Search

Background/aim: The lung immune prognostic index (LIPI), which is determined by assessing the derived neutrophil-to-lymphocyte ratio in conjunction with the level of lactate dehydrogenase, predicts outcomes in various cancers. Its utility as a preoperative biomarker in upper tract urothelial carcinoma (UTUC) patients remains unexplored., Patients and Methods: This is a retrospective study of UTUC patients who underwent radical nephroureterectomy. Patients were stratified into favorable, intermediate, and poor LIPI groups. Non-urothelial tract recurrence-free survival (NUTRFS) was evaluated using Kaplan-Meier analysis, and Cox regression analyses were performed to identify risk factors for NUTRFS., Results: A total of 567 UTUC patients were included, with 46.4% in the favorable, 44.6% in the intermediate, and 9.0% in the poor (9.0%) LIPI groups. The median participant age was 74 years, with a median follow-up of 26 months. Kaplan-Meier curves demonstrated that NUTRFS was significantly worse in patients with poor and intermediate LIPI scores than in those with favorable LIPI scores. Furthermore, combining LIPI status with pathological stages (pT3-4/ypT2-4) and lymph node metastasis status improved postoperative non-urothelial tract recurrence prognosis assessment., Conclusion: The preoperative LIPI is a prognostic indicator for patients with UTUC undergoing nephroureterectomy. Its predictive accuracy improves when combined with advanced pathological stages and lymph node metastasis status., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Androgen receptor-signaling inhibitors (ARSIs) have significantly changed the preferred treatments for metastatic castration-sensitive prostate cancer (mCSPC). Despite such advances, the prognostic significance of metastases at specific sites remains unclear. This study evaluated how metastatic site affected the oncological outcomes of mCSPC patients., Methods: This retrospective multicenter study included 716 mCSPC patients receiving androgen- deprivation therapy (ADT) alone, combined androgen blockade (CAB) therapy, or both ARSI and ADT (ARSI doublet) from February 2018 to June 2023. All patients were categorized based on their metastatic sites. The primary endpoint was the time to castration-resistant prostate cancer (CRPC) development; the secondary endpoints were progression-free survival 2 (PFS2), cancer-specific survival (CSS), and overall survival (OS). Kaplan-Meier curves and multivariate Cox's regression models were used to analyze the survival outcomes. We stratified mCSPC patients with bone metastases by the volumes of such metastases and lung metastasis status, and explored the clinical significance of lung metastasis., Results: Patients with lung-only metastases experienced better outcomes than those with other visceral metastases. On multivariate analysis, the bone metastasis volume, but not lung metastasis status, significantly affected CRPC-free survival status. No significant difference in any of CRPC, PFS2, CSS, or OS status was apparent among patients with bone metastases with or without lung metastases. In terms of interaction, lung metastasis did not significantly affect the prognoses of patients with either low- or high-volume bone metastases., Conclusion: In the present era of ARSI doublet therapy, lung-only metastases in mCSPC patients were associated with favorable outcomes. The negative prognostic effects of lung metastases were much lower than was the bone metastasis volume, indicating that treatments targeting low-volume disease may be adequate even when lung metastases are apparent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Objectives: Data regarding willingness to pay (WTP) for one quality-adjusted life year (QALY) may need to be updated given rapidly changing modern lifestyles and dynamic shifts of population's values related to healthcare and economic factors as influenced by the COVID-19 pandemic., Study Design: A cross-sectional study using online-based questionnaire surveys., Methods: We conducted an online survey in March 2024 of 2,000 Japanese adults aged 20-69 years to evaluate their individual WTP for one QALY gained. We constructed a case scenario in which participants were asked to answer a series of yes/no questions to evaluate their willingness to pay for a new treatment to prolong a patient's life with a certain health status for one year. The scenario was stratified by the treatment cost per case, the annual number of patients, and the health status of patients. A probit model was implemented to estimate the WTP for one QALY gained and included the total cost, the total QALYs gained, recruitment method, participant's age, sex, household income, and educational background as explanatory variables., Results: WTP per one QALY gained was estimated to be 16.98 [95%CI 14.43-19.91] million Japanese yen. A positive QALY gain (p < 0.001), male sex (p < 0.001), and higher household income (p < 0.001) were positively correlated with having a higher WTP. A higher total cost (p < 0.001), increased age (p = 0.002) and living alone (p < 0.001) were negatively correlated with WTP., Conclusion: Our study showed that the updated WTP threshold for a QALY gained was much larger than previously reported values. This suggests that WTP data should be reviewed and updated regularly., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A unified view on recovery from supplementary motor area syndrome after glioma resection is lacking. This study retrospectively examined the relationship between motor function, higher brain function, the ability to perform activities of daily living, and social reintegration and the extent of tumor resection in patients who underwent resection of tumors near the supplementary motor area. We assigned 24 consecutive patients into 3 groups according to the depth of tumor resection: resection involving (A) only the supplementary motor area (5 patients); (B) the supplementary motor area and cingulate gyrus (11 patients); and (C) the supplementary motor area, cingulate gyrus, and corpus callosum (8 patients). Motor paralysis, language function, and the ability to perform activities of daily living were evaluated perioperatively and 2 months postoperatively, whereas successful social reintegration was examined retrospectively. In group C, 62% of patients developed severe paralysis after surgery, with slow recovery and delayed ambulation (p = 0.0869). Patients with tumors in the left hemisphere, specifically those extending to the cingulate gyrus and corpus callosum, showed decreased scores for postoperative word recall; however, recovery was observed after 2 months. The Functional Instrumental Measure score, which indicates the activity of daily living ability, showed the largest difference preoperatively and postoperatively in group C. The World Health Organization tumor grade (p = 0.0445) and extent of tumor resection (p = 0.0011) were inversely correlated with social reintegration 6 months postoperatively. Overall, the findings suggest that early social reintegration is influenced by the World Health Organization tumor grade (2021 World Health Organization classification) and the extent of tumor resection.

