TGF-ß3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia.

Necrotising sialometaplasia (NSM) is a non-neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction and squamous metaplasia of salivary ducts and acini are observable. The aetiology of this lesion remains unknown, although it has a characteristic feature that sometimes requires clinical and histopathological differentiation from malignancy. In this study, we investigated upregulated genes in NSM compared with normal salivary glands, and focused on the TGF-ß3 (TGFB3) gene. The results of the histopathological studies clarified that fibroblasts surrounding the lesion express TGF-ß3. Moreover, in vitro studies using mouse salivary gland organoids revealed that TGF-ß3 suppressed salivary gland cell proliferation and induced squamous metaplasia. We demonstrated a possible aetiology of NSM by concluding that increased TGF-ß3 expression during wound healing or tissue regeneration played a critical role in cell proliferation and metaplasia. © 2024 The Pathological Society of Great Britain and Ireland.

Selective transarterial embolization for arterial hemorrhage after upper third molar extraction: illustrative cases.

BACKGROUND: The present report describes 2 cases of arterial bleeding after removal of the upper third molar that were successfully treated with selective transarterial embolization. OBSERVATIONS: The first patient underwent removal of the left upper third molar. A few hours later, facial swelling and massive bleeding appeared near the extraction socket involving the posterolateral wall of the maxillary sinus. Angiography showed a pseudoaneurysm involving the posterior superior dental artery, and the lesion was selectively embolized with an N-butyl cyanoacrylate (NBCA)-lipidiol mixture. The second patient underwent removal of the left upper third molar, and massive bleeding occurred from the extraction socket involving the greater palatine foramen. Angiography revealed the pseudoaneurysm of the greater palatine artery, and the lesion was selectively embolized with an NBCA-lipiodol mixture. Both patients were discharged uneventfully, and no recurrent bleeding was observed during the 82- and 5-month follow-up periods. LESSONS: Massive arterial bleeding after a third molar extraction occurs from either the posterior superior dental artery or the greater palatine artery, which is associated with the location of the extraction socket. Selective transarterial glue embolization is a useful option for the treatment of arterial bleeding after the removal of the upper third molars.

Perovskite Solar Cell Using Isonicotinic Acid as a Gap-Filling Self-Assembled Monolayer with High Photovoltaic Performance and Light Stability.

High photovoltaic performance and light stability are required for the practical outdoor use of lead-halide perovskite solar cells. To improve the light stability of perovskite solar cells, it is effective to introduce a self-assembled monolayer (SAM) between the carrier transport layer and the perovskite layer. Several alternative approaches in their molecular design and combination with multiple SAMs support high photovoltaic conversion efficiency (PCE). Herein, we report a new structure for improving both PCE and light stability, in which the surface of an electron transport layer (ETL) was modified by combining a fullerene-functionalized self-assembled monolayer (C60SAM) and a suitable gap-filling self-assembled monolayer (GFSAM). Small-sized GFSAMs can enter the gap space of the C60SAM and terminate the unterminated sites on the ETL surface. The best GFSAM in this study was formed using an isonicotinic acid solution. After a light stability test for 68 h at 50 °C under 1 sun illumination, the best cell with C60SAM and GFSAM showed a PCE of 18.68% with a retention rate of over 99%. Moreover, following outdoor exposure for six months, the cells with C60SAM and GFSAM exhibited almost unchanged PCE. From the valence band spectra of the ETLs obtained using hard X-ray photoelectron spectroscopy, we confirmed a decrease in the offset at the ETL/perovskite interface owing to the additional GFSAM treatment on the C60SAM-modified ETL surface. Time-resolved microwave conductivity measurements demonstrated that the additional GFSAM improved electron extraction at the C60SAM-modified ETL/perovskite interface.

Uncommon case of cytopathological features of sialadenoma papilliferum.

Sialadenoma papilliferum, a benign and rare salivary gland neoplasm, accounts for 0.4%-1.2% of all salivary gland tumors and occurs primarily in minor salivary glands of the oral cavity. Here, we report a case of sialadenoma papilliferum and its associated cytological findings. A papillary tumor was incidentally detected on the palate of an 86-year-old Japanese man. Conventional oral exfoliative cytology was performed; the cytology smear exhibited epithelial clusters composed of atypical epithelial cells with a high nuclear/cytoplasm ratio and arranged in sheet or small papillary-like projections. Cytoplasmic vacuoles were also observed in the papillae. It was difficult to make a definitive diagnosis due to the presence of uncommon cytological features. The excisional biopsy specimen revealed histological features characteristic of sialadenoma papilliferum. Mutational analysis detected BRAFV600E mutation, which confirmed the diagnosis of sialadenoma papilliferum. To the best of our knowledge, no prior cytomorphological evaluations of sialadenoma papilliferum have been reported in detail. Oral exfoliative cytology specimens from salivary gland tumors can demonstrate uncommon cytomorphological features. A differential diagnosis of sialadenoma papilliferum can be based on the observation of mildly atypical epithelial cells that form small papillary-like structures.

Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Influence of forward head posture on muscle activation pattern of the trapezius pars descendens muscle in young adults.

Forward head posture (FHP) is a serious problem causing head and neck disability, but the characteristics of muscle activity during long-term postural maintenance are unclear. This study aimed to investigate a comparison of electromyography (EMG) activation properties and subjective fatigue between young adults with and without habitual FHP. In this study, we examined the changes in the spatial and temporal distribution patterns of muscle activity using high-density surface EMG (HD-SEMG) in addition to mean frequency, a conventional measure of muscle fatigue. Nineteen male participants were included in the study (FHP group (n = 9; age = 22.3 ± 1.5 years) and normal group (n = 10; age = 22.5 ± 1.4 years)). Participants held three head positions (e.g., forward, backward, and neutral positions) for a total of 30 min each, and the EMG activity of the trapezius pars descendens muscle during posture maintenance was measured by HD-SEMG. The root mean square (RMS), the modified entropy, and the correlation coefficient were calculated. Additionally, the visual analogue scale (VAS) was evaluated to assess subjective fatigue. The RMS, VAS, modified entropy, and correlation coefficients were significantly higher in the FHP group than in the normal group (p < 0.001). With increasing postural maintenance time, the modified entropy and correlation coefficient values significantly decreased, and the mean frequency and VAS values significantly increased (p < 0.001). Furthermore, the forward position had significantly higher RMS, correlation coefficient, modified entropy, and VAS values than in the neutral position (p < 0.001). The HD-SEMG potential distribution patterns in the FHP group showed less heterogeneity and greater muscle activity in the entire muscle and subjective fatigue than those in the normal group. Excess muscle activity even in the neutral/comfortable position in the FHP group could potentially be a mechanism of neuromuscular conditions in this population.

Suicide Attitudes Among Suicide Loss Survivors and Their Adaptation to Loss: A Cross-Cultural Study in Japan and the United States.

Survivors' adaptation to a suicide loss is likely influenced by their attitudes toward suicide and their respective sociocultural contexts. Our study aimed to compare suicide attitudes and their association with depressive symptoms and sense of community safety in Japanese and American suicide loss survivors. A total of 193 Japanese survivors and 232 American survivors completed online surveys. The results show that Japanese survivors tended not to consider suicide as an illness or to recognize that others understood their experience but were more likely than American survivors to consider suicide as justifiable. Regression analyses indicated that taking suicide as a right was associated with depressive symptoms. Further, their sense of being understood by others was positively correlated with perceived community safety in both samples, but justifying suicide and considering it to be an illness was positively related to perceived community safety only among Japanese survivors.

A convolutional neural network for estimating synaptic connectivity from spike trains.

The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset. Here we present another method using a Convolutional Neural Network for Estimating synaptic Connectivity from spike trains. After adaptation to huge amounts of simulated data, this method robustly captures the specific feature of monosynaptic impact in a noisy cross-correlogram. There are no user-adjustable parameters. With this new method, we have constructed diagrams of neuronal circuits recorded in several cortical areas of monkeys.

Comparison of neuronal responses in primate inferior-temporal cortex and feed-forward deep neural network model with regard to information processing of faces.

Feed-forward deep neural networks have better performance in object categorization tasks than other models of computer vision. To understand the relationship between feed-forward deep networks and the primate brain, we investigated representations of upright and inverted faces in a convolutional deep neural network model and compared them with representations by neurons in the monkey anterior inferior-temporal cortex, area TE. We applied principal component analysis to feature vectors in each model layer to visualize the relationship between the vectors of the upright and inverted faces. The vectors of the upright and inverted monkey faces were more separated through the convolution layers. In the fully-connected layers, the separation among human individuals for upright faces was larger than for inverted faces. The Spearman correlation between each model layer and TE neurons reached a maximum at the fully-connected layers. These results indicate that the processing of faces in the fully-connected layers might resemble the asymmetric representation of upright and inverted faces by the TE neurons. The separation of upright and inverted faces might take place by feed-forward processing in the visual cortex, and separations among human individuals for upright faces, which were larger than those for inverted faces, might occur in area TE.

