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Background Extranodal extension (ENE) is a poor prognostic factor for oral squamous cell carcinoma (OSCC). Identifying ENE by clinical and/or radiological examination is difficult, thereby leading to unnecessary neck dissections. Currently, no definitive predictors are available for ENE. Thus, we aimed to determine the histological predictors of ENE by routine histopathological examination using biopsy and surgically resected specimens. Methods This retrospective study included 186 surgically resected OSCC and 83 matched biopsy specimens. Clinical features associated with the tumor microenvironment, including desmoplastic reaction (DR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs), were evaluated using hematoxylin and eosin-stained primary OSCC and neck dissection specimens. These histological features were divided into two groups: DR-immature (DR-I) and DR-mature (DR-M); TB-high (TB-H) and TB-low (TB-L); and TILs-low (TILs-L) and TILs-high (TILs-H). Clinical depth of invasion (cDOI) and pathological DOI (pDOI) were adapted for biopsies and resections, respectively; DOI was evaluated as DOI > 10 mm and DOI ≤ 10 mm. The clinicopathological relationships between these histopathological features and ENE and the independent risk factors for ENE were analyzed. The histological predictors of ENE were evaluated. Results The histological status of DR, TILs, and TB present in biopsy and resection specimens showed high accuracy with that of ENE. DR-I, TILs-L, and TB-H were significantly associated with lymph node metastasis, cDOI, and pDOI. Bivariate and multivariate analyses revealed that TB-H and pDOI > 10 mm in resections were independent factors for the presence of ENE (ENE +). The combination of TB-H/pDOI > 10 mm in resection specimens showed high specificity (91%) and accuracy (83%) regarding ENE + . Although there proved to be no independent factors in biopsies, DR-I and TILs-L were significantly associated with ENE + (p 10 mm in biopsies exhibited high sensitivity and specificity with ENE + (70% and 77%, respectively, p Conclusions The tumor microenvironment status in primary OSCC was significantly associated with that of ENE, and TB-H was an independent risk factor for ENE. The histological status of DR-I/TILs-L/cDOI > 10 mm in biopsy specimens and TB-H/pDOI > 10 mm in resection specimens is a useful predictor of ENE.

To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions.Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment.Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.

Background: Odontogenic tumors arising from extra-alveolar sites are extremerly rare. Dentinogenic ghost cell tumor (DGCT) is an uncommon odontogenic neoplasm characterized by CTNNB1 mutation, ghost cell appearance, and dentinoid-like calcification. We present a case of an ectopic DGCT arising from a calcifying odontogenic cyst in the floor of the mouth. Case presentation: A 72-year-old man presented with a painless sublingual swelling. Imaging revealed a multi-lobulated, solid-cyst mass on the floor of the mouth. Cytology showed folded epithelial clusters composed of basaloid cells, keratinized material, and dentinoid matrix. Histology also revealed a multi-cystic, cribriform to solid nest. Immunohistochemically, CK19, CK5/6, bcl-2, and p63 were diffuse positive. CTNTTB1 mutation was detected, leading to the final diagnosis of an ectopic DGCT. There was no recurrence during a 6-month follow-up. Conclusion: This is the first report to comprehensively describe the clinicopathological features of an ectopic DGCT of odontogenic origin, developing similarly to that of a true odontogenic DGCT. Accurate diagnosis of this rare entity is necessary to avoid overtreatment.

The mechanism whereby structural modification on the mesoscale order (10–100 μm) improves the electrochemical performance of anode-supported solid oxide fuel cells (SOFCs) is elucidated. After preparing two types of anode-supported SOFC having different electrode–electrolyte interfacial areas, we carry out their structural analyses and electrochemical characterization. Next, we develop a two-dimensional (2D) numerical model in which the structures of the cells are implemented and then verify its validity by comparing experimental and simulation results. It is found that the structural features in the mesoscale-modified cell, such as interfacial area enlargement and thickness inhomogeneity, cause nonuniform distributions of physicochemical quantities that contribute to electrochemical reactions. Consequently, the decreases in the ohmic and activation overpotentials of the mesoscale-modified cell relative to the flat cell are respectively larger and smaller than those estimated under the assumptions that the ionic and charge-transfer current densities are uniformly distributed in a cell. Moreover, the ionic current density distribution has a strong nonuniformity at a high current density, leading to a large relative decrease in ohmic loss. Furthermore, the cell overpotential is more reduced at a higher current density; thus, the mesostructural modification of anode-supported SOFCs can lead to a higher cell performance.

