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Objective Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. Methods To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1[beta] (IL-1[beta]), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). Results Elevations in night behavior and blood cortisol, IL-1[beta] and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1[beta]and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. Conclusions The increased IL-1[beta]and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Recent research in urothelial carcinoma (UC) has focused on coding mutations, leaving the significance of non-coding mutations unexplored. This study aims to evaluate non-coding DNA mutation frequencies compared to coding regions in normal urothelium and flat lesions, exploring their implications for tumor biology. Using targeted next-generation sequencing with UC-related gene panel, we analyzed non-coding and coding DNA mutation frequencies across 119 samples of flat urothelium encompassing various lesion types. Mutation patterns were examined based on the presence of associated flat or papillary tumors, and we investigated the correlation between mutation rates in target genes and genetic mutations within genomic regions. Intronic mutations (IMs) displayed variability across lesions, with normal urothelium (NU) exhibiting the highest frequency (43%) and urothelial carcinoma in situ (CIS) the lowest (9%). We observed similar sets of frequently mutated genes in both intronic and exonic regions, distinct from promoter region mutations. Although IMs paralleled exonic mutations in NU, reactive atypia, and atypia of unknown significance (AUS), they were less prevalent in dysplasia (DYS) and CIS. In contrast to CIS-associated AUS and DYS lesions, AUS-DYS lesions associated with papillary tumors exclusively exhibited recurrent intronic mutations involving FGFR3 and ERCC2, aligning with mutation patterns seen in exonic regions. ERCC2 intronic mutations correlated with the mutation rates of the gene panel. Our findings suggest that intronic mutations significantly contribute to tumor heterogeneity in urothelial lesions and may potentially be linked to genomic instability, warranting further investigation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Histological assessment of centroblasts is an important evaluation in the diagnosis of follicular lymphoma, but there is substantial observer variation in assessment among hematopathologists. We aimed to perform quantitative morphological analysis of centroblasts in follicular lymphoma using new artificial intelligence technology in relation to the clinical prognosis. Hematoxylin and eosin slides of lesions were prepared from 36 cases of follicular lymphoma before initial chemotherapy. Cases were classified into three groups by clinical course after initial treatment. The 'excellent prognosis' group were without recurrence or progression of follicular lymphoma within 60 months, the 'poor prognosis' group were those that had relapse, exacerbation, or who died due to the follicular lymphoma within 60 months, and the 'indeterminate prognosis' group were those without recurrence or progression but before the passage of 60 months. We created whole slide images and image patches of hematoxylin and eosin sections for all cases. We designed an object detection model specialized for centroblasts by fine-tuning YOLOv5 and segmented all centroblasts in whole slide images. The morphological characteristics of centroblasts in relation to the clinical prognosis of follicular lymphoma were analyzed. Centroblasts in follicular lymphoma of the poor prognosis group were significantly smaller in nuclear size than those in follicular lymphoma of the excellent prognosis group in the following points: median of nuclear area (p = 0.013), long length (p = 0.042), short length (p = 0.007), nuclear area of top 10 % cells (p = 0.024) and short length of top 10 % cells (p = 0.020). Cases with a mean nuclear area of <55 μm 2 had poorer event-free survival than those with a mean nuclear area of ≥55 μm 2 (p < 0.0123). AI methodology is suggested to be able to surpass pathologist's observation in capturing morphological features. Small-sized centroblasts will likely become a new prognostic factor of follicular lymphoma., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In 2020, acquired cystic disease-associated renal cell carcinomas (ACD-RCCs) were reported to harbor KMT2C and TSC2 variants: however, their carcinogenic implication has not yet been reported. This study aimed to explore the variant features of KMT2C and TSC2 in ACD-RCC and their implication in ACD-RCC tumorigenesis. Eleven ACD-RCCs, 10 ACD-RCC-like cysts, and 18 background kidneys were retrieved. The background kidneys consisted of atrophic thyroid follicle-like tubules. They included four with clustered cysts, two with eosinophilic changes, and one each with clear cell changes and sieve-like changes in the renal tubules. First, DNA-targeted sequencing of KMT2C and TSC2 whole exons was performed on eight ACD-RCC samples. Subsequently, a custom DNA panel was designed to include the recurrent KMT2C and TSC2 variants based on the sequencing results. Second, DNA-targeted sequencing was performed on the remaining samples using a custom panel targeting the recurrent variants. Additionally, immunohistochemistry was performed for KMTC, H3K4me1, H3K4me3, TSC2, and GPNMB on the ACD-RCCs. Six of the 11 ACD-RCC cases harbored KMT2C and TSC2 variants, including nine likely pathogenic variants. In contrast to ACD-RCC, 1 of the 9 ACD-RCC-like cysts harbored both variants. Immunohistochemical analysis did not support the loss of function in ACD-RCCs harboring KMT2C and TSC2 variants. KMT2C and TSC2 variant frequencies were higher in ACD-RCC than in other renal cell carcinomas. However, KMT2C and TSC2 are unlikely to be the primary drivers of ACD-RCC development., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Suvorexant is an orexin receptor antagonist that targets the wake-promoting system. Orexin is also known to regulate energy metabolism in rodents, but its role in humans remains largely unknown. Here, we assessed the effect of suvorexant (20 mg) on energy metabolism during sleep and shortly after awakening in a randomized, double-blind, placebo-controlled, crossover study in 14 healthy men. Suvorexant increased rapid eye movement (REM) but decreased nonrapid eye movement (NREM) stage 1. Energy expenditure during wake after sleep onset (WASO) was higher than that during NREM and REM sleep in the placebo but not in the suvorexant trial, suggesting that the increase in energy expenditure during WASO was due to an activation of the orexin system. Fat oxidation during sleep increased, and its effect remained after waking the next morning. Suvorexant decreased protein catabolism but did not affect overall energy expenditure. The orexin system may affect fat oxidation independent of its roles in sleep regulation in humans., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis., Patients and Methods: Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them., Results: Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis., Conclusions: Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer., (© 2024. Society of Surgical Oncology.)

