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The current study's objective was to elucidate some currently unknown biological indicators to evaluate the biological nature of cancer-associated fibroblasts (CAFs). For this purpose, four different CAFs, CAFS1, CAFS2, SCC17F and MO-1000, were established using surgical specimens from oral squamous cell carcinomas (OSCC) with different clinical malignant stages (CAFS1 and CAFS2, T2N0M0, stage II; SCC17F and MO-1000, T4aN2bM0, stage IVA). Fibroblasts unrelated to cancer (non-CAFs) were also prepared and used as controls. Initially, confirmation that these four fibroblasts were indeed CAFs was obtained by their mRNA expression using positive and negative markers for the CAF or fibroblasts. To elucidate possible unknown biological indicators, these fibroblasts were subjected to a cellular metabolic analysis by a Seahorse bioanalyzer, in conjugation with 3D spheroid cultures of the cells and co-cultures with a pancreas ductal carcinoma cell line, MIA PaCa-2. The mitochondrial and glycolytic functions of human orbital fibroblasts (HOF) were nearly identical to those of Graves'-disease-related HOF (GOF). In contrast, the characteristics of the metabolic functions of these four CAFs were different from those of human conjunctival fibroblasts (HconF), a representative non-CAF. It is particularly noteworthy that CAFS1 and CAFS2 showed markedly reduced ratios for the rate of oxygen consumption to the extracellular acidification rate, suggesting that glycolysis was enhanced compared to mitochondrial respiration. Similarly, the physical aspects, their appearance and stiffness, of their 3D spheroids and fibroblasts that were induced effects based on the cellular metabolic functions of MIA PaCa-2 were also different between CAFs and non-CAFs, and their levels for CAFS1 or SCC17F were similar to those for CAFS2 or MO-1000 cells, respectively. The findings reported herein indicate that cellular metabolic functions and the physical characteristics of these types of 3D spheroids may be valuable and useful indicators for estimating potential biological diversity among various CAFs. [ABSTRACT FROM AUTHOR]

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The cartilage-conduction hearing aid (CC-HA) is a new hearing device that is suitable for use in patients with conductive hearing loss. It has been 5 years since the introduction of the CC-HA. Although the number of users has increased, the CC-HA is not yet widely known. This study examines the effects of CC-HA on patients with conductive hearing loss and investigates factors that affect the willingness to use the device by comparing purchasers and non-purchasers of CC-HA in patients with unilateral conductive hearing loss. Eight patients had bilateral conductive hearing loss, and 35 had unilateral conductive hearing loss. Each patient underwent sound field tests and speech audiometry, and the effects of the CC-HA were compared with those of conventional bone conduction hearing aids (BC-HA). In patients with bilateral conductive hearing loss, the CC-HA was non-inferior to BC-HA. The CC-HA improved the hearing thresholds and speech recognition in patients with unilateral conductive hearing loss. Moreover, in patients with unilateral conductive hearing loss, experiencing the effect of wearing the CC-HA under conditions such as putting noise in the better ear could affect patients' willingness to use the CC-HA. [ABSTRACT FROM AUTHOR]

Background: The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. Methods: Publicly available single‐cell RNA‐sequencing (RNA‐seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α‐smooth muscle antigen (α‐SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co‐cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse‐transcription PCR. Results: Analysis of the RNA‐seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12‐positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α‐SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co‐cultured with OSCC cells. Conclusion: Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction. [ABSTRACT FROM AUTHOR]

Tubarial glands (TGs) are a collection of unidentified salivary glands overlying the torus tubarius in the nasopharyngeal wall. Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibroinflammatory state that often has multiple organ involvement. Involvement of the head and neck, especially the salivary glands, is common in IgG4-RD. This study aimed to elucidate the clinical significance of TGs in IgG4-RD. We investigated the local findings of TGs in ten patients with IgG4-RD. Nasopharyngeal endoscopic examination revealed oedematous swelling of the nasopharyngeal wall surrounding the TGs, which improved after steroid treatment. Moreover, sonotubometry showed a stenotic pattern in three out of seven patients with IgG4-RD. TGs may be involved in IgG4-RD. The swollen TGs may be responsible for obstructive Eustachian tube dysfunction. Further studies are required to clarify the clinical significance and physiological roles of TGs in IgG4-RD. [ABSTRACT FROM AUTHOR]

