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Abstract The globalization of food distribution has made it necessary to ensure the delivery of fresh food to the consumers. Protein‐rich foods produce a significant amount of tyramine when spoiled. Therefore, it was envisaged to develop localized surface plasmon resonance (LSPR)—sensor for monitoring tyramine content in beef, mackerel, and cheese. For this purpose, the sensors were developed by coating the LSPR chip with gold nanoparticles (AuNPs) followed by conjugation of tyramine‐specific peptide (TYR1). The TYR1 was synthesized and screened by phage display and binding efficiency was evaluated by DockThor. The optimized LSPR sensor showed highest binding efficiency at TYR1 concentration of 20 µg/mL with reaction time of 40 min. The sensor also showed an excellent detection range for beef, mackerel, and cheese were 0.01–10 ppb, 0.01–10 ppm, and 0.01–10 ppb, respectively, in comparison to standard. These findings indicated that this sensor can be used as a promising tool for on‐site monitoring of food quality.

Complement component 3 glomerulonephritis (C3GN) is a rare kidney disease characterized by complement dysregulation that results in prominent complement component 3 (C3) deposition in the kidneys. The clinical course of C3GN varies from mild hematuria to progressive chronic kidney disease. In most patients, C3GN is driven by acquired factors, namely, autoantibodies that target C3 or C5 convertases. Genetic variations in complement-related genes are less frequent. We report the case of a 9-year-old Korean boy who presented with microscopic hematuria and a persistently low C3 level and had biopsy findings of C3GN, with the presence of a C3 gene mutation: a frameshift mutation associated with C3 deficiency. However, the patient did not exhibit any other symptoms of complement deficiency. Direct DNA sequencing of his family members revealed the same genetic mutation in his father and older brother. This case report is significant because there are very few such reports worldwide concerning gene mutations related to C3 deficiency to be discovered in patients with C3GN. Explaining C3GN pathogenesis is challenging; therefore, additional research is required in the future.

Abstract To investigate the incidence and risk factors for neovascular glaucoma (NVG) after vitrectomy in patients with proliferative diabetic retinopathy (PDR). Patients were categorized into two subgroups based on their treatment regimen: one group received vitrectomy only (Group 1), while the other received combined phacovitrectomy (Group 2). A comparative analysis was conducted to evaluate the distinguishing characteristics of the two groups. Kaplan-Meier survival analysis was used to determine the incidence of NVG following surgery. Furthermore, multivariate analysis using the Cox proportional hazards model was conducted to identify the risk factors associated with the development of NVG after surgery. A total of 484 eyes of 484 patients were included in the study. When comparing Group 1 with Group 2, a significant difference was observed in the occurrence of NVG. In Group 1, there were 10 cases of NVG (3.9%), whereas 29 cases of NVG occurred in Group 2 (12.71%). Male sex, high preoperative intraocular pressure (IOP), and combined phacovitrectomy were found to be associated with the occurrence of NVG following phacovitrectomy. Higher creatinine levels had a protective effect in preventing the development of NVG. Male sex, high preoperative IOP, and combined phacovitrectomy were associated with a high incidence of NVG. Explore strategies to prevent NVG is important when performing combined phacovitrectomy in patients with PDR.

Abstract This study is aimed to investigate the effect of hemodialysis (HD) on the lamina cribrosa (LC) of the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT) and other ophthalmological parameters in patients with end-stage kidney disease (ESKD). This prospective observational study included 29 patients who underwent HD for ESKD. ONH parameters including neural canal diameter (NCD), peripapillary vertical height (PVH), and anterior LC depth (LCD), were assessed using SS-OCT. Changes in the ONH parameters before and after HD were statistically analysed. Correlations between changes in the LCD and other ocular and systemic measurements were identified using Pearson’s correlation analyses. The mean anterior LCD significantly decreased from 441.6 ± 139.8 μm before HD to 413.5 ± 141.7 μm after HD (P = 0.001). Mean NCD and PVH did not show significant changes after HD (P = 0.841 and P = 0.574, respectively). A significant correlation was found between changes in the anterior LCD and the mean ocular perfusion pressure (r = 0.397, P = 0.036). We observed a significant decrease in anterior LCD after HD. Our study suggests that HD can influence the ONH, especially in the LC.