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma and has characteristic nuclear features. Genetic abnormalities of PTC affect recent molecular target therapeutic strategy towards RET-altered cases, and they affect clinical prognosis and progression. However, there has been insufficient objective analysis of the correlation between genetic abnormalities and nuclear features. Using our newly developed methods, we studied the correlation between nuclear morphology and molecular abnormalities of PTC with the aim of predicting genetic abnormalities of PTC. We studied 72 cases of PTC and performed genetic analysis to detect BRAF p.V600E mutation and RET fusions. Nuclear features of PTC, such as nuclear grooves, pseudo-nuclear inclusions, and glassy nuclei, were also automatically detected by deep learning models. After analyzing the correlation between genetic abnormalities and nuclear features of PTC, logistic regression models could be used to predict gene abnormalities. Nuclear features were accurately detected with over 0.90 of AUCs in every class. The ratio of glassy nuclei to nuclear groove and the ratio of pseudo-nuclear inclusion to glassy nuclei were significantly higher in cases that were positive for RET fusions (p = 0.027, p = 0.043, respectively) than in cases that were negative for RET fusions. RET fusions were significantly predicted by glassy nuclei/nuclear grooves, pseudo-nuclear inclusions/glassy nuclei, and age (p = 0.023). Our deep learning models could accurately detect nuclear features. Genetic abnormalities had a correlation with nuclear features of PTC. Furthermore, our artificial intelligence model could significantly predict RET fusions of classic PTC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Haemangioblastomas arise in the central nervous system. Rarely, haemangioblastomas may develop in extra-neural sites, such as the kidneys. A few reported cases of renal cell carcinomas (RCCs) with haemangioblastoma-like features have exhibited both clear cell renal cell carcinoma (CCRCC)- and haemangioblastoma-like components. The clinicopathological and molecular characteristics of RCCs with haemangioblastoma-like features were analysed, focusing on VHL alterations, in comparison with CCRCCs partially resembling haemangioblastoma., Methods and Results: Four RCCs with haemangioblastoma-like features and five CCRCCs partially resembling haemangioblastoma were included. The RCCs with haemangioblastoma-like features were indolent and lacked adverse prognostic factors. All RCCs with haemangioblastoma-like features had a well-circumscribed appearance and a thick fibromuscular capsule, with fibromuscular bundles extending into the tumour to varying degrees in the three tumours. Each RCC with haemangioblastoma-like features exhibited CCRCC-like areas with indistinct tubular structures and foci of haemangioblastoma-like areas, in which vessels and short spindle cells overwhelmed tumour cells. Whereas haemangioblastoma-like areas in the CCRCCs partially resembling haemangioblastoma exhibited sparse vessels and spindle cells and distinct clear cells. The RCCs with haemangioblastoma-like features exhibited a unique immunohistochemical profile, with positive staining for inhibin-α, S100, carbonic-anhydrase-9, keratin7, and high molecular weight keratin and negative staining for (alpha-methylacyl-CoA racemase) AMACR. RCC with haemangioblastoma-like features did not display any VHL alterations, including VHL mutation, 3p LOH, and methylation of the VHL promoter region, and the two tumours harboured a likely oncogenic missense variant of MTOR (c.7280T>G)., Conclusion: The histopathological, immunohistochemical, and molecular findings suggest that RCC with haemangioblastoma-like features is a distinct entity from CCRCC., (© 2023 John Wiley & Sons Ltd.)