Objective: We determined the optimal timing for initiating androgen receptor signaling inhibitor (ARSI) therapy in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and assessed its impact on oncological outcomes., Materials and Methods: This retrospective study included 145 nmCRPC patients who received enzalutamide, apalutamide or darolutamide at the Jikei University Hospital or its affiliated institutions between May 2014 and November 2022. Patients were stratified based on prostate-specific antigen (PSA) doubling time (PSADT) at CRPC diagnosis and PSA levels at ARSI initiation. Oncological outcomes, including progression-free survival (PFS), metastasis-free survival (MFS), cancer-specific survival and overall survival, were assessed using the Kaplan-Meier curve and Cox regression analysis., Results: The median age of the patients was 73 (interquartile range [IQR]: 52-88) years, and the median follow-up duration was 36 (IQR: 2-104) months. The median PSA level at ARSI initiation was 5.4 (IQR: 2.2-48) ng/ml, and 44.8% of patients had a PSADT <3 months. Multivariate analysis revealed that PSADT and PSA levels at ARSI initiation were independent MFS predictors. Patients with a PSADT ≤3 months and a PSA level ≥5.4 ng/ml experienced significantly reduced PFS and MFS. Notably, ARSI initiation at a PSA level ≥5.4 ng/ml was associated with worse outcomes, suggesting the potential benefit of earlier intervention., Conclusions: Patients with rapid PSADT are at increased risk of early disease progression, suggesting that immediate treatment may be warranted. In addition, initiating therapy at a PSA level <5.4 ng/ml may be associated with improved patient outcomes in patients with low PSADT., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the effect of studying abroad on catch-up vaccination coverage for measles, rubella, mumps, varicella, and tetanus during the pretravel consultation among young adult travelers., Methods: This retrospective cohort study analyzed data from the Japan Pretravel Consultation Registry (J-PRECOR) on individuals aged 18-21 years with childhood vaccination records. Propensity score weighting was used to estimate the average treatment effect on the proportion of participants receiving catch-up vaccination., Results: Among 1091 eligible participants, the catch-up vaccination need was highest for mumps (65.7 %) and varicella (49.0 %) and lowest for measles (9.9 %) and rubella (14.0 %). In the unadjusted analysis, the catch-up vaccination rate was 70.6 % for tetanus, 50.9 % for measles, 47.7 % for rubella, 40.0 % for mumps, and 23.9 % for varicella. In the weighted analysis, the study-abroad group had significantly higher catch-up vaccination rates for measles (54.6 % vs. 29.8 %, P = 0.039), rubella (53.0 % vs. 22.1 %, P < 0.001), and varicella (26.8 % vs. 10.9 %, P = 0.002), whereas the non-study-abroad group had a higher catch-up vaccination rate for tetanus (62.4 % vs. 78.4 %, P = 0.024)., Conclusion: Compared with other travelers, the catch-up vaccination rate among travelers studying abroad was higher for measles, rubella, and varicella, but lower for tetanus. In clients planning to study abroad, vaccinations required for travel should be recommended in addition to those required by the host institution, and vaccination against highly infectious diseases with potential for complications, such as measles, rubella, mumps, and varicella, should be recommended to clients traveling for reasons other than studying abroad., Competing Interests: Competing interests T.Matono has received speaker honoraria from MSD, Pfizer, Gilead, and GSK., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: A nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases in 2020 provided insights into antimicrobial prescription practices among clinic doctors. This study aimed to investigate factors influencing changes in antimicrobial prescriptions post-implementation of the National Action Plan on Antimicrobial Resistance (NAPAR) and doctors' inclination to prescribe antimicrobials for common cold cases., Methods: In September 2020, randomly selected questionnaires were distributed to 3000 community-based medical clinics in Japan. The primary objective was to assess the reduction in antimicrobial prescriptions post-NAPAR implementation. Multivariate linear regression analysis was employed to identify associated factors., Results: Analysis of 632 responses (response rate: 21.1 %) revealed determinants of decreased antimicrobial prescriptions, including familiarity with the Guide to Antimicrobial Stewardship (β = .482, t = 3.177, p = 0.002) and awareness of NAPAR (β = .270, t = 2.301, p = 0.022)., Conclusion: Interventions such as the Guide to Antimicrobial Stewardship may have contributed to the reduction in antimicrobial prescriptions among Japanese physicians. However, targeted strategies are needed to address high-prescription groups. Enhancing awareness and education on appropriate antimicrobial use should be integral components of future initiatives to combat antimicrobial resistance effectively., Competing Interests: Declaration of competing interest Shigefumi Maezaki has received lecture fees from Pfizer Japan Inc., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co. Ltd., Shionogi & Co. Ltd., MSD K.K., KYORIN Pharmaceutical Co. Ltd., and Taisho Toyama Pharmaceutical Co. Ltd. Tetsuya Matsumoto has received lecture fees from MSD K.K., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., and Meiji Seika Pharma Co., Ltd., as well as research funding from Kewpie Corp. Norio Ohmagari, Yoshiaki Gu, Shinichiro Morioka, Shinya Tsuzuki, Hiroshi Soeda, Chikara Nakahama, Naoki Hasegawa, Yumiko Fujitomo, Masayuki Maeda, and Isao Miyairi have declared no conflicts of interest associated with this manuscript., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Overconsumption of fat contributes to obesity and low adherence to dietary therapy in patients with obesity. The frequency of consuming soup dishes containing "dashi" (Japanese broth), a characteristic element of the Japanese diet, is negatively associated with obesity indicators. The use of dashi is considered one of the reasons why the low-fat Japanese diet is popular; however, whether and how dashi controls the selection and intake of fat is unknown. In this study, we tested the hypothesis that bonito broth, a typical Japanese dashi, affects fat consumption in a mouse model. First, we examined the long-term or short-term intake of corn oil emulsion in adult mice fed bonito broth. No significant effect was observed. Next, mouse dams were fed bonito broth during gestation or lactation and licking of 0.5, 1, 2.5, 5, and 10% corn oil in their adult pups was evaluated in acute tests. Compared to the control group, there were significant decreases in licks for some corn oil concentrations in the gestation and lactation groups. Finally, corn oil licking was tested in pups fed bonito broth after weaning. No significant effect was detected. This study suggests that dams' intake of bonito broth during gestation or lactation reduces the intake of fat by their pups in adulthood., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The social contact data for Japan as of 2022 showed a substantially decreased number of contacts compared with before the COVID-19 pandemic. However, it is unclear whether social contact continues to be depressed following the end of countermeasures against the pandemic. There is also scarce evidence regarding the influence of influenza-like illnesses (ILIs) on social contacts in Japan. Therefore, this study examined whether the reduction in contact frequency during the pandemic was temporary or persists today and assessed the impact of ILIs on social mixing patterns., Methods: We conducted online questionnaire surveys of individuals who experienced symptoms of ILIs periodically from 2022 to 2024 to compare the number of contacts per day during and after their illnesses. Contact matrices were obtained from the survey data. The impacts of the timing of the survey and the ILIs were examined using negative binomial regression analysis., Results: Contact patterns were generally age-assortative, and the average contact numbers gradually increased from March 2022 to June 2024. Most recently, the median number of contacts per day during illness was 3 (interquartile range [IQR] 2-7) and then rose to 4.5 (IQR 2-11) after recovery. The earlier survey and ILIs showed a negative association with the frequency of social contacts., Conclusion: The frequency of social contacts in Japan tended to rise compared with that in 2021 but has not yet reached pre-pandemic levels. Individuals tended to decrease their contacts when they had symptoms caused by ILIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Co-infection with other pathogens can alter the severity and clinical outcomes of viral infections. However, the information regarding viral co-infections in pediatric coronavirus disease 2019 (COVID-19) cases is still limited., Methods: This is a nationwide, retrospective cohort study using the data from the COVID-19 Registry Japan. The pediatric (<18 years), laboratory confirmed, hospitalized COVID-19 patients in the Omicron variant of concern predominant period (January 2022 to January 2024) were included. Co-infection was investigated by multiplex PCR. We compared clinical characteristics, symptoms, severity, and outcomes between children with and without co-infection., Results: Among 245 hospitalized pediatric COVID-19 patients, 78 (31.8 %) had co-infections. The patient backgrounds of the "co-infection" and "SARS-CoV-2 alone" groups were similar, although age distribution was different, with a lower number of patients over 12 years in the co-infection group (n = 2, 2.6 % vs. n = 29, 17.4 %; P < 0.001). Among the patients with co-infection, the most common pathogen was enterovirus/rhinovirus (51.3 %), followed by parainfluenza virus (23.1 %) and adenovirus (12.8 %). Patients with co-infection more commonly had respiratory symptoms, including SpO 2 < 96 %, shortness of breath, runny nose, and wheezing. Requirement of non-invasive oxygen support was higher in the co-infection group (n = 27, 34.6 % vs. n = 28, 16.8 %, P = 0.006). By multivariable logistic regression analysis, co-infection and presence of any comorbidity were identified as significant risk factors for necessity of oxygen therapy (odds ratio [95 % confidence interval] 2.44 [1.29-4.63] and 3.99 [2.07-7.82], respectively)., Conclusions: Viral co-infection may increase the risk of respiratory distress in pediatric COVID-19 patients., Competing Interests: Declaration of competing interest K. Shoji received payment for lectures from bioMérieux Japan, Nippon Becton Dickinson Company, Ltd., Viatris, Inc., Meiji Seika Pharma Co., Ltd., AstraZeneca K.K., Novartis Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Gilead Sciences, Inc. S. Tsuzuki received payment for supervising medical articles from Gilead Sciences, Inc. I. Miyairi