Purpose To compare the Doppler sonographic findings of the left renal vein (LRV) of children diagnosed with nutcracker syndrome with and without orthostatic proteinuria. Methods Fifty and 53 consecutive children with and without orthostatic proteinuria, respectively, underwent renal Doppler ultrasonography examinations. The peak velocity (PV) was measured at the hilar portion of the LRV and between the aorta and superior mesenteric artery. Renal Doppler ultrasonography findings and clinical data including urine protein-to-creatinine ratio (UPCR) were compared according to the presence or absence of orthostatic proteinuria. Results Between the two groups, no significant differences were observed in terms of age or sex. The PV ratio between the aortomesenteric and hilar portions was 7.79±2.65 and 6.32±3.01 in children with and without orthostatic proteinuria, respectively (P=0.009). No significant differences were observed between the two groups in terms of the UPCR in the first morning urine sample. However, the UPCR in the afternoon urine sample was significantly higher in children with orthostatic proteinuria than in those without orthostatic proteinuria (0.49±0.46 mg/mg vs. 0.11±0.04 mg/mg, P

A 3-year-old boy with Glenn physiology exhibited refractory heart failure with reduced ejection fraction. To improve the patient’s oxygen saturation, he underwent ventricular assist device (VAD) implantation with concomitant Fontan completion. The extracardiac conduit Fontan operation was performed with a 4-mm fenestration. For VAD implantation, Berlin Heart cannulas were positioned at the left ventricular apex and the neo-aorta. Following weaning from cardiopulmonary bypass, a temporary continuous-flow VAD, equipped with an oxygenator, was utilized for support. After a stabilization period of 1 week, the continuous-flow VAD was replaced with a durable pulsatile-flow device. Following 3 months of support, the patient underwent transplantation without complications. The completion of the Fontan procedure at the time of VAD implantation, along with the use of a temporary continuous-flow device with an oxygenator, may aid in stabilizing postoperative hemodynamics. This approach could contribute to a safe transition to a durable pulsatile VAD in patients with Glenn physiology.

Matching for the rhesus (Rh) blood group is currently not taken into account in the organ allocation system. However, in Rh-mismatched transplantation, the primary concern is the potential for RhD-negative recipients to develop sensitization and produce anti-D antibodies if they receive a transfusion of RhD-positive blood. It is estimated that over 80% of RhD-negative recipients may experience Rh allosensitization when exposed to RhD-positive blood, although this occurrence is less common in recipients of solid organs. In theory, RhD-negative recipients who receive organs from RhD-positive donors are at risk of alloimmunization and the production of anti-D antibodies, which could complicate future blood product transfusions. However, our understanding of the impact of donor-recipient Rh mismatch on transplant outcomes, particularly in heart transplantation, is limited. We report a case of successful Rh-mismatched heart transplantation, which was effectively managed through the use of preoperative RhD immunoglobulin and plasmapheresis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects multiple organs. More than half of the patients with SLE have kidney involvement, and up to 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). Central nervous system (CNS) involvement in SLE occurs in 21% to 95% of patients. Severe neurological manifestations such as seizures, cerebrovascular disease, meningitis, and cerebrovascular accidents can develop in childhood-onset SLE, but cerebral infections, such as brain abscess and hemorrhage, are seldom reported in lupus nephritis, even in adults. Here, we report a rare case of childhood-onset SLE with ESRD, cerebral abscess, and hemorrhage. A 9-year-old girl diagnosed with lupus nephritis was administered high-dose steroids and immunosuppressant therapy to treat acute kidney injury (AKI) and massive proteinuria. The AKI deteriorated, and after 3 months, she developed ESRD. She received hemodialysis three times a week along with daily peritoneal dialysis to control edema. She developed seizures, and imaging showed a brain abscess. This was complicated by spontaneous cerebral hemorrhage, and she became unstable. She died shortly after the hemorrhage was discovered. In conclusion, CNS complications should always be considered in clinical practice because they increase mortality, especially in those with risk factors for infection.

Abstract Iontronic devices, recognized for user-friendly soft electronics, establish an electrical double layer (EDL) at the interface between ion gels and electrodes, significantly influencing device performance. Despite extensive research on ion gels and diverse electrode materials, achieving a stable interfacial formation remains a persistent challenge. In this work, we report a solution to address this challenge by employing CO2 irradiation as a bottom-up methodology to directly fabricate highly conductive, conformable laser-induced graphene (LIG) electrodes on a polyimide (PI)-based ion gel. The PI ion gel exhibits exceptional EDL formation at the electrode interface, primarily attributable to efficient ion migration. Particularly, ionic laser-induced graphene (i-LIG) electrodes, derived from the PI ion gel as a precursor, yield high-quality graphene with enhanced crystallinity and an expanded porous structure in the upward direction. This outcome is achieved through a pronounced thermal transfer effect and intercalation phenomenon between graphene layers, facilitated by the presence of ionic liquids (ILs) within the PI ion gel. Ultimately, in comparison to alternative soft electrode-based vertical capacitors, the utilization of i-LIGs and PI ion gels in the vertical capacitor demonstrates reduced interfacial resistance and increased EDL capacitance, emphasizing the extensive potential of iontronic devices. These results not only highlight these features but also introduce a new perspective for advancing next-generation iontronic devices.

