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Cadaveric surgical training (CST) can safely improve surgical skill. Recently, various innovations have made surgical training more realistic. Saturated salt solution (SSS) and urea methods are useful for plastic surgery training, because they better preserve the color and texture of soft tissues than formalin fixation (FA). Microvessels are invisible to the naked eye, and in this study, we visualized skin perforators by injecting dye into the flaps of nutrient vessels during hand and foot surgery. During each CST session, the instructor used three cadavers for demonstration. From 2017 to 2021, these cadavers were not stained, whereas from 2022 to 2023, the cadavers were stained to enhance the visualization of nutrient and perforating vessels. We compared the self-rated skill gains of participants who observed demonstrations on unstained cadavers from 2017 to 2021 and participants who observed demonstrations on stained cadavers from 2022 to 2023. Among 36 participants from the 2022-2023 group, 28 rated the staining of nutrient vessels and perforating branches as adequate. Of 32 participants, 29 preferred the use of dyed cadavers during training. Trainee skill increase for the digital artery flap, reverse digital artery flap, and dorsal metacarpal artery perforator flap was significantly higher in 2022-2023 (with stained cadavers) than in the earlier course without stained cadavers. SSS-fixed and urea-treated cadavers combined with vascular staining may be useful training models for flap elevation., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest. Research involving human participants and/or animals: This study was approved by the Ethics Committee of Tokyo Medical University (ethics review number: T2019-0125, SH3809). Informed consent: Informed consent was appropriately obtained either from the individuals before death or from their families after death., (© 2025. The Author(s).)

Ischemic stroke (IS) is a pathological condition characterized by the cessation of blood flow due to factors such as thrombosis, inflicting severe damage to the cranial nervous system and resulting in numerous disabilities including memory impairments and hemiplegia. Despite the critical nature of this condition, therapeutic options remain limited, with a pressing challenge being the development of treatments aimed at restoring neurological function. In this study, we leveraged zebrafish, renowned for their exceptional regenerative capabilities, to analyze the pathology of IS and the subsequent recovery process. We induced photothrombosis in the telencephalon utilizing rose bengal and conducted a temporal investigation of changes in cerebral vascular function and learning ability. Our findings revealed that blood flow in young zebrafish was restored approximately 7 days post-IS induction (dpi), with brain function recuperating by 14 dpi. Furthermore, we observed an escalation in the expression of the neural stem marker gene at 3dpi, followed by an upregulation of the differentiated neuron marker at 7 and 14dpi. In the aged IS model, symptoms were exacerbated. While cerebral blood flow was restored in 7 days, similar to young zebrafish, the recovery of learning ability was protracted in aged fish. Moreover, an upregulation of the differentiated neuron marker seen in young fish was not observed in the aged model. Collectively, our analysis of the zebrafish IS model and its comparison with existing rodent models may lay the groundwork for novel IS treatment strategies. Furthermore, the zebrafish IS model may prove beneficial for analyzing the impact of aging on the pathology of IS and the recovery process., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takamasa Mizoguchi reports financial support was provided by JSPS Grants-in-Aid for Scientific Research grant. Motoyuki Itoh reports financial support was provided by JSPS Grants-in-Aid for Scientific Research grant. Takamasa Mizoguchi reports financial support was provided by Research Grant for Public Health Science. Takamasa Mizoguchi reports financial support was provided by Smoking Research Foundation. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Tenomodulin (TNMD) is related to chondromodulin-1, a cartilage-derived growth regulator. It is specifically expressed in hypovascular connective tissues, including tendons and ligaments. Vascular endothelial growth factor A (VEGF-A) and calcitonin gene-related peptide (CGRP) correlate with angiogenesis and neurogenesis, respectively, during development. Because of that the morphological profiles of TNMD, VEGF-A, and CGRP distributions in developing diaphragm are still unclear, we aimed to determine the expression of mRNA and proteins of these 3 markers during the development of the central tendon of the diaphragm (CTD) and the surrounding diaphragm tissue in mice. Male mice from the embryonic and postnatal periods [embryonic day 14.5 (E14.5), E17.5, postnatal day 1 (P1), and P5] were used and their mRNA and protein expressions were assessed using in situ hybridization, immunohistochemistry and quantitative real-time polymerase chain reaction. The results showed that TNMD was preferentially detected in muscle-tendon junction of the CTD at E17.5 and P1, in contrast to scattered distribution of CGRP and VEGF-A throughout the diaphragm from E14.5 to P5. These findings may provide fundamental information concerning the role of the TNMD in the CTD development., Competing Interests: Declarations. Conflict of 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. Ethics statement: All experiments were conducted in accordance with the Ethics Committee of the Laboratory Animal Center of Tokyo Medical University (Approval number; No. R6-069), and all animal handling procedures conformed to acceptable guidelines on the ethical use of animals in this research. Credit authorship contribution statement: All authors had full access to all the data in the study and take responsibility for the integrity of data and the accuracy of the data analysis. Iwao Sato/Conceptualization; Ryutaro Nakagawa /Data curation; Iwao Sato, Shinichi Kawata, Yutaro Natsuyama, and Yoko Ueda/Formal analysis; Iwao Sato and Masahiro Itoh/Funding acquisition; Iwao Sato, Yoko Ueda, and Ryutaro Nakagawa/Investigation; Iwao Sato, Yutaro Natsuyama, and Hidenobu Miyaso/Methodology; Iwao Sato and Masahiro Itoh/Project administration; Ryutaro Nakagawa, and Zhong-Lian Li/Resources; Shinichi Kawata/Software; Masahiro Itoh/Supervision; Tomiko Yakura, and Yoko Ueda/Validation; Iwao Sato, Ryutaro Nakagawa, Tomiko Yakura and Hidenobu Miyaso/Visualization; Iwao Sato and Ryutaro Nakagawa/Writing – original draft; Iwao Sato, Ryutaro Nakagawa, Zhong-Lian Li, Hidenobu Miyaso, and Masahiro Itoh/Writing – review and editing., (© 2025. The Author(s), under exclusive licence to Japanese Association of Anatomists.)

