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Abstract The impact of resolving western boundary currents and mesoscale eddies on a carbon circulation simulation for the North Pacific Ocean is investigated to evaluate the merits of using high‐resolution ocean biogeochemical models for climate projections. Simulations by a 100‐km resolution global ocean biogeochemical model with and without embedding a 10‐km resolution model in the North Pacific Ocean are compared. The major improvement in the high‐resolution simulation is the representation of the Kuroshio, its extension current, and the recirculation gyres formed to its south and north, resulting in a proper representation of the North Pacific subtropical mode water (STMW) and an increase in storage of the anthropogenic CO2 (Canth) in STMW by about two‐thirds. The larger storage rate in STMW is caused by supply of a larger amount of warm surface water containing rich Canth to the formation region by the intensified Kuroshio. A huge buoyancy loss from this warm water results in the increased formation of STMW that occupies a vast area in the western subtropical gyre. The surface uptake of Canth in the formation region of STMW is slightly increased but is largely comparable to that of the low‐resolution model. Moreover, there is no structural difference in Canth uptake in other parts of the subtropical region. Thus, the improvement of Canth distribution can be understood as a redistribution of water mass in the subtropical gyre by the improved circulation. The present assessment motivates the use of a high horizontal resolution ocean model in next‐generation projection experiments with carbon cycles.

Most current databases for bodily emotion expression are created in Western countries, resulting in culturally skewed representations. To address the obvious risk this bias poses to academic comprehension, we attempted to expand the current repertoire of human bodily emotions by recruiting Asian professional performers to wear whole-body suits with 57 retroreflective markers attached to major joints and body segments, and express seven basic emotions with whole-body movements in a motion-capture lab. For each emotion, actors performed three self-created scenarios that covered a broad range of real-life events to elicit the target emotion within 2-5 seconds. Subsequently, a separate group of participants was invited to judge the perceived emotional category from the extracted biological motions (point-light displays with 18 or 57 markers). The results demonstrated that the emotion discrimination accuracy was comparable to Western databases containing standardized performance scenarios. The results provide a significant step toward establishing a database using a novel emotional induction approach based on personalized scenarios. This database will contribute to a more comprehensive understanding of emotional expression across diverse contexts., Competing Interests: Declarations. Conflicts of interest: The authors have no relevant financial or non-financial interests to disclose Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval: The University Human Research Ethics Committee of Tohoku University approved all the experimental procedures. All methods were performed in accordance with the relevant guidelines and regulations in accordance with the 1964 Helsinki Declaration. Consent to participate: All participants received instructions on the data collection and signed the informed consent form. Consent to publication: The authors affirm that human research participants provided informed consent for publication of all the data included in this research report., (© 2024. The Author(s).)

Background: In the first-line treatment of elderly patients with advanced-stage non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥ 50%), this study aimed to determine whether pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) should be selected., Methods: We performed a retrospective multicenter study (sub-analysis of the HOT/NJLCG2001 trial) of 299 patients with NSCLC with high PD-L1 expression who received MONO or COMB as the first-line treatment between December 2018 and January 2020. We selected patients aged 75 years and older and assessed the clinical efficacy and toxicity., Results: In total, 81 (median age: 79 years) and 19 (median age: 76 years) patients received MONO and COMB, respectively. Twenty patients with a performance status (PS) score of 2-3 were enrolled in the MONO group. The median progression-free survival (PFS) was 7.8 and 8.9 months in the MONO and COMB groups, respectively. The median overall survival (OS) was 14.6 and 20.3 months, and the 2-year survival rates were 38.8 and 49.9%, respectively. Furthermore, 29.6% and 26.3% of patients discontinued treatment due to adverse events, respectively. In MONO, patients with PS 0-1 had a longer PFS (10.5 months) and OS (21.7 months) than those with PS 2-3 (0.7 and 1.6 months, respectively)., Conclusion: Some elderly patients with NSCLC and high PD-L1 expression might benefit from COMB; however, MONO is considered the preferred treatment. MONO may not be an effective or feasible treatment for patients with PS 2-3, even with high PD-L1 expression., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Yeast and lactic acid bacteria (LAB) play an important part in the post-harvest fermentation of coffee. This study applied lab-scale fermentation to commercial green coffee beans using dry coffee pulp as the substrate, with the aim of modifying coffee-bean flavor. In addition to spontaneous fermentation, yeast and LAB isolated from coffee beans and dried coffee pulp were added during fermentation., Results: Co-inoculation of yeast and LAB showed a significant effect on the chlorogenic acid content after between 24 and 72 h of fermentation. Acetic, citric, malic, lactic, and quinic acids were shown to be affected significantly (P < 0.05) by fermentation and inoculation. Gas chromatography detected that esters, alcohols, aldehydes, furans, and pyrazines were the primary compounds in the coffee beans. Certain volatile groups were present in greater concentrations and broader varieties within the inoculated beans. The highest cupping scores were given to beans that had been co-inoculated with yeast and LAB., Conclusion: Overall, the use of yeasts and LAB starters showed potential to create coffee beverages with desirable characteristics by standardized fermentation. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Nondestructive spectroscopic analysis is widely used to evaluate food composition. However, distinguishing analytes of interest from other compounds remains challenging. Since most foods are heterogeneous when viewed under a microscope, we hypothesized that spectra measured at microscopic points would be "purer" than spectra acquired from a larger area. By coupling this data with nonnegative matrix factorization (NMF), the analytes of interest can be separated. This preliminary study discusses the quantification of glucose in mixtures of different sugars. Samples were made by mixing glucose with other powders in different ratios and Raman spectra were measured at 200 micro-points for each sample. NMF was applied to factorize the mixed spectra into spectra of pure compounds and their concentrations, leading to the accurate quantification of glucose, while eliminating the effects of other compounds. While this study targets simple powders, separation of analytes using microscale heterogeneity is applicable for measuring more complex foods., 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.)

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.)

Background: Osteoarthritis of the thumb carpometacarpal joint often presents pain and affects activity of daily life. There is no consensus regarding prevalence of primary radiographic osteoarthritis and symptomatic osteoarthritis of the thumb carpometacarpal joint, and their associated factors are not well investigated. The purpose of this study is to evaluate the prevalence and associated factors of primary radiographic and symptomatic osteoarthritis of the thumb carpometacarpal joint in a resident cohort., Methods: A total of 1297 residents aged 50 to 89 were randomly sampled from a small rural town in Japan, and their demographic data and questionnaire regarding lifestyle and job were obtained. All participants underwent posteroanterior radiographs of the bilateral hands. Participants with thumb carpometacarpal joint radiographic osteoarthritis were diagnosed if one of their thumb carpometacarpal joints was Kellgren-Lawrence grade 2, 3, or 4. Symptomatic osteoarthritis was diagnosed by tenderness or positive motion pain at the thumb base. Associated factors for the thumb carpometacarpal joint radiographic osteoarthritis were statistically analyzed., Results: A total of 646 thumbs with 323 participants (153 male and 170 female) were investigated. The mean age was 69.1 (range 50-89) years, The prevalence of thumb carpometacarpal joint radiographic osteoarthritis was 17.3 % (13.7 % males and 20.6 % females) and that of thumb carpometacarpal joint symptomatic osteoarthritis was 3.1 %. Associated factors for thumb carpometacarpal joint radiographic osteoarthritis were presence of finger joint radiographic osteoarthritis in the ipsilateral hand, increasing age, and female in order of degree of relevance. Dominant hand, body mass index, smoking history, heavy manual or agriculture work, use of vibrating tools, racket or bat sports, or scaphotapeziotrapezoidal joint radiographic osteoarthritis were not associated factors for thumb carpometacarpal joint radiographic osteoarthritis., Conclusions: The prevalence of thumb carpometacarpal joint primary radiographic osteoarthritis in general Japanese elderly aged 50-89 years was 17.3 %, most of carpometacarpal joint radiographic osteoarthritis was asymptomatic., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Spontaneous anterior interosseous nerve (AIN) palsy is characterized by the sudden onset of upper limb pain followed by weakness of muscles mainly innervated by the AIN. Although this palsy is conventionally treated conservatively, interfascicular neurolysis to release hourglass-like fascicular constrictions has been recommended. The present study aimed to establish the clinical characteristics and treatment strategy for this condition., Methods: One hundred limbs with spontaneous AIN palsy from 24 Japanese institutions were treated either conservatively or with interfascicular neurolysis according to the patient's intention. Patients were followed periodically from 3 months to either recovery or ≥36 months after onset. Limbs recovering to manual muscle testing grade 4 or better in both the flexor pollicis longus and flexor digitorum profundus of the index finger were rated as Good recovery, with all other results classified as Poor recovery. We performed logistic regression analysis to determine the independent factors associated with Good recovery., Results: Good recovery was achieved in 39 of 49 limbs treated conservatively and 44 of 51 limbs by interfascicular neurolysis. All 26 limbs with conservative treatment displaying ≥1 grade of manual muscle testing improvement within 6 months after onset achieved Good recovery. All 23 limbs with Group I palsy, in which weakness was recognized only in muscles innervated by the AIN, obtained Good recovery with interfascicular neurolysis regardless of when it was performed. In the 59 limbs with no recovery at 6 months by conservative treatment, Good recovery was achieved in 30 of 36 limbs by subsequent interfascicular neurolysis and 13 of 23 limbs continuing conservative treatment. In these 59 limbs, interfascicular neurolysis and Group I palsy were significantly associated with Good recovery., Conclusions: Conservative treatment is recommended within 6 months following symptom onset, after which time interfascicular neurolysis is advisable for cases of no improvement., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest associated with this study., (Copyright © 2024. Published by Elsevier B.V.)

