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Objectives: While studies have examined the effects of large-scale disasters on disaster-vulnerable individuals, these analyses may not capture the full impact. This study qualitatively explored the impacts of the March 2011 Fukushima triple disaster on patients with breast cancer and their families, aiming to highlight the importance of incorporating family narratives to grasp the full effect of large-scale disasters., Methods: Utilizing the medical records from two hospitals, deceased patients with breast cancer from the disaster period were identified. Relatives were interviewed using a semi-structured approach. Thematic analysis was conducted via the Braun and Clarke method and Taguette transcription software., Results: Interviews with seven family members of six patients revealed three main themes: the family's caregiving burden and their deepened bonds with the patient, the patients' extensive medical challenges and their physical and mental decline, and the shared confusion during the disaster due to resource shortages and evacuation dilemmas., Conclusions: This study uncovered significant infrastructural issues such as reduced medical support and the heavy caregiving load on families, amidst some strengthened relationships during a time of crisis. Future research should investigate these issues across various disaster contexts, and proactive measures should be implemented to prevent exacerbation of these challenges.

This position paper highlights the dire impacts of environmental and household air pollution, which were responsible for 6.7 million deaths globally in 2019. These deaths occurred predominantly in low- and middle-income countries, with Afghanistan reporting the highest age-adjusted mortality rate. The situation worsens during large-scale disasters like earthquakes, which release more pollutants into the air, exacerbating health risks and leading to severe conditions such as pulmonary diseases. Because political factors may hinder foreign NGOs and similar organizations from providing direct support, the frequent occurrence of earthquakes in Afghanistan underscores the critical need for emergency response training for local residents. Consequently, it is essential to provide ERT training, including the proper use of protective equipment, to local populations as well as disseminating risk communication through online technologies and other appropriate means.

Competing Interests: AO received personal fees from MNES, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer, Daiichi Sankyo Inc and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Regarding non-financial conflicts of interest among the study authors, AO is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan. The remaining 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.

In October 2023, Herat Province in Afghanistan was devastated by three earthquakes, resulting in 1,480 fatalities and 1,950 injuries, affecting approximately 154,000 people. The destruction included over 21,300 buildings, including 40 healthcare facilities, intensifying an existing humanitarian crisis under Taliban rule since August 2021. A comprehensive and coordinated response is vital for sustainable recovery and resilience, transcending political barriers to address the immediate and long-term needs of the Afghan population., Competing Interests: Dr Ozaki reported personal fees from Medical Network Systems Inc. and Kyowa Kirin co. ltd. outside the submitted work. No other conflicts of interest were reported., (Copyright © Japan Medical Association.)

The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors. Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines. Transcriptome and T cell receptor repertoire analyses revealed that HVJ-E + anti-OX40 antibody treatment activates CD4 and CD8 T cells and promotes T cell trafficking between tumors. These systemic anti-tumor effects required an association between Nkg2d and Nkg2d ligands. Our findings provide insights into how systemic anti-tumor effects are induced and may help the development of therapeutic strategies for eliciting such effects., Competing Interests: A.I. and K.N. applied for a patent based on the study with Osaka University., (© 2024 The Author(s).)

The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E's preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345)., (© 2024. The Author(s).)

Considering that a multifactorial lifestyle approach may prove more effective than a single factor approach to improve or maintain brain health, we evaluated the association of exercise (open skill exercise [OSE] or closed skill exercise [CSE]) combined with long-chain polyunsaturated fatty acid (LCPUFAs) (docosahexaenoic acid [C22:6n-3, DHA], eicosapentaenoic acid [C20:5n-3, EPA], and arachidonic acid [C20:4n-6, ARA]) intake with brain atrophy among older Japanese individuals (n = 795, aged 60-88 years) without a self-reported history of dementia based on the datasets of a two-year longitudinal study. Brain volumes were measured using three-dimensional T1-weighted brain magnetic resonance imaging for follow-up periods of two years. The associations between multivariate-adjusted changes in brain volumes and OSE or CSE frequency (≥ once/month and < once/month) along with LCPUFA intake (≥ median and < median) at the baseline were assessed using a general linear model. Subgroup analysis was performed by restricting DHA and EPA intakes (n = 263; median, 323 mg/d), which represented levels similar to those in countries with low fish consumption. Higher OSE frequencies, ARA intakes, and their combination were inversely associated with decreases in total gray matter and frontal cortex volumes. In subgroup analysis, a combination of higher OSE frequencies and DHA intakes was also associated with a smaller decrease in total gray matter volume. Overall, our findings suggest that regular OSE engagement and appropriate LCPUFA intake may contribute to preventing brain volume decreases in older individuals., Competing Interests: Declaration of competing interest HT, CH, YK, TI, and YN are employees of Suntory Wellness Ltd., which markets health food products that include LCPUFAs. The other authors declare no conflicts of interest regarding this study., (Copyright © 2024. Published by Elsevier B.V.)

