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Summary: Background: Basal cell carcinoma is the most common skin malignancy. The standard treatment is surgical excision with predetermined margins. Some argue that the currently recommended surgical margins are excessive, and it is questionable whether such wide surgical margins should be applied to all lesions. We statistically investigated excisions with narrow margins and tried to identify the risk factors for recurrence after one-step surgery. Methods: Basal cell carcinomas were excised at a single institute in Japan over a six-year period and the recurrence rates were retrospectively analyzed using pathological reports and case notes. We reviewed the microscopic findings of the excised specimens and examined the excisional margin status, tumor subtype, and perineural invasion. Results: Forty-eight basal cell carcinomas (45 primary and 3 recurrent) that were identified in Japanese patients were included in this study. Among the primary lesions, well-pigmented and well-defined lesions did not show any involvement of the surgical margins, perineural invasion, or development of local recurrence. Recurrent lesions were significantly associated with positive surgical margins (side margin, P

Abstract Purpose To investigate the utility of qualitative and semi-quantitative evaluation of DCE-MRI for detecting clinically significant prostate cancer (csPC). Methods This retrospective study analyzed 307 lesions in 231 patients who underwent 3.0T MRI. Experienced radiologists assessed PI-RADS v 2.1 assessment category, qualitative contrast enhancement (QCE), contrast enhancement pattern (CEP: type 1, 2, 3), tumor contrast ratio, and tumor size of PC lesions in consensus. Mean and 0–10th-percentile ADC value of the lesion (ADCmean and ADC0−10) were calculated. Specimens obtained from MRI–ultrasound fusion-guided prostate biopsy were used as the pathological reference standard. Results In assessment of tumor aggressiveness, PI-RADS assessment category, QCE, tumor size, and ratio of CEP 2 + 3 were significantly higher in PC with Gleason score (GS) ≥ 3 + 4 (n = 256) than in PC with GS = 6 (n = 51) (P ≤ 0.001). Tumor ADCmean and tumor ADC0−10 were comparable between PC with GS ≥ 3 + 4 and PC with GS = 6 (P = 0.164 to 0.504). Regarding diagnostic performance of csPC in 45 PI-RADS 3 transition zone lesions, only ratio of CEP 2 + 3 was significantly higher in PC with GS ≥ 3 + 4 (n = 31) than in PC with GS = 6 (n = 14) (P = 0.008). Conclusion Qualitative DCE-MRI indices may contribute to PC aggressiveness and improve detection of csPC in PI-RADS assessment category 3 lesions.

Abstract This study examines the association between posterior occlusal contact and the risk of dementia development in the Japanese population, utilizing Eichner classification to evaluate occlusal status. Data from Japanese health insurance claims were analyzed for the period from April 2016 to March 2022. Participants had undergone specific health checkups, had no prior history of dementia, and were classified according to their dental occlusal contact. Dementia diagnoses were determined using ICD-10 codes, and participants were divided into three groups—A, B, and C—based on the Eichner classification, which indicates the extent of occlusal contact. Over an average follow-up period of 35.6 months, 691 dementia were identified among 931,309 participants. Those diagnosed with dementia were more likely to belong to Eichner B and C groups, signifying reduced occlusal contact. After adjusting for covariates, the hazard ratios (95% confidence intervals) for Eichner B and C were 1.73 (1.31–2.28) and 2.10 (1.35–3.26), respectively. Sensitivity analyses confirmed these findings in adults aged 60–75. These findings suggest that reduced posterior occlusal contact correlates with an increased risk of dementia. Since the study is limited to participants under the age of 75, further research is required to determine its generalizability to older populations.

Background: The influence of the coronavirus disease 2019 (COVID-19) pandemic on dental care utilization may have differed according to individual characteristics or type of dental care provision. This study aimed to evaluate the changes in dental care utilization and per-attendance costs by age group and type of dental care during the COVID-19 pandemic in Japan. Methods: This time-series study used healthcare insurance claims data from 01/07/2019 to 09/27/2021 (143 weeks) from nine municipalities in Japan. Dental care utilization rate per week and average dental care cost per attendance by age groups (0–19 years/20–64 years/65–74 years/≥75 years) and types of dental care (outpatient/visiting) were used as outcome variables. COVID-19 pandemic waves in Japan were used as predictors: 1st (03/23/2020–05/17/2020), 2nd (06/22/2020–09/27/2020), 3rd (10/26/2020–02/21/2021), 4th (02/22/2021–06/07/2021), and 5th (07/05/2021–09/13/2021) waves. Fixed-effects models were employed to estimate the proportional changes. Results: In the fixed-effects model, we observed large declines in dental care utilization during the 1st (17.0–22.0%) and 2nd waves (3.0–13.0%) compared to the non-pandemic wave period in all age groups. In contrast, the average dental care cost per attendance increased in all age groups by 5.2–8.6% during the 1st wave. Conclusion: During the initial wave of the COVID-19 pandemic in Japan, dental care utilization decreased in all age groups, whereas the average dental care cost per attendance increased. The COVID-19 pandemic may have changed the dental care provision pattern towards less frequent and more concentrated dental care to avoid the risk of infection.

