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Geun Young Jang,1,&ast; Soo Jung Chang,2,&ast; Jun Hee Noh3,&ast; 1College of Nursing, Graduate School of Woosuk University, Wanju-gun, Jeonbuk, South Korea; 2Department of Nursing Gangneung-Wonju National University, Wonju, Gangwon-do, South Korea; 3College of Nursing, Woosuk University, Wanju-gun, Jeonbuk, South Korea&ast;These authors contributed equally to this workCorrespondence: Jun Hee Noh, College of Nursing, Woosuk University, Samnyero-ro 443, Samnye-eup, Wanju-gun, Jeonbuk, 55338, South Korea, Tel +82-63-290-1750, Fax +82-63-290-1548, Email Junhee0802@woosuk.ac.krPurpose: This study investigated the levels of health literacy, self-efficacy, self-management, and glycated hemoglobin (HbA1c) levels in older adults with diabetes to identify the relationships between these factors.Patients and Methods: This descriptive study consisted of 162 elderly outpatients with diabetes at the departments of endocrinology of three general hospitals in J Province, South Korea. Data were collected using a structured self-report questionnaire between October 21 and November 16, 2019. The data were analyzed using SPSS/WIN version 23.0.Results: Health literacy was positively correlated with self-efficacy (rs=0.64, p< 0.001) and self-management (rs=0.44, p< 0.001) and significantly negatively correlated with HbA1c levels (rs=− .42, p< 0.001). Self-efficacy showed a significantly positive correlation with self-management (rs=0.65, p< 0.001) and a significantly negative correlation with HbA1c levels (rs=− .30, p< 0.001). Moreover, a significant negative correlation was found between self-management and HbA1c levels (rs=− .35, p< 0.001). Hence, health literacy and patient self-management levels were associated with HbA1c levels in older adults with DM.Conclusion: Health education for community-dwelling older adults with diabetes should consider their health literacy levels. Moreover, measures to improve self-management abilities may be needed when developing educational programs for older adults with diabetes.Keywords: diabetes management, health education, prevention, public health, Korea, risk factors

We present a rare case of histiocytic sarcoma (HS) occurring in the foot of a 12-year-old male, initially misdiagnosed as localized tenosynovial giant cell tumor (TSGCT). HS is an exceptionally uncommon hematologic malignant neoplasm, with its occurrence in children and extranodal sites being even rarer. To our knowledge, this is the first reported case of extranodal HS in the foot, emphasizing comprehensive MRI findings. Initially, the patient was diagnosed with TSGCT based on histological results following surgical resection. However, after recurrence and subsequent surgical resection, histological and immunochemical analyses led to a revised diagnosis of HS. This report focuses on the MRI findings of HS, highlighting the distinctions from localized TSGCT. While both conditions share histopathological similarities, immunohistochemical tests are crucial for accurate diagnosis. The report underscores the importance of differentiating HS for appropriate treatment.

Abstract This study aimed to develop a deep learning (DL) algorithm for automated detection and localization of posterior ligamentous complex (PLC) injury in patients with acute thoracolumbar (TL) fracture on magnetic resonance imaging (MRI) and evaluate its diagnostic performance. In this retrospective multicenter study, using midline sagittal T2-weighted image with fracture (± PLC injury), a training dataset and internal and external validation sets of 300, 100, and 100 patients, were constructed with equal numbers of injured and normal PLCs. The DL algorithm was developed through two steps (Attention U-net and Inception-ResNet-V2). We evaluate the diagnostic performance for PLC injury between the DL algorithm and radiologists with different levels of experience. The area under the curves (AUCs) generated by the DL algorithm were 0.928, 0.916 for internal and external validations, and by two radiologists for observer performance test were 0.930, 0.830, respectively. Although no significant difference was found in diagnosing PLC injury between the DL algorithm and radiologists, the DL algorithm exhibited a trend of higher AUC than the radiology trainee. Notably, the radiology trainee's diagnostic performance significantly improved with DL algorithm assistance. Therefore, the DL algorithm exhibited high diagnostic performance in detecting PLC injuries in acute TL fractures.

Objectives: To develop an opportunistic screening model based on a deep learning algorithm to detect recent vertebral fractures in abdominal or chest CTs. Materials and Methods: A total of 1309 coronal reformatted images (504 with a recent fracture from 119 patients, and 805 without fracture from 115 patients), from torso CTs, performed from September 2018 to April 2022, on patients who also had a spine MRI within two months, were included. Two readers participated in image selection and manually labeled the fractured segment on each selected image with Neuro-T (version 2.3.3; Neurocle Inc.) software. We split the images randomly into the training and internal test set (labeled: unlabeled = 480:700) and the secondary interval validation set (24:105). For the observer study, three radiologists reviewed the CT images in the external test set with and without deep learning assistance and scored the likelihood of an acute fracture in each image independently. Results: For the training and internal test sets, the AI achieved a 99.86% test accuracy, 91.22% precision, and 89.18% F1 score for detection of recent fracture. Then, in the secondary internal validation set, it achieved 99.90%, 74.93%, and 78.30%, respectively. In the observer study, with the assistance of the deep learning algorithm, a significant improvement was observed in the radiology resident’s accuracy, from 92.79% to 98.2% (p = 0.04). Conclusion: The model showed a high level of accuracy in the test set and also the internal validation set. If this algorithm is applied opportunistically to daily torso CT evaluation, it will be helpful for the early detection of fractures that require treatment.

Background and Objective From the past, several researchers have studied and measured the partial pressure of carbon dioxide during sleep in normal children to establish diagnostic criteria for hypoventilation in children. Here we tried to verify the existing definition of sleep-related hypoventilation in Asian by evaluating and analyzing the carbon dioxide partial pressure in pediatric subjects who underwent polysomnography. Methods We retrospectively analyzed clinical information of 196 children who underwent polysomnography at our hospital from Feb 2011 to Apr 2021. Among Asian pediatric subjects, those with serious chronic or genetic diseases, craniofacial deformities, and hypoventilation confirmed by polysomnography were excluded. We evaluated partial pressure of carbon dioxide in target group by end-tidal carbon dioxide (EtCO2) measured with a stream capnometer through nasal cannula. The target group was classified by apnea-hypopnea index and analyzed. Results The mean value of the time with EtCO2 ≥ 45 mm Hg in total sleep time was 47.00% which is higher than previous studies. The mean value of the time with EtCO2 ≥ 50 mm Hg in total sleep time was 2.77% which is similar to previous studies. Also, our subjects showed the highest mean EtCO2 value in non-rapid eye movement (NREM) stage and lowest mean EtCO2 value when wake. Conclusions In this study, the diagnostic criteria for sleep-related hypoventilation at the American Academy of Sleep Medicine (AASM) in 2017 established by measuring the EtCO2 in western children seems appropriate to apply to Asian children to define hypoventilation.