Simple Summary: The p53 family p63 gene is essential for the proliferation and differentiation of various epithelial cells, and it is overexpressed in some salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways inhibited cell proliferation and migration, induced tight junctions, and promoted differentiation in p63-positive salivary duct adenocarcinoma (SDC). It is, therefore, useful in therapy for p63-positive SDC cells. Background: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. Methods: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). Results: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. Conclusions: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells. [ABSTRACT FROM AUTHOR]

The performance of two types of trailing shield perpendicular writers with either double coil or single coil are investigated. It has been found that signal-to-noise ratio (SNR) performance of different designs strongly depends on the tradeoff of field gradient and writability. Reverse DC noise analysis is used to understand the recording properties of head and media quantitatively. To realize the performance advantages of the single coil design and to suppress the trailing shield erasure, a novel single coil structure with double write gap is proposed. Index Terms--Adjacent track erasure, DC noise, perpendicular magnetic recording, trailing shield.

This paper presents micromagnetic modeling results in a perpendicular magnetic recording, which consists of a single-pole head and double-layered media. To know the inplane head field contribution, the relationship between applied angular field and media remanence is studied, and we propose a perpendicular corresponding field for the head field assessment, which can explain media remanence as well such as the main-pole footprint on the media. The shielded-pole/single-coil head shows the best signal-to-noise ratio but the overwrite performance is somewhat poorer than monopole heads, with a large positive to negative head field, which implies a large field gradient. Although the shielded-pole head has smaller erase bands with straight transitions, it can cause trailing-shield-related erasure by the negative field under the high write current input in the single-coil design. Index Terms--Magnetic recording head, micromagnetic modeling, parallel finite-element method, perpendicular magnetic recording.

We investigated the relationship between head design, pole-tip magnetization, head field, and media magnetization in longitudinal recording. At first we estimate the effective switching field of current mobile media with isotropic anisotropy, and introduce longitudinal corresponding field for the head field assessment. The smaller perpendicular component or large perpendicular field gradient of the head field at the upper pole improves the transition quality, but the small perpendicular field degrades the overwrite performance. So the ideal head field is large longitudinal and perpendicular field for good overwrite and fast attenuation with the large perpendicular field gradient for the transition quality. Some head designs make it possible to control the ratio of the perpendicular component to the longitudinal head field, by changing the pole-tip magnetization direction. As a project to control it, we discuss the effect of the bottom and upper poles configuration on the transition, overwrite, and adjacent track erasure in longitudinal recording. Index Terms--Finite-element method, head field, magnetization reversal, micromagnetic modeling.

We have developed a micromagnetic finite-element method (FEM) to treat a whole write head structure as a micromagnetic model, and it is utilized to study the magnetization dynamics and head field of a planar writer. As the head has a domain structure, the leakage field differs from what is calculated by a conventional FEM except for the gap region, and it can induce some adjacent track erasure (ATE) problems in the case of high write currents. This leakage field comes from the shoulder of the bottom yoke pedestal and the sidewall of the upper pole. A conventional FEM for electromagnetic eddy-current field does not show much time delay of the head field rise in core sizes of 10 [micro]m or below. On the other hand, the head field cannot follow the write current waveform perfectly, and shows time delay by the micromagnetic FEM analysis. This indicates that the delay mainly no longer comes from eddy-current effects but magnetization dynamics of the gyromagnetic precession, damping, and flux conduction. Furthermore, the head field rise time is affected by the damping constant, material, yoke length, and pole-tip dimension. Index Terms--FEM for electromagnetic field, field rise time, micromagnetic modeling, write head field.

