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Marine sediments play a crucial role in the global carbon cycle by acting as the ultimate sink of both terrestrial and marine organic carbon. To understand the spatiotemporal variability in the content, sources, and dynamics of organic carbon in marine sediments, a curated and harmonized database of organic carbon and associated parameters is needed, which has prompted the development of the Modern Ocean Sediment Archive and Inventory of Carbon (MOSAIC) database (http://mosaic.ethz.ch/, last access: 26 July 2023; https://doi.org/10.5281/zenodo.8322094, Paradis, 2023; https://doi.org/10.5168/mosaic019.1, Van der Voort et al., 2019​​​​​​​). MOSAIC version 2.0 has expanded the spatiotemporal coverage of the original database by >400 % and now holds data from more than 21 000 individual sediment cores from different continental margins on a global scale. Additional variables have also been incorporated into MOSAIC v.2.0 that are crucial to interpret the quantity, origin, and age of organic carbon in marine sediments globally. Sedimentological parameters (e.g. grain size fractions and mineral surface area) help understand the effect of hydrodynamic sorting and mineral protection on the distribution of organic carbon, while molecular biomarker signatures (e.g. lignin phenols, fatty acids, and alkanes) can help constrain the specific origin of organic matter. MOSAIC v.2.0 also stores data on specific sediment and molecular fractions, which provide further insight into the processes that affect the degradation and ageing of organic carbon in marine sediments. Data included within MOSAIC are continuously expanding, and version control will allow users to benefit from updated versions while ensuring reproducibility of their findings.

Abstract This article describes the setup and performance of the near and far detectors in the Double Chooz experiment. The electron antineutrinos of the Chooz nuclear power plant were measured in two identically designed detectors with different average baselines of about 400 m and 1050 m from the two reactor cores. Over many years of data taking the neutrino signals were extracted from interactions in the detectors with the goal of measuring a fundamental parameter in the context of neutrino oscillation, the mixing angle $$\theta _{13}$$ θ 13 . The central part of the Double Chooz detectors was a main detector comprising four cylindrical volumes filled with organic liquids. From the inside towards the outside there were volumes containing gadolinium-loaded scintillator, gadolinium-free scintillator, a buffer oil and, optically separated, another liquid scintillator acting as veto system. Above this main detector an additional outer veto system using plastic scintillator strips was installed. The technologies developed in Double Chooz were inspiration for several other antineutrino detectors in the field. The detector design allowed implementation of efficient background rejection techniques including use of pulse shape information provided by the data acquisition system. The Double Chooz detectors featured remarkable stability, in particular for the detected photons, as well as high radiopurity of the detector components.

Ferroelectric nematic liquid crystals (NFLCs) are promising electronic materials owing to their giant permittivity, polarization, and nonlinear optical coefficients. Although it is difficult to polymer-stabilize the NFLC orientation state due to their low affinity to polymers, in this study, we have succeeded in stabilizing the orientation into a blue phase (BP) three-dimensional structure by using BP polymer networks. This BP polymer-templated NFLC retains their ferroelectric properties and stabilizes with macroscopically canceled polarization due to the BP structure. The large polarization and dielectric constant of the NFLCs resulted in a large electro-optical Kerr effect. In addition, Curie point was observed in the BP polymer-templated NFLC, indicating the existence of multiple kinetic modes in the NFLCs themselves. This breakthrough expands the range of applications for both BPs and NFLCs.

Adhesive contact phenomena play a crucial role in various scientific and engineering fields. However, considering viscoelasticity, which is essential for understanding practical applications involving soft materials like polymers, makes analysis challenging. Traditional elastic contact models such as the Johnson-Kendall-Roberts and Maugis-Dugdale models often fail to account for viscoelastic behavior. In this study, rate-dependent viscoelastic adhesive contacts were analyzed using atomic force microscopy force-distance curve measurements, comparing the elastic models with the viscoelastic model proposed by Barthel. The force curve analysis, conducted with the Barthel model for the first time, reveals that viscoelastic behaviors inside the contact area and the interaction zone both affect the contact state. These viscoelastic behaviors result in phenomena specific to viscoelastic contact, such as the "stick region" and the apparent work of adhesion. The Barthel model successfully captures the rate dependence of the contact situation, promoting a comprehensive understanding of viscoelastic adhesive contact phenomena.