Abstract Objective Cone‐beam computed tomography (CBCT) is a promising imaging modality for sinonasal evaluation, with advantages of relatively low radiation dose, low cost, and quick outpatient imaging. Our study aimed to compare the diagnostic performance and image quality of CBCT with those of multi‐detector computed tomography (MDCT) with different slice thickness. Methods We retrospectively reviewed 60 consecutive patients who had undergone both CBCT and MDCT. MDCT images was reconstructed with 1 and 3 mm slice thickness. The quantitative image quality parameters (image noise, signal‐to‐noise ratio [SNR], and contrast‐to noise ratio [CNR] were calculated and compared between the two imaging modalities. Two observers (ENT surgeon and neuroradiologist) evaluated the presence of seven sinonasal anatomic variations in each patient and interobserver agreements were analyzed. The diagnostic performance of CBCT (0.3 mm) and MDCT (3 mm) was assessed and compared with that of high resolution MDCT (1 mm), which is considered as the gold standard. Results The image noise was significantly higher and SNR and CNR values were lower in the CBCT (0.3 mm) group than in the MDCT groups (1 and 3 mm). The diagnostic performance of CBCT (0.3 mm) was similar to that of MDCT (1 mm) and superior to that of MDCT (3 mm). The highest interobserver agreement was for high resolution MDCT (1 mm), followed by CBCT (0.3 mm), and MDCT (3 mm). Conclusion Considering its low radiation dose, low cost, and ease of clinical access, CBCT may be a useful imaging modality for as first line sinonasal evaluation and repeated follow up. Study design: Retrospective study in a tertiary referral university center. Level of evidence: NA.

Abstract Background The intraosseous ganglia is a benign cyst, rarely locate in the olecranon process. As intraosseous ganglia can mimic malignant bone tumor, computed tomography (CT) is important for diagnosis even when magnetic resonance imaging (MRI) suggests malignant bone tumor, such as chondrosarcoma. Case presentation In this paper, we report a 42-year-old woman with intraosseous ganglia in the olecranon process of the ulna. She complained pain in right elbow for 3 weeks. MRI revealed an intraosseous mass which initially diagnosed as chondrosarcoma. However, followed computed tomography (CT) demonstrated scattered intralesional gas and no underlying mineralization, and we can exclude chondrosarcoma from diagnosis. Conclusions The intraosseous ganglia can mimic bone tumor in MRI; therefore, CT is essential for accurate characterization of bone tumor. Even if MR imaging strongly suggests chondrosarcoma of the bone, CT should be performed as additional study.

Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by digital clubbing, periosteal bone formation, and synovial effusions. Secondary HOA is associated with intrathoracic malignancy in most cases; however, in rare cases, HOA can be caused by extrathoracic conditions. We report early ultrasound, computed tomography, magnetic resonance imaging, and bone scintigraphy findings of HOA in a patient with breast cancer. Its ambiguous clinical and imaging findings that mimicked malignant conditions are particularly interesting and informative.

Self-healable conductive materials are of importance for emerging electronic technologies. Here, Suh et al. report a nanocomposite exhibiting high conductivity facilitated by electron tunneling between silver nanoparticles and its 100% recovery of conductivity after 1000 breaking and healing cycles.

Abstract Background This study aimed to evaluate the potential value of 3D multiple gradient echo Dixon‐based magnetic resonance imaging (MRI) sequence as a tool for thigh intramuscular fat quantification in Charcot–Marie–Tooth disease (CMT) patients. Methods A prospective comparison study comprising 18 CMT patients and 18 age/sex‐matched volunteers was performed. MRI including 3D multiple gradient echo Dixon‐based imaging was performed for each subject. Region of interest analyses were performed at the upper and lower third of both thighs. The two‐sample t‐test or Wilcoxon rank sum test was used for intergroup comparison of the mean muscle fat fraction. Intraclass correlation coefficients were used to evaluate the interobserver agreement and test–retest reproducibility. Semiquantitive analysis using the Goutallier classification (Grades 0–4) was performed on T1‐weighted images in upper thigh muscles. For Goutallier Grade 0 muscles, comparison of the mean intramuscular fat fraction between volunteers and CMT patients was performed. Results The interobserver agreements were excellent for all measurements (intraclass correlation coefficients > 0.8). Mean muscle fat fractions were significantly higher in all the measured muscles of CMT patients (P

OBJECTIVES:To compare magnetic resonance imaging (MRI) parameters of small, deeply located non-malignant and malignant soft-tissue tumors (STTs). METHODS:Between May 2011 and December 2017, 95 MRIs in 95 patients with pathologically proven STTs of small size (

Pulmonary pleomorphic carcinoma is an uncommon malignant lesion of the lung. A chest radiograph of 53-year-old man who was suffering from a cough revealed a well-defined mass-like opacity with a broad base on the pleura at the apico-posterior segment of the right upper lobe of the lung. The subsequent chest computed tomography (CT) scan demonstrated an inhomogeneous enhancing mass with central low-attenuation in the right upper lobe. A lobectomy was performed and the mass was determined to be a pleomorphic carcinoma with visceral pleura invasion. Forty days after the operation, the patient complained of melena and an abdominal CT revealed an intraluminal and extraluminal protruding mass around the prepyloric antrum and duodenal bulb. The mass was removed by en-block surgery and diagnosed as metastatic pleomorphic carcinoma from the lung. Previous articles reported a median survival time of 3–10 months for pleomorphic carcinoma, but in this case, the patient has continued to survive, 11 years after surgery. Chest and abdominal CTs have revealed no evidence of tumor recurrence or metastasis.