In the current model, the auto-negative feedback action of Period (Per) and Cryptochrome (Cry) on their own transcription is the hallmark mechanism driving cell-autonomous circadian rhythms. Although this model likely makes sense even if Per and Cry undertake this action in a mutually independent manner, many studies have suggested the functional significance of direct physical interaction between Per and Cry. However, even though the interaction is a biochemical process that pertains to the fundamentals of the circadian oscillator, its in vivo contribution to circadian rhythm generation remains undefined. To answer this question, we focused on zinc coordination between Per and Cry, whose contribution to circadian rhythm generation remains undefined. Specifically, we aimed to impair endogenous Per-Cry association by introducing an amino acid substitution to zinc-coordinating residues located at the Per1 and Per2 C-terminal facing Cry in mice. These mice did not show severe impairment in the Per-Cry physical interaction, but rather a shortened period and decreased robustness in circadian rhythms at the tissue-autonomous and whole-body levels. Furthermore, these mice also showed a decrease in Per half-life, suggesting that impaired fine-tuning of Per half-life caused abnormal circadian period and robustness in vivo. We also found a minor but significant impact of a reindeer-specific Per2 mutation located in the Per-Cry interface on circadian rhythms in vivo. These lines of evidence indicate that only partial impairment of the Per-Cry physical interaction produces a substantial effect on circadian period and robustness, supporting the in vivo functional significance of the interaction., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Alanine dosemeters are widely used as solid dosemeters; however, evaluating doses in the mGy order of radiation is difficult because of their lower sensitivity for low doses. We applied the electron spin resonance dosimetry technique to investigate whether hydroxyapatite, the main component of teeth, is a suitable material for a new dosemeter to detect radiation from mGy to Gy. Commercially available synthetic hydroxyapatite possesses the essential characteristics required for a dosemeter material and has been demonstrated to accurately measure doses in the mGy to Gy range., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: The link between DNA repair gene polymorphisms and cancer susceptibility has gained significant attention. Thus, we investigated the impact of base excision repair (BER) gene polymorphisms on acute myeloid leukemia (AML) risk and pathogenesis., Methods: In total, 106 patients with AML and 191 healthy controls were included in the study, wherein polymorphisms in four BER genes (APEX1, MUTYH, OGG1, and XRCC1) were examined., Results: Notably, the APEX1-656 T>G polymorphism exhibited a significant association with AML risk in the recessive (TT vs. TG + GG) (p = 0.046) and co-dominant models (TT vs. GG) (p = 0.02). Assessing APEX1 expression levels, APEX1 expression was elevated in the bone marrow of patients with AML compared with that in controls (p = 0.02). Subsequently, we compared the percentages of CD34+ cells between the APEX1 high or low expression groups, revealing a significant difference (high vs. low = 29.9% vs. 11.5%, p = 0.01). Additionally, we observed reduced APEX1 expression in HL60 cells differentiated with all-trans retinoic acid (p < 0.001). We hypothesized that APEX1 expression could correlate with stemness and analyzed its expression in stem and differentiated cells., Conclusions: In the GSE48558 dataset, AML cells and normal CD34+ cells expressed APEX1 at higher levels than did granulocytes (p < 0.01). Functional experiments revealed that APEX1 knockdown led to a reduction in AML cell proliferation. These findings indicated that APEX1 polymorphisms were a potential risk factor for AML and highlighted the important role of APEX1 in regulating AML cell differentiation and proliferation., (© 2024 The Author(s). International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

Objectives: The impact of cGAS/STING tumor expression on PD-1/L1 inhibitor efficacy and the tumor microenvironment remain to be elucidated., Methods: In a post-hoc analysis of a prospective biomarker study with 106 advanced NSCLC patients treated with PD-1/L1 inhibitors from December 2015 to September 2018, tumor tissue before treatment from 68 patients was analyzed. cGAS and STING expression were measured using immunohistochemical staining and H-scores. Additionally, 40 serum proteins were quantified before and 4-6 weeks after treatment initiation., Results: Median cGAS and STING H-scores were 220 (range, 5-300) and 190 (range, 0-300), respectively. There were no differences in cGAS or STING H-scores between the high (tumor proportion score [TPS] ≥ 50) and low (TPS < 50) PD-L1groups (p = 0.990 and 0.283, respectively). Unexpectedly, patients with high cGAS (H-score ≥ 220) demonstrated significantly shorter progression-free survival (PFS) of PD-1/L1 inhibitors when the PD-L1 TPS was high (median PFS: 143 days vs. not reached; p = 0.028); PFS at 18 months was 7% and 53% in the high and low cGAS groups, respectively while STING expression did not impact PFS. In serum protein analyses, high cGAS H-score was associated with significantly higher TGF-β1 and TGF-β2 before PD-1/L1 inhibition (47.5 vs. 22.3 ng/l, p = 0.023; 2118 vs. 882 pg/ml, p = 0.037); additionally, the cGAS H-score significantly correlated with TGF-β1 (r = 0.451, p = 0.009) and TGF-β2 (r = 0.375, p = 0.031) basal levels., Conclusion: cGAS expression, but not STING, predicts poor PD-1/L1 inhibitor efficacy in NSCLC with high PD-L1, potentially due to a TGF-β-mediated immunosuppressive environment (UMIN000024414)., (© 2024. The Author(s).)