Abstract Diagnosing and monitoring glaucoma in high myopic (HM) eyes are becoming very important; however, it is challenging to diagnose this condition. This study aimed to evaluate the diagnostic ability of wide-field optical coherence tomography angiography (WF-OCTA) maps for the detection of glaucomatous damage in eyes with HM and to compare the diagnostic ability of WF-OCTA maps with that of conventional imaging approaches, including swept-source optical coherence tomography (SS-OCT) wide-field maps. In this retrospective observational study, a total 62 HM-healthy eyes and 140 HM eyes with open-angle glaucoma were included. Patients underwent a comprehensive ocular examination, including SS-OCT wide-field and 12 × 12 WF-OCTA scans. The WF-OCTA map represents the peripapillary and macular superficial vascular density maps. Glaucoma specialists determined the presence of glaucomatous damage in HM eyes by reading the WF-OCTA map and comparing its sensitivity and specificity with those of conventional SS-OCT images. The sensitivity and specificity of 12 × 12 WF-OCTA scans for HM-glaucoma diagnosis were 87.28% and 86.94%, respectively, while, the sensitivity and specificity of SS-OCT wide-field maps for HM-glaucoma diagnosis were 87.49% and 80.51%, respectively. The specificity of the WF-OCTA map was significantly higher than that of the SS-OCT wide-field map (p

Purpose. This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes-induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR). Methods. To establish diabetes-induced cell models, ARPE-19 cells were treated with high glucose. The expression levels of five miRNAs (miR-185, miR-17, miR-20a, miR-15a, and miR-15b) were measured in high glucose-treated ARPE-19 cells using real-time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR-17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR-17 mimic into high glucose-treated ARPE-19 cells. Results. In high glucose-treated ARPE-19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR-17 mimic into high glucose-treated ARPE-19 cells, the levels of inflammasome components were significantly decreased. Conclusions. This study investigated the relationship between miRNAs and inflammasomes in diabetes-induced cells using high glucose-treated ARPE-19 cells. These findings suggested that miR-17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR.

Abstract Background Cathepsin B, a cysteine protease, is considered a potential biomarker for early diagnosis of cancer and inflammatory bowel diseases. Therefore, more feasible and effective diagnostic method may be beneficial for monitoring of cancer or related diseases. Results A phage-display library was biopanned against biotinylated cathepsin B to identify a high-affinity peptide with the sequence WDMWPSMDWKAE. The identified peptide-displaying phage clones and phage-free synthetic peptides were characterized using enzyme-linked immunosorbent assays (ELISAs) and electrochemical analyses (impedance spectroscopy, cyclic voltammetry, and square wave voltammetry). Feasibilities of phage-on-a-sensor, peptide-on-a-sensor, and peptide-on-a-AuNPs/MXene sensor were evaluated. The limit of detection and binding affinity values of the peptide-on-a-AuNPs/MXene sensor interface were two to four times lower than those of the two other sensors, indicating that the peptide-on-a-AuNPs/MXene sensor is more specific for cathepsin B (good recovery (86–102%) and %RSD (

IntroductionLate diagnosis of hydroxychloroquine retinopathy remains a major concern, with the potential for irreversible visual impairment. This study aimed to investigate the causes of late diagnosis in a hospital-based cohort of Korean patients with hydroxychloroquine retinopathy and assess the trend of late diagnosis from 2015 to 2022.MethodsThirty-eight patients with a late diagnosis (severe stage at diagnosis) among 94 patients with hydroxychloroquine retinopathy were included in the analysis. The causes of late diagnosis were categorized as referral-related, patient-related, and screening-related factors.ResultsThe most prevalent cause was no or late referral to ophthalmologists, contributing to a significant gap in timely identification. Patient-related causes included delayed monitoring visits despite scheduled appointments and early-onset disease. Screening-related causes encompassed an insufficient number of sensitive tests, leading to inadequate evidence for diagnosis, and missed or wrong diagnoses by screening physicians. The proportion of late diagnoses decreased over time, indicating improvements in overall screening and detection. The decreasing proportions of screening-related causes suggest advancements in screening practices and the use of multiple sensitive tests for screening.DiscussionEfforts to further reduce late diagnoses and improve screening and diagnostic processes are necessary. Our data emphasize the importance of timely referral to ophthalmologists for early detection and management.

Abstract In this study, we investigated the clock-hour topographic characteristics and extent of photoreceptor and retinal pigment epithelium (RPE) damage and correlated the extent with functional defects in eyes with hydroxychloroquine retinopathy. A total of 146 eyes of 75 patients diagnosed with hydroxychloroquine retinopathy were included. The clock-hour topographic characteristics (relative to the fovea) and extent of the photoreceptor and RPE defects in the parafoveal and pericentral areas were evaluated by reviewing the radial-scan optical coherence tomography (OCT) and wide-field fundus autofluorescence (FAF) images. The extent of outer retinal damage in the parafoveal and pericentral areas were correlated with the perimetric parameters of the Humphrey 10–2 and 30–2 tests, respectively. Although the photoreceptor damage was most commonly noted at the temporal to inferior locations in both parafoveal and pericentral areas, the RPE damage in the pericentral eyes was most commonly noted in the nasal area and showed topographic discrepancies with photoreceptor damage. The extent of RPE damage was almost identical between OCT and FAF images, whereas photoreceptor defect extent was significantly greater on OCT images. The extent of parafoveal and pericentral photoreceptor damage on OCT images was significantly correlated with perimetric parameters of the 10–2 and 30–2 tests, respectively (all P

Objectives: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. Methods: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. Results: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). Conclusions: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.