Oxidative stress and lipid peroxide levels in the brain increase with aging. The carotenoids lutein and zeaxanthin have potent antioxidant properties and the ability to improve cognitive function. However, their effects on neuronal damage via lipid peroxidation remain unknown. Therefore, we aimed to elucidate the effects of these carotenoids on neuronal damage induced by accumulated peroxidized lipids. We developed an oxidative stress model of lipid peroxidation-induced neuronal damage using differentiated neuronal cells derived from human neuroblastoma SH-SY5Y cells in vitro . Combining rotenone and RSL3 increased mitochondrial oxidative stress and lipid reactive oxygen species (ROS), which resulted in enhanced neuronal damage. Lutein and zeaxanthin were added to the cells for 1 week, and these carotenoids suppressed mitochondrial oxidative stress and lipid peroxidation in differentiated neuronal cells and mitigated neuronal damage. Further investigation is required to clarify the underlying pathways in detail., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Satoshi Morita reports a relationship with Suntory Wellness Ltd. That includes: employment. Sueyasu Toshiaki reports a relationship with Suntory Wellness Ltd. That includes: employment. Hisanori Tokuda reports a relationship with Suntory Wellness Ltd. That includes: employment. Yoshihisa Kaneda reports a relationship with Suntory Wellness Ltd. That includes: employment. Takayuki Izumo reports a relationship with Suntory Wellness Ltd. That includes: employment. Yoshihiro Nakao reports a relationship with Suntory Wellness Ltd. That includes: employment., (© 2024 The Authors.)

Introduction: The introduction of new drugs often leads to aggressive promotion and potential financial conflicts of interest, which may bias treatment decisions and potentially harm patients. The breast cancer therapeutics market is rapidly evolving globally, and Japan is no exception. This study aimed to analyze trends in pharmaceutical payments to breast cancer specialists in Japan from 2016 to 2019, focusing on company-level data, relationships with new drug introductions, and individual specialist payment patterns., Methods: This retrospective study examined financial relationships between pharmaceutical companies and breast cancer specialists in Japan from 2016 to 2019. The analysis focused on certified specialists as of May 2023 and used payment data from 93 pharmaceutical companies for activities such as lecturing, writing, and consulting. First, a company-level analysis examined total payments, categories, and trends for all companies and the top 10 individually; second, a specialist-level analysis looked at payment amounts amount and counts. The Gini index was employed to assess the concentration of payments among specialists., Results: Total payments reached USD 13,329,911, growing at 10.1% annually, with 81.4% allocated to lecturing engagements. The top 10 companies, led by Chugai Pharmaceutical, Eisai, and AstraZeneca, accounted for 89.5% of all payments. Companies like Pfizer Japan and Eli Lilly Japan saw notable increases following the introduction of new drugs such as palbociclib and abemaciclib. Payment distribution was highly skewed, with an average of $7,692 per specialist but a median of only $2,884. A Gini index of 0.994 further confirmed that a small group of specialists received a disproportionately large share of the payments., Conclusion: From 2016 to 2019, pharmaceutical payments to Japanese breast cancer specialists increased significantly, coinciding with new drug introductions. The concentration of payments among a select group of specialists raises concerns about potential influences on clinical decision-making and guideline recommendations., Competing Interests: Dr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose. Regarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries., (Copyright: © 2024 Kaneda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose Follow-up examinations after health check-ups are important for early detection of noncommunicable diseases among workers. Nudging can serve as an effective intervention for individuals who avoid follow-up examinations due to cognitive biases. This study aims to evaluate the interest in nudge-based notification for follow-up examinations, targeting occupational health staff and undiagnosed workers in a randomized controlled trial. Methods Participants were randomly assigned to either a control group (receiving a text-based notification without nudges) or a nudge group (receiving a notification that modified the control group based on Easy-type nudges). An anonymous web survey was administered. Results Occupational health staff (n = 425) rated all items significantly higher, including "willingness to use the notification" which scored 2.22 for the control group vs. 3.62 for the nudge group on a 1- to 5-point scale (P < 0.001). Among undiagnosed workers (n = 871), there was no significant difference in "willingness to apply for the follow-up examinations" (3.01 vs. 3.09; P = 0.272), but all other items were rated significantly higher in the nudge group (P < 0.05). Conclusion Based on these findings, we suggest that occupational health staff should use nudge-based notifications. However, increasing the willingness of undiagnosed workers to undergo follow-up examinations remains challenging. To achieve this goal, it is necessary to incorporate multiple nudge elements into notifications., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Research Ethics Committee of the Aomori University issued approval 06-2023. This study was approved by the Research Ethics Committee of the Aomori University (Approval No. 06-2023). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Masaki Takebayashi and Yuri Mizota declare(s) a grant from Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly Japan, K.K. This research was funded by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly Japan, K.K., which was received by Masaki Takebayashi and Yuri Mizota on behalf of the research team. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Takebayashi et al.)