Aim: This study aimed to investigate the impact of preoperative gallbladder drainage and the specific drainage method used on surgical outcomes in patients undergoing surgery for acute cholecystitis., Methods: This single-center retrospective cohort study included 221 patients who underwent early cholecystectomy between January 2016 and December 2020. Clinical data and outcomes of 140 patients who did not undergo drainage, 22 patients who underwent preoperative percutaneous transhepatic gallbladder drainage (PTGBD), and 59 patients who underwent preoperative endoscopic naso-gallbladder drainage (ENGBD) were compared., Results: There was no difference in the operation time, blood loss, postoperative complications, or length of postoperative hospital stay between patients who did and did not undergo drainage. Among patients who underwent drainage, there was no difference between the ENGBD and PTGBD groups in operation time, blood loss, or postoperative complications; however, more patients in the PTGBD group underwent laparotomy and had a significantly longer postoperative hospital stay. The presence and type of drainage were not risk factors for postoperative complications., Conclusion: The presence or absence of preoperative gallbladder drainage for acute cholecystitis and the type of drainage may not significantly affect surgical outcomes., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: We previously investigated methods for separating mutagenic contaminants from aqueous solutions using cellulose-bearing covalently bound trisulfo-Cu-phthalocyanine (blue cotton and blue rayon). Mutagenic contaminants with three or more fused aromatic rings in their structures were adsorbed onto blue cotton and rayon. Since Cu-phthalocyanine is considered an unsuitable absorption ligand for byproducts of water chlorination, such as 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (Mutagen X or MX), we investigated the development of a new material for the elimination of MX from aqueous solvents., Results: We selected green cellulose powder bearing ferrous phthalocyanine (FePh), hereafter referred to as green cellulose or GP, as the candidate material. GP is composed of cationized cellulose (white cellulose, WP) and FePh tetracarboxylic acid. The mutagenicity of MX dissolved in buffer or dimethyl sulfoxide (DMSO) solution significantly decreased after treatment with GP. The effects of GP on the elimination of MX from the solvent were very close to being expired after 70 cycles of repeated adsorption of the same GP, and the capacity of GP for MX removal was estimated to be exhausted after 120 cycles of repeated adsorption based on the extrapolation of the obtained result; thus, the interacting ligands on GP may be saturated after complete MX adsorption. The mutagenicity of MX dissolved in aqueous buffer significantly decreased after treatment at pH7.4 but not at pH 4.0. Since MX is dissociated to be the anionic form at pH 6 or higher, the negative charge of MX in the buffer at pH 7.4 may interact with the positive charge of ferrous ions in GP to create a linkage between MX and GP. After GP adsorbed MX, mutagenicity was extracted with water or acetonitrile and recovered in the eluent. Thus, the reversible interaction between MX and FePh may have caused adsorption of MX onto GP., Conclusion: GP could be used as a new eliminator and recovery agent for MX in chlorinated drinking water. Developing new materials for the removal and recovery of agents for the detection of mutagenic contaminant-related chlorination in water is beneficial for environmental health., (© 2024. The Author(s).)

To enhance the pore structure of green coffee beans (GCB) and detect the sorption capacity and extraction characteristics of flavor compounds before roasting, this study employed several methods: hot air drying (HD), freeze-drying (FD), 3-levels short-time heating with puffing (SH 1 P, SH 2 P, and SH 3 P), and 3-levels microwave with puffing (MW 45 P, MW 60 P, and MW 75 P). These methods were applied to GCBs pre-soaked in water for different times. The effects of these treatments on color change, porosity, microstructure, citric acid sorption capacity, and caffeine and chlorogenic acid extraction yield were investigated. Results indicated that, except for GCBs treated with SH 1 P, SH 2 P, SH 3 P, and MW 75 P, all other modified GCBs showed minimal color change. GCBs treated with MW 60 P exhibited favorable pore structures. MW 60 P treatments significantly improved the extraction yield of caffeine and chlorogenic acid. Furthermore, the increased porosity and improved pore size distribution of GCB after MW 60 P resulted in a significant increase in the sorption of citric acid onto modified GCB. The rate of the sorption reaction followed the pseudo-first-order kinetics. In conclusion, MW 60 P are effective treatments for enhancing the microstructure of GCB, improving sorption capacity, and improving the extraction yield of flavor compounds.

Purpose: Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNETs) are the most common cause of acromegaly. The endoscopic endonasal transsphenoidal approach (EEA) is commonly employed to remove them. Although morphological differences in the nasal cavity exist between acromegaly patients and those with other types of PitNET, few quantitative studies have been performed. This study aimed to evaluate the anatomical features of the nasal cavity and paranasal sinuses in patients with acromegaly., Methods: Preoperative computed tomography images of the nasal cavity and paranasal sinuses were compared between 20 patients with a GH-secreting PitNET (acromegaly group) and 22 with a non-functioning PitNET (control group). In the acromegaly group, the relationships between preoperative GH and/or insulin-like growth factor 1 (IGF-1) levels and anatomical characteristics were assessed., Results: In the acromegaly group, the distance between the nostril and dorsum sellae was significantly longer and the distance between the parasellar internal carotid arteries was significantly shorter (p = 0.0022 and 0.0092, respectively). Pneumatization volume in the nasal cavity did not differ between the groups. Nasal mucosa and bony hypertrophy were observed in the acromegaly group. Preoperative GH level was correlated with the width of the piriform aperture (p = 0.0171)., Conclusion: The nasal and paranasal changes associated with acromegaly can make EEA challenging to perform. Widening the surgical corridor anterior to the sphenoid sinus is important in these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objectives: This randomized controlled trial compared the outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus carbonate apatite (CO 3 Ap) granules with rhFGF-2 alone in the treatment of intrabony periodontal defects., Materials and Methods: Patients with Stage III Grade B/C periodontitis who had completed initial periodontal therapy and had intrabony defects with a depth of ≥ 3 mm were included. Defects were treated solely with rhFGF-2 (control) or rhFGF-2 plus CO 3 Ap (test). Periodontal parameters and a patient-reported outcome measure (PROM) were assessed at baseline, at 6, 9 and 12 months postoperatively. The primary outcome was the change in clinical attachment level (CAL) from baseline to 12 months postoperatively. Using the Friedman test with Dunn's post-test, intragroup data were compared over time, and Mann-Whitney U test was used to assess intergroup data at each time point., Results: Forty-eight sites in 38 patients were subjected to analysis. At 12 months postoperatively, CAL in both groups showed a significant improvement from baseline (p < 0.001). CAL gain was 3.4 ± 1.3 mm in the test group and 3.2 ± 1.2 mm in the control group, with no significant intergroup difference (p = 0.567). Radiographic bone fill in the test group (67.2%) was significantly greater than in the control group (32.4%) (p < 0.001). PROM scores showed no difference between groups., Conclusions: At 12 months, the outcomes including CAL gain and PROM showed no significant differences between groups, although the combination treatment enhanced radiographic bone fill., Clinical Relevance: The use of rhFGF-2 (with/without CO 3 Ap) could lead to significant improvement in clinical parameters in the treatment of intrabony periodontal defects. The benefit of adding CO 3 Ap to rhFGF-2 therapy needs further evaluation., Clinical Trial Registration Number: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) : UMIN000040783., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: Many glioma patients struggle to return to work after surgery because of higher brain dysfunction. Although the right frontal lobe has historically been considered functionally silent, reports of performing awake surgery to evaluate higher brain functions in patients with tumors in this area have increased. We present two cases of patients who underwent awake surgery for malignant glioma in the right frontal lobe to preserve emotional recognition and facilitate an early return to work., Case Report: Case 1 was a 48-year-old right-handed woman employed as a nursery school teacher and case 2 was a 21-year-old right-handed man employed in sales. Both had contrast-enhancing right frontal lobe tumors exhibiting high signal intensity on fluid attenuated inversion recovery imaging and underwent awake surgery. During the operation, cortical mapping was performed using the Reading the Mind in the Eyes, calculation, and motor tasks. Resection of sites involved in motor and emotional recognition functions was avoided. In case 1, all regions of high signal intensity were completely resected; in case 2, all regions exhibiting enhancement were resected. Both patients were discharged home without neurological deficits and returned to work within 21 days after surgery., Conclusion: It may be important to focus not only on overall survival and progression-free survival in glioma patients, but also on factors associated with life satisfaction, such as time to return to work after surgery and time until work becomes difficult. Awake surgery aimed at preserving higher brain functions is useful and may also improve life satisfaction., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Repeat endoscopic submucosal dissection for metachronous recurrence of esophageal squamous cell carcinoma close to previous endoscopic submucosal dissection scars is challenging. Therefore, this study evaluated the efficacy and safety of repeat endoscopic submucosal dissection for recurrent esophageal squamous cell carcinoma., Methods: The study included 1680 patients. After propensity score matching, esophageal endoscopic submucosal dissection-related outcomes were compared between the post-endoscopic submucosal dissection scar group (n = 91) and first endoscopic submucosal dissection group (n = 910). The Kaplan-Meier method and log-rank tests were used to compare both groups' survival and local recurrence curves., Results: After propensity score matching, the two groups showed no significant difference in en bloc resection rate (97.80% vs. 99.56%, p = 0.096), treatment time (64.75 min vs 61.33 min, p = 0.448), recurrence rate (3.30% vs. 2.20%, p = 0.458), and stricture rate (7.69% vs. 4.07%, p = 0.110). However, the perforation rate was higher in the post-endoscopic submucosal dissection scar group than in the first endoscopic submucosal dissection group (4.40% vs. 1.10%, p = 0.031). The 5-year overall survival rates in the post-endoscopic submucosal dissection scar and first endoscopic submucosal dissection groups were 88.6% and 89.0%, respectively., Conclusions: Repeated esophageal endoscopic submucosal dissection for recurrent esophageal squamous cell carcinoma yielded satisfactory clinical outcomes and survival rates. Therefore, repeat endoscopic submucosal dissection may effectively treat esophageal squamous cell carcinoma recurrence close to the initial endoscopic submucosal dissection scars., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders characterized by the aberrant accumulation of α-synuclein (α-syn). Although no treatment is effective for synucleinopathies, the suppression of α-syn aggregation may contribute to the development of numerous novel therapeutic targets. Recent research revealed that nicotinic acetylcholine (nACh) receptor activation has neuroprotective effects and promotes the degradation of amyloid protein by activating autophagy. In an in vitro human-derived cell line model, we demonstrated that galantamine, the nAChR allosteric potentiating ligand, significantly reduced the cell number of SH-SY5Y cells with intracellular Lewy body-like aggregates by enhancing the sensitivity of α 7 -nAChR. In addition, galantamine promoted autophagic flux, and prevented the formation of Lewy body-resembled aggregates. In an in vivo synucleinopathy mouse model, the propagation of α-syn aggregation in the cerebral cortex was inhibited by galantamine administration for 90 days. These results suggest that α 7 -nAChR is expected to be a novel therapeutic target, and galantamine is a potential agent for synucleinopathies., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