To modify the thermal properties of pitch by adding polyvinyl chloride (PVC), co-pyrolysis of PVC and coal tar pitch was performed. PVC decomposes into HCl and de-HCl PVC (polyene) above 200 °C, and these substances affect the synthesis behavior of coal tar pitch. It was confirmed that HCl induces cracking, promotes the radical reaction and lowers the polycondensation initiation temperature of coal tar pitch. Furthermore, aromatic components produced by the cyclization reaction of polyene participate in the polycondensation reaction, which increases the molecular weight of the pitch. This leads to an increase in softening point and coking value of pitch. The related mechanisms were assessed using thermal analysis (TGA, DTG, DSC) and molecular weight distribution analysis (MALDI-TOF).

The accumulation of recombination events in selfing species may lead to a rapid fixation of both beneficial and deleterious mutations. Here, the authors resequence 781 soybean accessions, show purging of deleterious mutation during domestication, and report genome-wide associations for seed protein and oil traits.

Carbon/carbon composite has superior properties, so it has been expected to use various industrial fields. However, low mechanical strength (than conventional structural materials) works as a hurdle, so the use of oxidative stabilization to improve the mechanical strength of carbon/carbon composites was studied. The oxidation process was performed at 220–350 °C based on thermogravimetric analysis (TGA). The compressive strength of the oxidized sample at 290 °C was 212 MPa, which is 2.5 times greater than that of the non-oxidized sample (84 MPa). However, the oxidation temperature of more than 290 °C decreased the compressive strength (199 MPa at 350 °C). This tendency was in accordance with the TGA and X-ray photoelectron spectroscopy (XPS) results. The effect of oxidative stabilization can be explained by two factors: the polymerization of the used binder pitch by the crosslinking effect by induced oxygen and improvement of the affinity between the coke and binder pitch.

The seedlessness of grape derived from stenospermocarpy is one of the most prized traits of table or raisin grapes. It is controlled by a complex genetic system containing one dominant gene and multiple recessive genes. Here, we collected dense variation data from high-depth resequencing data of seeded, seedless, and wild relative grape genomes sequenced to > 37x mean depth. Variant calls were made using a modified variant calling pipeline that was suitable for highly diverse interspecific grape accessions. The modified pipeline enabled us to call several million more variants than the commonly recommended pipeline. The quality was validated by Sanger sequencing data and subsequently supported by the genetic population structure and the phylogenetic tree constructed using the obtained variation data, results of which were generally consistent with known pedigree and taxonomic classifications. Variation data enabled us to confirm a dominant gene and identify recessive loci for seedlessness. Incidentally, we found that grape cultivar Rizamat contains an ancestral chromosomal region of the dominant gene in Sultanina, a predominant seedlessness donor cultivar. Furthermore, we predicted new candidate causal genes including Vitvi01g00455, Vitvi08g01528, and Vitvi18g01237 associated with the recessive seedless-regulating loci, which showed high homology with genes that regulate seed development in Arabidopsis. This study provides fundamental insights relevant to variant calling from genome resequencing data of diverse interspecific hybrid germplasms such as grape and will accelerate future efforts aimed at crop improvement.

AbstractMassive resequencing efforts have been undertaken to catalog allelic variants in major crop species including soybean, but the scope of the information for genetic variation often depends on short sequence reads mapped to the extant reference genome. Additional de novode novoRsvde novo

It is known that the etiology and clinical outcomes of autoimmune diseases are associated with a combination of genetic and environmental factors. In the case of the genetic factor, the SNPs of the PTPN22 gene have shown strong associations with several diseases. The recent exploding numbers of genetic studies have made it possible to find these associations rapidly, and a variety of autoimmune diseases were found to be associated with PTPN22 polymorphisms. Proteins encoded by PTPN22 play a key role in the adaptative and immune systems by regulating both T and B cells. Gene variants, particularly SNPs, have been shown to significantly disrupt several immune functions. In this review, we summarize the mechanism of how PTPN22 and its genetic variants are involved in the pathophysiology of autoimmune diseases. In addition, we sum up the findings of studies reporting the genetic association of PTPN22 with different types of diseases, including type 1 diabetes mellitus, systemic lupus erythematosus, juvenile idiopathic arthritis, and several other diseases. By understanding these findings comprehensively, we can explain the complex etiology of autoimmunity and help to determine the criteria of disease diagnosis and prognosis, as well as medication developments.