Eosinophils are innate immune leukocytes and play important roles as terminal effector cells owing to their mediators, such as tissue-destructive cationic proteins, cytokines, chemokines, and lipid mediators. Historically, they are not only considered an important player in host defense against parasitic, viral, fungal, and bacterial infections but also implicated in the pathogenesis of eosinophil-associated diseases, such as allergic rhinitis, asthma, eosinophilic chronic rhinosinusitis, esophagitis, atopic dermatitis, myopathies, and hypereosinophilic syndrome. Moreover, recent studies have shown that eosinophils have an immune regulatory and homeostatic function. Interestingly, there is emerging evidence that eosinophils are accumulated through adoptive T-helper 2 (Th2) and innate Th2 responses, mechanisms of the classical allergen-specific immunoglobulin E (IgE)-mediated response, and group 2 innate lymphoid cell-derived interleukin-5, respectively. Furthermore, in agreement with current concepts of eosinophil subtypes, it has been shown that resident and phenotypically distinct eosinophils, i.e., resident and recruited inflammatory eosinophils, exist in inflamed sites, and each has different functions. Thus, the classical and novel studies suggest that eosinophils have multiple functions, and their roles may be altered by the environment. In this article, we review multiple biological aspects of eosinophils (novel and classical roles), including their beneficial and detrimental effects, immunoregulation, and homeostatic function.

Background/aim This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Patients and methods A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. Results Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. Conclusion The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.

An enhancement-mode (E-mode) AlGaN/GaN metal–insulator–semiconductor high-electron-mobility transistor (MIS-HEMT) with La2O3/SiO2 gate insulator is investigated for high power application. The La2O3/SiO2 composite oxide formed amorphous La-silicate after post deposition annealing. Good oxide film quality and excellent La-silicate/AlGaN interface properties were achieved as evidenced by the capacitance–voltage (C–V) curves and hysteresis effect of the La-silicate on AlGaN/GaN metal–oxide–semiconductor capacitors. As a result, the E-mode AlGaN/GaN MIS-HEMT with La-silicate gate insulator shows good threshold voltage (Vth) stability and demonstrated only slightly increase in the dynamic on-resistance (Ron) after high drain bias stress test. The device also exhibits high current density of 752 mA/mm, high maximum transconductance of 210 mS/mm, low subthreshold swing of 104 mV/decade, and ION/IOFF = 107 when tested at VDS = 10 V. Furthermore, low on-resistance of 7.6 Ω mm, high breakdown voltage of 670 V, and excellent delay time of 4.2 ps were achieved, demonstrating the La-silicate MIS-HEMTs have the potential to be used for power electronic applications.

Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands is a relatively rare carcinoma. The detection rate of the carcinoma component in the cytological specimens is not high and may be challenging in cytological examination. The purpose of the present study was to analyze the cytological specimens of CXPA with emphasis on the detection of the carcinoma component. We reviewed the cytological characteristics of patients histopathologically diagnosed with CXPA who underwent preoperative cytological examination. Of the 10 patients enrolled in the study, 8 had tumors located in the parotid gland, and 2 in the submandibular gland. A review of the cytological specimens revealed the presence of the carcinoma component in all 10 cases and the pleomorphic adenoma (PA) component in 6 cases, although initial cytodiagnosis detected the carcinoma component in 8 cases. The cytological feature of this component was the presence of variable-sized clusters of polygonal cells with relatively rich cytoplasm and large round to oval nuclei in a necrotic background. Interestingly, carcinoma cells mixed with the PA component were also present. On histopathological analysis, 7 cases were intracapsular, and the remaining 3 cases were widely invasive CXPA. Further, 9 cases had salivary duct carcinoma as carcinoma component. In conclusion, these findings show that careful detection of the carcinoma cells, particularly within the PA component, is crucial for early detection of CXPA, and the presence of necrosis might help with the detection of the carcinoma component.

A simple but physicochemically meaningful numerical model of a solid oxide fuel cell (SOFC) anode is developed as a tool to understand and reproduce its impedance spectra. The model considers conservations of electrons, ions and gas species within the anode, which are coupled by a non-linear electrochemical reaction model. The developed model is first calibrated by impedance spectra that are experimentally obtained at the open circuit conditions at several temperatures, by adjusting the ionic conductivity, exchange current density and electrostatic capacitance. All of these parameters are confirmed to be within an acceptable range of values found in literature. Also, real anode microstructural parameters obtained by three-dimensional FIB-SEM imaging is implemented to eliminate any other arbitrary fitting parameters from the model. Then, the model is used to reproduce impedance spectra obtained from another anode with different microstructure and also those measured at polarized conditions and at different temperatures, and gives good agreement with the experimental results. Considering the computational resources required to reproduce impedance spectra, the developed model is expected to be used as an alternative to the conventional equivalent circuit fitting.

