Age-related differences in the characteristics of persistent postural-perceptual dizziness.

Objective: To investigate differences in the clinical characteristics of patients with persistent postural-perceptual dizziness (PPPD) according to age. Methods: We retrospectively reviewed 143 patients diagnosed with PPPD. Patients were classified into three groups by age: young group (19 to 44 years, n = 60), middle-age group (45 to 64 years, n = 56), old group (65 to 85 years, n = 27). Demographic data, scores of the Dizziness Handicap Inventory (DHI), the Niigata PPPD Questionnaire (NPQ), the Hospital Anxiety and Depression Scale (HADS), precipitating conditions, and the results of vestibular function tests including caloric testing, video head impulse test (vHIT), cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs), and posturography, were compared among the three groups. Results: While there were no significant differences in the scores of the DHI or NPQ, the total score and anxiety score in HADS in the young group were significantly higher than in the old group (p < 0.05, each). On the other hand, for precipitating conditions, the rate of peripheral vestibular diseases was significantly greater in the old group (77.8%) compared to the young group (41.7%, p < 0.01). There was no significant difference in the results of caloric testing, vHIT, cVEMPs, or oVEMPs among the three groups. For posturography, the velocity of the center of pressure with eyes-open as well as with eyes-closed was significantly greater in the old group compared to the young group and the middle-age group (p < 0.005, respectively). Conclusion: The clinical characteristics of PPPD were different according to age. Young patients tended to have stronger anxiety than old patients whereas the old patients had a higher proportion of peripheral vestibular diseases among the precipitating conditions compared to young patients.

Comprehensive genomic profiling of salivary gland carcinoma: Analysis of the Center for Cancer Genomics and Advanced Therapeutics database in Japan.

Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C-CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Impact of salvage chemotherapy after immune checkpoint inhibitor for recurrent or metastatic head and neck cancer.

BACKGROUND: It is unclear witch regimen is optimal as salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) monotherapy for recurrent or metastatic head and neck cancer (RM-HNC). METHODS: This study enrolled 109 patients. Overall survival (OS) and progression-free survival 2 (PFS2) were compared between patients stratified by SCT regimen. RESULTS: Of the 109 patients, 55 underwent SCT after the failure of ICI monotherapy. The OS of these 55 patients was longer than that of patients who did not undergo SCT. The OS and PFS2 were similar between patients treated with paclitaxel (PTX) and cetuximab (Cmab) combination and those treated with PTX monotherapy. The occurrence of irAEs did not impact PFS2 nor OS. CONCLUSIONS: SCT can improve the survival outcomes of patients with RM-HNC. In addition to PTX and Cmab, PTX monotherapy is also considered an effective SCT regimen. SCT is effective regardless of the presence or absence of irAEs.

Estimated incidence and characteristics of vestibular neuritis in Japan: A nationwide survey.

OBJECTIVE: To assess the annual incidence of vestibular neuritis (VN) in the Japanese population. METHODS: We conducted a mail-based survey targeting otolaryngologic clinics and hospitals across Japan to estimate the annual number of patients who were newly-diagnosed with VN during the one-year period of 2021. Using a stratified sampling method, we selected 1,107 departments and asked them to report the number of new patients with VN and their demographics. The total number of VN patients was estimated by multiplying the reported numbers by the reciprocal of the sampling rate and response rate. RESULTS: The overall survey response rate was 40.5 % (448 departments). The estimated number of newly-diagnosed VN patients in 2021 was 8,861 (95 % confidential interval [CI], 2,290-15,432) The annual incidence of VN was 7.05 per 100,000 population in Japan. The male-to-female ratio of VN patients was 0.96, and the mean age was 60.3 ± 16.1 years (range 11-94 years). CONCLUSIONS: The annual incidence of VN in Japan in 2021 had almost doubled and the mean age had become older compared to the previous study in 1993 (annual incidence; 3.5 per 100,000 per year; mean age: 45 years).