Purpose: To investigate the positional change of the eyeball induced by horizontal and vertical gazing to deduce translatory movement, using three-dimensional (3D) magnetic resonance imaging (MRI).Methods: In this prospective observational study participants underwent orbital MRI during central, right, left, up, and down gazing. MRI scans were processed using self-developed software; this software enabled 3D MR image reconstruction and the superimposition of reconstructed image sets between different gazes. After acquiring the coordinates of the eyeball centroid in each gaze, the changes in centroid coordinates from central gaze to the other gazes were estimated, and correlations with associated factors were evaluated.Results: The mean distance of centroid movement was 0.69 ± 0.27 mm in abduction, 0.68 ± 0.27 mm in adduction, 0.43 ± 0.23 mm in elevation, and 0.44 ± 0.19 mm in depression. The mean angle of centroid movement in horizontal gaze, measured in terms of the movement of the left eye centroid in the axial plane, was 228.7° in abduction and −4.2° in adduction. In vertical gaze, the mean angle of centroid movement was −96.8° in elevation and 101.8° in depression. Axial length and ocular volume were negatively correlated with the distance of centroid movement in horizontal gaze.Conclusions: The position of the eyeball moved in the same direction as the gaze during horizontal gaze, but in the opposite direction during vertical gaze. For accurate eye movement analyses, such as the measurement of the deviation angle in strabismus, translation should be considered in addition to rotation.

Purpose Extended-spectrum β-lactamase-producing bacteria-induced urinary tract infections are increasing and require more potent antibiotics such as carbapenems. We evaluated the clinical significance of extended-spectrum β-lactamase urinary tract infection in children younger than 5 years to select proper antibiotics and determine prognostic factors. Differences were compared between age groups. Methods We retrospectively studied 288 patients with their first febrile urinary tract infection when they were younger than 5 years. Patients were divided into extended-spectrum β-lactamase-positive and extended-spectrum β-lactamase-negative urinary tract infection groups. Clinical characteristics and outcomes were compared between the groups; an infant group was separately analyzed (onset age younger than 3 months). Results Extended-spectrum β-lactamase urinary tract infection occurred in 11 % patients who had more frequent previous hospitalization (P=0.02) and higher recurrence rate (P=0.045). During the antimicrobial susceptibility test, the extended-spectrum β-lactamase-positive urinary tract infection group showed resistance to third-generation cephalosporins; however, 98% patients responded clinically. In the infant group, extended-spectrum β-lactamase-positive urinary tract infection occurred in 13% patients and was associated with a longer pre-onset hospitalization history (P=0.002), higher C-reactive protein level (P=0.04), and higher recurrence rate (P=0.02) than that in the older group. Conclusion Extended-spectrum β-lactamase urinary tract infection requires more attention because of its higher recurrence rate. The antimicrobial susceptibility test demonstrated resistance to third-generation cephalosporins, but they can be used as first-line empirical antibiotics because of their high clinical response rate. Aminoglycosides can be second-line antibiotics before starting carbapenems when third-generation cephalosporins do not show bactericidal effects for extended- spectrum β-lactamase urinary tract infection.

Purpose The American Society for Apheresis provides clinical guidelines for therapeutic apheresis in adults, but there are no guidelines for children. This study aimed to analyze the effect of therapeutic plasma exchange (TPE) in pediatric patients with various kidney diseases in Korea. Methods We retrospectively reviewed the data of 16 children (up to 18 years of age) who were admitted to Severance Children’s Hospital with refractory kidney disease. All patients received TPE between 1994 and 2016. Clinical and laboratory characteristics such as age, weight, sex, change in blood urea nitrogen (BUN), and creatinine level before and after TPE, and complications after TPE were analyzed. Results The mean age and weight of the 16 patients at the time of TPE was 11.3±4.0 years and 34.6±17.5 kg, respectively. The BUN level was 35.4 mg/dL before TPE and significantly decreased to 21.5 mg/dL (P=0.025) at 1 week and 20.5 mg/dL (P=0.01) at 1 month after TPE. The creatinine level significantly decreased from 1.20 mg/dL before TPE to 0.90 mg/dL (P=0.02) at 1 week after TPE. Four complications (hypovolemia, anemia, hypocalcemia, and thrombocytopenia) were reported, but were not fatal. Conclusion Our findings suggest that TPE is an effective therapeutic modality in children with refractory kidney disease and can be indicated for the treatment of various kidney diseases.

Retinoic acid (RA), a metabolite of vitamin A, has been found to influence regeneration in the adult central nervous system (CNS). There may be an effect of RA in the recovery/repair in multiple sclerosis (MS), an autoimmune and neurodegenerative disease of the CNS. We hypothesized that RA is a regulator of the further differentiation of oligodendrocyte precursor cells (OPCs) – cells key to the remyelination process in MS. We conducted studies utilizing RNA-sequencing in human embryonic stem cell (hESC)-derived neural stem cells (NSCs) and OPCs so as to understand the role of transcriptional regulators during transition from both ESCs to NSCs and NSCs to OPCs. We identified that expression of retinoic acid receptors β and γ (RARβ and RARγ ) was significantly increased following the transition from NSCs to OPCs. We also demonstrated that long term in vitro culture of hESC-derived OPC with different isoforms of RA led to the significant up-regulation of two known transcriptional inhibitors of oligodendrocyte differentiation: Hes5 following prolonged treatment with all-trans-RA, 9-cis RA and 13-cis RA; and Id4 following treatment with 13cisRA. These results suggest that long term exposure to certain RA isoforms may impact the continued differentiation of this population.

