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Background: Comprehensive genomic profiling (CGP) and specialized support for adolescent and young adult (AYA) cancer patients are crucial yet underexplored areas of healthcare in Japan. This study investigated awareness of CGP testing and support for AYA cancer patients among healthcare professionals in Osaka., Methods: An anonymous online survey was conducted from 31 January to 31 March 2024. The survey targeted all staff, including doctors, nurses, technicians, pharmacists and others, from eight Toyono Medical Area Cancer Medical Network Council hospitals. The survey included questions on basic demographics, awareness of CGP testing and support provided to patients with AYA cancer., Results: Among the 720 respondents, 41.9% were aware of CGP testing, while 20.3% were unaware. Regarding AYA cancer, 60.7% were aware and 14.3% were unaware. Only 7.5% had frequent contact with AYA patients and 96.8% recognized the need for education and information. Awareness of CGP was greater among doctors (72.5%) than among other professionals (34.4%); similarly, AYA cancer awareness was higher among doctors (73.9%) than among other professionals (57.7%). CGP awareness among doctors varied by years of experience and institutional type, being highest in core and cooperative hospitals (80 and 78.6%, respectively) and among doctors with more than 21 years of experience (90%)., Conclusions: This study reveals significant gaps in CGP and AYA cancer awareness among healthcare professionals in Osaka, Japan, with doctors demonstrating higher awareness levels than other professionals. There is a pressing need for targeted educational programs to enhance the understanding and implementation of CGP and support AYA cancer patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hypoattenuated area (HA) formation at the pancreatojejunostomy (PJ) site on contrast-enhanced computed tomography (CE-CT) is significantly associated with clinically relevant postoperative pancreatic fistula (CR-POPF) after open pancreaticoduodenectomy (PD) (O-PD). Here, we evaluated the impact of HA formation in robotic PD (R-PD) and surgical factors predictive of HA formation., Methods: The study retrospectively analyzed 66 patients who underwent either O-PD or R-PD and exhibited a drain amylase level exceeding three times the upper limit of normal range, with CE-CT assessment performed on postoperative days 3-14. Patients were divided into two groups, with evident HA (≥ 5 mm) (E-HA) and subtle HA (< 5 mm) (S-HA), and their data were analyzed by multivariate and propensity-score matching analyses., Results: Among the patients, 24 (36.3%) exhibited E-HA and 42 (63.7%) S-HA. The percentages of R-PD and CR-POPF in E-HA group were significantly lower and higher, respectively, than S-HA group (R-PD: 29.2% vs 54.8%, p = 0.0446; CR-POPF: 70.8% vs 4.8%, p < 0.0001). Multivariate analysis revealed the surgical approach as a significant factor associated with E-HA formation (odds ratio: 0.26; p = 0.0223). Propensity-score matching analysis revealed significantly fewer patients with E-HA formation and CR-POPF in R-PD group than O-PD group (E-HA: 14.3% vs 64.3%, p = 0.0068; CR-POPF: 14.3% vs 57.1%, p = 0.0180)., Conclusion: The impact of HA formation in predicting CR-POPF was confirmed in the patients undergoing PD, including O-PD and R-PD. Furthermore, the data suggest that R-PD, compared with O-PD, significantly decreased the incidence of E-HA formation, indicating an advantage of R-PD over O-PD in reducing CR-POPF via HA formation., Competing Interests: Declarations. Disclosures: Drs. Yoshito Tomimaru, Shogo Kobayashi, Kazuki Sasaki, Shinichiro Hasegawa, Daisaku Yamada, Hirofumi Akita, Takehiro Noda, Hidenori Takahashi, Hiroki Imamura, Yuichiro Doki, and Hidetoshi Eguchi have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s).)

Bilateral identical duplications of the middle cerebral artery are extremely rare. We report this anatomical variation in a 56-year-old woman. The anatomical variation was identified using magnetic resonance angiography, which was performed to evaluate cerebrovascular disease. Bilaterally, one middle cerebral artery originated from the internal carotid artery bifurcation and the other originated from the internal carotid artery terminal segment. The anatomical variations were incidental findings, and the patient was asymptomatic., Competing Interests: Declarations. Ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of Nakamura Memorial Hospital (No. 2024102501). Informed consent: Informed consent was obtained from the patient. Consent to publish: The participant has consented to the submission of the case report to the journal. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2025. Fondazione Società Italiana di Neurologia.)

Purpose: Neoadjuvant chemotherapy for upper tract urothelial carcinoma has shown favorable results. However, few studies have been conducted on dose-dense regimens that have demonstrated superior efficacy in bladder cancer. We aimed to retrospectively evaluate the efficacy and safety of dose-dense gemcitabine and cisplatin as neoadjuvant chemotherapy for upper tract urothelial carcinoma., Materials and Methods: Ninety-five patients who underwent radical nephroureterectomy for high-grade upper tract urothelial carcinoma (cT2-3N0M0) with dose-dense gemcitabine and cisplatin (n = 33) or without neoadjuvant chemotherapy (n = 62, Control) were included. Propensity score matching was performed based on the patient and tumor demographics. Efficacy was evaluated by the pathological response rate defined as pathological downstaging to ≤ pT1N0 and complete response (pT0N0). Progression-free survival, cancer-specific survival, and overall survival were estimated. All adverse events and postoperative complications were assessed., Results: Thirty-one matched patients were included in each cohort after adjusting for baseline propensity score matching. The pathological downstaging to ≤ pT1N0 rate of the neoadjuvant chemotherapy group was significantly higher than the Control group. The complete response rate was 6.5% in the neoadjuvant chemotherapy group; pT0N0 was not observed in the Control group. The 2-year progression-free survival and cancer-specific survival rates were significantly better in the neoadjuvant chemotherapy group. Of the 33 patients who received neoadjuvant chemotherapy, 7 severe adverse events (grade 3 or higher) were observed in 6 patients., Conclusions: Dose-dense gemcitabine and cisplatin showed a favorable pathological response and oncological outcome with good tolerability., 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 © 2025 Elsevier Inc. All rights reserved.)

Objectives: To elucidate the specific characteristics of fat-containing cells in the pancreas and the mechanism of intrapancreatic fat deposition in humans., Materials and Methods: Fifteen Japanese patients who had undergone pancreatic resection were enrolled, and the normal region from each samples was examined. Immunostaining for adiponectin and perilipin 1 was performed, and the relationships between the pancreatic fat-cell area or clinical parameters and the density or the diameter of the fat cells were analyzed., Results: The expression of adiponectin in the cytoplasm and perilipin 1 along the plasma membrane was observed in fat-containing cells in the pancreas. The fat-containing cell area had a significant positive correlation with cell density. In addition, fat-containing cell density was significantly positively correlated with homeostasis model assessment insulin resistance. The diameter of fat-containing cells had significant positive correlations with BMI, fasting immunoreactive insulin, and homeostasis model assessment insulin resistance. Of all fat-containing cells, 10.4% were intralobular cells, and the diameter of intralobular cells showed a tendency for positive correlation with age., Conclusions: The characteristics of fat-containing cells in the pancreas indicate that some of them may be mature adipocytes, and fat volume may be increased by hyperplasia of fat-containing cells associated with insulin resistance., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Radiation protection glasses reduce eye lens exposure in Interventional Radiology (IR). However, the protection ratio differs for the lead equivalent content and shape of the lenses. This study aimed to examine factors effective in reducing the lens dose by measuring the protection ratio of scattered radiation due to changes in the surgeon's face orientation, various lead equivalents, and shapes., Method: The examination model of endoscopic retrograde cholangiopancreatography. The simulated surgeon was positioned 60 cm from the center of the X-ray irradiation, beside the patient's head at a 45° angle relative to the patient's midline. The surgeon's face angle was altered between 45° left, 0°, and 45° right with respect to the bed. Respective lens equivalent doses were compared when the same dose was reached on the DAP meter. Nine types of radiation protection glasses (lead equivalent value range [0.07-0.75 mm Pb]) were used., Results: Single regression analysis showed a significant difference between the lead equivalent and lens equivalent dose when the surgeon's face was oriented at 0° or 45° right with standard coefficients of -0.944 and -0.963. At the 45° left orientation, a significant difference was observed between the skin and the lower gap area of the glasses, with a standard coefficient of 0.692, which is a factor in the incidence of scattered rays from the downward direction., Conclusions: For radiation protection glasses, increasing the lead equivalent of the lenses and minimizing the lower gap between the skin and lenses were effective in reducing lens exposure., 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 © 2025 Elsevier B.V. All rights reserved.)