received payment for lectures from Astellas Pharma, Sanofi K.K., Pfizer, Inc., Takeda Pharmaceutical Company, Ltd., Biken Group, Shionogi & Company, Ltd., bioMérieux Japan, Gilead Sciences, Inc., Meiji Seika Pharma, KM Biologics, Tanabe-Mitsubishi Pharmaceuticals, and Daiichi Sankyo. The other authors declare that they do not have any conflicts of interest directly associated with the study., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Despite its demonstrated efficacy in prolonging overall survival (OS) and delaying skeletal-related events in the ALSYMPCA trial, the optimal timing of radium-223 initiation remains unclear. This study investigated factors influencing radium-223 treatment outcomes, including completion rates and survival., Methods: This retrospective, multi-institutional study included 164 patients with metastatic castration-resistant prostate cancer (CRPC) who received radium-223 therapy. The primary endpoint was OS following radium-223 initiation. Secondary endpoints included factors associated with incomplete radium-223 treatment (< six cycles) and poor OS. Multivariate Cox regression and multivariate logistic regression analyses were conducted to identify prognostic factors., Results: The median OS times after CRPC diagnosis and radium-223 initiation were 39 and 12.5 months, respectively. Kaplan-Meier analysis showed that the OS of patients who completed six cycles of radium-223 treatment was longer than that of those who did not (18 vs. 5 months; P < .001). Multivariate Cox analysis identified Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 1 (hazard ratio [HR] = 1.74, P = .046), PSA > 17 ng/ml (HR = 2.93, P < .001), and radium-223 incompletion (HR = 3.23, P < .001) as independent predictors of poor OS. The radium-223 completion rate was 68.3%, and incompletion was significantly associated with prior docetaxel use (odds ratio [OR] = 5.97, P = .001), bone pain (OR = 2.64, P = .024), and PSA > 17 ng/ml at the start of radium-223 treatment (OR = 3.12, P = .013)., Conclusions: Completion of all six cycles of radium-223 treatment were associated with favorable survival outcomes in metastatic CRPC patients. Prior docetaxel use, bone pain, and elevated PSA levels were significant risk factors for radium-223 incompletion. These findings suggest the importance of initiating radium-223 earlier in the treatment course for patients with favorable clinical profiles to maximize the therapeutic benefits., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: The JAVELIN Bladder 100 trial demonstrated improved overall survival (OS) with maintenance avelumab in patients with locally advanced or metastatic urothelial carcinoma UC (la/mUC) who achieved disease control following first-line platinum-based chemotherapy (1 L-PBC). However, real-world data on eligibility, utilization, and outcomes of maintenance avelumab therapy remain limited., Methods: This retrospective study included patients with la/mUC who received 1 L-PBC. Eligibility for maintenance avelumab therapy was determined based on the best overall response to 1 L-PBC, with patients who achieved stable disease or a partial or complete response considered eligible. Survival outcomes were analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis was used to identify prognostic factors among patients with la/mUC who received maintenance avelumab., Results: Of 161 prospective patients, 67.1% were eligible for maintenance avelumab therapy, and 46.3% of eligible patients received the treatment. The median progression-free survival (PFS) following avelumab initiation was 10.2 months, whereas the median OS was not reached. Prognostic factors associated with PFS included the presence of liver metastases, elevated C-reactive protein (> 1.0 g/dL), and administration of more than five cycles of 1 L-PBC. Adverse events occurred in 60% of patients treated with avelumab, with 16% experiencing grade 3-4 adverse events., Conclusion: We emphasize the real-world applicability of maintenance avelumab for Japanese patients with la/mUC. Maintenance avelumab demonstrated favorable survival outcomes, consistent with clinical trial data. Identifying prognostic factors and optimizing treatment sequencing are essential strategies for improving outcomes in this patient population., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The COVID-19 pandemic was associated with a global decrease in antimicrobial consumption (AMC) in 2020. However, the persistence of this downwards trend is not known at a global level. This study examined the global and longer-term trends in AMC after the emergence of COVID-19., Methods: The change rate of AMC was compared (a) 2020 over 2019, (b) 2021 over 2020, and (c) 2022 over 2021 using monthly sales volume data of antimicrobials in 69 countries obtained from the IQVIA MIDAS information service. Changepoints were detected using time-series data of global monthly antimicrobial sales from November 2016 to December 2023. We defined antimicrobials as oral and parenteral drugs classified as J1 by the Anatomical Therapeutic Chemical code. Antimicrobial sales were reported in standard units, as defined by IQVIA. We assessed the data using standard units per 1000 population per day, with populations based on World Population Prospects data issued by the United Nations. In addition, interrupted time-series analysis was used to examine the impact of movement restrictions in G7 countries., Results: In the IQVIA MIDAS data, 68 of the 69 countries had more than one changepoint between 2016 and 2023. Of these 68 countries, 61 experienced a decrease in AMC after the COVID-19 pandemic started. However, 53 of these 61 countries showed a reverse increasing trend in AMC in 2022. Interrupted time-series analysis revealed that movement restrictions had a negative impact on AMC in all G7 countries., Discussion: The global decrease in AMC in 2020 might not have been because of COVID-19 itself but to non-pharmaceutical interventions such as movement restrictions. Human mobility could possibly be one of the key determinants of antimicrobial use at the population level., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite the availability of advanced imaging technologies, it remains difficult to achieve sufficient staging accuracy to ensure a tailored treatment strategy for patients with upper tract urothelial carcinoma (UTUC). The aim of the study was to identify preoperative risk factors for tumor upstaging in patients with UTUC initially staged as clinical T2 or lower and to analyze these factors separately for renal pelvic cancer and ureteral cancer., Methods: This retrospective study included data from patients with UTUC who underwent nephroureterectomy. Among them, patients who underwent a staging evaluation using computed tomography urography within 90 days before surgery were selected. Various preoperative factors were evaluated, and multivariate logistic regression analyses were conducted to identify predictors of pathological tumor upstaging., Results: The study included 496 patients, of whom 392 were diagnosed with clinical T2 stage or lower. Among these, 125 patients (31.9%) were upstaged to pathological T3 or T4 disease. Multivariate analysis identified positive voided urine cytology [hazard ratio (HR) =2.94, P<0.001] and tumor size ≥30 mm (HR =1.90, P=0.008) as independent predictors of upstaging. Subgroup analysis showed that positive voided urine cytology (HR =2.71, P=0.004) and tumor size ≥30 mm (HR =3.39, P=0.001) were significant risk factors for renal pelvic cancer. In contrast, significant predictors for ureteral cancer included positive voided urine cytology (HR =3.11, P=0.003) and hydronephrosis (HR =2.69, P=0.03)., Conclusions: Positive voided urine cytology and larger tumor size were significant predictors of pathological upstaging in patients with UTUC. Differences in the risk factors between renal pelvic and ureteral cancers highlight the need for tailored preoperative evaluations and management strategies. Further studies are required to refine these predictive models and improve clinical decision-making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-357/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: The EF-14 clinical trial demonstrated the safety and efficacy of tumor-treating fields (TTFields) for newly diagnosed glioblastoma. This study aimed to clarify the current status, safety, and efficacy of TTFields in Japanese patients who meet the EF-14 inclusion criteria., Methods: This was a multicenter retrospective cohort study. Background, treatment, and outcome data of patients who satisfied the inclusion criteria of the EF-14 trial were collected from 45 institutions across Japan. The rate, determinants, and current status of TTField use, including its safety and efficacy in terms of progression and survival, were retrospectively investigated. This study was conducted in accordance with the STROBE checklist., Results: Among the 607 patients enrolled, 70 were excluded due to progressive disease during radiation and temozolomide therapy, age > 80 years old, and Karnofsky Performance Status score of <70. Among the remaining 537 patients, 210 (39%) underwent TTField treatment. Multivariate analysis revealed younger age and spouse as a caregiver as significant factors for TTField use. The compliance rate of TTField use exceeded 75% in 60% of patients, with a median TTField usage duration of 11 months. Skin disorders requiring medical treatment occurred in 56% of patients. Multivariate Cox proportional hazards analysis in the whole series and propensity score-matched analysis revealed that TTField use was not a prognostic factor for progression-free survival (PFS) or overall survival (OS)., Conclusions: TTField use did not have a substantial effect on either PFS or OS in Japanese patients with glioblastoma, despite compliance rates comparable to those observed in the EF-14., Competing Interests: M.Ka. received honoraria from Novocure and Eisai and research funding from Eisai. K.S. received honoraria from Novocure and Eisai and research funding from Eisai and Nippon Kayaku. S.Y. received honoraria from Novocure. M.N. received honoraria from Novocure and Eisai. T.M. received honoraria from Novocure and Eisai. M.N. received honoraria from Novocure, Eisai, and Nippon Kayaku and research funding from Eisai and MSD. K.Y. received honoraria from Novocure. H.Y. received honoraria from Novocure and Eisai. Y.Nakahara received honoraria from Novocure and Eisai. Y.H. received honoraria from Novocure and Eisai and research funding from Eisai. M.Ki. received honoraria from Novocure and Eisai. A.Y. received research funding from Eisai. Y.K. received honoraria from Novocure and Eisai. M.T. received research funding for clinical trial from Eisai. Y.A. received honoraria from Novocure, Eisai, and Nippon Kayaku. Y.Narita received honoraria from Novocure and Eisai and research funding from Eisai. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

