Effect of water glass treatment for zirconia and silane coupling on bond strength of resin cement.

OBJECTIVE: To evaluate the ability of the water glass treatment to penetrate zirconia and improve the bond strength of resin cement. MATERIAL AND METHODS: Water glass was applied to zirconia specimens, which were then sintered. The specimens were divided into water-glass-treated and untreated zirconia (control) groups. The surface properties of the water-glass-treated specimens were evaluated using surface roughness and electron probe micro-analyser (EPMA) analysis. A resin cement was used to evaluate the tensile bond strength, with2 and without a silane-containing primer. After 24 h in water storage at 37 °C and thermal cycling, the bond strengths were statistically evaluated with t-test, and the fracture surfaces were observed using SEM. RESULTS: The water glass treatment slightly increased the surface roughness of the zirconia specimens, and the EPMA analysis detected the water glass penetration to be 50 µm below the zirconia surface. The application of primer improved the tensile bond strength in all groups. After 24 h, the water-glass-treated zirconia exhibited a tensile strength of 24.8 ± 5.5 MPa, which was significantly higher than that of the control zirconia (17.6 ± 3.5 MPa) (p < 0.05). After thermal cycling, the water-glass-treated zirconia showed significantly higher tensile strength than the control zirconia. The fracture surface morphology was mainly an adhesive pattern, whereas resin cement residue was occasionally detected on the water-glass-treated zirconia surfaces. CONCLUSION: The water glass treatment resulted in the formation of a stable silica phase on the zirconia surface. This process enabled silane coupling to the zirconia and improved the adhesion of the resin cement.

Upper gastrointestinal involvement of Behçet's disease in Japan: endoscopic findings and clinical features.

AIM: Behçet's disease (BD) can involve any gastrointestinal (GI) tract site. We analyzed the characteristics, risk factors, and treatment responses to upper GI (UGI) involvement in patients with BD. METHODS: This retrospective cohort study analyzed UGI findings in 101 patients with BD who underwent endoscopy between April 2005 and December 2022 at the University of Tokyo Hospital. The patients were divided into two groups based on the presence or absence of UGI findings. Patient backgrounds, clinical symptoms, colonoscopy (CS) findings, and blood test findings were compared between the groups. RESULTS: In total, 18.8% (19/101) of the patients had UGI lesions. The prevalence rates in the esophagus, stomach, and duodenum were 6.9%, 6.9%, and 8.9%, respectively. Of these 19 patients, BD treatment were intensified in 10 (52.6%) patients after esophagogastroduodenoscopy (EGD), and all showed improvement in symptoms or endoscopic findings. In the multivariate analysis, symptoms (OR: 37.1, P < 0.001), CRP > 1 mg/dL (OR: 11.0, P = 0.01), and CS findings (OR: 5.16, P = 0.04) were independent predictors of UGI involvement in BD patients. The prediction model for UGI involvement using these three factors was highly accurate, with an AUC of 0.899 on the ROC curve. In the subgroup analysis of intestinal BD, symptoms (OR: 12.8, P = 0.01) and ESR > 20 mm/h (OR: 11.5, P = 0.007) were independent predictors. CONCLUSIONS: EGD should be conducted in BD patients with high CRP, GI symptoms, and lower GI involvement, which leads to better management of BD in terms of improving symptoms and endoscopic findings.

Objective evaluation of tooth carving using homologous models.

PURPOSE/OBJECTIVES: Tooth carvings are evaluated subjectively. However, subjective evaluations are associated with low intra- and inter-evaluator reliability in providing feedback for the fabrication of better tooth carvings. Therefore, this study aimed to analyze the relationship between subjective evaluation and the morphological characteristics of tooth carvings and their morphological characteristics using the feedback method in the low-scoring group. METHODS: Between April 2013 and September 2021, 120 maxillary left first molar carvings fabricated by undergraduate students were subjectively evaluated by an experienced instructor using a five-point scale. The tooth carvings were scanned to obtain three-dimensional shape data and divided into two groups, the high- and low-scoring groups, for principal component analysis. Homologous models with dimensions matching those of the average model were created, and principal component analysis was performed to evaluate the morphological characteristics of the tooth. RESULTS: Principal component analysis indicated that an objective evaluation was possible using homologous model. On increasing the subjective evaluation, the occlusal inclination angle and the cervical region of the tooth became steeper, and the shape of the occlusal surface resembled a parallelogram. In addition, large morphological differences were observed in the position of the cervical region of the tooth, height of contour, and shape of the occlusal surface in the low-scoring group, whereas no such difference was observed in the high-scoring group. CONCLUSION: Objective evaluation of tooth carving was possible using homologous model. The evaluation of tooth morphological characteristics could be effective in providing feedback to undergraduate students.

Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases.

OBJECTIVES: Despite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalogue of five B cell subsets of patients with IMDs. METHODS: We mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under IMDs and health. We characterised the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment. RESULTS: Heavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed in naïve B cells and suggested the role for interferon in premature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE). We developed a scoring system to quantify this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extrafollicular pathway. Further, this skewing led to high usage of IGHV4-34 gene with 9G4 idiotypes in unswitched-memory B cells, which showed a prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment. CONCLUSIONS: Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.

Role of autotaxin in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the production of various autoantibodies and deposition of immune complexes. SLE is a heterogenous disease, and the pattern of organ involvement and response to treatment differs significantly among patients. Novel biological markers are necessary to assess the extent of organ involvement and predict treatment response in SLE. Lysophosphatidic acid is a lysophospholipid involved in various biological processes, and autotaxin (ATX), which catalyzes the production of lysophosphatidic acid in the extracellular space, has gained attention in various diseases as a potential biomarker. The concentration of ATX is increased in the serum and urine of patients with SLE and lupus nephritis. Recent evidence suggests that ATX produced by plasmacytoid dendritic cells may play an important role in the immune system and pathogenesis of SLE. Furthermore, the production of ATX is associated with type I interferons, a key cytokine in SLE pathogenesis, and ATX may be a potential biomarker and key molecule in SLE.

Effects of build orientation and bar addition on accuracy of complete denture base fabricated with digital light projection: An in vitro study.

PURPOSE: We evaluated the effects of build orientation and bar addition between lingual flanges on the accuracy of mandibular denture bases fabricated using a digital light processing (DLP) device. METHODS: Mandibular denture bases with and without a bar at the lingual flanges were virtually designed and assigned to eight build orientations. Six dentures per condition were fabricated using a DLP device with a methacrylate-based photopolymerizable monomer (Dima Print denture base) (n=96). The fabricated denture surfaces were digitized, and intaglio surfaces were obtained. These digitized surfaces were compared via superimposition using graphical software (Artec studio12 profession) to their original designed files, and root mean square estimates were obtained. The trueness of the entire and intaglio data was statistically analyzed non-parametrically. RESULTS: The range of trueness of the entire and intaglio denture bases was 0.15-0.31 mm and 0.11-0.38 mm, respectively. The trueness at 135° and 270° for the entire denture base and that at 270° for the intaglio data without the bar were significantly lower than those for the other build orientations. The trueness at 270° was <0.15 mm irrespective of the conditions. The trueness with the bar of all build orientations, except that of 0° for intaglio data, was significantly smaller than or equal to the trueness without the bar of the corresponding build orientations. CONCLUSIONS: Build orientation and bar addition influenced the accuracy of the complete dentures fabricated using DLP. A build orientation of 270° is recommended for fabricating a mandibular complete denture, irrespective of the bar addition.

An in vitro study of digital impressions and three-dimensional printed models of orbital defects using mobile devices and monoscopic photogrammetry.

PURPOSE: The purpose of this study was to perform an in vitro evaluation of digital impressions using a mobile device and monoscopic photogrammetry in cases of orbital defects with undercuts. METHODS: Three 10-mm-square cubes were attached to a diagnostic cast of a patient with a right orbital defect. Still images acquired with a mobile device were used to generate facial three-dimensional (3D) data. Two types of still images were used: one was a whole face image, and the other was a defect site-focused image. For comparison, an extraoral scanner was used to obtain facial 3D data. Five dental technicians fabricated 3D printed models using additive manufacturing and measured the distances between the measurement points using a digital caliper. The discrepancy between the distances measured on the diagnostic cast of the patient and the 3D printed model was calculated. Friedman test was used to analyze the discrepancy, and the Bonferroni test was used to verify the differences between the pairs. RESULTS: Statistical significance was found with respect to the type of 3D model fabrication method. CONCLUSION: Within the limitations of this in vitro study, the results suggested that the workflow can be applied to digital impressions of the maxillofacial region.

Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance.

OBJECTIVES: Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance. METHODS: We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis. RESULTS: Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s. CONCLUSIONS: An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response.

Transcriptome Profiling of Immune Cell Types in Peripheral Blood Reveals Common and Specific Pathways Involved in the Pathogenesis of Myositis-Specific Antibody-Positive Inflammatory Myopathies.

OBJECTIVE: Idiopathic inflammatory myopathies (IIM) demonstrate characteristic clinical phenotypes depending on the myositis-specific antibody (MSAs) present. We aimed to identify common or MSA-specific immunological pathways in different immune cell types from peripheral blood by transcriptome analysis. METHODS: We recruited 33 patients with IIM who were separated into the following groups: 15 patients with active disease at onset and 18 with inactive disease under treatment. All patients were positive for MSAs: anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in 10 patients, anti-Mi-2 Ab in 7, and anti-aminoacyl-transfer RNA synthetase (ARS) Ab in 16. The patients were compared with 33 healthy controls. Twenty-four immune cell types sorted from peripheral blood were analyzed by flow cytometry, RNA sequencing, and differentially expressed gene analysis combined with pathway analysis. RESULTS: The frequencies of memory B cell types were significantly decreased in active patients, and the frequency of plasmablasts was prominently increased in active patients with anti-MDA5 Ab in comparison with healthy controls. The expression of type I interferon (IFN)-stimulated genes of all immune cell types was increased in the active, but not inactive, patients. Endoplasmic reticulum stress-related genes in all IIM memory B cells and oxidative phosphorylation-related genes in inactive IIM double negative B cells were also increased, suggesting prominent B cell activation in IIM. Furthermore, active patients with anti-MDA5 Ab, anti-Mi-2 Ab, or anti-ARS Ab were distinguished by IFN-stimulated and oxidative phosphorylation-related gene expression in plasmablasts. CONCLUSION: Unique gene expression patterns in patients with IIM with different disease activity levels and MSA types suggest different pathophysiologies. Especially, B cells may contribute to common and MSA-specific immunological pathways in IIM.

Comparison of the accuracy of different handheld-type scanners in three-dimensional facial image recognition.

PURPOSE: Handheld-type scanners are widely used in clinical practice. This study examined the accuracy of handheld-type scanners using plaster statues to assess their performance in facial recognition. METHODS: Twelve 4-mm zirconia balls as measuring points were attached to the facial portions of three types of plaster statue. Six digital facial images of each plaster statue were obtained using one of the following five handheld-type scanners: Artec Eva, Artec Spider, Bellus 3D FaceApp, SNAP, and Vectra H1. Four-millimeter spherical objects were manually placed at the measurement points on the scanned data generated using computer-aided design software and coordinate positions were measured using a contact-type high-resolution three-dimensional measurement device. Consequently, the discrepancy between the distance measured using the contact-type device and that measured using the handheld-type scanner was calculated. The scanning time, processing time, and deviation of the distance between the measuring points were analyzed using two-way analysis of variance and t-test with Bonferroni correction. RESULTS: The scanning and processing times ranged from 15.2 to 42.2 s and 20.7 to 234.2 s, respectively. Overall, 97% of all measured distances by Spider were within ±1.00% deviation; 79%, Vectra; 73%, Eva; 70%, Bellus; and 42%, SNAP. CONCLUSIONS: The performance of handheld-type scanners using plaster statues varied among the different scanners. The scanning time of Eva and the processing time of Bellus were significantly shorter than those of other scanners. Furthermore, Spider exhibited the best accuracy, followed by Eva, Vectra, Bellus, and SNAP.

Wear behavior of materials for additive manufacturing after simulated occlusion of deciduous dentition.

