Clinical significance of serum cytokine profiles for differentiating between Kawasaki disease and its mimickers.

OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.

Safety and efficacy of vedolizumab in pediatric patients with ulcerative colitis: multicenter study in Japan.

BACKGROUND: Vedolizumab (VDZ) is a humanized monoclonal antibody that binds to α4ß7 integrin expressed in T-lymphocytes and is gut selective. Few studies have evaluated the safety and efficacy of VDZ in pediatric ulcerative colitis (UC) patients, especially from Asia. METHODS: A longitudinal multicenter retrospective study was conducted at 10 Japanese tertiary medical institutions. Patients aged ≤18 years old who received VDZ for UC between January 2019 and July 2021 were enrolled. Information on the clinical characteristics, prior/concomitant treatment, and safety during the observation period was collected. RESULTS: The data obtained from 48 patients (males, n = 30; females, n = 18) were analyzed. The median age at VDZ induction was 14 (range 4-18) years old. VDZ was indicated in 73% of patients as switching from previous biologics due to primary failure, loss of response, and adverse events (AEs) and was the first biologic in 27%. Remission was achieved or maintained at weeks 14, 30, and 54 in 79.2%, 75.0%, and 65.8% of patients, respectively. There were no significant differences between the number of previous biologics exposures and VDZ effectiveness. The hematocrit, serum albumin concentrations, and erythrocyte sedimentation rate (ESR) at baseline differed significantly by VDZ effectiveness. Nine AEs, including infusion reaction, were noted in seven (14.3%) patients. There were no severe AEs related to VDZ administration. CONCLUSIONS: VDZ was safe and effective in children with UC. The hematocrit, albumin, and ESR at VDZ initiation might be predictors for VDZ effectiveness. VDZ may be an important option for pediatric patients and can be used as an alternative to immunomodulators.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

Multisystem Imaging Manifestations of Kawasaki Disease.

Kawasaki disease (KD) is a common pediatric vasculitis syndrome involving medium- and small-sized arteries that is especially prevalent in early childhood (ie, age 6 months to 5 years). The diagnosis of KD is made on the basis of clinical features, such as fever, characteristic mucocutaneous changes, and nonsuppurative cervical lymphadenopathy. However, early diagnosis is often challenging because many children with KD present with atypical symptoms. The most serious complication of KD is coronary artery aneurysm caused by coronary arteritis. Prompt intravenous immunoglobulin therapy reduces the risk of cardiac morbidity. In addition, the systemic extension of KD-related vasculitis during the acute phase causes a variety of multisystem manifestations, including encephalopathy, stroke, retropharyngeal edema, pericarditis, myocarditis, KD shock syndrome, pulmonary lesions, intestinal pseudo-obstruction, gallbladder hydrops, arthritis, and myositis. These complications tend to be more common in affected children with atypical presentation. Radiologists can play an important role in the timely identification of diverse KD-associated morbidities and thus may contribute to the early diagnosis of atypical KD. Online supplemental material is available for this article. ©RSNA, 2021.

Na-ion mobility in P2-type Na0.5MgxNi0.17-xMn0.83O2 (0 ≤ x ≤ 0.07) from electrochemical and muon spin relaxation studies.

Sodium transition metal oxides with a layered structure are one of the most widely studied cathode materials for Na+-ion batteries. Since the mobility of Na+ in such cathode materials is a key factor that governs the performance of material, electrochemical and muon spin rotation and relaxation techniques are here used to reveal the Na+-ion mobility in a P2-type Na0.5MgxNi0.17-xMn0.83O2 (x = 0, 0.02, 0.05 and 0.07) cathode material. Combining electrochemical techniques such as galvanostatic cycling, cyclic voltammetry, and the galvanostatic intermittent titration technique with µ+SR, we have successfully extracted both self-diffusion and chemical-diffusion under a potential gradient, which are essential to understand the electrode material from an atomic-scale viewpoint. The results indicate that a small amount of Mg substitution has strong effects on the cycling performance and the Na+ mobility. Amongst the tested cathode systems, it was found that the composition with a Mg content of x = 0.02 resulted in the best cycling stability and highest Na+ mobility based on electrochemical and µ+SR results. The current study clearly shows that for developing a new generation of sustainable energy-storage devices, it is crucial to study and understand both the structure as well as dynamics of ions in the material on an atomic level.