Macaque monkeys show reversed ocular following responses to two-frame-motion stimulus presented with inter-stimulus intervals.

When two-frame apparent motion stimuli are presented with an appropriate inter-stimulus interval (ISI), motion is perceived in the direction opposite to the actual image shift. Herein, we measured a simple eye movement, ocular following responses (OFRs), in macaque monkeys to examine the ISI reversal effect on oculomotor. Two-frame movies with an ISI induced reversed OFRs. Without ISI, the OFRs to the two-frame movie were induced in the direction of the stimulus shift. However, with ISIs ≥10 ms, OFRs in the direction opposite to the phase shift were observed. This directional reversal persisted for ISIs up to 160 ms; for longer ISIs virtually no ocular response was observed. Furthermore, longer exposure to the initial image (Motion onset delay: MOD) reduced OFRs. We show that these dependences on ISIs/MODs can be explained by the motion energy model. Furthermore, we examined the dependence on ISI reversal using various spatial frequencies. To account for our findings, the optimal frequency of the temporal filters of the energy model must decrease between 0.5 and 1 cycles/°, suggesting that there are at least two channels with different temporal characteristics. These results are consistent with those from humans, suggesting that the temporal filters embedded in human and macaque visual systems are similar. Thus, the macaque monkey is a good animal model for the early visual processing of humans to understand the neural substrates underlying the visual motion detectors that elicit OFRs.

Macroglossia in Beckwith-Wiedemann Syndrome Is Attributed to Skeletal Muscle Hyperplasia.

Macroglossia is a common feature in patients with Beckwith-Wiedemann syndrome (BWS). The underlying cause of macroglossia in BWS remains unknown, and further histological studies are required to uncover its etiology. We present the case of a 5-year-old girl who was diagnosed with BWS and underwent partial tongue resection for difficulties in articulation and aesthetics. The keyhole-shaped partial resection revealed a harder posterior side than the anterior. Microscopically, the posterior side consisted of dense subepithelial eosinophilic areas composed of an abundance of tightly packed skeletal muscle fibers that were arranged in a fascicular or storiform pattern. BWS-associated macroglossia results from skeletal muscle hyperplasia, consistent with true macroglossia. Therefore, tongue resection may be beneficial for such patients. Further studies are required to develop personalized surgical interventions for each patient with BWS.

Improving the Open-Circuit Voltage of Sn-Based Perovskite Solar Cells by Band Alignment at the Electron Transport Layer/Perovskite Layer Interface.

Organic-inorganic lead halide perovskites are promising materials for realization of low-cost and high-efficiency solar cells. Because of the toxicity of lead, Sn-based perovskite materials have been developed as alternatives to enable fabrication of Pb-free perovskite solar cells. However, the solar cell performance of Sn-based perovskite solar cells (Sn-PSCs) remains poor because of their large open-circuit voltage (VOC) loss. Sn-based perovskite materials have lower electron affinities than Pb-based perovskite materials, which result in larger conduction band offset (CBO) values at the interface between the Sn-based perovskite and a conventional electron transport layer (ETL) material such as TiO2. Herein, the relationship between the VOC and the CBO in these devices was studied to improve the solar cell performances of Sn-PSCs. It was found that the band offset at the ETL/perovskite layer interface affects the VOC of the Sn-PSCs significantly but does not affect that of the Pb-PSCs because the Sn-based perovskite material is a p-type semiconductor, unlike the Pb-based perovskite. It was also found that Nb2O5 has the CBO that is closest to zero for Sn-based perovskite materials, and the VOC values of Sn-PSCs that use Nb2O5 as their ETL are higher than those of Sn-PSCs using TiO2 or SnO2 ETLs. This study indicates that control of the energy alignment at the ETL/perovskite layer interface is an important factor in improving the VOC values of Sn-PSCs.

A case of desmoplastic fibroma of bone with CTNNB1 point mutation.

Desmoplastic fibroma of bone (DFB), a bone tumor, is considered to be an osseous counterpart of desmoid-type fibromatosis (DF). Herein, we report a case of DFB with CTNNB1 point mutation. The 5-year-old male patient had complained of trismus and pain in the jaw. Magnetic resonance imaging revealed a mass in the left mandible. Radical treatment involved surgical resection. Microscopically, the lesion consisted of a bundle-like proliferation of uniform spindle-shaped cells with abundant collagenous stroma, which resembled DF. Immunohistochemical analysis revealed intranuclear accumulation of ß-catenin in the tumor cells. Based on clinical and histologic analysis, we diagnosed the patient as having DFB. We examined the CTNNB1 and APC sequence and found an A-to-G transition at codon 41 of CTNNB1; i.e., Thr was substituted by Ala. Our findings suggest that the dysregulation of Wnt/ß-catenin signaling pathway is related to the tumorigenesis of some cases of DFB. This hypothesis indicates that there are some cases of DFB in which nuclear positive expression of ß-catenin is useful for diagnosis.