Background: In recent years, there has been a diversification of working styles. The concept of workers' well-being is no longer limited to material wealth, such as how satisfied they are with their wages. Psychological enrichment, encompassing factors like motivation and interpersonal relationships, is also important. This study was established to develop a scale to evaluate the well-being of workers, named the Abundance Index for Workers (AIW). This new concept proposed by the authors comprehensively considers both job-related resources and personal and societal resources., Methods: This study was carried out as part of the Tsukuba Salutogenic Occupational Cohort Study (T-SOCS). We utilized data from a survey targeting workers affiliated with institutions under the Tsukuba Science City Network, examining aspects of their daily life, work, and mental health. The deviation scores for each survey item were averaged to calculate an overall score. The correlations of the comprehensive score with the Patient Health Questionnaire-9 (PHQ-9) index for depression and the Single-item Presenteeism Question (SPQ) index for presenteeism were analyzed to determine criterion-related validity., Results: The number of participants analyzed was 2,745. Factor analysis categorized the data into three factors: workplace mental health, societal resources, and lifestyle habits. Cronbach's α coefficient was 0.688. There were correlations of -0.363 (p < 0.001) between the total score and SPQ, and -0.558 (p < 0.001) between the total score and PHQ-9, suggesting a degree of criterion-related validity., Conclusions: In this study, we designed a test battery that assesses workers' well-being based on job-related resources and the richness of societal resources. The internal consistency of this battery was not as high as expected due to the broad scope of well-being. Although it is difficult to evaluate workers' well-being on a single scale, we believe that the AIW functions well as a test battery by combining scales with different attributes, which enables well-being to be captured from as many different perspectives as possible. This tool is designed to assist individuals in evaluating their own well-being and recognizing factors that can enhance it., Trial Registration: Not applicable; this study is not an intervention trial.

Laminin332 is a glycoprotein consisting of α3/β3/γ2 chains, of which the γ2 chain (Ln-γ2) is expressed in tumor cells at the invasive front in many types of malignant tumors. We have previously reported that Ln-γ2 is associated with tumor invasion of cutaneous squamous cell carcinoma (cSCC) in vivo and in vitro. Recently, tumor budding (TB; invasion patterns in small clusters of less than five cancer cells in the stroma at the invasive front) has been reported to be a risk factor for lymph node metastasis in cSCC. Based on these findings, we speculated that expression of Ln-γ2 is related to TB in cSCC and would be an invasive factor that causes lymph node metastasis. In this study, we investigated the relationship between Ln-γ2 expression and clinicopathological findings, including TB, in 102 cases of cSCC using immunohistochemistry. The results showed that high expression of Ln-γ2 at the invasive front correlated with a high TB score. In addition, high Ln-γ2 expression at the invasive front was also associated with lymphatic invasion, lymph node metastasis, and poor prognosis (death or recurrence), as in TB. Furthermore, we showed a positive association between Ln-γ2 expression at the invasive front and Yes-associated protein (YAP) expression in the Hippo pathway. Our results suggest that Ln-γ2 expression at the invasive front may have a role in TB formation via YAP and contribute to prognosis by causing lymphatic invasion and lymph node metastasis. The expression of Ln-γ2 would be useful for risk assessment of lymph node metastasis and poor prognosis in routine practice of cSCC., (© 2023 Japanese Dermatological Association.)

Background: The COVID-19 pandemic has brought to light the prevalence of mental health issues among nurses. Work engagement (WE) is a concept that describes work-related positive psychological states and is of importance within mental health measures. There is, however, a lack of research on factors associated with the WE of nurses during the COVID-19 pandemic., Objective: We aimed to determine which factors are associated with WE among nurses during the COVID-19 pandemic using the job demands-resources (JD-R) model as a framework., Methods: A web-based cross-sectional survey was conducted among nurses working in acute care and psychiatric institutions in the prefectures of Chiba and Tokyo in Japan. The survey period occurred between August 8 and September 30, 2021, during a time when the number of patients with a positive COVID-19 infection increased. The 3-item version of the Utrecht Work Engagement Scale (UWES-3) was used to measure WE. Factors such as age, gender, years of experience, affiliated ward, COVID-19-related stress, financial rewards from the government and hospital, encouragement from the government and patients, and workplace social capital were assessed. A total of 187 participants were included in the final analysis. Multiple regression analysis was performed to examine the factors related to WE. Partial regression coefficients (B), 95% CI, and P values were calculated., Results: The mean overall score for the UWES-3 was 3.19 (SD 1.21). Factors negatively associated with UWES-3 were COVID-19-related stress on work motivation and escape behavior (Β -0.16, 95% CI -0.24 to -0.090; P<.001), and factors positively associated with UWES-3 were affiliation of intensive care units (Β 0.76, 95% CI 0.020-1.50; P=.045) and financial rewards from the government and hospital (Β 0.40, 95% CI 0.040-0.76; P=.03)., Conclusions: This study examined factors related to WE among nurses during the COVID-19 pandemic using the JD-R model. When compared with findings from previous studies, our results suggest that nurses' WE was lower than before the COVID-19 pandemic. Negative motivation and escape behaviors related to COVID-19 were negatively associated with WE, while there were positive associations with financial rewards from the government and hospital and affiliation with an intensive care unit. Further research into larger populations is needed to confirm these findings., (©Kei Muroi, Mami Ishitsuka, Tomoko Hachisuka, Itsuka Shibata, Tomohiko Ikeda, Daisuke Hori, Shotaro Doki, Tsukasa Takahashi, Shin-ichiro Sasahara, Ichiyo Matsuzaki. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.11.2023.)

