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Background: There is a complex relationship between tobacco use and pain. Nicotine provides temporary pain relief but increases the risk of chronic pain. This study aimed to investigate use of tobacco for pain relief and its association with demographic and medical characteristics in Japan., Methods: We used a web-based survey to recruit 2000 individuals aged 20-69 who had experienced pain in the previous month. They answered questions on demographics, smoking status, lifestyle, socioeconomic status, and medical information. Smokers were asked if they smoked tobacco to relieve pain. Those who responded "strongly agree" or "agree" were labeled as using tobacco for pain relief. We used analysis of covariance to test the associations among smokers' background characteristics by whether they used tobacco for pain relief., Results: Overall, 6.6% of smokers with pain (3.5% with acute or subacute pain and 8.8% with chronic pain) used tobacco for pain relief. These individuals were generally younger, more likely to be treated for schizophrenia and use analgesics, with higher pain severity, more catastrophic thinking about pain, and a centralized symptom. However, they were less likely to engage in regular exercise., Conclusions: Overall, 6.6% of smokers (3.5% with acute or subacute pain and 8.8% with chronic pain) used tobacco to relieve their pain, even though most of them also received medical treatment and used pain medication. Healthcare providers and policy makers should account for this population of smokers in their planning., (© 2025 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The authors confirm that this study was approved by the institutional ethics committees of Kyoto University and participating institutions (G608) and was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from each participant.

Pituitary adenylate cyclase-activating polypeptide (PACAP) affects rodents' stress-related behaviors, such as anxiety-like behavior or fear conditioning. However, previous studies have investigated the effect of intracerebroventricular, but not hippocampal, injection of this PAC1R-selective antagonist (PACAP-6-38) on anxiety-like behavior. However, it has been reported that administration of PACAP-6-38 to the dorsal hippocampus reduces the fear response in a fear conditioning test. Therefore, this study aimed to determine whether the effect of dorsal hippocampal PACAP-6-38 injection in Sprague-Dawley rats can affect anxiety-like behavior assessed by an elevated plus-maze test. As a result, rats treated with PACAP-6-38 spent longer time in open arms than those with saline, suggesting that this drug has an anxiolytic effect. In conclusion, the role of PACAP in the dorsal hippocampus can promote anxiety-like behavior., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Introduction: According to International classification of sleep disorder (ICSD-3), overnight polysomnography (PSG) is the gold standard examination for the diagnosis of pediatric obstructive sleep apnea (OSA). However, most of the patients in Japan are not able to access the specialized sleep medical facilities for PSG due to less availability and cost issues. Purpose of this study is to examine whether combination of video monitoring items and other clinical examinations can reliably predict the severity of pediatric OSA compared with PSG., Methods: The study subjects were children diagnosed with sleep related breathing disorder (SRBD) who attended the Department of Otorhinolaryngology at Ota General Hospital between 2012 and 2019. A total of 175 cases were included in this individual retrospective-cohort study, consisting of 122 boys and 53 girls, with ages from 3 to 12 years (median: 8.00). Clinical data included the children's medical history, physical examinations, imaging cephalograms, rhinomanometry, and PSG with video monitoring performed by sleep technicians for all patients. Multiple linear regression analyses were performed to identify independent predictors significantly related to the severity of OSA (AHI: apnea hypopnea index, 5/h and 10/h)., Results: For AHI greater than 5/h, the independent predictors were nocturnal oximetry (PSG-ODI 3 % > 3/h), total nasal resistance, tonsil size, one video monitoring item, and the total video monitoring score. The accuracy of this predictive statistic model was 88.0 % (sensitivity 78.3 %, specificity 93.0 %). For AHI greater than 10/h, the independent predictors included facial axis of cephalogram, nocturnal oximetry (PSG-ODI 3 % > 5/h), and BMI <15, along with video monitoring parameters such as whole-night inspiratory noise (loud) and chest retraction. The sensitivity of this model was 88.7 %, specificity was 84.1 %, and accuracy was 86.9 %, which is much higher than the accuracy of the model without video monitoring score., Conclusions: Instead of relying solely on PSG, the combination of video monitoring score and multiple clinical examinations could provide a reliable diagnostic approach for pediatric OSA. These results will support the establishment of more efficient diagnostic strategies for both patients and physicians., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking. Cardiac reprogramming is a promising therapeutic approach for myocardial infarction that facilitates cardiac regeneration and antifibrosis action through Mef2c/Gata4/Tbx5/Hand2 (MGTH) overexpression in resident CFs. However, the efficacy of this approach on HFpEF is yet to be established., Methods: Herein, we examined the effects of cardiac reprogramming in HFpEF using Tcf21 iCre /Tomato/MGTH2A transgenic mice, which expressed both MGTH and reporter expression in CFs for cardiac reprogramming and lineage tracing upon tamoxifen administration. To establish HFpEF model mice, we used a combination of a high-fat diet and nitric oxide synthase inhibition. Bulk RNA-sequencing, single-cell RNA-sequencing, and spatial transcriptomics were conducted to determine fibrotic mechanisms and the efficacy of cardiac reprogramming in HFpEF. We generated new tamoxifen-inducible transgenic mice overexpressing each reprogramming factor in CFs to investigate the effect of single factors. Last, we analyzed the effect of reprogramming factors in human CFs., Results: Cardiac reprogramming with MGTH overexpression improved diastolic dysfunction, cardiac hypertrophy, fibrosis, inflammation, and capillary loss in HFpEF. Cardiac reprogramming converted approximately 1% of resident CFs into induced cardiomyocytes. Bulk RNA-seq indicated that MGTH overexpression upregulated genes related to heart contraction and suppressed the fetal gene program ( Nppa and Nppb ) and proinflammatory and fibrotic signatures. Single-cell RNA-sequencing and spatial transcriptomics revealed that multiple CF clusters upregulated fibrotic genes to induce diffuse interstitial fibrosis, whereas distinct CF clusters generated focal perivascular fibrosis in HFpEF. MGTH overexpression reversed these profibrotic changes. Among 4 reprogramming factors, only Gata4 overexpression in CFs reduced fibrosis and improved diastolic dysfunction in HFpEF by suppressing CF activation without generating new induced cardiomyocytes. Gata4 overexpression also suppressed profibrotic signatures in human CFs., Conclusions: Overexpressing Gata4 in CFs may be a promising therapeutic approach for HFpEF by suppressing fibrosis and improving diastolic dysfunction., Competing Interests: None.

