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Working memory (WM) load has been well-documented to impair selective attention and inhibitory control. However, its effects on motor function remain insufficiently explored. To extend the existing literature, we investigated the impact of WM load on force control and movement-related brain activity. Sixteen healthy young participants performed a visual static force matching task using a pinch grip under varying WM loads. The task included low and high WM load conditions (memorizing one digit or six digits), and the precision level required to control force was adjusted by manipulating visual gain (low vs. high visual gains), with higher visual gain necessitating more precise force control. Peri-movement alpha and beta event-related desynchronization (ERD), along with force accuracy and steadiness, were measured using electroencephalography recorded over the central areas during the force control task. Results indicated that while force accuracy and steadiness significantly improved with higher visual gain, there was no significant effect of WM load on these measures. Alpha and beta ERD were greater under high than low visual gain, and also greater under high than low WM load. These findings suggest that in young adults, increased WM load leads to compensatory increases in sensorimotor cortical activity to mitigate potential declines in static force control performance that may result from the depletion of neural resources caused by WM load. Our findings extend current understanding of the interaction between WM and sensorimotor processes by offering new insights into how movement-related brain activity is influenced by heightened WM load., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests.

A 46-year-old woman on low-dose estrogen-progestin (LEP) therapy for endometriosis developed a right-sided pneumothorax. Surgical findings included a pulmonary bulla in the right middle lung lobe and a small hole in the center tendon of the diaphragm, both of which were partially resected. Histopathology confirmed the presence of endometrial tissue, leading to a diagnosis of thoracic endometriosis. This case demonstrates that catamenial pneumothorax can occur despite LEP therapy, which is intended to suppress endogenous hormones. Clinicians should remain vigilant for this condition in patients with a history of endometriosis, even when hormonal treatment is in use., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Ethics Committee of Tohoku Medical and Pharmaceutical University issued approval 2024-4-060-0000. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ishibashi et al.)

Cocrystallization of trans-aconitic acid (TACA) and isonicotinamide (INA) using liquid assisted mechanochemical grinding results in a unique supramolecular hydrogen-bonded organic framework (HOF) system encapsulating various organic solvents (liquid guest) with the formation of channel inclusion compounds. Dimension and shape of the framework is dependent on the solvent used during liquid assisted grinding (LAG). Although crystal structure of the cocrystal (TACA)•(INA)2•(H2O)@(INA)0.5 has been determined by Single Crystal X-ray diffraction (SCXRD), crystal structures of 3 cocrystal HOFs were determined by microcrystal electron diffraction (MicroED) and synchrotron X-ray diffraction due to lack of suitable single crystal. PXRD analysis confirms isostructurality of various host-guest systems; whereas guest incorporation as well as stability of the HOFs were further confirmed using thermogravimetric analysis. This study demonstrates that the framework of HOFs can be tuned by varying solvent molecules used during LAG., (© 2024 Wiley‐VCH GmbH.)

Japanese encephalitis virus (JEV) genotype IV (GIV) is one of the least common and most neglected genotypes worldwide, having been identified only on a few Indonesian islands until it was recently found to be the cause of outbreaks that occurred in several Australian states in early 2022. Given the limited availability of information, the vector range for JEV GIV remains unknown; thus, understanding this range could prove invaluable for future prevention efforts in new areas. Herein, we experimentally exposed four mosquito colonies originated from various countries with no previous reports of GIV to JEV GIV strain 19CxBa-83-Cv, which was isolated from Culex vishnui Theobald collected in Bali in 2019. At 7 and 14 days post-JEV GIV exposure through a membrane feeding method, mosquito bodies, head-wings-legs, and saliva were harvested for infection, dissemination, and transmission efficiency analyses. The results showed robust transmission efficiencies of the virus by Culex tritaeniorhynchu s Giles (∼74%) and Aedes albopictus Skuse (∼52%) from Japan, followed by Culex quinquefasciatus Say from Vietnam (∼35%) and Culex pipiens form molestus from Turkey (∼18%). Although significant differences were observed, we found that the four mosquito species could transmit JEV GIV. The efficiency of biological transmission of this restricted genotype by mosquitoes from various origins suggests that these mosquito species could support localized transmission if the genotype were introduced to their respective areas. This study emphasizes the importance of remaining vigilant and continuing arbovirus surveillance in all locations.

The demand for alternatives to animal testing has increased, but there has been no significant progress in developing alternatives for repeated-dose toxicity tests despite their importance in chemical risk assessment. A comprehensive analysis of existing toxicity studies is the first step toward understanding toxicity and developing alternatives. However, such an analysis has yet to be performed for industrial chemicals. Therefore, we collected and organized publicly available repeated-dose subacute toxicity studies in male rats and constructed a database consisting of more than 2000 toxicity studies with about 500 toxicity-related findings. We then analyzed the no observed effect and lowest observed effect levels, toxicity-related findings, and organ categories in the database. The analyses revealed commonly and uncommonly observed toxicity-related findings and organ categories, as well as toxicity-related findings and organ categories with low and high median lowest observed effect levels. In addition, we extracted the toxicity studies registered in the Japanese and European chemical regulatory systems and conducted the same analysis for these datasets as the entire database. The results suggest that commonly observed toxicity-related findings were similar, but some toxicity-related findings differed in the frequency of observations between the two datasets.