Introduction Prolonged standing during surgery is a cause of musculoskeletal disorders in surgeons. Wearable chairs have reportedly reduced musculoskeletal strain effectively when used in industry. However, discomfort and instability issues may remain. This study examines whether using a wearable chair for surgical procedures imposes negative effects, such as mental or physical strain on surgeons prior to its clinical implementation. Methods This prospective cross-over study compared mental strain and subjective sensations in simulated suturing tasks with and without using Archelis®, a wearable chair (Archelis Inc, Yokohama, Japan). Six surgeons participated in the study. Mental strain was examined using heart rate variations calculated during tasks. Four subjective sensations (fatigue, comfort, balance, and workability) after each task and differences in body localized pain pre- and post-task were compared using a 10 centimetres (cm)-visual analog scale (VAS) score questionnaire. Results Results showed no significant differences in mental strain nor subjective sensations with or without the wearable chair. The mean VAS scores for all four subjective sensations with the wearable chair were relatively positive. There was a slight yet insignificant post-task increase in VAS mean scores for body-localized pain in the lower legs. Conclusions Significant negative effects on surgeons from the wearable chair were not observed during simulated suturing procedures. This demonstrates no major barriers in the initial phases of wearable chairs integration into the surgery environment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Ethics Committee of Jichi Medical University issued approval A18-158. We hereby notify you that based on the results of the review by the University Ethics Review Committee for Clinical Research, etc., we have decided to permit you to conduct research on the proposal for which an application was submitted on February 7, 2019. Issue Title: Sensitivity measurement during the use of medical simulation based on psychological, physiological, and behavioral indicators. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shinohara et al.)

A vertical external cavity surface emitting laser (VECSEL) that uses intracavity second harmonic generation (SHG) and the twisted mode technique for power scaling was explored. The effects of the twisted mode technique are shown and discussed by examining the mode structure and spectrum of the fundamental mode. The maximum SHG output was 1 W at 458 nm while the fundamental was lasing in the TEM 00 mode. We conclude that the twisted mode technique does not interfere with intracavity SHG and is a reasonable path for power scaling intracavity frequency doubled VECSELs.

Rationale: Cytokine release syndrome (CRS) is a common adverse event of chimeric antigen receptor T (CAR-T) cell therapy. CRS is generally a systemic inflammatory reaction, but in rare cases, it can occur in specific body areas and is referred to as "local CRS (L-CRS)." A case of laryngeal edema due to L-CRS that required tracheal intubation because of the lack of response to tocilizumab (TCZ) and dexamethasone (DEX) is reported., Patient Concerns: A 67-year-old woman with relapsed transformed follicular lymphoma was treated with CAR-T cell therapy. Although she had been given TCZ and DEX for CRS, neck swelling appeared on day 4 after infusion., Diagnoses: Laryngoscopy showed severe laryngeal edema, which was presumed to be due to L-CRS, since there were no other apparent triggers based on history, physical examination, and computed tomography., Interventions: Tracheal intubation was performed because of the risk of upper airway obstruction. Ultimately, 4 doses of tocilizumab (8 mg/kg) and 6 doses of dexamethasone (10 mg/body) were required to improve the L-CRS., Outcomes: On day 7, laryngeal edema improved, and the patient could be extubated., Lessons: The lessons from this case are, first, that CAR-T cell therapy may induce laryngeal edema in L-CRS. Second, TCZ alone may be ineffective in cervical L-CRS. Third, TCZ, as well as DEX, may be inadequate. In such cases, we should recognize L-CRS and manage it early because it may eventually progress to laryngeal edema that requires securing the airway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: ChatGPT, a large-scale language model, is a notable example of AI's potential in health care. However, its effectiveness in clinical settings, especially when compared to human physicians, is not fully understood. This study evaluates ChatGPT's capabilities and limitations in answering questions for Japanese internal medicine specialists, aiming to clarify its accuracy and tendencies in both correct and incorrect responses., Methods: We utilized ChatGPT's answers on four sets of self-training questions for internal medicine specialists in Japan from 2020 to 2023. We ran three trials for each set to evaluate its overall accuracy and performance on nonimage questions. Subsequently, we categorized the questions into two groups: those ChatGPT consistently answered correctly (Confirmed Correct Answer, CCA) and those it consistently answered incorrectly (Confirmed Incorrect Answer, CIA). For these groups, we calculated the average accuracy rates and 95% confidence intervals based on the actual performance of internal medicine physicians on each question and analyzed the statistical significance between the two groups. This process was then similarly applied to the subset of nonimage CCA and CIA questions., Results: ChatGPT's overall accuracy rate was 59.05%, increasing to 65.76% for nonimage questions. 24.87% of the questions had answers that varied between correct and incorrect in the three trials. Despite surpassing the passing threshold for nonimage questions, ChatGPT's accuracy was lower than that of human specialists. There was a significant variance in accuracy between CCA and CIA groups, with ChatGPT mirroring human physician patterns in responding to different question types., Conclusion: This study underscores ChatGPT's potential utility and limitations in internal medicine. While effective in some aspects, its dependence on question type and context suggests that it should supplement, not replace, professional medical judgment. Further research is needed to integrate Artificial Intelligence tools like ChatGPT more effectively into specialized medical practices., (© 2024 John Wiley & Sons Ltd.)