Association of worker's mental health with changes in exercise time, going-out time, and screen time (TV time, internet time, and game time) before and after the COVID-19 pandemic: A cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic and government regulations have affected the daily lives and mental health of individuals worldwide. This study aimed to determine how much the change in time spent on exercise (exercise time), outdoor activities ("going-out" time), and screen usage (screen time) before and after the COVID-19 pandemic has affected mental health (depression, anxiety, and insomnia). In June 2021, during the third wave of the COVID-19 pandemic, a web-based, cross-sectional survey was conducted in Japan through an online research company. A total of 824 workers participated in this study. Depression, anxiety, and insomnia were assessed using the Patient Health Questionnaire-9, General Anxiety Disorder-7, and Insomnia Severity Index, respectively. The symptoms of depression were associated with age and decreased exercise time. Symptoms of anxiety were associated with not decreased going-out time. Symptoms of insomnia were associated with reduced exercise time. The results indicated that during the COVID-19 pandemic, an increase in exercise time could have prevented depression and insomnia. Similarly, a decrease in going-out time could have prevented anxiety. Furthermore, in the event of future outbreaks of unpredictable infections, such as COVID-19, decreased going out and increased exercise may help maintain mental health.

Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.

Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites.

Preliminary Experience with 3-Dimensional Exoscope-Assisted Laryngoplasty.

OBJECTIVE: Laryngoplasty requires the manipulation of the vocal folds, which are not visible during the operation. The widespread use of this technique is limited by the need for adequate knowledge of anatomy, the small surgical field, and the high level of skill required for the procedure. An exoscope has been developed to provide a stereoscopic view similar to that of a microscope while using the same compact endoscopic tool. This study aimed to determine whether the three-dimensional (3D) exoscopic surgical technique could be applied to laryngoplasty and explore its possibility to ultimately replace the current approach. METHODS: This was a retrospective case series analysis, which included 28 patients with hoarseness who underwent surgery with (Exoscope; n = 12) or without (Macrosurgery; n = 16) a 3D exoscope between July 2018 and February 2021. The feasibility of performing all surgical steps with the 3D exoscope was evaluated. The Exoscope and Macrosurgery groups were compared for surgical time, vocal function outcomes, and complications. Questionnaires were completed by medical staff regarding the usefulness of medical education. RESULTS: No intraoperative or postoperative complications occurred in either procedure. The operative time was similar in both groups. The vocal function outcomes were also comparable between the groups. Questionnaires revealed that the exoscope was useful in terms of sharing information on surgical procedures and anatomy, as well as functioning as an educational tool. CONCLUSION: While this was a preliminary study, our results indicated that the exclusive use of the 3D exoscope was feasible for open approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1813-1819, 2024.

The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer.

Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HRT3-T1) = 0.42, 95%CI, 0.25-0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1: 0.83, 95%CI, 0.49-1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Inter-day and intra-day variations in effective intensity of noisy galvanic vestibular stimulation to improve postural stability in bilateral vestibulopathy.

BACKGROUND: The reproducibility of the effective intensity of noisy galvanic vestibular stimulation (nGVS) to improve postural stability is not well known. OBJECTIVE: We aimed to investigate inter-day and intra-day variations in effective intensity in patients with bilateral vestibulopathy (BVP). METHODS: Thirteen BVP patients were measured for center-of-pressure movements in the standing posture at five time points: morning of the first test day, morning and evening of the second test day, and morning and evening of the third test day. The mean velocity, the envelopment area, and the root mean square were measured in the eyes-closed condition for 30 s during nGVS application ranging from 0 to 1000µA. The effective intensity was defined as the intensity at which all the three parameters measured during the stimulation were simultaneously smaller than the values at baseline (0µA). RESULTS: Seven of the 13 patients had a common effective intensity throughout the three test days. Six patients on the second test day and five patients on the third test day had no common effective intensity between morning and evening. CONCLUSIONS: The effective intensity of nGVS changes depending on the time during the day as well as between the days.

Dosimetric and radiobiological analyses of a de-escalation strategy for elective nodal regions in human papillomavirus-associated oropharyngeal cancer.