PurposeKawasaki disease (KD) is an immune-related multisystemic vasculitis that occurs in children, especially ensuing from a coronary artery abnormality. Sodium level is known to be related to vascular injury, which could affect the progress of KD. The purpose of this study was to determine the serum sodium levels that could predict the occurrence of cardiac and coronary artery events in KD.MethodsWe conducted a retrospective review of medical records for 104 patients with KD from January 2015 to December 2015. Patients with serum Na levels of

Dengue virus (DENV) nonstructural 1 (NS1) protein is a specific and sensitive biomarker for the diagnosis of dengue. In this study, an efficient electrochemical biosensor that uses chemically modified affinity peptides was developed for the detection of dengue virus NS1. A series of amino acid-substituted synthetic peptides was rationally designed, chemically synthesized and covalently immobilized to a gold sensor surface. The sensor performance was monitored via square wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS). Potential affinity peptides specific for NS1 were chosen according to the dynamic current decrease in SWV experiments. Using circular dichroism, the molar ellipticity of peptides (DGV BP1-BP5) was determined, indicating that they had a mostly similar in random coil structure, not totally identical. Using SWV, DGV BP1 was selected as a promising recognition peptide and limit of detection for NS1 was found to be 1.49 μg/mL by the 3-sigma rule. DGV BP1 showed good specificity and stability for NS1, with low signal interference. The validation of the sensor to detect NS1 proteins was confirmed with four dengue virus culture broth (from serotype 1 to 4) as proof-of-concept. The detection performance of our sensor incorporating DGV BP1 peptides showed a statistically significant difference. These results indicate that this strategy can potentially be used to detect the dengue virus antigen, NS1, and to diagnosis dengue fever within a miniaturized portable device in point-of-care testing.

Purpose. To investigate the effect of hemodialysis (HD) on the anterior chamber angle by anterior segment optical coherence tomography (ASOCT) and other ophthalmologic parameters in patients with end-stage kidney disease (ESKD). Methods. A prospective observational study was performed on 20 patients who underwent HD for ESKD. Anterior chamber angle images were obtained by 16 mm line scan of ASOCT. The angle opening distance (AOD) and the trabecular-iris space area (TISA) were determined using the ImageJ program. Additional 12 mm horizontal and 9 mm vertical wide-field scans centered on the posterior pole were performed for the measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness. Changes in intraocular pressure (IOP), AOD, TISA, pRNFL thickness, and mGCIPL thickness before and after HD were statistically analyzed. Results. The IOP decreased significantly from 17.5 ± 3.4 before HD to 16.2 ± 2.3 after HD (P=0.017). There was a statistically significant decrease in AOD 750 and TISA 750 (P=0.005 and P=0.007, respectively). AOD 500 and TISA 500 also decreased, which was almost statistically significant (P=0.061 and P=0.081, respectively). Mean pRNFL thickness and mGCIPL thickness did not show significant change after HD. Conclusion. We observed a significant decrease in IOP and anterior chamber angle measurements after HD. Our study suggests that HD can influence the anterior segment structure of eyes.

[This corrects the article DOI: 10.1371/journal.pone.0204069.].

PurposeAcute pyelonephritis (APN) is a serious bacterial infection that can cause renal scarring in children. Early identification of APN is critical to improve treatment outcomes. The neutrophil-lymphocyte ratio (NLR) is a prognostic marker of many diseases, but it has not yet been established in urinary tract infection (UTI). The aim of this study was to determine whether NLR is a useful marker to predict APN or vesicoureteral reflux (VUR).MethodsWe retrospectively evaluated 298 pediatric patients (age≤36 months) with febrile UTI from January 2010 to December 2014. Conventional infection markers (white blood cell [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), and NLR were measured.ResultsWBC, CRP, ESR, and NLR were higher in APN than in lower UTI (P

PURPOSE:To investigate the effect of eye movement on the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT), and to measure the degree of ONH changes. METHODS:We enrolled 52 healthy subjects, 20 to 40 years of age, and performed a prospective observational study. Both ONH and macula were imaged simultaneously using wide volume scan of the SS-OCT in the primary and different gaze positions. Horizontal eye movements were used to obtain OCT images in abducted and adducted eyeball positions. Multilateral 3-dimensional registration was used to process and analyze the images to measure the degree of ONH changes. RESULTS:The mean axial length (AXL) was 25.73 ± 1.42mm and the mean spherical equivalents was -4.49 ± 2.94 D (The proportion of high myopia was 39.4%). Significant morphologic changes were observed in the ONH during both abduction and adduction. In abduction, the overall ONH tissues were elevated, and the mean area of elevation was 115,134 ± 9,424 μm2 (p