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive malignant small cell neoplasm occurring mainly in the abdominal cavity, but it is extremely rare in the pleura. In this case, a 15-year-old male presented with a 1-month history of left chest pain. Chest radiographs revealed pleural thickening in the left hemithorax and chest computed tomography showed multifocal pleural thickening with enhancement in both hemithoraces. A needle biopsy of the left pleural lesion was performed and the final diagnosis was DSRCT of the pleura. We report this unusual case arising from the pleura bilaterally. The pleural involvement of this tumor supports the hypothesis that it typically occurs in mesothelial-lined surfaces.

Abstract Buttock abscess is a rare clinical manifestation from unusual extrapelvic extension of psoas abscess. A 48-year-old woman presented with painful swelling of the buttock with a sense of local heat. Magnetic resonance imaging revealed a large subfascial abscess over the glutei muscles and was traced into the intraabdominal cavity over the iliac wing to the psoas muscle. Both the psoas abscess and the buttock abscess were evacuated via separate approaches. Empirical antibiotic therapy was delivered for 3 weeks. After 6 months, no evidence of recurrence was found. Psoas abscess could be included in the differential diagnosis of buttock abscess.

Background: In patients with hyperlipidemia, the risk of retear increases after rotator cuff repair (RCR). In particular, it has been reported that preoperative low-density lipoprotein cholesterol (LDL-C) level affects cuff integrity. However, there are no studies assessing whether lipidemic control affects cuff healing., Purpose: To evaluate the effect of preoperative lipidemic control on cuff integrity after arthroscopic RCR across cardiovascular disease risk groups in patients with hyperlipidemia., Study Design: Case-control study; Level of evidence, 3., Methods: The authors retrospectively reviewed the charts of patients with hyperlipidemia who underwent arthroscopic double-row suture bridge RCR between 2014 and 2019. The included patients had LDL-C tested within 1 month before surgery. Magnetic resonance imaging was conducted 6 months after surgery to evaluate the integrity of the repaired cuff tendon. Patients were divided into groups of low, moderate, high, and very high risk according to the 4th Korean Dyslipidemia Guidelines. On the basis of the target LDL-C set in each risk group, patients were categorized into 2 groups: group C (controlled hyperlipidemia, less than target LDL-C) and group U (uncontrolled hyperlipidemia, target LDL-C or greater). The correlation between serum lipid profile, lipidemic control, and post-RCR integrity was evaluated., Results: A total of 148 patients were analyzed, 51 in group U and 97 in group C. The retear rate was significantly higher in group U than in group C (23/51 [45.1%] vs 18/97 [18.6%], respectively; P = .001). The proportion of group U was significantly higher in the retear group than in the healing group (56.1% vs 26.2%; P = .001). In addition, the proportions of patients with uncontrolled diabetes mellitus (DM) (19.5% vs 3.7%; P = .002) and mediolateral (2.6 ± 1.2 cm vs 1.7 ± 1.1 cm; P < .001) and anteroposterior (2.2 ± 1.1 cm vs 1.6 ± 0.8 cm; P = .003) tear sizes were significantly different between the retear and healing groups, respectively. No significant difference in serum lipid profile, including LDL-C level (119.6 ± 31.3 vs 116.7 ± 37.2; P = .650), was observed between the retear and healing groups. Multivariate regression analysis identified uncontrolled hyperlipidemia (OR, 4.005; P = .001), uncontrolled DM (OR, 5.096; P = .022), and mediolateral tear size (OR, 1.764; P = .002) as independent risk factors for retear. The 2.0-cm mediolateral size cutoff and the 3 independent risk factors had significant associations with retear., Conclusion: Poor preoperative lipidemic control was significantly associated with poor healing after RCR. In addition to large mediolateral tear size, uncontrolled hyperlipidemia and DM were significant risk factors for retear. Moreover, poor lipidemic control compared with the recommended target level before surgery was more correlated with an increased retear rate than a preoperative LDL-C level., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients., Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases)., Results: Six male-specific susceptibility loci, PDE1C , NOS3 , DLG2 , CPNE8 , FUNDC1 , and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10 -6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD., Conclusions: A sex-stratified GWAS identified 6 male-specific ( PDE1C , NOS3 , DLG2 , CPNE8 , FUNDC1 , and GABRQ ) and 2 female-specific ( SMAD3 and IL1RAPL1 ) CAA susceptibility loci in patients with KD., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Background/objectives: Platycodon grandiflorum (PG) is used in traditional oriental medicine to treat several ailments., Methods: The study investigated the anti-inflammatory and neuroprotective effects of PGW ( P. grandiflorum ) extract in Aβ25-35-induced inflammation in BV2 microglia cells., Result: PGW demonstrated significant inhibition of nitric oxide (NO) production, with reductions of 30.4, 36.7, and 61.2% at concentrations of 50, 100, and 200 μg/mL, respectively. Moreover, PGW effectively suppressed the production of pro-inflammatory cytokines IL-1β and IL-6 and exhibited significant inhibitory activity against TNF-α at 200 μg/mL. Furthermore, PGW treatment mitigated apoptosis in Aβ-induced BV2 cells by modulating the mitochondrial apoptosis pathway, regulating Bcl-2 family protein synthesis, and inhibiting caspase activation. Mechanistically, PGW attenuated the activation of the MAPK (JNK, ERK, p38) pathway induced by Aβ, showing a concentration-dependent decrease in phosphorylation levels of these proteins. Additionally, PGW inhibited the NF-κB pathway activation by reducing the phosphorylation levels of p65 and IκBα in a concentration-dependent manner., Conclusion: PGW demonstrated anti-inflammatory and neuroprotective effects in Aβ-induced neuronal cells, suggesting its potential as a therapeutic agent for neuroinflammatory associated with neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ji, Kang, Kim, Kim and Jang.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Aβ deposition. Thus, we aim to identify the mechanism through which PGE inhibits Aβ deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H 2 O 2 - and Aβ-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Aβ deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Aβ-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Aβ-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Aβ, and inhibits neuroinflammation and Aβ deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background/aim: The survival of patients with congenital heart disease (CHD) has dramatically improved over recent decades. However, a disparity exists depending on the country and medical system. This study aimed to analyze the survival of infants with CHD until the age of 18 years using large-scale population data in South Korea and investigate the effect of neonatal conditions at birth., Patients and Methods: We retrospectively extracted the Korean National Health Insurance Service claims data from January 2002 to December 2020. We included patients diagnosed with CHD who were less than one year of age. The follow-up duration was until their death or until they were censored before the age of 18 years. The CHD lesions were classified hierarchically (conotruncal, severe non-conotruncal, coarctation of the aorta, ventricular septal defect, atrial septal defect, and others). Several neonatal conditions were adopted as risk factors., Results: Overall, 127,958 infants had been diagnosed with CHD and 2,275 died before the age of 18 years. The survival rate of infants with CHD during childhood was 97.9%. The highest childhood mortality rate was associated with non-conotruncal defects (19.7%), followed by conotruncal defects (10.2%). The significant risk factors for childhood mortality were complex CHD, pulmonary hypertension, birth asphyxia, small for gestational age, respiratory distress, pulmonary hemorrhage, bronchopulmonary dysplasia, and convulsions., Conclusion: The survival of infants with CHD has been favorable in South Korea. Several neonatal conditions are risk factors for childhood mortality. Individualized risk assessment and optimal treatment strategies may help improve their survival rate., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Pulmonary artery catheterization (PAC) has been used as a clinical standard for cardiac output (CO) measurements on humans. On animals, however, an ultrasonic flow sensor (UFS) placed around the ascending aorta or pulmonary artery can measure CO and stroke volume (SV) more accurately. The objective of this paper is to compare CO and SV measurements using a noninvasive electrical impedance tomography (EIT) device and three invasive devices using UFS, PAC-CCO (continuous CO) and arterial pressure-based CO (APCO). Thirty-two pigs were anesthetized and mechanically ventilated. A UFS was placed around the pulmonary artery through thoracotomy in 11 of them, while the EIT, PAC-CCO and APCO devices were used on all of them. Afterload and contractility were changed pharmacologically, while preload was changed through bleeding and injection of fluid or blood. Twenty-three pigs completed the experiment. Among 23, the UFS was used on 7 pigs around the pulmonary artery. The percentage error (PE) between CO UFS and CO EIT was 26.1%, and the 10-min concordance was 92.5%. Between SV UFS and SV EIT , the PE was 24.8%, and the 10-min concordance was 94.2%. On analyzing the data from all 23 pigs, the PE between time-delay-adjusted CO PAC-CCO and CO EIT was 34.6%, and the 10-min concordance was 81.1%. Our results suggest that the performance of the EIT device in measuring dynamic changes of CO and SV on mechanically-ventilated pigs under different cardiac preload, afterload and contractility conditions is at least comparable to that of the PAC-CCO device. Clinical studies are needed to evaluate the utility of the EIT device as a noninvasive hemodynamic monitoring tool., (© 2024. The Author(s).)