Recent rapid sea ice reduction in the Pacific sector of the Arctic Ocean is potentially associated with inflow of Pacific-origin water via the Bering Strait. For the first time, we detected remarkable subsurface warming around the Chukchi Borderland in the Arctic Ocean over the recent two decades (i.e., the early 21 st century). A statistically significant decadal trend of 16.6 ± 10.6 MJ m - 2 year - 1 in the subsurface ocean heat content during 1999-2020 was captured by shipboard hydrographic data, and associated with the transport of Pacific Summer Water from Barrow Canyon northwest of the Alaskan coast, where similar warming appeared. Satellite-derived geostrophic ocean velocity indicated that the northwestward ocean current flowing from Barrow Canyon to the Chukchi Borderland became faster in the late 2010s, in association with southeastward shift of the Beaufort Gyre, circulating clockwise around the Canada Basin. Therefore, we suggest that warming of the Pacific Summer Water passing over the Chukchi shelf and intensification of the northwestward ocean current along the shelf-basin boundary both acted to enhance the heat transport and contributed to the positive trend in downstream subsurface ocean heat content. Our findings fill important gaps in the understanding of ocean heat distribution/transport, which is a key factor for sea ice freezing/melting, in the central Arctic., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The rete ovarii and epoophoron in females are homologous structures of the rete testis and efferent/epididymal duct in males and are derived from the developing rete cells and mesonephric tubules, respectively. Sex steroid hormones play a critical role in reproductive function for both sexes, and we recently reported expression patterns of sex steroid receptors in developing male reproductive tracts. However, their expression patterns in females remain unclear. We, therefore, investigated the three-dimensional structure and expression patterns of sex steroid receptors in the rete ovarii and epoophoron of fetal and adult female mice. In adult females, the epoophoron was not adherent to the rete ovarii. The rete ovarii had a bursa-like structure, with its extra-ovarian region protruding toward the epoophoron. A marker for mesonephric tubules, PAX2 (Paired box 2), was detected in the epoophoron and a small population of epithelial cells in the extra-ovarian rete ovarii. These epithelial cells expressed estrogen receptor and androgen receptor. During development, mesonephric tubules were adherent to the rete ovarii at first, but as the development proceeded, the continuity was lost due to the interruption of the tubule rather than separation between the tip of the tubule and rete ovarii. These findings suggest that epithelial cells, originating from the mesonephric tubules, persist even in the adult rete ovarii with maintained expressions of receptors for estrogen and androgen., Competing Interests: Declarations. Ethical Approval (Research involving Human Participants and/or Animals): Institutional Animal Care and Use Committee of Tokyo Medical University (Permission #R3-0066). Informed consent: Not Applicable. Conflicts of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Hereditary breast and ovarian cancers (HBOC) carry a high risk of breast cancer, and detailed screening with contrast-enhanced breast MRI (breast MRI surveillance) is recommended. With the increase in the number of individuals diagnosed with HBOC, the demand for breast MRI surveillance is also rising. However, the current system is inadequate, with factors such as lack of knowledge and indifference among healthcare professionals, and insufficient understanding of breast MRI surveillance being cited. This study aims to investigate the knowledge of HBOC and the awareness of breast MRI surveillance among radiological technologists, and to analyze the factors that promote these practices., Methods: A web-based survey was conducted among radiological technologists at 1278 facilities with MRI installations., Results: Responses were obtained from 433 individuals. The knowledge of HBOC was insufficient, with 49.6% unaware that breast MRI surveillance is recommended. Factors promoting awareness included the amount of knowledge about HBOC, age, and the presence of MRI specialists and mammography screening specialists., Conclusion: By enhancing the acquisition of knowledge about HBOC and raising awareness of breast MRI surveillance, it is expected that discussions towards building a robust system will deepen.

Purpose: The aim of this study was to investigate the utility of native T 1 and T 2 mapping in the bowel to evaluate disease activity in Crohn disease (CD) using endoscopy as the reference standard., Methods: This was a prospective study. Magnetic resonance imaging was performed by using a 1.5-T Philips scanner. We used a modified look-locker inversion recovery and a multiecho gradient-spin-echo sequences for single breath-hold native T 1 and T 2 maps, respectively, for the short-axis image of the intestine, and the measurement at the most severe site was compared with partial Simple Endoscopic Score for Crohn's Disease (pSES-CD, assessed by an expert endoscopist). A pSES-CD ≥ 4 indicated active disease. Statistical analyses were performed using the Student t test, Spearman correlation, and receiver operating characteristic curve analysis., Results: A total of 27 patients (mean age ± standard deviation, 37 ± 18 years; 20 men, 7 women) were included in this study. The native T 1 value of active disease was significantly higher than that of inactive disease (1170.8 ± 100.5 milliseconds vs 924.5 ± 95.3 milliseconds; P = 0.018), but the T 2 value was not significantly different between active and inactive disease (76.1 ± 7.8 milliseconds vs 69.3 ± 10.9 milliseconds; P = 0.424). A good correlation was found between native T 1 value and pSES-CD (ρ = 0.71; P < 0.001) but not between T 2 value and pSES-CD (ρ = 0.06; P = 0.790). The area under the receiver operating characteristic curve for differentiating the disease activity was 0.96 (95% confidence interval [CI]: 0.90-1.00) for T 1 values and 0.68 (95% confidence interval: 0.41-0.96) for T 2 values., Conclusions: Native T 1 mapping could be potentially used as a noninvasive method to differentiate disease activity in patients with CD and may be superior to T 2 mapping for this purpose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intraoral anastomosis is a widely used technique for microvascular alveolar ridge augmentation and midface reconstruction. However, the predictable anatomical positioning of facial structures, such as the vessels, parotid duct, and facial nerve in the buccal region, has remained unclear. Therefore, we aimed to obtain the anatomical characteristics of these locations to establish surgical landmarks for the intraoral anastomosis of facial vessels., Methods: A total of 26 sides from 13 formaldehyde-fixed cadavers approximately a month after fixation with a mean age at death of 86.6 ± 11.2 years (range: 55-104 years) were anatomically examined. Facial vessels, nerves, and the parotid duct were dissected intraorally. From the oral cavity side, the X-axis was defined as the line from the labial commissure to the lowest point of the intertragic notch., Results: From the oral cavity side, all branches of the facial nerve were found under the facial artery and vein. The positioning order along the X-axis was the facial artery, vein, and parotid duct exit. The facial artery was 21.3 ± 2.2 mm and the facial vein was 39.2 ± 2.7 mm from the labial commissure. Ninety-two percent of facial veins were found within 15-20 mm of the facial artery on the X-axis. The parotid duct exit was 46.8 ± 2.0 mm from the labial commissure. In the buccal region, the vessel calibers of the facial artery and vein were 1.8 ± 0.2 and 2.1 ± 0.2 mm, respectively., Conclusion: Knowledge of the anatomical relations among the facial artery, vein, parotid duct, and facial nerve from the oral cavity side can enhance the safety and efficacy of midface reconstruction surgeries involving intraoral anastomosis procedures., (© 2024 The Author(s). Microsurgery published by Wiley Periodicals LLC.)