Two dimensional (2D) crystals have attracted strong interest as a new class of proton-conducting materials that can block atoms, molecules and ions while allowing proton transport through the atomically thin basal planes. Although 2D materials exhibit this perfect selectivity, the reported proton conductivities have been relatively low. Here we show that vacancy-rich titania monolayers are highly permeable to protons while remaining impermeable to helium with proton conductivity exceeding 100 S cm -2 at 200 °C and surpassing targets set by industry roadmaps. The fast and selective proton transport is attributed to an extremely high density of titanium-atom vacancies (one per square nm), which effectively turns titania monolayers into angstrom-scale sieves. Our findings highlight the potential of 2D oxides as membrane materials for hydrogen-based technologies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The interplay between cardiac and kidney functions is mediated by the autonomic nervous system. Cardiovascular autonomic neuropathy (CAN) is a well-documented dysfunction of this system, with heart rate variability (HRV) serving as the principal diagnostic tool. CAN is recognized as a prognostic marker for adverse kidney outcomes in diabetic kidney disease (DKD). However, the pathogenesis of CAN in patients with nondiabetic chronic kidney disease (CKD) remains underexplored. This study elucidated the prevalence of CAN and its clinicopathologic characteristics in patients with nondiabetic CKD., Methods: This cross-sectional analysis evaluated 165 nondiabetic CKD patients who underwent kidney biopsy from 2020 to 2023. HRV was quantified using the coefficient of variation of the RR interval (CVRR). CAN was diagnosed based on the CVRR and defined using the CVRR reference value-derived by defining the age and sex-dependent lower normal limits as the 2.5 percentile point of the distribution of the CVRR values in healthy individuals., Results: The median patient age was 47.0 (34.0-57.0) years, and 50.9% were male. The median estimated glomerular filtration rate was 65.0 (42.0-85.0) mL/min/1.73m 2 , and the CVRR was 3.5 (2.4-4.7)% and 16 patients (9.7%) were diagnosed with CAN. CAN was frequently associated with kidney dysfunction, dyslipidemia, and advanced interstitial fibrosis/tubular atrophy (IF/TA). Multivariable analysis revealed that IF/TA was associated with CVRR, independent of established risk factors for CAN (P = 0.045)., Conclusions: The prevalence of CAN diagnosed using the CVRR in this nondiabetic CKD cohort was 9.7%, which is four times higher than that in healthy individuals. Nondiabetic CKD patients with CAN was associated with advanced IF/TA., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the ethics review board of the Jikei University School of Medicine, and the need for informed consent was waived by the Ethical Review Board of the Jikei University School of Medicine (approval number 33-265 10883). Consent for publication: Not applicable. Competing interests: Author Dr. Sasaki is a member of the Editorial Board of this journal. To ensure impartiality, Dr. Sasaki was not involved in the editorial or peer-review process for this manuscript. The manuscript was handled and reviewed independently by other editorial members to maintain objectivity and fairness. All other authors declare that they have no competing interests., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Objective: This study aimed to clarify perceptions of the transition from pediatric to adult care for patients with childhood-onset epilepsy in Japan., Methods: A qualitative descriptive study design was used. Semi-structured interviews were conducted with patients with childhood-onset epilepsy who had transitioned to adult care attending a tertiary hospital's adult outpatient care unit specializing in treating epilepsy. Data were analyzed using content analysis to extract perceptions regarding the transition from pediatric to adult care., Result: Six male and seven female patients between the ages of 18 and 49 years participated in the study. Seventeen perception categories regarding the experience of transitioning from pediatric to adult care were identified: {I followed a specific transfer process}, {I want to transition to adult care}, {I want to remain in pediatrics},{I have noticed something after transitioning to adult care}, {I recall trust in pediatricians}, {increased motivation for self-management}, and {I want detailed explanations about illness}., Conclusions: The patients wanted to transition to adult medicine, but were passive, waiting for their physicians to suggest the transition. Furthermore, their perceptions of their own self-care varied. Pediatric healthcare providers should discuss and support the decision to transition from pediatric to adult care and provide information to help patients with childhood-onset epilepsy accept their future and understand their self-management requirements. These patients may become independent through the transition to adult care, and collaboration between pediatric and adult medicine is important to pass the responsibility of self-support to medical providers in adult care., 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. Published by Elsevier Inc.)

Soluble CLEC-2 is anticipated to have various clinical applications as a novel biomarker for in vivo platelet activation, assessable using plasma obtained through routine sampling procedures. While sCLEC-2 has been measured using ELISA, we have developed a highly sensitive chemiluminescence enzyme immunoassay (CLEIA) reagent that can yield results in approximately 19 minutes. This study aims to assess its fundamental performance and explore the molecular forms of sCLEC-2 measured in patient samples. We examined the sensitivity, precision, linearity, influence of endogenous substances, residual platelets, as well as the correlation with the ELISA method, for the sCLEC-2 CLEIA reagent. The CLEIA method demonstrated sufficient sensitivity for levels observed in healthy donors, and its basic performance was satisfactory. It exhibited a strong correlation with the previously described ELISA method, with reference ranges that did not significantly differ from the ELISA data. The sCLEC-2 reference range for males was significantly higher than that for females. Since it is known that sCLEC-2 exists in shed form and microparticle form, we investigated molecular forms of sCLEC-2 measured by the CLEIA in in vitro-activated platelets and in patients' plasma using gel filtration. It is considered that the CLEIA method shows significantly stronger reactivity with the shed form compared to the microparticle form. Studies using gel filtration of patient samples also suggest that the shed form is being primarily measured. The sCLEC-2 CLEIA reagent exhibits robust performance and is promising for clinical applications.

Background: Sodium-glucose cotransporters (SGLTs) play a crucial role in glucose regulation and are essential therapeutic targets for diabetes management. Recent advancements have leveraged SGLT-targeted PET imaging to examine these transporters' roles in both health and disease., Scope of Review: This review highlights recent innovations in PET imaging targeting SGLTs, with a particular focus on SGLT-specific radiotracers, such as alpha-methyl-4-deoxy-4- 18 F-fluoro-d-glucopyranoside (Me-4FDG). It emphasizes the advantages of these radiotracers over conventional 18 F-2-fluoro-2-deoxy-d-glucose (2-FDG) imaging, especially in assessing SGLT activity. Additionally, the review addresses their potential in evaluating the pharmacodynamics of SGLT inhibitors, investigating metabolic changes in diabetes, and staging cancers., Major Conclusions: SGLT-targeted PET imaging offers promising improvements in diagnostic accuracy and therapeutic planning. The findings underscore the physiological and pathological significance of SGLTs, indicating that this imaging approach could shape future diagnostic and therapeutic strategies in metabolic and oncologic fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Microtubules (MTs) are dynamic cytoskeletal polymers that play a critical role in determining cell polarity and shape. In plant cells, acentrosomal MTs are localized on the cell surface and are referred to as cortical MTs. Cortical MTs nucleate in the cell cortex and detach from nucleation sites. The released MT filaments perform treadmilling, with the plus-ends of MTs polymerizing and the minus-ends depolymerizing. Minus-end targeting proteins, -TIPs, include Spiral2, which regulates the minus-end dynamics of acentrosomal MTs. Spiral2 accumulates autonomously at MT minus-ends and inhibits filament shrinkage, but the mechanism by which Spiral2 specifically recognizes minus-ends of MTs remains unknown. Here we describe the crystal structure of Spiral2's N-terminal MT-binding domain. The structural properties of this domain resemble those of the HEAT repeat structure of the tumor overexpressed gene (TOG) domain, but the number of HEAT repeats is different and the conformation is highly arched. Gel filtration and co-sedimentation analyses demonstrate that the domain binds preferentially to MT filaments rather than the tubulin dimer, and that the tubulin-binding mode of Spiral2 via the basic surface is similar to that of the TOG domain. We constructed an in silico model of the Spiral2-tubulin complex to identify residues that potentially recognize tubulin. Mutational analysis revealed that the key residues inferred in the model are involved in microtubule recognition, and provide insight into the mechanism by which end-targeting proteins stabilize MT ends., 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 B.V. All rights reserved.)