In this study, we investigated the measurable residual leukemic stem cell (MR-LSC) population after allogeneic stem cell transplantation (allo-SCT) for high-risk acute myeloid leukemia (AML), utilizing T-cell immunoglobulin mucin-3 (TIM-3) expression as a functional marker of AML leukemic stem cells (LSCs). Analysis of the CD34 + CD38 - fraction of bone marrow cells immediately after achievement of engraftment revealed the presence of both TIM-3 + LSCs and TIM-3 - donor hematopoietic stem cells (HSCs) at varying ratios. Genetic analysis confirmed that TIM-3 + cells harbored patient-specific mutations identical to those found in AML clones, whereas TIM-3 - cells did not, indicating that TIM-3 + CD34 + CD38 - cells represent residual AML LSCs. In 92 allo-SCT occasions involving 83 AML patients, we enumerated the frequencies of TIM-3 + LSCs immediately after achieving hematologic complete remission with complete donor cell chimerism. Notably, only 22.2% of patients who achieved a TIM-3 + MR-LSC low status (<60%) experienced relapse, with a median event-free survival (EFS) of 1581 days (median follow-up duration was 2177 days among event-free survivors). Conversely, 87.5% of patients with TIM-3 + MR-LSC int/high (≥60%) relapsed, with a median EFS of 140.5 days. Furthermore, MR-LSC status emerged as a significant independent risk factor for relapse (hazard ratio, 8.56; p < 0.0001), surpassing the impact of patient disease status prior to allo-SCT, including failure to achieve complete remission (hazard ratio, 1.98; p = 0.048). These findings suggest that evaluating TIM-3 + MR-LSCs immediately after engraftment, which reflects the competitive reconstitution of residual TIM-3 + LSCs and donor HSCs, may be valuable for predicting outcomes in AML patients undergoing allo-SCT., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Acute myocarditis (AM) is an inflammatory disease of the heart muscle that can progress to fulminant myocarditis (FM), a severe and life-threatening condition. The cytokine profile of myocarditis in children, especially in relation to fulminant myocarditis, is not well understood. This study aims to evaluate the cytokine profiles of acute and fulminant myocarditis in children. Pediatric patients diagnosed with myocarditis were included in the study. Cytokine levels were measured using a multiplexed fluorescent bead-based immunoassay. Statistical analysis was performed to compare patient characteristics and cytokine levels between FM, AM, and healthy control (HC) groups. Principal component analysis (PCA) was applied to cytokine groups that were independent among the FM, AM, and HC groups. The study included 22 patients with FM and 14 with AM patients. We identified four cytokines that were significantly higher in the FM group compared to the AM group: IL1-RA (p = 0.002), IL-8 (p = 0.005), IL-10 (p = 0.011), and IL-15 (p = 0.005). IL-4 was significantly higher in the AM group compared to FM and HC groups (p = 0.006 and 0.0015). PDGF-AA, and VEGF-A were significantly lower in the FM group than in the AM group (p = 0.013 and <0.001). Similar results were obtained in PCA. Cytokine profiles might be used to differentiate pediatric FM from AM, stratify severity, and predict prognosis. The targeted therapy that works individual cytokines might provide a potential treatment for reducing the onset of the FM and calming the condition, and further studies are needed., Competing Interests: Declarations. Conflict of interest: All the authors have no conflict of interest and no financial relationships relevant to this article to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Kawasaki disease (KD) is an acute vasculitis that mostly affects children and is characterized by inflammation of medium-sized arteries, particularly the coronary arteries. The absent in melanoma 2 (AIM2) inflammasome senses cytosolic dsDNA and regulates IL-1β-driven inflammation. We investigated the role of AIM2 in Candida albicans water-soluble fraction (CAWS)-induced vasculitis in a murine model mimicking KD. Aim2 -/- mice exhibited reduced vasculitis, inflammatory cell infiltration, and vascular fibrosis in the aorta and coronary arteries. In addition, dsDNA damage was detected in Dectin-2 + cells infiltrating vasculitis areas. In vitro experiments showed that CAWS induced dsDNA damage in Dectin-2 + bone marrow-derived dendritic cells (BMDCs) isolated from wild-type (WT) and Aim2 -/- mice. Furthermore, CAWS induces nuclear membrane deformation and DNA leakage into the cytosol, leading to AIM2 inflammasome activation and subsequent IL-1β production in WT BMDC. These findings suggest that AIM2 inflammasome activation in dendritic cells, triggered by dsDNA damage and leakage, contributes to the development of CAWS-induced vasculitis, and provides important insights into the inflammatory mechanisms underlying KD. NEW & NOTEWORTHY The AIM2 inflammasome in dendritic cells is a significant component of the murine model of Kawasaki disease-like vasculitis induced by CAWS injection. The AIM2 deficiency reduces vasculitis via reduced inflammatory cell infiltration and vascular fibrosis in CAWS-induced vasculitis. CAWS induces the damage and leakage of nuclear DNA in dendritic cells, which triggers AIM2 inflammasome activation, leading to an IL-1β-driven inflammatory response.

Background: The association between tumor-infiltrating lymphocytes and tumor immunity has long been recognized. Among T-cell types, CD45RO-positive memory T cells (CD45RO + ) are reported to correlate with survival in several cancer types, but clinical evidence is lacking in esophageal squamous cell carcinoma (ESCC)., Methods: In surgical specimens from 162 preoperatively untreated patients, immunohistochemistry for CD45RO was performed to evaluate the density of CD45RO + in the tumor core (CT) and invasive margin (IM) using an auto-count method. Patients were classified into high- versus low-CD45RO + groups based on CD45RO + density in CT and IM separately and combined. The relationship between CD45RO + density and clinicopathological factors, including prognosis, was evaluated., Results: Average CD45RO + density was 133/mm 2 in CT and 372/mm 2 in IM. No significant differences in clinicopathological factors according to high- versus low-CD45RO + scores were identified. Using CT scores, the CD45RO + -high group had a better 5-year overall survival (OS) rate (77.2% vs. 54.7% CD45RO + -low, P = 0.0433), but OS rates did not differ statistically between the two groups by IM scores (75.7% vs. 50.3%, P = 0.0576). Using immunohistochemical scores for CT+IM, the survival difference was significant, with a 5-year OS rate of 73.7% for the CD45RO + -high group versus 46.3% for the CD45RO + -low group (P = 0.0141). Multivariate analysis identified CD45RO + CT+IM density as an independent prognostic variable in OS (hazard ratio 2.27, 95% confidence interval 1.43-3.62, P = 0.0006)., Conclusions: Density of CD45RO + expression in the CT and IM might be a predictor of long-term survival in ESCC., Competing Interests: Disclosures: There are no conflicts of interest., (© 2024. The Author(s).)

Competing Interests: Declarations. Conflict of interest: Tomoharu Yoshizumi is Editor-in-Chief, and Soichiro Ishihara, Shigeru Imoto, Tomoki Ebata and Aya Saito are editorial board members of Surgery Today. Arata Takahashi is affiliated with the Department of Healthcare Quality Assessment at the University of Tokyo that is a social collaboration department supported by grants from the National Clinical Database. Ethical standards: No applicable.

Introduction: Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, showed significantly longer progression-free survival (PFS) than crizotinib in the phase 3 CROWN trial (NCT03052608) in patients with previously untreated advanced ALK-positive non-small cell lung cancer (NSCLC). Efficacy was similar in the Asian subgroup. We present an updated subgroup analysis in Asian patients after 5 years of follow-up., Methods: Patients were randomly (1:1) assigned to receive lorlatinib 100 mg once daily (n=59) or crizotinib 250 mg twice daily (n=61). This post hoc analysis presents updated investigator-assessed efficacy outcomes, safety, and biomarker analyses., Results: After a median follow-up of 62.4 months for lorlatinib and 55.1 months for crizotinib, median PFS was not reached (NR; 95% confidence interval [CI]: 64.3‒NR) and 9.2 months (95% CI: 7.2‒12.7), respectively (hazard ratio [HR], 0.22; 95% CI: 0.13‒0.37); 5-year PFS was 63% (95% CI: 49-74) and 7% (95% CI: 2-17). Objective response rate (ORR) was 81% (95% CI: 69-90) with lorlatinib and 59% (95% CI: 46‒71) with crizotinib. In patients with baseline brain metastases, intracranial (IC) ORR was 69% (95% CI: 39‒91) with lorlatinib and 6% (95% CI: <1‒30) with crizotinib. Median time to IC progression was NR (95% CI: NR‒NR) and 14.6 months (95% CI: 9.2‒27.4), respectively (HR, 0.01; 95% CI: <0.01‒0.11). Safety profiles were consistent with the entire population., Conclusions: After 5 years of follow-up, lorlatinib efficacy and safety in the Asian subgroup of CROWN continue to be consistent with those in the overall population, with PFS remaining unreached with lorlatinib., (Copyright © 2025. Published by Elsevier Inc.)