Background: In CAPItello-291, capivasertib-fulvestrant significantly improved progression-free survival (PFS) versus placebo-fulvestrant in the overall and PIK3CA/AKT1/PTEN-altered population with hormone receptor-positive (HR-positive)/human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer. Capivasertib-fulvestrant is approved in Japan for the treatment of patients with one or more tumor biomarker alterations (PIK3CA, AKT1 or PTEN). Here, we report outcomes in the CAPItello-291 subgroup of patients from Japan., Methods: Adults with HR-positive/HER2-negative advanced breast cancer whose disease had relapsed or progressed during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy, were randomly assigned (1:1 ratio) to receive capivasertib or placebo, plus fulvestrant. The dual primary endpoint was investigator-assessed PFS in the overall and PIK3CA/AKT1/PTEN-altered population. Safety was a secondary endpoint., Results: Of 708 patients randomized in CAPItello-291, 78 were from Japan (37 randomized to capivasertib-fulvestrant and 41 to placebo-fulvestrant). In the Japan subgroup, PFS numerically favored the capivasertib-fulvestrant arm (hazard ratio 0.73; 95% CI 0.40-1.28), consistent with the analysis of PFS in the global population. Similarly, in the Japan subgroup of patients with PIK3CA/AKT1/PTEN-altered tumors, PFS favored the capivasertib-fulvestrant arm (hazard ratio 0.65; 95% CI 0.29-1.39), consistent with the global population. The adverse event profile of capivasertib-fulvestrant in the Japan subgroup was broadly similar to that in the global population; no new safety concerns were identified., Conclusion: Outcomes in the Japan subgroup were broadly similar to those of the global population, supporting the clinical benefit of capivasertib-fulvestrant in treating HR-positive/HER2-negative advanced breast cancer that has progressed on, or after, an endocrine-based regimen., Competing Interests: Declarations. Conflict of interest: Eriko Tokunaga has received payment or honoraria from AstraZeneca, Chugai, Daiichi-Sankyo and Eli Lilly. Hiroji Iwata has received consultancy fees and payment or honoraria from AstraZeneca, Chugai, Daiichi-Sankyo, Lilly, MSD and Pfizer; has received consultancy fees from Giliead and has received payment or honoraria from Kyowa Kirin and Taiho. His institution has also received grants from AstraZeneca, Chugai, and Daiichi-Sankyo. Tetsuhiko Taira has received payment or honoraria from Chugai, Daiichi-Sankyo, Eli Lilly, Kyowa Kirin, MSD, and Taiho. Tatsuya Toyama has received lecture fees from Chugai, Daiichi-Sankyo, Pfizer, MSD, Lilly, Novartis, and Taiho. Toshiro Mizuno has received payment or honoraria from AstraZeneca, Ono Pharmaceutical, Daiichi-Sankyo, Pfizer, Lilly, MSD, Eisai, Chugai Pharmaceutical, Kyowa Kirin, and Nippon Kayaku. Akihiko Osaki has received grants from AstraZeneca plc, Chugai Pharmaceutical Co., Ltd, Daiichi-Sankyo co., Ltd., Eisai Co., Ltd., Eli Lilly Japan KK, LabCorp Japan, G.K., MSD K.K., Nippon Kayaku Co., Ltd., Nipro Corp, Novartis Pharma K.K., Sanofi S.A., Taiho Pharmaceutical Co., Ltd.., Takeda Pharmaceutical Co., Ltd and WJOG. They have also received lecture fees from Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo co., Ltd., Eisai Co., Ltd., Eli Lilly Japan KK, Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd. and Pfizer Japan Inc. Seigo Nakamura has received payment or honoraria from AstraZeneca. Rikiya Nakamura has received payment or honoraria from AstraZeneca, Chugai, Daiichi-Sankyo, Eisai and Eli Lilly. Sacha J Howell has received grants from Eli Lily through a joint working initiative, has received consulting fees from AstraZeneca, Eli Lilly and Pfizer, has received payment or honoraria from AstraZeneca, Eli Lilly, Novartis, and Pfizer, and has received support for travel from Novartis. Masakazu Toi has received research grants from Chugai, Takeda, Pfizer, Taiho, JBCRG assoc., KBCRN assoc., Eisai, Eli Lilly and companies, Daiichi-Sankyo, AstraZeneca, Astellas, Shimadzu, Yakult, Nippon Kayaku, AFI technology, Luxonus, Shionogi, GL Science and Sanwa Shurui. They have received fees for lecturing from Chugai, Takeda, Pfizer, Kyowa Kirin, Taiho, Eisai, Daiichi-Sankyo, AstraZeneca, Eli Lilly and companies, MSD, Exact Science, Novartis, Shimadzu, Yakult, Nippon Kayaku, Devicore Medical Japan, Sysmex and advisory board fees from Daiichi-Sankyo, Eli Lilly and companies, BMS, Bertis, Terumo, Kansai Medical Net. Toshiaki Ozaki, Tomoko Sambe, and Gaia Schiavon are employees of AstraZeneca. Mitsuya Itoh and Yasuhiro Yanagita report no conflicts of interest. Research involving human participants and/or animals: 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, as well as Good Clinical Practice guidelines and the AstraZeneca policy on bioethics. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Background: Multiplex genetic testing is recommended when treating nonsmall cell lung cancer. A certain percentage of test failures in RNA assays owing to poor surgical specimen quality have been documented, and fixation failure is a possible cause. At our institution, sheet-like fixation is performed to reduce fixation time. This study aimed to compare the quality of RNA from resected lung cancer specimens following different fixation methods., Methods: Sheet-like fixation specimens (n = 15), conventional fixation specimens of the same resected lungs (n = 15), and other lung cancer specimens collected for conventional fixation and subjected to multiplex gene-panel testing (n = 22) were retrospectively examined. RNA was extracted from each specimen. RNA quality and quantity were compared, and the success rate of multiplex gene-panel testing was determined., Results: The DV 200 value was significantly higher in RNA extracted from sheet-like fixation samples (median 47.5%, interquartile range [IQR]:40.3-51.5) compared with RNA extracted from conventionally fixed samples or conventionally fixed samples of other patient specimens (median 21%, IQR:5.3-29.8 and median 16.3%, IQR:9.5-27.1, respectively). No significant difference was observed in nucleic acid concentration. The multiplex genetic analysis success rate was 95% with conventional methods (one failure); however, it was 100% with the sheet-like fixation method., Conclusion: Sheet-like fixation preserved RNA extracted from lung cancer specimens, resulting in lesser degradation than with conventional fixation., (© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Objectives: To examine the association between maternal plasma cotinine concentrations during pregnancy and attention-deficit/hyperactivity disorder (ADHD) related characteristics in children., Design: Prospective birth cohort study from the Hokkaido Study on Environment and Children's Health., Setting: Hokkaido, Japan., Participants: A total of 7217 children were included in the analysis. Their mothers were recruited to this study between 2003 and 2012 during early pregnancy. Blood samples of mothers in their third trimester of pregnancy were obtained., Main Outcome Measures: ADHD-related characteristics screened by the ADHD-Rating Scale (ADHD-RS) in children at 6 and 8 years of age., Results: The mothers were classified into three groups according to plasma cotinine levels (median=0.22 ng/mL)-non-smokers (≤0.21 ng/mL), passive smokers (0.22-11.48 ng/mL) and active smokers (≥11.49 ng/mL). ADHD was suspected in 302 (8.6%), 334 (10.9%) and 90 (14.5%) children in the non-smoker, passive smoker and active smoker groups, respectively. Children born to mothers in the smoking group had a statistically significant increased risk of ADHD-related characteristics (adjusted RR=1.49, 95% CI=1.19-1.86 and adjusted RR=1.20, 95% CI=1.03-1.40 for the active and passive smoking groups, respectively)., Conclusion: This large Japanese cohort study suggests an association between smoking during pregnancy and the risk of ADHD in children 6 and 8 years of age., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Medial open wedge high tibial osteotomy (MOWHTO) is a well-established surgical procedure for osteoarthritis (OA) of the knee with varus malalignment. However, it is uncertain whether MOWHTO is an effective surgical procedure for early OA. This study aimed to evaluate the clinical results of MOWHTO for early OA of the knee with varus malalignment., Materials and Methods: This was a retrospective analysis of 87 patients in whom varus malalignment was corrected by MOWHTO between January 2017 and December 2022. Kellgren-Lawrence grade 0-1 was defined as early OA and grade ≥ 2 as established OA. Range of motion at the knee, Forgotten Joint Score-12, Knee Injury and Osteoarthritis Outcome Score, and radiological findings were compared between the early OA group and the established OA group., Results: The established OA group (n = 49) was significantly older than the early OA group (n = 38) (p = 0.02). There were no differences between the groups in preoperative or postoperative hip-knee-ankle angle or range of motion or in improvements in the Forgotten Joint Score-12 or Knee Injury and Osteoarthritis Outcome Score. The median follow-up duration was more than 24.0 months in both groups., Conclusion: MOWHTO had a good clinical outcome in patients with early OA and varus malalignment over a median follow-up of 2 years., Level of Evidence: III, retrospective study., Competing Interests: Declarations. Conflict of interest: The authors declare no potential conflicts of interest regarding the research, authorship, or publication of this article. Ethical approval: This study was approved by the Institutional Ethics Committee of Tokyo Women’s Medical University (approval number: 4578) and was conducted in accordance with the Declaration of Helsinki. Informed consent: Informed consent was obtained via an opt-out procedure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This retrospective comparative study aimed to compare the native patellar alignment and clinical outcomes of the Rotating Concave-Convex (ROCC) knee, which features a saddle-shaped rotating platform (RP) insert and a deep trochlea, versus the low contact stress (LCS) knee, which has favourable long-term outcomes and features an anatomically shaped trochlea and a cruciate-sacrificing RP insert. We hypothesized that the deeper trochlea of the ROCC would further stabilize the native patella, resulting in superior clinical outcomes compared to LCS-RP., Methods: Consecutive patients who underwent patellar-nonresurfacing primary total knee arthroplasty (TKA) using ROCC or LCS-RP were retrospectively reviewed. Patients with over 1-year post-TKA follow-up were included. Patients with neurologic disorders affecting knee function or additional ipsilateral knee surgery before evaluation were excluded. Patellar alignment was evaluated using the patella tilting angle (PTA), patella shift (PS), and the ratio of patella fitting depth into the trochlea ( F ) on axial radiographs. Primary and secondary outcomes were evaluated using the patellar score assessing patellofemoral function and Knee Injury and Osteoarthritis Outcome Score. Multiple regression analyses were performed with primary and secondary outcomes as dependent variables., Results: The analysis included 113 ROCC knees and 94 LCS-RP knees (median follow-up: 25 months, follow-up rate: 92.3%). For ROCC and LCS-RP, respectively, the mean PTA was 0.3 (3.2)° and 4.3 (2.9)°; PS was 0.5 (1.8) and 2.0 (2.5) mm; and F was 29.6 (8.1)% and 21.4 (6.5)% (all p  < 0.001). On multivariate analysis, ROCC positively affected both primary and secondary outcomes ( p  = 0.004 and 0.0003-0.02, respectively)., Conclusion: At short-term follow-up, ROCC stabilized the patella further horizontally, centrally, and deeply into the trochlea, thus outperforming LCS-RP clinically. Orthopaedic surgeons should consider these potential advantages when selecting TKA models, especially those featuring cruciate-sacrificing RP mechanisms in patellar-nonresurfacing procedures., Level of Evidence: III. Retrospective comparative study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background/aim: Extracellular signal-regulated kinases (ERK)1/2 are important regulatory proteins that control cell proliferation and survival, playing a significant role in cancer progression, metastasis, and chemoresistance. This study investigated the effects of ERK1/2 inhibitors on the in vitro growth of acute leukemia cell lines., Materials and Methods: Three ERK1/2 inhibitors were used: SCH772984, temuterkib (LY3214996), and ulixertinib (BVD-523). Four acute myeloid leukemia cell lines (OCI/AML3, HL-60, THP-1, and U-937) and two T-lymphoblastic leukemia cell lines (Jurakt and KOPT-K1) were treated with these inhibitors. Cell growth was assessed using a colorimetric assay, and cell-cycle progression and apoptosis were analyzed using flow cytometry. The expression of intracellular signaling proteins was evaluated via immunoblotting. The effects of small interfering RNA (siRNA)-mediated ERK1/2 knockdown were also evaluated., Results: The inhibitors suppressed the growth of three leukemia cell lines (OCI/AML3, HL-60, and THP-1) harboring neuroblastoma rat sarcoma virus (NRAS) mutations. Growth suppression occurred through G0/G1 arrest in all three cell lines and through apoptosis in OCI/AML3 cells. Immunoblotting demonstrated that these inhibitors suppressed the expression of MYC proto-oncogene, bHLH transcription factor (MYC), in the three cell lines. The additional molecular mechanisms of growth suppression varied depending on the specific inhibitor and cell line. The inhibitors had milder suppressive effects on normal lymphocytes compared to the leukemia cell lines., Conclusion: ERK1/2 inhibitors may serve as novel molecular-targeted drugs for treating leukemia with NRAS mutations., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Control of nutrient homeostasis plays a central role in cell proliferation/survival during embryonic development and tumor growth. Activation of the Notch signaling pathway, a major contributor to cell-cell interactions, is a potential mechanism for cell adaptation to nutrient-poor conditions. Our previous study also demonstrated that during embryogenesis when nutrients such as glutamine and growth factors are potentially maintained at lower levels, Notch signaling suppresses mRNA expression of hexokinase 2 (hk2), which is a glycolysis-associated gene, in the central nervous system. However, whether and how the genetic regulation of HK2 via Notch signaling contributes to cellular adaptability to nutrient-poor environments remains unknown. In this study, we performed gene expression analysis using a U87-MG human glioma cell line and revealed that under conditions where both glutamine and serum were absent, Notch signaling was activated and HK2 expression was downregulated by Notch signaling. We also found that Notch-mediated HK2 suppression was triggered in a Notch ligand-selective manner. Furthermore, HK2 was shown to inhibit cell proliferation of U87-MG gliomas, which might depend on Notch signaling activity. Together, our findings suggest the involvement of Notch-mediated HK2 suppression in an adaptive mechanism of U87-MG glioma cells to nutrient-poor conditions., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: Marsupials have a narrower range of forelimb morphological features than placental mammals. It is hypothesized that this is due to a constraint in the reproductive biology of marsupials. The constraint is that newborn marsupials must crawl into their mother's pouch. However, anatomical knowledge of the brachial plexus in marsupials is scarce and has not been discussed. In the present study, the purpose is to examine the anatomy of the brachial plexuses of a koala, a Tasmanian devil, and a common ringtail possum and to discuss the brachial plexus of marsupials with reference to the previous reports., Materials and Methods: One adult koala (Phascolarctos cinereus) specimen, one adult Tasmanian devil (Sarcophilus harrisii), and one adult common ringtail possum (Pseudocheirus peregrinus) were used in this study., Discussion: The ventral rami of C5, C6, C7, C8, and T1 formed the brachial plexus in all 3 marsupials. Each nerve branch differed by one segment among the 3 marsupials. Therefore, the brachial plexus was considered in the form of a few differences among marsupials., Conclusions: Because of a quite difficulty of getting an opportunity for anatomical examination on marsupials, an accumulation of cases like the present study is needed for future quantitative and qualitative analyses of the brachial plexus pattern of the marsupials.