Background: Detection of synaptic connections is essential for understanding neural circuits. By using optogenetics, current injection, and glutamate uncaging to activate presynaptic cells and simultaneously recording the subsequent response of postsynaptic cells, the presence of synaptic connections can be confirmed. However, these methods present throughput challenges, such as the need for simultaneous multicellular patch-clamp recording and two-photon microscopy. These challenges lead to a trade-off between sacrificing resolution and experimental throughput., New Method: We adopted the laser, typically used for local field ablation, and combined this with post hoc analysis. We successfully approximated the synaptic connection probabilities using only an epi-fluorescence microscope and single-cell recordings., Results: We sequentially stimulated the channelrhodopsin 2-expressing cells surrounding the recorded cell and approximated the synaptic connection probabilities. This probability value was comparable to that obtained from simultaneous multi-cell patch-clamp recordings, which included more than 600 pairs., Comparison With Existing Methods: Our setup allows us to estimate connection probabilities within 100 s, outperforming existing methods. We successfully estimated synaptic connection probabilities using only the optical path typically used by an epi-fluorescence microscope and single-cell recordings. It may also be suitable for dendritic ablation experiments., Conclusions: The proposed method simplifies the estimation of connection probabilities, which is expected to advance the study of neural circuits in conditions such as autism and schizophrenia where connection probabilities vary. Furthermore, this approach is applicable not only to local circuits but also to long-range connections, thus increasing experimental throughput., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest concerning this research., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

A high-fat diet (HFD) causes inflammation with an increase in microglial activity in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA), resulting in insulin resistance in both regions. This leads to a deterioration in glucose and energy metabolism. The effect of voluntary exercise on HFD-induced inflammation in the central nervous system (CNS) remains unclear. To clarify the effects of voluntary exercise on the CNS, 8-week-old male C57BL6 mice were fed a chow diet (CHD) or HFD for 4 weeks; each group was further divided into running exercise (EX+) on a wheel and no exercise (EX-) groups. The expression of the inflammatory cytokine, tumor necrosis factor alpha (TNFα), in the ARC and VTA was significantly increased in the HFD/EX- group, with an increase of microglial activity noted, compared to the CHD/EX- group. The expression of TNFα was significantly suppressed, with a decrease of microglial activity, in the HFD/EX+ compared to HFD/EX- group. Insulin resistance in the ARC and VTA was improved with the suppression of TNFα expression. The HFD/EX- group showed significant weight gain and impaired glucose metabolism compared to the CHD/EX- group. The HFD/EX+ group showed an improvement in glucose and energy metabolism compared to the HFD/EX- group. In addition, voluntary wheel running suppressed HFD-induced inflammation in the ARC, with a decrease in microglial activity observed independently of weight changes. Our data suggest that voluntary exercise prevents obesity and improves glucose metabolism by suppressing inflammation in the ARC and VTA under HFD conditions., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Transformers achieve great performance on Visual Question Answering (VQA). However, their systematic generalization capabilities, i.e., handling novel combinations of known concepts, is unclear. We reveal that Neural Module Networks (NMNs), i.e., question-specific compositions of modules that tackle a sub-task, achieve better or similar systematic generalization performance than the conventional Transformers, even though NMNs' modules are CNN-based. In order to address this shortcoming of Transformers with respect to NMNs, in this paper we investigate whether and how modularity can bring benefits to Transformers. Namely, we introduce Transformer Module Network (TMN), a novel NMN based on compositions of Transformer modules. TMNs achieve state-of-the-art systematic generalization performance in three VQA datasets, improving more than 30% over standard Transformers for novel compositions of sub-tasks. We show that not only the module composition but also the module specialization for each sub-task are the key of such performance gain.

Purpose: Outcomes of unresectable biliary tract cancer (BTC) with varying extents of liver involvement remain unclear. We evaluated characteristics and outcomes of BTC patients with liver metastases who underwent chemotherapy., Methods: We retrospectively reviewed consecutive BTC patients with synchronous or metachronous intrahepatic metastases who started first-line chemotherapy at our institution between January 2016 and December 2021., Results: Ninety-six patients were included, of which 57 only had liver metastases and 39 had multiorgan involvement. The liver only group had longer median overall survival (OS) (11.8 vs. 7.4 months, P = 0.006) and median progression-free survival (PFS) (4.1 vs. 2.7 months, P = 0.035) than the multiorgan group. Patients with oligometastases (defined as no more than three liver metastases) achieved longer OS than those with polymetastases (four or more liver metastases) in the entire cohort. Within the liver only group, there were no significant differences in OS or PFS between the oligometastasis and polymetastasis groups. Patients who underwent subsequent surgery had significantly longer median OS than those who did not (44.4 vs. 7.7 months, P < 0.001). Age ≥ 75 years, liver-only metastasis, modified Glasgow prognostic score ≥ 1 carcinoembryonic antigen ≥ 5 μg/L, and subsequent surgery were independent predictors of OS. Liver oligometastasis was only a significant predictor of longer OS in univariate Cox analysis., Conclusions: Outcomes in BTC patients with metastases limited to the liver, particularly those with oligometastasis, were more favorable than those with multiorgan metastases. Selected cases, generally with liver oligometastases, may achieve prolonged OS through subsequent surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Steatotic liver disease after pancreatoduodenectomy occurs due to various factors, such as exocrine pancreatic insufficiency, impaired intestinal absorption, and malnutrition. The mechanism of steatogenesis differs to that of conventional steatotic liver disease associated with obesity and insulin resistance. We experienced a rare case of rapidly progressive steatotic liver disease accompanied by portal vein stenosis in the early postoperative period after subtotal stomach-preserving pancreaticoduodenectomy for distal cholangiocarcinoma. Although there was a complication due to postoperative drain infection, the patient was discharged from hospital with no nutritional problems. Two months postoperatively, the patient presented to the emergency room with dyspnea. CT showed a markedly steatotic liver, ascites, and portal vein stenosis. A portal vein stent was inserted transhepatically and the steatotic liver disease gradually improved. During the postoperative course, there were no problems indicated by nutritional markers; although the patient had diarrhea associated with postoperative pancreatic exocrine insufficiency, the symptoms were mild and improved after administration of oral pancrelipase. Before the intervention, the patient had intestinal edema, exacerbation of diarrhea, and a low serum zinc concentration, suggesting that impaired absorption caused by intestinal blood stasis and gut barrier dysfunction contributed to the development of steatotic liver disease., (© 2024. The Author(s).)

Getah virus (GETV), belonging to the genus Alphavirus within the family Togaviridae, is a mosquito-borne virus that causes fever, rash, and edema in horses and fatalities and pregnancy disorders in pigs. It has caused occasional outbreaks in horse populations in Japan, China, and India, and endemic areas are gradually expanding, particularly in Asia and Oceania. In this study, we isolated a new GETV strain from Culex tritaeniorhynchus mosquitoes collected from Nagasaki Prefecture, Japan in 2022. Phylogenetic analysis revealed that this new strain, 22IH8, is more closely related to previous Chinese strains than to the strains prevalent in Japan in the 2010s. Furthermore, some amino acid substitutions in the viral proteins of strain 22IH8 were found to be common with those in previous Chinese strains. These results suggest that 22IH8 strain may have recently invaded the Japanese archipelago from mainland Asia. The antiserum against the current vaccine strain, MI-110, showed high neutralization activity against the 22IH8 strain indicating the efficiency of the current vaccine for horses in Japan.