The spread of antimicrobial resistant organisms (AROs) poses a major threat to animal and human health. In Japan, the estimated disability-adjusted life years (DALYs) due to ARO infections is 137.9 per 100,000 persons, with methicillin-resistant Staphylococcus aureus (MRSA) being the main contributor. Factors that can contribute to DALYs in Japan include younger age and a higher number of deaths in patients with MRSA bacteremia. Moreover, longer hospital stays may contribute to the higher rates of MRSA bacteremia in Japan than in western countries. We reviewed the diagnostic procedure combination data collected from January 1, 2016 to December 31, 2020, in an acute care hospital in Tokyo, Japan. We found that the median time from admission to MRSA bacteremia onset was 26 days, which is longer than that observed in western countries however similar to that in South Korea. Furthermore, our cohort was older than those in the United States and South Korea, potentially contributing to the higher number of years of life lost in Japan. These results underscore the need to develop strategies to reduce hospitalization rates in Japan. Larger multicenter studies are needed to comprehensively evaluate the economic and health burdens of MRSA bacteremia in Japan.

Purpose: To re-evaluate images recovered from JCOG0911, a randomized phase 2 trial for newly diagnosed glioblastoma (nGBM) conducted by the Japan Clinical Oncology Group (JCOG) Brain Tumor Study Group., Methods: The correlation between tumor volumes and survival was evaluated, followed by progression-free survival (PFS) analysis by independent central review based on Response Assessment in Neuro-Oncology (RANO) criteria using MRI recovered from 118 nGBM patients enrolled in the JCOG0911 trial. A radiomic analysis was also performed to identify radiomic features predictive of nGBM prognosis., Results: The distribution of the Gd-enhancing and T2-weighted image/fluid attenuated inversion recovery-high intensity lesions mainly occupied white matter. JCOG0911 consisted of more subjects with right-sided lesions. The median extent of resection of the Gd-enhancing lesions was 99%. The overall survival showed a nonsignificant negative trend with postoperative Gd-enhancing lesion volume (P = 0.22), with the hazard ratio increasing in parallel with its volume. The median PFS after registration was 302 and 308 days for local Response Evaluation Criteria in Solid Tumors (RECIST)-based and central RANO-based diagnoses. However, an apparent discrepancy was observed between the two in the early phase, presumably due to the misdiagnosis of pseudoprogression by local RECIST-based diagnosis. Radiomic analysis identified 28 radiomic features predictive of nGBM prognosis, 5 of which were those previously identified in a separate cohort. The constructed radiomics-based prognostic model stratified the cohort into high- and low-risk groups (P = 0.028)., Conclusion: Novel analytical methods that could be incorporated into future clinical trials were successfully tested. RANO and RECIST may not differ in progression calls if pseudoprogression is appropriately handled.