The major genetic group of Toxoplasma gondii, known as type I, generally displays high lethality in laboratory Mus musculus (mouse) strains, with few exceptions. However, because rodents are the primary reservoir hosts for T. gondii, if this characteristic manifests in the wild, type I strains would be extinct. Therefore, we hypothesized that populations of wild rodents capable of harboring type I T. gondii asymptomatically exist globally and are not limited to a few localized areas, as previously thought. The strength of mouse resistance to T. gondii is known to depend on the affinity of the mouse-expressed immunity-related GTPases B2 (IRGB2) protein for the T. gondii-expressed rphoptry protein 5B (ROP5B) protein. Therefore, the Irgb2 gene sequences of 12 individuals mice captured at two animal farms in Gifu Prefecture, and on an island in Okinawa Prefecture, Japan were determined, and subjected to a molecular phylogenetic analysis together with those of various mouse strains worldwide. The Irgb2 gene of M. musculus individuals captured on one farm and one island showed diverse sequences. The sequences from two individual mice captured in an animal farm formed a single clade with a wild mouse derived CAST/EiJ strain, known for its exceptional resistance to type I T. gondii lethality. These results suggest that M. musuculus individuals resistant to the Type I T. gondii strain may be present in Japan, in addition to the previously known populations in South Asia, Thailand and India.

Objectives: Lobes occasionally displace after lobectomy, referred to as "lobar shifting". However, the benefits, especially in postoperative pulmonary function, remain controversial. This study aimed to measure the effect of lobar shifting on postoperative pulmonary function especially in the right upper lobe., Methods: This retrospective study includes 273 right upper lobectomy patients (lobectomy group) and 24 right upper segmentectomy patients (segmentectomy group) from 2012 to 2021. The lobectomy group was further subdivided based on their Synapse Vincent ® image: with their postoperative middle lobe bronchus shifted toward the head (shift group: 176 cases) and without (non-shift group: 97 cases). Several factors were examined to determine the cause of lobar shifting. The rate of measured actual postoperative forced expiratory volume in 1 s (FEV1.0) to predicted postoperative FEV1.0 was analyzed and compared among the three groups., Results: Factors that correlated with lobar shifting included age (p < 0.001), a relatively small middle lobe volume (p = 0.03), no adhesions (p < 0.001), and good upper/middle and middle/lower lobulation (p = 0.04, p = 0.02). The rate of measured actual postoperative FEV1.0 to predicted postoperative FEV1 for the shift, non-shift, and segmentectomy groups were 112.5%, 107.9%, and 103.1% (shift vs non-shift: p = 0.04, shift vs segmentectomy: p = 0.02, non-shift vs segmentectomy: p = 0.19)., Conclusions: Lobar shifting after right upper lobectomy is influenced by morphological factors and may have a beneficial impact on postoperative pulmonary function., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

The persistent symptoms of anxiety, depression, and fatigue that follow severe acute respiratory syndrome coronavirus 2 infection and accompany pulmonary inflammation pose significant clinical challenges. However, the correlation between pulmonary inflammation and mental health remains unclear. This study sought to examine the effects of intratracheal injection of lipopolysaccharide (LPS), a bacterial endotoxin, on anxiety-like behaviour in a mouse model suffering with pulmonary inflammation. The reactions of these animal models to new environments were evaluated using light-dark box and hole-board tests as anxiety-inducing stimuli. Microglial responses were evaluated via immunohistochemistry, and serum concentrations of tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. Both intraperitoneal and intratracheal injections of LPS induced anxiety-like behaviours, as indicated by the outcomes of the light-dark box and hole-board tests. Serum levels of TNF-α and IL-6 considerably increased following both injection routes. The protein levels of the 5-HT 2A and 5-HT 1A receptors, which are crucial for neuropsychological function, in the frontal cortex and hippocampus of mice remained unchanged following LPS injections. Notably, hippocampal levels of brain-derived neurotrophic factor (BDNF) remarkably decreased following LPS injections. In the lungs, the administration of LPS via the intratracheal route led to a significant rise in the number of white blood cells present in the bronchoalveolar lavage fluid compared to the intraperitoneal injection method. These findings suggest that inflammation induced by intratracheal LPS injection may lead to anxiety-like behaviours in mice, potentially involving mechanisms related to hippocampal BDNF expression, which contributes to anxiety after pulmonary inflammation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Colonic metastasis from lung cancer is very rare and is typically associated with poor prognosis. Herein, we report the case of a patient who achieved intermediate-term survival using a multimodal treatment approach, including chemotherapy, immunotherapy, radiotherapy, and surgical resection for obstructive colonic metastasis from primary lung adenocarcinoma., Case Presentation: A woman in her 50s presented with anemia and a positive fecal occult blood test. Computed tomography revealed a tumor in the right upper lobe of the lung with mediastinal lymphadenopathy and wall thickening in the transverse colon. Colonoscopy revealed a stricture involving 50% of the colonic lumen. Biopsy revealed a poorly differentiated adenocarcinoma positive for CK-7 and TTF-1, very focally positive for napsin A, and negative for CK-20 and CDX-2. Furthermore, positron emission tomography/CT (PET/CT) showed a high maximum standardized uptake value (SUVmax) of 8.2 in the iliac bone. Based on these findings, the patient was diagnosed with primary lung adenocarcinoma with simultaneous metastasis to the transverse colon and iliac bone (cT4N3M1c, cStage IVB). After receiving first-line chemotherapy with atezolizumab, pemetrexed, and carboplatin, the tumors shrank after 4 courses. Subsequently, the patient received maintenance therapy with atezolizumab and pemetrexed. However, the tumor enlarged after 10 courses. Second-line chemotherapy with docetaxel and ramucirumab (3 courses) failed to achieve tumor reduction. Colonoscopy revealed an impassable colonic tumor. Nineteen months after diagnosis, surgery was planned for imminent intestinal obstruction. We determined that the colonic tumor was resectable, because laparoscopic exploration revealed no other metastases. The tumor was resected by partial colectomy with ileocolonic anastomosis. The postoperative course was uneventful. Pathological examination revealed a resection margin that was negative for malignancy, and the histological type was consistent with metastatic lung adenocarcinoma. The patient then received nab-paclitaxel therapy; however, she developed symptoms of superior vena cava syndrome after 3 courses. The patient received palliative irradiation (30 Gy/10 fr) followed by nivolumab. She soon developed a solitary brain metastasis, and stereotactic irradiation was planned. After 3 courses of nivolumab, the metastasis was reduced significantly, and stereotactic brain irradiation was canceled. The lung tumor and mediastinal lymphadenopathy gradually shrank, and the patient survived for 13 months after surgery without disease progression., Conclusions: In this case, surgical resection of colonic metastasis from primary lung adenocarcinoma may have contributed to the short-term prognosis as a bridge-to-next available multimodal treatment., (© 2024. The Author(s).)