Airway and intestinal epithelial permeability barriers are crucial in epithelial homeostasis. High mobility group box 1 (HMGB1), increased by various stimuli, is involved in the induction of airway inflammation, as well as the pathogenesis of inflammatory bowel disease. HMGB1 enhances epithelial hyperpermeability. Two-and-a-half dimensional (2.5D) culture assays are experimentally convenient and induce cells to form a more physiological tissue architecture than 2D culture assays for molecular transfer mechanism analysis. In 2.5D culture, treatment with HMGB1 induced permeability of FITC-dextran into the lumen formed by human lung, nasal and intestinal epithelial cells. The tricellular tight junction molecule angulin-1/LSR is responsible for the epithelial permeability barrier at tricellular contacts and contributes to various human airway and intestinal inflammatory diseases. In this review, we indicate the mechanisms including angulin-1/LSR and multiple signaling in dysfunction of the epithelial permeability barrier induced by HMGB1 in 2.5D culture of human airway and intestinal epithelial cells. [ABSTRACT FROM AUTHOR]

Objectives: Tubarial glands (TGs) are recently refocused gland tissues localized near the tori tubarius in the nasopharynx and their clinical relevance is not clear yet. IgG4-related disease (IgG4-RD) is a progressive fibrosing condition and salivary glands are well-affected lesions. The aim of the present study is to examine [18F]fluorodeoxyglucose ([18F]FDG) accumulation to the tori tubarius in IgG4-related disease (IgG4-RD). Methods: 48 patients with IgG4-RD who underwent positron emission tomography (PET) scanning with [18F]FDG were included and semi-quantitative analysis of [18F]FDG accumulation to tori tubarius was performed along with the clinical features and histopathological analysis. Results: Of the 48 patients, abnormal [18F]FDG accumulation (metabolic tumour volume ≥ 1) to tori tubarius was observed in 15 (31.3%), all of whom had lesions in other head and neck glands. IgG4-RD patients with abnormal [18F]FDG accumulation to tori tubarius showed swollen nasopharyngeal walls around tori tubarius and forceps biopsy of the lesion revealed acinar cells and IgG4-positive plasma cells histologically. Abnormal [18F]FDG accumulation (maximum standard uptake value, metabolic tumour volume and total lesion glycolysis) to tori tubarius correlated with higher IgG4 and lower IgA serum concentrations. Conclusions: Abnormal [18F]FDG accumulation to tori tubarius can be observed in patients with IgG4-RD and the abnormal [18F]FDG accumulation to tori tubarius can be a clue of TG involvement in IgG4-RD. [ABSTRACT FROM AUTHOR]

We developed a micromagnetic modeling program for magnetic recording head analysis, taking eddy current effects into account, and studied the 1-GHz high-frequency response. When gyromagnetic precession is dominant with a small damping parameter of 0.01, the eddy current field causes the delay of the response, but the head field intensity increases a lot, compared to the no eddy current case, because the eddy current field cancels the precessional motion and improves the magnetization alignment. Since magnetic soft films have an intrinsic small damping, low-resistivity material is preferable for high-end magnetic recording heads. Index Terms--Eddy current, finite-element method (FEM), magnetic heads, micromagnetic modeling.

We develop a parallel micromagnetic finite-element method (micromagnetic-FEM) to handle a large number of micromagnetic elements and utilize it to analyze full head and media models. When the calculation domain decomposition and the one-one node communication are applied, the program shows four times faster calculation in eight CPU operation, as compared with one CPU calculation. We study head field and media magnetization reversal on the frequency of 714 MHz, using different yoke length heads of 6, 10, and 15 [micro]m. The shorter yoke head shows faster head field reversal and stronger head field strength, and the recorded media magnetization is also larger. The small damping parameter of the head causes not only smaller head field but also the disorder of the media transition. Index Terms--Finite-element method (FEM), magnetic heads, micromagnetic modeling, parallel calculation.