Construction of hierarchical pore structure in supported titanium silicalites was an effective strategy to enhance catalytic performance and avoid the separation process in industrial applications. Herein, the hierarchical TS-2 zeolites were successfully prepared on the TiO 2 -modified α-Al 2 O 3 pellets by "bottom-up" method, which had good and stable catalytic performance for the allyl chloride epoxidation. TritonX-100 could construct a mesopore structure, restrain nucleation, and affect titanium coordination of the zeolites, which was beneficial for preparing large size, much hexa-coordination titanium content, and hierarchically supported TS-2 zeolites in this work. Besides, the TiO 2 -modified layer greatly increased the density and surface reactivity of hydroxyl groups on the α-Al 2 O 3 pellet, which were well-situated to prepare homogeneous and anatase-free hierarchical TS-2 zeolite layers. The hierarchically supported TS-2 zeolites were applied to the epoxidation of allyl chloride with hydrogen peroxide, and allyl chloride conversion and epichlorohydrin selectivity were up to 99.13% and 96.53%, respectively.

Background: DNA flow cytometry using LC-1000 is utilized for analyzing cellular and nuclear lengths and DNA content in individual cells with samples in cell preservation solutions to acquire the cell proliferation index (CPIx). This study aimed to evaluate the performance of body cavity fluid cytology using LC-1000. As cell preservation solutions, liquid-based cytology (LBC) by Cellprep (CP) was compared with CelVerse (CeV), specifically designed for the LC-1000., Methods: Overall, we evaluated 43 samples (20 malignant and 23 benign) of body cavity fluids suspended in CeV and 59 samples (28 malignant and 31 benign) suspended in CP. The CPIx was compared between malignant and benign cases of CeV and CP. Further, the subject groups were divided according to the SubG1% in a sample., Results: The CPIx in CeV was 0.14-10.22 (median 0.62) in malignant cases and 0.09-4.64 (median 0.19) in benign cases (p < 0.001); additionally, CP displayed 0.14-9.87 (median 0.84) in malignant cases and 0.11-3.02 (median 0.22) in benign cases (p < 0.001). The area under the curve (AUC) was 0.811 for CeV and 0.776 for CP. The difference in SubG1% between the CeV and CP groups was statistically significant (p < 0.0001) and influenced the AUC in CP., Conclusion: The CPIx in CeV or CP samples using the LC-1000 may be applicable as an objective indicator in body cavity fluid cytology. Samples preserved in CeV provided more consistent results, unaffected by SubG1%, when compared to those stored in CP., (© 2025 Wiley Periodicals LLC.)

Background and Objectives: Spinocerebellar ataxia type 6 (SCA6) is caused by expansion of CAG repeat units (RUs) in CACNA1A . While the pathologic threshold has been considered to be 20 or 21 RUs, the lower limit remains controversial. This study aimed to clarify the pathologic significance of RUs in SCA6, including the role of opposite alleles (OAs)., Methods: This was an observational study of patients with suspected spinocerebellar ataxia who underwent SCA6 genetic testing. We analyzed the relationship between CACNA1A RUs and age at onset (AAO). Family history positivity rates were examined for different RUs of the expanded allele (EA). Regression analyses were performed for AAO estimation based on the EA RUs. The influence of OAs on AAO was investigated, particularly in cases with 21-22 EA RUs., Results: In total, 2,768 participants were enrolled. Family history positivity rates increased progressively above 19 RUs and plateaued at ≥23 RUs. Regression analysis of cases with ≥23 RUs showed that 96.20% of cases with ≥23 RUs, 90.67% of cases with 22 RUs, 91.15% of cases with 21 RUs, 61.54% of cases with 20 RUs, and 33.33% of cases with 19 RUs fell within the 95% prediction interval for AAO. However, no patients with ≤18 RUs were included. In the 21-22 RU group, OAs significantly influenced AAO, and ≥17 RUs had a significant effect. For ≥23 RUs, no significant OA effect was observed. Cases with 19-20 RUs showed a higher prevalence of OA with ≥19 RUs compared with cases with ≥23 RUs., Discussion: Our findings suggest that clinical manifestation within a typical lifespan likely requires at least 19 RUs. The 19-20 RU range represents an intermediate zone where OA may influence disease likelihood. For 21-22 RUs, OA significantly affects AAO, indicating a complex interplay between EA and OA. ≥23 RUs seem sufficient to cause disease onset within a typical lifespan, regardless of OA. These results provide a new paradigm for SCA6 diagnosis and genetic counseling, emphasizing the need for cautious interpretation of the intermediate RU range and consideration of OA., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

We investigated the potential of adipose-derived stem cells (ADSCs) in preventing post-hepatectomy liver failure, emphasizing the necessity of direct administration using a scaffold. A fibrin gel scaffold was employed for ADSCs (gelADSC) to assess their therapeutic impact on liver regeneration in both in vitro and in vivo settings. Experiments were conducted on C57BL/6 mice with normal livers and those with chronic hepatitis. We also explored the role of extracellular vesicles (EVs) secreted by ADSCs in conjunction with fibrin gel. GelADSC showed sustained release of hepatocyte growth factor, vascular endothelial growth factor, and stromal cell-derived factor 1 for at least 7 days in vitro. In vivo, gelADSC significantly enhanced postoperative liver regeneration by upregulating the cell cycle and fatty acid oxidation in both normal and chronically hepatitis-affected mice. The therapeutic effects of gelADSC were potentially favorable over those of intravenously administered ADSCs, especially in mice with chronic hepatitis. Increased EV secretion associated with fibrin gel use was significantly linked to enhanced liver regeneration post-surgery through the promotion of fatty acid oxidation. The findings underscore the enhanced therapeutic potential of gelADSC, particularly in the context of chronic hepatitis, possibly compared to intravenous administration., Competing Interests: Declarations. Competing interests: HI received a research fund from Rohto Pharmaceutical Co., Ltd., and SK (Shogo Kobayashi) received honoraria from AstraZeneca and Taiho. The other authors (YT, AH, SK (Shunbun Kita), KS, YI, DY, TN, HT, DH, TK, KT, TK, SS, IS, SM, YD, HE) declare no competing financial interests., (© 2025. The Author(s).)

Background: This randomized controlled trial provided LC16m8 pre-exposure prophylaxis to high-risk individuals to assess its efficacy for mpox prevention, safety, and immunogenicity., Methods: This multicenter, randomized, open-label trial enrolled men and women aged ≥18 years at high risk of mpox. Participants were randomly assigned 1:1 to early- or late-vaccination groups. The primary endpoint was vaccine efficacy (VE) against mpox. Secondary endpoints included VE against severe mpox, symptoms, "take" incidence, adverse events (AEs), and immunogenicity in participants with human immunodeficiency virus (HIV)., Results: In total, 570 and 565 participants were assigned to early- and late-vaccination groups, respectively, with 530 and 476 vaccinated. The median age was 41 years; 99.7% were male, 89.7% were Japanese, and 34.4% had HIV. No mpox cases occurred, precluding VE calculations. The take rates were 89.5% (with HIV) and 93.9% (without HIV). AEs occurred in 97.2% and 98.2% of participants with and without HIV, respectively. No fatal AEs were observed. Serious adverse events (SAEs) were observed in 2/352 (0.6%) and 3/654 (0.5%) of participants with and without HIV, respectively, of which one SAE causally related to vaccination occurred in a participant without HIV. Seroconversion rates for LC16m8 and MPXV were 96.2% and 69.2%, respectively, in participants with HIV, and 92.0% and 52.0%, respectively, in individuals without HIV., Conclusions: LC16m8 efficacy in mpox remains inconclusive. However, in individuals with well-controlled HIV, it was immunogenic and raised no significant safety concerns, suggesting its suitability for targeted vaccination of at-risk groups. (Japan Registry of Clinical Trials number, jRCT1031230137)., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Nucleated red blood cells (NRBCs) are precursors of red blood cells (RBCs), but also possess variety of immunomodulatory effects. However, among the three types of NRBCs, the immunological effects of human CD45- NRBCs remain largely unknown. We have previously shown that cord blood-derived CD45- NRBCs and adult peripheral blood-derived monocytes cocultured in a lipopolysaccharide (LPS)-stimulated indirect coculture system that avoided cell-to-cell contact, increase IL-10 and decrease TNF- α secretion, suggesting an immunosuppressive function of CD45- NRBCs via an unknown soluble factor. The peripheral blood of fetuses and neonates has abundant NRBCs and is physiologically polycythemic, which may lead to the peripheral accumulation of toxic plasma-free hemoglobin. Plasma-free hemoglobin binds to haptoglobin, forming a haptoglobin-hemoglobin complex, which is processed within monocytes via the CD163- heme oxygenase 1 (HO-1) axis and secretes IL-10. Therefore, we hypothesized that NRBCs secrete haptoglobin and induce the immunosuppressive function of monocytes by activating the CD163-HO-1 axis. We found that immunosuppressive response decreased when the coculture medium was supplemented with an anti-CD163 blocking antibody or the HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX). Haptoglobin levels in the culture medium containing NRBCs were high and expressed the haptoglobin gene. Thus, CD45- NRBCs secreted haptoglobin and activated the immunosuppressive function of monocytes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Shusuke Takeuchi et al. Journal of Immunology Research published by John Wiley & Sons Ltd.)