The stiffness of human cancers may be correlated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p < 0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p < 0.001 for all). Our findings suggest that tissue stiffness may be a useful marker to distinguish brain tumors from surrounding parenchymal tissue during microsurgery, and that haptic forceps may help neurosurgeons to sense minute changes in tissue stiffness., (© 2024. The Author(s).)

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) is a tumor suppressor gene, and SMARCB1 deficits have been associated with numerous malignant tumors. Carcinomas with a SMARCB1 deficit generally have a poor prognosis. In the head and neck region, there have been many recent cases of SMARCB1-deficient sinonasal carcinoma, but reports of extrasinonasal sites are extremely rare. This study reports a case of SMARCB1-deficient tumor in the right parapharyngeal space. A 64-year-old woman with right neck swelling was presented to our hospital, and imaging revealed a tumor in the right parapharyngeal space. After four years of follow-up, the tumor had increased in size, and a biopsy revealed deficits in SMARCB1 in the tumor cells. No definitive histological diagnoses were made. Radiation reduced the size of the tumor, and the patient survived without progression, three years after completion of treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kamimura et al.)

Background: fluoride is a beneficial ion that has been used in various fields, from industrial products to therapeutics. However, due to its narrow therapeutic index, fluoride sometimes acts as a toxic agent at relatively higher concentrations in the human body. Based on the interest in genetic stability, its cytotoxic effects have been investigated mainly in nucleated, adherent cells, such as fibroblasts. However, the sensitivity of blood cells, especially anucleate platelets, to fluoride is poorly understood. To fill this gap in the literature, we investigated the effects of relatively low levels of fluoride on platelet energy metabolism, function, and viability., Methods: Platelet-rich plasma (PRP) was prepared from 15 non-smoking healthy male adults (age: 28-63) and treated with NaF (0.5 or 1.0 mM) in microtubes for up to 3 days. Platelet function was evaluated based on aggregation and adhesion activities. Platelet energy metabolism was evaluated based on intracellular ATP levels, extracellular lactate levels, and respiration activities. The mitochondrial membrane potential (Em) and localization of reactive oxygen species (ROS) were visualized using cytochemical methods. Platelet viability was evaluated by cell counting and tetrazolium reduction., Result: NaF (1 mM) significantly reduced platelet viability and inhibited functions. Behind these phenomena, NaF substantially decreased mitochondrial Em and increased ROS production along with significant decreases in oxygen consumption and ATP levels. Simultaneously, NaF increased the lactate levels. Although not statistically significant, similar effects were observed at 0.5 mM NaF., Conclusion: At relatively low levels, NaF has the potential to attenuate platelet function probably primarily through the inhibition of mitochondrial energy generation. Cytotoxicity may be directly related to ROS production. These findings suggest that when used topically, for example, for caries prevention in the oral cavity, NaF could interfere with wound healing and tissue regeneration by endogenous and exogenously added platelets in the form of PRP., Competing Interests: The authors declare no conflicts of interest. Particularly, the authors have no benefit in writing the innovativeness of the dye (MT-1) used in the present study., (Copyright © 2024 Tsujino, Kasahara, Kawabata, Watanabe, Nishiyama, Kitamura, Watanabe, Okudera, Mochizuki, Ushiki and Kawase.)

Introduction: In this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice., Methods: To induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light-dark test 24 h after LPS treatment., Results: Repeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT 1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT 2A receptor agonist, enhanced anxiety-like behavior in mice. LPS treatment significantly increased serotonin (5-HT) 2A receptor mRNA expression in the frontal cortex, whereas 5-HT 1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT 2A receptor., Discussion: These findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT 2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors., Competing Interests: 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 Okawa, Ushio, Izushi, Kitamura, Zamami and Sendo.)

Many improvements have been made to bring infant formula (IF) closer to human milk (HM) regarding its nutritional and biological properties. Nevertheless, the protein components of HM and IF are still different, which may affect their digestibility. This study aimed to evaluate and compare the protein digestibility of HM and IF using the infant INFOGEST digestion method. Pooled HM and a commercial IF were subjected to the infant INFOGEST method, which simulates the physiological digestion conditions of infants, with multiple directions, i.e. the curd state, gel images of SDS-PAGE, molecular weight distribution, free amino acid concentrations and in vitro protein digestion rate. HM underwent proteolysis before digestion and tended to have a higher protein digestion rate with finer curds during gastric digestion, than the IF. However, multifaceted analyses showed that the protein digestibility of HM and IF was not significantly different after gastrointestinal digestion. In conclusion, the infant INFOGEST method showed that the digestibility of HM and IF proteins differed to some extent before digestion and after gastric digestion, but not at the end of gastrointestinal digestion. The findings of this study will contribute to the refinement of IF with better protein digestibility in infant stomach.

The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGO) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the ovarian reserve. Conditional loss of CHD4 in perinatal mouse oocytes results in acute death of NGOs and depletion of the ovarian reserve. CHD4 establishes closed chromatin at regulatory elements of pro-apoptotic genes to prevent cell death and at specific genes required for meiotic prophase I to facilitate the transition from meiotic prophase I oocytes to meiotic arrested NGOs. In addition, CHD4 establishes closed chromatin at the regulatory elements of pro-apoptotic genes in male germ cells, allowing male germ cell survival. These results demonstrate a role for CHD4 in defining a chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of both female and male germ cells., Competing Interests: Ethics declarations Competing Interests The authors declare no competing interests.

The global challenge of on-site detection of highly enriched uranium (HEU), a substance with considerable potential for unauthorized use in nuclear security, is a critical concern. Traditional passive nondestructive assay (NDA) techniques, such as gamma-ray spectroscopy with high-purity germanium detectors, face significant challenges in detecting HEU when it is shielded by heavy metals. Addressing this critical security need, we introduce an on-site detection method for lead-shielded HEU employing a transportable NDA system that utilizes the 252 Cf rotation method with a water Cherenkov neutron detector. This cost-effective NDA system is capable of detecting 4.17 g of 235 U within a 12 min measurement period using a 252 Cf source of 3.7 MBq. Integrating this system into border control measures can enhance the prevention of HEU proliferation significantly and offer robust deterrence against nuclear terrorism., (© 2024. The Author(s).)

Background: The study aim was to elucidate the effect of the 2024 Noto Peninsula earthquake on outpatient chemotherapy treatment of cancer survivors at Kanazawa Medical University Hospital (KMUH), Japan., Methods: Medical and nursing records for January 4-31, 2024, from KMUH were retrospectively collected, and data for 286 participants were analyzed., Results: Of the 286 participants, 95.1% were able to attend their first scheduled appointment. Of the 12 (4.2%) who could not attend because of the earthquake, 7 (58.3%) rescheduled their appointments. A total of 8 participants (2.8%) were unable to attend their second scheduled appointment in January, despite being able to attend their first appointment; 3 (37.5%) of these participants reported that they were unable to attend their appointments because of the effect of the earthquake. Chemotherapy was not administered to 53 (18.5%) participants who did attend, mainly owing to neutropenia, progressive disease, rash, and anemia. Evacuation information was available for 25 participants (8.7%); of these, 8 (28.6%) evacuated to their homes, 7 (25.0%) to public shelters, and 4 (14.3%) to apartments near the hospital. Disaster status information was obtained from 62 participants (21.7%), and indicated experiences such as home damage, water outages, and relying on transportation assistance from family to attend appointments., Conclusions: Most cancer survivors receiving chemotherapy at KMUH were able to maintain outpatient visits. However, a few could not attend because of the earthquake. Further studies are needed to provide more detailed information on the effect of disasters on cancer survivors and the potential factors underlying non-attendance at medical appointments., (© 2024. The Author(s).)

Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet. Here, we conducted the structure-activity relationship studies of pyrogallol and its structurally related compounds to understand the mechanism of IL-9 gene suppression by pyrogallol. 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay showed that the antioxidative activity of catechol, resorcinol, phloroglucinol, and gallic acid is 60.1%, 10.4%, 18.8%, and 113.5% of pyrogallol, respectively. Catechol, resorcinol, and phloroglucinol did not suppress NFAT dephosphorylation. Gallic acid suppressed dephosphorylation of NFAT. Gallic acid also suppressed ionomycin-induced up-regulation of IL-9 gene expression with the IC 50 value of 82.6 μM. However, catechol, resorcinol and phloroglucinol showed no suppressive activity. In addition, using gallic acid-immobilized beads, we isolated and identified Poly(U)-binding-splicing factor 60 (PUF60) as a pyrogallol binding protein. These results suggest that the antioxidative activity of pyrogallol is not likely to be the mechanism of IL-9 gene suppression. Data also suggest that PUF60 is one of its target molecules responsible for the suppression of calcineurin/NFAT signaling by pyrogallol., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Objectives: Hikikomori is commonly defined as a social condition in which individuals avoid social participation and relationships beyond their family members by confining themselves to a room or their house for 6 months or longer. Hikikomori has been predominantly considered a problem among young people; however, as the population is ageing, hikikomori has also emerged as a social issue among adults. Nevertheless, no comparative studies have examined the differences in the factors associated with hikikomori among teenagers/young adults and middle-aged/older adults. Thus, this phenomenon has not been thoroughly examined, and it remains unclear whether the risk factors vary between teenagers/young adults and middle-aged/older adults. Based on the Japan Cabinet Office's definition of hikikomori, this cross-sectional study evaluated the prevalence and related factors of hikikomori among the working age population (15-64 years), utilising univariate and multivariate analyses. The study also compared differences in the prevalence of and factors related to hikikomori between teenagers/young adults and middle-aged/older adults., Methods: We distributed self-administered questionnaires to individual participants and their families between 24 December 2020 and 18 January 2021., Results: Data from an anonymised sample of 3,092 individuals (split into two groups of 15-39 and 40-64 years) were subjected to analysis. The results revealed a hikikomori prevalence of 2.3% in the target population; the prevalence rate was 2.12% among individuals aged 15 to 39 years and 2.42% among those aged 40 to 64 years. The analysis demonstrated strong correlations between hikikomori and several factors, including unemployment, truancy, a history of psychiatric consultation or hospitalisation, being male and the absence of ibasho , which is defined as a place where individuals can feel peace, security, acceptance and belonging. The factors associated with hikikomori differed between teenagers/young adults and middle-aged/older adults., Conclusion: Our findings, thus, contribute to existing research by providing a comparative analysis of risk factors across different age groups.

Objective: In Japan, intravenous injection of a 7 % solution of sodium bicarbonate (NaHCO 3 ) had been originally developed to inhibit motion sickness and then have long been used to treat vertigo. Previously, we reported that Fos-positive neurons appear in the amygdala after hypergravity stimulation in rats. In the present study, we examined whether injection of 7 % NaHCO 3 inhibits hypergravity-induced Fos expression in the neurons in the central nucleus of the amygdala in rats., Methods: Rats were exposed to 2 G hypergravity in an animal centrifuge device for 3 h. A solution of 7 % NaHCO 3 at a dose of 4 mM/kg was injected intraperitoneally before 2 G hypergraviy. Fos-positive neurons in the amygdala were stained immunohistochemically., Results: The number of Fos-positive neurons in the central nucleus of the amygdala was significantly increased after 2 G hypergravity in rats that received no drugs or saline, compared to that in rats exposed only to the noise of the centrifuge and received 7 % NaHCO 3 solution. The number of Fos-positive neurons in the central nucleus of the amygdala after 2 G hypergravity was significantly decreased in rats that received 7 % NaHCO 3 solution, compared to that in rats that received no drugs or saline., Conclusion: Since Fos expression is a marker of activated neurons, the present findings suggest that hypergravity activates the amygdala and that administration of 7 % NaHCO 3 suppresses hypergravity-induced activation of the amygdala. Hypergravity disturbs spatial orientation to produce motion sickness and the amygdala is involved in fear response. Recently, Ziemann et al. suggested that fear-evoking stimuli reduce the pH in the amygdala to activate it, leading to induction of fear behavior and that administering HCO 3 - attenuates fear behavior [Cell 2009; 139: 1012-1021]. Therefore, it is possible that hypergravity reduces the pH in the amygdala to activate it, thereby inducing the fear associated with motion sickness and that administration of 7 % NaHCO 3 increases the brain pH thereby suppressing hypergravity-induced activation of the amygdala and inhibiting the fear associated with motion sickness. In patients with vertigo, 7 % NaHCO 3 therapy may increase the brain pH thereby suppressing the activation of the amygdala and inhibiting the fear associated with vertigo to elicit a beneficial clinical effect., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in this study., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study aimed to evaluate the safety and feasibility of early chest tube removal after anatomic pulmonary resection, regardless of the drainage volume., Methods: We conducted a multicenter, randomized, controlled, noninferiority trial. Patients with greater than 300 mL drainage volume during postoperative day 1 were randomly assigned to group A (tube removed on postoperative day 2) and group B (tube retained until drainage volume ≤300 mL/24 hours). The primary end point was the frequency of respiratory-related adverse events (grade 2 or higher based on the Clavien-Dindo classification) within 30 days postoperatively., Results: Between April 2019 and October 2021, 175 patients were assigned to group A (N = 88) or group B (N = 87). One patient in group B who experienced chylothorax was excluded from the study. Respiratory-related adverse events were observed in 10 patients (11.4%) in group A and 12 patients (14.0%) in group B (P = .008). The frequencies of thoracentesis or chest tube reinsertion were not significantly different (8.0% and 9.3% in groups A and B, respectively, P = .752). Additionally, the duration of chest tube placement was significantly shorter in group A than in group B (median, 2 vs 3 days; P < .001). No significant difference between groups A and B was found in postoperative hospital stay (median, 6 vs 7 days, P = .231)., Conclusions: Early chest tube removal, regardless of drainage volume, was safe and feasible in patients who underwent anatomic pulmonary resection., Competing Interests: Conflict of Interest Statement K.T.: honoraria from AstraZeneca, Chugai, Ono, Nippon Kayaku, Johnson & Johnson, and Covidien. T.H.: payment or honoraria from Intuitive Surgical and Johnson and Johnson. M.T.: payment or honoraria Johnson & Johnson Japan, AstraZeneca KK, Eli Lilly Japan, Chugai Pharmaceutical Co, Ltd, Taiho Pharma, Medtronic Japan, Ono Pharmaceutical Co, Ltd, MSD, Bristol-Myers Squibb KK, and Novartis. N.O.: payment or honoraria from Johnson & Johnson. N.I.: payment or honoraria from Taiho Pharma, Bristol Myers, Chugai Pharma, Fuji Film Nihon Mediphysics, MSD, Daiichi-Sankyo, Boehringer Ingelheim, Shionogi, Medtronic, Johnson & Johnson, Olympus, Roche, and Ono Pharma. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We examine the effect of auditory cues occurring in reality on redirection. Specifically, we set two hypotheses: the auditory cues emanating from fixed positions in reality (Fixed sound, FS) increase the noticeability of redirection, while the auditory cues whose positions are manipulated consistently with the visual manipulation (Redirected sound, RDS) decrease the noticeability of redirection. To verify these hypotheses, we implemented an experimental environment that virtually reproduced FS and RDS conditions using binaural recording, and then we conducted a user study ( N=18) to investigate the detection thresholds (DTs) for rotational manipulation and the sound localization accuracy of the auditory cues under FS and RDS, as well as the baseline condition without auditory cues (No sound, NS). The results show, against the hypotheses, FS gave a wider range of DTs than NS, while RDS gave a similar range of DTs to NS. Combining these results with those of sound localization accuracy reveals that, rather than the auditory cues affecting the participants' spatial perception in VR, the visual manipulation made their sound localization less accurate, which would be a reason for the increased range of DTs under FS. Furthermore, we conducted a follow-up user study ( N=11) to measure the sound localization accuracy of FS where the auditory cues were actually placed in a real setting, and we found that the accuracy tended to be similar to that of virtually reproduced FS, suggesting the validity of the auditory cues used in this study. Given these findings, we also discuss potential applications.

This study presents a case of a 72-year-old man diagnosed with non-small cell lung cancer (cT4N0M0) referred to our hospital for possible surgical treatment of a solitary nodule detected in the mesorectum. The patient had received combined chemoradiotherapy and achieved a complete response 13 months before the presentation. On examination, the mesorectal nodule was incidentally detected during surveillance computed tomography, and the maximum standardized uptake value of the nodule was 10.3. Because of the potential malignancy and need for en-bloc resection of the nodule, we performed laparoscopically assisted high anterior resection of the rectum. The postoperative course was uneventful. Notably, while pathological examination revealed that the mesorectal nodule comprised an intravenous organized thromboembolism, malignancy was not observed. These findings suggest that although positron emission tomography/computed tomography with 18 F-fluorodeoxyglucose is useful for the diagnosis of malignant diseases, surgical resection might be the most reliable option for complex cases such as ours., Competing Interests: The authors declare that they have no conflict of interest., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background An increased risk of anemia during edoxaban thromboprophylaxis in orthopedic surgery has been reported. However, the risk factors for the exacerbation of anemia requiring transfusion with irradiated red blood cell concentrates during postoperative edoxaban thromboprophylaxis remain unknown. Therefore, this study investigated the factors that increase the possibility of transfusion during edoxaban thromboprophylaxis after orthopedic surgery by reanalyzing clinical data from a previous collection. Methods A total of 221 patients who underwent total hip or knee arthroplasty at a single center between July 2011 and June 2012 were included in this study. Among these, 167 patients who received 30 mg of postoperative edoxaban thromboprophylaxis were retrospectively analyzed to identify critical factors for transfusion during edoxaban thromboprophylaxis after orthopedic surgery. Results Lower preoperative hemoglobin levels and higher intraoperative blood loss per body weight were significantly associated with an increase in the frequency of transfusion during postoperative edoxaban thromboprophylaxis. These factors were also potentially related to increased coagulation parameters during edoxaban thromboprophylaxis. Conclusion Our study shows that lower preoperative hemoglobin levels and higher intraoperative blood loss are associated with increased coagulation parameters with edoxaban thromboprophylaxis after orthopedic surgery and may lead to worsening of anemia, thereby requiring blood transfusion., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of the National Hospital Organization at the Okayama Medical Centre issued approval 2019–056. This study was approved by the Institutional Review Board of the National Hospital Organization (NHO) at the Okayama Medical Centre (approval number: 2019–056). All procedures involving human participants were performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan and the principles of the Declaration of Helsinki. Since this study had a retrospective design, and anonymity was secured, the Institutional Review Board of the NHO at the Okayama Medical Centre waived the requirement for written informed consent, and an opt-out method was applied by notifications displayed on the hospital’s website. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Izushi et al.)

Purpose: We developed new deep learning-based hierarchical brain segmentation (DLHBS) method that can segment T1-weighted MR images (T1WI) into 107 brain subregions and calculate the volume of each subregion. This study aimed to evaluate the repeatability and reproducibility of volume estimation using DLHBS and compare them with those of representative brain segmentation tools such as statistical parametric mapping (SPM) and FreeSurfer (FS)., Methods: Hierarchical segmentation using multiple deep learning models was employed to segment brain subregions within a clinically feasible processing time. The T1WI and brain mask pairs in 486 subjects were used as training data for training of the deep learning segmentation models. Training data were generated using a multi-atlas registration-based method. The high quality of training data was confirmed through visual evaluation and manual correction by neuroradiologists. The brain 3D-T1WI scan-rescan data of the 11 healthy subjects were obtained using three MRI scanners for evaluating the repeatability and reproducibility. The volumes of the eight ROIs-including gray matter, white matter, cerebrospinal fluid, hippocampus, orbital gyrus, cerebellum posterior lobe, putamen, and thalamus-obtained using DLHBS, SPM 12 with default settings, and FS with the "recon-all" pipeline. These volumes were then used for evaluation of repeatability and reproducibility., Results: In the volume measurements, the bilateral thalamus showed higher repeatability with DLHBS compared with SPM. Furthermore, DLHBS demonstrated higher repeatability than FS in across all eight ROIs. Additionally, higher reproducibility was observed with DLHBS in both hemispheres of six ROIs when compared with SPM and in five ROIs compared with FS. The lower repeatability and reproducibility in DLHBS were not observed in any comparisons., Conclusion: Our results showed that the best performance in both repeatability and reproducibility was found in DLHBS compared with SPM and FS.

Background: Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death-ligand 1 (PD-L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD-L1 expression who received MONO or COMB as a first-line treatment. Here, we report updated data and evaluate the long-term outcomes., Methods: We performed a retrospective multicenter study of 298 patients with NSCLC and high PD-L1 expression who received MONO or COMB as first-line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff., Results: In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0-1). At the prolonged data cutoff, the median follow-up was 20.2 (range: 0.1-41.4) months. The median progression-free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow-up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO., Conclusions: COMB may be effective as a first-line treatment for NSCLC with high PD-L1 expression in a selected subset of patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The compound 15-deacetylcalonectrin (15-deCAL) is a common pathway intermediate in the biosynthesis of Fusarium trichothecenes. This tricyclic intermediate is metabolized to calonectrin (CAL) by trichothecene 15- O -acetyltransferase encoded by Tri3 . Unlike other trichothecene pathway Tri gene mutants, the Δ tri3 mutant produces lower amounts of the knocked-out enzyme's substrate 15-deCAL, and instead, accumulates higher quantities of earlier bicyclic intermediate and shunt metabolites. Furthermore, evolutionary studies suggest that Tri3 may play a role in shaping the chemotypes of trichothecene-producing Fusarium strains. To better understand the functional role of Tri3p in biosynthesis and evolution, we aimed to develop a method to produce 15-deCAL by using transgenic Fusarium graminearum strains derived from a trichothecene overproducer. Unfortunately, introducing mutant Tri3 , encoding a catalytically impaired but structurally intact acetylase, did not improve the low 15-deCAL production level of the Δ Fgtri3 deletion strain, and the bicyclic products continued to accumulate as the major metabolites of the active-site mutant. These findings are discussed in light of the enzyme responsible for 15-deCAL production in trichothecene biosynthesis machinery. To efficiently produce 15-deCAL, we tested an alternative strategy of using a CAL-overproducing transformant. By feeding a crude CAL extract to a Fusarium commune strain that was isolated in this study and capable of specifically deacetylating C-15 acetyl, 15-deCAL was efficiently recovered. The substrate produced in this manner can be used for kinetic investigations of this enzyme and its possible role in chemotype diversification.

Background: Acute myeloid leukemia (AML) is the second most common type of leukemia in children. Although prognostic and diagnostic tests of AML patients have improved, there is still a great demand for new reliable clinical biomarkers for AML. Read-through fusion transcripts (RTFTs) are complex transcripts of adjacent genes whose molecular mechanisms are poorly understood. This is the first report of the presence of the PPP1R1B::STARD3 fusion transcript in an AML patient. Here, we investigated the presence of PPP1R1B::STARD3 RTFT in a case of AML using paired-end RNA sequencing (RNA-seq)., Case Presentation: A Persian 12-year-old male was admitted to Dr. Sheikh Hospital of Mashhad, Iran, in September 2019 with the following symptoms, including fever, convulsions, hemorrhage, and bone pain. The patient was diagnosed with AML (non-M3-FAB subtype) based on cell morphologies and immunophenotypical features. Chromosomal analysis using the G-banding technique revealed t (9;22) (q34;q13)., Conclusions: Single-cell RNA sequencing (scRNA-seq) analysis suggested that the PPP1R1B promoter may be responsible for the PPP1R1B::STARD3 expression. Alterations in the level of lipid metabolites implicate cancer development, and this fusion can play a crucial role in the cholesterol movement in cancer cells. PPP1R1B::STARD3 may be considered a candidate for targeted therapies of the cholesterol metabolic and the PI3K/AKT signaling pathways involved in cancer development and progression., (© 2024. The Author(s).)