Detection and Determination of Fumonisins B1, B2, and B3 Contaminating Japanese Domestic Wine by Liquid Chromatography Coupled to Tandem Mass Spectrometry (LC-MS/MS).

Nine domestic wine samples collected from a Japanese winery were examined for the presence of fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), as well as ochratoxin A (OTA) and ochratoxin B (OTB). Wine samples spiked with 13C-labeled internal standards (13C34-FB1 and 13C20-OTA) were diluted with phosphate buffered saline (PBS) buffer, loaded on immunoaffinity cartridges to purify of fumonisins and ochratoxins, and subjected to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. The data revealed that the domestic wine samples were possibly contaminated with FB1 and FB3, in addition to FB2, whereas none of the tested wine samples were contaminated with OTA and OTB. These results suggest that Fusarium fungi can be associated with the fumonisin contamination of Japanese domestic wine, whereas Aspergillus niger seems to be frequently reported as the major causal fungus of fumonisin contamination of wine in Europe. Analysis of the intermediate samples during the wine brewing indicated that fumonisin concentrations did not increase during wine production, suggesting that fumonisin contamination did not occur during the brewing process, but was derived from the raw materials of grape berries.

Clinical Safety and Utility of Pediatric Balloon-assisted Enteroscopy: A Multicenter Prospective Study in Japan.

OBJECTIVES: The benefit of balloon-assisted enteroscopy (BAE) had been recently documented in pediatric patients, but previous reports are based on single institution experiences. We evaluated the feasibility of pediatric BAE in 8 tertiary referral hospitals throughout Japan. METHODS: This was a prospective, multi-institutional study. Patients younger than 18 years were enrolled between April 2014 and March 2017 to undergo double-balloon or single-balloon enteroscopy. Data were collected prospectively using a standardized questionnaire. RESULTS: We enrolled 79 pediatric patients (96 procedures, 70 boys, 26 girls; median age 12.7 years, range 1-17 years). Antegrade (oral-route) BAE was performed in 20 procedures (lowest body weight 12.9 kg, youngest age 3.7 years), and retrograde (anal-route) BAE in 76 (lowest body weight 10.8 kg, youngest age 1.6 years). Severe adverse events were associated with BAE in 2 patients: 1 with hemorrhage due to polypectomy and 1 with pancreatitis after double-balloon endoscopic retrograde cholangioscopy. No intestinal perforation was reported. Procedure duration of oral-route BAE for diagnosis was significantly longer than anal-route for diagnosis (P < 0.001). The overall diagnostic yield for rectal bleeding/positive fecal occult blood test and abdominal pain was 48%. Among 40 patients referred for diagnosis who did not undergo capsule endoscopy, diagnoses were confirmed in 17 (42.5%) patients after BAE. CONCLUSIONS: This prospective multicenter observational study documents the efficacy of BAE in pediatric patients.

Mycophenolate mofetil therapy for two cases of antiphospholipid antibody-associated chorea.

Chorea is associated with involuntary movement and may occur via an autoimmune mechanism. Until now, we treated immune-mediated chorea with glucocorticoids and cyclophosphamide as the efficacy of mycophenolate mofetil (MMF) therapy for this condition was unknown. Here, we report two cases of antiphospholipid antibody (aPL)-associated chorea that were cured by MMF. Measurement of aPL could help for future management of chorea patients. This report provides new insight into the beneficial effects of MMF on aPL-associated chorea.

PlantExpress: A Database Integrating OryzaExpress and ArthaExpress for Single-species and Cross-species Gene Expression Network Analyses with Microarray-Based Transcriptome Data.