Aqueous photoelectrochemical (PEC) cells have long been considered a promising technology to convert solar energy into hydrogen. However, the solar-to-H 2 (STH) efficiency and cost-effectiveness of PEC water splitting are significantly limited by sluggish oxygen evolution reaction (OER) kinetics and the low economic value of the produced O 2 , hindering the practical commercialization of PEC cells. Recently, organic upgrading PEC reactions, especially for alternative OERs, have received tremendous attention, which improves not only the STH efficiency but also the economic effectiveness of the overall reaction. In this review, PEC reaction fundamentals and reactant-product cost analysis of organic upgrading reactions are briefly reviewed, recent advances made in organic upgrading reactions, which are categorized by their reactant substrates, such as methanol, ethanol, glycol, glycerol, and complex hydrocarbons, are then summarized and discussed. Finally, the current status, further outlooks, and challenges toward industrial applications are discussed., (© 2023 Wiley-VCH GmbH.)

Kawasaki disease (KD) is an acute pediatric vasculitis that predominantly affects children under the age of 5 years. To date, genome-wide association studies (GWAS) have identified several KD susceptibility genes (e.g., BLK, CD40, FCGR2A, BCL2L11, and IGHV), which are mainly involved in B cell immunity. In this study, we aimed to identify additional KD susceptibility genes mainly involved in B cell development and functions by analyzing our previous GWAS data and conducting a replication study using new sample. Initially, we selected 30 single nucleotide polymorphisms (SNPs) in B-cell-related genes that were significantly (P < 0.01) associated with KD in our previous GWAS analysis of 247 KD cases with complete type and 1,000 healthy controls. Replication study was performed by genotyping the new 837 KD case samples with Fluidigm system and comparing them with 3,553 control genotypes. Among the 30 candidate SNPs, two were significantly associated with KD (P < 0.001) in the replication study. An even greater association between these SNPs and KD was observed in the combined analysis of GWAS and replication samples: odds ratio (OR) = 1.97 (P = 8.61 × 10 -6 ) for rs2270699 (nonsynonymous SNP: c.10588C > T, p.Arg3530Trp) in the heparan sulfate proteoglycan 2 (HSPG2) gene and OR = 1.28 (P = 1.34 × 10 -6 ) for rs3130992 (intronic SNP) in both the corneodesmosin (CDSN) and psoriasis susceptibility 1 candidate 1 (PSORS1C1) genes. These results suggest that the B-cell-related genes, HSPG2 and CDSN or PSORS1C1, play a role in the development of KD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Facile synthesis of hierarchically porous metal-organic frameworks (MOFs) with adjustable porosity and high crystallinity attracts great attention yet remains challenging. Herein, a micromolar amount of dye-based modulator (Rhodamine B (RhB)) is employed to easily and controllably tailor the pore size of a Ti-based metal-organic framework (MIL-125-NH 2 ). The RhB used in this method is easily removed by washing or photodegradation, avoiding secondary posttreatment. It is demonstrated that the carboxyl functional group and the steric effects of RhB are indispensable for enlarging the pore size of the MIL-125-NH 2 . The resulting hierarchically porous MIL-125-NH 2 (RH-MIL-125-NH 2 ) exhibits optimized adsorption and photocatalytic activity because the newly formed mesopore with defects concurrently facilitates mass transport of guest molecules (toluene) and photogenerated charge separation. This work offers a meaningful basis for the construction of hierarchically porous MOFs and demonstrates the superiority of the hierarchical pore structure for adsorption and heterogeneous catalysis., (© 2023 Wiley-VCH GmbH.)