Is Suicide Beautiful?

Background: The sociocultural context shapes attitudes toward suicide. Japanese literary works such as the Hagakure and the Bunraku Sonezaki-Shinju depict suicide as beautiful and honorable. Although suicide acceptance is likely to affect suicide rates and prevention efforts in Japan, studies in this area are limited. Aims: This study aimed to explore suicide acceptance and related factors among Japanese participants. Method: Using an Internet research company, questionnaires were distributed that measured acceptance of suicide, suicide stigma, mental health, an opinion on suicide prevention efforts, and demographic variables. Data from 2,051 participants were analyzed using t tests, analysis of variance (ANOVA), and hierarchical regression analysis. Results: We found a two-factor model (comprising beautification and justification factors) for the suicide acceptance scale and confirmed the scale's validity and reliability. The results showed significant differences in suicide acceptance by gender, age, educational level, employment status, and bereavement experience. A hierarchical regression analysis model revealed that suicide beautification was negatively related to positive opinion on suicide prevention efforts. Limitations: This study only focused on Japanese participants; therefore, further studies and cross-cultural comparisons are needed. Conclusion: The results revealed that suicide beautification was negatively associated with positive opinion on suicide prevention efforts after controlling for other variables.

Model of optokinetic responses involving two different visual motion processing pathways.

To understand visual motion processing underlying the optokinetic response (OKR), we developed a biomimetic model that reproduces the findings from behavioral experiments. We recorded OKRs induced by drifting gratings with different spatiotemporal frequencies from humans and non-human primates. The characteristics of the initial open-loop responses and the closed-loop eye velocity gains were analyzed using a model developed in this study. The model consists of two pathways with different dynamics. One mediates the transient response (transient pathway) and the other the sustained response (sustained pathway). Each pathway has a different spatiotemporal frequency dependence. Assuming there are different visual sensitivities for these pathways, one tuned to lower spatial and higher temporal frequencies on the retina and the other tuned to stimulus velocity, we successfully reproduced the course of OKRs. Our results suggest that two different neural circuitries/populations contribute to visual processing in the different stages of OKRs.

Parental Grief After Offspring Suicide and Adaptation to the Loss in Japan.

Several reports have indicated that grief and mental health outcomes of people bereaved by suicide vary by their relationship to the deceased. Parents who have lost offspring experience higher levels of distress than those with other relationships to the deceased. However, there are limited studies investigating the experience of parental bereavement by suicide, and further research is needed. The present study aimed to clarify the differences in grief reactions between bereaved parents and those with other relationships to the deceased in Japan and explore a statistical model of adaptation to the loss. In total, 105 bereaved participants completed a questionnaire covering grief reaction, meaning reconstruction, mental health, social context, and demographic variables. Parents scored higher on several grief reaction items and lower in sense-making than those with other relationships. In addition, path analysis showed that sense-making acted as a moderator in the experience of loss of offspring and grief reaction.

Two-frame apparent motion presented with an inter-stimulus interval reverses optokinetic responses in mice.

Two successive image frames presented with a blank inter-stimulus interval (ISI) induce reversals of perceived motion in humans. This illusory effect is a manifestation of the temporal properties of image filters embedded in the visual processing pathway. In the present study, ISI experiments were performed to identify the temporal characteristics of vision underlying optokinetic responses (OKRs) in mice. These responses are thought to be mediated by subcortical visual processing. OKRs of C57BL/6 J mice, induced by a 1/4-wavelength shift of a square-wave grating presented with and without an ISI were recorded. When a 1/4-wavelength shift was presented without, or with shorter ISIs (≤106.7 ms), OKRs were induced in the direction of the shift, with progressively decreasing amplitude as the ISI increased. However, when ISIs were 213.3 ms or longer, OKR direction reversed. Similar dependence on ISIs was also obtained using a sinusoidal grating. We subsequently quantitatively estimated temporal filters based on the ISI effects. We found that filters with biphasic impulse response functions could reproduce the ISI and temporal frequency dependence of the mouse OKR. Comparison with human psychophysics and behaviors suggests that mouse vision has more sluggish response dynamics to light signals than that of humans.