Tumor angiogenesis is an important therapeutic target in colorectal cancer (CRC). We aimed to identify novel genes associated with angiogenesis in CRC. Using RNA sequencing analysis in normal and tumor endothelial cells (TECs) isolated from primary CRC tissues, we detected frequent upregulation of adipocyte enhancer‐binding protein 1 (AEBP1) in TECs. Immunohistochemical analysis revealed that AEBP1 is upregulated in TECs and stromal cells in CRC tissues. Quantitative RT‐PCR analysis showed that there is little or no AEBP1 expression in CRC cell lines, but that AEBP1 is well expressed in vascular endothelial cells. Levels of AEBP1 expression in Human umbilical vein endothelial cells (HUVECs) were upregulated by tumor conditioned medium derived from CRC cells or by direct coculture with CRC cells. Knockdown of AEBP1 suppressed proliferation, migration, and in vitro tube formation by HUVECs. In xenograft experiments, AEBP1 knockdown suppressed tumorigenesis and microvessel formation. Depletion of AEBP1 in HUVECs downregulated a series of genes associated with angiogenesis or endothelial function, including aquaporin 1 (AQP1) and periostin (POSTN), suggesting that AEBP1 might promote angiogenesis through regulation of those genes. These results suggest that upregulation of AEBP1 contributes to tumor angiogenesis in CRC, which makes AEBP1 a potentially useful therapeutic target. [ABSTRACT FROM AUTHOR]

Epithelial integrity and barrier function are maintained during cytokinesis in vertebrate epithelial tissues. The changes in localization and the roles of tricellular tight junction molecule lipolysis-stimulated lipoprotein receptor (LSR) during cytokinesis are not well known, although new tricellular tight junctions form at the flank of the midbody during cytokinesis. In this study, we investigated the changes in localization and the role of LSR at the midbody and centrosome during cytokinesis using human endometrial carcinoma cell line Sawano, comparing the tricellular tight junction molecule tricellulin; bicellular tight junction molecules occludin, claudin-7, zonula occludens-1, and cingulin; and the epithelial polarized related molecules apoptosis-stimulating of p53 protein 2, PAR3, and yes-associated protein. During cytokinesis induced by treatment with taxol, the epithelial barrier was maintained and the tricellular tight junction molecules LSR and tricellulin were concentrated at the flank of the acetylated tubulin–positive midbody and in γ-tubulin-positive centrosomes with the dynein adaptor Hook2, whereas the other molecules were localized there as well. All the molecules disappeared by knockdown using small interfering RNAs. Furthermore, by the knockdown of Hook2, the epithelial barrier was maintained and most of the molecules disappeared from the centrosome. These findings suggest that LSR may play crucial roles not only in barrier function but also in cytokinesis. [ABSTRACT FROM AUTHOR]

The magnetization configuration of various pole-tip design perpendicular magnetic recording heads is studied by using finite element method (FEM) based micromagnetic simulation. The magnetic charge of the side-shield wall has induced off-track peaks of the fringing field and so it should be minimized for optimizing the side-shield structure.

Primary cilia, regulated via distinct signal transduction pathways, play crucial roles in various cellular behaviors. However, the full regulatory mechanism involved in primary cilia development during cellular differentiation is not fully understood, particularly for the sensory hair cells of the mammalian cochlea. In this study, we investigated the effects of the Rho-kinase inhibitor Y27632 and PKCα inhibitor GF109203X on primary cilia-related cell behavior in undifferentiated and differentiated temperature-sensitive mouse cochlear precursor hair cells (the conditionally immortalized US/VOT-E36 cell line). Our results indicate that treatment with Y27632 or GF109203X induced primary cilia elongation and tubulin acetylation in both differentiated and undifferentiated cells. Concomitant with cilia elongation, Y27632 treatment also increased Hook2 and cyclinD1 expression, while only Hook2 expression was increased after treatment with GF109203X. In the undifferentiated cells, we observed an increase in the number of S and G2/M stage cells and a decrease of G1 cells after treatment with Y27632, while the opposite was observed after treatment with GF109203X. Finally, while both treatments decreased oxidative stress, only treatment with Y27632, not GF109203X, induced cell cycle-dependent cell proliferation and cell migration. [ABSTRACT FROM AUTHOR]