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

Introduction: Balloon kyphoplasty (BKP) for osteoporotic vertebral fracture (OVF) has been reported to maintain quality of life (QOL). This study aimed to investigate the effectiveness of ultra-early BKP performed within two weeks of injury (ultra-early group) to cases after two to four weeks post-injury (early group) and over four weeks (conventional group), assessing radiographic assessment such as subsequent fracture etc, questionarre such as QOL and back pain-related activities of daily living (ADL) one year after surgery., Methods: Ninety cases of OVF treated with BKP (23 males, 67 females, average age 78.0 years) were included. Radiographic assessments were examined and QOL parameters (SF-36 and EQ-5D-5L) and back pain-related ADL (ODI score) were assessed using self-administered questionnaires before and one year after surgery. Analysis of Variance (ANOVA) was used to compare changes in evaluation parameters among 3 groups. When significant differences were detected, post-hoc multiple comparisons were performed using the Steel-Dwass test., Results: The mean follow-up duration was 16.6 months. The ultra-early group consisted of 29 cases (10 males, 19 females, average age 77.0 years), the early group consisted of 39 (6 males, 33 females, average age 79.3 years), while the conventional group consisted of 22 cases (7 males, 15 females, average age 80.0 years). There was no significant difference in the preoperative score of SF-36, EQ-5D-5L, and ODI score. At the 1 year follow up, presence of subsequent fracture was significantly difference among 3 groups (3.4 % vs. 10.3 % vs. 31.8 %) (ANOVA, p < 0.05). Moreover, subsequent Steel-Dwass multiple comparisons also revealed that ultra-early group showed significantly less subsequent fracture compared to the conventional group (p < 0.05). Furthermore, Significant differences were observed in the changes of bodily pain in SF-36, EQ-5D-5L and ODI among 3 groups (ANOVA, p < 0.05). Steel-Dwass multiple comparisons also revealed that ultra-early group showed significantly greater improvement in EQ-5D-5L compared to the early group and conventional group (p < 0.05). ODI scores in ultra-early group also showed greater recover compared to the conventional group (p < 0.005)., Conclusions: Ultra early BKP within two weeks of OVF demonstrates effectiveness for less complication such as subsequent fracture, QOL and back pain-related ADL one year post-surgery, enabling early return to society., Competing Interests: Declaration of competing interest The authors declare that there are no relevant conflicts of interest., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Megakaryocytes are classified into several subtypes including LSP1-positive immune-skewed, MYLK4-positive hematopoietic stem cell (HSC)-regulating, and BMAL1-positive platelet-producing megakaryocytes. Podoplanin (PDPN)-expressing stromal cells generate a microenvironment that promotes megakaryopoiesis in the bone marrow. In this context, PDPN interacts with C-type lectin-like receptor-2 (CLEC-2) on megakaryocyte progenitors, which induces megakaryocyte proliferation. However, the megakaryocyte subtypes developed by the regulation of the PDPN/CLEC-2 axis have not yet been elucidated., Materials and Methods: We established an immortalized bone marrow PDPN-expressing stromal cell line and a PDPN-knockout line (PDPN WT and KO feeder cells, respectively). Bone marrow hematopoietic progenitors were committed to megakaryocytes in co-culture with PDPN WT or KO feeder cells. The number and ploidy of megakaryocytes, resultant platelets, and the polarization of megakaryocyte subtypes were investigated., Results: The number of megakaryocytes was significantly increased in the co-culture with PDPN WT feeder cells compared to that with PDPN KO feeder cells. The megakaryocytes on the PDPN WT and KO feeders showed their main ploidy at 16 N∼32 N and 8 N∼16 N, respectively. The number of platelets was decreased in the co-culture with the PDPN WT feeder compared to that in the co-culture with the PDPN KO feeder. For each megakaryocyte subtype, the percentage of MYLK4-positive megakaryocytes significantly increased and the percentage of BMAL1-positive megakaryocytes significantly decreased when co-cultured with the PDPN WT feeder. These results were also confirmed in the co-culture of CLEC-2 conditional KO megakaryocytes with PDPN WT feeder cells., Conclusion: The PDPN/CLEC-2 axis modulates megakaryocyte subtype differentiation, with a predominance of HSC-regulating megakaryocytes., 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 solid-solution aqueous-solution (SSAS) system often involves dissolution/precipitation and redox reactions simultaneously. Comprehensive understanding of the SSAS system requires mechanistic insights into the dissolution mechanism of the solid solution based on reliable characterisation of the solid phases. Given this background, this study investigates the dissolution behaviour of zirconium-cerium oxide solid solution ((Zr,Ce)O 2 /(Ce,Zr)O 2 ), which contains the redox-active metal Ce (Ce(III/IV)) and is of particular importance in the nuclear industry. The solid phases of the solid solution were comprehensively characterised by powder X-ray diffraction (PXRD) with Rietveld analysis and X-ray absorption spectroscopy (XAS) with factor analysis, indicating that the solid solution was primarily composed of tetragonal-(Zr,Ce)O 2 and cubic-(Ce,Zr)O 2 . Water immersion of the solid solution leads to the dissolution of the solid phase at the solid-liquid interface. The addition of a reductant to the system reduces Ce(IV) in the solid solution to -(III) at the surface, promoting the dissolution of Ce from the solid-solution phase. The release of Ce from the solid solution also enriches the Zr content in the remaining solid-solution phase at the surface, which makes it more insoluble. This results in the formation of a protective layer at the solid surface, retarding further dissolution of the solid-solution phase.