Publicly available microarray-based transcriptome data on plants are remarkably valuable in terms of abundance and variation of samples, particularly for Oryza sativa (rice) and Arabidopsis thaliana (Arabidopsis). Here, we introduce the web database PlantExpress (http://plantomics.mind.meiji.ac.jp/PlantExpress/) as a platform for gene expression network (GEN) analysis with the public microarray data of rice and Arabidopsis. PlantExpress has two functional modes. The single-species mode is specialized for GEN analysis within one of the species, while the cross-species mode is optimized for comparative GEN analysis between the species. The single-species mode for rice is the new version of OryzaExpress, which we have maintained since 2006. The single-species mode for Arabidopsis, named ArthaExpress, was newly developed. PlantExpress stores data obtained from three microarrays, the Affymetrix Rice Genome Array, the Agilent Rice Gene Expression 4x44K Microarray, and the Affymetrix Arabidopsis ATH1 Genome Array, with respective totals of 2,678, 1,206, and 10,940 samples. This database employs a 'MyList' function with which users may save lists of arbitrary genes and samples (experimental conditions) to use in analyses. In cross-species mode, the MyList function allows performing comparative GEN analysis between rice and Arabidopsis. In addition, the gene lists saved in MyList can be directly exported to the PODC database, which provides information and a platform for comparative GEN analysis based on RNA-seq data and knowledge-based functional annotation of plant genes. PlantExpress will facilitate understanding the biological functions of plant genes.

TOMATOMICS: A Web Database for Integrated Omics Information in Tomato.

Solanum lycopersicum (tomato) is an important agronomic crop and a major model fruit-producing plant. To facilitate basic and applied research, comprehensive experimental resources and omics information on tomato are available following their development. Mutant lines and cDNA clones from a dwarf cultivar, Micro-Tom, are two of these genetic resources. Large-scale sequencing data for ESTs and full-length cDNAs from Micro-Tom continue to be gathered. In conjunction with information on the reference genome sequence of another cultivar, Heinz 1706, the Micro-Tom experimental resources have facilitated comprehensive functional analyses. To enhance the efficiency of acquiring omics information for tomato biology, we have integrated the information on the Micro-Tom experimental resources and the Heinz 1706 genome sequence. We have also inferred gene structure by comparison of sequences between the genome of Heinz 1706 and the transcriptome, which are comprised of Micro-Tom full-length cDNAs and Heinz 1706 RNA-seq data stored in the KaFTom and Sequence Read Archive databases. In order to provide large-scale omics information with streamlined connectivity we have developed and maintain a web database TOMATOMICS (http://bioinf.mind.meiji.ac.jp/tomatomics/). In TOMATOMICS, access to the information on the cDNA clone resources, full-length mRNA sequences, gene structures, expression profiles and functional annotations of genes is available through search functions and the genome browser, which has an intuitive graphical interface.

Occult hepatitis B virus infection in immunized children born to carrier mothers.

BACKGROUND: The prevalence of occult hepatitis B virus (HBV) infection (OBI) in children due to mother-to-child transmission (MTCT) despite immunoprophylaxis remains controversial and is still unknown in Japan. The aim of this study was to determine the OBI prevalence in such children in Japan and identify the genomic mutations that might be associated with the pathogenesis of OBI in children. METHODS: The data on 158 children born to HBV carrier mothers and who received complete passive-active immunoprophylaxis after birth in 2002-2014 were reviewed. HBV markers were detected using commercial enzyme-linked immunosorbent assay kits. HBV-DNA was detected using real-time and nested polymerase chain reaction. Complete genomic sequences were determined. RESULTS: Among the 158 children studied, three had HBV MTCT: two had OBI, and one had resolved HBV infection (RBI). The prevalence of OBI and RBI was estimated to be 1.3% and 0.6%, respectively. The HBV genomes of the two OBI children were wild type and 100% identical to those of their mothers. Of these two children, one received repeated hepatitis B immunoglobulin (HBIG) and developed overt HBV infection. Her HBV genome had a G145R mutation in the S gene that might have been induced by HBIG treatment. The RBI child was persistently positive for antibody to HBV core antigen (10-12 signal/cut-off ratio; S/CO). CONCLUSIONS: A low prevalence of OBI was observed in children who received immunoprophylaxis for preventing MTCT in Japan. The development of overt HBV infection in infants with OBI indicates the necessity of close and long-term monitoring.