Background: The administration of eltrombopag, used to restore low blood count, demonstrates a positive interference of blood bilirubin levels when analyzed through the diazo assay. However, research on bilirubin measurements using other methods is limited. Therefore, using an enzymatic assay, this study aimed to investigate the effect of serum eltrombopag on bilirubin measurements in patients with aplastic anemia. It further assessed the concentration-dependent effect of eltrombopag on bilirubin measurements using enzymatic and vanadate oxidation assays., Methods: Total and conjugated bilirubin concentrations measured using an enzymatic assay and serum eltrombopag concentrations were examined in 227 serum samples collected from 30 patients with aplastic anemia receiving eltrombopag. Eltrombopag-spiked samples were analyzed using the enzymatic and vanadate oxidation assays for total and conjugated bilirubin to determine its concentration-dependent effects., Results: A strong positive correlation was observed between total bilirubin and serum eltrombopag concentrations in patients receiving eltrombopag (r = 0.820). However, the correlation between conjugated bilirubin and serum eltrombopag concentrations was weaker (r = 0.413). In eltrombopag-spiked serum samples, the enzymatic assay showed significant false elevation of total bilirubin concentrations at ≥6.0 mcg/mL; no interference with conjugated bilirubin measurements was observed. The vanadate oxidation assay showed mild positive biases of 0.2 and 0.1 mg/dL for total and conjugated bilirubin concentrations, respectively, at a high eltrombopag concentration (50 mcg/mL)., Conclusions: Eltrombopag causes clinically significant concentration-dependent interference in total blood bilirubin, but not in conjugated bilirubin measurements through the enzymatic assay in patients with aplastic anemia. The vanadate oxidation assay may be used as an alternative to measure total blood bilirubin when the eltrombopag concentration is below 50 mcg/mL., Competing Interests: The authors declare no conflict of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A (IL-31RA), is used to treat atopic dermatitis and prurigo nodularis. These inflammatory skin diseases affect a wide range of age groups, including pregnant women and children; however, little is known about their biological effects on pre- and postnatal development. Therefore, we report and discuss the results of an enhanced pre- and postnatal development study in cynomolgus monkeys treated with nemolizumab, which also incorporates an assessment of juvenile toxicities., Methods: Nemolizumab was subcutaneously administered at doses of 1 or 25 mg/kg to pregnant cynomolgus monkeys once every 2 weeks (biweekly) from Gestation Day 20 until delivery, to investigate the potential toxicities on pre- and postnatal development. Additionally, their offspring were subcutaneously dosed biweekly with 1 or 25 mg/kg from approximately 1 to 7 months after birth to investigate the potential toxicities on juveniles, considering the age of the target patient population. The examination included tests for immune function and nervous system involvement by IL-31, as well as the standard assessments outlined in the ICH S5 guideline to comprehensively assess the safety profile., Results: No nemolizumab-related toxicities were observed in both dams and offspring up to 25 mg/kg. Maternal plasma nemolizumab concentrations were well maintained during the gestation period, gradually decreasing after delivery. Plasma concentrations in the offspring, higher than in dams, was maintained until scheduled necropsy., Conclusion: Blocking IL-31 signaling with repeated dosing of nemolizumab did not adversely affect pregnancy, parturition, nursing, or postnatal physical and functional development in cynomolgus monkeys., (© 2025 Wiley Periodicals LLC.)