Purpose: To establish an ultra-high dose rate (UHDR) radiation system using a synchrotron proton beam accelerator and to compare the effects by irradiation positions on cultured cells and chick embryos., Methods and Materials: Protons for UHDR were obtained by applying high-frequency power at much higher levels than usual to extract all protons within approximately 50 ms. Subsequently, monitoring with a Faraday cup was performed immediately after synchrotron extraction and the waveform was adjusted accordingly. Four cultured tumor lines, two normal cell lines, and chick embryos were used. Ultra-high dose-rate radiation (UHDR-RT) at 6-18 Gy (200-300 Gy/s, single exposure) and conventional dose-rate radiation (Conv-RT) at 6-18 Gy (3 Gy/s) were administered to the 1-cm spread-out Bragg peak (SOBP) and the plateau region preceding SOBP. Following irradiation, disparities in cell growth rates and cell cycle progression were assessed, and cell survival was evaluated via colony assay. Chick embryos were also examined for survival., Results: UHDR-RT was achieved at a range of 40 to 800 Gy/s, encompassing both plateau and peak phases. In vitro studies demonstrated similar cell-killing effects between UHDR-RT and Conv-RT in cancer cells. Significant apoptotic effects and G2 arrest were observed during the cell cycle under peak UHDR-RT conditions. The FLASH effect was not observed in normal single cells under normal atmospheric conditions. Stronger cell-killing effects were noted in V79 spheroids exposed to peak UHDR-RT than peak Conv-RT. Moreover, in chick embryos, an increase in survival rate, indicative of the FLASH effect, was observed., Conclusions: The FLASH effect was also achieved with UHDR-RT using a synchrotron proton beam accelerator in chick embryos. The cell-killing effects in cancer cells were higher with peak UHDR-RT which may be due to the higher linear energy transfer at the SOBP., Competing Interests: Declaration of competing interest Masumi Umezawa and Masashi Yamada are the permanent employees of Hitachi High-Tech Corporation. The authors declare this does not alter their adherence to IJROBP policies on sharing data and materials., (Copyright © 2024. Published by Elsevier Inc.)

Background: Various techniques have been used to prevent smudge on a laparoscope when inserting through trocars; however, there has been no standardized method. The purpose of this study was to compare the performance of different cleaning techniques with or without using dedicated devices, and to evaluate the features of cleaning devices., Methods: The smudge was created in the standard 12-mm and 5-mm ports using pseudo-blood, and port cleaning was attempted using 5 different methods: (1) a surgical gauze + surgical forceps, (2) a surgical gauze + laparoscopic forceps, (3) a small laparoscopic gauze + laparoscopic forceps, (4) a cylinder-type cleaner (Endo Wiper; Osaki Medical), and (5) a swab-type cleaner (Port Cleaner; Hakuzo Medical). The "port cleaning rate" was calculated by measuring the absorbance of remained pseudo-blood after single cleaning procedure using UV spectrophotometry. In addition, the port cleaning rate was compared between two dedicated devices after multiple (5 times) cleaning procedures., Results: The two dedicated devices had a statistically higher cleaning rate for 12-mm port than the methods using surgical gauze (p < 0.05). Regarding the 5-mm port, a swab-type cleaner showed the highest cleaning rate than the gauze method and a cylinder-type cleaner (p < 0.05). After multiple cleaning procedures for 12-mm port, cleaning rate of a swab-type cleaner decreased by an average of 5.4% (p = 0.044), but cleaning rate did not decrease for a cylinder-type cleaner. Regarding the 5-mm port, cleaning rate statistically decreased for both two dedicated devices (p < 0.01)., Conclusion: Higher port cleaning rates were observed in techniques using dedicated devices. A swab-type cleaner had better port cleaning rate in single use, especially for the 5-mm port. A cylinder-type cleaner showed higher durability in cleaning 12-mm port. The features of these dedicated devices should be well understood, and cleaning methods should be selected according to the environment and surgical techniques., Competing Interests: Declarations Disclosures All the authors (Shinnosuke Nagano, Shota Fujii, Kota Momose, Kotaro Yamashita, Takuro Saito, Koji Tanaka, Kazuyoshi Yamamoto, Tomoki Makino, Tsuyoshi Takahashi, Yukinori Kurokawa, Hidetoshi Eguchi, Yuichiro Doki, Kiyokazu Nakajima) have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s).)

