clinical findings and laboratory results of patients who underwent KT below 19 years of age, between 1996 and 2016 at our hospital. Patients were followed up for more than 1 year after KT. We calculated the mean ± standard deviation or median [minimum - maximum] for each parameter. We included a total of 46 patients (male:female = 26:20). Twelve patients (26.1%) were included in the PHPT group, and 34 (73.9%) were in the nPTH group. The dialysis duration was 57.1 ± 49.9, 44 [0-145] months in the PHPT group and 23.5 ± 25.8, 15 [1-121] months in the nPTH group (P = .040). The post-KT total CO2 level was significantly higher in the PHPT group (P = .022). The pre- (P = .021) and post-KT (P = .005) and 3-month average (P = .018) iPTH levels were also significantly higher in PHPT group. The height z-score showed a negative correlation, and the pre-KT, 3-month average phosphorus and alkaline phosphate levels showed positive correlations with iPTH levels, at 1 year after KT. Patients who undergo prolonged durations of dialysis, have increased iPTH levels before and after KT, and have low bicarbonate levels after KT are at risk of PHPT and should be monitored carefully.

Enhancing the natural killer cell activity and anti-influenza effect of heat-treated Lactobacillus plantarum nF1-fortified yogurt in mice.

Influenza A virus (IAV) infection is a global public health concern. It causes respiratory diseases ranging from mild illness to fatal disease. Natural killer (NK) cells are an innate immune component that kill infected cells and secrete cytokines to modulate the adaptive immune system; they constitute the first-line defense and play important roles in controlling IAV infection. This study evaluated the effect of daily administration of heat-treated Lactobacillus plantarum nF1-fortified yogurt on immunity and protection against IAV infection. Mice administered with heat-treated L. plantarum nF1-fortified yogurt showed elevated NK cell-related cytokine expression levels. Daily administration of the L. plantarum nF1-fortified yogurt before IAV infection also enhanced splenic NK activity, lung inflammatory cytokine responses, and survival rate. Thus, daily administration of nF1-fortified yogurt enhances host immunity and helps prevent IAV infection.

CD19 CAR-expressing iPSC-derived NK cells effectively enhance migration and cytotoxicity into glioblastoma by targeting to the pericytes in tumor microenvironment.

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment. Given this context, our study aimed to target the GBM TME, with a special focus on pericytes expressing CD19, to evaluate the potential effectiveness of CD19 CAR-iNK cells against GBM. We performed CD19 CAR transduction in induced pluripotent stem cell-derived NK (iNK) cells. To determine whether CD19 CAR targets the TME pericytes in GBM, we developed GBM-blood vessel assembloids (GBVA) by fusing GBM spheroids with blood vessel organoids. When co-cultured with GBVA, CD19 CAR-iNK cells migrated towards the pericytes surrounding the GBM. Using a microfluidic chip, we demonstrated CD19 CAR-iNK cells' targeted action and cytotoxic effects in a perfusion-like environment. GBVA xenografts recapitulated the TME including human CD19-positive pericytes, thereby enabling the application of an in vivo model for validating the efficacy of CD19 CAR-iNK cells against GBM. Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

Spectral Graph Neural Network-Based Multi-Atlas Brain Network Fusion for Major Depressive Disorder Diagnosis.