We investigate resonance (true resonance and pre-resonance) Raman (RR) effects in glucose, galactose, N -acetylglucosamine, and N -acetylgalactosamine with ultraviolet resonance Raman (UVRR) and far-ultraviolet (FUV) spectroscopies. Electronic transitions in the FUV region are attributed to electronic orbitals due to σ and π electrons. Their geometric orientations that participate in the resonance effect have not yet been well studied, unlike those for visible and near-infrared RR spectroscopies. In this study, we have employed monosaccharides and their derivatives with an amino group, which has strong FUV absorption near 190 nm. Quantum chemical calculation indicates that the band at 190 nm consists of multiple electric transitions. Their UVRR spectra measured with 213, 226, and 250 nm excitation suggest that Raman bands due to the amino group are enhanced via multiple electronic transitions, but those due to the saccharide groups are enhanced slightly. The results demonstrate that a combined study with UVRR and FUV spectroscopies provides new insights into the geometry and symmetry of the electronic transitions in σ and π orbitals.

To evaluate the effects of the soluble fiber isomaltodextrin in a protein-biased diet, a 21-day protein diet trial was conducted in rats, with 60% of the calories derived from protein. The results revealed that the high-protein diet alone led to a significant increase in kidney weight. In contrast, the consumption of water with 5% isomaltodextrin dissolved in it, along with a high-protein diet, suppressed this weight gain. To elucidate this mechanism, an analysis of serum urea toxins confirmed that the concentrations of phenyl sulfate were significantly higher with high protein, and significantly lower with isomaltodextrin. The impact of a high-protein diet increased phenol in cecal contents, an increase that was mitigated by isomaltodextrin. This suggests that the inhibitory effect of isomaltodextrin on renal hypertrophy was due to the suppression of urea toxin precursor production by the gut microbiota., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Aim: The impact of maternal mental illness on children's neurodevelopment has been insufficiently investigated, particularly in large populations. In this study, we examined the association between maternal mental health history and child neurodevelopment during the first 3 years postpartum, using large-scale data from the Japan Environment and Children's Study (JECS)., Methods: We analyzed data from 64,389 mother-offspring pairs enrolled in JECS. Maternal history of mental illness was assessed using questionnaires administered during early pregnancy. Child neurodevelopment was assessed at ages 1, 2, and 3 years by mothers or guardians using the Japanese version of the Ages and Stages Questionnaires, 3rd Edition (J-ASQ-3), across five domains. In this study, we employed multivariate logistic regression analysis., Results: Children whose mothers have a history of mental illness exhibited significantly higher risks of developmental delays in gross motor skills and problem-solving domains at age 1, and across all J-ASQ-3 domains at ages 2 and 3, compared to those whose mothers do not have such a history., Conclusion: Our findings indicate that children born to mothers with a history of mental illness may exhibit early neurodevelopmental delays in gross motor skills and problem-solving as early as age 1 year, potentially leading to broader neurodevelopmental impairments observed in later childhood. Additionally, childcare support aimed at enhancing neurodevelopment may be essential for mothers with a history of mental illness within the first year postpartum., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Although various self-expandable metallic stents (SEMSs) for malignant hilar biliary obstruction (MHBO) have been introduced, the optimal SEMS for MHBO has not yet been established., Purpose: This study aimed to evaluate outcomes of the transpapillary placement of an uncovered laser-cut SEMS with an ultra-thin delivery sheath (YABUSAME) for MHBO., Methods: This multicenter, prospective study was conducted in 11 hospitals for 10 months (from March 2022 to December 2022). The primary outcome was the stent patency rate at 6 months. Key secondary outcomes were the technical success rate, clinical success rate, time to recurrent biliary obstruction (RBO), overall survival (OS), and adverse events., Results: Of 45 enrolled patients, 43 patients underwent biliary drainage, including 42 patients who underwent YABUSAME placement; 66.7% of patients received chemotherapy, and 60% had previously undergone biliary drainage. Drainage methods were partial stent-in-stent, side-by-side, and unilateral in 65.1%, 7.0%, and 27.9% of patients, respectively. Technical and clinical success rates were 93.2% (41/45) and 79.1% (34/45), respectively. The incidence rate of early postprocedural adverse events was 2.2%. The stent patency rate at 6 months was 55.3%. The median time to RBO was 231 days. The median OS was 125 days., Conclusion: This study showed that the primary outcome, the 6-month stent patency rate, exceeded the expected rate of 55%, which indicates the efficacy of YABUSAME placement for MHBO., Competing Interests: Declarations. Competing interests: Kotaro Takeshita, Susumu Hijioka, Kenji Ikezawa, Takeshi Ogura, Masaki Kuwatani, Nao Fujimori, Shinpei Doi, Masato Endo, Saburo Matsubara, Reiko Yamada, Hirosato Mashima, Mikinori Kataoka, Ryoji Takada, Atsushi Okuda, Akihisa Ohno, Nobuhiro Katsukura, Hirokiyo Suzuki, Takamitsu Tanaka, Masanari Sekine, Hidetoshi Kitamura, and Takuji Okusaka have no conflicts of interest to disclose. Ethical approval: The protocol was developed before the initiation of the trial and was approved by the National Cancer Center Institutional Review Board (2021-224). Consent to participate: Written informed consent was obtained from all participants before their inclusion in the study. Consent to publish: Not applicable., (© 2025. The Author(s).)