Skeletal muscle comprises slow and fast myofibers, with slow myofibers excelling in aerobic metabolism and endurance. Quercetin, a polyphenol, is reported to induce slow myofibers in rodent skeletal muscle both in vitro and in vivo. However, its effect on human myofiber types remains unexplored. In this study, we evaluated quercetin's impact on slow myofiber induction using human skeletal muscle satellite cells. In a two-dimensional culture, quercetin enhanced gene expression, contributing to muscle differentiation, and significantly expanded the area of slow-type myosin heavy chain positive cells. It also elevated the gene expression of Pgc1α, an inducer of slow myofibers. Conversely, quercetin did not affect mitochondrial abundance, fission, or fusion, but it did increase the gene expression of Cox7A2L, which aids in promoting mitochondrial supercomplexity and endurance, and Mb, which contributes to oxidative phosphorylation. In a three-dimensional culture, quercetin significantly extended the time to peak tension and half relaxation time of the engineered human skeletal muscle tissues constructed on microdevices. Moreover, quercetin enhanced the muscle endurance of the tissues and curbed the rise in lactate secretion from the exercised tissues. These findings suggest that quercetin may induce slow myofibers in human skeletal muscle., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Health information seeking via the internet among patients with cancer in disaster-affected areas is underresearched., Objective: This study aims not only to assess the extent and means of web-based health information seeking among patients with cancer living in the disaster-affected area of the 2011 Fukushima triple disaster but also to compare these patterns with those without cancer, identifying distinct and shared factors influencing their web-based health information behaviors., Methods: We surveyed 404 patients (263 with and 141 without cancer) from the surgery department outpatient office at Minamisoma Municipal General Hospital, from October 2016 to January 2017. The survey included self-administered questions on internet and digital device use. Descriptive analyses were performed to examine the use patterns of digital devices and the internet and their impact on health information seeking across different age groups of patients with and without cancer. Multivariable logistic regression was used to examine factors associated with web-based health information seeking, stratifying by cancer diagnosis., Results: The proportion of participants who sought health information on the internet was comparable between patients with cancer and patients without cancer (19% vs 17.4%; P=.71). Digital device use varied significantly with age, with peak smartphone use occurring among the youngest cohorts for both groups. Multivariable logistic regression revealed that patients with cancer using smartphones or tablets daily were significantly more likely to gather web-based health information (odds ratio [OR] for smartphones 3.73, 95% CI 1.58-8.80; OR for tablets 5.08, 95% CI 1.27-20.35). Trust in institutional websites also significantly influenced web-based health information gathering among patients with cancer (OR 2.87, 95% CI 1.13-7.25). Conversely, among patients without cancer, unemployment was associated with a lower likelihood of seeking web-based health information (OR 0.26, 95% CI 0.08-0.85), whereas trust in both institutional and personal websites significantly increased this likelihood (OR for institutional websites 6.76, 95% CI 2.19-20.88; OR for personal websites 6.97, 95% CI 1.49-32.58)., Conclusions: This study reveals that a small proportion of both patients with cancer and patients without cancer engage in health information seeking via the internet, influenced by age, digital device use, and trust in institutional websites. Given the growing prevalence of digital literacy, strategies to enhance accessible and reliable web-based health information should be developed, particularly for patients with cancer in postdisaster settings. Future efforts should focus on tailored health communication strategies that address the unique needs of these populations., (©Yudai Kaneda, Akihiko Ozaki, Michio Murakami, Toyoaki Sawano, Shuhei Nomura, Divya Bhandari, Hiroaki Saito, Masaharu Tsubokura, Kazue Yamaoka, Yoshinori Nakata, Manabu Tsukada, Hiromichi Ohira. Originally published in JMIR Cancer (https://cancer.jmir.org), 21.08.2024.)