Zolpidem, a non-benzodiazepine hypnotic, is primarily used to treat insomnia. In a previous study, pior treatment with non-benzodiazepine receptor agonists was associated with inflammation. The present study aimed to clarify the association between the effects of zolpidem and inflammation in mice treated with lipopolysaccharide (LPS), a known model of inflammation. We assessed the zolpidem-induced loss of righting reflex (LORR) duration 24 h after LPS treatment in mice. Additionally, the expressions of γ-aminobutyric acid (GABA)A receptor subunit and K+-Cl- cotransporter isoform 2 (KCC2) mRNA in the hippocampus and frontal cortex were examined in LPS-treated mice. Pretreatment with LPS was associated with significantly prolonged duration of zolpidem-induced LORR compared to control mice. This effect was significantly attenuated by administering bicuculline, a GABAA receptor antagonist, or flumazenil, a benzodiazepine receptor antagonist, in LPS-treated mice. Compared to controls, LPS-treated mice showed no significant change in the expression of GABAA receptor subunits in the hippocampus or frontal cortex. Bumetanide, an Na+-K+-2Cl- cotransporter isoform 1 blocker, attenuated the extended duration of zolpidem-induced LORR observed in LPS-treated mice. LPS significantly decreased Kcc2 mRNA expression in the hippocampus and the frontal cortex. These findings suggest that inflammation increases zolpidem-induced LORR, possibly through a reduction in KCC2 expression., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective: There have been several reports on rechallenge with docetaxel, cabazitaxel, abiraterone acetate, or ethinylestradiol for metastatic castration-resistant prostate cancer (mCRPC). However, the efficacy of enzalutamide rechallenge for mCRPC has not been evaluated., Methods: We retrospectively reviewed 63 consecutive patients who received enzalutamide for mCRPC at our institution between 2014 and 2022. Eight of these patients underwent rechallenge with enzalutamide after disease progression on prior enzalutamide and other therapy and were the focus of this study. The prostate-specific antigen (PSA) response (PSA decrease >50%), PSA progression-free survival, treatment duration, overall survival (OS) after CRPC, and treatment-related adverse events were evaluated., Results: PSA decline to enzalutamide rechallenge was observed in 6 patients (75%), of which 2 patients had a PSA response. The median treatment duration was 4 months (range 1-12) and median PSA progression-free survival was 3 months (range 1-7). Median OS after CRPC was 41 months. OS after CRPC was not increased in patients with a PSA response. No toxicities were worse than grade ≥3., Conclusion: Enzalutamide rechallenge achieved a PSA response in a quarter of our patients with mCRPC after disease progression on prior enzalutamide. However, no improvement of OS was identified in these patients.

Objective: This review will identify the effectiveness of non-pharmacological interventions in preventing iron deficiency anemia in pregnant women with a normal course of pregnancy., Introduction: The global prevalence of anemia among pregnant women is 36.5%, posing risks to women and fetuses. This underscores the need for effective prevention; however, the effectiveness of non-pharmacological approaches in preventing pregnancy anemia remains unclear., Inclusion Criteria: This review will encompass experimental and quasi-experimental studies on the following approaches to prevent anemia during pregnancy: recommendations for dietary supplements, oral iron supplements (over the counter), provision of supplements to promote iron absorption, participation in anemia prevention education, and provision of information. There will be no restrictions on the duration or frequency of intervention, and longitudinal intervention studies will be included. In studies with a control group, the comparator may be usual care or pharmacological interventions; in studies without, it may involve no intervention, temporal comparisons, or baseline periods without non-pharmacological interventions. Evaluation of hemoglobin, hematocrit, and ferritin will be included as primary outcomes. Low birth weight, preterm birth, amount of blood loss at delivery, small for gestational age, and Apgar scores will be included as secondary outcomes., Methods: A search will be conducted in MEDLINE (Ovid), Embase, CINAHL (EBSCOhost), Scopus, Australian New Zealand Clinical Trials Registry, Cochrane Central Register of Controlled Trials, and ICHUSHI-Web. Researchers will screen studies, extract data, assess the quality of studies, and analyze the data in accordance with the JBI guidance for systematic reviews of effectiveness. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the certainty of the findings., Review Registration: PROSPERO CRD42022344155., Competing Interests: The authors declare no conflict of interest., (COPYRIGHT © 2023 THE AUTHORS. PUBLISHED BY WOLTERS KLUWER HEALTH, INC. ON BEHALF OF JBI.)

Background: Mirtazapine blocks 5-hydroxytryptamine type (5-HT) 2A , 5-HT 2C , 5-HT 3 and histamine H 1 receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers., Methods: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h)., Results: Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0., Conclusions: Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute., Competing Interests: Declaration of competing interest Dr. Iihara has received personal fees from Taiho, Chugai, Yakult, Astellas, Eli Lilly, Daiichi Sankyo, AstraZeneca, Nippon Kayaku, Ono, and Nippon Boehringer Ingelheim and consulting fees for their institution from Taiho and Eisai outside the submitted work. Dr. Morita has received personal fees from AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Amgen, Eli Lilly, Takeda, Taiho, Thermo Fisher, Nihon Kayaku, MSD, Novartis, Pfizer outside the submitted work. Ms. Hirose has received personal fees from Eli Lilly, Eisai, Merck, Chugai, and Nippon Kayaku outside the submitted work. Dr. Kawazoe has received grants for their institution from Eli Lilly outside the submitted work. Dr. Fukunaga has received personal fees from Boehringer Ingelheim, Novartis, Sanofi, GlaxoSmithKline, AstraZeneca, and Kyorin outside the submitted work and grants for their institution from Boehringer Ingelheim and Chugai outside the submitted work. Dr. Fukunaga has received personal fees from Boehringer Ingelheim, Novartis, Sanofi, GlaxoSmithKline, AstraZeneca, and Kyorin outside the submitted work and grants for their institution from Boehringer Ingelheim and Chugai outside the submitted work. Dr. Suzuki has received personal fees from Toa Eiyo, Asahi Kasei, Daiichi Sankyo, Pfizer, Eisai, Nippon Shinyaku, Celltrion Healthcare Japan, Otsuka, Sandoz, Tsumura, Nipro, Taiho, Kyowa-Kirin, Nippon Chemiphar, Japan Blood Products Organization, Takeda, and Nippon Boehringer Ingelheim and grants for their institution from Nippon Kayaku, Asahi Kasei, Chugai, Taiho, Daiichi Sankyo, Japan Blood Products Organization, Mochida, and Sun Pharma outside the submitted work. Other authors do not have conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Epigenetic priming presets chromatin states that allow the rapid induction of gene expression programs in response to differentiation cues. In the germline, it provides the blueprint for sexually dimorphic unidirectional differentiation. In this review, we focus on epigenetic priming in the mammalian male germline and discuss how cellular memories are regulated and inherited to the next generation. During spermatogenesis, epigenetic priming predetermines cellular memories that ensure the lifelong maintenance of spermatogonial stem cells and their subsequent commitment to meiosis and to the production of haploid sperm. The paternal chromatin state is also essential for the recovery of totipotency after fertilization and contributes to paternal epigenetic inheritance. Thus, epigenetic priming establishes stable but reversible chromatin states during spermatogenesis and enables epigenetic inheritance and reprogramming in the next generation., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

An efficient method for the azidomethylation of amines using azidomethyl esters with silyl triflates is described. This protocol enables the azidomethylation of various amines that can be activated with silyl groups, including nucleobases.