OBJECTIVES: To evaluate wear characteristics of materials for additive manufacturing (AM) after a simulated occlusal test in primary teeth. Wear was simulated by means of impacting - sliding wear testing (ISWT) between specimens prepared from materials for AM against enamel derived from deciduous teeth. METHODS: The prepared hemispherical upper specimens were subjected to impacting-sliding wear test (ISWT) machine against the flattened enamel of deciduous molars on lower specimens. The samples were subjected to 20,000 load cycles using a contact force of 30 N between the opposing surfaces under controlled conditions. In the upper specimens, five groups (n=9): four types of additively manufactured materials Dima, Zenith, Detax, Veltz and a deciduous enamel groups were tested in this study. The enamel-to-enamel group was used as the control. Wear characteristics comprised wear surface area, wear depth, wear volumetric loss, and surface roughness were measured with a confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Data obtained were statistically analyzed by Kruskal-Wallis test and Dunn's test with Bonferroni correction (p < 0.05). RESULTS: Dima showed significantly higher worn surface area (p = 0.009, 0.001, and < 0.001 for Zenith, Detax, and control enamel, respectively), volumetric loss (p = 0.027, 0.007, and < 0.001 for Zenith, Detax, and control enamel, respectively), and damaged opposing enamel (p = 0.002, 0.001, and 0.01 for Detax, Veltz, and control enamel, respectively). There was no significant difference among the volumetric loss in Zenith and Detax. However, SEM revealed that Zenith showed rough worn surfaces and chipping, Detax showed rather a smooth circular worn surface. The worn area of Veltz was smaller than Detax and Zenith at 5,000 cycles, but higher at 15,000 and 20,000 cycles, and SEM showed detachment. CONCLUSION: Wear behavior was different among different materials for AM. In the upper specimens, DM and VZ showed large wear. In the lower specimens, DM caused largest enamel wear and damage. In contrast, ZT and DX showed lower wear and caused less damage to the antagonistic primary enamel. SEM image of ZT showed large losses due to chipping, whereas DX showed the rather smooth. DX was confirmed to have lowest wear and caused least damage to the opposing deciduous enamel, which might be applicable as restorative treatments in deciduous dentition. SIGNIFICANCE: Additive manufactured dental materials could be considered as a treatment modality in deciduous teeth.

Discoloration of fiber-reinforced composite resin disc for computer-aided design/computer-aided manufacturing after immersion in coffee and curry solutions.

The purpose of this study was to clarify the discoloration of fiber-reinforced composite resin (FRC) disc materials. The color differences (ΔEs) of three CAD/CAM disc materials, FRC with different fiber orientations, composite resin, and polyether-ether-ketones were evaluated after month-long immersion in water, coffee, and curry. The ΔEs of all materials after coffee and curry immersion increased with increasing immersion periods, while those after water immersion barely increased. FRC exhibited a smaller color difference and water sorption value than composite resin and a greater color difference and water sorption value than polyether-ether-ketones. The ΔEs after coffee immersion were significantly correlated with the water sorption value. The ΔE of FRC with fiber orientations perpendicular to the surface was greater than that of FRC with fiber orientations parallel to the surface, likely due to greater exposure of the matrix-fiber interface. This result suggested that the fiber orientations of FRC affected the discoloration.

Serum extracellular traps associate with the activation of myeloid cells in SLE patients with the low level of anti-DNA antibodies.

Neutrophil extracellular traps (NETs) are involved in systemic lupus erythematosus (SLE). We sought to cluster SLE patients based on serum NET levels. Serum NET levels were higher in SLE patients than healthy controls. Frequencies of pleuritis and myositis were increased in patients with high serum NET levels. Serum NET levels negatively correlated with anti-double stranded DNA (anti-dsDNA) antibody titers and C1q-binding immune complexes, but positively correlated with C-reactive protein (CRP) and monocyte counts. Neutrophil transcriptome analysis demonstrated no difference in NET-associated signatures, irrespective of serum NET levels, suggesting anti-dsDNA antibody-mediated clearance of NETs. In serum, NET levels were significantly correlated with myeloid cell-derived inflammatory molecules. Serum NET-based cluster analysis revealed 3 groups of patients based on serum NET and CRP levels, anti-dsDNA antibody titers, and monocyte count. Monocytes were consistently activated following NET-containing immune complex (NET-IC) stimulation. In conclusion, SLE patients with high serum NET levels had lower anti-dsDNA antibody titers and higher inflammatory responses. NET-IC-stimulated monocytes might associate with an inflammatory response characterized by elevated CRP levels. These findings can apply to precision medicine, as inflammatory processes, rather than antibody-dependent processes, can be targeted in specific subpopulations of SLE patients.