Electrical impedance tomography (EIT) can monitor the real-time hemodynamic state of a conscious and spontaneously breathing patient noninvasively. However, cardiac volume signal (CVS) extracted from EIT images has a small amplitude and is sensitive to motion artifacts (MAs). This study aimed to develop a new algorithm to reduce MAs from the CVS for more accurate heart rate (HR) and cardiac output (CO) monitoring in patients undergoing hemodialysis based on the source consistency between the electrocardiogram (ECG) and the CVS of heartbeats. Two signals were measured at different locations on the body through independent instruments and electrodes, but the frequency and phase were matched when no MAs occurred. A total of 36 measurements with 113 one-hour sub-datasets were collected from 14 patients. As the number of motions per hour (MI) increased over 30, the proposed algorithm had a correlation of 0.83 and a precision of 1.65 beats per minute (BPM) compared to the conventional statical algorithm of a correlation of 0.56 and a precision of 4.04 BPM. For CO monitoring, the precision and upper limit of the mean ∆CO were 3.41 and 2.82 L per minute (LPM), respectively, compared to 4.05 and 3.82 LPM for the statistical algorithm. The developed algorithm could reduce MAs and improve HR/CO monitoring accuracy and reliability by at least two times, particularly in high-motion environments.

Ginsenoside is the primary active substance of ginseng and has many pharmacological effects, such as anti-cancer, immune, regulating sugar and lipid metabolism, and antioxidant effects. It also protects the nervous and cardiovascular systems. This study analyzes the effects of thermal processing on the bioactivities of crude ginseng saponin. Heat treatment increased the contents of minor ginsenosides in crude saponins, such as Rg3, and heat-treated crude ginseng saponin (HGS) had better neuroprotective effects than non-treated crude saponin (NGS). HGS reduced glutamate-induced apoptosis and reactive oxygen species generation in pheochromocytoma 12 (PC12) cells, significantly more than NGS. HGS protected PC12 cells against glutamate-induced oxidative stress by upregulating Nrf2-mediated antioxidant signaling and downregulating MAPK-mediated apoptotic signaling. HGS has the potential for the prevention and treatment of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease.

Aster koraiensis Nakai (AK) leaf reportedly ameliorates health problems, such as diabetes. However, the effects of AK on cognitive dysfunction or memory impairment remain unclear. This study investigated whether AK leaf extract could attenuate cognitive impairment. We found that AK extract reduced the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, phosphorylated-tau (p-tau), and the expression of inflammatory proteins in lipopolysaccharide- or amyloid-β-treated cells. AK extract exhibited inhibitory activity of control specific binding on N-methyl-D-aspartate (NMDA) receptors. Scopolamine-induced AD models were used chronically in rats and acutely in mice. Relative to negative controls (NC), hippocampal choline acetyltransferase (ChAT) and B-cell lymphoma 2 (Bcl2) activity was increased in rats chronically treated with scopolamine and fed an AK extract-containing diet. In the Y-maze test, spontaneous alterations were increased in the AK extract-fed groups compared to NC. Rats administered AK extract showed increased escape latency in the passive avoidance test. In the hippocampus of rats fed a high-AK extract diet (AKH), the expression of neuroactive ligand-receptor interaction-related genes, including Npy2r, Htr2c, and Rxfp1, was significantly altered. In the Morris water maze assay of mice acutely treated with scopolamine, the swimming times in the target quadrant of AK extract-treated groups increased significantly to the levels of the Donepezil and normal groups. We used Tg6799 Aβ-overexpressing 5XFAD transgenic mice to investigate Aβ accumulation in animals. In the AD model using 5XFAD, the administration of AK extract decreased amyloid-β (Aβ) accumulation and increased the number of NeuN antibody-reactive cells in the subiculum relative to the control group. In conclusion, AK extract ameliorated memory dysfunction by modulating ChAT activity and Bcl2-related anti-apoptotic pathways, affecting the expression of neuroactive ligand-receptor interaction-related genes and inhibiting Aβ accumulation. Therefore, AK extract could be a functional material improving cognition and memory.