Infective endocarditis (IE) rarely results in mitral stenosis (MS), but MS in patients with IE can be life-threatening. We present a case of prosthetic MS secondary to IE. A 69-year-old Japanese man underwent mitral valve replacement with a bioprosthetic valve 2 years previously. The patient presented with a 1-month history of illness, and we diagnosed prosthetic valve IE with severe MS and planned for time-sensitive surgery. However, the patient developed cardiogenic shock in response to prosthetic mitral valve obstruction while awaiting surgery. The patient then had to undergo emergency surgery. There are no management guidelines for IE-induced valve stenosis, whose treatment differs from that of valve regurgitation. Our literature review reveals that achieving survival in patients with MS secondary to IE is difficult without surgical intervention. Patients with MS caused by IE may require surgery, and specific criteria should be outlined in future guidelines., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objectives: As part of the "Japan Environment and Children's Study (JECS)," a national prospective birth cohort study, we examined the association between the maternal work environment and psychological distress during pregnancy in Japan., Methods: Employing a cross-sectional design, we analyzed data from 42,797 participants, originally collected between 2011 and 2014. Associations between the maternal work environment and psychological distress (Kessler 6) were examined using generalized estimation equation models adjusted for confounding factors., Results: Pregnant women who worked ≥51 h/week had a 1.19-fold higher odds ratio (OR) of psychological distress than those who worked 36-40 h/week (95% confidence intervals [CI], 1.07-1.32). Pregnant women who worked ≥5 days/month of shift work had a 1.11-fold higher OR of psychological distress than those who worked 0 days/month (1.00-1.24)., Conclusions: We observed an association between the maternal work environment and psychological distress during pregnancy., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Objective: We examined the association between the occupations of pregnant women's partners and infant low birth weight (LBW) and preterm birth (PB)., Methods: Birth outcome data were collected from 46,540 participants enrolled in the Japan Environment and Children's Study. Participants were recruited from January 2011 to March 2014. Associations between the occupations of pregnant women's partners and birth outcomes were examined using logistic regression models adjusted for confounding factors., Results: LBW and PB incidences were 7.5% and 4.1%, respectively. In the major occupational group, the odds ratios (95% confidence intervals) of LBW for clerical (1.19; 1.03-1.37) and service workers (1.21; 1.05-1.39) were higher than those for professional and engineering workers. However, no associations existed between the major occupational groups of the pregnant women's partners and PB., Conclusion: Partner's employment in clerical and service work increases the risk for LBW., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Background Aims: Methotrexate (MTX) is used as standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. However, the optimal dosing regimen among the various MTX regimens available remains unclear., Methods: We used the registration data of Kyoto Stem Cell Transplantation Group to compare six MTX dosing protocols in a multicenter retrospective analysis of 816 cases of unrelated bone marrow or peripheral blood stem cell transplantation., Results: Our findings indicated increased risks of grade Ⅱ-Ⅳ acute GVHD and extensive chronic GVHD in the cohort given the shortened mini-dose MTX regimen (5 mg/m 2 infusions on days 1, 3, and 6) compared with patients that received any of the other protocols. In addition, transplantation outcomes did not differ significantly between cohorts according to the inclusion or absence of leucovorin rescue., Conclusion: The original short-term, reduced short-term, and mini-dose MTX methods were all effective for GVHD prophylaxis. However, omission of the day 11 MTX dose from the mini-dose regimen elevated the risks of grade Ⅱ-Ⅳ acute GVHD and extensive chronic GVHD. Moreover, leucovorin rescue might be ineffective in terms of reducing complications., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Developmental coordination disorder (DCD) presents motor skill delays in early childhood and has been associated with later maladaptation, necessitating early intervention. However, research on the potential risk factors, particularly in preschool-aged children, remains scarce., Aims: We aimed to explore the association between small for gestational age (SGA) and other factors and motor coordination problems in 5-6-year-olds from the Hokkaido Study on Environment and Children's Health Cohort., Study Design: Prospective., Subjects: We analyzed data from >3500 participants from the Hokkaido Study, a prospective birth cohort, and assessed children aged 5-6 years., Outcome Measures: Participants underwent assessment with the Developmental Coordination Disorder Questionnaire Japanese version (DCDQ-J). We conducted linear regression analyses adjusted for variables such as the child's sex, maternal age, and maternal smoking history during pregnancy, while also examining the independent associations of each risk factor., Results: Among the 3883 children analyzed for SGA, children with SGA exhibited significantly lower DCDQ-J total scores than non-SGA children (mean difference: -2.25, 95 % confidence interval [-4.19, -0.30], p = 0.02). On the subscales, children with SGA demonstrated significantly lower "Control During Movement" scores than non-SGA children (mean difference: -0.96, 95 % confidence interval [-1.78, -0.13], p = 0.02). Furthermore, the child's sex, maternal smoking, maternal age, and preterm birth were independently associated with DCD., Conclusions: SGA was shown to be one of the risk factors for the manifestation of motor coordination difficulties in 5-6-years old children. In combination with other factors, screening for motor coordination difficulties in SGA children will be an important means of initiating appropriate interventions., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2024. Published by Elsevier B.V.)