The Arabidopsis TAC Position Viewer: a high-resolution map of transformation-competent artificial chromosome (TAC) clones aligned with the Arabidopsis thaliana Columbia-0 genome.

We present a high-resolution map of genomic transformation-competent artificial chromosome (TAC) clones extending over all Arabidopsis thaliana (Arabidopsis) chromosomes. The Arabidopsis genomic TAC clones have been valuable genetic tools. Previously, we constructed an Arabidopsis genomic TAC library consisting of more than 10,000 TAC clones harboring large genomic DNA fragments extending over the whole Arabidopsis genome. Here, we determined 13,577 end sequences from 6987 Arabidopsis TAC clones and mapped 5937 TAC clones to precise locations, covering approximately 90% of the Arabidopsis chromosomes. We present the large-scale data set of TAC clones with high-resolution mapping information as a Java application tool, the Arabidopsis TAC Position Viewer, which provides ready-to-go transformable genomic DNA clones corresponding to certain loci on Arabidopsis chromosomes. The TAC clone resources will accelerate genomic DNA cloning, positional walking, complementation of mutants and DNA transformation for heterologous gene expression.

Pleurochrysome: A Web Database of Pleurochrysis Transcripts and Orthologs Among Heterogeneous Algae.

Pleurochrysis is a coccolithophorid genus, which belongs to the Coccolithales in the Haptophyta. The genus has been used extensively for biological research, together with Emiliania in the Isochrysidales, to understand distinctive features between the two coccolithophorid-including orders. However, molecular biological research on Pleurochrysis such as elucidation of the molecular mechanism behind coccolith formation has not made great progress at least in part because of lack of comprehensive gene information. To provide such information to the research community, we built an open web database, the Pleurochrysome (http://bioinf.mind.meiji.ac.jp/phapt/), which currently stores 9,023 unique gene sequences (designated as UNIGENEs) assembled from expressed sequence tag sequences of P. haptonemofera as core information. The UNIGENEs were annotated with gene sequences sharing significant homology, conserved domains, Gene Ontology, KEGG Orthology, predicted subcellular localization, open reading frames and orthologous relationship with genes of 10 other algal species, a cyanobacterium and the yeast Saccharomyces cerevisiae. This sequence and annotation information can be easily accessed via several search functions. Besides fundamental functions such as BLAST and keyword searches, this database also offers search functions to explore orthologous genes in the 12 organisms and to seek novel genes. The Pleurochrysome will promote molecular biological and phylogenetic research on coccolithophorids and other haptophytes by helping scientists mine data from the primary transcriptome of P. haptonemofera.

Double-balloon Enteroscopy for Pediatric Patients: Evaluation of Safety and Efficacy in 257 Cases.

OBJECTIVES: The safety and efficacy of double-balloon enteroscopy (DBE) in pediatric patients has not been well documented. We aimed to evaluate the clinical efficacy and safety of DBE in children, especially those under 10. METHODS: We retrospectively analyzed our database of DBE procedures performed between September 2000 and September 2013. Procedures performed in pediatric patients (under 18) were selected from a total of 3980, including double-balloon endoscopic retrograde cholangioscopy (DBERC). RESULTS: Two hundred fifty-seven DBE procedures were performed in 117 pediatric patients (median age 12.5 years). Antegrade (oral-route) DBE was performed in 166 procedures including 104 DBERC procedures (lowest body weight 13.5 kg, youngest age 3 years), and retrograde (anal-route) DBE in 91 (lowest body weight 12.0 kg, youngest age 2 years). The overall diagnostic yield for obscure gastrointestinal bleeding and abdominal pain was 58.8%. The purpose of DBERC was achieved in 76.9% of procedures. The overall complication rate in our series was 5.4% (1.9% with the DBERC cases removed); in patients under 10, it was 10.4% (7/67). No severe complications associated with enteroscope insertion and sedation were observed. Serum amylase levels tended to be elevated in patients who underwent oral-route DBE. CONCLUSIONS: DBE is safe and feasible for diagnostic evaluation of small bowel disorders in pediatric patients, even those younger than 10 years. Special attention for possible complications must, however, be paid during therapeutic DBE procedures, including DBERC, especially for patients under 10.