Objective: Facet joint destruction causes postoperative spinal instability, resulting in poor clinical outcomes after lumbar decompression surgery. However, the effect of facet joint destruction on radiographic and clinical outcomes after microendoscopic laminectomy (MEL) is unknown. Therefore, the current study aimed to examine the effect of facet joint resection on radiographic and clinical outcomes after single-level MEL surgery., Methods: This study included 116 patients with lumbar spinal canal stenosis (LSCS) who underwent single-level (L4/5) MEL surgery. Eligible patients were divided into the following groups: group P (facet joint preservation rate = 100%) (n = 70); group PR (50% ≤ the facet joint preservation rate <100%) (n = 27); and group R (the facet joint preservation rate <50%) (n = 19). The demographic characteristics of the patients, surgical data, preoperative and 1-year postoperative radiographic measurements, and clinical outcomes were compared among the 3 groups. Moreover, preoperative and postoperative radiographic and clinical outcomes were compared after adjusting the demographic characteristics of the patients and surgical data by the inverse probability weighting method with propensity scores., Results: The 3 unweighted groups did not significantly differ in terms of demographic characteristics, surgical data, and preoperative and postoperative radiographic and clinical outcomes. Even after adjusting for the demographic characteristics and surgical data, the preoperative and postoperative radiographic and clinical outcomes were comparable among the 3 weighted groups., Conclusions: The extent of facet joint resection might have a minimal impact on radiographic and clinical outcomes at 1 year after single-level MEL surgery., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effects of trabeculectomy on the rate of deterioration of the central visual field (VF) in patients with normal-tension glaucoma (NTG), as revealed by refraction values., Study Design: Retrospective case series., Methods: We retrospectively analyzed 28 eyes, including 12 high myopic (spherical equivalent [SE] < - 6 diopters without pathological myopia) and 16 non-high myopic (SE ≥ - 6 diopters) eyes. The rate of VF deterioration (dB/year) was determined using linear regression analysis of 30 -2 and 10 -2 VF tests. The Wilcoxon signed-rank test was used to compare deterioration rates between groups. To assess the influence of initial post-surgery effects, statistical analyses were conducted with and without data from the initial postoperative VF exam., Results: Trabeculectomy significantly reduced intraocular pressure (IOP) in myopic (14.1 to 9.0 mmHg, P ≤ 0.01) and non-myopic (13.4 to 9.5 mmHg, P ≤ 0.01) eyes. Postoperatively, the 10-2 VF deterioration rate significantly decreased in myopic (- 1.31 to - 0.55 dB/year, P = 0.01) and non-myopic (- 0.80 to - 0.30 dB/year, P = 0.03) eyes. Excluding the first postoperative VF exam, the deterioration rates were - 0.51 ± 0.24 dB/year and - 0.54 ± 0.89 dB/year, respectively, indicating a minor impact on progression assessment., Conclusions: Trabeculectomy may mitigate central VF deterioration in myopic NTG patients, emphasizing the potential benefits of timely surgical intervention. Further studies are needed to determine the optimal timing for surgery., (© 2024. The Author(s).)

Smoc1 and Smoc2, members of the SPARC family of genes, encode signaling molecules downstream of growth factors such as the TGF-β, FGF, and PDGF families. Smoc1 has been implicated in playing a crucial role in microphthalmia with limb anomalies in humans and mice, while Smoc2 deficiency causes dental developmental defects. Although developmental cytokines/growth factors including TGF-β superfamily have been shown to play critical roles in postnatal spermatogenesis, there are no reports analyzing the spatial and temporal expression of Smoc1 and Smoc2 in the postnatal testis. In this study, we investigated the mRNA and protein expression of Smoc1 and Smoc2 in neonatal, juvenile, and adult mouse testes by RNA in situ hybridization, immunofluorescence, and single-cell RNA-seq analysis. We show that Smoc1 and Smoc2 have distinct expression patterns in male germ cells: Smoc1 is more highly expressed than Smoc2 in the germline. In contrast, Smoc2 is highly expressed in testicular somatic cells from neonatal to juvenile stages. The Smoc2-expressing cells then switch from somatic cells to germ cells in adults. Thus, although SMOC1 and SMOC2 proteins are structurally very similar, their spatial and temporal expression patterns in the postnatal testis differ significantly, suggesting their distinct roles in reproduction., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Magnesium alloys have great potentials as bioabsorbable implants, whereas the difficulty in evaluating hydrogen gas produced in the degradation process has hindered their research and development. In this study, we investigated the possibility of industrial microfocus X-ray computed tomography (micro-CT) for the precise evaluation of subcutaneous emphysematous changes in a rabbit implantation model., Methods: Magnesium plates with/without porous venting were implanted under skin defects on the backs of rabbits. The graft sites were examined by industrial micro-CT after sacrificing. The captured images were reconstructed three-dimensionally for volumetric analyses. The tissues of the graft site were also examined in the traditional histological investigation., Results: We were able to image and numerate the shape and volume of subcutaneous emphysema using industrial micro-CT. The volume of emphysema was suppressed by pores punched in samples, and this trend increased as the number of pores increased. In the traditional histological examination, inflammatory changes were observed, but the emphysema could not be measured quantitatively., Conclusions: Industrial micro-CT imaging makes it possible to visualize and evaluate magnesium-induced subcutaneous emphysema in animal experiment. This cross-border technology has the potential to be widely applied to other life science fields.