Background and Objectives: In the past, microscopic transcranial approach was the mainstay of treatment of trigeminal schwannomas. In recent years, several endoscopic procedures have been reported for trigeminal schwannomas. For trigeminal schwannomas arising around the Meckel cave, we introduced a fully endoscopic procedure with a small temporal craniotomy in June 2020 and have performed radical tumor removal as in the conventional approach. This article describes the details of the purely endoscopic subtemporal keyhole approach (PESKA) surgical procedure and reports the initial surgical results., Methods: Between June 2020 and November 2023, 8 cases of trigeminal schwannoma were treated with PESKA. The mean tumor diameter was 33.1 mm. The surgical procedure for PESKA consists of a 7-cm linear skin incision made upward from the anterior to the auricle on the side of the lesion, followed by a 4-cm temporal craniotomy and then endoscopic manipulation. The intradural part of the middle cranial fossa is observed, and the Meckel cave is identified and opened. The tumor is removed with preserving most normal trigeminal nerve fibers. The site of the lesion, the extent of resection, complications, operative time, Karnofsky Performance Status, and intraoperative blood loss were evaluated., Results: All 8 patients underwent gross total resection. Only one patient had new temporal edema on the side of the lesion, which was asymptomatic. The mean operative time was 4 hours and 21 minutes., Conclusion: We report on PESKA, a fully endoscopic procedure with a small temporal craniotomy for a trigeminal schwannoma arising around the Meckel cave. The use of an endoscope allowed for a wide field of view, even in a narrow operative field, reducing brain traction and allowing radical resection of the tumor while preserving normal trigeminal nerve fibers. This method may represent an effective surgical alternative for trigeminal schwannomas., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Aim: Atezolizumab/bevacizumab is a first-line therapy for unresectable hepatocellular carcinoma (HCC). Among several adverse events, grade ≥2 proteinuria is considered a significant adverse event that may cause bevacizumab interruption. Studies have shown that proteinuria might predict improved prognosis, although data are scarce and the association remains controversial, and the mechanisms and predictive factors remain unclear. We aimed to clarify these., Methods: In this multicenter retrospective study, we screened patients with HCC treated with atezolizumab/bevacizumab. The prognostic impact of grade ≥2 proteinuria was examined in patients with proper clinical data and preserved serum for growth factor analysis. For biomarker analysis predicting proteinuria, baseline serum vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D levels were analyzed., Results: This study included 75 patients, and 32 (42.7%) experienced grade ≥2 proteinuria. No significant differences were observed between those with or without proteinuria, except for aspartate transaminase and alanine transaminase levels. Time-dependent Cox proportional hazards analysis revealed that grade ≥2 proteinuria was significantly associated with better prognosis (hazard ratio 0.221; 95% confidence interval 0.082-0.592; p = 0.003). In biomarker analysis, low baseline serum VEGF-C and VEGF-D levels were significantly associated with proteinuria, and multivariate analysis demonstrated that baseline serum VEGF-D level was significantly associated with grade ≥2 proteinuria (hazard ratio 0.101; 95% confidence interval 0.029-0.357; p < 0.001)., Conclusions: Grade ≥2 proteinuria in patients with unresectable HCC treated with atezolizumab/bevacizumab indicates a better prognosis, and baseline serum VEGF-D levels can help predict its occurrence. These findings can help in managing adverse events and prognosis in advanced HCC treated with atezolizumab/bevacizumab., (© 2024 Japan Society of Hepatology.)

To reveal the differences in the properties of visceral adipose tissue in healthy unstimulated mice, we performed transcriptome analysis using RNA sequencing. Among visceral adipose tissues, perinephric adipose tissue was found to exclusively express beige adipocyte markers while expressing white adipocyte markers. These results imply potential specific roles of perinephric adipose tissue in both physiological and pathological conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Objectives: Advances in diagnosing carpal tunnel syndrome (CTS) using ultrasonography (US) and artificial intelligence (AI) aim to replace nerve conduction studies. However, a method for accurate severity diagnosis remains unachieved. We explored the potential of comprehensive video data formats for constructing an effective model for diagnosing CTS severity., Methods: We studied 75 individuals (52 with CTS) from 2019 to 2022, categorizing them into 3 groups based on disease severity. We recorded 132 US videos of carpal tunnel during finger movement. Features of the median nerve (MN) were extracted from automatically segmented US video frames, from which 3 datasets were created: a comprehensive video dataset with full information, a key metrics dataset, and an initial frame dataset with the least information. We compared the accuracy of machine learning algorithms for classifying CTS severity into 3 groups across these datasets using 63-fold cross-validation., Results: The cross-sectional area of the MN correlated with severity (P < .05) but MN displacement did not. The algorithm using the comprehensive video dataset exhibited the highest sensitivity (1.00) and accuracy (0.75)., Conclusions: Our study demonstrated that utilizing comprehensive video data enables a more accurate US-based diagnosis of CTS severity. This underscores the value of capturing the patterns of MN deformation and movement, which cannot be captured by representative metrics such as medians or maximums. By further developing an AI model based on our findings, a simpler and painless method for assessing CTS severity can be achieved., (© 2024 The Author(s). Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

The persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among wildlife populations poses a potential risk for the emergence of novel variants. Therefore, monitoring SARS-CoV-2 infections in animals is crucial. As urban rodents live in close proximity to human habitats, there is a concern that they may be a potential source of zoonoses. To examine the prevalence of SARS-CoV-2 in rodent populations, we analyzed 128 serum samples and 129 oral swabs collected from 128 brown rats (Rattus norvegicus) and two black rats (Rattus rattus) captured for pest control purposes in Tokyo, Japan, between May and December 2023. A virus-neutralizing test using the omicron variant revealed no evidence of SARS-CoV-2 infection. Real-time reverse transcription- PCR of oral swabs did not detect any SARS-CoV-2 RNA-positive rats. These results indicate a low probability of SARS-CoV-2 circulation among rat populations in Tokyo.

Introduction: We encountered a case of adenocarcinoma of the ectopic pancreas, causing intussusception., Case Presentation: A 76-year-old man presented with complaints of abdominal distention and vomiting to the emergency department in March 2022. Computed tomography showed that the small bowel piled up approximately 20 cm from the ligament of the traits. Endoscopic repair was challenging; therefore, laparoscopic repair and partial resection of the small bowel were performed. The specimen showed a mass in the small bowel arising from an ectopic pancreas that had caused accumulation. Pathological examination revealed ectopic pancreatic cancer. Two years postoperatively, no apparent recurrence has been observed. We report a relatively rare case of a cancerous ectopic jejunal pancreas causing a mass, with a discussion in the literature., Conclusions: Detection typically requires surgery due to advanced-stage intestinal obstruction or accumulation, as observed in the present case. However, preoperative diagnosis and early detection of ectopic pancreatic cancer are challenging. The disease progresses similarly to pancreatic cancer, highlighting the need for early detection methods. Additionally, accumulating more case reports is essential for establishing an effective treatment strategy., Competing Interests: Declarations Ethics approval and consent to participate Our case report was approved by the ethics committee and the director of our hospital. Consent for publication The patient provided informed consent for the publication of this report. Competing interests The authors declare no competing interests with respect to this report., (© 2024. The Author(s).)

The advancement of irradiation technology has increased the demand for quality control of radiation therapy equipment. Consequently, the number of quality control items and required personnel have also increased. However, differences in the proportion of qualified personnel to irradiation techniques have caused bias in quality control systems among institutions. To standardize the quality across institutions, researchers should conduct mutual quality control by analyzing the quality control data of one institution at another institution and comparing the results with those of their own institutions. This study uses failure mode and effects analysis (FMEA) to identify potential risks in 12 radiation therapy institutions, compares the results before and after implementation of mutual quality control, and examines the utility of mutual quality control in risk reduction. Furthermore, a cost-effectiveness factor is introduced into FMEA to evaluate the utility of mutual quality control., Competing Interests: Declarations Conflict of interest The authors have no relevant financial or non-financial interests to disclose. Partial financial support was received from NHO Radiological Technologists. Ethical approval All procedures performed in this study involving human participants were in accordance with the ethical standards of the Institutional Research Committee and the 1964 Helsinki Declaration. Standards of animal rights This study did not involve any animal experimentation. Informed consent Informed consent was obtained from all the participants included in the study., (© 2024. The Author(s).)