The progress of LSCF cathode degradation by sulfur poisoning is numerically investigated. A few degradation models are developed on the bases of different assumptions and available material properties and applied to 1D simulations. The results of 1D simulations are compared with the experimental data to see if the model can phenomenologically reproduce them. The model which gives a reasonable prediction is applied to 2D CFD simulations of a single planar-type anode-supported SOFC. The 2D simulation model consists of the conservation equations of mass, momentum, energy, species and charge carriers, which are coupled by the electrochemical reaction models. A volume-averaging method is applied to the porous electrodes. The simulation results show that the developed model fairly predicts the formation of SrSO4 near the cathode–electrolyte interface particularly in the upstream region of the air channel.

The phase-inversion tape casting technique is used for fabrication of Ni-YSZ anode substrate for solid oxide fuel cells to form anisotropic pore structures and hence to improve its gas transport property. Microstructure of the fabricated anode substrates is analyzed using the scanning electron microscope with dual resolutions: one at 10 µm scale to analyze the sponge-like pores and the other at 500 µm scale to analyze the anisotropic finger-like pores. Depth profile of the microstructural parameters is also obtained. SOFC cells are prepared with the anode substrates and their electrochemical performance is evaluated by the electrochemical impedance spectroscopy and compared with that of the conventional cell. The anode fabricated using the phase-inversion tape casting is found to have excellent gas transport property even at high current and diluted hydrogen conditions.

Anode ridge structures are fabricated by printing anode pastes having different rheological properties to increase the electrode–electrolyte interfacial area in anode-supported solid oxide fuel cells. Homogeneous anode pastes are prepared by varying solid loadings, then their rheological characteristics are evaluated. It is confirmed that the shear stress at the same shear rate increases with increasing solid loading. The prepared pastes are printed onto flat anode substrates and then the width and height of the printed pastes are observed before and after drying and after sintering. As increasing solid loading in the paste, not only the width and height become smaller and larger, respectively, but also the shrinkage rate of the aspect ratio becomes smaller. Consequently, a large extension of the interfacial area of about 285% is obtained by printing the paste with the solid loading of 80%., [Solid Oxide Fuel Cells 16 - SOFC-XVI] September 8, 2019 - September 13, 2019 (Kyoto, Japan)

Yttria-stabilized zirconia (YSZ) is the most popular electrolyte material for solid oxide fuel cells (SOFCs). However, when cobaltite-based perovskite cathode materials, for example lanthanum strontium cobalt ferrite (LSCF), are used, an insulating layer is easy to be formed at the cathode-electrolyte interface. For preventing the interfacial reaction, a gadolinium-doped ceria (GDC) interlayer is usually employed between YSZ and cathode. In this work, we investigated the fabrication of YSZ/GDC bilayer electrolyte thin films by a simple spray coating process and co-sintering. Dense YSZ/GDC bilayer electrolyte thin films were successfully fabricated. There is no crack and delamination observed for the YSZ/GDC bilayer. A Ni-YSZ/YSZ/GDC/LSCF-GDC anode-supported single cell with 4 µm thick YSZ layer and 2 µm thick GDC layer shows an open-circuit voltage of 1.1 V and a maximum power density of about 0.6 W/cm2 with humidified H2 as fuel and air as oxidant at 700°C.

Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab’s effects on restoration of corticosteroid sensitivity via PP2A activation, thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.

Background/Aim: We previously presented the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This study aimed to evaluate the prognostic significance of pretreatment inflammatory biomarkers in patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy as a supplementary study of our previous retrospective cohort study. Patients and Methods: The treatment outcomes of 100 patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy were compared according to patient characteristics and pretreatment inflammatory biomarkers using a Cox proportional hazards regression model. Survival was evaluated using the Kaplan-Meier method. Results: In multivariate analysis, a lymphocyte-to-monocyte ratio (LMR) of