Background Context: Low back pain (LBP) frequently occurs in patients with lumbar disc herniation (LDH), however the extent to which discectomy ameliorates it and how preoperative LBP influences postoperative outcomes remains unclear., Purpose: To evaluate the improvement in LBP and its impact on postoperative patient-reported outcome measures (PROMs)., Study Design/setting: Multicenter retrospective observational study., Patient Sample: Patients undergoing discectomy for LDH at 8 hospitals from April 2017 to March 2021., Outcome Measures: Data were collected on patients' backgrounds, operative factors, and PROMs, including the Numeric Rating Scale (NRS) for pain in the low back, buttock, or leg, EuroQol 5 Dimension (EQ-5D), Oswestry Disability Index (ODI) scores, and postoperative satisfaction., Methods: Patients were categorized into mild (NRS 0-3), moderate (NRS 4-7), or severe (NRS 8-10) LBP groups. Inverse probability weighting with propensity scores was used to adjust for demographic and clinical differences between groups. Chi-square tests and one-way analysis of variance were conducted to compare background data and clinical characteristics. Additionally, multivariate logistic regression was performed to identify risk factors for less than 50% improvement in LBP., Results: This study included 928 patients: 270 mild, 343 moderate, and 315 severe. After adjustment, preoperative NRS scores were significantly different across groups, with scores of 1.6 (SD 1.3), 5.6 (SD 1.0), and 8.8 (SD 0.9), respectively. Postoperative NRS scores also varied significantly, with worse outcomes observed in the severe group compared to the mild group, yet similar to the moderate group. A total of 46.8% of the mild group, 86.6% of the moderate group, and 72.9% of the severe group achieved a 50% decrease in NRS scores of LBP. Preoperative EQ-5D and ODI scores were significantly worse in the severe group compared to the mild or moderate groups, but postoperative scores were not significantly different between the severe and moderate groups. No significant differences in postoperative satisfaction were observed among the groups. Being female was a significant risk factor for less than 50% improvement in LBP (odds ratio = 1.56, p=.022)., Conclusions: Discectomy significantly improved LBP in patients with LDH, including those with moderate or severe LBP. Patients with severe LBP showed similar improvements in PROMs as those with moderate LBP. Female gender emerged as a significant risk factor for less than optimal improvement in LBP., Competing Interests: Declaration of competing interest During the preparation of this work, the authors used ChatGPT4 in order to assist with the English language editing. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer., Methods: We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo., Results: In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index., Conclusions: We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: There is an increasing demand for automated surgical skill assessment to solve issues such as subjectivity and bias that accompany manual assessments. This study aimed to verify the feasibility of assessing surgical skills using a surgical phase recognition model., Methods: A deep learning-based model that recognizes five surgical phases of laparoscopic sigmoidectomy was constructed, and its ability to distinguish between three skill-level groups-the expert group, with a high Endoscopic Surgical Skill Qualification System (ESSQS) score (26 videos); the intermediate group, with a low ESSQS score (32 videos); and the novice group, with an experience of < 5 colorectal surgeries (27 videos)-was assessed. Furthermore, 1 272 videos were divided into three groups according to the ESSQS score: ESSQS-high, ESSQS-middle, and ESSQS-low groups, and whether they could be distinguished by the score calculated by multiple regression analysis of the parameters from the model was also evaluated., Results: The time for mobilization of the colon, time for dissection of the mesorectum plus transection of the rectum plus anastomosis, and phase transition counts were significantly shorter or less in the expert group than in the intermediate (p = 0.0094, 0.0028, and < 0.001, respectively) and novice groups (all p < 0.001). Mesorectal excision time was significantly shorter in the expert group than in the novice group (p = 0.0037). The group with higher ESSQS scores also had higher AI scores., Conclusion: This model has the potential to be applied to automated skill assessments., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Surgical site infections are common in spinal surgeries. It is uncertain whether outcomes in spine surgery patients with vs. without surgical site infection are equivalent. Therefore, we assessed the effects of surgical site infection on postoperative patient-reported outcomes., Methods: We enrolled patients who underwent elective spine surgery at 12 hospitals between April 2017 and February 2020. We collected data regarding the patients' backgrounds, operative factors, and incidence of surgical site infection. Data for patient-reported outcomes, namely numerical rating scale, Neck Disability Index/Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 1 year postoperatively. We divided the patients into with and without surgical site infection groups. Multivariate logistic regression analyses were performed to identify the risk factors for surgical site infection. Using propensity score matching, we obtained matched surgical site infection-negative and -positive groups. Student's t-test was used for comparisons of continuous variables, and Pearson's chi-square test was used to compare categorical variables between the two matched groups and two unmatched groups., Results: We enrolled 8861 patients in this study; 74 (0.8 %) developed surgical site infections. Cervical spine surgery and American Society of Anesthesiologists physical status classification ≥3 were identified as risk factors; microendoscopy was identified as a protective factor. Using propensity score matching, we compared surgical site infection-positive and -negative groups (74 in each group). No significant difference was found in postoperative pain or dysesthesia of the lower back, buttock, leg, and plantar area between the groups. When comparing preoperative with postoperative pain and dysesthesia, statistically significant improvement was observed for both variables in both groups (p < 0.01 for all variables). No significant differences were observed in postoperative outcomes between the matched surgical site infection-positive and -negative groups., Conclusions: Patients with surgical site infections had comparable postoperative outcomes to those without surgical site infections., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma., Methods: VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment., Findings: Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0-74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0-73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8-13·8). 52 (44%; 95% CI 35-53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3-4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported., Interpretation: These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile., Funding: Daiichi Sankyo., Competing Interests: Declaration of interests PLZ has received consulting fees from lncyte, Novartis, BeiGene, and SOBI, and honoraria from Takeda, AstraZeneca, MSD, Bristol Myers Squibb (BMS), lncyte, Roche, Gilead, Recordati, Kyowa Kirin, Novartis, BeiGene, Janssen, and SOBI, unrelated to this study. KIz has received manuscript support from Daiichi Sankyo to their institution, related to this work; research funding Chugai, BMS, Incyte, Genmab, LOXO Oncology, Daiichi Sankyo, BeiGene, AbbVie, AstraZeneca, Regeneron, Yakult, Chugai, Otsuka, Novartis, Pfizer, MSD, Bayer, Kyowa Kirin, Eisai, Janssen, Ono Pharmaceutical, Gilead, Astellas, and Amgen to their institution, unrelated to this work; consulting fees from AstraZeneca, Ono Pharmaceutical, Mitsubishi Tanabe, Eisai, Chugai, BMS, AbbVie, Takeda, Zenyaku, Genmab, Kyowa Kirin, MSD, Carna Biosicences, Novartis, Yakult, Nihon Shinyaku, Novartis, and BeiGene, unrelated to this work; and honoraria from AstraZeneca, Ono Pharmaceutical, Eisai, Chugai, Janssen, Symbio, BMS, Daiichi Sankyo, Otsuka, AbbVie, Takeda, Eli Lilly, Genmab, Kyowa Kirin, MSD, Astellas, Pfizer, Meiji Seika Pharma, Novartis, Nihon Kayaku, and Gilead, unrelated to this work. NM-S has received research funding from AstraZeneca, BMS, C4 Therapeutics, Celgene, Corvus Pharmaceuticals, Daiichi Sankyo, Dizal Pharmaceuticals, Genetech/Roche, Incyte, Innate Pharmaceuticals, Secura Bio, Verastem, and Yingli Pharmaceuticals, to their institutions, unrelated to this work; consulting fees from AstraZeneca, Kyowa Hakka Kirin, Karyopharm, Ono Pharmaceuticals, Secura Bios, Daiichi Sankyo, Genentech, and Janssen, unrelated to this work; and participated on a data safety monitoring board and an advisory board for Daiichi Sankyo, unrelated to this work. SKB received manuscript support from Daiichi Sankyo, related to this work; consulting fees and honoraria from Acrotech, Kyowa Kirin, and Seagen, unrelated to this work; and participated on a data safety monitoring board or advisory board for Janssen, unrelated to this work. KIs has received manuscript support from Daiichi Sankyo, related to this work; research funding from Ono Pharmaceutical and Kyowa Kirin to their institutions, unrelated to this work; honoraria from Kyowa Kirin, Takeda, Chugai Pharmaceutical, Celgene, BMS, Daiichi Sankyo, Ono Pharmaceutical, Astellas, Eisai, Pfizer, Otsuka, Sanofi, CSL Behring, AbbVie, Yakult, Janssen Pharmaceutical, and Nippon Shinyaku, unrelated to this work; participated on data safety monitoring board or advisory board for Meiji Seika Pharma and Daiichi Sankyo, unrelated to this work; and received materials from Ono Pharmaceutical to their institution, unrelated to this work. SK has received support from Daiichi Sankyo, related to this work; research funding from Chugai, Kyowa Kirin, and Janssen, unrelated to this work; and honoraria from Daiichi Sankyo, Chugai, Kyowa Kirin, and Janssen, unrelated to this work. EB has received research funding from Amgen and BMS, to their institution, unrelated to this work; honoraria from Novartis, Kite/Gilead, Roche, Takeda, Janssen, and AbbVie, unrelated to this work; support for attending meetings or travel from Roche and Kite/Gilead, unrelated to this work; and participated on data safety monitoring board or advisory board from Novartis, Kite/Gilead, Roche, Incyte, ADC Therapeutics, and AbbVie, unrelated to this work. KC received consulting fees from Roche, Takeda, Celgene, and AbbVie, unrelated to this work; honoraria from Roche and Takeda, unrelated to this work; support for attending meetings or travel from Roche, Takeda, and BMS, to their institution; and participated on data safety monitoring board or advisory board for Daiichi Sankyo, unrelated to this work. GG received honoraria from Ideogen and Takeda, unrelated to this work; support for attending meetings or travel from Roche, Kite-Gilead, Sandoz, BeiGene, and Janssen, unrelated to this work; and participated on data safety monitoring board or advisory board for AbbVie, Roche, Takeda, Kite-Gilead, Italfarmaco, Ideogen, and Genmab, unrelated to this work. EJ received research funding from Celgene, Merck, Pharmacyclics, and F Hoffman-LaRoche, unrelated to this work; honoraria from Merck, Daiichi, BMS, and Bayer, unrelated to this work; and has patents planned, issued, or pending with UpToDate, unrelated to this work. TF has received research funding from ADCT, AstraZeneca, BMS, Corvus, Daiichi, Genmab, Kymera, Merck, Seagen, TESSA, Trillium, Alexion, and Portola, unrelated to this work; consulting fees from ADCT, AstraZeneca, BMS, Epizyme, Genmab, Seagen, Pharmacyclics, and Celgene, unrelated to this work; honoraria from Takeda, Seagen, Genmab, Epizyme, ADCT, AstraZeneca, BMS, Pharmacyclics, AbbVie, and Pfizer, unrelated to this work; and owns stock in OMI and Genomic Testing Cooperative, unrelated to this work. DE received research funding from Nippon Shinyaku Pharmaceutical, Chugai Pharmaceutical, and Eisai Pharmaceutical, to their institution, unrelated to this work; and honoraria from Eisai Pharmaceutical, Chugai Pharmaceutical, SymBio Pharmaceuticals, BMS, Kyowa Kirin Pharmaceutical, and Nippon Shinyaku Pharmaceutical, unrelated to this work. EDD received consulting fees from Takeda, unrelated to this work; honoraria from Takeda and BeiGene, unrelated to this work; and funding for attending meetings or travel from Takeda, unrelated to this work. JZ received research funding from Secura Bio, Astex, CRSPR, Myeloid Therapeutics, and Daichi Sankyo, unrelated to this work; consulting fees from Seattle genetics, Secura Bio, Kyowa Kirin, and Myeloid Therapeutics, unrelated to this work; and honoraria from Kyowa Kirin, unrelated to this work. JJ, SW, TM, AI, and KN are employed by Daiichi Sankyo. TM has received support for attending meetings or travel from Daiichi Sankyo, unrelated to this work. AI, TM, and YC own stock options in Daiichi Sankyo, unrelated to this work. KN owns stock in Daiichi Sankyo, unrelated to this work. SH received research funding from the US National Institutes of Health/National Cancer Institute Cancer Center, (support grant P30 CA008748); research funding from ADC Therapeutics, Affimed, Aileron, Celgene, Crispr Therapeutics, Daiichi Sankyo, Forty Seven, Kyowa Hakko Kirin, Takeda, Seattle Genetics, Trillium Therapeutics, and SecuraBio; and honoraria from Abcuro, Autolus, Auxilius Pharma, Corvus, Cimeio Therapeutics, Daiichi Sankyo, Dren Bio, Kyowa Hakko Kirin, March, Bio, Ono Pharmaceuticals, SecuraBio, Shore line, Biosciences, Takeda, Tubulis and Yingli Pharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