Objective: Traumatic childhood experiences such as domestic violence and bullying have been reported to be associated with insomnia in adulthood. However, little evidence is available for the long-term effects of childhood adversity on workers' insomnia worldwide. Our objective was to examine whether childhood experiences of bullying and domestic violence are associated with insomnia in workers in adulthood., Methods: We used survey data from a cross-sectional study of the Tsukuba Science City Network in Tsukuba City, Japan. Workers aged 20 to 65 years (4509 men and 2666 women) were targeted. Binomial logistic regression analysis was performed with the Athens Insomnia Scale as the objective variable., Results: Binomial logistic regression analysis showed that childhood bullying and domestic violence experience of childhood bullying and domestic violence were associated with insomnia. As for the experience of domestic violence, the higher the time of experience, the higher the odds ratio of insomnia., Conclusions: It may be useful to focus on childhood traumatic experiences regarding insomnia in workers. In the future, objective sleep time and sleep efficiency should be evaluated using an activity meter and other methods to verify the effects of bullying and domestic violence experiences., Competing Interests: Competing interests: Daisuke Hori, Shotaro Doki, Shinichiro Sasahara, and Ichiyo Matsuzaki are volunteer members of the Occupational Health Committee of Tsukuba Science City Network., (Copyright: © 2023 Muroi K et al.)

Background: The present study aimed to investigate whether insomnia is associated with suicidal ideation (SI) among Japanese workers by conducting a multi-level analysis with sense of coherence (SOC) as a random effect., Participants and Procedure: A cross-sectional survey was conducted among 19,481 workers in Tsukuba, Japan. Data from 7,175 participants aged 20-65 years were included in the analysis. The Athens Insomnia Scale (AIS) was used as the independent variable, and SI over the past year was used as the dependent variable. SOC was measured using the five-point SOC-13 scale, and socioeconomic and health factors were investigated as covariates. Participants were divided into three groups (low, medium, and high) based on their SOC scores. Multilevel logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI)., Results: In the high-SOC group, only one person had SI. In a multi-level logistic analysis that excluded the high SOC group, insomnia was found to be associated with SI (OR = 2.26, 95% CI [1.75, 2.93]). Furthermore, the AIS sub-items "Final awakening earlier than desired" (OR = 1.26, 95% CI [1.05, 1.50]) and "Sense of well-being during the day" (OR = 1.63, 95% CI [1.34, 1.99]) were associated with SI. 8.95% or 11% of the variation in the presence or absence of SI was found to be explained by differences between SOC groups., Conclusions: The study highlights that insomnia is associated with SI, and that high SOC may reduce SI even under insomnia. Future longitudinal studies are needed to confirm whether high SOC reduces SI due to insomnia., Competing Interests: The authors declare no conflict of interest., (Copyright © Institute of Psychology, University of Gdansk.)

Tumors exhibiting histopathological findings similar to those of hemangioblastoma of the central nervous system (CNS-HB) rarely develop in the kidneys. Currently, renal hemangioblastoma (RHB) is considered analogous to CNS-HB; however, they differ in gross appearance, as well as immunohistochemical and molecular findings. In contrast, some renal cell carcinomas reportedly comprise distinct, clear cell renal cell carcinoma (CCRCC)- and hemangioblastoma (HB)-like areas. Initially, renal cell carcinomas with HB-like features (RCC-HBs) were considered a morphological variant of CCRCC owing to their diverse histological findings. However, the immunohistochemical and molecular findings of RCC-HBs suggest that RCC-HB is distinct from CCRCC. Additionally, one of the RCC-HBs had a focal leiomyomatous stroma and TSC2 variant, suggesting that RCC-HB and RCC with fibromyomatous stroma (RCC-FMS) might belong to the same disease entity. Therefore, we comprehensively reviewed the clinical, pathological, and molecular features of RHB, RCC-HB, and the related tumors and discussed the similarities, differences, and relationships between them. We believe that our review would serve as a foundation for further investigation on elucidating the relationship between CNS-HB, RHB, RCC-HB, and RCC-FMS.