In the medical field, the importance of online reviews is escalating. However, the complexity of responding to these reviews is profound, as such anonymous critiques may encompass not only emotionally distressing content but also potentially malicious criticisms directed at healthcare professionals. While recognizing the vital role of patient feedback, there exists a necessity for a collective approach to managing online commentary. This effort seeks to strike a balance between patient satisfaction and the safeguarding of healthcare practitioners and administrative staff. We believe the global medical community must establish guidelines to effectively handle such scenarios, thereby contributing to the sustainability of patient-centered services., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, and involved in various cellular processes. Two RNP granules in male germ cells, intermitochondrial cement and the chromatoid body (CB), are associated with PIWI-interacting RNAs (piRNAs) and are required for transposon silencing and spermatogenesis. Other RNP granules in male germ cells, the reticulated body and CB remnants, are also essential for spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, in mice and found numerous membraneless electron-dense granules accumulated in sperm flagella. Fbxo24 knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility, likely due to the accumulation of abnormal granules. The amount and localization of known RNP granule-related proteins were not disrupted in Fbxo24 KO mice, suggesting that the accumulated granules were distinct from known RNP granules. Further studies revealed that RNAs and two importins, IPO5 and KPNB1, abnormally accumulated in Fbxo24 KO spermatozoa and that FBXO24 could ubiquitinate IPO5. In addition, IPO5 and KPNB1 were recruited to stress granules, RNP complexes, when cells were treated with oxidative stress or a proteasome inhibitor. These results suggest that FBXO24 is involved in the degradation of IPO5, disruption of which may lead to the accumulation of abnormal RNP granules in sperm flagella., Competing Interests: YK, HM, ZX, KS, MK, TN, CE, MI No competing interests declared, (© 2024, Kaneda et al.)

Objective: Prior research has implied that promoting sustaining physical activity through nudges is challenging and boosting health literacy is important for the long-term establishment of behaviors. This study aimed to investigate the effects of commitment-based health application on step count and health literacy., Methods: A control experiment was conducted involving employees from companies located in Shizuoka Prefecture, Japan. Participants were divided into three groups: the commitment app group (utilizing a commitment-based application "Minchalle," where teams of around five members were randomly assigned to declare a target step count and report daily step count with pictures), the self-commitment group (individuals declaring a target step count and endeavoring on their own), and the control group (no intervention). Changes in step count and health literacy were examined over one month., Results: A total of 109 employees from 7 companies participated. The changes in step count were an increase of 893 steps for the commitment app group, 243 steps for the self-commitment group, and 178 steps for the control group, with a significant increase in the commitment app group compared to the control group. Regarding health literacy measures, there was significant progress in four items out of five for the commitment app group compared to the control group, and significant progress in one item for the self-commitment group compared to the control group., Conclusion: Communication within the app teams, such as commitment, sharing photos of their goal achievements and provide encouraging comments to others, functioned as social nudges, suggesting the potential for an immediate increase in step count and long-term behavioral reinforcement through improved health literacy., Competing Interests: Hiroyuki Kawaguchi, Chiaki Uemura, Megumi Shibuya and Shin Murakami are employees of A10 Lab Inc. The other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Takebayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0-27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77-2.5] for a low SMI and 3.2 [95% CI 1.8-5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

Multifactorial lifestyle approaches could be more effective than a single factor for maintaining cognitive function. This study investigated the association of combining cognitively stimulating leisure activities (CSLAs), including puzzles, quizzes, and cognitive training games, with intake of long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), on cognitive function in the older Japanese individuals without dementia. Participants were community-dwelling Japanese individuals without a self-reported history of dementia ( n = 906, aged 60-88 years) from datasets of a 2-year longitudinal study (baseline: 2006-2008 and follow-up: 2008-2010). CSLA engagement and LCPUFA intake were divided into high and low groups according to frequency (≥once/week and