Objectives: To clarify what urinary condition causes post micturition dribble (PMD) in non-elderly healthy men. We focused on men with PMD who do not have PMD every time they void. We clarified what urinary condition associated with PMD in individuals to prevent PMD., Materials and Methods: Twenty healthy volunteer men who had experienced PMD were included in the study between 2018 and 2021 using a portable uroflowmeter for 48 hours. They recorded symptoms of PMD and strength of desire to void (none, weak, normal or strong) for each void. We investigated the risk factors of PMD and the correlation between strength of desire to void and PMD or parameters measured by uroflowmeter., Results: The mean age of the volunteer men was 35.9±6.9 years. During the study, 20 volunteers experienced a total of 208 episodes of voiding. Of them, 57 (27%) were associated with PMD. Lower voided volume than usual was a significant risk factor for PMD in univariate analysis (p<0.01). There was a statistically significant correlation between the strength of the desire to void and the voided volume (p<0.01). The voiding with none or weak desire to void significantly caused PMD compared to voiding with normal or strong desire to void (36% vs. 21%, p=0.03)., Conclusions: Lower voided volume than usual and voiding with less strength of desire to void are risk factors for PMD. Instructing male patients with PMD to refrain from voiding when the desire to do so is ambiguous can contribute to preventing PMD., Competing Interests: Declaration of Competing Interest no conflict of interest, (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Endovascular treatment (EVT) for patients with an occlusive lesion of the femoropopliteal artery is performed worldwide due to its effectiveness. However, lesions in chronic limb-threatening ischemia (CLTI) are complex and a major concern in superficial femoral artery (SFA) EVT. Despite this, a detailed study of SFA EVT, and especially selection of the final device as a drug-coated balloon (DCB) or a stent, has not been performed in patients with CLTI., Objectives: To compare the clinical outcomes of SFA EVT using a DCB or a stent in patients with CLTI., Methods: A multicenter retrospective observational study was performed at 21 Japanese centers. Comparisons were made between patients undergoing initial SFA EVT with a DCB or stenting after inverse probability of treatment weighting (IPTW) using the propensity score to control for potential confounding (patient demographics, comorbidities, medications, and procedural details). The primary outcome measure was major adverse limb events (MALE). We adopted cause-specific hazard models, using Fine and Gray's proportional hazards model in which death was treated as a competing risk. Secondary outcome measures were also evaluated: 1) technical success, 2) slow flow, 3) death within 30 days, 4) major adverse events within 30 days, 5) restenosis, 6) target lesion revascularization (TLR), 7) acute occlusion, 8) wound healing, 9) major amputation, and 10) all-cause mortality., Results: The study included 900 CLTI cases that underwent EVT with a DCB (n=458) or stenting (n=442) and had a median follow-up period of 17.5 (interquartile range, 6.2-31.9) months. The DCB group had a lower risk of MALE than the stent group, with a hazard ratio of .68 (95% confidence interval (CI), .52-.89; P=.005). Subsequent analysis for the secondary outcome measures demonstrated that the DCB group had a higher prevalence of postprocedural slow flow and a lower incidence rate of acute occlusion (both P < .005 after Bonferroni correction)., Conclusions: DCB angioplasty had a lower risk of MALE than stenting. These results suggest that a DCB might be more beneficial in initial SFA intervention in patients with CLTI., (Copyright © 2025. Published by Elsevier Inc.)

Long-standing Crohn's disease (CD) is well known to be associated with gastrointestinal malignancies. Patients with CD have a higher risk of developing small bowel adenocarcinoma (SBA) compared to healthy individuals. However, CD-associated SBA is not as common as colorectal cancer. While patients with CD often present with complicated stricture lesions in the small intestine, it is difficult to confirm all lesions by endoscopy. There is still no consensus on the surgical treatment of small bowel strictures with suspected CD-associated SBA. We report a case of small bowel high-grade dysplasia and two cases with advanced SBA. Case 1 involved a 53-year-old man whose high-grade dysplastic lesion of the small intestine was discovered incidentally postoperatively and successfully resected curatively. Case 2 was that of a 60-year-old man and Case 3 involved a 69-year-old man. Both patients had multiple small bowel stenotic lesions and were diagnosed with advanced small bowel cancer during follow-up. In conclusion, for patients with long-standing Crohn's disease who are refractory to treatment or have stenotic lesions, surgical resection should be considered as a treatment option with CD-associated SBA in consideration., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Human and animal rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed consent: Informed consent was obtained from all patients to be included in the study., (© 2025. The Author(s), under exclusive licence to Japanese Society of Gastroenterology.)

Background and Objectives: Although carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke, their efficacy in improving decreased vision is unclear. This study aims to evaluate the effects of CEA and CAS on ocular blood flow (OBF) and visual acuity (VA) in patients with carotid artery stenosis, while also exploring the possible relevance of postoperative microembolisms to visual recovery., Methods: The results of 78 procedures (CEA, 39; CAS, 39) performed in 76 patients with carotid artery stenosis were prospectively analyzed. OBF was measured using laser speckle flowgraphy to assess the mean blur ratio, which reflects the absolute retinal blood flow. VA was assessed using Contrast Sensitivity Vision-1000, which measures contrast sensitivity, and the area under the log contrast sensitivity function (AULCSF) was calculated as a measure of VA. Microembolisms were evaluated using magnetic resonance imaging immediately after surgery, and their effects on retinal vessels were assessed using optical coherence tomography of the central fovea., Results: Both treatments significantly enhanced OBF (MBR: 31.4 to 37.9 [P < .0001] for CEA; 33.9 to 37.8 [P = .007] for CAS). VA improved significantly after CEA (AULCSF: 1.03 to 1.06, P = .02), but not after CAS (1.08 vs 1.06, P = .37). In the analysis of all 78 patients, those with postoperative microembolisms showed poorer visual improvement (AULCSF change 0.01 vs -0.07, P = .01). In addition, among 39 patients assessed with optical coherence tomography, retinal vessel density decreased significantly more after CAS than CEA (-0.5 vs 1.1, P = .04)., Conclusion: Although carotid revascularization can enhance OBF, VA improved only after CEA. Microembolisms appear to impair visual recovery. These findings emphasize the importance of assessing visual function in patients with carotid artery stenosis and the need for personalized treatment approaches based on individual visual profiles and stroke risk., (Copyright © Congress of Neurological Surgeons 2025. All rights reserved.)

Objective: Brain metastases from renal cell carcinoma (RCC) present considerable treatment challenges and poor prognoses. In this study, we evaluated the efficacy of cabozantinib, a multi- tyrosine kinase inhibitors (TKIs), in improving the progression-free survival (PFS) and overall survival (OS) of patients with RCC with brain metastases., Methods: This retrospective study included 30 patients with RCC and brain metastases treated at a single institution between 2010 and 2024. Patient demographics, treatment modalities, and survival outcomes were analyzed. Systemic therapies included cabozantinib, TKIs, and immune checkpoint inhibitors (ICIs). Local therapies included Gamma Knife surgery (GKS) and whole-brain radiation therapy (WBRT). Survival outcomes were evaluated using Kaplan-Meier analysis and Cox proportional hazards models., Results: Cabozantinib-treated patients (n = 12) exhibited significantly longer median PFS (21.6 vs. 4.1 months; P < .001) and OS (25.7 vs. 8.3 months; P = .019) compared to non-cabozantinib patients (n = 18). In patients treated with GKS, cabozantinib further improved PFS (29.6 vs. 3.9 months; P < .001) and OS (25.7 vs. 12.8 months; P < .001). Cox regression analysis identified cabozantinib as the sole independent predictor of improved PFS (hazard ratio [HR], 0.09; P = .004) and OS (HR, 0.17; P = .009)., Conclusion: Cabozantinib significantly improved survival outcomes in RCC patients with brain metastases, underscoring its role as an effective systemic therapy. However, potential risks such as brain hemorrhage highlight the importance of careful patient selection and close monitoring. Further prospective studies are warranted to explore optimal combination strategies., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Minimally invasive esophagectomy for esophageal cancer has become increasingly common to reduce postoperative pneumonia. However, the usefulness of pure laparoscopic abdominal manipulation without an upper abdominal incision remains unclear., Methods: We evaluated the utility of pure laparoscopic surgery (LAP) vs. hand-assisted laparoscopic surgery (HALS) in esophagectomy. A total of 344 consecutive patients who underwent curative esophagectomy for esophageal cancer from 2019 to 2023 were enrolled; 235 patients were treated with HALS and 109 with LAP. The peri- and postoperative outcomes were compared between the two groups using a propensity score-matched analysis., Results: Propensity score matching was used to compare 92 patients each in the HALS and LAP groups. Clinicopathological characteristics did not differ between the two groups. The incidence of postoperative pneumonia was significantly higher in the HALS group than in the LAP group (30% vs. 11%, respectively; P = 0.001). Multivariate logistic analysis showed that HALS was independently associated with postoperative pneumonia (odds ratio 3.82, P = 0.002), along with older age and male sex., Conclusions: LAP may reduce the incidence of postoperative pneumonia in esophageal cancer patients who undergo esophagectomy., Competing Interests: Declarations. Ethical approval: All procedures were performed in accordance with the Helsinki Declaration. The Ethical Review Board of Osaka University Hospital approved the protocol of this study. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Consent to participate: Consent to participate was not considered necessary., (© 2025. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Silk fiber, produced by the silkworm Bombyx mori , is a protein fiber with an excellent mechanical strength and broad biocompatibility. Multiple approaches, including genetic and chemical methods, must be combined to tailor silk fiber properties for wide applications, such as textiles and biomaterials. Genetic code expansion (GCE) is an alternative method to alter proteins' chemical and physical properties by incorporating synthetic amino acids into their primary structures. Here, we report an efficient system for selecting variants of B. mori tyrosyl-tRNA synthetase (BmTyrRS) used for GCE in silkworms. Four BmTyrRS variants with expanded substrate recognition toward halogenated tyrosine (Tyr) derivatives were selected, and transgenic silkworms expressing these variants were generated. The silkworms incorporated halogenated Tyr derivatives into silk fibroin to produce halogenated silk fiber with improved thermal stability. These results demonstrate the power of GCE to create protein materials with improved physical properties.