Flat urothelial lesions are controversial diagnostic and prognostic urologic entities whose importance relies mainly on their ability to progress to muscle-invasive tumors via urothelial carcinoma in situ (CIS). However, the carcinogenetic progression of preneoplastic flat urothelial lesions is not well established. Moreover, predictive biomarkers and therapeutic targets of the highly recurrent and aggressive urothelial CIS lesion are lacking. Using a targeted next-generation sequencing (NGS) panel of 17 genes directly involved in bladder cancer pathogenesis, we investigated alterations of genes and pathways with clinical and carcinogenic implications on 119 samples of flat urothelium, including normal urothelium (n = 7), reactive atypia (n = 10), atypia of unknown significance ( n = 34), dysplasia ( n = 23), and CIS (n = 45). The majority of the flat lesions were tumor-associated but grossly/microscopically or temporally separated from the main tumor. Mutations were compared across flat lesions and concerning the concomitant urothelial tumor. Associations between genomic mutations and recurrence after intravesical bacillus Calmette-Guerin treatment were estimated with Cox regression analysis. TERT promoter mutations were highly prevalent in intraurothelial lesions but not in the normal or reactive urothelium, suggesting that it is a critical driver mutation in urothelial tumorigenesis. We found that synchronous atypia of unknown significance-dysplasia-CIS lesions without concomitant papillary urothelial carcinomas had a similar genomic profile that differed from atypia of unknown significance-dysplasia lesions associated with papillary urothelial carcinomas, which harbored significantly more FGFR3, ARID1A, and PIK3CA mutations. KRAS G12C and ERBB2 S310F/Y mutations were exclusively detected in CIS and were associated with recurrence after bacillus Calmette-Guerin treatment (P = .0006 and P = .01, respectively). This targeted NGS study revealed critical mutations involved in the carcinogenetic progression of flat lesions with putative pathobiological pathways. Importantly, KRAS G12C and ERBB2 S310F/Y mutations were identified as potential prognostic and therapeutic biomarkers for urothelial carcinoma., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: It remains unclear how fear of COVID-19 and resilience are related to psychological distress based on occupations among healthcare workers (HCWs) in hospitals treating patients with COVID-19. We conducted a survey on the mental health of HCWs during the COVID-19 pandemic to determine the relationship between factors such as fear of COVID-19 and resilience as well as mental distress in each occupation of HCWs., Methods: We conducted a web-based survey among HCWs at seven hospitals treating COVID-19 patients in Japan from December 24, 2020 to March 31, 2021. A total of 634 participants were analyzed, and information regarding their socio-demographic characteristics and employment status was collected. Several psychometric measures were used, including the Kessler's Psychological Distress Scale (K6), the fear of COVID-19 Scale (FCV-19S), and the Resilience Scale (RS14). Factors related to psychological distress were identified by logistic regression analysis. The association between job title and psychological scales was examined by one-way ANOVA, and t -tests were conducted to examine the association between the FCV-19S and hospital initiatives., Results: It was found that nurses and clerical workers were associated with psychological distress without considering FCV-19S or RS14; in a model that included FCV-19S, FCV-19S was associated with psychological distress, but job title was not; when RS14 was considered, resilience was protective. In terms of occupation, FCV-19S was lower among physicians and higher among nurses and clerical workers, while RS14 was higher among physicians and lower among other occupations. Having access to in-hospital consultation regarding infection control as well as to psychological and emotional support was associated with lower FCV-19S., Conclusion: Based on our findings, we can conclude that the level of mental distress differed by occupation and the differences in the fear of COVID-19 and resilience were important factors. In order to provide mental healthcare for HCWs during a pandemic, it is important to create consultation services that enable employees to discuss their concerns. In addition, it is important to take steps to strengthen the resilience of HCWs in preparation for future disasters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Midorikawa, Tachikawa, Kushibiki, Wataya, Takahashi, Shiratori, Nemoto, Sasahara, Doki, Hori, Matsuzaki, Arai and Yamagata.)