The expression pattern of tight junction proteins (TJPs) varies among organs and tumor types. In this study, we examined the immunoreactivity of claudin (CLDN)-1, -4, and -7, and JAM-A in salivary gland tumors (SGTs) by histological types and cell types to estimate their usefulness as differential diagnostic markers. Immunoreactivity of CLDN1 was higher in ductal epithelium cells of SGTs than in non-tumor tissues. Conversely, immunoreactivity of CLDN1 was significantly decreased in basal/myoepithelium cells of SGTs compared with that in non-tumor tissues. There was no significant difference between the immunoreactivity of CLDN1 in benign tumors and that in malignant tumors. Immunoreactivity of CLDN4, CLDN7, and JAM-A in ductal epithelium cells was higher in many SGTs than in non-tumor tissues. There was a difference depending on the histological type of SGT in immunoreactivity of CLDN4, CLDN7, and JAM-A in basaloid/myoepithelial cells. It was possible to classify SGTs by a hierarchical clustering using immunoreactivity of TJPs. The results suggest that an immunohistochemical marker panel including these TJPs may be useful for differential diagnosis of SGTs and that CLDN1 is associated with tumorigenesis of SGTs. [ABSTRACT FROM AUTHOR]

Summary: Background: Skin hydration is generally assessed using the parameters of skin surface water content (SWC) and trans‐epidermal water loss (TEWL). To date, few studies have characterized skin conditions using correlations between skin hydration parameters and corneocyte parameters. Aims: The parameters SWC and TEWL allow the classification of skin conditions into four distinct Groups. The purpose of this study was to assess the characteristics of skin conditions classified by SWC and TEWL for correlations with parameters from corneocytes. Methods: A human volunteer test was conducted that measured SWC and TEWL. As corneocyte‐derived parameters, the size and thick abrasion ratios, the ratio of sulfhydryl groups and disulfide bonds (SH/SS) and CP levels were analyzed. Results: Volunteers were classified by their median SWC and TEWL values into 4 Groups: Group I (high SWC/low TEWL), Group II (high SWC/high TEWL), Group III (low SWC/low TEWL), and Group IV (low SWC/high TEWL). Group IV showed a significantly smaller size of corneocytes. Groups III and IV had significantly higher thick abrasion ratios and CP levels. Group I had a significantly lower SH/SS value. The SWC/TEWL value showed a decline in order from Group I to Group IV. Conclusion: Groups classified by their SWC and TEWL values showed characteristic skin conditions. We propose that the SWC and TEWL ratio is a comprehensive parameter to assess skin conditions. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The aim of this study was to evaluate the utility of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for accurately diagnosing immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS).Study Design: Retrospective cohort study.Methods: We reviewed the records of 64 patients with IgG4-SS (35 male and 29 female patients) and 10 patients with clinically suspected IgG4-SS. Pathological diagnoses of patients clinically suspected with IgG4-SS included four cases of malignant lymphoma, one case of multicentric Castleman disease, one case of Sjögren's syndrome, and four cases of sialadenitis. All patients underwent submandibular gland (SMG) biopsies and baseline FDG-PET/CT evaluation. Clinical, serological, pathological, and PET/CT findings were analyzed. We also investigated maximum standardized uptake values (SUVmax) in the salivary glands of 15 patients with malignant disease of the salivary glands during the same period.Results: Increased FDG uptake in the SMG and parotid gland was found in 63 (98%) and 23 (35%) patients with IgG4-SS, respectively. FDG uptake of the bilateral SMG and unilateral SMG was recorded in 57 patients (89%) and six patients (9%), respectively. Mean SUVmax in patients with malignant disease of the salivary glands was significantly higher than that in patients with IgG4-SS (P = .035). We defined a positive test for IgG4-SS diagnosis as high SMG FDG uptake and serum IgG4 level ≥135 mg/dL, resulting in a sensitivity, specificity, and accuracy of 96.9%, 90.0%, and 86.4%, respectively.Conclusions: FDG-PET/CT findings in combination with serological and clinical findings may have the capacity to diagnose IgG4-SS and lead to less-invasive biopsy procedures.Level Of Evidence: 4. Laryngoscope, 128:1120-1125, 2018. [ABSTRACT FROM AUTHOR]