With higher temperatures expected in the future due to global climate change, addressing health risks such as heat illness is increasingly important. In Japan, thousands of heat illness cases occur annually during school sports club activities. The risk may vary by sport, location, and region, but how heat safety thresholds (HSTs) should be adjusted to provide effective guidelines remains uncertain. Thus, we conducted a case-crossover study using data of heat illness cases and wet-bulb globe temperature (WBGT) throughout Japan to evaluate the heat illness risk for the current HSTs and propose adjustments. A significant relationship was found between heat illness incidence and WBGT at the time of the incident, as well as the average WBGT one and two days prior. The risk significantly varies with factors such as club, region, location, year, month, and the average WBGT in summer. Therefore, we recommend lowering the current HSTs by one category (3 °C) in the following cases: (1) clubs at high risk (baseball, softball, soccer/futsal, tennis, track and field, kyudo, and other with sustained exercise or thick uniforms); (2) from April to June; (3) in cooler regions (Hokkaido, Tohoku, Hokuriku, or where the average WBGT in summer≦18℃); (4) for outdoor activities; (5) when heat rapidly increases without adequate heat acclimatization. These findings may inform educators, students, sports authorities, and policymakers in adjusting HSTs to reduce the incidence of heat illness, thereby ensuring safer environments for school sports activities., (© 2024. The Author(s).)