Olfactory disorders, which are closely related to cognitive deterioration, can be caused by several factors, including infections, such as COVID-19; aging; and environmental chemicals. Injured olfactory receptor neurons (ORNs) regenerate after birth, but it is unclear which receptors and sensors are involved in ORN regeneration. Recently, there has been great focus on the involvement of transient receptor potential vanilloid (TRPV) channels, which are nociceptors expressed on sensory nerves during the healing of damaged tissues. The localization of TRPV in the olfactory nervous system has been reported in the past, but its function there are unclear. Here, we investigated how TRPV1 and TRPV4 channels are involved in ORN regeneration. TRPV1 knockout (KO), TRPV4 KO, and wild-type (WT) mice were used to model methimazole-induced olfactory dysfunction. The regeneration of ORNs was evaluated using olfactory behavior, histologic examination, and measurement of growth factors. Both TRPV1 and TRPV4 were found to be expressed in the olfactory epithelium (OE). TRPV1, in particular, existed near ORN axons. TRPV4 was marginally expressed in the basal layer of the OE. The proliferation of ORN progenitor cells was reduced in TRPV1 KO mice, which delayed ORN regeneration and the improvement of olfactory behavior. Postinjury OE thickness improved faster in TRPV4 KO mice than WT mice but without acceleration of ORN maturation. The nerve growth factor and transforming growth factor ß levels in TRPV1 KO mice were similar to those in WT mice, and the transforming growth factor ß level was higher than TRPV4 KO mice. TRPV1 was involved in stimulating the proliferation of progenitor cells. TRPV4 modulated their proliferation and maturation. ORN regeneration was regulated by the interaction between TRPV1 and TRPV4. However, in this study, TRPV4 involvement was limited compared with TRPV1. To our knowledge, this is the first study to demonstrate the involvement of TRPV1 and TRPV4 in OE regeneration., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Flat urothelial lesions are important because of their potential for carcinogenesis and development into invasive urothelial carcinomas. However, it is difficult for pathologists to detect early flat urothelial changes and accurately diagnose flat urothelial lesions. To predict the pathologic diagnosis and molecular abnormalities of flat urothelial lesions from pathologic images, artificial intelligence with an interpretable method was used. Next-generation sequencing on 110 hematoxylin and eosin-stained slides of normal urothelium and flat urothelial lesions, including atypical urothelium, dysplasia, and carcinoma in situ, detected 17 types of molecular abnormalities. To generate an interpretable prediction, a new method for segmenting urothelium and a new pathologic criteria-based artificial intelligence (PCB-AI) model was developed. κ Statistics and accuracy measurements were used to evaluate the ability of the model to predict the pathologic diagnosis. The likelihood ratio test was performed to evaluate the logistic regression models for predicting molecular abnormalities. The diagnostic prediction of the PCB-AI model was almost in perfect agreement with the pathologists' diagnoses (weighted κ = 0.98). PCB-AI significantly predicted some molecular abnormalities in an interpretable manner, including abnormalities of TP53 (P = 0.02), RB1 (P = 0.04), and ERCC2 (P = 0.04). Thus, this study developed a new method of obtaining accurate urothelial segmentation, interpretable prediction of pathologic diagnosis, and interpretable prediction of molecular abnormalities., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objectives: Pathologic diagnosis of flat urothelial lesions is subject to high interobserver variability. We expected that deep learning could improve the accuracy and consistency of such pathologic diagnosis, although the learning process is a black box. We therefore propose a new approach for pathologic image classification incorporating the diagnostic process of the pathologist into a deep learning method., Methods: A total of 267 H&E-stained slides of normal urothelium and urothelial lesions from 127 cases were examined. Six independent convolutional neural networks were trained to classify pathologic images according to six pathologic criteria. We then used these networks in the main training for the final diagnosis., Results: Compared with conventional manual analysis, our method significantly improved the classification accuracy of images of flat urothelial lesions. The automated classification showed almost perfect agreement (weighted κ = 0.98) with the consensus reading. In addition, our approach provides the advantages of reliable diagnosis corresponding to histologic interpretation., Conclusions: We used deep learning to establish an automated subtype classifier for flat urothelial lesions that successfully combines traditional morphologic approaches and complex deep learning to achieve a learning mechanism that seems plausible to the pathologist., (© Crown copyright 2022.)