The prediction of cytochrome P450 inhibition by a computational (quantitative) structure-activity relationship approach using chemical structure information and machine learning would be useful for toxicity research as a simple and rapid in silico tool. However, there are few in silico models focusing on the species differences between rat and human in the P450s inhibition. This study aimed to establish in silico models to classify chemical substances as inhibitors or non-inhibitors of various rat and human P450s, using only molecular descriptors. Using the in-house test results from our in vitro experiments, we used 326 substances for model construction and internal validation data. Apart from the 326 substances, 60 substances were used as external validation data set. We focused on seven rat P450s (CYP1A1, CYP1A2, CYP2B1, CYP2C6, CYP2D1, CYP2E1, and CYP3A2) and 11 human P450s (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). Most of the models established using XGBoost showed an area under the receiver operating characteristic curve (ROC-AUC) of 0.8 or more in the internal validation. When we set an applicability domain for the models and confirmed their generalization performance through external validation, most of the models showed an ROC-AUC of 0.7 or more. Interestingly, for CYP1A1 and CYP1A2, we discovered that a human P450 inhibitory activity model can predict rat P450 inhibitory activity and vice versa. These models are the first attempts to predict inhibitory activity against a wide variety of P450s in both rats and humans using chemical structure information. Our experimental results and in silico models would be helpful to support information for species similarities and differences in chemical-induced toxicity.

TEPCO planned the release of Advanced Liquid Processing System (ALPS)-treated water, which is decontaminated stagnated water by ALPS, to the Pacific Ocean in 2023 after diluting it more than a hundred times in accordance with the policy of the Japan government. Since the low level of I-129 can remain in ALPS-treated water, the background I-129 concentration in seaweed samples around 1F NPS before the release of ALPS-treated water was recorded in this study. The iodine in seaweed samples was extracted via TMAH alkali-dissolution, and the I-129 concentration was measured by 8900 Triple Quadrupole ICP-MS. The resulting I-129 concentration was <5.4 × 10-2 Bq/kg-wet (sargassum) and <2.7 × 10-2 Bq/kg-wet (laminaria), respectively., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: The purpose of this study was to evaluate the effect of patient transfer slide boards with automatic couch height positioning compensation (AHC) on image quality and radiation dose during computed tomography (CT) examinations., Methods: The chest phantom for Kyoto Kagaku (Kyoto) Type PBU-SS 2 was performed helical scan using a Canon Medical Systems (Tochigi) 80-row CT Aquilion Prime SP/i Edition. Scan parameters were tube voltage: 120 kV, tube current: min 50 mA max 500 mA with AHC for noise index: 15, slice thickness: 5.0 mm, rotation time: 0.35 s/rotation, pitch factor: 0.813, reconstruction kernel: FC03. Filtered back projection was used for image reconstruction. We compared the image noise and volume computed tomography dose index (CTDI vol ) displayed on the console with and without the patient transfer slide boards by using or not using the AHC., Results: When using the AHC, CTDI vol was increased (p<0.05), and image noise was decreased (p<0.05). Without the AHC, there was no significant difference in CTDI vol (p=0.11) and image noise (p=0.29)., Conclusion: The slide board utilized in this experiment did not have a notable impact on either image quality or exposure dose. Nonetheless, the use of the slide board was found to result in excessive exposure during CT scans that employed AHC.

Calcium oscillations in primary neuronal cultures and iPSCs have been employed to investigate arrhythmogenicity and epileptogenicity in drug development. Previous studies have demonstrated that Ca 2+ influx via NMDA and nicotinic acetylcholine receptors (nAChRs) modulates Ca 2+ oscillations. Nevertheless, there has been no comprehensive investigation into the impact of ischemia or nAChR-positive allosteric modulators (PAM) drugs on Ca 2+ oscillations at a level that would facilitate high-throughput screening. We investigated the effects of ischemia and nAChR subtypes or nAChR PAM agonists on Ca 2+ oscillations in high-density 2D and 3D-sphere primary neuronal cultures using 384-well plates with FDSS-7000. Ischemia for 1 and 2 h resulted in an increase in the frequency of Ca 2+ oscillations and a decrease in their amplitude in a time-dependent manner. The NMDA and AMPA receptor inhibition significantly suppressed Ca 2+ oscillation. Inhibition of NR2A or NR2B had the opposite effect on Ca oscillations. The potentiation of ischemia-induced Ca 2+ oscillations was significantly inhibited by the NMDA receptor antagonist, MK-801, and the frequency of these oscillations was suppressed by the NR2B inhibitor, Ro-256981. In the 3D-neurosphere, the application of an α7nAChR agonist increased the frequency of Ca 2+ oscillations, whereas the activation of α4β2 had no effect. The combination of nicotine and PNU-120596 (type II PAM) affected the frequency and amplitude of Ca 2+ oscillations in a manner distinct from that of type I PAM. These systems may be useful not only for detecting epileptogenicity but also in the search for neuroprotective agents against cerebral ischemia., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics approval All experiments were performed following the Use of Laboratory Animals and ARRIVE guidelines. The Institutional Animal Care and Use Committee of Osaka University Graduate School of Medicine approved all animal protocols and experiments (Permission number: 30-091-001, 05-078-0000). Consent for publication All authors give their consent and approval for publication of this manuscript., (© 2024. The Author(s).)