Purpose: To investigate the effectiveness and safety of thoracic endovascular aortic repair (TEVAR) for infectious aortic diseases., Materials and Methods: Patients who underwent TEVAR for infectious aortic diseases including infected thoracic aortic aneurysm, aortobronchial fistula (ABF), and aortoenteric fistula from December 2011 to October 2022 at 4 institutions were retrospectively studied. The primary outcome of the study was overall survival, whereas the secondary outcome was comprehensive adverse events. Comprehensive adverse events were defined as a combination of deaths, aortic events, and infectious adverse events., Results: A total of 28 patients were included in the analysis, with 13 patients having infected thoracic aortic aneurysms, 12 ABFs, and 3 aortoenteric fistulae. Seven patients (25%) underwent additional procedures (abscess drainage, 6 cases; total esophagectomy, 1 case). The mean follow-up period was 30.0 months (SD ± 33.9). The 1-year and 5-year survival rates were 85.7% and 67.9%, respectively. The 1-year and 5-year aorta-related complication-free survival rates were 64.3% and 42.9%, respectively. On univariate analysis, the presence of an ABF was associated with a higher risk of comprehensive adverse events (odds ratio = 11; P = .04)., Conclusions: TEVAR might be a promising treatment for infectious thoracic aortic diseases. Among the infectious pathologies, ABF was considered ominous in terms of late outcomes., (Copyright © 2024. Published by Elsevier Inc.)