To evaluate choroidal changes in eyes with acute anterior uveitis associated with human leukocyte antigen (HLA)-B27.In 44 patients with first-onset, unilateral, acute-onset (

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, often underdiagnosed or misdiagnosed in children. We describe the case of a 12-year-old boy who presented to Severance Hospital with a 1-month history of bilateral conjunctival injection. He was first evaluated by an Ophthalmologist in another hospital and diagnosed with panuveitis. Laboratory tests indicated renal failure, and a renal biopsy confirmed the diagnosis of acute tubulointerstitial nephritis. An extensive exclusion of all possible causes allowed a diagnosis of TINU syndrome. The patient was treated with a systemic corticosteroid (initially prednisolone, 2 mg/kg and later deflazacort 1 mg/kg) and topical steroid drops for 1 month. Azathioprine was later added to the treatment regimen and the systemic steroid was slowly tapered. The final outcome of renal-ocular disease was favorable in the patient. However, long-term follow-up is necessary to properly manage frequent relapses and incomplete renal recovery. TINU should be considered as a differential diagnosis in children with uveitis or acute renal failure.

Leaf senescence is a finely regulated complex process; however, evidence for the involvement of epigenetic processes in the regulation of leaf senescence is still fragmentary. Therefore, we chose to examine the functions of DRD1, a SWI2/SNF2 chromatin remodeling protein, in epigenetic regulation of leaf senescence, particularly because drd1-6 mutants exhibited a delayed leaf senescence phenotype. Photosynthetic parameters such as Fv/Fm and ETRmax were decreased in WT leaves compared to leaves of drd1-6 mutants after dark treatment. The WT leaves remarkably lost more chlorophyll and protein content during dark-induced senescence (DIS) than the drd1-6 leaves did. The induction of senescence-associated genes was noticeably inhibited in the drd1-6 mutant after 5-d of DIS. We compared changes in epigenetic regulation during DIS via quantitative expression analysis of 180-bp centromeric (CEN) and transcriptionally silent information (TSI) repeats. Their expression levels significantly increased in both the WT and the drd1-6 mutant, but did much less in the latter. Moreover, the delayed leaf senescence was observed in ddm1-2 mutants as well as the drd1-6, but not in drd1-p mutants. These data suggest that SWI2/SNF2 chromatin remodeling proteins such as DRD1 and DDM1 may influence leaf senescence possibly via epigenetic regulation.

Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as >1700 µg/dL (range, 0 to 45 µg/dL). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.

Objectives: Various cytokines induced by inhalation of coal dust may mediate inflammation and lead to tissue damage or fibrosis, such as coal workers' pneumoconiosis (CWP). Methods: To investigate the relevance of serum cytokines in CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP subjects) were related to cross sectional findings and 1-year progressive changes of the pneumoconiosis. Progressive changes of CWP were evaluated by paired comparison of chest radiographs. Analysis by a receiver operating characteristic (ROC) curve assessed the biomarker potential of each cytokine. Results: The mean serum IL-8 level was significantly higher in CWP compared to controls and IL-8 levels correlated with the degree of CWP. The median serum TNF-α level was significantly higher in subjects with progressive CWP compared to subjects without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF-α (0.72) for CWP identification and progression, respectively, indicated the biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF-α were 11.63 pg/ml (sensitivity 69%; specificity 64%) and 4.52 pg/ml (sensitivity 67%; specificity 79%), respectively. Conclusion: The results suggest that high levels of serum IL-8 are associated with the presence of CWP and those of serum TNF-α are associated with the progression of CWP.

Preoperative liver stiffness (LS) measurement using transient elastography (TE) is useful for predicting late recurrence after curative resection of hepatocellular carcinoma (HCC). We developed and validated a novel LS value-based predictive model for late recurrence of HCC.Patients who were due to undergo curative resection of HCC between August 2006 and January 2010 were prospectively enrolled and TE was performed prior to operations by study protocol. The predictive model of late recurrence was constructed based on a multiple logistic regression model. Discrimination and calibration were used to validate the model.Among a total of 139 patients who were finally analyzed, late recurrence occurred in 44 patients, with a median follow-up of 24.5 months (range, 12.4-68.1). We developed a predictive model for late recurrence of HCC using LS value, activity grade II-III, presence of multiple tumors, and indocyanine green retention rate at 15 min (ICG R15), which showed fairly good discrimination capability with an area under the receiver operating characteristic curve (AUROC) of 0.724 (95% confidence intervals [CIs], 0.632-0.816). In the validation, using a bootstrap method to assess discrimination, the AUROC remained largely unchanged between iterations, with an average AUROC of 0.722 (95% CIs, 0.718-0.724). When we plotted a calibration chart for predicted and observed risk of late recurrence, the predicted risk of late recurrence correlated well with observed risk, with a correlation coefficient of 0.873 (P