Secretory carcinoma (SC) of the salivary gland is a rare distinct clinicopathological entity characterized by the presence of the ETV6-NTRK3 fusion. Although the characteristic cytological features of SC have been recognized, its cytodiagnosis, especially differentiating SC from acinic cell carcinoma, is challenging. Recent studies have revealed that immunohistochemistry for pan-tyrosine receptor kinase (Trk) and nuclear receptor subfamily 4 group member 3 (NR4A3) are specific for SC and acinic cell carcinoma, respectively. However, the usefulness of immunocytochemical detection of these markers in the diagnosis of SC has not been addressed. Hence, the present study aimed to analyze the usefulness of immunocytochemical staining for pan-Trk and NR4A3 in the cytodiagnosis of SC. We enrolled eight patients with a histopathological diagnosis of SC who underwent preoperative fine-needle aspiration cytological examination. The cytological characteristics were reviewed and immunocytochemical staining for pan-Trk and NR4A3 was performed. The characteristic cytological features noted in the patient cohort included neoplastic cell clusters with a sheet-like and papillary cluster arrangement as well as single cells. Additionally, neoplastic cells with mild to moderately enlarged nuclei and small nucleoli, multi-vacuolated cytoplasm, and intracytoplasmic mucin were also observed. The immunocytochemical analyses clearly demonstrated that all eight specimens showed positive nuclear staining for pan-Trk, but were negative for NR4A3 expression. Although all cases of SC do not always show positive immunoreactivity for pan-Trk, immunocytochemical analysis for pan-Trk may be useful for the cytodiagnosis of SC along with assessment of the characteristic cytological features.

Silicon trench-gate insulated gate bipolar transistors (IGBTs) were analyzed using technology CAD (TCAD). Excellent agreement was confirmed between the $J_{\mathrm{C}^{-}}V_{\text{CE}}$ characteristics obtained by 3D- TCAD simulations and experiments. The carrier lifetime requirement for scaled trench-gate IGBTs was determined by extraction of the on-resistance of the n-base layer derived from the electric potential profile.

Background: Biomarkers predicting therapeutic response to immunotherapy have been widely explored via monitoring the liquid and tissue-derived components. Increasing treatment options for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) mandates prediction of the therapeutic response of anti-PD-1 antibody alone as well as optimization of the treatment sequence. In view of improving biomarkers predicting the efficacy of immunotherapy for R/M HNSCC, we hypothesized that biomarkers can be personalized depending on clinicopathological backgrounds and treatment sequence. Methods: In this study, we retrospectively included formalin-fixed paraffin-embedded (FFPE) samples, peripheral blood cell counts at treatment, clinicopathological information, and outcome data for patients with R/M HNSCC receiving nivolumab across 22 institutions in Japan (N = 100). FFPE samples were subjected to 14-marker multiplex immunohistochemistry (IHC) and image cytometry analysis (Tsujikawa T et al. Cell Reports, 2017) to quantitatively evaluate CD8+ T cells, helper T cells, regulatory T cells, B cells, natural killer (NK) cells, macrophages, dendritic cells, CD66b+ granulocytes, mast cells, programmed death ligand 1 (PD-L1) and PD-1 expression in a single slide. Intratumoral and circulating immune cell frequencies were comparatively analyzed between responders (CR, n = 14; PR, n = 39) and non-responders (SD, n = 2; PD, n = 45). Results: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-L1 expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. Next, focusing on the history of prior therapy, stratified analysis revealed that the frequency of NK cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Furthermore, stratified analysis by patient age revealed that nivolumab response was significantly associated with high CPS and lymphoid-inflamed profiles based on cell densities of nine immune cell lineages in the group aged 65 years or older, but not in the group under 65 years of age. On the contrary, the neutrophil/lymphocyte ratios (NLR) in peripheral blood counts at nivolumab treatment were significantly lower in responders (mean 4.96) than those in non-responders (mean 10.46) in the group under 65 years of age, but not in those over 65 years of age (7.41 versus 8.47). Conclusions: Using peripheral blood data and tumor tissue profiling stratified by patient age and prior treatment might provide better predictive biomarkers in nivolumab response to HNSCC. Further preclinical and clinical studies elucidating immune mechanisms in different patient backgrounds will be warranted. Citation Format: Takahiro Tsujikawa, Kazuchika Ohno, Sumiyo Saburi, Junichi Mitsuda, Kanako Yoshimura, Alisa Kimura, Hiroki Morimoto, Gaku Ohmura, Akihito Arai, Hiroshi Ogi, Saya Shibata, Yosuke Ariizumi, Akihisa Tasaki, Ryosuke Takahashi, Yumiko Tateishi, Hiroaki Kawabe, Sadakatsu Ikeda, Kei-ichi Morita, Tatsuhiko Tsunoda, Takumi Akashi, Morito Kurata, Issei Imoto, Yasushi Shimizu, Akihito Watanabe, Yukinori Asada, Ryuichi Hayashi, Yuki Saito, Hiroyuki Ozawa, Kiyoaki Tsukahara, Nobuhiko Oridate, Arata Horii, Takashi Maruo, Nobuhiro Hanai, Hidenori Inohara, Hiroshi Iwai, Takashi Fujii, Ken-ichi Nibu, Shigemichi Iwae, Tsutomu Ueda, Ryuji Yasumatsu, Hirohito Umeno, Muneyuki Masuda, Kyoko Itoh, Shigeru Hirano, Takahiro Asakage. Tumor immune characterization identifies age-stratified biomarkers for nivolumab in patients with head and neck squamous cell carcinoma: A nationwide collaborative study in Japan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5210.

We investigated the association between cellular immunity and age-related hearing loss (ARHL) development using three CD4

Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor. Due to the rarity, there are scarce reports describing the cytological features of ONB. Thus, we aimed to analyze these cytological features and discuss their differences depending on the histological grading of ONB. Patients with a histopathological diagnosis of ONB who underwent fine-needle aspiration cytology were enrolled in the study. The cytological features, including arrangement and shape of neoplastic cells, nuclear features, and presence of rosettes, were analyzed. Eight patients with ONB were enrolled; cytological specimens of seven patients were obtained from metastatic lesions and that of one patient were obtained from the nasal cavity tumor. The cytological specimens demonstrated variable-sized clusters of neoplastic cells and single cells. Two-cell pattern, composed of large-sized viable neoplastic cells and small-sized apoptotic cells, was noted in 3 of 4 high-grade ONBs but in none of 4 low-grade ONBs. This reflects that the presence of the two-cell pattern may represent higher proliferation in neoplastic cells. The neoplastic cells had scant cytoplasm and round to oval nuclei containing fine to granular chromatin without conspicuous nucleoli. Rosettes and paranuclear blue bodies were observed in one patient. Most cytological specimens of ONB were obtained from metastatic lesions, especially from the cervical lymph node. Thus, ONB should be differentiated from malignant lymphoma and small cell neuroendocrine carcinoma. Recognition of these cytological features of ONB while considering patient history can aid in correctly diagnosing ONBs. Moreover, the presence of two-cell pattern might reflect high-grade histology of ONB.

BACKGROUNDS Data on risk factors for deep neck infection including descending necrotizing mediastinitis (DNM) have been limited. Using a nationwide database, the aim was identifying the factors related to patient death and delay in recovering oral intake. METHODS Data of 4949 patients were extracted from a Japanese inpatient database between 2012 and 2017. The main outcome was survival at discharge. In a subgroup analysis of the 4949 patients with survival, the second outcome was delay in the interval between admission and full recovery of oral intake. RESULTS Only a few factors (advanced-age, ventilation) were associated with both mortality and delayed oral dietary intake by logistic regression analyses. Conversely, several factors including DNM (adjusted-odds ratio [OR] 1.41) and repeated surgery (adjusted-OR 1.70) were significantly related only to delayed oral dietary intake. CONCLUSIONS Although DNM was not necessarily related to mortality, patients with DNM should receive careful attention to avoid delayed oral dietary intake.

Full integration of a back-gate-controlled IGBT (BC-IGBT), which comprises top and bottom independently controlled MOS gates, is experimentally demonstrated. By using the back side MOS gate for accelerating electron drain and blocking of hole injection, more than 60% reduction of turn-off loss was achieved. Instead of the conventional wafer bonding approach, a cost effective process flow using double side lithography has been developed and used. Thanks to the process flexibility, back side design was carefully optimized to achieve stable operation and manufacturability, in addition to low switching loss. BC-IGBT will provide a new technological option for expanding the applicable switching frequency / voltage range of Si power devices.