A 48-year-old woman with a history of bronchial asthma and allergic rhinitis presented with cardiac arrest due to ventricular fibrillation and was resuscitated by defibrillation. Coronary angiography revealed coronary vasospasm. Various antispastic agents were unable to control recurrent coronary spasms. We searched for other points of intervention and found a significant increase in the eosinophil count. The patient received mepolizumab for bronchial asthma with eosinophilia, which normalized the eosinophil count. Since then, the patient has remained free from coronary vasospasm, suggesting that mepolizumab may be a viable option for treating refractory coronary angina associated with bronchial asthma and eosinophilia.

Minor acidic glycans, such as sulfated and phosphorylated glycans, constitute only a small fraction of biological glycome, making their analysis a considerable challenge. In this study, we developed a technique to analyze minor acidic O -glycans in biological samples. First, efficient reaction conditions for the release of O -glycans from the proteins were determined. Next, a high-throughput method was established for the recovery of minor acidic glycans using NH 2 spin columns. The performance of the established method was evaluated using mucin samples, and sulfated O -glycans were successfully detected in bovine submaxillary gland mucin and porcine stomach mucin. We also analyzed the minor acidic O -glycans in cultured cancer cells. In addition to trifucosylated sulfated O -glycans and disulfated O -glycans, sulfated O -glycans with KDN were detected in LS174T cells. The relative amount of sulfated glycans in LS174T cells was almost 10-fold higher than that in the other cells. Moreover, a large polylactosamine-type sulfated O -glycan with a molecular weight >3500 was detected in MKN45 cells. Interestingly, phosphorylated ribose, possibly bound to serine/threonine, was observed in all the cells used in this study. Thus, our established analytical method allows for the analysis of minor acidic O -glycans that cannot be detected using existing glycomics methods.

We developed a novel clamping device for laparoscopic surgery, free from conventional pinch structure, capable of uniformly occluding any ductal organ. This study aimed to evaluate performance of the new clamper compared to the pinch-type clamper. The new clamper consists of two metal bars with ties at each end, which enables parallel clamping. A resected porcine stomach was used, with an infusion tube at the anal end to increase intra-luminal pressure. The oral side of the stomach was clamped with either the new clamper or the pinch-type clamper, and their performances were evaluated in qualitative and semi-quantitative manner. Qualitative evaluation involved imaging the clamping site at intra-gastric pressures from 0 to 15 mmHg using microfocus computed tomography. The new clamper showed no gap even under increased intra-luminal pressure, while the pinch-type clamper showed a gap on the distal side. Quantitative evaluation measured bursting pressure under continuous air insufflation. Air leakages were observed in the new clamper at higher intra-luminal pressures than in the pinch-type clamper (46.1 mmHg vs. 13.6 mmHg, P < 0.01). Our new clamping device showed superior performance in preclinical setting compared to the conventional pinch-type clamper. We are currently working on its design freezing and aiming for early commercialization., (© 2024. The Author(s).)

Background: Salivary α-amylase plays a crucial role in the glucose metabolism. However, postprandial salivary α-amylase activity (SAA) and its relationship with blood glucose (BG) are poorly understood. Therefore, we investigated SAA and BG after starch loading in healthy young women., Methods: In 60 healthy non-obese young women, we investigated SAA, BG, and blood 3-hydroxybutyrate (3HB) after the consumption of 150 g rice (starch 48.8 g). Participants were classified into two groups based on the changes (Δ) in SAA from baseline at 60 min: small- and large-increase in ΔSAA groups (SI-ΔSAA and LI-ΔSAA)., Results: BG levels were significantly higher at 60, 90, and 120 min in participants with SI-ΔSAA (n = 31) than LI-ΔSAA (n = 29). Baseline 3HB concentration was also higher in participants with SI-ΔSAA. ΔSAA at 60 min was most closely and inversely correlated with BG and ΔBG at 90 min (r = -0.53 and -0.50, both P < 0.0001). Generalized linear model analysis also indicated that ΔSAA at 60 min was the most predictive of ΔBG at 90 min., Conclusions: Higher levels of BG and ΔBG were observed after starch loading in healthy young women with smaller increase in salivary amylase, suggesting another crucial role of postprandial salivary amylase for the postprandial glucose metabolism., Competing Interests: The authors declare no conflict of interest., (Copyright 2024, Sekine et al.)