The challenge in developing molecule-based electronic materials lies in the uncontrollable or unpredictable nature of their crystal structures, which are crucial for determining both electrical properties and thin-film formability. This review summarizes the findings of a research project focused on the systematic development of crystalline organic semiconductors (OSCs) and organic ferroelectrics by integrating experimental, computational, and data sciences. The key outcomes are as follows: 1) Data Science: We developed a method to identify promising materials from crystal structure databases, leading to the discovery of unique molecule-based ferroelectrics. 2) Computational Science: The origin of high layered crystallinity in π-core - alkyl-chain-linked molecules was clarified based on intermolecular interaction calculations. We proposed a stepwise structure optimization method tailored for layered OSCs. 3) Material Development: We developed various alkylated layered OSCs, which exhibit high mobility, heat resistance, and solubility. We discovered several unique phenomena, including frozen liquid crystal phases, significant polar/antipolar control, and phase control through mixing, leveraging the variability of alkyl chain length. We also developed molecule-based ferroelectrics showing peculiar ferroelectricity, including multiple polarization reversal, competing ferroelectric/antiferroelectric order, and spinner-type configurations with π-skeletons. 4) Advanced Structural Analysis: By combining cryo-electron microscopy and X-ray-free electron laser (XFEL), we enabled crystal structure analysis for ultrathin crystals that are usually difficult to analyse. 5) Device Development: Utilizing the self-organized growth of layered OSCs through solution processes, we developed a method to produce exceptionally clean semiconductor - insulator interfaces, achieving field-effect transistors that show sharp (near theoretical limit) and stable switching at low voltages., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

The attraction between π-conjugated planar electron donor and acceptor molecules that form many stable charge-transfer (CT) complexes has been explained by quantum chemical CT interactions, although the fundamental origin remains unclear. Here, we demonstrate the mechanism of CT complex formation by potential energy map analysis for TTF-CA and BTBT-TCNQ, using energy decomposition of intermolecular interaction by symmetry-adapted perturbation theory (SAPT) combined with coupled cluster calculation. We find that the source of attraction between donor and acceptor molecules is ascribed primarily to the dispersion force and also to the electrostatic force. In contrast, the contribution of CT interactions to the attractive forces is minimal. We demonstrate that the highly directional feature of the exchange repulsion force, coupled with the attractive dispersion and electrostatic forces, is crucial in determining the intermolecular arrangements of actual CT crystals. These findings are key for understanding the unique structural and electronic properties of π-conjugated CT complexes., (© 2024. The Author(s).)

Objectives: This study explored the impacts of peri-operative changes in the neutrophil-to-lymphocyte ratio (NLR) on the survival rate after radical nephroureterectomy., Methods: This retrospective analysis included a multicentric cohort of patients diagnosed with upper tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy from 2012 to 2021. We assessed the preoperative NLR, postoperative NLR, delta-NLR (difference between postoperative and preoperative NLRs), and NLR change (ratio of postoperative to preoperative NLR). Additionally, patients were categorized according to increases in their preoperative and/or postoperative NLRs. Associations of survival with peri-operative changes in the NLR were investigated using Cox multivariate regression models., Results: A total of 488 patients were included in the study, with a median age of 73 years. Among the patients, 105 (21.5%) exhibited elevated preoperative and postoperative NLRs, 88 (18.0%) exhibited elevated preoperative NLR only, 53 (10.9%) exhibited elevated postoperative NLR only, and 242 (49.6%) exhibited normal NLRs. Multivariate analysis indicated significant negative correlations between both preoperative and postoperative increased NLRs and oncological outcomes, including nonurothelial tract recurrence-free survival and cancer-specific survival (hazard ratio [HR]: 1.65, P = 0.017; HR: 2.12, P = 0.014, respectively)., Conclusion: This is the first study to evaluate the association between peri-operative changes in the NLR and the outcomes of patients with UTUC who underwent radical nephroureterectomy. Patients with elevated NLRs at both time points experienced considerably worse outcomes. Further research should explore whether increases in the NLR during long-term follow-up could indicate impending disease recurrence., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Two randomized trials demonstrated that the survival benefits afforded by triplet therapy were greater than those of doublet therapy, thus changing the treatment paradigm for metastatic castration-sensitive prostate cancer (mCSPC). This is the first study to assess the real-world use, performance, and safety of triplet therapy in Japanese patients., Methods: This retrospective multicenter study included 45 consecutive mCSPC patients who received triplet therapy composed of androgen deprivation therapy (ADT), docetaxel, and darolutamide between January 2023 and June 2024. Baseline patient characteristics and their clinical parameters during triplet therapy were collected. Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events version 5.0, and imaging responses were evaluated following the RECIST criteria. The prostate-specific antigen (PSA) nadir was defined as the lowest PSA value during follow-up, and the PSA decrease was the initial PSA value minus the PSA nadir., Results: The median patient age was 70 years and the median follow-up duration was 10 months. High-volume disease was present in 82.2% of patients. Concurrent administration of docetaxel and darolutamide was scheduled for 22.2% of cases. The incidence of any AE was 86.7%, with 55.5% of patients experiencing grade 3-4 AEs. Neutropenia was common, but prophylactic granulocyte colony-stimulating factor (G-CSF) significantly reduced the incidence of neutropenia of grade 3 or higher. Febrile neutropenia occurred in four patients (8.9%); these patients had not received prophylactic G-CSF. A decline in PSA of 90% was observed in 95.6% of patients, and an imaging response was seen in 97.8%., Conclusions: Triplet therapy with ADT, darolutamide, and docetaxel was highly efficacious and tolerable in Japanese mCSPC patients, particularly those with high-volume disease. Prophylactic G-CSF prescription is crucial to manage neutropenia effectively. Further studies with longer follow-ups are needed to confirm these findings and explore the long-term outcomes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs)., Methods: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan-Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed., Results: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Kaplan-Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grades 3-4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT., Conclusions: Initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes., (© 2024 The Japanese Urological Association.)

Some reports suggest that coronavirus disease 2019 (COVID-19) may affect male reproductive function. There is also concern in Japan that COVID-19 may contribute to the pre-existing decline in male fertility; however, no studies have investigated the effects of COVID-19 on male reproductive function. In this study, we aimed to analyze the semen quality of men who had recovered from COVID-19. Male patients who had recovered from COVID-19 between February 2020 and September 2021 were recruited for this study. Participants were sent a semen collection kit; they were asked to collect semen at home and deliver it to a laboratory at Osaka University. We used these samples to analyze sperm concentration, total sperm count, and semen volume. In total, 125 participants were included in this study. The median age of all patients was 46 years (interquartile range (IQR): 38-52 years). The severity of COVID-19 was mild in 80 patients; 19 were moderate I, 22 were moderate II, and four were severe. The median semen volume was 2.5 mL (IQR: 1.8-3.1), the median sperm concentration was 98.9 million/mL (IQR: 43.8-162.2), and the median total sperm count was 212.1 million (IQR: 89.7-368.2). In a previous study in Japan, the median sperm count in adult men was reported to be 201 million. Participants in our study did not have lower sperm counts than this, despite their older age. Our results suggest that the long-term effects of COVID-19 on spermatogenesis are minimal., Competing Interests: Declarations of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Gelation of sulfolane-based highly concentrated electrolytes using a partially fluorinated polymer enhances the Li-ion transference number of the electrolytes because acidic protons surrounded by fluorine atoms in the polymer network trap anions, and the high Li + transference number is effective in suppressing the concentration polarization in Li batteries.