Abstract A spatiotemporal understanding of gene function requires the precise control of gene expression in each cell. Here, we use an infrared laser–evoked gene operator (IR-LEGO) system to induce gene expression at the single-cell level in the moss Physcomitrium patens by heating a living cell with an IR laser and thereby activating the heat shock response. We identify the laser irradiation conditions that provide higher inducibility with lower invasiveness by changing the laser power and irradiation duration. Furthermore, we quantitatively characterize the induction profile of the heat shock response using a heat-induced fluorescence reporter system after the IR laser irradiation of single cells under different conditions. Our data indicate that IR laser irradiation with long duration leads to higher inducibility according to increase in the laser power but not vice versa, and that the higher laser power even without conferring apparent damage to the cells decelerates and/or delayed gene induction. We define the temporal shift in expression as a function of onset and duration according to laser power and irradiation duration. This study contributes to the versatile application of IR-LEGO in plants and improves our understanding of heat shock-induced gene expression.

Abstract The association between visceral fat area (VFA) and locomotive syndrome (LS) has been extensively studied in the older population; however, the association between VFA and early-stage LS (stage 1 [LS1]) remains unclear. In this cross-sectional study, we investigated this association across different age groups. The study involved 1,236 (524 male and 712 female) participants (aged 20–85 years). Multiple regression analysis adjusted for sex, body mass index, skeletal muscle mass index, T-score, exercise habits, smoking status, and alcohol consumption revealed a significant association between LS1 and VFA across all VFA quartiles. The adjusted odds ratio OR for quartiles 2, 3, and 4 was 1.84, 2.68, and 4.12, respectively. The association between LS1 and VFA across the age groups—high VFA (> 73 cm2) and non-older (

ABSTRACT Ca2+/calmodulin-dependent protein kinase II (CaMKII) is one of hundreds of host-cell factors involved in the propagation of type A influenza virus (IAV), although its mechanism of action is unknown. Here, we identified CaMKII inhibitory peptide M3 by targeting its kinase domain using affinity-based screening of a tailored random peptide library. M3 inhibited IAV cytopathicity and propagation in cells by specifically inhibiting the acute-phase activation of retinoic acid-inducible gene I (RIG-I), which is uniquely regulated by CaMKII. Downstream of the RIG-I pathway activated TBK1 and then IRF3, which induced small but sufficient amounts of transcripts of the genes for IFN α/β to provide the capped 5’-ends that were used preferentially as primers to synthesize viral mRNAs by the cap-snatching mechanism. Importantly, knockout of RIG-I in cells almost completely inhibited the expression of IFN mRNAs and subsequent viral NP mRNA early in infection (up to 6 h after infection), which then protected cells from cytopathicity 24 h after infection. Thus, CaMKII-dependent acute-phase activation of RIG-I promoted IAV propagation, whereas the canonical RIG-I pathway stimulated antiviral activity by inducing large amounts of mRNA for IFNs and then for antiviral proteins later in infection. Co-administration of M3 with IAV infection rescued mice from the lethality and greatly reduced proinflammatory cytokine mRNA expression in the lung, indicating that M3 is highly effective against IAV in vivo. Thus, regulation of the CaMKII-dependent non-canonical RIG-I pathway may provide a novel host-factor-directed antiviral therapy.IMPORTANCEThe recent emergence of IAV strains resistant to commonly used therapeutic agents that target viral proteins has exacerbated the need for innovative strategies. Here, we originally identified CaMKII-inhibitory peptide M3, which efficiently inhibits IAV-lethality in vitro and in vivo. M3 specifically inhibited the acute-phase activation of RIG-I, which is a novel pathway to promote IAV propagation. Thus, this pathway acts in an opposite manner compared with the canonical RIG-I pathway, which plays essential roles in antiviral innate immune response later in infection. The CaMKII-dependent non-canonical RIG-I pathway can be a promising and novel drug target for the treatment of infections.