Autoimmune sialadenitis is associated with the upregulation of chemokine/chemokine receptor pairs in T cell-specific TRAF6-deficient mice.

Sialadenitis is an inflammatory condition affecting the salivary glands including the parotid, submandibular, and sublingual glands. There are several different types of sialadenitis, each with different sites of predilection. However, the pathogenic mechanism underlying the tissue specificity of sialadenitis is largely unknown. TRAF6 is a cytoplasmic adaptor protein that is necessary for the activation of dendritic cells in response to Toll-like receptor ligands, thereby regulating innate immune responses. We previously demonstrated that T cell-specific TRAF6-deficient mice (TRAF6ΔT mice) spontaneously develop systemic inflammatory disease. Here, we show that salivary secretion is reduced in TRAF6ΔT mice due to sialadenitis that occurs in the parotid and submandibular glands, but not the sublingual glands. Consistent with pathological findings, both CD4+ and CD8+ T cells predominantly infiltrated the submandibular glands; however, sublingual infiltration was rare in TRAF6ΔT mice. The TH1 cytokine IFN-γ, the TH1 cell attractant chemokine CCL2, and its cognate receptor CCR2 were upregulated concomitantly in both the submandibular and sublingual glands. Interestingly, the TH17 cell attractant chemokine CCL20 and its cognate receptor CCR6 were selectively increased in the submandibular glands, but not in the sublingual glands of TRAF6ΔT mice. Thus, the expression of TRAF6 in T cells might be implicated in tissue-specific sialadenitis by regulating the chemokine-chemokine receptor system.

Difference in transducin-like enhancer of split 1 protein expression between basal cell adenomas and basal cell adenocarcinomas - an immunohistochemical study.

BACKGROUND: Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are benign and malignant, basaloid salivary gland neoplasms, respectively. These tumors show a dual-cell proliferation of inner luminal/ductal cells and outer abluminal/myoepithelial or basal cells. The only difference between them is defined as a malignant morphology such as invasion. Recently, the nuclear expression of ß-catenin and a catenin beta-1 (CTNNB1) mutation were found in BCA. Transducin-like enhancer of split 1 (TLE1) belongs to the Groucho/TLE family, and it functions in the "off" state in the Wnt/ß-catenin signaling pathway. We hypothesized that if the dysregulation of the Wnt/ß-catenin signaling pathway could be attributed to the tumorigenesis of BCA/BCAC, there might be differences in TLE1 expression between BCA and BCAC. METHOD: The study included 35 BCA and 4 BCAC cases. We performed immunohistochemistry to detect TLE1 and ß-catenin and investigated the catenin beta-1 (CTNNB1) mutational profile among BCA and BCAC cases. RESULTS: In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of ß-catenin in abluminal cells. The BCA cases harbored CTNNB1 gene mutations (12/35). In BCAC, luminal cell staining of TLE1 was identical to BCA in non-invasive areas (4/4) but indistinct in invasive areas (3/4). The BCAC cases were ß-catenin positive for abluminal cells in both areas. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. CONCLUSIONS: Immunohistochemical analysis for TLE1 can identify BCA and BCAC by luminal cell staining difference, especially indistinct luminal cell expression for TLE1 in invasive areas of BCAC. Moreover, TLE1 can be luminal/ductal cell markers.

Aggregatibacter actinomycetemcomitans infection causes DNA double-strand breaks in host cells.

Periodontal disease, an inflammatory disease, is caused by infection with periodontal pathogens. Long-term periodontal disease increases the risk of oral carcinogenesis. Similar to other peptic cancers, oral carcinogenesis also requires multiple genome instabilities; however, the risk factors related to the accumulation of genome instabilities are poorly understood. Here, we suggested that specific periodontal pathogens may increase the risk of genome instability. Accordingly, we screened several periodontal pathogens based on the ability to induce DNA double-strand breaks (DSBs) in host cells. We found that Aggregatibacter actinomycetemcomitans Y4 infection induced DSB formation in host cells. To assess whether DSB formation induced by infection with A. actinomycetemcomitans occurred through apoptotic chromosome fragmentation, cells were treated with a caspase inhibitor, Z-VAD-FMK. DSB accumulation induced by infection with A. actinomycetemcomitans was observed, even in the presence of Z-VAD-FMK, suggesting that this breakage occurred independently of apoptosis. These results suggested that some periodontal pathogens can increase the risk of genome instabilities in host cells and subsequently increase the risk of carcinogenesis.