Introduction: Comprehensive evidence about the burden of infectious diseases in the Western Pacific Region is scarce. We thus examined the disease burden of infectious diseases in Japan in terms of disability-adjusted life years (DALYs)., Methods: We extracted national claims data from Japan's universal health insurance system to estimate the burden of disease for selected infections between 2015 and 2020 using DALYs. The mortality rate, disability duration and severity weight of each disease were estimated based on national data and literature reviews., Results: Disease burden per 100,000 population was 1307.0 in 2015 and 972.1 in 2020 for bloodstream infections (BSI), 796.5 DALYs in 2015 and 498.9 DALYs in 2020 for pneumonia, 171.5 in 2015 and 149.4 in 2020 for meningitis and 11.6 in 2015 and 11.4 in 2020 for urinary tract infections (UTI). Only surgical site infections (SSI) showed a slightly increasing trend over the 5-year period, from 2.2 in 2015 to 2.8 in 2020., Conclusions: Our results showed that the disease burden of the five major infectious diseases was higher in Japan than in other countries. However, while the burden of SSI increased, the burden of pneumonia, meningitis, BSI and UTI gradually decreased year on year. The possible causes of the decreased morbidity should be examined in future work., Competing Interests: Declaration of competing interest All authors have nothing to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Li-S batteries have attracted attention as next-generation rechargeable batteries owing to their high theoretical capacity and cost-effectiveness. Sparingly solvating electrolytes hold promise because they suppress the dissolution and shuttling of polysulfide intermediates to increase the coulombic efficiency and extend the cycle life. This study investigated the solubility of polysulfide (Li 2 S 8 ) in a range of liquid electrolytes, including organic electrolytes, highly concentrated electrolytes, and ionic liquids. The Li 2 S 8 solubility was well correlated with the donor number (DN NMR ), estimated via 23 Na-NMR, and was lower than 100 mM&#95;(elemental sulfur) in electrolytes with DN NMR -butyl methyl ether (BME), and ethyl propyl ether (EPE) were studied as sparingly solvating electrolytes for Li-S batteries. Monomethyl ethers, such as BME, showed more pronounced Li-ion coordination and higher ionic conductivity, whereas the steric hindrance of the longer alkyl chains in EPE lowered the solvation number, enhanced ion association, and lowered the ionic conductivity despite the solvents having similar dielectric constants. The charge-discharge rate capabilities of Li-S cells with dialkyl ether-based electrolytes were more impressive than those of cells with a localized high-concentration electrolyte using sulfolane (SL) and hydrofluoroether (HFE), [Li(SL) n -butyl methyl ether (BME), and ethyl propyl ether (EPE) were studied as sparingly solvating electrolytes for Li-S batteries. Monomethyl ethers, such as BME, showed more pronounced Li-ion coordination and higher ionic conductivity, whereas the steric hindrance of the longer alkyl chains in EPE lowered the solvation number, enhanced ion association, and lowered the ionic conductivity despite the solvents having similar dielectric constants. The charge-discharge rate capabilities of Li-S cells with dialkyl ether-based electrolytes were more impressive than those of cells with a localized high-concentration electrolyte using sulfolane (SL) and hydrofluoroether (HFE), [Li(SL) 2 ][TFSA]-2HFE. The higher rate performance was attributed to the superior Li-ion transport properties of the dialkyl ether-based electrolytes. A pouch-type cell using lightweight [Li(BME) 3 ][TFSA] demonstrated an energy density exceeding 300 W h kg -1 under lean electrolyte conditions.

Background: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved., Methods: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL., Results: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month)., Conclusions: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The effect of radical nephroureterectomy (RNUx) on postoperative renal function in patients diagnosed with upper tract urothelial carcinoma (UTUC) has not been thoroughly explored., Methods: We conducted a retrospective analysis including 785 patients who underwent RNUx for UTUC. We assessed the preoperative and postoperative estimated glomerular filtration rates (eGFRs) and factors related to the decline in eGFR. Additionally, we examined the effect of comorbidities (diabetes or hypertension) on the postoperative eGFR at 1 year. Cox proportional hazard models were employed to investigate the clinical effect of RNUx on oncological outcomes, including non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS)., Results: The median preoperative and postoperative eGFR levels were 54.7 and 40.6 ml/min/1.73 m 2 respectively. The proportions of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m 2 were 35.9% and 5.1%, respectively. The median decline in the eGFR after surgery was 26.8%. Patients with preoperative eGFR <60 ml/min/1.73 m 2 demonstrated significantly lower odds of a postoperative decline in eGFR of 25% or more. The effect of comorbidities on postoperative eGFR at 1 year was significant (P = 0.048). The 3-year NUTRFS, CSS, and OS rates were 72.9%, 85.2%, and 81.5%, respectively. Preoperative chronic kidney disease was an independent factor associated with inferior NUTRFS, CSS, and OS., Conclusion: Different degrees of impairment of renal function occur among UTUC patients. Only 5.1% of patients retain a postoperative eGFR ≥60 ml/min/1.73 m 2 . Preoperative renal impairment was linked to reduced odds of postoperative eGFR decrease and associated with survival. In addition, the presence of comorbidities had a significant effect on the decline in eGFR. These findings emphasize the importance of developing evidence-based perioperative treatment strategies for UTUC patients with impaired renal function., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Multiparametric magnetic resonance imaging (mpMRI) is increasingly used for the early detection of clinically significant prostate cancer (csPCa). However, the achievement of accurate detection rates, particularly for transition zone (TZ) lesions, remains challenging. We investigated the relationship between apparent diffusion coefficient (ADC) values in Prostate Imaging Reporting and Data System (PI-RADS) 3-5 lesions and csPCa within the TZ., Methods: We retrospectively evaluated TZ lesions in patients who underwent 3.0 Tesla MRI followed by MRI-targeted/transrectal ultrasound fusion biopsies (MRI-FBx). Fusion biopsies were performed for potentially cancerous lesions, defined as lesions with PI-RADS scores 3-5. We analyzed 196 lesions for which fusion biopsies were performed., Results: The overall prostate cancer (PCa) detection rate was 53.6% (105/196); csPCa constituted 33.7% (66/196) of cases. The minimum ADC value was significantly lower for patients with csPCa (484.9±112.3 µm 2 /s) than for patients with benign histology or non-csPCa (P<0.001). Older age, higher initial prostate-specific antigen level, larger region of interest, and minimum and mean ADC values were associated with the presence of csPCa. Multivariate analysis indicated that only the minimum ADC value was an independent predictor of csPCa. Using a cutoff minimum ADC value <561 µm 2 /s to detect csPCa in TZ lesions increased the detection rate to 57.4% (54/94)., Conclusions: The minimum ADC value provides substantial additional information regarding the presence of csPCa in the TZ, potentially improving the detection rates for lesions rated as PI-RADS 3-5 and informing the need for follow-up biopsies in areas that are initially cancer-free., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-235/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