Sexual selection drives rapid evolution of morphological, physiological, and behavioral traits, especially in males, and it may also drive the rapid evolution of hybrid male sterility. Indeed, the faster male theory of speciation was once viewed as a major cause of Haldane's rule in male-heterogametic XY taxa, but is increasingly being replaced by the genetic conflict hypothesis partly because it cannot explain the faster evolution of hybrid female sterility in female-heterogametic ZW taxa. The theory nonetheless predicts that there should be more genes for hybrid male sterility than for hybrid female sterility even in such taxa, but this remains untested. Thus, finding evidence for the faster male theory of reproductive isolation beyond the F1 generation in ZW systems still represents a challenge to studying the impact of sexual selection. In this study, we examined F2 hybrids between the domesticated silkworm Bombyx mori and the wild silk moth Bombyx mandarina, which have ZW sex determination. We found that although only females showed reduced fertility in the F1 generation, the F2 hybrid males had a significant reduction in fertility compared with the parental and F1 males. Importantly, 27% of the F2 males and 15% of the F2 females were completely sterile, suggesting the presence of recessive incompatibilities causing male sterility in female-heterogametic taxa., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The influx of microplastics (MPs) into the Arctic Ocean poses a collective risk, particularly with pronounced sea ice depletion due to global warming. A total of 73 replicate sediment samples were collected at different depths (38 to 79 m) from Chukchi and the Beaufort Seas at 8 stations in the Arctic region during the R/V Mirai cruise (MR22-06C) from August to September 2022. The average concentration of MPs is 79.25 ± 31.08 items/kg d.w. Fibrous MPs of 0-1 mm size range are predominant, with blue being the most prevalent colour. Polymer characterization identified polyethylene (PE) as the predominant polymer. Arctic Ocean regions face heightened health risks from the coexistence of MPs and harmful additives, amplifying concerns over plastic pollution. The alarming surge in MPs within Arctic sediment underscores the urgent need for a proactive, collaborative approach to mitigate this environmental threat and its far-reaching impacts., 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 Elsevier Ltd. All rights reserved.)