The purpose of this study was to compare complications and the number of ghrelin-expressing cells (GECs) after bariatric arterial embolization (BAE) using soluble gelatin sponge particles (SGSs) or tris-acryl gelatin microspheres (MSs) in swine. Twelve swine underwent embolization of gastric fundal arteries with SGSs (n = 4) or MSs (n = 4) or underwent saline infusion (n = 4, control group). One week later, the number of gastric ulcers and the percentage of GECs were compared among the 3 groups. There were no ulcers in the SGS and control groups. Two swine in the MS group had 4 large ulcers (12-50 mm in size). The mean percentages of GECs were significantly lower in the SGS (2.7% ± 0.9%) and MS (2.5% ± 1.0%) groups compared with the control group (3.7% ± 1.3%; P = .038 and P = .016, respectively). SGSs may be safer than MSs for BAE while inducing a similar reduction of GECs in swine., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Objectively measured sleep efficiency has recently been shown to be associated with health problems. Although several factors have previously been reported to be associated with sleep efficiency, most of these studies were conducted on older or younger adults, and the factors associated with sleep efficiency in healthy workers remain unknown. The aim of this study was to investigate the relationship between sleep efficiency and lifestyle factors using sleep measurement data recorded by an activity meter worn by workers. In total, 693 workers (male, 43.6%; mean age, 42.7 ± 11.3 years) were recruited from five offices in 2017. Sleep was measured over the period of 1 week by actigraphy. Workers' attributes, lifestyle habits, and occupational stress were identified using a questionnaire, and the association of sleep efficiency with lifestyle, occupational stress, and attributes was explored by logistic regression analysis. A logistic regression analysis using attributes and occupational stress as adjustment variables revealed that "longer sleeping hours on weekends than on weekdays" [odds ratios (OR), 0.66; 95% confidence interval (CI), 0.47-0.94], "water ingestion at bedtime" [OR, 2.09; 95% CI, 1.28-3.41], and "smartphone use at bedtime" [OR, 1.90; 95% CI, 1.28-2.83] were associated with decreased sleep efficiency. This study found that lifestyle habits were associated with sleep efficiency among workers. It is necessary to verify whether intervention in these lifestyle habits would contribute to the improvement of sleep efficiency in future studies., Competing Interests: Yu Ikeda, Emi Morita, Kei Muroi, Yo Arai, Tomohiko Ikeda, Tsukasa Takahashi, Nagisa Shiraki, Shotaro Doki, Daisuke Hori, Yuichi Oi, Shin-ichiro Sasahara, Asuka Ishihara, Sumire Matsumoto, Masashi Yanagisawa, Makoto Satoh, and Ichiyo Matsuzaki are members of the SLEPT Study. The authors declare no financial relationships.

Background: The rapid introduction of teleworking due to the coronavirus disease 2019 pandemic has led to concerns about increases in cyberbullying (CB) worldwide. However, little is known about workplace CB in non-Western countries. The first objective was to clarify the prevalence and characteristics regarding workplace CB victimization in Japan. The second objective was to demonstrate the psychological outcomes of CB victimization in combination with traditional bullying (TB)., Methods: We conducted an anonymous, cross-sectional, Internet-based survey targeting regular employees in Japan (N = 1200) in January 2021. We investigated CB victimization using the Inventory of Cyberbullying Acts at Work and TB victimization by using the Short Negative Act Questionnaire. Possible explanatory factors for TB/CB victimization were sociodemographic variables, personality trait, chronic occupational stress, organizational climate, and gratitude at work. We also measured psychological distress, insomnia, and loneliness to assess adverse effects of workplace bullying. Two-step cluster analysis was used in determining the patterns combined with TB and CB victimization. Hierarchical binomial logistic regression analysis was used., Results: In total, 8.0% of employees reported experiencing CB on a weekly basis. CB victimization was associated with younger age, managerial position, higher qualitative workload, and active information dissemination via the Internet, and frequency of teleworking. Three clusters based on TB and CB victimization patterns were identified: those who belong to the first cluster suffered neither from TB and CB (81.0%), the second cluster suffered only from TB (14.3%), and the third cluster suffered from both TB and CB (4.8%). The third cluster exhibited higher odds ratios (ORs) and 95% confidence intervals (CIs) for psychological distress (OR = 12.63, 95% CI = 4.20-38.03), insomnia (OR = 6.26, 95% CI = 2.80-14.01), and loneliness (OR = 3.24, 95% CI = 1.74-6.04) compared to the first cluster., Conclusions: These findings firstly clarify the prevalence and correlated factors of CB victimization among employees in Japan. Further, we showed that psychological wellbeing can be impaired by the coexistence of TB and CB. Our research could be the first step to develop the effective countermeasures against workplace CB., (© 2022. The Author(s).)

Research on mental health in working populations has predominantly focussed on negative outcomes, while studies on the positive aspects of life remain very limited, especially in Japan. Although morningness has recently been considered a factor for being happy, the role of sleep characteristics as it relates to the association between morningness and happiness has not been substantiated. The aim of this study is to investigate the associations between diurnal preference and level of subjective happiness in healthy, full-time, daytime workers in Japan. We also tested the moderation effect of sleep parameters on the relationship between diurnal preference and subjective happiness. This is an exploratory analysis from the cross-sectional data of the SLeep Epidemiology Project at the University of Tsukuba (SLEPT Study). Subjective happiness was evaluated using a single-item question. Diurnal preference was assessed using the Morningness-Eveningness Questionnaire (MEQ), in which higher scores indicate greater tendency to have morning preference. The participants underwent assessment of sleep parameters for 7 consecutive days using a waist-worn actigraphy device and kept a sleep diary. Sleep parameters investigated were subjective sleep quality, sleep disturbance, daytime sleepiness, weekend oversleep, total sleep time, sleep onset time, wake time, and sleep efficiency. A total of 205 males (average 42.6 ± 10.4 years) and 272 females (41.1 ± 9.8 years) were eligible for analysis. Hierarchical liner regression analysis was used to show the relationships of subjective happiness with MEQ score, and the sleep parameters. Further, moderation analysis was conducted by adding the interaction between MEQ score and the sleep parameters. After adjusting for age, psychological distress, self-rated health, and occupational stress, we found that subjective happiness was significantly associated with higher MEQ score and sleep efficiency but only in female. The moderating role of sleep parameters was not found. We discussed the implications of the obtained results and a possible strategy to maintain and improve subjective happiness of female workers who have evening preference.