Sleep insufficiency and sleep disorders pose serious health challenges. This study aimed to determine the potential discrepancy between subjective and objective sleep assessments, including the latter made by physicians, by analyzing a 421-participant dataset in Japan comprising multiple nights of in-home sleep electroencephalogram (EEG) data and questionnaire responses on sleep habits or subjective experiences. We employed logistic regression models to examine which subjective and objective sleep parameters physicians are paying attention to when assessing sleep insufficiency, insomnia, sleep quality, and sleep apnea. Questionnaire responses, including subjective sleep assessments, exhibited poor performance predicting physicians' assessments, whereas objective data demonstrated good predictive performance, indicating a discrepancy between subjective and objective sleep assessments. Although the in-home sleep EEG measurements had minimal first night effects, incorporating measurements over multiple nights can improve the detection of objective insomnia. Moreover, we found that participants with severe sleep insufficiency overestimated their sleep duration, whereas those with subjective insomnia but without objective insomnia underestimated it. Additionally, subjective sleep quality reflected sleep efficiency but not the frequency of short awakenings or objective sleep depth. In particular, the effects of apnea on objective sleep quality were not subjectively perceived. Collectively, our findings suggest that subjective sleep assessments alone are insufficient for evaluating sleep health and that health checkups and advice based on sleep EEG measurements may be useful in improving sleep habits and for early detection of sleep disorders., Competing Interests: Competing interests statement:M.Y. is Chief Executive Officer of S’UIMIN Inc. M.Y. and T.H. are the board members of S’UIMIN Inc. and hold stock in the company. A.T., M.T., and T.A. are employees of S’UIMIN Inc.

Influenza B viruses pose a significant threat to global public health, leading to severe respiratory infections in humans and, in some cases, death. During the last 50 years, influenza B viruses of two antigenically distinct lineages (termed 'Victoria' and 'Yamagata') have circulated in humans, necessitating two different influenza B vaccine strains. In this study, we devised a novel vaccine strategy involving reciprocal amino acid substitutions at sites where Victoria- and Yamagata-lineage viruses differ, leading to the generation of 'hybrid' vaccine viruses with the potential to protect against both lineages. Based on antigenic characterization, we selected two candidates and assessed their protective efficacy in a ferret model. Notably, both recombinant HA proteins conferred enhanced protection against heterologous challenges compared to their respective wild-type antigens. These findings show the potential of our novel strategy to develop cross-lineage protective influenza B virus vaccines., Competing Interests: Competing interests: Y.K. has received grant support from Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., Otsuka Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Otsuka Pharmaceutical, KM Biologics, Kyoritsu Seiyaku, Shinya Corporation, and Fuji Rebio. Y.K. and G.N. are co-founders of FluGen. The other authors have no conflicts of interest., (© 2024. The Author(s).)