The current study was a preliminary evaluation of the feasibility and biologic features of three-dimensionally bio-printed tissue-engineered (3D bio-printed) vascular grafts comprising dermal fibroblast spheroids for venous replacement in rats and swine. The scaffold-free tubular tissue was made by the 3D bio-printer with normal human dermal fibroblasts. The tubular tissues were implanted into the infrarenal inferior vena cava of 4 male F344-rnu/rnu athymic nude rats and the short-term patency and histologic features were analyzed. A larger 3D bio-printed swine dermal fibroblast-derived prototype of tubular tissue was implanted into the right jugular vein of a swine and patency was evaluated at 4 weeks. The short-term patency rate was 100%. Immunohistochemistry analysis showed von Willebrand factor positivity on day 2, with more limited positivity observed on the luminal surface on day 5. Although the cross-sectional area of the wall differed significantly between preimplantation and days 2 and 5, suggesting swelling of the tubular tissue wall (both p < 0.01), the luminal diameter of the tubular tissues was not significantly altered during this period. The 3D bio-printed scaffold-free tubular tissues using human dermal or swine fibroblast spheroids may produce better tissue-engineered vascular grafts for venous replacement in rats or swine., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Proper regulation of N-methyl-D-aspartate-type glutamate receptor (NMDA receptor) expression is responsible for excitatory synaptic functions in the mammalian brain. NMDA receptor dysfunction can cause various neuropsychiatric disorders and neurodegenerative diseases. Posttranslational protein S-palmitoylation, the covalent attachment of palmitic acid to intracellular cysteine residues via thioester bonds, occurs in the carboxyl terminus of GluN2B, which is the major regulatory NMDA receptor subunit. Mutations of three palmitoylatable cysteine residues in the membrane-proximal cluster of GluN2B to non-palmitoylatable serine (3CS) lead to the dephosphorylation of GluN2B Tyr1472 in the hippocampus and cerebral cortex, inducing a reduction in the surface expression of GluN2B-containig NMDA receptors. Furthermore, adult GluN2B 3CS homozygous mice demonstrated a definite clasping response without abnormalities in the gross brain structure, other neurological reflexes, or expression levels of synaptic proteins in the cerebrum. This behavioral disorder, observed in the GluN2B 3CS knock-in mice, indicated that complex higher brain functions are coordinated through the palmitoylation-dependent regulation of NMDA receptors in excitatory synapses., (© 2024. The Author(s).)

Background and Objectives: Recent reports have highlighted that allogeneic blood transfusions decrease immune responses and affect patient outcomes. However, the effects of allogeneic red blood cell transfusions on the composition of immune cells are unclear. We aimed to clarify the alterations in host immune cells in patients who received allogeneic red blood cell transfusions during the perioperative period of cardiovascular surgery., Materials and Methods: Eight non-transfused, 22 intraoperative autotransfusions, and 36 allogeneic red blood cell-transfused patients undergoing surgery were grouped, and lymphocyte subsets were analyzed using flow cytometry. Blood samples collected before surgery, approximately 1-week, and 1-month after surgery were used for analysis. Surgical parameters, operation time, blood loss, and length of hospital stay were also assessed., Results: The group receiving transfusions showed statistical significance compared to non-transfused in the above-mentioned surgical parameters. When comparing the autologous and allogeneic transfusion groups, only the allogeneic red blood transfusion group had a longer hospital stay. In comparing preoperative and 1-week and 1-month postoperative samples, there were almost no differences in CD4, CD20, or NK counts between the autotransfusions and the allogenic red blood cell transfusion groups. In contrast, a significant decrease in lymphocyte count was observed in the allogenic red blood cell transfused group 1-week postoperatively compared to preoperatively. Moreover, the number of CD8 + cells was statistically lowest in the allogeneic transfusion group 1 week after the operation., Conclusion: Our results suggest that allogeneic red blood cell transfusion could alter immune cell composition especially CD8 + cells, potentially impacting immune function., (Copyright © 2024 Society francophone de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

The liver is a complex organ with a highly organized structure in which tight junctions (TJs) play an important role in maintaining their function by regulating barrier properties and cellular polarity. Dysfunction of TJs is associated with liver diseases, including progressive familial intrahepatic cholestasis (PFIC). In this study, we investigated the molecular alterations in a liver-specific ZO-1 and ZO-2 double-knockout (DKO) mouse model, which exhibits features resembling those of PFIC4 patients with mutations in the ZO-2 gene. RNA-seq analysis revealed the upregulation of genes involved in the oxidative stress response, xenobiotic metabolism, and cholesterol metabolism in DKO livers. Conversely, the expression of genes regulated by HNF4α was lower in DKO livers than in the wild-type controls. Furthermore, age-associated analysis elucidated the timing and progression of these pathway changes as well as alterations in molecules related to TJs and apical polarity. Our research uncovered previously unknown implications of ZO-1 and ZO-2 in liver physiology and provides new insights into the molecular pathogenesis of PFIC4 and other tight junction-related liver diseases. These findings contribute to a better understanding of the complex mechanisms underlying liver function and dysfunction and may lead to the development of novel therapeutic strategies for liver diseases associated with tight junction impairment.Key words: tight junctions, ZO-1/ZO-2 knockout mouse, liver, transcriptome analysis, molecular pathological progression.

Competing Interests: The authors declare no conflict of interest.