Introduction: In this simulation study, we examined the effects of a de-escalation strategy with a reduced dose to subclinical nodal regions in patients with human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC). Methods: We created two patterns of intensity-modulated radiotherapy for 16 patients with HPV-associated OPC. In the standard and de-escalation plans, the initial field including elective nodal regions received 46 and 30 Gy, followed by 20 and 36 Gy to the cutdown field, respectively. Comparison metrics were set for each organ at risk (OAR). We compared these metric values and the probability of adverse effects based on the normal tissue complication probability (NTCP) model between the two plans. Results: Both plans generally met the dose constraints for the targets and all OAR. Among the comparison metrics, the mean doses to the brain, pharyngeal constrictor muscle, thyroid, and skin and the dose to a 1 % volume of the skin were higher in the standard plan than in the de-escalation plan (P = 0.031, 0.007, < 0.001, < 0.001, and 0.006, respectively). NTCP analyses revealed that the probability of adverse effects in the ipsilateral parotid gland and thyroid was higher in the standard plan than in the de-escalation plan (standard vs. de-escalation plans: ipsilateral parotid gland, 6.4 % vs. 5.0 %, P = 0.016; thyroid, 3.3 % vs. 0.5 %, P < 0.001). Conclusions: A de-escalation strategy with elective nodal regions is a promising treatment to prevent a decline in the quality of life in patients with HPV-associated OPC, particularly xerostomia, dysphagia, and hypothyroidism.

Importance of the Number and Location of Lymph Node Metastasis in Oropharyngeal Cancer.

BACKGROUND/AIM: The 8th edition of the American Joint Committee on Cancer staging system classifies oropharyngeal cancer (OPC) by the expression of p16. The discrepancy observed in this system between pathological and clinical N-stages in p16-positive OPC has provoked controversy. Therefore, this study investigated prognostic factors not included in the new staging system for p16-positive OPC patients. PATIENTS AND METHODS: Patients with non-metastatic OPC receiving radiotherapy were reviewed. Clinical lymph node statuses were reassessed based on contrast-enhanced computed tomography and fluorodeoxyglucose positron emission tomography. Overall survival (OS) and cause-specific survival (CSS) were analyzed using multivariate analyses to adjust baseline imbalances. RESULTS: In total, 166 OPC patients were reviewed. Among them, 81 patients with p16-positive were analyzed. Three or more lymph node metastases (LNM) were observed in 21 p16-positive OPCs. Retropharyngeal lymph node metastasis (Rp) was found in 12. Three-year OS, CSS, and progression-free survival rates in p16-positive patients were 76, 88, and 81%, respectively. In multivariate analyses of p16-positive OPC, LNM ≥3 was a prognostic factor of OS (hazard ratio=9.30, p<0.001) and CSS (hazard ratio=17.80, p=0.005). Rp was associated with poor CSS (hazard ratio=8.73, p=0.03). In N0-1 p16-positive patients, LNM ≥3 trended to be associated with poor OS (hazard ratio=3.93, p=0.06). CSS in patients with Rp was unfavorable (hazard ratio=70.16, p=0.05). CONCLUSION: LNM ≥3 and Rp may be predictive of OS and CCS in p16-positive OPC. These are also possibly used to subcategorize p16-positive cN0-1 OPC. Further validation of lymph node staging is needed to refine the clinical staging system.

Etiology, Severity, Audiogram Type, and Device Usage in Patients with Unilateral Moderate to Profound Sensorineural Hearing Loss in Japan.

BACKGROUND: Few studies have reported on the etiology, severity, or device usage of unilateral sensorineural hearing loss (UHL) compared to bilateral hearing loss. Therefore, this study investigated the characteristics of UHL in adults and children. METHODS: We performed a survey using questionnaires for secondary and tertiary otolaryngology institutions. RESULTS: We included 15,981 patients (1549 children and 14,432 adults) from 196 institutions with otolaryngology residency programs and 2844 patients (336 children and 2508 adults) from 27 institutions with board members of the Japan Audiology Society. The latter submitted audiological data. Among children, most diagnoses were made at age 0. Approximately half of them had profound hearing loss, and 37 children (2.2%) used hearing devices. Among adults, the number of cases increased with age, but decreased when people reached their 80s and 90s. More than half of them had moderate hearing loss. Sudden sensorineural hearing loss was the most common cause of UHL of all ages; 4.4% of UHL patients used hearing devices, and most of the device users (98.6%) selected a conventional hearing aid. CONCLUSIONS: Hearing aid use is limited in children and adults with UHL in Japan. There could be many candidates with UHL for intervention such as a cochlear implant.

Presence of corrective saccades in patients with normal vestibulo-ocular reflex gain in video head impulse test.