Mycobacterium abscessus causes severe lung infections in cystic fibrosis patients and exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in the S-to-R transition but the underlying molecular mechanisms of this transition remain incompletely understood. Herein, we characterized MAB&#95;4111c in relation to GPL synthesis and investigated the effects of MAB&#95;4111c deletion in M. abscessus pathogenicity. An enzymatic assay indicated that MAB&#95;4111c, also designated Tle for Talose epimerase, is converting dTDP-L-Rhamnose into dTDP-6-deoxy-L-Talose. A tle deletion mutant was constructed in the S variant of M. abscessus and relative areas of Rhamnose and 6-deoxy-Talose and their methylated forms expressed as ratios of total monosaccharides, showed an altered GPL profile lacking 6-deoxy-Talose. Thus, Tle provides dTDP-6-deoxy-L-Talose, subsequently used by the glycosyltransferase Gtf1 to transfer 6-deoxy-Talose to the GPL backbone. Strikingly, the tle mutant exhibited an R morphotype, showed impaired sliding motility and biofilm formation, and these phenotypes were rescued upon functional complementation. Moreover, deletion of tle in M. abscessus results in increased pathogenicity and killing in zebrafish embryos. Together, our results underscore the importance of the dTDP-L-Rhamnose 4-epimerase activity in GPL biosynthesis and in influencing M. abscessus virulence., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interests with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: This study aimed to investigate the utility of low-energy virtual monochromatic imaging (VMI) combined with deep-learning image reconstruction (DLIR) in improving the delineation of endoleaks (ELs) after endovascular aortic repair (EVAR) in contrast-enhanced dual-energy CT (DECT)., Methods: A total of 61 consecutive patients (mean age, 77 years; 46 men) after EVAR who underwent contrast-enhanced DECT were enrolled. Virtual monochromatic 40- and 70-keV images were reconstructed using DLIR (TrueFidelity-H) and conventional hybrid iterative reconstruction (IR). Contrast-to-noise ratio (CNR) of the EL on the venous-phase CT was calculated. Four different reconstructed image series (hybrid IR and DLIR at two energy levels, 40- and 70-keV) were displayed side-by-side and visually assessed for EL conspicuity on a 5-point comparative scale from 0 (best) to -4 (significantly inferior). Two experienced radiologists independently conducted a qualitative evaluation of the CT images., Results: A total of 30 out of 61 patients presented with an EL. On both 40- and 70-keV images, the CNR of the EL was significantly higher in DLIR than in hybrid IR (40-keV, 14.5 ± 7.3 vs 8.6 ± 4.2, P<0.001; 70-keV, 8.7 ± 4.5 vs 5.5 ± 2.6, P<0.001). The comparative scale of EL conspicuity in the 40-keV DLIR images (Observer1, -0.2 ± 0.4; Observer2, 0.0 ± 0.0) was significantly higher than 40-keV hybrid IR (Observer1, -0.5 ± 0.5; Observer2, -1.0 ± 0.0; P<0.05), 70-keV DLIR (Observer1, -1.8 ± 0.4; Observer2, -2.0 ± 0.0; P<0.001) and 70-keV hybrid IR images (Observer1, -1.8 ± 0.4; Observer2, -2.4 ± 0.5; P<0.001), respectively., Conclusions: Using 40-keV VMI in combination with DLIR improves EL delineation after EVAR compared with the 70-keV VMI with hybrid IR or DLIR., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We aimed to establish a practical diagnostic index for Lewy body diseases (LBD), such as Parkinson's disease and dementia, with Lewy bodies in outpatient settings and criteria for exempting patients from late imaging., Methods: We acquired early and late 123 I-metaiodobenzylguanidine (MIBG) images from 108 consecutive patients with suspected LBD and standardized heart-to-mediastinum (H/M) ratios for collimator conditions. Exclusions included young-onset Parkinson's disease (age < 50 years) and genetic transthyretin-type amyloidosis. We developed logistic models incorporating H/M ratios with or without age (n = 92). The sympathetic MIBG index for LBD (SMILe index), categorized LBD likelihood from 0 (lowest) to 1 (highest). Diagnostic accuracy was assessed as the area under the receiver operating characteristic (ROC) curve (AUC). The characteristics of the new index were compared with H/M ratios. The need for late imaging was explored using the SMILe index., Results: Early or late SMILe indexes using a single H/M ratio variable discriminated LBD from non-LBD. The AUC values for early and late SMILe indexes were 0.880 and 0.894 (p < 0.0001 for both), identical to those for early and late H/M ratios. The sensitivity and the specificity of early SMILe indexes with a 0.5 threshold were 76% and 90%, achieving accuracy of accuracy 86%. Similarly, the late SMILe index demonstrated a sensitivity of 76% and specificity of 87%, with an accuracy of 84%. Early SMILe indexes < 0.3 or > 0.7 (representing 84% patients) indicated a diagnosis without a late MIBG study., Conclusion: The 123 I-MIBG-derived SMILe indexes provide likelihood of LBD, and those with a 50% threshold demonstrated optimal diagnostic accuracy for LBD. The index values of either < 0.3 or > 0.7 accurately selected patients who do not need late imaging., (© 2024. The Author(s).)