Yunosuke Usui,1 Miki Ono,1 Rintaro Nibuya,1 Masayuki Kikkawa,1 Shunichiro Ito,1 Chihiro Morishita,1 Mina Honyashiki,1 Yu Tamada,1,2 Takeshi Inoue,1 Jiro Masuya1 1Department of Psychiatry, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan; 2Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, Hachioji-shi, Tokyo, JapanCorrespondence: Jiro Masuya, Department of Psychiatry, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan, Tel +81-(0)3-3342-6111, Email j-masuya@tokyo-med.ac.jpBackground: Prior research has shown that inappropriate childhood nurturing experiences (low care and high overprotection), trait anxiety, and depressive rumination are risk factors for depression. However, no studies to date have analyzed the overall association between these factors and depressive symptoms. In the present study, we hypothesized that depressive rumination mediates the impacts of inappropriate childhood nurturing experiences on depressive symptoms, and that these mediating effects are moderated by trait anxiety, and tested these hypotheses in adult volunteers.Methods: The subjects were adult volunteers who were investigated between April 2017 and April 2018. A self-report questionnaire on demographic data, childhood nurturing experiences, trait anxiety, depressive rumination, and depressive symptoms was distributed to conduct the survey, and written informed consent and valid responses were obtained from 585 subjects. Mediation and moderated-mediation analyses were performed by SPSS 28 and macro PROCESS 4.0 software. This study was approved by the Ethics Committee of Tokyo Medical University.Results: Parental care showed a significant negative indirect effect on depressive symptoms via its effect on depressive rumination (p < 0.01), whereas parental overprotection showed the opposite effect (p < 0.01). Furthermore, the mediation effect of depressive rumination on depressive symptoms was increased by trait anxiety (p < 0.05).Conclusion: Our present study demonstrated that the main factor affecting depressive symptoms is inappropriate childhood nurturing experiences, which indirectly enhance depression by intensifying depressive rumination, and that depressive rumination and trait anxiety mutually reinforce each other to enhance depressive symptoms. These findings may be useful for the prevention of depressive symptoms. Large-scale prospective studies are needed to confirm the causal associations among these factors in the future.Keywords: childhood parenting experiences, depressive rumination, trait anxiety, depressive symptoms, moderated-mediation analysis

Abstract Aim Various risk factors, such as childhood nurturing experiences and subjective social status, have been identified to be involved in the onset of depression. However, the mechanism of depression is not yet fully understood. In this study, we hypothesized that nurturing experienced in childhood affects subjective social status and current personality traits, which in turn influence depressive symptoms in adulthood, and verified this hypothesis through structural equation modeling. Methods A questionnaire survey was conducted on 404 adults. Multiple regression analysis and structural equation modeling were conducted using demographic information and scores for the Patient Health Questionnaire‐9, Parental Bonding Instrument, and NEO Five‐Factor Inventory. Results Subjective social status was found to mediate the association between nurturing experiences and neuroticism (0.029 for Overprotection and –0.034 for Care). On the other hand, neuroticism was found to mediate the association between subjective social status and depressive symptoms (–0.097 in Care model and –0.103 in Overprotection model), as well as the association between nurturing experiences and depressive symptoms (0.144 for Overprotection and –0.134 for Care). Furthermore, it was also shown that complex paths, in which the association of nurturing experiences with depressive symptoms was mediated by two factors, namely, subjective social status and neuroticism, were statistically significant as indirect effects (0.016 for Overprotection and –0.018 for Care). Conclusion In this study, we clarified that nurturing experienced in childhood affects neuroticism in adulthood, which is mediated by subjective social status, and furthermore, the effects of nurturing on neuroticism lead to varying levels of depressive symptoms in adulthood. The mediation effects demonstrated in the present study may contribute towards unraveling the causes of depression and developing effective treatments for depressive symptoms.

Abstract Aim In the DSM‐5, it is specified that severe cases of major depressive disorder with anxious distress (ANXD) may be accompanied with motor agitation. Agitation, on the other hand, is one of the main characteristics of major depressive disorder with melancholic features (MEL). The purpose of this study was to compare ANXD and MEL in terms of psychomotor disturbance. Methods A total of 106 patients with major depressive disorder were included in the study. Psychomotor disturbance was assessed using the CORE measure. The associations of ANXD and MEL with the CORE measure subscales of psychomotor retardation, agitation, and noninteractiveness were analyzed using multivariate logistic analysis. Results Retardation scores (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.52–0.77) were associated with fewer diagnoses of ANXD, whereas agitation scores (OR = 2.23, 95% CI = 1.60–3.13) were associated with more diagnoses of ANXD. Both noninteractiveness (OR = 1.23, 95% CI = 1.06–1.42) and agitation (OR = 1.27, 95% CI = 1.02–1.58) scores were associated with increased diagnoses of MEL. Conclusion Among the characteristics of psychomotor disturbance, agitation is a common feature of both ANXD and MEL, and ANXD and the agitated type of MEL may be overlapping concepts. On the other hand, ANXD is distinguished from the retarded type of MEL by its low level of retardation, whereas MEL but not ANXD is characterized by noninteractiveness.