Continuous monitoring of both hemodynamic and respiratory parameters would be beneficial to patients, e.g., those in intensive care unit. The objective of this exploratory animal study was to test the feasibility of simultaneous measurements of relative tidal volume (rTV) and relative stroke volume (rSV) using an electrical impedance tomography (EIT) device equipped with a new real-time source separation algorithm implemented as two spatial filters. Five pigs were anesthetized and mechanically ventilated. The supplied tidal volume from a mechanical ventilator was reduced to 70, 50 and 30% from the 100% normal volume to simulate hypoventilation. The respiratory volume signal and cardiac volume signal were generated by applying the spatial filters to the acquired EIT data, from which values of rTV and rSV were extracted. The measured rTV values were compared with the TV values from the mechanical ventilator using the four-quadrant concordance analysis method. For changes in TV, the concordance rate in each animal ranged from 81.8% to 100%, while it was 92.5% when the data from all five animals were pooled together. When the measured rTV values for each animal were scaled to the absolute TV EIT values in mL using the TV Vent data from the mechanical ventilator, the smallest 95% limits of agreement (LoA) were - 6.04 and 7.44 mL for the 70% ventilation level, and the largest 95% LoA were - 18.1 and 19.4 mL for the 50% ventilation level. The percentage error between TV EIT and TV Vent was 10.3%. Although similar statistical analyses on rSV data could not be performed due to limited intra-animal variability, changes in rSV values measured by the EIT device were comparable to those measured by an invasive hemodynamic monitor. In this animal study, we were able to demonstrate the feasibility of an EIT device for noninvasive and simultaneous measurements of rTV and rSV in real time. However, the performance of the real-time source separation method needs to be further validated on animals and human subjects, particularly over a wide range of SV values. Future clinical studies are needed to assess the potential usefulness of the new method in dynamic cardiopulmonary monitoring and explore other clinical applications., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Various cancer therapies, such as surgery, radiotherapy, chemotherapy, and immunotherapy, have been used to treat cancer. Among cancer immunotherapies, stimulators of interferon genes (STING) activate various immune cells and induce them to attack cancer cells. However, the secretion of type I interferon (IFN α and β) increases after stimulation of the immune cell as a side effect of STING agonist, thereby increasing the expression of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Therefore, it is necessary to reduce the side effects of STING agonists and maximize cancer treatment by administering combination therapy. Tumor-bearing mice were treated with cisplatin, tumor-specific peptide, neoantigen, DMXAA (STING agonist), and immune checkpoint inhibitor (ICI). The combination vaccine group showed a reduction in tumor mass, an increased survival rate, and IFN-γ + (interferon gamma) CD8 + (cluster of differentiation 8) T cells in the spleen and TME. The distribution of immune cells in the spleen and TME was confirmed, and the number of active immune cells increased, whereas that of immunosuppressive cells decreased. When measuring cytokine levels in the tumor and serum, the levels of pro-inflammatory cytokines increased and anti-inflammatory cytokines decreased. This study demonstrated that when various cancer therapies are combined to treat cancer, it can lead to an anticancer immune synergistic effect by increasing the immune response and reducing side effects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemotherapy promotes phosphatidylserine (PS) externalization in tumors undergoing apoptosis, forms an immunosuppressive tumor microenvironment (TME), and inhibits dendritic cell (DC) maturation and antigen presentation by binding PS receptors expressed in DCs, thereby limiting naive T cell education and activation. In this study, we demonstrate a selective nanocarrier system composed of annexin A5-labeled poly (lactide-co-glycolide) nanoparticles (PLGA&#95;NPs) encapsulating tumor specific antigen or neoantigen, to target apoptotic tumor cells expressing PS as an innate immune checkpoint inhibitor (ICI) that induces active cancer immunotherapy. Moreover, PLGA&#95;NPs enhanced tumor-specific antigen-based cytotoxic T cell immunity via the original function of DCs by converting the tumor antigen-rich environment. Therefore, chemotherapy combined with an immunomodulatory nanocarrier system demonstrated an enhanced anticancer immune response by increasing survival rates, immune-activating cells, and pro-inflammatory cytokines in the spleen and TME. In contrast, the tumor mass, immune-suppressive cells, and anti-inflammatory cytokines were decreased. Furthermore, the combination of a nanocarrier system with other ICIs against large tumors showed therapeutic efficacy by immunosuppression in the TME and further amplified the anticancer immunity of interferon gamma + (IFN-γ) CD8 + (cluster of differentiation 8) T cells. Taken together, our Annexin A5-labeled PLGA-NPs can be applied in various combination therapeutic techniques for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The objectives of this study were to develop a multi-channel trans-impedance leadforming method for beat-to-beat stroke volume (SV) and breath-by-breath tidal volume (TV) measurements and assess its feasibility on an existing in vivo animal dataset., Methods: A deterministic leadforming algorithm was developed to extract a cardiac volume signal (CVS) and a respiratory volume signal (RVS) from 208-channel trans-impedance data acquired every 20 ms by an electrical impedance tomography (EIT) device. SV EIT and TV EIT values were computed as a valley-to-peak value in the CVS and RVS, respectively. The method was applied to the existing dataset from five mechanically-ventilated pigs undergoing ten mini-fluid challenges. An invasive hemodynamic monitor was used in the arterial pressure-based cardiac output (APCO) mode to simultaneously measure SV APCO values while a mechanical ventilator provided TV Vent values., Results: The leadforming method could reliably extract the CVS and RVS from the 208-channel trans-impedance data measured with the EIT device, from which SV EIT and TV EIT were computed. The SV EIT and TV EIT values were comparable to those from the invasive hemodynamic monitor and mechanical ventilator. Using the data from 5 pigs and a simple calibration method to remove bias, the error in SV EIT and TV EIT was 9.5% and 5.4%, respectively., Conclusion: We developed a new leadforming method for the EIT device to robustly extract both SV and TV values in a deterministic fashion. Future animal and clinical studies are needed to validate this leadforming method in various subject populations., Significance: The leadforming method could be an integral component for a new cardiopulmonary monitor in the future to simultaneously measure SV and TV noninvasively, which would be beneficial to patients.

The importance of perioperative respiration monitoring is highlighted by high incidences of postoperative respiratory complications unrelated to the original disease. The objectives of this pilot study were to (1) simultaneously acquire respiration rate (RR), tidal volume (TV), minute ventilation (MV), SpO 2 and PETCO 2 from patients in post-anesthesia care unit (PACU) and (2) identify a practical continuous respiration monitoring method by analyzing the acquired data in terms of their ability and reliability in assessing a patient's respiratory status. Thirteen non-intubated patients completed this observational study. A portable electrical impedance tomography (EIT) device was used to acquire RR EIT , TV and MV, while PETCO 2 , RR Cap and SpO 2 were measured by a Capnostream35. Hypoventilation and respiratory events, e.g., apnea and hypopnea, could be detected reliably using RR EIT , TV and MV. PETCO 2 and SpO 2 provided the gas exchange information, but were unable to detect hypoventilation in a timely fashion. Although SpO 2 was stable, the sidestream capnography using the oronasal cannula was often unstable and produced fluctuating PETCO 2 values. The coefficient of determination (R 2 ) value between RR EIT and RR Cap was 0.65 with a percentage error of 52.5%. Based on our results, we identified RR, TV, MV and SpO 2 as a set of respiratory parameters for robust continuous respiration monitoring of non-intubated patients. Such a respiration monitor with both ventilation and gas exchange parameters would be reliable and could be useful not only for respiration monitoring, but in making PACU discharge decisions and adjusting opioid dosage on general hospital floor. Future studies are needed to evaluate the potential clinical utility of such an integrated respiration monitor., (© 2021. The Author(s).)

Although Platycodon grandiflorum saponins exhibit many beneficial biological effects in various diseases and conditions, how they protect nerve cells against neurodegenerative diseases and Alzheimer's disease (AD) pathology is unknown. We investigated whether P. grandiflorum crude saponin (PGS) protects neurons from neurodegeneration caused by amyloid beta (Aβ)-induced oxidative stress. Hippocampal neuron HT-22 cells were used in the in vitro experiment, and AD mice (5XFAD mice) were used as the in vivo model. Intracellular reactive oxygen species (ROS) was stained with DCF-DA and assessed using fluorescence microscopy. To elucidate the mechanism underlying neuroprotection, intracellular protein levels were assessed by western blotting. In 5XFAD mice, an animal model of AD, nerve damage recovery due to the induction of Aβ toxicity was evaluated by histological analysis. PGS attenuates Aβ-induced neurotoxicity by inhibiting Aβ-induced reactive oxygen species (ROS) production and apoptosis in HT-22 cells. Furthermore, PGS upregulated Nrf2-mediated antioxidant signaling and downregulated NF-κB-mediated inflammatory signaling. Additionally, PGS inhibited apoptosis by regulating the expression of apoptosis-associated proteins. In addition, PGS ameliorated Aβ-mediated pathologies, leading to AD-associated cognitive decline. Conclusions: Taken together, these findings suggest that PGS inhibits Aβ accumulation in the subiculum and cerebral cortex and attenuates Aβ toxicity-induced nerve damage in vitro and in vivo. Therefore, PGS is a resource for developing AD therapeutics.