Backgrounds: Data on risk factors for deep neck infection (DNI) including descending necrotizing mediastinitis (DNM) have been limited. Using a nationwide database, the aim was to identify the factors related to patient death and delay in recovering oral intake.Methods: We retrospective reviewed a Japanese inpatient database between 2012 and 2017, and data of 4,949 patients with DNM and DNI were extracted. The main outcome was survival at discharge. In a subgroup analysis of the 4,791 patients with survival at discharge, the second outcome was delay in the interval between admission and full recovery of oral intake. In both of the setting, logistic regression analyses were conducted to determine the risk factors.Results: Regarding survival at discharge, logistic regression analysis showed that age (≥75 years), comorbid diabetes mellitus, sepsis, receiving mechanical ventilation, and duration of empirical antibiotic therapy were significantly associated with mortality [adjusted-odds ratios (ORs) (95% confidence intervals (CIs)] as follows: 5.57 (2.80-11.1), 2.47 (1.69-3.62), 3.32 (2.29-4.82), 3.96 (2.51-6.23), and 1.00 (1.00-1.02), respectively. In a subgroup analysis of the 4,791 patients with survival at discharge, logistic regression analysis showed the following factors to be significantly associated with delayed oral dietary intake (>9 days), as follows [adjusted OR (95% CIs)]: age ≥75 years 1.89 (1.48-2.41); body mass index (BMI) 2 1.39 (1.13-1.71); DNM 1.41 (1.04-1.92); repeated surgical interventions 1.70 (1.16-2.48); tracheotomy 1.70 (1.44-2.00); mechanical ventilation 1.92 (1.53-2.41); intensive care unit (ICU) admission 1.54 (1.22-1.93); rehabilitation for oral dietary intake 2.05 (1.44-2.92); and duration of empirical antibiotic therapy 1.18 (1.17-1.20).Conclusions: In this study, a few factors (advanced age, ventilation) were associated with both mortality and delayed oral dietary intake. Conversely, several factors including DNM and repeated surgery were significantly related only to delayed oral dietary intake. Although DNM was not necessarily related to mortality, patients with DNM should receive postoperative care with careful attention to avoid delayed oral dietary intake.

Eosinophils not only play a critical role in the pathogenesis of eosinophil-associated diseases, but they also have multiple important biological functions, including the maintenance of homeostasis, host defense against infections, immune regulation through canonical Th1/Th2 balance modulation, and anti-inflammatory and anti-tumorigenic activities. Recent studies have elucidated some emerging roles of eosinophils in steady-state conditions; for example, eosinophils contribute to adipose tissue metabolism and metabolic health through alternatively activated macrophages and the maintenance of plasma cells in intestinal tissue and bone marrow. Moreover, eosinophils exert tissue damage through eosinophil-derived cytotoxic mediators that are involved in eosinophilic airway inflammation, leading to diseases including asthma and chronic rhinosinusitis with nasal polyps characterized by fibrin deposition through excessive response by eosinophils-induced. Thus, eosinophils possessing these various effects reflect the heterogenous features of these cells, which suggests the existence of distinct different subpopulations of eosinophils between steady-state and pathological conditions. Indeed, a recent study demonstrated that instead of dividing eosinophils by classical morphological changes into normodense and hypodense eosinophils, murine eosinophils from lung tissue can be phenotypically divided into two distinct subtypes: resident eosinophils and inducible eosinophils gated by Siglec-Fint CD62L+ CD101low and Siglec-Fhigh CD62L– CD101high, respectively. However, it is difficult to explain every function of eosinophils by rEos and iEos, and the relationship between the functions and subpopulations of eosinophils remains controversial. Here, we overview the multiple roles of eosinophils in the tissue and their biological behavior in steady-state and pathological conditions. We also discuss eosinophil subpopulations.

Technology CAD (TCAD) has been recognized as a powerful design tool for Si insulated gate bipolar transistors (IGBTs). Here, physical models, such as a mobility model for carrier-carrier scattering, were investigated for a predictive TCAD. Simulated currentvoltage characteristics of the trench-gate IGBTs were compared with measurements. The difference between 3D- and 2D-TCAD simulations was observed in a high current region, which was explained by a bias-dependent current flow. A test element group (TEG) for separation of the emitter currents for holes and electrons was also determined as effective for calibration of lifetime model parameters.