Background/objective: Laparoscopic myomectomy (LM) is primarily conducted using the pneumoperitoneum method, with only few LMs performed using the gasless method (GLM). We aimed to assess the feasibility of GLM., Methods: This retrospective chart review was performed in a university-affiliated hospital. We included 1301 patients who underwent GLM with the subcutaneous steel wire-lifting method (GLMS) between 2008 and 2021., Results: A total of 6287 fibroids were removed (nodes per patient: 4.83 ± 4.51). Systematic reviews showed that compared with conventional LM, GLMS had longer operation time, greater number and larger size of fibroids removed, and lower intraoperative blood loss. The rates of severe perioperative complications, homologous blood transfusion, and open conversion were acceptable at 0.8 %, 0.5 %, and 0.3 %, respectively. Operation time, weight of surgical specimen, body mass index (BMI), and the maximum diameter of fibroids removed were important predictors of higher risk, including massive surgical bleeding. The prediction model of massive surgical bleeding showed a relatively good out-of-bag estimate of error rate of 8.6 %, with a high negative predictive value, albeit a low positive predictive value, making it unsuitable for real-world clinical applications., Conclusions: GLMS is an excellent procedure that combines safety, proficiency, and economic efficiency for fibroid removal, except in patients with severe obesity. Beyond the cost-benefit perspective, GLMS appears well-suited to countries with low average BMI, such as Japan, East-Asian countries, and LMICs in Africa., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Structural changes in Ru- and Rh-loaded magnesium oxide (MgO) subjected to thermal treatment were investigated by using X-ray absorption spectroscopy. The thermal treatment of the MgO-loaded Ru and Rh nanoparticles led to the formation of Ru-MgO and Rh-MgO solid solutions, respectively. The valences of Ru and Rh in the solutions were 4+ and 3+, respectively, as determined by the Ru and Rh K-edge X-ray absorption near-edge structure (XANES). The degree of solid solution formation was the highest at 873 and 1073 K in Ru-MgO and Rh-MgO, respectively, as observed in the extended X-ray absorption fine structure and XANES analyses. The nearest neighboring Ru-O and Rh-O bond distances were shorter than the Mg-O bond in MgO. The dispersion of Ru and Rh on the MgO surface, measured by CO adsorption, increased for samples thermally heated at 1273 K, suggesting that the segregation of Ru or Rh from the solid solutions occurred at this temperature. Consequently, a relatively high dispersion was realized in the sample thermally heated to 1273 K. A good correlation was found between the dispersion value of Ru in Ru/MgO and the NH 3 decomposition activity., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: The optimal neoadjuvant regimen before radical prostatectomy (RP) in patients with high-risk (HR) prostate cancer (PCa) remains to be determined. This retrospective multicenter cohort study assessed the effectiveness and safety of neoadjuvant chemohormonal therapy (NCHT) in patients with HR-PCa undergoing robot-assisted laparoscopic radical prostatectomy (RALP)., Methods: We reviewed the datasets of 1023 subjects who underwent RALP at nine Japanese facilities between September 2012 and October 2023. The enrolled patients were divided into two groups using propensity score matching: a RALP-alone group and those who underwent NCHT followed by RALP (NCHT group). The NCHT regimen consisted of a luteinizing hormone-releasing hormone antagonist and tegafur-uracil for at least 3 months before RALP. The primary endpoint was biochemical recurrence (BCR) after RALP. The secondary endpoint was the surgical specimen pathology findings., Results: Propensity score matching identified 139 individuals for each group. Median follow-up was 18.2 months. During follow-up, BCR was observed in 41 patients (29.5%) in the RALP-alone group and 22 patients (15.8%) in the NCHT group (p = 0.010). Pathological results showed significantly more organ-confined PCa and significantly fewer positive surgical margins or lymphovascular invasion in the NCHT group than in the RALP-alone group. The 2-yr biochemical recurrence-free survival (BRFS) was 72.7% and 74.7% in the RALP-alone and NCHT groups, respectively (p = 0.086). Two patients (1.4%) experienced grade 3 liver disorder as an NCHT-related adverse event., Conclusion: The results suggest that NCHT can safely treat HR-PCa and may reduce the incidence of BCR when combined with RALP., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit both T cell and B cell immune responses in immunocompetent individuals. However, the mechanisms underlying the antiviral effects mediated by CD4 + T cells are not fully understood. In this study, we analyzed the culture supernatant (SN) from polyclonally stimulated human CD4 + T cells as a model for soluble mediators derived from SARS-CoV-2-stimulated CD4 + T cells. Interestingly, this SN inhibited SARS-CoV-2 propagation in a viral strain- and host cell type-dependent manner. The original wild-type showed the highest susceptibility, whereas the Delta variant exhibited resistance in the human monocyte cell line. In addition, antibody-dependent enhancement (ADE) of infection with the original strain was also abolished in the presence of the SN. The findings showed that the inhibitory effect on viral propagation by the SN was mostly attributed to interferon-γ (IFN-γ) that was present in the SN. These results highlight the potential role of IFN-γ as an anti-SARS-CoV-2 mediator derived from CD4 + T cells, and suggest that we need to understand the SARS-CoV-2 strain-dependent sensitivity to IFN-γ in controlling clinical outcomes. In addition, characterization of new SARS-CoV-2 variants in terms of IFN-γ-sensitivity will have important implications for selecting therapeutic strategies., (© 2024. The Author(s).)

Diabetic kidney disease (DKD) is a major disease characterized by early albuminuria and heightened risk of renal deterioration. Increased reactive oxygen species (ROS) production, especially in glomeruli, plays an important role in the progression of DKD. ROS also cause activation of Apoptosis signal-regulating kinase 1 (ASK-1), which is implicated in various organ injuries. However, the detailed mechanisms remain unclear. This study investigates ASK-1 activation in advanced DKD and its underlying mechanisms using GS442172, an ASK-1 inhibitor. In the DKD mouse model, activation of ASK-1 was observed. Although inhibition of ASK-1 activation improved hyperpermeability in glomerular endothelial cells. ASK-1 inhibition significantly reduced glomerular injury and albuminuria, while also attenuating tubular damage and interstitial fibrosis. RNA-seq analysis revealed an aging phenotype associated with ASK-1 activation in DKD. In vitro experiments demonstrated ASK-1 activation-induced cellular senescence in tubular cells via redox signaling. These results suggested that the critical role of ASK-1 activation in DKD pathogenesis, implicating glomerular injury, tubular damage, and cellular senescence. ASK-1 inhibitors are promising therapeutic strategies to mitigate the progression of DKD., (© 2024. The Author(s).)

Background: Transbronchial lung cryobiopsy is primarily used for diagnosing interstitial lung diseases and tumors, providing larger tissue samples with reduced tissue crushing than traditional biopsies. However, freezing during cryobiopsy may damage cells, potentially affecting diagnostic methods that require live cells, such as flow cytometry (FCM). We aimed to determine the extent of freezing-related cell damage in cryobiopsies using cells cultured in vitro., Methods: To investigate the relationship between freezing duration and sample volume, Jurkat cells underwent freezing for durations ranging from 2 to 6 s, with 1-s intervals, using either 1-mm- or 1.7-mm cryoprobes. FCM was conducted to assess both cell viability (2, 4, and 6 s) and cell-surface molecule expression (3 and 6 s) over varying freezing times. Additionally, we describe a clinical case involving a 70-year-old man suspected of malignant lymphoma, in which tissue samples were obtained via both forceps biopsy and cryobiopsy methods to compare the pathological and cytological features between the methods., Results: Harvested cell count increased with freezing duration, with a notable increase in viable cell percentage. Moreover, cells distant from the cryoprobe exhibited higher survival rates under milder freezing conditions. FCM revealed significantly higher marker expression levels in viable cryobiopsy samples than in non-viable samples. The clinical case demonstrated that cryobiopsy yields a significant proportion of live cells (>90%), with cytological findings consistent with those of non-frozen samples., Conclusions: Cryobiopsy may be beneficial for histopathological diagnosis, providing sufficient viable cells for FCM, and can be used for diagnosing malignant lymphomas and other pulmonary conditions., Competing Interests: Declaration of competing interest YM has received honoraria from AstraZeneca and GlaxoSmithKline. The other authors have no conflicts of interest., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Background/objective: Caveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC)., Methods: Tissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1 high vs. cCav1 low ) or cancer-associated fibroblasts (fCav1 high vs. fCav1 low )., Results: Among all 615 patients, 40.7% were cCav1 high and 72.7% were fCav1 high . cCav1 high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1 low , and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1 high patients with NAC showed better OS than those without, while there was no significant difference between cCav1 low patients with NAC and those without. cCav1 high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1 high as an independent predictor of liver metastasis., Conclusions: cCav1 high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1 high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: Endothelial dysfunction plays an important role in the pathogenesis of chronic kidney disease. Prostacyclin (PGI 2 ), an endothelial cell-produced endogenous prostaglandin, plays a crucial role in maintaining endothelial function. However, its effects on intestinal microcirculation and barrier function are not fully understood. We hypothesized that PGI 2 improves intestinal microcirculation and barrier function via endothelial protective effects., Methods: ICR and ICGN (a spontaneous nephrotic model) mice were used in this study. Intestinal microcirculation was visualized in vivo to investigate PGI 2 effects. Beraprost served as PGI 2 . PGI 2 administration spanned 4 weeks, following which we assessed its influence on intestinal endothelial, intestinal barrier, and renal functions., Results: We visualized intestinal microcirculation and endothelial glycocalyx in the intestinal blood vessels. Beraprost administration induced a 1.2-fold dilatation of the vascular diameter of the small intestine. Intestinal blood flow in ICGN mice was significantly reduced compared that in ICR mice but improved with beraprost administration. ICGN mice exhibited reduced serum albumin levels, decreased ambulation, an imbalance in intestinal reactive oxygen species (ROS)/nitric oxide (NO), and impaired tight junctions; all were ameliorated by beraprost administration., Conclusions: Beraprost improves intestinal microcirculation and barrier function by ameliorating ROS/NO imbalances, thereby reducing physical inactivity during renal failure., (© 2024 The Author(s). Microcirculation published by John Wiley & Sons Ltd.)