Self-exercise during hemodialysis reportedly prevents functional decline. This study aimed to assess the effects of exercise on physical function during hemodialysis. From September 2014 to March 2018, 35 elderly dialysis patients participated in an exercise program 3 times a week for 24 weeks during hemodialysis under staff supervision. The Short Physical Performance Battery and muscle strength test were used to measure physical function, and the Short Form Version 2 and Self-Rating Questionnaire for Depression were used to measure psychological function. For Short Physical Performance Battery, walking speed and standing time improved significantly. Other significant improvements were observed in both knee extension muscle strength and right side of grip strength. There was also an improving trend in both Short Form Version 2 and Self-Rating Questionnaire for Depression after the intervention compared with the baseline. A long-term supervised self-exercise program during dialysis led to maintenance and improvement of physical and psychological functioning in elderly dialysis patients., Competing Interests: Ozaki received personal fees from MNES, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer, Daiichi Sankyo Inc and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Other authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose This study aimed to investigate the willingness to use and the application interest toward a smoking cessation program flyer among occupational health staff and smokers, utilizing a nudge approach. Methods A control group (typical flyer) and a nudge group (flyer improved according to the Easy, Attractive, Social, Timely (EAST) framework from the control flyer) were established. Occupational health staff and workers with a desire to quit smoking were randomly divided into two groups, and a web survey was conducted. Results Among occupational health staff, the nudge group flyers received significantly higher evaluations with desires "to apply" (control group: 1.7±0.7 vs. nudge group: 3.7±1.2: 5-point scale) and "to recommend to colleagues in the same profession" (control group: 1.7±2.4 vs. nudge group: 6.6±2.4: 11-point scale), and the reading completion rates were 7.0% for the control group vs. 70.7% for the nudge group (p<0.001). Although there was no significant difference in smokers' willingness "to apply" (control group: 2.9±1.2 vs. nudge group: 3.1±1.2: 5-point scale; p=0.388), the nudge group flyer was significantly more likely to be "want to recommend to other smokers" (control group: 4.9±2.4 vs. nudge group: 5.5±2.4: 11-point scale; p=0.032), with reading completion rates of 73.1% for the control group and 87.4% for the nudge group (p=0.001). Conclusion Typical flyers were not preferred by occupational health staff and may not have been effectively promoted to workers wishing to quit smoking. This study suggests that the combination of the EAST nudges could potentially increase the appeal to occupational health staff. To enhance the application interest among workers wishing to quit smoking, introducing other methods such as incentives might be necessary., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Aomori University issued approval 07-2023. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Masaki Takebayashi declare(s) personal fees from Sangyoui Inc. Mayumi Ouchi and Kazushi Yasaka declare(s) employment from Sangyoui Inc. Takao Sensui declare(s) employment from Linkage Inc. Other relationships: This study was funded by the existing budget of the participating company (Sangyoui Inc.) with contributions from the researchers’ personal research funds (Aomori University)., (Copyright © 2024, Takebayashi et al.)

In recent years, Japan has faced a significant demographic crisis, which was further exacerbated by the coronavirus disease 2019 (COVID-19) pandemic. By 2022, the country experienced a 1.5% decrease in population, which is in contrast to other G7 nations, and had the highest rate of excess mortality among Organization for Economic Co-operation and Development (OECD) countries. This crisis is mainly attributed to aging population, with Japan's aging rate reaching 29.9%, the highest among its peer countries. The Japanese government, led by Prime Minister Fumio Kishida, has proposed policies aimed at addressing these challenges, focusing on increasing fertility rates. Despite these efforts, an evidence-based policymaking (EBPM) analysis reveals that the anticipated impact on fertility rates is marginal, with financial interventions estimated to yield only a slight population increase by 2060. Furthermore, the analysis highlighted the need for a more comprehensive approach, indicating that addressing societal issues such as gender norms and workplace culture might be crucial for a sustainable solution to Japan's demographic challenges. This emphasizes the need for Japan to consider broader societal changes alongside fiscal policies to effectively combat its demographic decline., Competing Interests: Dr Ozaki reported personal fees from Medical Network Systems Inc. and Kyowa Kirin Co., Ltd., outside the submitted work. Dr Tanimoto reported personal fees from Medical Network Systems Inc., and Bionics Co., Ltd., outside the submitted work. No other disclosures were reported., (Copyright © Japan Medical Association.)

Competing Interests: None

Infertility is a global health problem affecting one in six couples, with 50% of cases attributed to male infertility. Spermatozoa are male gametes, specialized cells that can be divided into two parts: the head and the flagellum. The head contains a vesicle called the acrosome that undergoes exocytosis and the flagellum is a motility apparatus that propels the spermatozoa forward and can be divided into two components, axonemes and accessory structures. For spermatozoa to fertilize oocytes, the acrosome and flagellum must be formed correctly. In this Review, we describe comprehensively how functional spermatozoa develop in mammals during spermiogenesis, including the formation of acrosomes, axonemes and accessory structures by focusing on analyses of mouse models., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Competing Interests: The authors declare no conflict of interest.