Real-world work environments require operators to perform multiple tasks with continual support from an automated system. Eye movement is often used as a surrogate measure of operator attention, yet conventional summary measures such as percent dwell time do not capture dynamic transitions of attention in complex visual workspace. This study analyzed eye movement data collected in a controlled a MATB-II task environment using gaze transition entropy analysis. In the study, human subjects performed a compensatory tracking task, a system monitoring task, and a communication task concurrently. The results indicate that both gaze transition entropy and stationary gaze entropy, measures of randomness in eye movements, decrease when the compensatory tracking task required more continuous monitoring. The findings imply that gaze transition entropy reflects attention allocation of operators performing dynamic operational tasks consistently., (© 2024. The Author(s).)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic vascular dementia characterized by age-related degeneration of vascular mural cells and accumulation of a NOTCH3 mutant protein. NOTCH3 functions as a signaling receptor, activating downstream gene expression in response to ligands like JAG1 and DLL4, which regulate the development and survival of mural cells. This signal transduction process is thought to be connected with NOTCH3 endocytic degradation. However, the specific cellular circumstances that modulate turnover and signaling efficacy of NOTCH3 mutant protein remain largely unknown. Here, we found elevated NOTCH3 and Radical fringe (RFNG) expression in senescent human pericyte cells. We then investigated impacts of RFNG on glycosylation, degradation, and signal activity of three NOTCH3 CADASIL mutants (R90C, R141C, and C185R) in EGF-like repeat-2, 3, and 4, respectively. Liquid chromatography with tandem mass spectrometry analysis showed that RFNG modified NOTCH3 WT and C185R to different degrees. Additionally, coculture experiments demonstrated that RFNG significantly promoted JAG1-dependent degradation of NOTCH3 WT but not that of R141C and C185R mutants. Furthermore, RFNG exhibited a greater inhibitory effect on JAG1-mediated activity of NOTCH3 R141C and C185R compared to that of NOTCH3 WT and R90C. In summary, our findings suggest that NOTCH3 R141C and C185R mutant proteins are relatively susceptible to accumulation and signaling impairment under cellular conditions of RFNG and JAG1 coexistence., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Fecal corticosterone metabolite (FCM) concentrations, which can be determined noninvasively, have recently been explored as a stress indicator in birds. In our study, we measured FCM concentrations in penguins under nonmolting or molting conditions, cool or hot season, diseased condition, and incubation period. These measurements were conducted in an aquarium that housed king penguins, gentoo penguins, and African penguins. This study aimed to investigate the validity of fecal matter as a stress indicator. Our findings revealed that FCM concentrations were significantly higher in molting individuals than in nonmolting individuals. Compared with the cool season, FCM concentrations were significantly higher in penguins housed outdoors during the hot season. However, no differences were observed in penguins housed indoors. Diseased individuals and an incubating individual showed notably higher FCM concentrations than healthy individuals. Interestingly, the FCM concentration in king penguin that underwent cataract surgery was extremely high before the surgery. However, 1 month postsurgery, it decreased to a level similar to that of healthy individuals. We observed increased FCM concentrations in penguins considered to be exposed to stressors. Notably, FCM concentration decreased after removing the stress factor. The FCM concentration was found to be consistent with the stress state of penguins, suggesting its usefulness as a stress indicator.

Previous studies have reported that the lateral meniscus (LM) has two regions, the popliteal hiatus area (PH) with a scarce blood supply and the roots with an abundant one. However, the description of its vascular anatomy remains insufficient. We hypothesized that the difference in the width of the meniscus hilum (MH) affects the scarcity and abundance of blood supply to the LM. The MH is a concept proposed by us and is the only site of entrance or exit of blood vessels and nerves associated with the meniscus. The purpose of this study was to provide a structural explanation for the disparity of blood supply to the LM using the concept of MH. Sixteen knees were examined to investigate the blood supply to LM. In most areas, the femoral joint capsule (FJC) and tibial joint capsule (TJC) continued to the cranial and caudal edges of the LM, respectively. In the roots, the FJC and TJC covered the femoral and the outer-femoral surfaces. In contrast, the FJC in the PH did not attach to the cranial edge and only the TJC there did to the caudal edge of the LM. Histochemical examination showed that the blood vessels enter the LM via the MH. In the PH, the MH at the caudal edge was extremely narrow; and in the roots, the MH on the outer-femoral surfaces was wide. The results suggest that the difference in the width of the MH affected the scarcity and abundance of blood supply to the LM., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest in association with the present study., (© 2024. The Author(s).)

Purpose: One of the most common types of coronal plane alignment of the knee (CPAK) is type I, which is characterised by varus alignment and apex distal joint line obliquity. The purpose of this study was to evaluate the association of changes in arithmetic hip-knee-ankle angle (aHKA) with both postoperative joint laxity and patient-reported outcome measures (PROMs) in patients with CPAK type I following mechanical alignment (MA) total knee arthroplasty (TKA)., Methods: Of 111 consecutive knees in 92 patients with osteoarthritis who underwent primary TKA, 80 knees (72.0%) with CPAK type I phenotype preoperatively were evaluated. All TKAs were performed to achieve neutral MA by a medial stabilising gap balancing technique. Pre- to postoperative change in aHKA was defined as ΔaHKA. The 80 CPAK type I knees were divided into a larger ΔaHKA group (>7°) and a smaller ΔaHKA group (≤7°). PROMs, including the Knee Society Score and Forgotten Joint Score-12, were assessed before and 2 years after surgery. Pre- and postoperative joint laxity was assessed using a Telos arthrometer., Results: Twenty-two knees showed a larger ΔaHKA, and postoperative lateral joint laxity in varus stress was significantly greater in these patients than in those with a smaller ΔaHKA (6.8° vs. 4.5°, p  = 0.006). There were no significant differences between the groups in PROMs ( p  = n.s.)., Conclusions: Postoperative lateral laxity was associated with larger aHKA changes than smaller aHKA changes in CPAK type I knees after TKA. However, no statistically significant differences in PROMs were found according to the amount of change in aHKA., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

The strength distributions of the Isoscalar Giant Monopole Resonance (ISGMR) and Isoscalar Giant Quadrupole Resonance (ISGQR) in 142,146−150Nd have been determined via inelastic α -particle scattering with the Grand Raiden (GR) Spectrometer at the Research Center for Nuclear Physics (RCNP), Japan. In the deformed nuclei 146−150Nd, the ISGMR strength distributions exhibit a splitting into two components, while the nearly spherical nucleus 142Nd displays a single peak in the ISGMR strength distribution. A noteworthy achievement in this study is the first-time detection of overtones in the Isoscalar Giant Quadrupole Resonance (ISGQR) strength distributions within Nd isotopes at an excitation energy around 25 MeV obtained through Multipole Decomposition Analysis (MDA). [ABSTRACT FROM AUTHOR]