Functional dyspepsia and irritable bowel syndrome in teenagers: Internet survey.

BACKGROUND: Only a handful of studies have investigated children with functional dyspepsia (FD) and irritable bowel syndrome (IBS) classified according to the Rome III criteria, and limited information is available on the lifestyle of affected patients. METHODS: We conducted an Internet questionnaire survey of 2060 parents among the general public in Japan who lived with their children aged 10-15, who were screened for FD and IBS. RESULTS: The prevalence of FD and IBS was 2.8% and 6.1%, respectively, and 1.4% of the subjects met the criteria for both FD and IBS. The lifestyles of 155 subjects who met the criteria for FD, IBS, or both were compared with those of 1745 control subjects. In comparison with the controls, a significantly higher percentage of subjects with FD, IBS, or both thought that their sleep was insufficient, ate meals irregularly, were susceptible to stress and to dizziness on standing, had difficulty in getting out of bed or felt sluggish in the morning, had a tendency to faint when standing, and had migraine/chronic headache. CONCLUSIONS: Children with FD and IBS are susceptible to stress, have impaired sleep and eating habits, and have more frequent symptoms of comorbid orthostatic dysregulation and headache.

Eosinophilic enteritis due to cow's milk allergy: Possible cause of anastomosis failure following repair of focal intestinal perforation.

Reports of cow's milk allergy (CMA) after neonatal gastrointestinal surgery have recently increased. In recent years it has been suggested that the development of CMA after gastrointestinal surgery in newborn infants is due to an immune function. In addition, the development of CMA might be synergistically exacerbated by congenital abnormalities of the intestinal mucosa, general conditional changes and local damage to the intestine by invasive surgery, and poor pre- or post-surgical nutrition. CMA manifests as a variety of symptoms, such as mild vomiting and bloody stool, decreased activity, poor oral intake, and ileus. CMA may also rarely cause gastrointestinal perforation. Here, we report the case of a newborn infant who developed CMA following repair of focal small intestinal perforation, in which eosinophilic enteritis was suspected to be a possible cause of anastomosis leakage.

Plant Omics Data Center: an integrated web repository for interspecies gene expression networks with NLP-based curation.

Comprehensive integration of large-scale omics resources such as genomes, transcriptomes and metabolomes will provide deeper insights into broader aspects of molecular biology. For better understanding of plant biology, we aim to construct a next-generation sequencing (NGS)-derived gene expression network (GEN) repository for a broad range of plant species. So far we have incorporated information about 745 high-quality mRNA sequencing (mRNA-Seq) samples from eight plant species (Arabidopsis thaliana, Oryza sativa, Solanum lycopersicum, Sorghum bicolor, Vitis vinifera, Solanum tuberosum, Medicago truncatula and Glycine max) from the public short read archive, digitally profiled the entire set of gene expression profiles, and drawn GENs by using correspondence analysis (CA) to take advantage of gene expression similarities. In order to understand the evolutionary significance of the GENs from multiple species, they were linked according to the orthology of each node (gene) among species. In addition to other gene expression information, functional annotation of the genes will facilitate biological comprehension. Currently we are improving the given gene annotations with natural language processing (NLP) techniques and manual curation. Here we introduce the current status of our analyses and the web database, PODC (Plant Omics Data Center; http://bioinf.mind.meiji.ac.jp/podc/), now open to the public, providing GENs, functional annotations and additional comprehensive omics resources.