The stability of adsorbed molecules on surfaces is fundamental and important for various applications, such as coating, lubrication, friction, and self-assembled structure formation. In this study, we investigated the structures and interaction energies ( E int ) of propane, n -pentane, n -heptane, perfluoropropane, n -perfluoropentane, and n -perfluoroheptane adsorbed on the surface of C 96 H 24 (a model surface of graphite). The changes in E int (Δ E int = E int - E int (0)) associated with the horizontal displacement from the stable position were calculated using dispersion-corrected density functional theory (DFT; B3LYP-D3), where E int (0) is the E int at the stable position. The maximum value of Δ E int (Δ E int(max) ) associated with the horizontal displacement increased as the chain length increased. The Δ E int(max) for the three n -alkanes were 1.10, 1.82, and 2.35 kcal mol -1 , respectively. The values for n -perfluoroalkanes were 0.57, 0.83, and 1.04 kcal mol -1 , respectively. The Δ E int(max) values for the n -alkanes were significantly larger than those for the corresponding n -perfluoroalkanes. The E int(max) value per carbon atom of the n -alkanes ( ca. 0.30 kcal mol -1 ) is approximately 2.5 times as large as that of n -perfluoroalkanes ( ca. 0.12 kcal mol -1 ). The Δ E int associated with the horizontal displacement of propane and perfluoropropane on circumcoronene (C 54 H 18 ) obtained by the B3LYP-D3 calculations are close to those obtained by the second order Møller-Plesset (MP2) and dispersion-corrected double hybrid DFT calculations, suggesting the sufficient accuracy of the Δ E int obtained by the B3LYP-D3. Thus, our quantitative analysis revealed the higher stability of n -alkanes against horizontal displacement on a graphite surface than that of n -perfluoroalkanes.

Resection of a glioma from the dorsomedial frontal lobe, including the supplementary motor area (SMA), can result in postoperative SMA syndrome. SMA syndrome may occur during awake craniotomies. However, it is often difficult to intraoperatively distinguish between motor dysfunction due to pyramidal tract damage from that due to SMA syndrome. Patients with suspected intraoperative SMA syndrome are indifferent to their surroundings, have stiff facial muscles, and maintain a fixed gaze. We defined this condition as "apathetic look." The present study aimed to investigate whether intraoperative "apathetic look" is useful for identifying intraoperative SMA syndrome in patients with glioma close to motor-related areas, including the SMA, during awake craniotomy. This study included 33 consecutive patients with glioma included in the SMA. We excluded patients whose tumors extended to motor-related areas. We also assessed whether intraoperative SMA syndrome occurred in each patient. We evaluated the correlation between the occurrence of intraoperative SMA syndrome and various clinical factors, including intraoperative "apathetic look." Of the 33 patients, 12 had intraoperative SMA syndrome. Intraoperative "apathetic look" showed strong correlation with intraoperative SMA syndrome (p < 0.0001). Additionally, higher extent of resection (EOR) and resection of the corpus callosum showed a significantly higher incidence of intraoperative "apathetic look." All 12 patients with intraoperative SMA syndrome showed intraoperative "apathetic look" and recovered from SMA syndrome with high EOR. In conclusion, intraoperative "apathetic look" shows strong correlation with intraoperative SMA syndrome. Therefore, "apathetic look" may be a valuable indicator of intraoperative SMA syndrome during awake craniotomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis., (© 2024 Park et al.)

Background: Streptococcal toxic shock syndrome (STSS) is a life-threatening condition caused by beta-hemolytic streptococci (BHS). Streptococcus pyogenes is the main causative agent of this disease; other BHS such as Streptococcus agalactiae or Streptococcus dysgalactiae could also cause STSS. However, the clinical characteristics of STSS caused by other types of BHS remain poorly understood. In this study, we evaluated the likelihood of STSS development in various streptococcal species., Methods: We conducted a retrospective observational study using adult medical records of patients with invasive BHS in a tertiary care institution from 2002 to 2022 and classified them into STSS or non-STSS groups. Multivariable analysis of bacterial species adjusted for age and diabetes mellitus was conducted. S pyogenes cases were propensity-matched (1:4) to non-pyogenes BHS cases., Results: A total of 43 STSS and 285 non-STSS cases were identified. S pyogenes , S agalactiae , and S dysgalactiae accounted for 17, 13, and 13 STSS cases, respectively. The crude mortality of STSS was approximately 35% in all groups. A multivariable analysis suggested that STSS was less frequent in S agalactiae and S dysgalactiae cases with odds ratio 0.24 (95% confidence interval [CI], 0.10-0.54; P < .001) and 0.23 (95% CI, .10-.55; P < .001), respectively. Propensity score matching showed that S pyogenes caused STSS more frequently than other BHS cases with an odds ratio of 3.28 (95% CI 1.21-8.77; P = .010)., Conclusions: This study described and compared the clinical characteristics of STSS caused by different BHS. We demonstrated that S pyogenes caused STSS more often than other BHS., Competing Interests: Potential Conflicts of Interest. The authors declare that there is no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The indole ring of tryptophan can form NH/π hydrogen bonds, acting both as a hydrogen donor at the NH group in the pyrrole subring and as a hydrogen acceptor at the benzene subring. In the structural core of the trimeric stable protein Pholiota squarrosa lectin (PhoSL), three indoles are symmetrically arranged and form NH/π hydrogen bonds among each other. Here, we conducted quantum chemical calculations on this indole triad by using various methods and basis sets. The analyses revealed cooperativity in triad formation, with the many-body effect contributing approximately -2 kcal mol -1 , which significantly stabilizes this protein. Symmetry-adapted perturbation theory ascribed this effect to the induced polarization. The electrostatic potential and atomic charges indeed revealed a charge redistribution through the NH/π hydrogen bond, which was favorable for triad formation.