Background: Childhood asthma is known to be affected by a range of factors, including conditions in the indoor environment. While flooring material influences indoor air conditions, the potential association between flooring materials and childhood asthma remains poorly understood in Japan., Objective: The present study aims to assess the association between childhood asthma incidence and the primary flooring material with the ongoing prospective nationwide birth cohort data of the Japan Environment and Children's Study (JECS)., Methods: The JECS gathered data on mothers and children through 15 Regional Centres across Japan. The present study assessed flooring materials used in the home and asthma incidence at age four among children born between 2011 and 2014. We implemented logistic regressions, setting asthma incidence among the children as the outcome and home floor type as the exposure. Additional analyses were conducted, stratifying the home's age as a proxy for tatami age, to assess whether the potential effect of tatami flooring on asthma risk is influenced by its age., Results: The present study included total of 75,629 infants. For tatami flooring, the main multivariable regression and additional sub-group regression for homes over ten years old produced odds ratios of 1.09; 95% Confidence Interval (CI) [1.01-1.17] and 1.10; 95% CI [1.00-1.21] compared with flooring, respectively., Conclusion: These results imply that exposure to tatami flooring, particularly in older homes, may be associated with childhood asthma incidence. Moreover, our study highlights the importance of evaluating the relationship between regional and cultural differences between asthma and flooring materials., Competing Interests: None., (Copyright: © 2024 Iwata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Delta receptors (GluD1 and GluD2), members of the large ionotropic glutamate receptor (iGluR) family, play a central role in numerous neurodevelopmental and psychiatric disorders. The amino-terminal domain (ATD) of GluD orchestrates synapse formation and maturation processes through its interaction with the Cbln family of synaptic organizers and neurexin (Nrxn). The transsynaptic triad of Nrxn-Cbln-GluD also serves as a potent regulator of synaptic plasticity, at both excitatory and inhibitory synapses. Despite these recognized functions, there is still debate as to whether GluD functions as a "canonical" ion channel, similar to other iGluRs. A recent report proposes that the ATD of GluD2 imposes conformational constraints on channel activity; removal of this constraint by binding to Cbln1 and Nrxn, or removal of the ATD, reveals channel activity in GluD2 upon administration of glycine (Gly) and d-serine (d-Ser), two GluD ligands. We were able to reproduce currents when Gly or d-Ser was administered to clusters of heterologous human embryonic kidney 293 (HEK293) cells expressing Cbln1, GluD2 (or GluD1), and Nrxn. However, Gly or d-Ser, but also l-glutamate (l-Glu), evoked similar currents in naive (i.e., untransfected) HEK293 cells and in GluD2-null Purkinje neurons. Furthermore, no current was detected in isolated HEK293 cells expressing GluD2 lacking the ATD upon administration of Gly. Taken together, these results cast doubt on the previously proposed hypothesis that extracellular ligands directly gate wild-type GluD channels., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: CDKL5 deficiency disorder (CDD), an epileptic encephalopathy for which novel therapeutics are under development, lacks valid and reliable measures of therapeutic efficacy. We aimed to elucidate the neurophysiological and brain structural features of CDD patients and identify objective indicators reflecting the clinical severity., Methods: Twelve CDD patients and 12 healthy controls (HCs) participated. The clinical severity of CDD was scored using the CDD severity assessment (CDD-SA). The participants underwent visual evoked potential (VEP), auditory brainstem response (ABR), structural MRI, and diffusion tensor imaging (DTI) analyses. Measurements from each modality were compared with normal values of age-matched cohorts (VEP and ABR) or statistically compared between CDD patients and HCs (MRI)., Results: VEP showed a significant correlation between P100 latency and CDD-SA in CDD patients. ABR showed abnormalities in six patients (50%), including prolonged V-wave latency (n = 2), prolonged inter-peak latency between waves I and V (n = 3), and mild hearing loss (n = 4). Structural MRI showed a significant reduction in cortical volume in the left pars triangularis and right cerebellum compared with HCs. DTI showed a widespread decrease in fractional anisotropy and an increase in mean and radial diffusivity compared with HCs., Conclusion: CDD patients had reduced cortical volume in the left pars triangularis, a brain region crucial for speech, and one-third of patients had mild hearing loss. These changes may be involved in language impairments in CDD patients. Additionally, P100 latency significantly correlated with the clinical severity. These features can be used to assess the clinical severity of CDD., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.

Although ovarian cancer is generally unilateral, a few cases of bilateral ovarian cancer have been reported, most of which originate from metastases of unilateral ovarian cancer. However, synchronous primary bilateral ovarian cancer (SBOC), comprising two different histological types of ovarian cancer, is extremely rare, with limited reports on its clinical course and prognosis. Herein, we report the case of a 56-year-old postmenopausal Japanese woman with stage IVB SBOC with combined left ovarian clear cell and right ovarian mucinous carcinomas. The patient underwent surgery and received postoperative taxane/platinum-based chemotherapy, which temporarily reduced the tumor size. However, an increase in tumor size and brain metastases were subsequently identified. Treatment was accordingly discontinued, and the patient died of the disease 12 months after diagnosis. In this case report, we detail the clinical course of a case of SBOC. To the best of our knowledge, this is the first report of SBOC with combined histological types of clear cell and mucinous carcinomas, and it is also the first report of SBOC with the eventual discovery of brain metastases., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© 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.)

Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function., 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 article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In visceral and mucocutaneous leishmaniasis, humoral immune response can reflect disease severity and parasite burden. Cutaneous leishmaniasis (CL) in Sri Lanka is caused by a usually visceralizing parasite, Leishmania donovani. We assessed the parasite burden (relative quantity-RQ) in 190 CL patients using quantitative real-time PCR (qPCR-with primers designed for this study) and smear microscopy, then correlated it with clinical parameters and IgG response. RQ of parasite DNA was determined with human-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the internal control. The qPCR sensitivity was tested with serially diluted DNA from cultured L. donovani parasites. Smears were assigned a score based on number of parasites per high power field. Data from previous studies were used for comparison and correlation; nested Internal Transcribed Spacer 1 (ITS1) PCR as reference standard (RS) and IgG antibody titers to the Leishmania rKRp42 antigen as the immune response. The qPCR amplified and quantified 86.8% of the samples while demonstrating a fair and significant agreement with ITS1-PCR and microscopy. Parasite burden by qPCR and microscopy were highly correlated (r = 0.76; p = 0.01) but showed no correlation with the IgG response (r = 0.056; p = 0.48). Corresponding mean RQs of IgG titers grouped by percentiles, showed no significant difference (p = 0.93). Mean RQ was higher in early lesions (p = 0.04), decreased with lesion size (p = 0.12) and slightly higher among papules, nodules and wet ulcers (p = 0.72). Our study established qPCR's efficacy in quantifying parasite burden in Sri Lankan CL lesions but no significant correlation was observed between the parasite burden and host IgG response to the Leishmania rKRP42 antigen., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We present the measured spin correlation coefficient C y , y for p- 3 He elastic scattering at 100 MeV at the angles θ c. m. = 46. 9 ∘ – 149. 2 ∘ in the center of mass system. The experiment was performed using a 100 MeV polarized proton beam in conjunction with the polarized 3 He target. Proton beams were injected to the target, and scattered protons were detected by using E- Δ E detectors which consisted of plastic and NaI(Tl) scintillators. The data are compared with rigorous numerical calculations based on realistic NN potentials as well as with the Δ -isobar excitation. The obtained results indicate that the C y , y expands the knowledge of the nuclear interactions with Δ -isobar or those including 3NFs that are masked in nucleon-deuteron elastic scattering. [ABSTRACT FROM AUTHOR]

Cryptosporidiosis is a major cause of diarrhea and is associated with high morbidity in calves. Changes in the gut microbiota exacerbate diarrhea caused by Cryptosporidium parvum infection in neonatal and weaned calves. However, information on the gut microbiota of neonatal calves with C. parvum infection is scarce, and research into the microbiome of calves is essential for developing preventive and therapeutic interventions. This study aimed to elucidate the gut microbiota of neonatal calves with cryptosporidiosis. We collected 31 fecal samples from 31 neonatal calves on a dairy farm with or without C. parvum antigen [CP(+) or CP(-)] using a kit and analyzed the differences in the microbiota between diarrheal (D) and normal (N) fecal samples with C. parvum infection based on the fecal score. The analyses revealed the α diversity indexes of fecal microbiota in CP(+)-N samples were higher than that in CP(+)-D samples. Megasphaera spp. and other rumen microbes were identified, and significantly associated with CP(+)-N samples compared with CP(+)-D samples by linear discriminant analysis effect size (LEfSe). We conclude that the specific gut microbiota could characterize fecal microbiota in calves with neonatal cryptosporidiosis without clinical symptoms., (© 2024.)