Major Depressive Disorder (MDD) imposes a substantial burden within the healthcare domain, impacting millions of individuals worldwide. Functional Magnetic Resonance Imaging (fMRI) has emerged as a promising tool for the objective diagnosis of MDD, enabling the investigation of functional connectivity patterns in the brain associated with this disorder. However, most existing methods focus on a single brain atlas, which limits their ability to capture the complex, multi-scale nature of functional brain networks. To address these limitations, we propose a novel multi-atlas fusion method that incorporates early and late fusion in a unified framework. Our method introduces the concept of the holistic Functional Connectivity Network (FCN), which captures both intra-atlas relationships within individual atlases and inter-regional relationships between atlases with different brain parcellation scales. This comprehensive representation enables the identification of potential disease-related patterns associated with MDD in the early stage of our framework. Moreover, by decoding the holistic FCN from various perspectives through multiple spectral Graph Convolutional Neural Networks and fusing their results with decision-level ensembles, we further improve the performance of MDD diagnosis. Our approach is easily implemented with minimal modifications to existing model structures and demonstrates a robust performance across different baseline models. Our method, evaluated on public resting-state fMRI datasets, surpasses the current multi-atlas fusion methods, enhancing the accuracy of MDD diagnosis. The proposed novel multi-atlas fusion framework provides a more reliable MDD diagnostic technique. Experimental results show our approach outperforms both single- and multi-atlas-based methods, demonstrating its effectiveness in advancing MDD diagnosis.

Outcomes of carotid endarterectomy in octogenarians compared to their younger counterparts: a retrospective observational study.

Purpose: This study was performed to analyze the association between age and outcomes of carotid endarterectomy (CEA) by comparing postoperative outcomes between octogenarians and younger patients. Methods: From November 1994 to December 2022, 1,585 internal carotid arteries of 1,434 patients were enrolled. Patients were stratified into 2 groups: octogenarians (≥80 years old) and non-octogenarians (<80 years old). Primary endpoints were early (≤30 days) outcomes of ipsilateral stroke, any stroke, myocardial infarction, death, and major adverse cardiovascular events (MACE). We also compared overall any stroke and death between the 2 groups. Results: One of 132 octogenarians (0.8%) and 17 of 1,453 non-octogenarians (1.1%) experienced ipsilateral stroke within 30 days. Thirty-day MACE occurred in 4 of 132 octogenarians (3%) and 44 of 1,453 non-octogenarians (3%). There were no significant differences in any early (≤30 days) outcomes. Symptomatic status was associated with increased 30-day MACE (odds ratio [OR], 2.610; 95% confidence interval [CI], 1.450-4.696; P = 0.003) and 30-day any stroke (OR, 3.999; 95% CI, 1.627-9.828; P = 0.003). Symptomatic status was also associated with overall any stroke (hazard ratio [HR], 2.885; 95% CI, 1.865-4.463; P < 0.001), but age of ≥80 years was not associated with 30-day MACE, 30-day any stroke, or overall stroke. Age of ≥80 years was only associated with overall survival (HR, 2.644; 95% CI, 1.967-3.555; P < 0.001). Conclusion: CEA would be a safe and effective treatment for octogenarians with low 30-day complications and long-term stroke rates, comparable with that of younger counterparts. Advanced age is not a contraindication for CEA.

Comparison of the clinical characteristics and clinical outcomes of culture-positive septic shock and culture-negative septic shock among pediatric patients.

OBJECTIVES: Among pediatric patients with septic shock, culture-negative septic shock (CNSS) is common but there have been limited data on its clinical characteristics and prognosis. We compared the clinical characteristics and clinical outcomes between culture-positive septic shock (CPSS) and CNSS in pediatric patients. DESIGN: Retrospective single-center study. SETTING: Pediatric intensive care unit (PICU) of a tertiary referral hospital. PATIENTS: All pediatric patients who were admitted to the PICU due to septic shock between January 2010 and November 2021, except for those with fungal or viral infections and those who expired on the day of admittance to the PICU. The primary outcome was 30-day mortality and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 294 patients (CPSS group, n = 185 [62.9%]; CNSS group, n = 109 [37.1%]) were included. The rates of 30-day mortality and in-hospital mortality (30-day mortality 22.7% vs 22%, in-hospital mortality 29.7% vs 25.7%) were not significantly different between the CPSS group and the CNSS group. The two groups showed comparable results in clinical outcomes such as the requirement for mechanical ventilator and renal replacement therapy, PICU stay duration, and the duration of MV and vasopressor/inotrope support. Among the CPSS group, 98 (53%) patients who were infected with multi-drug resistance (MDR) bacteria had significantly higher rates of 30-day mortality and in-hospital mortality than those infected with non-MDR bacteria. CONCLUSIONS: Among pediatric patients, the CPSS group and CNSS group did not show significant differences in clinical features and mortality. Among the CPSS group, those with MDR bacteria had poorer prognosis.