Autotaxin is a potential link between genetic risk factors and immunological disturbances of plasmacytoid dendritic cells in systematic lupus erythematosus.

BACKGROUND: The importance of autotaxin, an enzyme that catalyzes lysophospholipid production, has recently been recognized in various diseases, including cancer and autoimmune diseases. Herein, we examined the role of autotaxin in systemic lupus erythematosus (SLE), utilizing data from ImmuNexUT, a comprehensive database consisting of transcriptome data and expression quantitative trait locus (eQTL) data of immune cells from patients with immune-mediated disorders. METHODS: Serum autotaxin concentrations in patients with SLE and healthy controls (HCs) were compared. The transcriptome data of patients with SLE and age- and sex-matched HCs were obtained from ImmuNexUT. The expression of ENPP2, the gene encoding autotaxin, was examined in peripheral blood immune cells. Next, weighted gene correlation network analysis (WGCNA) was performed to identify genes with expression patterns similar to ENPP2. The ImmuNexUT eQTL database and public epigenomic databases were used to infer the relationship between autotaxin and pathogenesis of SLE. RESULTS: Autotaxin levels were elevated in the serum of patients with SLE compared to HCs. Furthermore, the expression of ENPP2 was higher in plasmacytoid dendritic cells (pDCs) than in other immune cell subsets, and its expression was elevated in pDCs of patients with SLE compared to HCs. In WGCNA, ENPP2 belonged to a module that correlated with disease activity. This module was enriched in interferon-associated genes and included genes whose expression was influenced by single-nucleotide polymorphisms associated with SLE, suggesting that it is a key module connecting genetic risk factors of SLE with disease pathogenesis. Analysis utilizing the ImmuNexUT eQTL database and public epigenomic databases suggested that the increased expression of ENPP2 in pDCs from patients with SLE may be caused by increased expression of interferon-associated genes and increased binding of STAT3 complexes to the regulatory region of ENPP2. CONCLUSIONS: Autotaxin may play a critical role in connecting genetic risk factors of SLE to disease pathogenesis in pDCs.

Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles.

OBJECTIVE: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets. METHODS: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls. RESULTS: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling. CONCLUSION: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.

Splicing QTL analysis focusing on coding sequences reveals mechanisms for disease susceptibility loci.

Splicing quantitative trait loci (sQTLs) are one of the major causal mechanisms in genome-wide association study (GWAS) loci, but their role in disease pathogenesis is poorly understood. One reason is the complexity of alternative splicing events producing many unknown isoforms. Here, we propose two approaches, namely integration and selection, for this complexity by focusing on protein-structure of isoforms. First, we integrate isoforms with the same coding sequence (CDS) and identify 369-601 integrated-isoform ratio QTLs (i2-rQTLs), which altered protein-structure, in six immune subsets. Second, we select CDS incomplete isoforms annotated in GENCODE and identify 175-337 isoform-ratio QTL (i-rQTL). By comprehensive long-read capture RNA-sequencing among these incomplete isoforms, we reveal 29 full-length isoforms with unannotated CDSs associated with GWAS traits. Furthermore, we show that disease-causal sQTL genes can be identified by evaluating their trans-eQTL effects. Our approaches highlight the understudied role of protein-altering sQTLs and are broadly applicable to other tissues and diseases.

Transcriptome analysis of immune cells from Behçet's syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet's syndrome.