Rationale: Fahr syndrome is a rare, degenerative neurological condition characterized by bilateral idiopathic calcification of the periventricular region, especially the basal ganglia. This condition is often misdiagnosed as other neurological or psychiatric disorders due to its rarity and overlapping symptoms., Patient Concerns: A 34-year-old man had been experiencing seizures and cognitive dysfunction for few years, which were further compounded by slurred speech and motor difficulties as acute conditions., Diagnosis: After investigations, severe hypocalcemia, and hypoparathyroidism were detected and his brain computed tomography showed extensive bilateral calcifications in basal ganglia, thalamus, dentate nuclei, and some parts of subcortical white matter, suggestive of Fahr syndrome. Although, the patient was initially misdiagnosed due to a lack of information and the rarity of this disease., Intervention: The patient was treated with intravenous calcium gluconate, vitamin D3, l-ornithine l-aspartate syrup, and levetiracetam, replacing carbamazepine., Outcome: His symptoms, including slurred speech, muscle pain, and stiffness improved, serum calcium normalized, and he was discharged with medications for memory deficit and depression., Lessons: This case underscores the importance of raising awareness among physicians, especially in areas with limited medical resources, about the significance of prompt diagnosis and appropriate symptomatic treatment in enhancing patient prognosis and quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This joint issue of Optics Express and Optical Materials Express features 23 peer-reviewed articles primarily by authors who participated in the Advanced Solid State Lasers conference, which was part of the Optica Laser Congress held in Tacoma, Washington, USA on October 8-12, 2023. This review provides a brief summary of these articles covering the latest developments in laser gain materials and nonlinear crystals, mode-locked lasers, fiber lasers and amplifiers, nonlinear optical sources, and novel concepts in laser design.

Atopic dermatitis is a multi-pathogenic disease characterized by chronic skin inflammation and barrier dysfunction. Therefore, improving the skin's ability to form an epidermal barrier and suppressing the production of cytokines that induce type 2 inflammatory responses are important for controlling atopic dermatitis symptoms. (-)-Blebbistatin, a non-muscle myosin II inhibitor, has been suggested to improve pulmonary endothelial barrier function and control inflammation by suppressing immune cell migration; however, its efficacy in atopic dermatitis is unknown. In this study, we investigated whether (S)-(-)-blebbistatin O-benzoate, a derivative of (-)-blebbistatin, improves dermatitis symptoms in a mite antigen-induced atopic dermatitis model using NC/Nga mice. The efficacy of the compound was confirmed using dermatitis scores, ear thickness measurements, serum IgE levels, histological analysis of lesions, and filaggrin expression analysis, which is important for barrier function. (S)-(-)-Blebbistatin O-benzoate treatment significantly reduced the dermatitis score and serum IgE levels compared to those in the vehicle group (p < 0.05). Furthermore, the histological analysis revealed enhanced filaggrin production and a decreased number of mast cells (p < 0.05), indicating that (S)-(-)-blebbistatin O-benzoate improved atopic dermatitis symptoms in a pathological model. In vitro analysis using cultured keratinocytes revealed increased expression of filaggrin, loricrin, involucrin, and ceramide production pathway-related genes, suggesting that (S)-(-)-blebbistatin O-benzoate promotes epidermal barrier formation. Furthermore, the effect of (S)-(-)-blebbistatin O-benzoate on type 2 alarmin cytokines, which are secreted from epidermal cells upon scratching or allergen stimulation and are involved in the pathogenesis of atopic dermatitis, was evaluated using antigens derived from mite feces. The results showed that (S)-(-)-blebbistatin O-benzoate inhibited the upregulation of these cytokines. Based on the above, (S)-(-)-blebbistatin O-benzoate has the potential to be developed as an atopic dermatitis treatment option that controls dermatitis symptoms by suppressing inflammation and improving barrier function by acting on multiple aspects of the pathogenesis of atopic dermatitis., Competing Interests: A patent including part of this work has been filed by PIAS Corporation and Osaka University [PCT/JP2021/047502]. There are no more patents, products in development or marketed products to declare. This does not alter the authors’ adherence to the policies of PLOS ONE on sharing data and materials., (Copyright: © 2024 Sahara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is limited information on whether the COVID-19 pandemic was associated with decreased breast cancer screening uptake and if COVID-19 vaccination was associated with an increase in screening uptake. Our study explored the uptake of breast cancer screening in Japan after the COVID-19 pandemic and assessed its association with the COVID-19 vaccination. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based prospective cohort survey, and we included 6110 women without cancer history who were aged 40 to 74 years that participated in the 2012 and 2022 surveys. We examined the regular breast cancer screening uptake before and after the pandemic and employed a multivariable Poisson regression model to seek any association between COVID-19 vaccination and screening uptake. Of 6110, 38.2% regularly participated in screening before the pandemic and 46.9% did so after the pandemic. Individuals unvaccinated due to health reasons (incidence rate ratio (IRR) = 0.47, 95% CI: 0.29-0.77, p = 0.003) and for other reasons (IRR = 0.73, 95% CI: 0.62-0.86, p < 0.001) were less likely to undergo screening compared to fully vaccinated individuals. There was no long-term decrease in breast cancer screening uptake after the pandemic in Japan. Vaccination was linked to increased uptake, but there was no dose relationship.

Competing Interests: The author declares no conflict of interest.

Competing Interests: The author has no conflict of interest to declare.