Background and Aim: Qualitative diagnosis of ulcerative colitis-associated neoplasia (UCAN) is crucial for surveillance colonoscopy in patients with ulcerative colitis (UC). Although the utility of magnifying endoscopy with narrow-band imaging (ME-NBI) in sporadic neoplasia diagnosis has been reported, its efficacy in UCAN remains unclear. This study aimed to evaluate the usefulness of ME-NBI for qualitative diagnosis of UCAN., Methods: We generated 60 ME-NBI images (30 UCANs and 30 nonneoplasia lesions, including 10 polypoid and 20 nonpolypoid lesions) from patients with UC who underwent colonoscopy at our hospital between 2015 and 2023. Eleven endoscopists (seven experts and four trainees) independently assessed these images. Lesions were categorized into high- (≥ 80%), moderate- (50%-79%), and low- (< 50%) accuracy groups on the basis of the correct diagnostic rate., Results: Overall sensitivity, specificity, and correct diagnostic rates were 66.5%, 79.0%, and 71.8%, respectively. Experts tended to exhibit higher specificity than trainees (83% vs. 70%). Polypoid lesions showed higher sensitivity (92% vs. 54%) and lower specificity (61% vs. 88%) than nonpolypoid lesions. Overall, the kappa value was 0.411. In UCAN, 37%, 37%, and 24% were classified into the high-, moderate-, and low-accuracy groups, respectively. All endoscopists assessed one case of UCAN in the low-accuracy group as a nonneoplastic vessel with a surface pattern. Only two nonneoplasias were identified as having nonneoplastic vessel and surface patterns by all endoscopists., Conclusions: This study demonstrated the usefulness of ME-NBI for qualitative diagnosis, along with its limitations. A unique endoscopic diagnostic algorithm for UCAN, incorporating ME-NBI and other modalities, is necessary., (© 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI)., Methods: This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts., Results: The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively., Conclusions: Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials., (© 2024 Wiley Periodicals LLC.)

Objective: To confirm the structural validity of the Trunk Assessment Scale for Spinal Cord Injury (TASS)., Participants and Methods: We evaluated 104 Japanese individuals with a spinal cord injury (SCI) (age 63.5 ± 12.2 years; 64 with tetraplegia) with the TASS 1-3 times. We conducted a Rasch analysis to assess the TASS' unidimensionality, fit statistics, category probability curve, ceiling/floor effects, local independence, reliability, and difference item function (DIF)., Results: The TASS was observed to be a unidimensional and highly reproducible scale of item difficulty hierarchy that sufficiently identifies the superiority of the examinee's ability. The TASS was easy for the participants of this study. One TASS item was a misfit based on the infit and outfit mean square; another item also showed a DIF contrast for age. Several items were found to require a synthesis or modification of the content. The TASS showed a floor effect, and most of the non-scorers were individuals with a complete SCI., Conclusion: Our findings clarify the structural validity of the TASS, and our analyses revealed that the TASS includes an unfitness item and was less challenging for individuals with SCIs. The improvements suggested by these results provide important information for modifying the TASS to a more useful instrument.

Objective: To confirm the responsiveness and minimal clinically important differences (MCIDs) of the Trunk Assessment Scale for Spinal Cord Injury (TASS)., Participants and Methods: We evaluated 48 Japanese individuals with spinal cord injury (SCI) (age 64.1 ± 10.4 yrs, 28 with tetraplegia) admitted to two institutions at admission, at 1 month of hospitalization, and at discharge with the TASS, the Trunk Control Test in individuals with an SCI (TCT-SCI) motor score, the Functional Independence Measure motor score (mFIM), and the Global Rating of Change Scale (GRCS). We assessed the TASS responsiveness by determining the correlation coefficients for the changes in the TASS' and other assessments' scores. We calculated the MCIDs by five anchor-based methods., Results: The changes in the TASS and those in the other assessments were weakly correlated at 1 month and moderately correlated at discharge. The TASS MCIDs were observed at 1 month and at discharge., Conclusion: Our findings confirmed that the change in TASS scores had weak-to-moderate correlations with the changes in the participants' upper- and lower-limb function and activities of daily living. Using the MCID for the TASS determined by anchor-based methods may lead to a better interpretation of changes in the trunk function of individuals with SCIs.