Silicalite-2 membranes were successfully prepared on tubular α-Al 2 O 3 supports by secondary hydrothermal synthesis, and the pervaporation performance of the membrane was evaluated by separation of a 5 wt% ethanol/H 2 O mixture at 60 °C. The effects of templating agent content, water-silicon ratio and crystallization time on the separation performance of Silicalite-2 membranes were investigated. When the TBAOH/SiO 2 and H 2 O/SiO 2 molar ratios of the precursor synthesis solution were 0.2 and 120, a dense Silicalite-2 membrane could be prepared on the surface of the tubular α-Al 2 O 3 support after 72 h. The silane coupling agent was utilized to treat the Silicalite-2 membranes, and the effects of silane coupling agent dosage on their properties were also explored. The pervaporation performance of the Silicalite-2 membrane was greatly improved with a 5.7 wt% trimethylchlorosilane (TMCS) solution and the flux and separation factor of the membrane reached 1.75 kg·m -2 ·h -1 and 22 for separation of 5 wt% EtOH/H 2 O at 60 °C, respectively.

We found signatures of current-induced sliding motion in helimagnetic MnAu&#95;{2} thin films. An abrupt change in differential resistivity occurred at a threshold bias current in the helimagnetic state, whereas it was absent in the induced ferromagnetic state. Broadband voltage noise also emerged above the threshold current in the helimagnetic state. Based on the similarity to canonical charge and spin density wave systems, we ascribed the origin of these phenomena to the sliding motion of the helimagnetic structure.

Background: Islet transplantation in type 1 diabetes mellitus restores endogenous insulin secretion and hypoglycemia awareness. Although high-quality prospective clinical trials have demonstrated the efficacy of islet transplantation, reports on the clinical outcomes in Asia remain scarce. Therefore, we conducted a clinical trial in Japan to verify the effectiveness of islet transplantation., Methods: This multicenter, single-arm study aimed to evaluate the clinical efficacy and safety of immunosuppressive therapy for allogeneic islet transplantation. The immunosuppressive regimens included antithymocyte globulin, calcineurin inhibitors, and mycophenolate mofetil. The primary endpoint was a glycated hemoglobin level of <7.4% on day 365 and the absence of severe hypoglycemic events from 1 mo to 1 y after the first transplantation., Results: Eight recipients with evaluation data obtained 1 y after the initial transplantation were included in the efficacy analysis. Of the 8 recipients, 3, 3, and 2 recipients received 1, 2, and 3 islet infusions, respectively. Six recipients (75%) achieved the primary endpoint. The median glycated hemoglobin levels declined from an initial 7.3% to 6.3% and 6.1% on days 375 and 730, respectively, with related improvements in hypoglycemia awareness and glucose variability. No complications associated with intraportal transplantation, such as intraperitoneal hemorrhage or portal vein embolism, were observed., Conclusions: Islet transplantation provided near-normal glycemic control and protection against severe hypoglycemic events in patients with type 1 diabetes mellitus in this Japanese cohort. Future studies are needed to confirm whether long-term graft survival can be achieved and whether it is possible to prevent the progression of diabetic complications., (Copyright © 2025 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objective: The definitive influence of prestroke disability on outcomes in patients with a low Alberta Stroke Program Early CT Score (ASPECTS) treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) remains unknown. This study aimed to investigate the impact of prestroke disability on outcomes in this specific population., Methods: Data from 32 international centers for AIS-LVO patients with a low ASPECTS who underwent EVT between January 2013 and December 2022 were analyzed retrospectively. Low ASPECTS and prestroke disability were defined as ASPECTS values of 2-5 and prestroke modified Rankin Scale (mRS) score ≥ 2. The primary outcome was a return to the prestroke mRS score at 90 days. Secondary outcomes were independent ambulation (mRS scores of 0-3) or a return to the prestroke mRS score at 90 days, good functional outcome (mRS scores of 0-2) or a return to the prestroke mRS score at 90 days, successful recanalization, and 90-day mortality. Safety outcomes were any intracranial hemorrhage or symptomatic intracranial hemorrhage. A symptomatic intracranial hemorrhage was defined as an intracranial hemorrhage with an associated worsening of ≥ 4 points in the National Institutes of Health Stroke Scale score. Outcomes were compared between patients with and without prestroke disability., Results: Of 293 patients, 50 (17.1%) had a prestroke disability. Of 50 patients, 20 (40.0%), 24 (48.0%), and 6 (12.0%) had prestroke mRS scores of 2, 3, and 4, respectively. The primary outcome showed no significant difference between the two groups. Compared with patients without prestroke disability, those with prestroke disability had a significantly smaller proportion of independent ambulation or return to prestroke mRS score (adjusted OR 0.13, 95% CI 0.03-0.53) and good functional outcome or return to prestroke mRS score (adjusted OR 0.21, 95% CI 0.05-0.91). Other secondary and safety outcomes showed no significant difference between the two groups., Conclusions: The present study indicated that prestroke disability was not associated with a return to the prestroke mRS score at 90 days or intracranial hemorrhage. Physicians should not routinely exclude AIS-LVO patients with a low ASPECTS who have prestroke disability from EVT based on prestroke disability alone.

This study explored the impact of hydrolyzed gelatin (HG) concentration on the retention and therapeutic efficacy of human iPS cell-derived cardiomyocytes (hiPSC-CMs) when injected into the myocardium. The solubility of HG allows precise control over its concentration, influencing the distribution and leakage of injected solutions, which may affect therapeutic outcomes. Using both ex vivo and in vivo rat models, we investigated how varying HG concentrations affect the retention of solution and diffusion within the myocardium. In ex vivo static rat hearts, 10% HG minimized leakage but allowed significant diffusion. However, in pulsating in vivo hearts, 20% HG provided the best retention. In a rat myocardial infarction model, hiPSC-CMs suspended in 20% HG resulted in the highest cell retention. Echocardiogram showed a significant increase in the ejection fraction two weeks after transplantation compared to before transplantation. Additionally, cardiac magnetic resonance imaging (MRI) revealed that the ejection fraction was significantly higher than that of the sham group four weeks after transplantation. These findings suggest that optimizing HG concentration is crucial for enhancing the retention and therapeutic efficacy of hiPSC-CM transplants in treating heart disease., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Declaration of generative AI and AI-assisted technologies in the writing process: The authors utilized ChatGPT to enhance the language and readability of this work, with careful consideration. Following the use of this tool/service, the authors thoroughly reviewed and revised the content as necessary, taking full responsibility for the final version of the publication., (© 2025. The Author(s).)

Estrogen receptor positive (ER + ) subtypes of mammary adenocarcinoma comprise 79% of all breast cancer diagnosis and 67% of all breast cancer mortality. The paucity of models of ER + mammary cancer that mimic human disease and response to treatment has limited critical preclinical study of mechanisms and new therapies for ER + breast cancer. The Stat1 knockout, 129S6/SvEvTac-Stat1 tm1Rds ( Stat1 -/- ), females develop luminal type FoxA1 + , ER + , and PR + mammary carcinomas after prolonged latencies. Initial studies showed that a cell line derived from a Stat1-/- mammary carcinoma was tumorigenic in syngeneic mice, but non-tumorigenic in ovariectomized (Ovx) mice. Here, data shows that Ovx performed after SSM2 tumors establish growth results in ovarian hormone independent growth. The viable post-Ovx tumors were primarily composed of metaplastic CK14 + basal type cells with a high percentage p53 immunohistochemistry (IHC) positive "mutation pattern", rather than the original luminal type tumors with low percent "wild type" pattern p53. Comparing whole exome sequences of ER + Stat1 -/- mammary tumors before and after Ovx, revealed basal keratins, mesenchymal (EMT) phenotypes, and unique mutation profiles in genes, including Trp53 and Prlr, in the estrogen-independent tumors. Our experimental findings are consistent with the clinical evidence of tumor heterogeneity of ER + breast cancers in patients in recent whole genome sequencing studies. Similarly, spontaneous Stat1-/- tumors with high percentage p53 "mutation pattern" were more basaloid and grew rapidly after Ovx, while retaining high expression of ER and FoxA1. This study demonstrates that the STAT1 -/- , ER + estrogen dependent breast cancers can become resistant to through clonal selection of mammary cells comprised of metaplastic p53 + /CK14 + basaloid cells.