Background: Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data., Methods: Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin-tazobactam [PIP/TAZ], ampicillin-sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated., Results: In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection., Conclusion: CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH., Methods: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality., Results: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test)., Conclusions: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Objective: Phase III clinical trials demonstrated the efficacy of enzalutamide and apalutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and PSA doubling time ≤10 months. Although these drugs have been shown to vary in their adverse event (AE) profiles, the differences in their efficacy profiles remain to be evaluated. Therefore, this retrospective study was conducted to evaluate the efficacy of these drugs in patients with nmCRPC., Methods: This study evaluated 191 patients with nmCRPC treated with enzalutamide (n = 137) or apalutamide (n = 54) in the first-line setting at Jikei University Hospital or its affiliated hospitals between May 2014 and November 2022. Endpoints were defined as oncological outcomes (i.e., PSA response, PFS, PSA-PFS, MFS, CSS, and OS) and AEs., Results: No significant differences were noted in patient backgrounds between the two groups. Patients exhibiting a maximum PSA response of >50% and >90% accounted for 74.5% and 48.9% of patients in the enzalutamide group, and 75.9% and 42.6% of patients in the apalutamide group, respectively, with no significant difference between the groups. The median PSA-PFS was 10 months in the enzalutamide group but not in the apalutamide group, with no significant difference between the groups (P = 0.48). No significant differences were observed in MFS, CSS, or OS between the groups. Patients reporting AEs of all grades and grade 3 or higher accounted for 56.2% and 4.3% of those in the enzalutamide group and 57.4% and 7.4% of those in the apalutamide group, respectively. The most common AE was fatigue (26.3%) in the enzalutamide group and skin rash (27.8%) in the apalutamide group., Conclusion: In this retrospective study of their efficacy and safety, enzalutamide and apalutamide were shown to exhibit comparable oncological outcomes but quite different AE profiles, suggesting that their differential use may be warranted based on these findings., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: This study aimed to investigate the epidemiology of post-coronavirus disease 2019 (COVID-19) conditions (PCCs) beyond 3 years and identify factors associated with their persistence longer than 2 years., Study Design: Cross-sectional questionnaire-based survey., Methods: We surveyed patients who had recovered from COVID-19 and visited our institution from February 2020 to November 2021. Demographic and clinical data and information on the presence and duration of PCCs were obtained. We identified factors associated with the persistence of PCCs longer than 2 years using multivariate linear regression analyses., Results: Among 935 patients surveyed, 407 completed the survey. Among them, 360 patients had mild disease in the acute phase. The proportions of participants with at least one symptom at 1, 2, and 3 years after symptom onset or COVID-19 diagnosis were 33.2%, 29.8%, and 5.7%, respectively. The numbers of participants with and without any residual symptoms 2 years after the onset of COVID-19 were 87 and 193, respectively. After multivariate adjustment, persistence of PCCs longer than 2 years was associated with lower body mass index, presence of any underlying medical conditions, and number of symptoms lasting for more than 1 month ≥ 5., Conclusions: The prevalence of PCCs decreased 2 years after symptom onset or COVID-19 diagnosis. We also identified factors associated with PCC persistence longer than 2 years, which could help primary care physicians and patients with PCCs predict the duration of PCCs and better understand their natural history, thus reducing patients' anxiety about their duration., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Delays in nerve transmission are an important topic in the field of neuroscience. Spike signals fired or received by the dendrites of a neuron travel from the axon to a presynaptic cell. The spike signal then triggers a chemical reaction at the synapse, wherein a presynaptic cell transfers neurotransmitters to the postsynaptic cell, regenerates electrical signals via a chemical reaction through ion channels, and transmits them to neighboring neurons. In the context of describing the complex physiological reaction process as a stochastic process, this study aimed to show that the distribution of the maximum time interval of spike signals follows extreme-order statistics. By considering the statistical variance in the time constant of the leaky Integrate-and-Fire model, a deterministic time evolution model for spike signals, we enabled randomness in the time interval of the spike signals. When the time constant follows an exponential distribution function, the time interval of the spike signal also follows an exponential distribution. In this case, our theory and simulations confirmed that the histogram of the maximum time interval follows the Gumbel distribution, one of the three forms of extreme-value statistics. We further confirmed that the histogram of the maximum time interval followed a Fréchet distribution when the time interval of the spike signal followed a Pareto distribution. These findings confirm that nerve transmission delay can be described using extreme value statistics and can therefore be used as a new indicator of transmission delay., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Satori Tsuzuki. 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.)

Renal cell carcinoma (RCC) is known for its potential to metastasize to various sites but metastasis to the area posterior to the seminal vesicles is exceedingly rare. We present the case of a 44 year-old male patient with a history of clear cell RCC (ccRCC) who was found to have suspected metastases to the region posterior to the seminal vesicles and the greater omentum during follow-up after radical nephrectomy. The patient was classified as having a favorable risk according to the International Metastatic RCC Database Consortium criteria. Due to the rarity of this metastasis site, a treatment strategy combining immune-oncology therapy and tyrosine kinase inhibitors (IO-TKI) was initiated. This treatment led to significant reduction of the metastatic lesions, allowing for their complete removal via laparoscopic surgery. Pathologic examination confirmed that the metastatic lesions were consistent with primary ccRCC. No clinical progression was observed 2 months postoperatively. This case highlights the rare occurrence of ccRCC metastasizing posterior to the seminal vesicles and demonstrates the potential effectiveness of combined IO-TKI therapy followed by surgical resection in treating such atypical metastases., Competing Interests: Conflict of interestThe authors have no conflicts of interest to report., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: ZNF384-fusion (Z-fusion) genes were recently identified in B-cell acute lymphoblastic leukemia (B-ALL) and are frequent in Japanese adult patients. The frequency is about 20% in those with Philadelphia chromosome-negative B-ALL. ZNF384 is a transcription factor and Z-fusion proteins have increased transcriptional activity; however, the detailed mechanisms of leukemogenesis of Z-fusion proteins have yet to be clarified., Methods: We established three transfectants of cell lines expressing different types of Z-fusion proteins, and analyzed their gene expression profile (GEP) by RNA-seq. We also analyzed the GEP of clinical ALL samples using our previous RNA-seq data of 323 Japanese ALL patients. We selected upregulated genes in both Z-fusion gene-expressing transfectants and Z-fusion gene-positive ALL samples, and investigated the binding of Z-fusion proteins to regulatory regions of the candidate genes by ChIP-qPCR., Results: We selected six commonly upregulated genes. After the investigation by ChIP-qPCR, we finally identified CREB5 and RGS1 as direct and common target genes. RGS1 is an inhibitor of CXCL12-CXCR4 signaling that is required for the homing of hematopoietic progenitor cells to the bone marrow microenvironment and development of B cells. Consistent with this, Z-fusion gene transfectants showed impaired migration toward CXCL12., Conclusions: We identified CREB5 and RGS1 as direct and common transcriptional targets of Z-fusion proteins. The present results provide novel insight into the aberrant transcriptional regulation by Z-fusion proteins., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98-BPTF (NB) fusion in patients with T-cell acute lymphoblastic leukemia (T-ALL) using next-generation sequencing. The FG-repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown., Materials and Methods: To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline-inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T-ALL cells., Results: NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto-oncogene Pim1, which encodes a serine/threonine kinase. NB transcriptionally regulated Pim1 expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB-induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T-ALL cells by inactivating the pro-apoptotic protein BCL2-associated agonist of cell death (BAD)., Conclusion: We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion-positive leukemia., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding., Methods: The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection., Results: Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days., Conclusion: Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: To clarify the relationships between 11 C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification., Methods: A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients., Results: The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2-3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values., Conclusions: MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC., Materials and Methods: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups., Results: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019)., Conclusion: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC., (Copyright © 2024 Elsevier Inc. All rights reserved.)