Immune checkpoint inhibitors (ICIs), including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 have shown promising cancer clinical outcomes. However, IC therapy has low patient response rates (10%-15%). Thus, ICIs and sufficient antigen combinations into the tumor microenvironment (TME) is important to produce strong tumor-specific adaptive immune responses. Mice were treated with cisplatin, and human cancer cells were exposed to inflammatory cytokines, to confirm increased PD-L1 and major histocompatibility complex (MHC) I expression by tumor cells or dendritic cells. TC-1, CT26, B16-F1, or B16-F10 tumor cells, and bone marrow-derived dendritic cells, were treated with interferon (IFN)-β, IFN-γ, or tumor necrosis factor-α to identify the molecular mechanisms underlying tumor PD-L1 and MHC I upregulation, and to examine MHC I, CD40, CD80, CD86, or PD-L1 levels, respectively. For synergistic combination therapy, αPD-L1 monoclonal antibody (mAb) covalently linked to the long E7 peptide was generated. Chemotherapy shifted the TME to express high PD-L1 and MHC I, resulting in targeted ICI cargo delivery and enhanced generation and activation of tumor antigen-specific T cells. Synergistic effects of vaccination and IC blockade in the TME were demonstrated using an anti-PD-L1 mAb covalently conjugated to the E7 long peptide., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Breath-by-breath tidal volume (TV) and beat-by-beat stroke volume (SV) were continuously measured in patients with OSA undergoing polysomnography (PSG). The objectives were to (1) determine the changes in TV/SV in response to respiratory events and (2) assess the relationship between these changes and the disease severity., Methods: From the PSG data of nine patients with OSA, six different types of respiratory events were identified, i.e., flow limitation (FL), respiratory effort related arousal (RERA), hypopnea with arousal only (Ha), hypopnea with desaturation only (Hd), hypopnea with arousal and desaturation (Had), and apnea. The measured TV and SV values during and after each respiratory event were compared with the pre-event baseline values., Results: The mean TV/SV reductions during all hypopneas and apneas were 38.1%/4.2% and 70.5%/8.8%, respectively. Among three different hypopnea types, the reductions in TV during Hd and Had were significantly greater than those during Ha. The TV reductions during Ha and FL were similar. After RERA, Ha, Had, and apnea, there was an overshoot in TV and SV values, whereas there was no overshoot after FL and Hd. During RERA, there was no reduction in TV/SV., Conclusions: The changes in TV during and after each type of respiratory event were significantly different in most cases. The changes in SV between hypopnea and apnea were different with statistical significance. The AHI does not properly account for the ventilation losses caused by respiratory events. Thus, TV measurements might be useful in the future in assessing the OSA severity in conjunction with the AHI., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18 to 4.41; p = 0.0027-0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89 to 37.3; p = 0.0058-0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

Abstract: Cardiac output (CO) is an important parameter in fluid management decisions for treating hemodynamically unstable patients in intensive care unit. The gold standard for CO measurements is the thermodilution method, which is an invasive procedure with intermittent results. Recently, electrical impedance tomography (EIT) has emerged as a new method for noninvasive measurements of stroke volume (SV). The objectives of this paper are to compare EIT with an invasive pulse contour analysis (PCA) method in measuring SV during mini-fluid challenge in animals and determine preload responsiveness with EIT. Five pigs were anesthetized and mechanically ventilated. After removing 25% to 30% of the total blood from each animal, multiple fluid injections were conducted. The EIT device successfully tracked changes in SV beat-to-beat during varying volume states, i.e., from hypovolemia and preload responsiveness to target volume and volume overload. From a total of 50 100-mL fluid injections on five pigs (10 injections per pig), the preload responsiveness value was as large as 32.3% in the preload responsiveness state while in the volume overload state it was as low as -4.9%. The bias of the measured SV data using EIT and PCA was 0 mL, and the limits of agreement were ±3.6 mL in the range of 17.6 mL to 51.0 mL. The results of the animal experiments suggested that EIT is capable of measuring beat-to-beat SV changes during mini-fluid challenge and determine preload responsiveness. Further animal and clinical studies will be needed to demonstrate the feasibility of the EIT method as a new tool for fluid management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Melanin is a brown or black pigment that protects skin from ultraviolet radiation and reactive oxygen species (ROS). However, overproduction of melanin is associated with lentigines, melasma, freckles and skin cancer. Licorice has shown antioxidant, anti-tumor, anti-platelet, anti-inflammatory and immunomodulatory activities and is used as a natural treatment for skin whitening. We aimed to confirm the potential of Wongam, a new cultivar of licorice developed by the Rural Development Administration (RDA), as a whitening agent in cosmetics. In addition, we verified the effect of heat treatment on the bioactivity of licorice by comparing antioxidant and anti-melanogenic activities of licorice extract before and after heating (130 °C). The heat-treated licorice extract (WH-130) showed higher radical-scavenging activities in the ABTS + (2,2'-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays. In addition, WH-130 inhibited melanogenesis more effectively due to downregulation of tyrosinase in B16F10 melanoma cells than non-heated licorice extract. Moreover, heat treatment increased total phenolic content. In particular, isoliquiritigenin, an antioxidant and anti-melanogenic compound of licorice, was produced by heat treatment. In conclusion, WH-130, with increased levels of bioactive phenolics such as isoliquiritigenin, has potential for development into a novel skin whitening material with applications in cosmetics.