Objective Japanese cedar pollinosis is an endemic disease affecting a large proportion of Japan's population. Five seasons have passed since sublingual immunotherapy (SLIT) for Japanese cedar pollinosis was included in the public insurance coverage in Japan. In this study, we evaluated the clinical effects of long-term SLIT for Japanese cedar pollinosis on upper respiratory symptoms primarily represented by nasal symptoms and inflammation of the respiratory tract in the 2019 season, in which considerable amount of cedar pollen was dispersed. Methods This study involved 95 patients who were undergoing SLIT for Japanese cedar pollinosis after the initiation at some point between 2014 and 2018, and this group of patients was compared with a control group comprising 21 patients receiving preseasonal prophylactic treatment (with a second-generation antihistaminic drug). We evaluated the patients’ nasal/eye symptoms, total nasal symptom and medication score (TNSMS), and quality of life according to relevant guidelines. In addition, the levels of peripheral blood eosinophils, serum total IgE, Japanese cedar antigen-specific IgE, Cryj1-specific IgG4, and fractional exhaled nitric oxide (FENO) were measured as objective indices. Results From the fourth season (SLIT4), nasal discharge, sneezing, nasal obstruction symptoms, and TNSMS significantly decreased compared with those in the preseasonal prophylactic treatment and SLIT1 groups. In the patients suspected to have eosinophilic airway inflammation (with a baseline FENO ≥25 ppb), the interannual variability of FENO levels significantly reduced after 5 years of treatment. Conclusion The efficacy of SLIT was noted from the first year of treatment, even in a year when pollen profusely dispersed. Thus, long-term continuous treatment with SLIT may alleviate nasal symptoms as well as eosinophilic airway inflammation.

Background Secretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC. Case presentation Three cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis. Conclusions High-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

Purpose In cases of unilateral vocal fold paralysis (UVFP), voice disorders caused by glottic insufficiency can lead to a considerable reduction in the patient's quality of life. Voice therapy (VT) is an effective treatment that must be started early after the onset of vocal fold paralysis. This study examined the effect of early VT for patients with UVFP occurring after esophagectomy. Materials and methods Patients who had residual UVFP at 1 month postoperatively after esophagectomy for esophageal cancer between November 2014 and March 2017 were evaluated. Seventeen patients were divided into the VT group (n = 6) and non-VT group (n = 11). We compared these two groups and retrospectively examined the effect of early VT. The study endpoints included aerodynamic tests, laryngeal endoscopy, laryngeal stroboscopy, and glottal closure. All of these evaluations were performed at preoperatively and at 1 and 3 months postoperatively. Results Subglottal pressure reduced notably in the VT group, and both the mean flow rate and maximum phonation time tended to improve after VT. Conversely, there were no significant differences in MFR and MPT in the non-VT group. Furthermore, although UVFP remained after VT, we achieved glottal closure for all three patients. Conversely, only two of the six patients with glottic insufficiency in the non-VT group achieved glottal closure. Conclusion VT may be effective for improving impaired vocal function in patients with UVFP. It is reasonable to expect that VT can be initiated 1 month after the onset of vocal fold paralysis.

Background Basal cell adenoma (BCA) of the salivary gland is a relatively rare benign tumor. Although the presence of stromal spindle cells is a characteristic histopathological feature, this finding has not been the focus of much attention in the cytodiagnosis of BCA. Thus, we analyzed the cytological features of BCA, especially the presence of stromal spindle cells. Methods Patients who were histopathologically diagnosed with BCA and underwent preoperative fine-needle aspiration cytological examination were enrolled in this study. The cytological characteristics including arrangement and shape of the neoplastic cells, nuclear and cytoplasmic features, and the presence of stromal spindle cells were reviewed. Results Nineteen patients were enrolled in the study. The cytological specimens were cellular and composed of small or large clusters or both. The neoplastic cells had scant cytoplasm and small round to oval nuclei. Basement membrane-like material was observed in 57.9%, and peripheral palisading was noted in 84.2%. Loose aggregates of stromal spindle cells were present in 63.2%, and the stromal spindle cells shown in the histological examination of 85.7% of cases were expressed in the cytological specimens. Conclusion This study clearly demonstrated the relatively high frequency of stromal spindle cells in cytological specimens of BCA. This finding is characteristic of BCA, and therefore, the combination of cytological features, including packed clusters of neoplastic cells with scant cytoplasm and small nuclei, peripheral palisading, and basement membrane-like material, and the presence of stromal spindle cells could increase the diagnostic success of BCA.

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4+ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

Infarction after the fine-needle aspiration (FNA) procedure is a well-recognized phenomenon of salivary gland lesions. Though extremely rare, spontaneous infarction without previous FNA can occur in pleomorphic adenoma (PA). The present report describes a fourth cytological case of spontaneous infarction of PA of the parotid gland using immunocytochemical analysis, to the best of our knowledge, for the first time. A 57-year-old Japanese female presented with persistent swelling of the right neck region. Physical examination revealed a tumour in the right parotid gland, and FNA examination of the tumour was performed following surgical resection. The Papanicolaou smear demonstrated the presence of fully necrotic cell clusters of varying sizes in a necrotic background. Only a few viable cell clusters were observed. These cells were polygonal to spindle-shaped, and exhibited large round to oval nuclei with a conspicuous nucleoli. Although nuclear pleomorphism was noted, the nuclear chromatin was fine. No neoplastic myoepithelial cells were observed. Therefore, it was suspected that these cells were malignant. Immunocytochemical analysis indicated that these atypical cells were positive for p40. Histopathological examination of the resected parotid gland tumour revealed infarcted PA. Our study revealed that the presence of atypical squamous metaplastic cells in a necrotic background was a characteristic cytological feature of infarcted PA, and that these atypical squamous cells can have large nuclei with conspicuous nucleoli and exhibit pleomorphism. Although cytological diagnosis of infarcted PA is difficult, pathologists and cytopathologists must consider the presence of atypical metaplastic squamous cells in benign salivary gland tumours, including infarcted PA.