Introduction: Post-operative complications of corpus callosotomy (CC) in children, prolonged hospitalization due to inactivity as acute disconnection syndrome is occasionally experienced. We aimed to clarify this issue and its risk factors with a hypothesis that electroencephalogram (EEG) findings as measures of functional lateralization may be among prognostic factors for post-operative recovery., Materials and Methods: Twenty-three patients with childhood-onset drug-resistant epilepsy who underwent total CC between April 2017 and December 2023 were included in the study and they were divided into two groups based on the duration of post-operative hospitalization as an indicator of recovery of daily living activity. We compared scalp EEG findings and the other factors including clinical characteristics between the two groups., Results: Of 22 patients (14 males) without specific complications, post-operative hospitalization clustered in 9-14 days in 15 patients (Group A) with range 16-118 days in seven patients (Group B). The ratios of patients with non-lateralized spikes on pre-operative EEG and that of patients with symmetric background activity on post-operative EEG were significantly greater in Group B (7/7, 100 %; 6/7, 86 %, respectively) than in Group A (8/15, 53 %; 4/15, 27 %, respectively) (p = 0.038; p = 0.020, respectively, by Fisher's exact test), while other factors were not significantly different between the two groups., Conclusions: Delayed recovery of living activity should be anticipated, especially in patients with non-lateralized epileptic discharges on pre-operative EEG., Competing Interests: Declaration of competing interest The authors have no other conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps., Methods: We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC., Results: A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC., Conclusions: In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis., (© 2024 John Wiley & Sons Ltd.)

Background: Acute kidney injury (AKI) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition., Methods: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values., Results: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m 2 ) = 0.375 × PV (cm 3 ) + (- 0.395) × age (years) + (- 2.93) × male sex + (- 13.3) × hypertension + (- 14.0) × diabetes + (- 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001)., Conclusions: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted., Competing Interests: Declarations Conflict of interest The are no conflicts of interests to be disclosed.Ethical approval.This study was approved by the Institutional Review Board of the Jikei University School of Medicine (IRB nos. 35–159 [11788] and 35–165 [11794]) and was conducted in accord with the Declaration of Helsinki. Informed consent Because this was a retrospective cohort study, information on the research plan was posted; an opportunity to refuse participation was provided, and individual informed consent was not required., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Osteoporosis is a global issue with a worldwide prevalence of 18.3%, and the presence of coexisting fragility fractures can reduce the survival rate by approximately 20%. In Japan, the prevalence of osteoporosis is estimated to be 12.8 million, and the annual occurrence of hip fractures is approximately 193,400. Remarkably, coexisting hip or spinal fragility fractures caused by slight external force meet the Japanese diagnostic criterion for osteoporosis regardless of bone mineral density. However, only 191 deaths due to osteoporosis were published in 2021 in Japan. With the concern that some cases of hip and spinal fragility fractures were assigned an underlying cause of death of traumatic fracture instead of osteoporosis, this study aimed to elucidate the actual number of deaths due to osteoporosis in Japan., Methods: We used the data from Japan in 2018. First, the number of deaths due to osteoporosis and hip or spinal fractures was reviewed using published vital statistics. Second, we calculated the number of elderly deaths (age ≥80 years) resulting from hip or spinal fractures caused by falls on the same level using data from approximately 1.4 million annual individual death certificates. Combining the above data, the actual number of deaths due to osteoporosis was estimated., Results: Only 190 deaths due to osteoporosis were reported in the published data. The individual certificate data revealed 3437 elderly deaths due to hip or spinal fractures caused by falls on the same level, which could meet the criteria of osteoporotic fragility fractures. Accordingly, the estimated number of deaths caused by osteoporosis was calculated as 3,627, approximately 19 times the published value., Conclusions: After researching the individual death certificate data focusing on the coexisting hip or spinal fragility fracture, it was implied that osteoporosis may have a higher mortality rate in Japan than what is published., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.

Background: Safety data of the latest radiofrequency (RF) technologies during atrial fibrillation (AF) ablation in real-world clinical practice are limited., Objectives: We sought to evaluate the acute procedural safety of the four latest ablation catheters commonly used for AF ablation., Methods: A total of 3957 AF ablation procedures performed between January 2022 and December 2023 at 20 centers with either the THERMOCOOL SMARTTOUCH SF (STSF), TactiCath (TC), QDOT Micro (QDM), or TactiFlex (TF) were retrospectively analyzed., Results: In total, QDM, STSF, TF, and TC were used in 343 (8.7%), 1793 (45.3%), 1121 (28.4%), and 700(17.7%) procedures. Among 2406 index procedures, electrical pulmonary vein isolations were successfully achieved in 99.5%. Despite similar total procedure times in the four groups, the total fluoroscopic time was significantly shorter for QDM/STSF with CARTO than TF/TC with EnSite (18.7 ± 14 vs. 27.6 ± 20.6 min, p < .001) and longest in the TF group. The incidence of cardiac tamponade was 0.7% (0.5% and 0.9% during index and redo procedures, 0.8% and 0.3% for paroxysmal and non-paroxysmal AF) and was significantly lower for QDM/STSF than TF/TC (0.2% vs. 1.1%, p = .008) and highest in the TF group. The incidence of cardiac tamponade was higher for TF than TC and STSF than QDM. In the multivariate analysis, TF/TC with EnSite was a significant independent predictor of cardiac tamponade during both the index (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.5, p = .02) and all procedures (OR = 3.0, 95% CI = 1.3-7.2, p = .01)., Conclusions: The incidence of cardiac tamponade and the fluoroscopic time during AF ablation significantly differed among the latest RF catheters and mapping systems in real-world clinical practice., (© 2024 Wiley Periodicals LLC.)