Background: Seismocardiography measures the vibrations produced by the beating heart using an accelerometer sensor placed on the chest. We evaluated the ability of smartphone seismocardiography to distinguish between the presence and absence of spontaneous circulation., Methods: Seismocardiography signals were obtained using a smartphone placed on the sternum in a convenience sample of 60 adult patients (30 comatose patients with spontaneous circulation and 30 deceased patients). The maximum, minimum, and standard deviation (SD) of acceleration values for head-to-foot, right-to-left, and dorsoventral axes and the three axis-root mean square (RMS) of the acceleration signals were calculated. Blinded observers (n = 156) were each asked to determine the presence or absence of spontaneous circulation based on seismocardiography video clips for each of the 60 patients., Results: The seismocardiography revealed periodic large positive peaks in the patients with spontaneous circulation, which were absent in the patients without spontaneous circulation. For each of the four output measurements (three independent axes plus the three-axis RMS), the acceleration maxima and SD were significantly higher and the minima significantly lower in the patients with spontaneous circulation than in those without spontaneous circulation (all P < 0.001 except the minimum of three axis-RMS results [P = 0.009]). The observers accurately identified the seismocardiography signals from patients without spontaneous circulation, with a sensitivity of 97.6% (95% confidence interval, 97.0%-98.2%) and a specificity of 98.4% (95% confidence interval, 97.8%-99.0%)., Conclusions: In conclusion, blinded observers accurately distinguished between seismocardiography signals from patients with and without spontaneous circulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10 -9 ). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10 -10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.

Cancer immunotherapy has fewer side effects and higher efficiency than conventional methods. Dendritic cell (DC)-based vaccine, a cancer immunotherapeutic, is prepared by processing mature DCs and pulsing with tumor antigen peptide ex vivo, to induce the activation of tumor-specific T lymphocytes followed by tumor clearance in vivo. Unfortunately, clinical trials of this method mostly failed due to low patient response, possibly due to the absence of novel adjuvants that induce DC maturation through Toll-like receptor (TLR) signals. Interestingly, immune checkpoint inhibitor (ICI) therapy has shown remarkable anti-tumor efficacy when combined with cancer vaccines. In this study, we identified 60S acidic ribosomal protein P2 (RPLP2) through pull-down assay using human cancer cells derived proteins that binds to Toll-like receptor 4 (TLR4). Recombinant RPLP2 induced maturation and activation of DCs in vitro. This DC-based vaccine, followed by pulsing with tumor-specific antigen, has shown to significantly increase tumor-specific CD8 + IFN-γ + T cells, and improved both tumor prevention and tumor treatment effects in vivo. The adjuvant effects of RPLP2 were shown to be dependent on TLR4 using TLR4 knockout mice. Moreover, ICIs that suppress the tumor evasion mechanism showed synergistic effects on tumor treatment when combined with these vaccines.

Background and Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined., Methods: Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease., Results: Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs). Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022)., Conclusions: High IgA levels in patients with KD are prognostic for the risk of CALs., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2021. The Korean Society of Cardiology.)

Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.

Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7-12 months and 13-60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet ( p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD.

Currently, there is no noninvasive method available for simultaneous measurements of tidal volume and stroke volume. Electrical impedance tomography (EIT) has been used for regional lung ventilation imaging. Cardiac EIT imaging, however, has not been successful due to the technical difficulty in extracting weak cardiogenic components. Instead of regional imaging, in this paper, we use the EIT technique to simultaneously measure two global variables of tidal volume and stroke volume. Time-varying patterns of boundary voltage data originating from lung ventilation and cardiac blood flow were extracted from measured boundary voltage data using the principal component analysis (PCA) and independent component analysis (ICA). The source consistency theory was adopted to separately synthesize time-series of boundary voltage data associated with lung ventilation and cardiac blood flow. The respiratory volume signal (RVS) and cardiac volume signal (CVS) were extracted from reconstructed time-difference EIT images of lung ventilation and cardiac blood flow, respectively. After calibrating the volume signals using the mechanical ventilator and the invasive transpulmonary thermodilution (TPTD) method, tidal volume and stroke volume were computed as valley-to-peak values of the RVS and CVS, respectively. The difference in the tidal volume data between EIT and mechanical ventilator was within ± 20 ml from six pigs. The difference in the stroke volume data between EIT and TPTD was within ± 4.7 ml from the same animals. The results show the feasibility of the proposed method as a new noninvasive cardiopulmonary monitoring tool for simultaneous continuous measurements of stroke volume and tidal volume that are two most important vital signs.

Kawasaki disease (KD) is an acute, self-limited vasculitis, mainly affecting children younger than 5 years old, with accompanying fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) is the standard treatment for KD; however, ~15% of patients are resistant to IVIG treatment. To identify protein coding genetic variants influencing IVIG resistance, we re-analyzed our previous genome-wide association study (GWAS) data from 296 patients with KD, including 101 IVIG non-responders and 195 IVIG responders. Five nonsynonymous SNPs (nsSNPs) in five immune-related genes, including a previously reported SAMD9L nsSNP (rs10488532; p.Val266Ile), were associated with IVIG non-response (odds ratio [OR] = 1.89-3.46, P = 0.0109-0.0035). In a replication study of the four newly-identified nsSNPs, only one in the interleukin 16 (IL16) gene (rs11556218, p.Asn1147Lys) showed a trend of association with IVIG non-response (OR = 1.54, P = 0.0078). The same IL16 nsSNP was more significantly associated with IVIG non-response in combined analysis of all data (OR = 1.64, P = 1.25 × 10 -4 ). Furthermore, risk allele combination of the IL16 CT and SAMD9L TT nsSNP genotypes exhibited a very strong effect size (OR = 9.19, P = 3.63 × 10 -4 ). These results implicate IL16 as involved in the mechanism of IVIG resistance in KD.

The interaction between immune cells and phosphatidylserine (PS) molecules exposed on the surface of apoptotic-tumor bodies, such as those induced by chemotherapies, contributes to the formation of an immunosuppressive tumor microenvironment (TME). Annexin A5 (AnxA5) binds with high affinity to PS externalized by apoptotic cells, thereby hindering their interaction with immune cells. Here, we show that AnxA5 administration rescue the immunosuppressive state of the TME induced by chemotherapy. Due to the preferential homing of AnxA5 to the TME enriched with PS+ tumor cells, we demonstrate in vivo that fusing tumor-antigen peptide to AnxA5 significantly enhances its immunogenicity and antitumor efficacy when administered after chemotherapy. Also, the therapeutic antitumor effect of an AnxA5-peptide fusion can be further enhanced by administration of other immune checkpoint inhibitors. Our findings support the administration of AnxA5 following chemotherapy as a promising immune checkpoint inhibitor for cancer treatment.