The aims of this study were to evaluate the efficacy of partial parotidectomy using retrograde dissection of the marginal mandibular branch of the facial nerve for benign tumours of the parotid gland and to establish the indications for its use. We examined 106 consecutive patients with previously untreated benign tumours in the lower portion of the parotid gland who were treated by parotidectomy. The first group (anterograde group, n=52) consisted of those who had standard anterograde parotidectomy. The remaining patients, who underwent retrograde parotidectomy, were further divided into two groups: those in whom the upper edge of the tumour was located below the mastoid tip (below mastoid group, n=46) or those in whom it was above the mastoid tip (above mastoid group, n=8). The operating time was significantly shorter in the below mastoid group (141.2, 127.5, and 98.1minutes, respectively) as was intraoperative blood loss (41.1, 53.0, and 24.4ml, respectively), compared with the other two groups. There was a higher incidence of facial nerve dysfunction in the above mastoid group postoperatively (4/8) than in the other two groups. The results suggested that the presence of a tumour of any size located below the mastoid tip is a good indication for parotidectomy using retrograde dissection of the marginal mandibular branch of the facial nerve.

The effects of flow configuration in solid oxide fuel cell (SOFC) stacks are investigated using a quasi-three-dimensional numerical model. Flow configurations with alternated air flows in parallel and perpendicular to the fuel flows are considered in addition to the conventional co-, counter-, and cross-flow configurations. The stacks have eight cells with unity aspect ratio and an active area of 4900 mm2 and are compared at fuel utilization of 0.193, 0.386, 0.579, and 0.772. The numerical model is capable of analyzing both the streamwise and spanwise directions of the cells. Although the counter-flow stack achieves the highest voltage efficiency among the stacks with the conventional flow configurations, it has the highest dispersion of the current density distribution on the cells. Air-flow alternation is effective to achieve uniform and high cell temperature and hence low dispersion of the current density. Alternate air flows parallel to the fuel flows achieve the highest voltage efficiency of 0.797 at a fuel utilization of 0.772, while alternate air flows perpendicular to the fuel flows reduce the risk of local fuel depletion as compared with the cross-flow stacks. Appropriate selection of the air-flow configuration within stacks allows operation at higher efficiency without fuel depletion.

In this paper a fully three dimensional, multiphase, micro-scale solid oxide fuel cell anode transport phenomena numerical model is proposed and verified. The Butler-Volmer model was combined with empirical relations for conductivity and diffusivity - notably the Fuller-Shetler-Giddings equation, and the Fickian model for transport of gas reagents. FIB-SEM tomography of a commercial SOFC stack anode was performed and the resulting images were processed to acquire input data. A novel method for estimating local values of Triple Phase Boundary length density for use in a three-phase, three-dimensional numerical mesh was proposed. The model equations are solved using an in-house code and the results were verified by comparison to an analytical solution within the range of its applicability. A limited parametric study was performed to qualitatively assess simulation performance and impact of heterogeneity. Despite the high dependence of the SOFC anode performance on the geometry of its anisotropic, three-phase microstructure there are very few micro-scale numerical models simulating transport phenomena within these electrodes.

The effect of La-silicate interface layer (IL) on the electrical characteristics of 4H-SiC metal-oxide-semiconductor (MOS) capacitors with atomic-layer-deposited SiO2 (ALD-SiO2) gate dielectrics was investigated. In addition to a slight reduction in the interface state density (Dit), the surface potential fluctuation was greatly reduced due to the reduction in the fixed charges (Qfix) with La-silicate IL. Moreover, two orders of magnitude reduction in the oxide trap density in the ALD-SiO2 layer adjacent to the La-silicate IL was confirmed. Physical analysis revealed the reduction in carbon concentration and incorporation of La atoms adjacent to the La-silicate IL.