Introduction: The interaction of CD155 with its ligand, the T cell immunoreceptor with Ig and ITIM domains (TIGIT), is being studied owing to its potential to act as a target in the treatment of various solid tumors. However, the relationship between CD155 and TIGIT in colorectal cancer (CRC) prognosis is not known. We hypothesized that the TIGIT-CD155 pathway suppresses the attack of T cells on tumors, thereby affecting CRC prognosis., Methods: We examined the expression of CD155 and TIGIT using immunohistochemical staining in 100 consecutive patients with CRC who underwent complete resection of ≤Stage III tumors at Wakayama Medical University Hospital between January and December 2013. We assessed the correlation between CD155 and TIGIT expressions and prognosis as well as the clinicopathological background of CD155 and TIGIT., Results: Patients with high CD155 and TIGIT expressions showed worse prognosis than those with other levels of expression (p = 0.026). In multivariate analysis that also included the existing prognostic markers, high CD155 and TIGIT expressions were identified as independent poor prognostic factors., Conclusions: The interaction between CD155 and TIGIT possibly plays an important role in the immunological mechanism of CRC. Therefore, it may be possible to effectively predict the postoperative prognosis of CRC by evaluating the combined expression of CD155 and TIGIT. The study findings suggest that CD155 and TIGIT can predict clinical outcomes, thereby contributing to the personalized care of CRC., Competing Interests: The authors have declared that no competing interests exist.

Background: Although several molecular analyses have shown that the Kras gene status is related to long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC), the results remain controversial. Here, we examined the Kras gene status in a cohort of unresectable PDAC patients who underwent first-line therapy with gemcitabine and nab-paclitaxel (GA) and assessed differences in chemotherapy responses and survival., Methods: Patients with a histological diagnosis of PDAC (based on EUS-guided fine-needle aspiration) from 2017 to 2019 were enrolled. Tumor genomic DNA was extracted from residual liquid-based cytology specimens and Kras mutations were assessed using the quenching probe method. The relationships between the Kras status and progression-free survival (PFS) and overall survival (OS) were assessed., Results: Of the 110 patients analyzed, 15 had wild-type Kras . Those with the wild-type gene showed significantly longer PFS and OS than those with mutant Kras (6.9/5.3 months ( p = 0.044 ) vs. 19.9/11.8 months ( p = 0.037 ), respectively). Multivariate analyses identified wild-type Kras as a significant independent factor associated with longer PFS and OS (HR = 0.53 ( p = 0.045 ) and HR = 0.35 ( p = 0.007 ), respectively)., Conclusions: The analysis of the Kras gene status could be used to predict therapeutic responses to GA and prognosis in unresectable PDAC patients.

Background: Ibaraki's Amabie-chan is a COVID-19 infection control system unique to Ibaraki prefecture, Japan. It requires residents to register each time they visit events, commercial facilities, and restaurants. The number of registrations has been limited, and its function alerting about people positive for COVID-19 infection seems not to be working. Nevertheless, registration with the system might have some impact on the user's behavior. In the current preliminary survey, the possible impact of Ibaraki's Amabie-chan on infection prevention behavior and fear of COVID-19 was investigated., Methods: A cross-sectional, web-based, anonymous, and self-administered survey was conducted at two workplaces in Tsukuba Science City, Ibaraki, Japan. The first survey was conducted at one of the workplaces in November 2020, and the second survey, at the other workplace in February 2021. Variables of interest were sex, age group, marital status, employment status, Ibaraki's Amabie-chan use, COVID-19 Contact-Confirming Application use, ten items of infection prevention behaviors, and fear of COVID-19. Hierarchical linear regression analysis was performed., Results: In both surveys, use of Ibaraki's Amabie-chan was significantly associated with COCOA use and with "physical condition management such as body temperature measurement." No association was found with other infection prevention behaviors or with fear of COVID-19., Conclusions: Our findings did not provide sufficient evidence for the effectiveness of Ibaraki's Amabie-chan in regard to users' infection control behavior. Further detailed study is needed to investigate the effectiveness in terms of infection prevention and the cost-effectiveness of Ibaraki's Amabie-chan.