Cadherin-6 (CDH6) is expressed in several cancer types, but no CDH6-targeted therapy is currently clinically available. Here, we generated raludotatug deruxtecan (R-DXd; DS-6000), a novel CDH6-targeting antibody-drug conjugate with a potent DNA topoisomerase I inhibitor, and evaluated its properties, pharmacologic activities, and safety profile. In vitro pharmacologic activities and the mechanisms of action of R-DXd were assessed in serous-type ovarian cancer and renal cell carcinoma cell lines. In vivo pharmacologic activities were evaluated with several human cancer cell lines and patient-derived xenograft mouse models. The safety profile in cynomolgus monkeys was also assessed. R-DXd exhibited CDH6 expression-dependent cell growth-inhibitory activity and induced tumor regression in xenograft models. In this process, R-DXd specifically bound to CDH6, was internalized into cancer cells, and then translocated to the lysosome. The DXd released from R-DXd induced the phosphorylation of Chk1, a DNA damage marker, and cleaved caspase-3, an apoptosis marker, in cancer cells. It was also confirmed that the DXd payload had a bystander effect, passing through the cell membrane and impacting surrounding cells. The safety profile of R-DXd was favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys. R-DXd demonstrated potent antitumor activity against CDH6-expressing tumors in mice and an acceptable safety profile in monkeys. These findings indicate the potential of R-DXd as a new treatment option for patients with CDH6-expressing serous-type ovarian cancer and renal cell carcinoma in a clinical setting., (©2024 The Authors; Published by the American Association for Cancer Research.)

Predicting prognosis is crucial in older patients with diffuse large B-cell lymphoma (DLBCL). This study evaluated the prognostic impact of the controlling nutritional status (CONUT) score, a simple nutritional index, for older DLBCL patients (≥65 years of age) treated with R-CHOP-like regimens in a retrospective, cohort study including 203 patients. The CONUT score was an independent prognostic factor for overall survival (hazard ratio 1.11, 95% confidence interval (CI) 1.01-1.21, p  = 0.032) in a multivariable Cox proportional hazards model. On receiver-operating characteristic analysis, the optimal cutoff value was 3. The CONUT score (≥3 or <3) effectively stratified older DLBCL patients, regardless of the International Prognostic Index ( p  = 0.71 for interaction). Further, the CONUT score independently affected initial dose intensity (odds ratio 0.84, 95% CI 0.73-0.95, p  = 0.008), likely reflecting the patients' status at diagnosis and affecting dose adjustments. In conclusion, the CONUT score is associated with a poorer prognosis in older DLBCL patients.

Background: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated., Methods: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height., Results: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3-4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA., Conclusion: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA.

While vaccines are pivotal in combating COVID-19, concerns about side effects and complex procedures have hindered complete vaccination. Prior studies suggest that individuals defaulted to opt-out exhibit higher COVID-19 vaccination rates compared to those in opt-in systems. However, these studies were conducted in countries with a tolerant attitude towards vaccination and default changes, targeting specific age groups, and did not address potential deterrents like the increase in cancellation rates on the day, discomfort towards changing defaults, or the possibility of the opt-out effect being a one-time occurrence. Under the hypothesis that the default nature of the COVID-19 vaccination system influences attitudes towards vaccination even in countries conservative about vaccination and default changes like in Japan, we aimed to examine the differences in the first and second dose vaccination rates, cancellation rates, and the number of complaints between the opt-in and opt-out systems for COVID-19 vaccination. An email survey was conducted in 10 cities in A Prefecture, Japan. The results showed not only higher COVID-19 vaccination rates across all comparable age groups in the opt-out group but also a notably smaller decrease in the second-dose vaccination rate compared to the opt-in group, all achieved without any complaints about the system's introduction. Consequently, it can be inferred that the potential inhibiting factors were largely overcome. Despite some limitations, such as regional specificity, the study suggests that opt-out systems might increase COVID-19 vaccination coverage without leading to significant cancellations or complaints, presenting a promising strategy to facilitate vaccination efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Takebayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Japan, inactivated vaccines, including the influenza vaccine, are administered subcutaneously, which is contrary to global recommendations for intramuscular injections. This practice is attributed to historical medical incidents and unchallenged conventions. However, this outdated method, which differs from that of international standards and is linked with less immunogenicity and more adverse reactions, may contribute to vaccination hesitancy. Therefore, with the adoption of intramuscular vaccination administration, which was widely adopted in the coronavirus disease 2019 vaccination, a shift in the Japanese health policy to conform to international standards potentially improves vaccine acceptance and effectiveness., Competing Interests: Dr. Ozaki reported personal fees from Medical Network Systems Inc. and Kyowa Kirin Co. Ltd. outside the submitted work. Dr. Tanimoto reported personal fees from Medical Network Systems Inc. and Bionics Co. Ltd. outside the submitted work., (Copyright © Japan Medical Association.)