Background and Study Aims: Blunt dissection is not commonly performed in flexible endoscopic procedures. We developed a novel blunt dissection device and evaluated its feasibility, safety, and potential effectiveness in third space endoscopy procedures., Materials and Methods: The device consists of a cotton swab and a flexible shaft. To evaluate its functionality, creation of 4-cm submucosal tunnels in live swine stomachs was attempted by either blunt dissection using our device or sharp dissection using a standard monopolar knife. Data on factors such as completion rate, operating time, adverse events, necessity of submucosal injection, and dissected submucosal thickness were collected., Results: Eighteen submucosal tunnels were successfully created (sharp: 9, blunt: 9) by two experienced endoscopists and one novice endoscopist. Median operating time was significantly shorter in the blunt dissection group (239 vs. 429 s, P = 0.008). In the sharp dissection group, the experienced endoscopists did not cause any muscle layer injuries, but the novice endoscopist caused muscle layer injuries in all cases. In the blunt dissection group, neither experienced nor novice endoscopists caused muscle layer injuries. The blunt dissection group required significantly fewer submucosal injections (0 vs. 5, P < 0.001). Median dissected submucosal thickness was similar between the groups., Conclusions: Blunt dissection using our device was feasible, safe, and potentially effective in third space endoscopy procedures by shortening operating time, reducing submucosal injections, and potentially minimizing muscle layer injury., Competing Interests: Conflict of Interest Shota Fujii is a full-time employee of Sanyo CO. Ltd. The remaining authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Hidradenitis suppurativa is a disabling inflammatory skin disease., Objective: To investigate the efficacy and safety of upadacitinib, a selective Janus kinase inhibitor., Methods: In this phase 2, randomized, placebo-controlled, double-blind clinical trial (NCT04430855), adults with moderate-to-severe hidradenitis suppurativa were randomized 2:1 to once-daily upadacitinib 30 mg or placebo. At 12 weeks, placebo patients switched to blinded upadacitinib 15 mg, and patients receiving upadacitinib 30 mg continued assigned treatment through week 48. The primary endpoint was ≥50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining fistula count relative to baseline (Hidradenitis Suppurativa Clinical Response [HiSCR50]) at week 12., Results: Forty-seven patients received upadacitinib; 21 patients received placebo. At week 12, a significantly greater proportion of patients receiving upadacitinib achieved HiSCR50 vs a prespecified historical placebo rate (38.3% vs 25.0%; 1-sided P = .018). Comparison with the in-trial placebo group showed an adjusted difference of 14.7% (nominal P = .087). HiSCR50 achievement with upadacitinib was consistent across baseline Hurley stage and prior tumor necrosis factor inhibitor exposure and maintained through week 40. Upadacitinib's safety profile was consistent with previous reports on dermatologic conditions., Limitations: Sample size was small., Conclusion: Findings support further investigation of upadacitinib for moderate-to-severe hidradenitis suppurativa., Competing Interests: Conflicts of interest Dr Ackerman is an investigator for AbbVie, Amgen, AstraZeneca, Argenx, Biofrontera, Bristol Myers Squibb, CASTLE Biosciences, ChemoCentryx, Corrona, DermTech, Eli Lilly, Incyte, Janssen, Kymera, LEO Pharma, Mindera, Regeneron, Sun, Timber, Trevi, and UCB. She is a consultant and/or advisor for AbbVie, Bristol Myers Squibb, Janssen, Eli Lilly, Novartis, Sanofi, Timber, and UCB, and a speaker for AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Helsinn, Janssen, Kyowa Kirin, Pfizer, Sun Pharma, and UCB. Dr Fretzin is on the speakers' bureau for AbbVie, Celgene, Eli Lilly, Janssen, Incyte, and UCB. He is an investigator for AbbVie, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, and has received other financial benefits from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Pfizer. Dr Kimball's institution has received grants from AbbVie, Admirx, AnaptysBio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, Sonoma Bio, and UCB. She has received consulting fees from AbbVie, Alumis, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, FIDE, Janssen, Moonlake, Novartis, Pfizer, Priovant, Sanofi, Sonoma Bio, Target RWE, UCB, Union Therapeutics, and Ventyx. She receives royalties from BIDMC, holds stock in Ventyx, and serves on the board of directors of Almirall. Dr Prajapati has served as an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Apogee Therapeutics, Aralez, Arcutis, Aspen, Bausch Health, BioScript Solutions, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Concert, CorEvitas, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, J&J Innovative Medicine, Jamp Pharma, Janssen, Johnson & Johnson, LEO Pharma, Medexus, Novartis, Organon, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant; has served as an investigator for AbbVie, Alumis, AnaptysBio, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Meiji Pharma, Nektar Therapeutics, Nimbus Lakshmi, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and VYNE Therapeutics; and has received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme. Dr Takahashi has received honoraria from AbbVie, Amgen, Eli Lilly, Janssen, Kaken Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Novartis, Sanofi, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Torii, and UCB. Dr Camp, Dr Huang, Dr Schlosser, and Dr Zhan are full-time employees of AbbVie, and may hold AbbVie stock and/or stock options., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study developed a three-dimensional ultrastructural analysis application using serial block-face scanning electron microscopy (SBF-SEM) to investigate surgically acquired human skin tissues containing the arrector pili muscle. We utilized the en bloc staining, including reduced osmium, thiocarbohydrazide, and lead aspartate, as well as the embedding using a carbon-based conductive resin. Next, we obtained serial images with SBF-SEM. The results revealed dense nerve fiber networks branching from nearby nerve fiber bundles outside the muscle and running among muscle fibers. Additionally, the dense nerve network running through and along arrector pili muscle fibers rarely penetrates the connective tissues between smooth muscle fibers and epithelial cells. Furthermore, in the observation area, no individual smooth muscle fibers formed adhesion structures with the epithelial cells of the hair follicle, ending in the dermal extracellular matrix near the epithelial cells. These results indicate the usefulness of this approach for three-dimensional ultrastructural analyses of human skin tissues comprising follicular units and revealing structural changes in skin tissues, especially the arrector pili muscle and nerve fibers with hair follicular epithelium, in aging and diseased conditions., Competing Interests: Declarations. Competing interests: The authors declare that this study was supported by the collaborative research funding from Shiseido Co., Ltd. to N.O. and K. M., and T.E. is an employee of Shiseido Co., Ltd. U.H. declares no competing interests., (© 2025. The Author(s).)

Axial chirality is the key physiochemical element, yet its chiroptical utilities have been largely limited to covalent synthesis and infinitely assembled systems so far. Here we report a new application of axially chiral binaphthyls for efficient, optical chirality enhancement and transfer upon noncovalent encapsulation by achiral aromatic micelles in water. The CD activities of dialkoxy binaphthyls are significantly enhanced (up to 7-fold) upon encapsulation by an anthracene-based aromatic micelle. Large emission enhancement (∼4-fold) and efficient guest-to-guest, optical chirality transfer are achieved through coencapsulation of the binaphthyls with achiral cycloparaphenylenes, in a guest-within-guest fashion, by the micelle. The observed unusual properties are derived from the tight inclusion of the chiral guests into the macrocyclic guests, efficiently generated only in the aromatic cavity. Moderate CPL can be observed from the coencapsulated macrocycles within the ternary composites. Furthermore, more than ∼4-fold enhanced guest-to-guest chiroptical transfer is demonstrated with a functionalized cycloparaphenylene through the present coencapsulation strategy., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)

Purpose: To investigate the association between aqueous humor (AH) suppressant eye drops and the concentration of aflibercept at 1 month after intravitreal injection., Methods: This retrospective study included 17 eyes of 17 patients with neovascular age-related macular degeneration (nAMD) who used eye drops for their glaucoma and received their first intravitreal aflibercept (IVA) at two centers between July 2013 and November 2020. As controls, we enrolled 40 age-, sex-, and axial length-matched eyes of 40 patients with nAMD who were not using any medication that would affect AH circulation. AH was collected 1 month after the first IVA. Aflibercept levels were measured by enzyme-linked immunosorbent assay and were compared between controls and cases using the Kruskal-Wallis test and Dunn's test. The drugs were categorized into two groups based on their mechanism of action on the AH: outflow drugs (e.g., prostaglandin analog) and inflow drugs (e.g., carbonic anhydrase inhibitor, beta-blockers, and alpha-2 agonists)., Results: Mean (interquartile range) aflibercept levels in the AH in controls and in cases who used outflow and inflow drugs were 6.83 µg/mL (1.94-10.34), 9.93 µg/mL (2.58-17.44), and 15.95 µg/mL (7.20-22.57), respectively. A Kruskal-Wallis test showed a significant difference among the control, inflow, and outflow drugs (P = 0.0075). Dunn's test showed that aflibercept levels in the aqueous humor were significantly higher in cases using inflow drugs compared to both controls and cases using outflow drugs (P = 0.0085 and P = 0.044, respectively)., Conclusions: Aflibercept levels in the AH 1 month after the first IVA were higher in cases using eye drops that reduce AH secretion than in controls., Translational Relevance: Our results, together with previous studies in animals, suggest that combined use of these eye drops might extend the half-life of intravitreally injected drugs.