Fabrication and Evaluation of a pH-Responsive Nanocomposite-Based Colonic Delivery System for Improving the Oral Efficacy of Liraglutide.

Purpose: Oral administration of liraglutide, a protein drug, suffers from low intestinal absorption and instability in the gastrointestinal tract, resulting in low bioavailability. The present study aimed to develop a pH-responsive nanocomposite based-colonic delivery system to improve the oral efficacy of liraglutide. Methods: Nanocomplex (AC-Lira) between aminoclay and liraglutide was prepared by a spontaneous self-assembly. After surface charge reversal using citric acid, AC-Lira was coated with poly(methacrylic acid-co-methyl methacrylate) (1:2). The fabricated nanocomplex underwent various in vitro studies to characterize its physicochemical properties, drug release, and cellular transport. In vivo efficacy studies were also conducted using streptozotocin-induced diabetic rats. Results: Both uncoated (AC-Lira) and coated nanocomplex (EAC-Lira) achieved high entrapment efficiency (> 90%) and showed a narrow size distribution. While exhibiting low drug release at pH 1.2 (approximately 30%), EAC-Lira achieved rapid and extensive drug release (~90%) at pH 7.4, displaying pH-dependent drug release. EAC-Lira showed significant size reduction and surface charge reversal during dissolution at pH 7.4, probably due to the removal of the outer coating layer. Furthermore, EAC-Lira was effective at protecting the entrapped proteins against enzymatic degradation. EAC-Lira also increased the membrane transport of liraglutide by 3.5 folds in Caco-2 cells. Owing to enhanced membrane transport and metabolic stability, EAC-Lira improved in vivo efficacy of orally administered liraglutide, significantly reducing blood glucose concentrations, intake of food and water, and body weight in type 2 diabetes rats. Conclusion: These results suggest EAC-Lira is a promising approach to improving the oral bioavailability and efficacy of liraglutide.

Bridging the BCI illiteracy gap: a subject-to-subject semantic style transfer for EEG-based motor imagery classification.

Introduction: Brain-computer interfaces (BCIs) facilitate direct interaction between the human brain and computers, enabling individuals to control external devices through cognitive processes. Despite its potential, the problem of BCI illiteracy remains one of the major challenges due to inter-subject EEG variability, which hinders many users from effectively utilizing BCI systems. In this study, we propose a subject-to-subject semantic style transfer network (SSSTN) at the feature-level to address the BCI illiteracy problem in electroencephalogram (EEG)-based motor imagery (MI) classification tasks. Methods: Our approach uses the continuous wavelet transform method to convert high-dimensional EEG data into images as input data. The SSSTN 1) trains a classifier for each subject, 2) transfers the distribution of class discrimination styles from the source subject (the best-performing subject for the classifier, i.e., BCI expert) to each subject of the target domain (the remaining subjects except the source subject, specifically BCI illiterates) through the proposed style loss, and applies a modified content loss to preserve the class-relevant semantic information of the target domain, and 3) finally merges the classifier predictions of both source and target subject using an ensemble technique. Results and discussion: We evaluate the proposed method on the BCI Competition IV-2a and IV-2b datasets and demonstrate improved classification performance over existing methods, especially for BCI illiterate users. The ablation experiments and t-SNE visualizations further highlight the effectiveness of the proposed method in achieving meaningful feature-level semantic style transfer.