Background: The video head impulse test (vHIT) is a valuable clinical tool that can help identify dysfunction of the semicircular canals. While in cases with semicircular canal dysfunction, both decreased vestibulo-ocular reflex (VOR) gain and corrective saccades (CS) are usually observed, there are cases which show CS despite normal VOR gain in vHIT. Objective: This study aimed to investigate the clinical characteristics of patients who showed CS with normal VOR gain in vHIT. Materials and methods: Among 390 patients who underwent vHIT, 51 patients (20 males and 31 females, age 31-87 years, average 61.3 years old) who showed CS with normal VOR gain unilaterally during horizontal vHIT were included. All patients had normal vHIT (normal VOR gain and absent CS) on the contralateral side.The VOR gain of vHIT, the maximum slow phase velocity in the caloric test, and the amplitude of cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were analyzed. Results: The VOR gain on the affected side (0.95 ± 0.08) was significantly smaller than that on the contralateral side (1.03 ± 0.13) in horizontal vHIT (p < 0.001). The maximum slow phase velocity in the caloric test on the affected side (17.9 ± 17.8 degrees/s) was significantly smaller than that on the contralateral side (21.3 ± 16.6 degrees/s, p = 0.020). There were no significant differences in the amplitude of cVEMPs or oVEMPs between the affected side and the contralateral side (p = 0.096 for cVEMP; p = 0.770 for oVEMP). Conclusion: The side that showed CS with normal VOR gain in horizontal vHIT showed significantly smaller VOR gain as well as smaller caloric responses compared to the contralateral side. Having CS with normal VOR gain could be a sensitive indicator of mild dysfunction of the semicircular canals.

Assessment of semicircular canal function in benign paroxysmal positional vertigo using the video head impulse test and caloric test.

Objective: To assess semicircular canal function in benign paroxysmal positional vertigo (BPPV) using the video head impulse test (vHIT) and caloric test. Methods: We retrospectively reviewed 39 patients with idiopathic BPPV who underwent both vHIT and the caloric test. Twenty-one patients had posterior BPPV (p-BPPV) and eighteen had horizontal BPPV (h-BPPV). Vestibulo-ocular reflex (VOR) gain and corrective saccades (CS) were analyzed in vHIT and canal paresis (CP) was calculated in the caloric test. Results: The mean VOR gain of the posterior canal in p-BPPV was 0.75 ± 0.28 on the affected side, which was significantly smaller than that on the contralateral side (0.93 ± 0.24, p = .00738). On the other hand, there were no significant differences in the VOR gain of the horizontal canal in h-BPPV between the affected and the contralateral sides (p = .769). The rates of the presence of CS were not significantly different between the affected canal and the contralateral canal either in p-BPPV (p = .111) or h-BPPV (p = .0599). The mean CP value in h-BPPV patients (43.5 ± 31.3%) was significantly higher than that in p-BPPV patients (22.2 ± 22.9%; p = .0184). Conclusion: The VOR gain of vHIT in the affected canal was significantly smaller than that in the contralateral canal in p-BPPV, but not in h-BPPV. The caloric responses of the affected canal are reduced to a significantly larger extent in h-BPPV compared to p-BPPV. These results suggest that BPPV affects the semicircular canal function differently depending on which semicircular canal is involved.

Oral Administration of TrkB Agonist, 7, 8-Dihydroxyflavone Regenerates Hair Cells and Restores Function after Gentamicin-Induced Vestibular Injury in Guinea Pig.

The causes of vestibular dysfunction include the loss of hair cells (HCs), synapses beneath the HCs, and nerve fibers. 7, 8-dihydroxyflavone (DHF) mimics the physiological functions of brain-derived neurotrophic factor. We investigated the effects of the orally-administered DHF in the guinea pig crista ampullaris after gentamicin (GM)-induced injury. Twenty animals treated with GM received daily administration of DHF or saline for 14 or 28 days (DHF (+) or DHF (-) group; N = 5, each). At 14 days after GM treatment, almost all of the HCs had disappeared in both groups. At 28 days, the HCs number in DHF (+) and DHF (-) groups was 74% and 49%, respectively, compared to GM-untreated control. In the ampullary nerves, neurofilament 200 positive rate in the DHF (+) group was 91% at 28 days, which was significantly higher than 42% in DHF (-). On day 28, the synaptic connections observed between C-terminal-binding protein 2-positive and postsynaptic density protein-95-positive puncta were restored, and caloric response was significantly improved in DHF (+) group (canal paresis: 57.4% in DHF (+) and 100% in DHF (-)). Taken together, the oral administration of DHF may be a novel therapeutic approach for treating vestibular dysfunction in humans.