BACKGROUND: Behçet's syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationship to genetic risk factors still remain unclear. To address these points, we performed immunophenotyping and transcriptome analysis of immune cells from BS patients and healthy donors. METHODS: ImmuNexUT is a comprehensive database consisting of RNA sequencing data and eQTL database of immune cell subsets from patients with immune-mediated diseases and healthy donors, and flow cytometry data and transcriptome data from 23 BS patients and 28 healthy donors from the ImmuNexUT study were utilized for this study. Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify genes associated with BS and clinical features of BS. eQTL database was used to assess the relationship between genetic risk factors of BS with those genes. RESULTS: The frequency of Th17 cells was increased in BS patients, and transcriptome analysis of Th17 cells suggested the activation of the NFκB pathway in Th17 cells of BS patients. Next, WGCNA was used to group genes into modules with similar expression patterns in each subset. Modules of antigen-presenting cells were associated with BS, and pathway analysis suggested the activation of antigen-presenting cells of BS patients. Further examination of genes in BS-associated modules indicated that the expression of YBX3, a member of a plasmacytoid dendritic cell (pDC) gene module associated with BS, is influenced by a BS risk polymorphism, rs2617170, in pDCs, suggesting that YBX3 may be a key molecule connecting genetic risk factors of BS with disease pathogenesis. Furthermore, pathway analysis of modules associated with HLA-B51 indicated that the association of IL-17-associated pathways in memory CD8+ T cells with HLA-B51; therefore, IL-17-producing CD8+ T cells, Tc17 cells, may play a critical role in BS. CONCLUSIONS: Various cells including CD4+ T cells, CD8+ T cells, and antigen-presenting cells are important in the pathogenesis of BS. Tc17 cells and YBX3 may be potential therapeutic targets in BS.

Rheumatoid arthritis in a patient with compound heterozygous variants in the COL11A2 gene and progressive hearing loss: A case report.

RATIONALE: Collagen type XI alpha 2 chain is a component of type XI collagen and is expressed in various tissues including articular cartilage and tectorial membrane of the cochlea. Variants in the COL11A2 gene, which encodes collagen type XI alpha 2 chain, has been reported to cause hearing loss and has been associated with osteoarthritis and ossification of the posterior longitudinal ligament of the spine. Despite the importance of type XI collagen in the joints, association of rheumatoid arthritis (RA) with COL11A2 has not been reported. PATIENT CONCERNS: The patient is a 60-year-old female, born to Japanese parents of no known consanguinity. She had progressive hearing loss since childhood. Her father also had progressive hearing loss before middle age. She developed joint pain in the knees and the hips in her forties. When she was 56, she developed polyarthritis. Rheumatoid factor and anti-CCP antibodies were positive. DIAGNOSES: She was diagnosed with osteoarthritis and RA. Whole exome analysis detected 2 rare variants, c.4201C>T, p.(Arg1401Trp) and c4265C>T, p.(Pro1422Leu), in the COL11A2 gene (NM_080680.2). Whole genome analysis with a long insert size confirmed 2 variants that are in trans. INTERVENTIONS AND OUTCOMES: She received a cochlear implant, which improved her hearing. She was treated with methotrexate, golimumab, tocilizumab, and upadacitinib with partial responses for her RA. LESSONS: We herein report a patient with RA with compound heterozygous variants in the COL11A2 gene. Autoantibodies against type XI collagen are detected in the sera of patients with RA, suggesting the possibility that type XI collagen may be involved in the pathogenesis of RA as an autoantigen. The hearing loss and osteoarthritis in this patient may be due to the compound heterozygous variants in the COL11A2 gene, and the conformational changes induced by the variants may have changed the immunogenicity of type XI collagen, leading to the development of RA.

Effect of thickness on color appearance of multilayer CAD/CAM composite resin blocks.

The aim of this study was to evaluate the effect of thickness on the color appearance and translucency parameter (TP) of multilayer CAD/CAM composite resin blocks. Four brands of A3-shade multilayer CAD/CAM composite resin blocks were examined (Katana Avencia, CERASMART Multi, KZR-CAD HR Block 4 E-va, and Block HC Hard AN). Six specimens of five thicknesses were prepared for each brand, yielding 120 specimens in total. CIEL*a*b* values were determined using a spectrophotometer against black and white backgrounds, and the TP was calculated. The color differences (ΔE00) between layers (cervical/middle/incisal) and brands for each thickness against the black background were calculated using the CIEDE2000 system. As a result, on the black background, L* of the incisal layer was greater while a* and b* were smaller than those of the cervical layer for all brands. The ΔE00 values between the cervical and middle layers (1.23-3.27) were smaller than those between the cervical and incisal layers (3.98-5.67) and those between the middle and incisal layers (3.14-5.92). TP decreased with increasing block thickness. Some TP differences between layers were significant, but they were less than 2.75. In conclusion, the color appearance of CAD/CAM blocks was significantly influenced by both the thickness and layer. L*a*b* decreased with thickness, and a negative exponential relationship between TP and thickness was observed for all layers and brands.