Pelvic ring fractures are often accompanied by complications, including vascular injuries such as life-threatening intra-abdominal bleeding and urinary tract damage resulting from direct external force. While urethral and bladder injuries are the most common urologic complications, testicular dislocation is rarely reported. Traumatic testicular dislocation (TTD), although uncommon, is frequently associated with motorcycle accidents and remains relatively unfamiliar to orthopedic surgeons, which can lead to delayed diagnosis. However, prolonged untreated dislocation may result in impaired spermatogenesis and endocrine dysfunction. Early detection and prompt urologic consultation are therefore essential. Treatment typically requires careful reduction, and in this case, testicular repositioning was achieved alongside pelvic fracture stabilization. We present a case of pelvic ring fracture complicated by TTD., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. 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 © 2025, Nunotani et al.)

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations. We compared the progression-free survival (PFS), overall survival (OS), and pretreatment co-occurring genetic alterations detected in plasma between patients with stages IVA (n = 83) and IVB disease (n = 84). Multivariate analysis of PFS and OS revealed that stage IVB was associated with a poor prognosis (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.36-3.04, p < 0.001, HR: 2.35, 95% CI: 1.45-3.90, p < 0.001, respectively). Pre-osimertinib treatment, significantly more TP53- (52.4% vs. 27.7%, p = 0.002), EGFR amplification- (58.3% vs. 23.2%, p < 0.001), and MET amplification-positive cases (22.6% vs. 7.2%, p = 0.008) were found among stage IVB than among stage IVA or lower cases. Patients with EGFR-positive NSCLC in stage IVB exhibited significantly shorter PFS and OS than those in earlier stages when treated with first-line osimertinib. The prevalence of baseline TP53 mutations, EGFR amplification, and MET amplification in plasma were significantly higher in stage IVB cases, implicating them in the worse outcomes of this group., Competing Interests: Declarations. Ethical approval and consent to participate: This prospective observational study was registered on December 10, 2018, in the Japanese Register of Clinical Trials (JRCT; Clinical Trial Number: jRCTs031180051). Written informed consent was obtained from all patients before the study began, and the National Hospital Organization Review Board for Clinical Trials approved this protocol prior to the start of the study. Consent for publication: Not applicable. Competing interests: Taniguchi Y has received honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, AstraZeneca, and MSD. Tamiya A received honoraria from Eli Lilly, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb, Amgen, Taiho Pharmaceutical, Kyowa-Kirin, MSD, Takeda Pharmaceutical, Nihon-Kayaku, Novartis, Thermo Fischer, Amgen, Tsumura, Daiich-Sankyo, and Merck BioFarma, and research funding from Daiichi-Sankyo, Beigene, and AstraZeneca. Oki M has received Honoraria from AMCO, AstraZeneca, Canon Medical Systems, Chugai Pharmaceutical, Fujifilm Toyama Chemical, Kaneka Medix, Merit Medical Japan, Novartis Pharma, Olympus and Sanofi, and research funding from AbbVie, AstraZeneca, Chugai Pharmaceutical, Fujifilm Toyama Chemical, GlaxoSmithKline, Janssen Pharmaceutical, MSD, Ono Pharmaceutical, Parxel International, Pfizer, Sanofi. Mori M received honoraria from AstraZeneca, Boehringer Ingelheim, MSD, Eli Lilly, Novartis, Chugai Pharmaceutical, Taiho Pharmaceutical, Kyowa-kirin, Ono Pharmaceutical, Otsuka, Nihon-kayaku, Pfizer, Daiici-Sankyo, Takeda Pharmaceutical, and Shionogi and research funding from Chugai Pharmaceutical, Ono Pharmaceutical, MSD, and Delt-fly. Koh Y has received honoraria from Chugai Pharmaceutical, Guardant Health, Amgen, Takeda Pharmaceutical, and Tosoh Corporation and has received consulting or advisory roles from Tosoh Corporation and research funding from Boehringer Ingelheim, AstraZeneca, Chugai Pharmaceutical, Tosoh Corporation, Daiichi Sankyo, Zeon Corporation, Amgen, and Takeda Pharmaceutical. The other co-authors received no honoraria or research funding., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recognizing rare molecular variants of driver mutations poses a challenge in precision oncology, particularly for treatment of non-small cell lung cancer (NSCLC). In this study, we aimed to determine whether Oncomine Dx Target Test Multi-CDx System (ODxTT), the most widely used genetic test for NSCLC in Japan, potentially overlooks druggable EGFR mutations., Materials and Methods: Among 418 patients who underwent molecular testing using ODxTT at our hospital, 267 were diagnosed with adenocarcinoma. No mutations were reported in 82 of these cases. For these 82 cases, we searched for EGFR mutations in exons 18-21 by examining the binary alignment map file. Once a mutation was identified, its pathological significance was evaluated using the ClinVar database to determine whether ODxTT had overlooked any actionable EGFR mutations., Results: Mutations in EGFR exons 19 and 18 were identified in six and four cases, respectively. Three, six, and none of these variants were detectable using the Cobas EGFR Mutation Test v2, Lung Cancer Compact Panel, and Amoy Dx, respectively. Of the 10 patients, five were subsequently treated with EGFR TKI; three showed partial response, one had stable disease, and one had progressive disease., Conclusions: ODxTT failed to identify 10 actionable EGFR mutations, accounting for 12.2% (10/82) of the cases initially reported as not carrying actionable mutations. Therefore, comprehensive genomic profiling should be actively performed early in cases with high clinical suspicion of EGFR mutations., (© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Study Design: This was a multicenter retrospective cohort study., Objective: We investigated the incidence of postoperative shoulder imbalance (PSI) and its risk factors in patients with Lenke types 1 and 2 scoliosis corrected using vertebral coplanar alignment (VCA)., Summary of Background Data: PSI in scoliosis affects patient quality of life. While other correction methods have reported a high correction rate for the main thoracic curve (MTC) in relation to PSI, this correlation has not been confirmed for the VCA technique., Materials and Methods: We studied 176 patients with Lenke types 1 and 2 scoliosis who underwent posterior corrective fusion surgery using the VCA technique at 11 institutions. At 2 years postoperatively, patients were divided into two groups based on radiographic shoulder height (RSH): PSI- (RSH<2 cm) and PSI+ (RSH ≥2 cm) groups. We analyzed the risk factors for PSI., Results: The overall incidence of PSI 2 years postoperatively was 11.4% (20/176), with 9.2% (11/119) and 15.8% (9/57) in patients with Lenke types 1 and 2, respectively. Contrary to a previous study, a high MTC correction rate did not emerge as a risk factor for PSI. Instead, preoperative left shoulder elevation, low postoperative thoracic kyphosis, greater T1 tilt, and high apical vertebral body-to-rib ratio were associated with PSI in patients with Lenke type 1. Preoperative left shoulder elevation and a low postoperative proximal thoracic curve (PTC) correction rate were identified as risk factors for PSI in patients with Lenke type 2., Conclusion: Our results suggest that proper PTC correction, rather than compromising MTC correction, may help prevent PSI in the VCA technique. This method is particularly advantageous for addressing Lenke type 1 scoliosis and yields favorable outcomes in shoulder balance. Patients with preoperative left shoulder elevation, especially Lenke type 2, are at high risk of developing PSI., Level of Evidence: Level 4., Competing Interests: H.T. received a scholarship donation from Medtronic Sophamore Danek Inc. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)