Disseminated Intravascular Coagulation as a Risk Factor for Clinical Outcome After Liver Transplantation in Pediatric Patients With Kasai Portoenterostomy Failure.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication in critically ill pediatric patients. This study aimed to evaluate the association between pretransplant DIC and perioperative clinical outcomes of liver transplantation (LT) in pediatric patients with Kasai portoenterostomy (KPE) failure. METHODS: We enrolled pediatric patients who received LT after KPE failure between January 2005 and April 2021. We retrospectively reviewed the electronic medical records of included patients and evaluated the presence of DIC using the International Society on Thrombosis and Hemostasis (ISTH) criteria and association with perioperative clinical outcome. RESULTS: The study included 106 patients. Their median age and body weight at the time of pediatric intensive care unit (PICU) admission were 28.7 months and 9.25 kg, respectively. Of these patients, 23 had undergone pretransplant DIC (22%). Patients with pretransplant DIC required significantly more blood transfusions during operation. They had significantly higher serum lactate levels, pediatric end-stage liver disease scores, pediatric risk for mortality III (PRISM III) scores, longer durations of mechanical ventilator support, and longer PICU stays (all P < .05). CONCLUSIONS: The presence of pretransplant DIC in pediatric patients requiring LT after KPE failure was associated with poor clinical outcomes, which required more intensive and meticulous supportive management in the perioperative period of LT. DIC would be a promising prognostic factor in these patients.

Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation.

Decellularized extracellular matrix scaffold, widely utilized for organ engineering, often undergoes matrix decomposition after transplantation and produces byproducts that cause inflammation, leading to clinical failure. Here we propose a strategy using nano-graphene oxide to modify the biophysical properties of decellularized liver scaffolds. Notably, we demonstrate that scaffolds crosslinked with nano-graphene oxide show high resistance to enzymatic degradation via direct inhibition of matrix metalloproteinase activity and increased mechanical rigidity. We find that M2-like macrophage polarization is promoted within the crosslinked scaffolds, which reduces graft-elicited inflammation. Moreover, we show that low activities of matrix metalloproteinases, attributed to both nano-graphene oxide and tissue inhibitors of metalloproteinases expressed by M2c, can protect the crosslinked scaffolds against in vivo degradation. Lastly, we demonstrate that bioengineered livers fabricated with the crosslinked scaffolds remain functional, thereby effectively regenerating damaged livers after transplantation into liver failure mouse models. Overall, nano-graphene oxide crosslinking prolongs allograft survival and ultimately improves therapeutic effects of bioengineered livers, which offer an alternative for donor organs.

Safety and efficacy of pediatric sedation protocol for diagnostic examination in a pediatric emergency room: A retrospective study.

Pediatric patients undergoing diagnostic tests in the pediatric emergency room are frequently sedated. Although efforts are made to prevent adverse events, no sedation protocol has specified the optimal regimen, dosage, and interval of medication to prevent adverse events. This study analyzed the safety and efficacy of sequential pediatric sedation protocols for pediatric patients undergoing diagnostic tests in the pediatric emergency room of a single tertiary medical center. The medical records of patients aged < 18 years who visited the pediatric emergency room of Seoul Asan Medical Center between January and December 2019 for diagnostic testing were retrospectively reviewed. Sedation protocols consisted of 50 mg/kg and 25 mg/kg chloral hydrate, 0.1 mg/kg and 0.1 mg/kg midazolam, and 1 mg/kg and 0.5 to 1 mg/kg ketamine, administered sequentially at intervals of 30, 20, 10, 10, and 10 minutes, respectively. Patients were assessed prior to sedation, and adverse events were investigated. Of the 289 included patients, 20 (6.9%) experienced adverse events, none serious, and nine (3.1%) failed to reach the depth of sedation required to complete the test. The regimen (P = .622) and dosage (P = .777) of the sedatives were unrelated to the occurrence of adverse events when sedation was performed according to protocol. The sedation protocol used in these patients, consisting of sequential administration of minimum dosages, achieved a sufficient depth of sedation with relatively few adverse events, indicating that this protocol can be used safely and effectively for painless sedation in pediatric patients undergoing diagnostic testing.