Mature dendritic cells enriched in regulatory molecules may control regulatory T cells and the prognosis of head and neck cancer.

We previously reported that regulatory T (Treg) cells expressing CTLA-4 on the cell surface are abundant in head and neck squamous cell carcinoma (HNSCC). The role of expanded Treg cells in the tumor microenvironment of HNSCC remains unclear. In this study, we reveal that the tumor microenvironment of HNSCC is characterized by the high expression of genes related to Treg cells, dendritic cells (DCs), and interleukin (IL)-17-related molecules. Increased expression of IL17A, IL17F, or IL23A contributes to a favorable prognosis of HNSCC. In the tumor microenvironment of HNSCC, IL23A and IL12B are expressed in mature dendritic cells enriched in regulatory molecules (mregDCs). The mregDCs in HNSCC are a migratory and mature phenotype; their signature genes strongly correlate with Treg signature genes in HNSCC. We also observed that IL17A was highly expressed in Th17 cells and exhausted CD8+ T cells in HNSCC. These data suggest that mregDCs in HNSCC may contribute to the prognosis by balancing Treg cells and effector T cells that produce IL-17. Targeting mregDCs may be a novel strategy for developing new immune therapies against HNSCC.

The red ruffed lemur, Varecia rubra (É. Geoffroy Saint-Hilaire, 1812): a comparative morphology investigation of lingual papillae and connective tissue cores.

The morphology of the lingual papillae (filiform, foliate, fungiform, and vallate papillae) and the underlying connective tissue core of the red ruffed lemur (Varecia rubra) of a strepsirrhines species were studied using light and scanning electron microscopy. The filiform papillae distributed at the root of the tongue were larger than the structures distributed at the body and apex. Six to eight vallate papillae were arranged in a Y-shape at the border between the lingual body and the lingual root. Foliate papillae were observed at the posterior lateral border of the tongue. Scanning electron microscopy revealed a primary process and numerous auxiliary processes in the epithelial layer of filiform papillae. After epithelial removal, the connective tissue core of the filiform papilla showed several protrusions surrounding an oval-shaped depression that extended slightly posteriorly, and a large, maple-shaped filiform papilla was seen in the posterior portion of the tongue. The connective tissue cores of the fungiform papillae exhibited a longitudinally ridged cylindrical structure. The connective tissue core of the foliate papillae had numerous tubular projections arranged along a groove with a salivary gland conduit at the base. As a Lemuridae species, the appearance of the fungiform and filiform papillae of the red ruffed lemur is similar to that reported in previous studies of the ring-tailed lemur, with some differences, especially in the filiform papillary connective tissue core at the base and tongue body border. These findings suggest the taxonomic and phylogenetic origins of the lemurs as well as the influence of dietary diversity.

Ten-year trends in long-term sickness absence among Japanese public servants: 2009-2018.

Sickness absences are a significant public health and economic problem worldwide. However, sickness absence diagnoses and trends have not been reported in much detail in Japan. This study was a retrospective cohort study. We examined data on certified diagnoses and the durations of sickness absence lasting over 90 days (long-term sickness absence) from 2009-2018 among city public servants in Japan. We found that 1) "Mental and behavioral disorders" (495.0-780.6 per 100,000 employees) was the most prevalent reason for long-term sickness absence, and "Mood disorders" (318.6-584.3 per 100,000 employees) was the most prevalent mental disorders diagnosis in each study year; 2) the prevalence of long-term sickness absence for mental disorders showed decreasing trends (781/100,000 in 2009 to 622/100,000 in 2018; [p=0.005, for the trend test]); 3) the trends differed by gender (p<0.05) and age (p<0.001); and 4) the duration of long-term sickness absence related to mental disorders (13.2 ± 9.0 months) was longer than long-term sickness absence resulting from all physical disorders except for diseases of the circulatory system (15.1 ± 11.6 months). Increased focus on significant depressive and neurotic disorders is needed when promoting mental health in the workplace.