Background: Atrial fibrillation (Afib) is a marker of increased cardiovascular morbidity and mortality. Owing to the increased prevalence of Afib in patients undergoing cardiac surgery, assessing the effect of Afib on postsurgical outcomes is important. We aimed to analyze the effect of preoperative Afib on clinical outcomes in patients undergoing cardiac surgery using a large surgical database. Methods: This retrospective cohort study was based on the national health claims database established by the National Health Insurance Service of the Republic of Korea from 2009 to 2015. Diagnosis and procedure codes were used to identify diseases according to the International Statistical Classification of Diseases, 10th revision. Results: We included 1,037 patients (0.1%) who had undergone cardiac surgery from a randomized 1,000,000-patient cohort, and 15 patients (1.5%) treated with isolated surgical Afib ablation were excluded. Of these 1,022 patients, 412 (39.7%), 303 (29.2%), and 92 (9.0%) underwent coronary artery bypass, heart valve surgery, and Cox-maze surgery, respectively. Preoperative Afib was associated with higher patient mortality (p=0.028), regardless of the surgical procedure. Patients with preoperative Afib (n=190, 18.6%) experienced a higher cumulative risk of overall mortality (hazard ratio [HR], 1.435; 95% confidence interval [CI], 1.263–2.107; p=0.034). Subgroup analysis revealed a reduced risk of overall mortality with Cox-maze surgery in Afib patients (HR, 0.500; 95% CI, 0.266–0.938; p=0.031). Postoperative cerebral ischemia or hemorrhage events were not related to Afib. Conclusion: Preoperative Afib was independently associated with worse long-term postoperative outcomes after cardiac surgery. Concomitant Cox-maze surgery may improve the survival rate.

In this study, we aimed to develop a new automated method for kidney volume measurement in children using ultrasonography (US) with image pre-processing and hybrid learning and to formulate an equation to calculate the expected kidney volume. The volumes of 282 kidneys (141 subjects,

Transmembrane p24 trafficking protein 3 (TMED3) is a metastatic suppressor in colon cancer and hepatocellular carcinoma. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that TMED3 could be a new prognostic marker for ccRCC. Patient data were extracted from cohorts in the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Differential expression of TMED3 was observed between the low stage (Stage I and II) and high stage (Stage III and IV) patients in the TCGA and ICGC cohorts and between the low grade (Grade I and II) and high grade (Grade III and IV) patients in the TCGA cohort. Further, we evaluated TMED3 expression as a prognostic gene using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno’s C-index, and the AUC of the receiver operating characteristics at 5 years. The Kaplan-Meier analysis revealed that TMED3 overexpression was associated with poor prognosis for ccRCC patients. Analysis of the C-indices and area under the receiver operating characteristic curve further supported this. Multivariate analysis confirmed the prognostic significance of TMED3 expression levels (P = 0.005 and 0.006 for TCGA and ICGC, respectively). Taken together, these findings demonstrate that TMED3 is a potential prognostic factor for ccRCC.

In addition to single-nucleotide polymorphisms (SNP), copy number variation (CNV) is a major component of human genetic diversity. Among many whole-genome analysis platforms, SNP arrays have been commonly used for genomewide CNV discovery. Recently, a number of CNV defining algorithms from SNP genotyping data have been developed; however, due to the fundamental limitation of SNP genotyping data for the measurement of signal intensity, there are still concerns regarding the possibility of false discovery or low sensitivity for detecting CNVs. In this study, we aimed to verify the effect of combining multiple CNV calling algorithms and set up the most reliable pipeline for CNV calling with Affymetrix Genomewide SNP 5.0 data. For this purpose, we selected the 3 most commonly used algorithms for CNV segmentation from SNP genotyping data, PennCNV, QuantiSNP; and BirdSuite. After defining the CNV loci using the 3 different algorithms, we assessed how many of them overlapped with each other, and we also validated the CNVs by genomic quantitative PCR. Through this analysis, we proposed that for reliable CNV-based genomewide association study using SNP array data, CNV calls must be performed with at least 3 different algorithms and that the CNVs consistently called from more than 2 algorithms must be used for association analysis, because they are more reliable than the CNVs called from a single algorithm. Our result will be helpful to set up the CNV analysis protocols for Affymetrix Genomewide SNP 5.0 genotyping data.

We have discovered copy number variations (CNVs) in 3,578 Korean individuals with the Affymetrix Genome-Wide SNP array 5.0, and 4,003 copy number variation regions (CNVRs) were defined in a previous study. To explore the details of the variants easily in related studies, we built a database, cataloging the CNVs and related information. This system helps researchers browsing these variants with gene and structure variant annotations. Users can easily find specific regions with search options and verify them from system-integrated genome browsers with annotations.

BACKGROUND: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort. METHODOLOGY/PRINCIPAL FINDINGS: Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation. CONCLUSION/SIGNIFICANCE: We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations.