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Katsuhiko Shimizu,1 Masao Nakata,1 Shinsuke Saisho,1 Masayuki Inubushi,2 Norihito Okumura,3 Tomohiro Murakawa,4 Motohiro Yamashita,5 Hiroshige Nakamura,6 Yoshifumi Sano,7 Kazuhiko Kataoka,8 Shinichi Toyooka9 1Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Japan; 2Division of Nuclear Medicine, Department of Radiology, Kawasaki Medical School, Kurashiki, Japan; 3Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan; 4Department of Thoracic Surgery, Kansai Medical University, Osaka, Japan; 5Department of Thoracic Surgery, Shikoku Cancer Center, Matsuyama, Japan; 6Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan; 7Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, Japan; 8Department of Thoracic Surgery, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan; 9Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, JapanCorrespondence: Katsuhiko Shimizu, Department of General Thoracic Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan, Tel +81-86-462-1124, Fax +81-86-464-1124, Email kshimizu@med.kawasaki-m.ac.jpBackground: Induction therapy followed by surgery is recommended as an alternative treatment strategy for locally advanced non-small cell lung cancer (NSCLC). Patients who achieve pathologic response after induction therapy have better outcomes than non-responders; therefore, therapeutic response must be evaluated. Recently, new approaches for monitoring therapeutic responses, which are based on 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET), have been developed. In this study, we evaluated the predictive value of Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST), which uses standardized uptake values corrected for lean body mass (SUL) and total lesion glycolysis (TLG).Methods: A total of 130 patients in the Setouchi Lung Cancer Group who underwent FDG-PET imaging before and after induction therapy prior to a planned surgical resection for NSCLC between 2007 and 2016 were studied retrospectively. The pathologic responses of the primary lung tumors and metastatic lymph nodes were compared with their responses based on evaluation using PERCIST.Results: Postoperative pathologic studies revealed pathologic complete response (pCR) in 42 (32.3%) patients. PERCIST was significantly correlated with pathologic response (p < 0.001). The sensitivity, specificity, and accuracy of PERCIST for predicting pCR were 16.7% (7/42), 88.6% (78/88), and 65.4% (85/130), respectively. Patients with pCR had significantly higher reduction rates in SULpeak for both primary lung tumors and metastatic lymph nodes and TLG for primary tumors than non-responders. In a multivariate Cox regression analysis, tumor site in upper lobes, reduction rate of TLG in primary tumor, and pathologic N0 were independent predictors of favorable recurrence-free survival (RFS).Conclusion: Our study suggested that PERCIST, especially the rate of TLG reduction rate, are useful to predict the pathological response and prognosis after induction therapy. Although improvement is necessary, PERCIST can be a promising method of the post-induction status in lung cancer. Further research is needed to confirm our findings.Keywords: non-small cell lung cancer, FDG PET, PERCIST, SUL, TLG

This article presents a case study of an 83-year-old man who was admitted to the hospital with symptoms including fever, pain, and loss of consciousness. The patient was diagnosed with septic shock and underwent whole blood transcriptome analysis to understand the pathogenesis of the disease. The analysis revealed changes in biological pathways related to inflammatory responses and immune suppression. The patient ultimately died of multiple organ failure due to septic shock. The study suggests that whole blood transcriptomic analysis can provide insights into the process of acute systemic inflammatory response and the challenges of maintaining homeostasis. [Extracted from the article]

Aromatic sensitizers and related substances (SRCs), which are crucial in the paper industry for facilitating color-forming and color-developing chemical reactions, inadvertently contaminate effluents during paper recycling. Owing to their structural resemblance to endocrine-disrupting aromatic organic compounds, concerns have arisen about potential adverse effects on aquatic organisms. We focused on SRC effects via the aryl hydrocarbon receptor (AHR), employing molecular docking simulations and zebrafish (Danio rerio) embryo exposure assessments. Molecular docking revealed heightened binding affinities between certain SRCs in the paper recycling effluents and zebrafish Ahr2 and human AHR, which are pivotal components in the SRC toxicity mechanism. Fertilized zebrafish eggs were exposed to SRCs for up to 96 h post fertilization; among these substances, benzyl 2-naphthyl ether (BNE) caused morphological abnormalities, such as pericardial edema and shortened body length, at relatively low concentrations (1 μM) during embryogenesis. Gene expression of cytochrome P450 1A (cyp1a) and ahr2 was also significantly increased by BNE. Co-exposure to the AHR antagonist CH-223191 only partially mitigated BNE's phenotypic effects, despite the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin being relatively well restored by CH-223191, indicating BNE's AHR-independent toxic mechanisms. Furthermore, some SRCs, including BNE, exhibited in silico binding affinity to the estrogen receptor and upregulation of cyp19a1b gene expression. Therefore, additional insights into the toxicity of SRCs and their mechanisms are essential. The present results provide important information on SRCs and other papermaking chemicals that could help minimize the environmental impact of the paper industry. Environ Toxicol Chem 2024;43:2176-2188. © 2024 SETAC., (© 2024 SETAC.)

Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6-6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

We isolated ten compounds from methanolic extract of the peels of sacred lotus (Nelumbo nucifera) rhizomes which were identified as β-sitosterol linoleate 1, β-sitosterol 2, lupeol 3, stigmasterol 3-O-β-D-glucoside 4, oleanolic acid 5, betulinic acid 6, pinoresinol 7, 4-hydroxybenzoic acid 8, catechin 9 and gallocatechin 10. All of the isolated compounds from the peels of sacred lotus rhizomes are reported for the first time, and were investigated for their anti-allergic activity. We found that three of them, stigmasterol 3-O-β-D-glucoside 4, oleanolic acid 5 and pinoresinol 7, were capable of inhibiting A23187-induced degranulation in RBL-2H3 cells with IC 50 values 0.18 ± 0.01 mM, 0.28 ± 0.06 mM, and 0.27 ± 0.01 mM, respectively. With an exception to 4, compounds 5 and 7 achieved the anti-allergic effect without affecting the cells viability even at higher concentrations with their selectivity indices (SI) being >5. By reducing A23187-induced degranulation, it is suggestive of a mechanism attenuation of Ca 2+ elevation. Our findings suggest that, the peels of sacred lotus rhizomes would be beneficial for providing an inexpensive source for the production of bioactive compounds with anti-allergic effect., Competing Interests: Declaration of competing interest The authors declared no potential conflict of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: The treatment and prognosis of de novo metastatic hormone-sensitive prostate cancer (mHSPC) vary. We established and validated a novel prognostic model for predicting cancer-specific survival (CSS) in patients with mHSPC using retrospective data from a contemporary cohort., Methods: 1092 Japanese patients diagnosed with de novo mHSPC between 2014 and 2020 were registered. The patients treated with androgen deprivation therapy and first-generation anti-androgens (ADT/CAB) were assigned to the Discovery (N = 467) or Validation (N = 328) cohorts. Those treated with ADT and androgen-receptor signaling inhibitors (ARSIs) were assigned to the ARSI cohort (N = 81)., Results: Using the Discovery cohort, independent prognostic factors of CSS, the extent of disease score ≥ 2 or the presence of liver metastasis; lactate dehydrogenase levels > 250U/L; a primary Gleason pattern of 5, and serum albumin levels ≤ 3.7 g/dl, were identified. The prognostic model incorporating these factors showed high predictability and reproducibility in the Validation cohort. The 5-year CSS of the low-risk group was 86% and that of the high-risk group was 22%. Approximately 26.4%, 62.7%, and 10.9% of the patients in the Validation cohort defined as high-risk by the LATITUDE criteria were further grouped into high-, intermediate-, and low-risk groups by the new model with significant differences in CSS. In the ARSIs cohort, high-risk group had a significantly shorter time to castration resistance than the intermediate-risk group., Conclusions: The novel model based on prognostic factors can predict patient outcomes with high accuracy and reproducibility. The model may be used to optimize the treatment intensity of de novo mHSPC., (© 2024. The Author(s).)

Regional cerebral oxygen saturation (ScO 2 ) determined by near-infrared spectroscopy, monitoring both arterial and venous blood oxygenation of the brain, could reflect the balance between oxygen delivery and consumption. The aim of this study was to determine the predictabilities of ScO 2 and estimated oxygen extraction ratio (eO 2 ER) with outcomes in infants with congenital heart disease (CHD). This study was a two-center, retrospective study of patients at 12 months of age or younger with CHD who underwent cardiac surgery. The primary outcome was a composite of one or more major adverse events (MAEs) after surgery: death from any cause, circulatory collapse that needed cardiopulmonary resuscitation, and requirement for extracorporeal membrane oxygenation. Based on the assumptions of arterial to venous blood ratio, eO 2 ER was calculated. A total of 647 cases were included in this study. MAEs occurred in 16 patients (2.5%). There were significant differences in post-bypass ScO 2 [46.61 (40.90, 52.05) vs. 58.52 (51.52, 66.08), p < 0.001] and post-bypass eO 2 ER [0.66 (0.60, 0.78) vs. 0.52 (0.43, 0.61), p < 0.001] between patients with MAEs and patients without MAEs. Area under the receiver operating curve (AUROC) of post-bypass ScO 2 was 0.818 (95% confidence interval: 0.747-0.889), AUROC of post-bypass eO 2 ER was 0.783 (0.697-0.870) and AUROC of post-bypass maximum serum lactate level was 0.635 (0.525-0.746). Both ScO 2 and eO 2 ER, especially after weaning off bypass, are acceptable predictive markers for predicting MAEs after cardiac surgery in infants.(227 words)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A recent meta-analysis has found that patients who have achieved remission of major depressive disorder (MDD) show cognitive dysfunction. Moreover, anticholinergic activity levels are associated with cognitive dysfunction, although the extent of these effects is unclear. Therefore, we measured serum anticholinergic activity (SAA) in blood samples of patients with remitted MDD and examined its relationship with cognitive function., Methods: We recruited 49 patients with remitted MDD following treatment and 165 healthy subjects. Subjects completed the Stroop test and the logical memory (LM) and visual reproduction (VR) subtests from the Wechsler Memory Scale-Revised. We compared cognitive function scores among those with SAA below the limit of quantification (SAA [-]), those with SAA above the limit of quantification (SAA [+]), and healthy controls., Results: The SAA (+) group scored significantly lower (p < 0.001) than the healthy control group on all tests, and the VR score of the SAA (-) group was significantly lower than that of the healthy control group (p = 0.024). LM scores in the SAA (+) group were significantly lower than that of the SAA (-) group (p = 0.033). Multiple regression analysis revealed a significant effect of SAA on the LM score (p = 0.015)., Limitations: Our study was a cross-sectional analysis of a small number of patients., Conclusions: Our results support previous findings that the anticholinergic effect of antidepressants adversely affects cognitive function. Additionally, the cognitive impairment observed may persist because of MDD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hitoshi Maeshima reports a relationship with The Juntendo Institute of Mental Health that includes: funding grants. Hitoshi Maeshima reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees and travel reimbursement. Hitoshi Maeshima reports a relationship with Lundbeck Japan that includes: speaking and lecture fees. Hitoshi Maeshima reports a relationship with Sumitomo Pharma Co Ltd that includes: speaking and lecture fees. Hitoshi Maeshima reports a relationship with Kyowa Pharmaceutical Industry Co Ltd that includes: speaking and lecture fees. Hitoshi Maeshima reports a relationship with Meiji Seika Pharma Co Ltd that includes: speaking and lecture fees. Hitoshi Maeshima reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: speaking and lecture fees. Hitoshi Maeshima reports a relationship with Janssen Pharmaceuticals Inc Japan that includes: speaking and lecture fees. Hitoshi Maeshima reports a relationship with Viatris Inc Japan that includes: speaking and lecture fees. Hajime Baba reports a relationship with The Japan Society for the Promotion of Science that includes: funding grants. Hajime Baba reports a relationship with Eisai Co Ltd that includes: funding grants and speaking and lecture fees. Hajime Baba reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with Sumitomo Pharma Co Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with Janssen Pharmaceuticals Inc Japan that includes: speaking and lecture fees. Hajime Baba reports a relationship with Kyowa Pharmaceutical Industry Co Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with Mitsubishi Tanabe Pharma Corporation that includes: speaking and lecture fees. Hajime Baba reports a relationship with Viatris Inc Japan that includes: speaking and lecture fees. Hajime Baba reports a relationship with Takeda Pharmaceutical Company Limited that includes: speaking and lecture fees. Hajime Baba reports a relationship with Lundbeck Japan that includes: speaking and lecture fees. Hajime Baba reports a relationship with Mylan EPD that includes: speaking and lecture fees. Hajime Baba reports a relationship with Mochida Pharmaceutical Co Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with Sawai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with Kowa Company Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with Towa Pharmaceutical Co Ltd that includes: speaking and lecture fees. Hajime Baba reports a relationship with EA Pharma Co Ltd that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aim: This study aimed to examine the cardiac and overall safety and pharmacokinetic (PK) profiles of soticlestat (TAK-935), an oral, first-in-class selective cholesterol 24-hydroxylase inhibitor., Methods: Data came from a randomised, phase 1 study of soticlestat in 33 healthy Japanese adults (NCT04461483); 24 adults in Part 1 (single-dose soticlestat 200-1200 mg or placebo) and 9 in Part 2 (soticlestat 100-300 mg twice daily or placebo for 21 days). PK sample collection was paired with 12-lead electrocardiogram data from continuous Holter recordings. The concentration-QTc relationship was analysed using a linear mixed-effects model. QTc prolongation safety margins were determined for two scenarios of calculated high clinical exposures: scenario 1 (NCT05064449) involved coadministration of single-dose soticlestat 300 mg with itraconazole or mefenamic acid and scenario 2 (NCT05098054) involved single-dose soticlestat 300 mg administration in participants with mild/moderate hepatic impairment (implementing a 3-fold dose reduction for moderate severity)., Results: Based on concentration-QTc analysis, placebo-corrected change-from-baseline QT values (90% confidence intervals), corrected for heart rate (Fridericia's method), were 0.94 ms (-2.35, 4.23) for soticlestat and 0.63 ms (-3.15, 4.41) for its N-oxide metabolite plasma concentrations at therapeutic doses (soticlestat 300 mg twice daily); safety margins were >2-fold for scenarios of calculated high clinical exposures. No (Part 1) and five (83.3%; Part 2) participants experienced treatment-emergent adverse events (all mild)., Conclusion: There was no evidence for QT prolongation with soticlestat at therapeutic doses or in two scenarios of high clinical exposures, which resulted in regulatory agencies waiving requirements of a thorough QT study. Safety/PK findings aligned with previous soticlestat clinical studies., (© 2024 Takeda Development Center Americas, Inc. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Co-administration of mirogabalin besylate and nonsteroidal anti-inflammatory drugs is effective for neuropathic pain; however, mechanism of its action remains unknown. We aimed to evaluate the mechanism of this synergistic effect of the concomitant administration for neuropathic pain using chronic constriction injury model rats. Fifty male Wister rats of 7-week-old were used. Right sciatic nerve ligation was performed in 40 rats and they were sub-divided into four groups: vehicle, mirogabalin, diclofenac sodium and co-administration of them. Ten rats underwent sham surgery. Fluorogold was attached to sciatic nerve during surgery. Von Frey filament and weight bearing tests were performed on postoperative Day 6 as behavioral assessments and drug was administrated intraperitoneally. Half rats in each group underwent behavioral assessment and perfusion fixation using 4% paraformaldehyde on postoperative Day 7 and remaining on postoperative Day 14. Subsequently, dorsal root ganglion at L4 to L6 was collected and examined immunohistochemistry for calcitonin gene-related peptide, and their immunoreactivity in fluorogold-labeled neurons was measured. Spinal cord at lumbar swelling was resected, immunostained for ionized-calcium-binding adapter molecule-1 and glial fibrillary acidic protein, and immunoreactive neurons in dorsal horn of spinal cords were calculated as the occupancy of them. Mirogabalin suppresses the neuropeptide-release from presynaptic afferent neuron directly and it resulted in suppressing glia cells activation. Diclofenac sodium inhibits cyclooxygenase-2 and prostaglandin production, related to allodynia. These effects of mirogabalin and diclofenac sodium, respectively, inhibited glia cells strongly, which is presumed to be one of the mechanisms for the effectiveness of their co-administration for neuropathic pain., (© 2024 Orthopaedic Research Society.)

The efficacy of transplanting human cranial bone-derived mesenchymal stem cells (hcMSCs) cultured under simulated microgravity (sMG) conditions has been previously reported; however, their effect on cerebral infarction remains unknown. Here, we examined the efficacy of transplanting hcMSCs cultured in an sMG environment into rat models of cerebral infarction. For evaluating neurological function, hcMSCs cultured in either a normal gravity (1G) or an sMG environment were transplanted in rats 1 day after inducing cerebral infarction. The expression of endogenous neurotrophic, axonal, neuronal, synaptogenic, angiogenic, and apoptosis-related factors in infarcted rat brain tissue was examined using real-time polymerase chain reaction and western blotting 35 days after stroke induction. The RNAs of hcMSCs cultured under 1G or sMG environments were sequenced. The results showed that neurological function was significantly improved after transplantation of hcMSCs from the sMG group compared with that from the 1G group. mRNA expressions of nerve growth factor, fibroblast growth factor 2, and synaptophysin were significantly higher in the sMG group than in the 1G group, whereas sortilin 1 expression was significantly lower. RNA sequencing analysis revealed that genes related to cell proliferation, angiogenesis, neurotrophy, neural and synaptic organization, and inhibition of cell differentiation were significantly upregulated in the sMG group. In contrast, genes promoting microtubule and extracellular matrix formation and cell adhesion, signaling, and differentiation were downregulated. These results demonstrate that hcMSCs cultured in the sMG environment may be a useful source of stem cells for the recovery of neurological function after cerebral infarction., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, products, or services that may be related to the subject matter of the article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Histone modifications are catalyzed and recognized by specific proteins to regulate dynamic DNA metabolism processes. NSD2 is a histone H3 lysine 36 (H3K36)-specific methyltransferase that is associated with both various transcription regulators and DNA repair factors. Specifically, it has been implicated in the repair of DNA double-strand breaks (DSBs); however, the role of NSD2 during DSB repair remains enigmatic. Here, we show that NSD2 does not accumulate at DSB sites and that it is not further mobilized by DSB formation. Using three different DSB repair reporter systems, which contained the endonuclease site in the active thymidine kinase gene (TK) locus, we demonstrated separate dose-dependent effects of NSD2 on homologous recombination (HR), canonical-non-homologous end joining (c-NHEJ), and non-canonical-NHEJ (non-c-NHEJ). Endogenous NSD2 has a role in repressing non-c-NHEJ, without affecting DSB repair efficiency by HR or total NHEJ. Furthermore, overexpression of NSD2 promotes c-NHEJ repair and suppresses HR repair. Therefore, we propose that NSD2 has functions in chromatin integrity at the active regions during DSB repair., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Objective: To compare the incidence of hypotension between remimazolam and sevoflurane under general anesthesia for cardiac catheterization in patients with congenital heart disease., Design: Retrospective observational study., Setting: A single university hospital with 300 pediatric cardiac catheterizations by general anesthesia performed annually., Participants: Patients younger than 15 years who underwent cardiac catheterization under general anesthesia between March 1, 2021, and December 31, 2022. Exclusion criteria were general anesthesia maintained with other than remimazolam or sevoflurane, receipt of remifentanil, American Society of Anesthesiologists score 4 or 5, emergency procedures, and no direct arterial pressure measurement., Interventions: General anesthesia was maintained with remimazolam or sevoflurane., Measurements and Main Results: A total of 309 patients were analyzed, including 28 in the remimazolam group and 281 in the sevoflurane group. Propensity score matching adjusted for confounding factors resulted in 28 patients in each arm, with no apparent differences in background factors. Hypotension was defined as a time-averaged area > 1, in which systolic arterial pressure fell below 80% of the baseline from the start of anesthesia to the end of procedure. The significance level was set at P < .05. The incidence of hypotension was 39.3% in the remimazolam arm and 46.4% in the sevoflurane arm, with no significant difference (P = .79), although the ratio of the median systolic arterial pressure to the baseline value was significantly higher in the remimazolam arm (91.4 ± 15.2% vs 83.2 ± 11.4% in the sevoflurane arm; P = .03)., Conclusions: Remimazolam was not associated with a lower incidence of hypotension compared to sevoflurane during pediatric cardiac catheterization for congenital heart disease while maintaining significantly higher blood pressure overall., 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 Inc. All rights reserved.)

Toll-like receptors (TLRs) are pattern recognition receptors expressed in immune cells, including neutrophils, macrophages, and dendritic cells. Microbe-associated molecular patterns, including bacterial components, membranes, nucleic acids, and flagella are recognized by TLRs in inflammatory immune responses. Periodontal disease is an inflammatory disease known to cause local infections associated with gingival inflammation, subsequently leading to alveolar bone resorption. Prostaglandin E2 (PGE2) is a key mediator of TLR-induced inflammatory bone resorption. We previously reported that membrane-bound PGE synthase (mPGES-1)-deficient mice failed to induce bone resorption by lipopolysaccharide (LPS), a major pathogenic factor involved in periodontal bone resorption. Further experiments exploring specific pathogen-promoting osteoclast differentiation revealed that various TLR ligands induced osteoclast differentiation in a co-culture model. The ligands for TLR2/1, TLR2/6, TLR3, and TLR5, as well as TLR4, induce osteoclast differentiation associated with the production of PGE2 and the receptor activator of nuclear factor-kappa B ligand (RANKL), an inevitable inducer of osteoclast differentiation in osteoblasts. In vivo, local injection of TLR ligands, including TLR2/1, TLR2/6, and TLR3, resulted in severe alveolar bone resorption. This review summarizes the latest findings on TLR-mediated osteoclast differentiation and bone resorption in inflammatory diseases, such as periodontal diseases.

Objectives: Spread through air spaces (STAS) is a form of lung cancer invasion that extends beyond the tumor edge and is associated with a worse prognosis. Recent advances in immunotherapy highlight the importance of understanding the tumor microenvironment. This study aimed to investigate the prognostic significance of immune-cell distribution in lung cancer, focusing on the association with STAS., Materials and Methods: We retrospectively analyzed 283 patients who underwent curative-intent lung resection for primary lung cancer. Multiplex immunofluorescence staining/phenotyping was performed on tissue microarrays to assess the distribution of CD4, CD8, CD20, CD68, and FoxP3 immune cells within the center and tumor edge. We defined the delta-Edge value (Δ) as the difference in the number of immune cells between the tumor edge and center. Recurrence-free probability (RFP) was analyzed using Kaplan-Meier and Cox proportional hazard models., Results: High ΔCD4 and ΔCD8 values were significantly associated with worse RFP. In stage I adenocarcinoma patients, STAS, and high ΔCD8 were independent risk factors for recurrence. Effect modification analysis revealed that high ΔFoxP3 was significantly associated with worse RFP in patients with STAS, but not in those without STAS. Patients with STAS and high Δimmune cell values had the lowest RFP among all groups., Conclusion: Immune-cell distribution, particularly CD4, CD8, and FoxP3, is a crucial prognostic factor in lung cancer. STAS and specific immune cell distribution patterns can be used to further stratify patient prognosis. Understanding these interactions may provide insights into potential therapeutic targets for personalized lung cancer treatment., Competing Interests: None declared., (© 2024 The Authors.)

Neoantigen-based immunotherapy is an attractive potential treatment for previously intractable tumors. To effectively broaden the application of this approach, stringent biomarkers are crucial to identify responsive patients. ARID1A, a frequently mutated subunit of SWI/SNF chromatin remodeling complex, has been reported to determine tumor immunogenicity in some cohorts; however, mutations and deletions of ARID1A are not always linked to clinical responses to immunotherapy. In this study, we investigated immunotherapeutic responses based on ARID1A status in targeted therapy-resistant cancers. Mouse and human BRAFV600E melanomas with or without ARID1A expression were transformed into resistant to vemurafenib, an FDA-approved specific BRAFV600E inhibitor. Anti-PD-1 antibody treatment enhanced antitumor immune responses in vemurafenib-resistant ARID1A-deficient tumors but not in ARID1A-intact tumors or vemurafenib-sensitive ARID1A-deficient tumors. Neoantigens derived from accumulated somatic mutations during vemurafenib resistance were highly expressed in ARID1A-deficient tumors and promoted tumor immunogenicity. Furthermore, the newly generated neoantigens could be utilized as immunotherapeutic targets by vaccines. Finally, targeted therapy resistance-specific neoantigen in experimental human melanoma cells lacking ARID1A were validated to elicit T-cell receptor responses. Collectively, the classification of ARID1A-mutated tumors based on vemurafenib resistance as an additional indicator of immunotherapy response will enable a more accurate prediction to guide cancer treatment. Furthermore, the neoantigens that emerge with therapy resistance can be promising therapeutic targets for refractory tumors. Significance: Chemotherapy resistance promotes the acquisition of immunogenic neoantigens in ARID1A-deficient tumors that confer sensitivity to immune checkpoint blockade and can be utilized for developing antitumor vaccines, providing strategies to improve immunotherapy efficacy., (©2024 American Association for Cancer Research.)

Introduction: Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes., Materials and Methods: This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan-Meier analyses and Cox proportional hazards model were conducted., Results: Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan-Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18-7.65; and P = 0.02)., Conclusion: This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes., (© 2024. The Author(s).)

The increased difference in the sulfur isotopic compositions of sedimentary sulfate (carbonate-associated sulfate: CAS) and sulfide (chromium-reducible sulfur: CRS) during the Ediacaran Shuram excursion is attributed to increased oceanic sulfate concentration in association with the oxidation of the global ocean and atmosphere. However, recent studies on the isotopic composition of pyrites have revealed that CRS in sediments has diverse origins of pyrites. These pyrites are formed either in the water column/shallow sediments, where the system is open with respect to sulfate, or in deep sediments, where the system is closed with respect to sulfate. The δ 34 S value of sulfate in the open system is equal to that of seawater; on the contrary, the δ 34 S value of sulfate in the closed system is higher than that of seawater. Therefore, obtaining the isotopic composition of pyrites formed in an open system, which most likely retain microbial sulfur isotope fractionation, is essential to reconstruct the paleo-oceanic sulfur cycle. In this study, we carried out multiple sulfur isotope analyses of CRS and mechanically separated pyrite grains (>100 μm) using a fluorination method, in addition to secondary ion mass spectrometry (SIMS) analyses of in situ δ 34 S values of pyrite grains in drill core samples of Member 3 of the Ediacaran Doushantuo Formation in the Three Gorges area, South China. The isotope fractionation of microbial sulfate reduction (MSR) in the limestone layers of the upper part of Member 3 was calculated to be 34 ε = 55.7‰ and 33 λ = 0.5129 from the δ 34 S and Δ 33 S' values of medium-sized pyrite grains ranging from 100 to 300 μm and the average δ 34 S and Δ 33 S' values of CAS. Model calculations revealed that the influence of sulfur disproportionation on the δ 34 S values of these medium-sized pyrite grains was insignificant. In contrast, within the dolostone layers of the middle part of Member 3, isotope fractionation was determined to be 34 ε = 47.5‰. The 34 ε value in the middle part of Member 3 was calculated from the average δ 34 S values of the rim of medium-sized pyrite grains and the average δ 34 S values of CAS. This observation revealed an increase in microbial sulfur isotope fractionation during the Shuram excursion at the drill core site. Furthermore, our investigation revealed correlations between δ 34 S CRS values and CRS concentrations and between CRS and TOC concentrations, implying that organic matter load to sediments controlled the δ 34 S CRS values rather than oceanic sulfate concentrations. However, these CRS and TOC concentrations are local parameters that can change only at the kilometer scale with local redox conditions and the intensity of primary production. Therefore, the decreasing δ 34 S CRS values likely resulted from local redox conditions and not from a global increase in the oceanic sulfate concentration., (© 2024 John Wiley & Sons Ltd.)

Background: The use of sublobar resection has increased with advances in imaging technologies. However, it is difficult for thoracic surgeons to identify small lung tumours intraoperatively. Radiofrequency identification (RFID) lung-marking systems are useful for overcoming this difficulty; however, accurate placement is essential for maximum effectiveness., Methods: We retrospectively reviewed patients who underwent RFID tag placement via fluoroscopic bronchoscopy under virtual bronchoscopic navigation (VBN) guidance before our institution's sublobar resection of lung lesions. Thirty-one patients with 31 lung lesions underwent RFID lung-marking with fluoroscopic bronchoscopy under VBN guidance., Results: Of the 31 procedures, 26 tags were placed within 10 mm of the target site, 2 were placed more than 10 mm away from the target site, and 3 were placed in a different area from the target bronchus. No clinical complications were associated with RFID tag placement, such as pneumothorax or bleeding. The contribution of the RFID lung-marking system to surgery was high, particularly when the RFID tag was placed at the target site and tumour was located in the intermediate hilar zone., Conclusions: An RFID tag can be placed near the target site using fluoroscopic bronchoscopy in combination with VBN guidance. RFID tag placement under fluoroscopic bronchoscopy with VBN guidance is useful for certain segmentectomies., (© 2024. The Author(s).)

Purpose: This study aimed to examine changes in salivary immunoglobulin A (s-IgA) secretion at different intensities or durations of acute exercise., Methods: Twelve healthy untrained young males were included in randomized crossover trials in Experiment 1 (cycling exercise for 30 min at a work rate equivalent to 35%, 55%, and 75% maximal oxygen uptake [ V ˙ O 2max ]) and Experiment 2 (cycling exercise at 55% V ˙ O 2max intensity for 30, 60, and 90 min). Saliva samples were collected at baseline, immediately after, and 60 min after each exercise., Results: Experiment 1: The percentage change in the s-IgA secretion rate in the 75% V ˙ O 2max trial was significantly lower than that in the 55% V ˙ O 2max trial immediately after exercise (- 45.7%). The percentage change in the salivary concentration of cortisol, an s-IgA regulating factor, immediately after exercise significantly increased compared to that at baseline in the 75% V ˙ O 2max trial (+ 107.6%). A significant negative correlation was observed between the percentage changes in saliva flow rate and salivary cortisol concentration (r = - 0.52, P < 0.01). Experiment 2: The percentage change in the s-IgA secretion rate in the 90-min trial was significantly lower than that in the 30-min trial immediately after exercise (-37.0%). However, the percentage change in salivary cortisol concentration remained the same., Conclusion: Our findings suggest that a reduction in s-IgA secretion is induced by exercise intensity of greater than or equal to 75% V ˙ O 2max for 30 min or exercise duration of greater than or equal to 90 min at 55% V ˙ O 2max in healthy untrained young men., (© 2024. The Author(s).)

Introduction: Occlusal and percussion pain may manifest occasionally following endodontic treatment, influencing retreatment decisions. Two cases of periapical neuropathic pain, classified as post-traumatic trigeminal neuropathic pain according to the International Classification of Orofacial Pain, are presented. Although mirogabalin is effective in managing neuropathic pain, there is a lack of clinical reports on its use for occasional post-traumatic trigeminal neuropathic pain after endodontic treatment. These cases highlight clinical symptoms and successful treatment with mirogabalin for post-traumatic trigeminal neuropathic pain after endodontic treatment, providing clinicians a "take-away" lesson for improving patient condition., Methods: The patients, referred by their primary dentist due to postendodontic abnormal pain, found no relief with antibiotics or nonsteroidal anti-inflammatory drugs. Although no findings including swelling or periapical radiolucency were observed around the tooth, they experienced occlusal and percussion pain. Local anesthetic testing showed that the pain originated from the peripheral area around the tooth rather than from central sensitization. Dental radiography and cone-beam computed tomography revealed no abnormal findings. Root canal retreatment was performed by a specialist in endodontic treatment. Although endodontic retreatment drastically decreased visual analog scale pain score, pain persisted. Based on the International Classification of Orofacial Pain criteria, diseases other than post-traumatic trigeminal neuropathic pain were excluded. Mirogabalin (10 mg/d) was prescribed once daily before bedtime., Results: Visual analog scale scores gradually and drastically decreased 2 weeks after mirogabalin therapy. Several months later, no recurrence of postendodontic pain was observed after tapering off and discontinuing mirogabalin., Conclusions: These findings suggest the possibility of a new treatment method for post-traumatic trigeminal neuropathic pain after endodontic treatment., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Ciprofloxacin (CFX) and ofloxacin (OFX) are commonly found as residual contaminants in aquatic environments, posing potential risks to various species. To ensure the safety of aquatic wildlife, it is essential to determine the toxicity of these antibiotics and establish appropriate concentration limits. Additionally, in (eco)toxicological studies, addressing the issue of multiple hypothesis testing through p -value adjustments is crucial for robust decision-making. In this study, we assessed the no observed adverse effect concentration (NOAEC) of CFX and OFX on Moina macrocopa across a concentration range of 0-400 µg L -1 . Furthermore, we investigated multiple p -value adjustments to determine the NOAECs. Our analysis yielded consistent results across seven different p -value adjustments, indicating NOAECs of 100 µg CFX L -1 for age at first reproduction and 200 µg CFX L -1 for fertility. For OFX treatment, a NOAEC of 400 µg L -1 was observed for both biomarkers. However, further investigation is required to establish the NOAEC of OFX at higher concentrations with greater certainty. Our findings demonstrate that CFX exhibits higher toxicity compared to OFX, consistent with previous research. Moreover, this study highlights the differential performance of p -value adjustment methods in terms of maintaining statistical power while controlling the multiplicity problem, and their practical applicability. The study emphasizes the low NOAECs for these antibiotics in the zooplanktonic group, highlighting their significant risks to ecological and environmental safety. Additionally, our investigation of p -value adjustment approaches contributes to a deeper understanding of their performance characteristics, enabling (eco)toxicologists to select appropriate methods based on their specific needs and priorities.

Juncus decipiens is a member of the Juncaceae family and has culinary, medicinal, and decorative properties. It is also used in traditional Chinese Medicines for many years that promotes diuresis for strangury and clears out heart fire. This species has recently gained medicinal attention as a source of phenanthrenes, phenolic compounds, glycerides, flavonoids, and cycloartane triterpenes. This plant was also shown to be active, and researchers explored its antioxidant, anti-inflammatory, antialgal, antibacterial, and psychological behaviour-boosting properties. Preliminary research suggests that this species might be used for skin protection and brain disorders if proper clinical trials are conducted. The ethnomedicinal, phytochemistry, biological potencies, dangers, and scopes of Juncus decipiens have been examined in this respect.

Introduction : We previously reported a case of a patient with bilateral congenital cataract identified in the Ogasawara village, Bonin Islands, Japan, on a visit by an ophthalmologist and describe its course over 17 years from initial surgery. Here, we report on a secondary intraocular lens (IOL) implantation that was subsequently performed at 22 years and 5 months of age. Methods : After cataract surgery at 7 months, the aphakic patient began amblyopia treatment using extended-wear soft contact lenses (SCLs). After 10 years of age, SCLs were chosen to achieve crossed monovision considering the cosmetic appearance when facing other people. At 22 years of age, a secondary IOL implantation was performed. Secondary implant in the patient considered appearance and postoperative vision without glasses, we selected the crossed monovision method using a monofocal IOL. The postoperative targeted refraction for the right (non-dominant eye) and left eyes (dominant eye) planed - 0.33D and - 2.25D, respectively. Results : At 3 months after surgery, the corrected distance visual acuity (CDVA) with IOLs for the right and left eyes was 20/16 and 20/60, respectively, and the binocular visual acuity was 20/16 for distant vision and 20/25 for near vision. The CDVA for the right eye was: 20/13 × IOL = sph-0.25D and that for the left eye was: 20/13 × IOL = sph -1.75D D/cyl -0.50D/Ax170°. Although the exotropia was complicated by dissociated horizontal deviation and dissociated vertical deviation, there were no significant changes in ocular position before and after surgery. The patient was satisfied with achieving independence from spectacles and SCLs. Conclusion : The use of the crossed monovision method with monofocal IOLs in this patient and defective binocular function created a visual environment with no inconvenience in everyday life after secondary IOL implantation. In terms of secondary implant after amblyopia treatment, the IOL type or postoperative targeted refraction must be chosen to maintain or improve the visual environment obtained with the amblyopia treatment.

Skeletal muscle comprises slow and fast myofibers, with slow myofibers excelling in aerobic metabolism and endurance. Quercetin, a polyphenol, is reported to induce slow myofibers in rodent skeletal muscle both in vitro and in vivo. However, its effect on human myofiber types remains unexplored. In this study, we evaluated quercetin's impact on slow myofiber induction using human skeletal muscle satellite cells. In a two-dimensional culture, quercetin enhanced gene expression, contributing to muscle differentiation, and significantly expanded the area of slow-type myosin heavy chain positive cells. It also elevated the gene expression of Pgc1α, an inducer of slow myofibers. Conversely, quercetin did not affect mitochondrial abundance, fission, or fusion, but it did increase the gene expression of Cox7A2L, which aids in promoting mitochondrial supercomplexity and endurance, and Mb, which contributes to oxidative phosphorylation. In a three-dimensional culture, quercetin significantly extended the time to peak tension and half relaxation time of the engineered human skeletal muscle tissues constructed on microdevices. Moreover, quercetin enhanced the muscle endurance of the tissues and curbed the rise in lactate secretion from the exercised tissues. These findings suggest that quercetin may induce slow myofibers in human skeletal muscle., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Chronic obstructive pulmonary disease (COPD) and asthma are common lung diseases with heterogeneous clinical presentations. Lung imaging allows evaluations of underlying pathophysiological changes and provides additional personalized approaches for disease management. This narrative review provides an overview of recent advances in chest imaging analysis using various modalities, such as computed tomography (CT), dynamic chest radiography, and magnetic resonance imaging (MRI). Visual CT assessment localizes emphysema subtypes and mucus plugging in the airways. Dedicated software quantifies the severity and spatial distribution of emphysema and the airway tree structure, including the central airway wall thickness, branch count and fractal dimension of the tree, and airway-to-lung size ratio. Nonrigid registration of inspiratory and expiratory CT scans quantifies small airway dysfunction, local volume changes and shape deformations in specific regions. Lung ventilation and diaphragm movement are also evaluated on dynamic chest radiography. Functional MRI detects regional oxygen transfer across the alveolus using inhaled oxygen and ventilation defects and gas diffusion into the alveolar-capillary barrier tissue and red blood cells using inhaled hyperpolarized 129 Xe gas. These methods have the potential to determine local functional properties in the lungs that cannot be detected by lung function tests in patients with COPD and asthma. Further studies are needed to apply these technologies in clinical practice, particularly for early disease detection and tailor-made interventions, such as the efficient selection of patients likely to respond to biologics. Moreover, research should focus on the extension of healthy life expectancy in patients at higher risk and with established diseases., Competing Interests: Declaration of competing interest N.T. received honoraria for lectures from AstraZeneca and research funding from Fujifilm and Daiichi Sankyo. H. Nakagawa and S.S. have no conflicts of interest. Y.O. received research funding from Canon Medical Systems Corporation and the Smoking Research Foundation. K.S. and H Nakamura has no conflicts of interest. M.H. received honoraria for lectures from AstraZeneca and Nippon Boehringer Ingelheim. Y.N. received honoraria for lectures from AstraZeneca, GSK, and Nippon Boehringer Ingelheim; research funding from GSK and Clairvo Technologies; and subsidies from Nippon Boehringer Ingelheim and Fukuda Life Tech. T.H. received research funding from Fujifilm and Daiichi Sankyo., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Introduction Wearable trackers are instrumental in monitoring various health indicators, notably daily physical activity, which is crucial for managing chronic diseases and improving overall health. This study examined the relationship between physical activity levels measured using JINS MEME, an eyeglass-type wearable device equipped with motion sensors, and subjective activity assessments reported through the International Physical Activity Questionnaire (IPAQ). Methods Healthy volunteers aged 20-60 were recruited for an observational study. Participants wore the JINS MEME throughout the day for one week, and data on walking activity were collected and analyzed alongside IPAQ responses to evaluate subjective physical activity levels. The correlation between the two sets of data was evaluated using the nonparametric Spearman's rho (ρ) correlation coefficient for both the assessed metabolic equivalents (METs) score of the JINS MEME and the IPAQ. Similarly, the relationship between the IPAQ questionnaire items and the measurements from the JINS MEME. Results The study included 42 participants and revealed a strong correlation (R=0.719, P<0.01) between the metabolic equivalents (METs) calculated from the JINS MEME and IPAQ scores, especially for walking activities. Similarly, a significant association was found between the IPAQ data and walking speed (R=0.129, P=0.02). METs showed significant relationships with all physical activities, except sitting or reclining time. Conclusion This study validated the use of eyeglass-type wearable devices, such as the JINS MEME, to accurately assess physical activity levels, demonstrating a strong correlation with subjective assessments using the IPAQ. This highlights the potential of wearable devices in comprehensive health monitoring and management strategies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethics Committees of Graduate School of Medicine, Chiba University issued approval No. 5-185. This is to certify that the Research protocol “Evaluating the Correlation between Eyeglass-Type Wearable Device Measurements and Subjective Physical Activity Assessments” planned by Seiji Ohtori was approved by the Research Ethics Committees of Graduate School of Medicine, Chiba University. 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: Sumihisa Orita declare(s) a grant from JINS Inc. 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, Inoue et al.)

Objectives Pneumocystis pneumonia (PCP) has a poor prognosis in patients with autoimmune diseases. Additionally, the mortality of PCP in autoimmune diseases is higher than that of human immunodeficiency virus-PCP. Therefore, this study aimed to assess the risk factors associated with mortality in patients with autoimmune diseases complicated with PCP. Methods We conducted a retrospective observational study involving 38 patients treated for PCP at Showa University School of Medicine from January 2010 to August 2014. Diagnoses were established based on clinical symptoms, imaging, and laboratory tests, including hypoxemia (partial pressure of oxygen (PaO2) < 70 mmHg), chest computed tomography findings, elevated (1,3)-β-D-glucan, and positive Pneumocystis jirovecii polymerase chain reaction tests from sputum samples. Data regarding patient demographics, underlying diseases, therapeutic interventions, and laboratory findings were collected. Statistical comparisons between survivors and non-survivors were performed using Fisher's exact probability test and Mann-Whitney U test for independence test with Stata/SE version 17.0 (StataCorp LLC, College Station, TX). Results The median age of the study group was 72.4 years old, with the majority having rheumatoid arthritis. Mortality occurred in 18% (seven out of 38) of cases. Factors associated with increased mortality include males, higher serum creatinine and C-reactive protein levels, lower albumin and immunoglobulin A levels, and lower PaO2/fraction of inspired oxygen (FiO2) ratio. No significant difference was observed in the rate of intratracheal intubation, ICU management, and hospitalization period. Prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX) was not performed in any of the cases. Conclusions This study examined the risk of mortality for PCP in patients with autoimmune diseases. The male gender, low IgA and albumin levels, low PaO2/FiO2 ratio, as well as high creatinine and CRP levels, were identified as significant factors for poor prognosis. These factors can help identify patients at high risk for PCP and guide the consideration of prophylactic TMP-SMX administration. They may also provide insights into when to discontinue prophylactic treatment. Future studies should investigate the administration of prophylactic TMP-SMX. Additionally, the risk of mortality for PCP under the administration of new biological agents, such as anifrolumab, belimumab, and rituximab, or immunosuppressants, such as mycophenolate mofetil and voclosporin, should be evaluated. These findings can contribute to improving PCP prevention and treatment strategies in patients with autoimmune diseases, ultimately leading to better patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Bio-Ethical Committee of Showa University School of Medicine issued approval 1644. 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: Yusuke Miwa declare(s) a grant from Mitsubishi Tanabe Pharma Corporation. Yusuke Miwa received research grants from Mitsubishi Tanabe Pharma Corporation. Yusuke Miwa declare(s) a grant from AbbVie CK. Yusuke Miwa received research grants from AbbVie CK. Yusuke Miwa declare(s) a grant from Chugai Pharmaceutical Co., Ltd. Yusuke Miwa received research grants from Chugai Pharmaceutical Co., Ltd. Yusuke Miwa declare(s) a grant from Eizai Co., Ltd. Yusuke Miwa received research grants from Eizai Co., Ltd. Yusuke Miwa declare(s) a grant from Astellas Pharma Inc. Yusuke Miwa received research grants from Astellas Pharma Inc. 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, Shimizu et al.)

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the numerous studies on the inhibition of amyloid formation, the prevention and treatment of a majority of amyloid-related disorders are still challenging. In this study, we investigated the effects of various plant extracts on amyloid formation of α-synuclein. We found that the extracts from Eucalyptus gunnii are able to inhibit amyloid formation, and to disaggregate preformed fibrils, in vitro. The extract itself did not lead cell damage. In the extract, miquelianin, which is a glycosylated form of quercetin and has been detected in the plasma and the brain, was identified and assessed to have a moderate inhibitory activity, compared to the effects of ellagic acid and quercetin, which are strong inhibitors for amyloid formation. The properties of miquelianin provide insights into the mechanisms controlling the assembly of α-synuclein in the brain., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Lower skeletal muscle density may reflect muscle adiposity and metabolic dysregulation that potentially impair disease control and lung function independent of high body mass index (BMI) in patients with asthma., Objective: To investigate whether lower density of pectoralis muscles (PM) and erector spinae muscles (ESM) on chest computed tomography (CT) was associated with airway structural changes in patients with asthma., Methods: Consecutive patients with asthma and healthy control subjects undergoing chest CT were retrospectively analysed. The ESM and PM density, areas of subcutaneous adipose tissue (SAT) near the PM and epicardial adipose tissue (EAT), wall area percent of the airways (WA%), and airway fractal dimension (AFD) were quantified on CT., Results: The study included 179 patients with asthma (52% women) and 88 control subjects (47% women). All the control subjects were ≤ 60 years old. PM and ESM density in female patients with asthma who were ≤ 60 years old were significantly lower than those in control subjects after adjustment for BMI. In female patients with asthma at all ages, lower PM and ESM density (but not SAT or EAT area) was associated with greater WA% and lower AFD after adjusting for age, height, BMI, smoking status, blood eosinophil count, and oral corticosteroid use. The only association between ESM density and AFD was found in male patients with asthma., Conclusion: Lower skeletal muscle density may be associated with airway wall thickening and less complexity of the airway luminal tree in female patients with asthma., Competing Interests: Declaration of competing interest N.T. and T.H. received research grants from Daiichi Sankyo and FUJIFILM Co., Ltd., outside of the submitted work. S.S. received grants from Nippon Boehringer Ingelheim, Philips-Respironics, Fukuda Denshi, Fukuda Lifetec Keiji, and ResMed outside of the submitted work. None of these companies played a role in the design or analysis of the study or in the writing of the manuscript. The other authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To investigate clinical outcomes and return to sport timeline for athletes with acetabular dysplasia after endoscopic shelf acetabuloplasty (ESA)., Design: A retrospective review., Setting: Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan between 2012 and 2019., Patients: Fifteen elite athletes (median age: 20 years) of 253 patients undergoing ESA, arthroscopic labral repair/reconstruction, cam osteochondroplasty, and capsular plication. The mean follow-up period was 27.8 months after surgery., Main Outcome Measures: Patient-reported outcome scales (PROSs), including the modified Harris Hip Score, Nonarthritic Hip Score, International Hip Outcome Tool 12, Hip Outcome Score-Sports, and Vail Hip Score., Results: After ESA, all 15 elite athletes were able to return to sport effectively and compete at a preoperative level. The mean time between the operation and the first practice was 6.5 months, while the mean time between the ESA procedure and the first game was 9.6 months. Approximately 27.8 months after surgery, PROS outcomes improved significantly with no hips requiring emergency revision surgery at the final follow-up. At a mean of 47.1 months after surgery, 7 athletes decided to retire from their sport. Up to 71.1 months after surgery, the additional 8 patients continued to compete in their sport at an elite level., Conclusions: ESA enables elite athletes with acetabular dysplasia to return to competition at a mean of 9.6 months postsurgery. The ESA procedure is an effective and promising method of treating elite athletes with acetabular dysplasia., Level of Evidence: IV., Competing Interests: S.U. is a consultant for Smith & Nephew, a board member of ISHA hip preservation society. For remaining authors report no conflicts of interest. Informed consent has been obtained from the patient., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Antimicrobial peptides, key players of innate mucosal immunity in the oral cavity, exert antibacterial and bacteriolytic effects. This study aimed to clarify the effects of acute exercise at different intensities and durations on salivary antimicrobial peptide levels. In a randomized crossover trial, 14 young healthy untrained men performed intensity trials (cycling at 35%, 55%, and 75% of maximal oxygen uptake [VO 2max ] for 30 min) and duration trials (cycling at 55% VO 2max for 30, 60, and 90 min). Saliva samples were collected at baseline and 0 and 60 min after exercise. In intensity trials, the change in salivary Lactoferrin levels from baseline to 0 min after 30-min exercise was greater at 75% VO 2max exercise intensity compared to that at 35% VO 2max . Furthermore, the change in salivary human beta defensin-2 (HBD-2) levels was greater at 75% VO 2max compared to that at 35% and 55% VO 2max . Salivary Lysozyme levels increased after exercise, independent of exercise intensity. However, salivary LL-37 levels did not change after exercise at any intensity. Additionally, in duration trials, the change in salivary levels of LL-37 and HBD-2 from baseline to 0 min after exercise at 55% VO 2max was greater after 60 min and 90 min of exercise compared to that after 30 min of exercise. However, salivary Lactoferrin and Lysozyme levels increased after exercise, independent of exercise duration. Our findings suggest that secretory responses to acute exercise with exercise intensity and duration differ among salivary antimicrobial peptides.

Background : The respiratory adjusted shock index (RASI) is a risk score whose usefulness in patients with sepsis and trauma has previously been reported. However, its relevance in elderly emergency patients with medical diseases is yet to be clarified. This study assessed the usefulness of the RASI, which can be evaluated without requiring special equipment, to provide objective and rapid emergency responses. Methods : In this retrospective study, we recruited patients with medical diseases, aged 65 years or older, who were transported to the emergency room from Tokushima Prefectural Kaifu Hospital and underwent arterial blood gas testing from 1 January 2022 to 31 December 2023. We investigated the association of the RASI with other indices, including the lactate level, National Early Warning Score 2 (NEWS2), Shock Index (SI), Sequential Organ Failure Assessment (SOFA) score, quick SOFA (qSOFA) score, and systemic inflammatory response syndrome (SIRS). Results: In this study, we included 260 patients (mean age, 86 years), of whom 234 were admitted to the hospital; 27 and 49 patients died within 7 and 30 days of admission, respectively. The RASI was positively correlated with the lactate level, NEWS2, SI, and increase in the SOFA score ( p < 0.001). The RASI was higher in patients with a SIRS or qSOFA score ≥ 2 than in those without ( p < 0.001). It predicted death within 7 and 30 days of admission with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.73-0.87), sensitivity of 96.3%, and specificity of 53.6% when the cutoff value was set to 1.58 and with an AUC of 0.73 (95% CI: 0.66-0.81), sensitivity of 69.4%, and specificity of 70.6% when the cutoff value was set to 1.83, respectively. Conclusions : The RASI is a simple indicator that can be used for predicting in-hospital outcomes in elderly emergency patients with medical diseases. Larger prospective studies based on this study are needed.

Tumor microscopic structure is crucial for determining properties such as cancer type, disease state (key for early diagnosis), and novel therapeutic strategies. Magnetic particle imaging is an early cancer diagnostic tool using magnetic nanoparticles as a tracer, which actualizes cancer theranostics in combination with hyperthermia treatment using the abilities of magnetic nanoparticles as a heat source. This study focuses on the microscopic structures associated with cancer cell distribution, the stromal compartment, and vascularization in different kinds of living tumors by analyzing the intratumor magnetic relaxation response of magnetic nanoparticles injected into the tumors. Furthermore, this study describes a sequential system for the measurement of magnetic relaxation time and analysis of the intratumor structure using nonbiological samples such as viscous fluids and solidified magnetic nanoparticles. Particularly, the fine discriminability achieved by reconstructing a distribution map representing the relationship between magnetic relaxation time and viscosity of medium is demonstrated, based on experimental data with a limited condition number. Observing tumor microscopic structure through the dynamic magnetization response of intratumor magnetic nanoparticles is a low-invasive tool for analyzing tumor tissue without dissection. It holds promise for the advancement of biomedical applications, such as early cancer theranostics, using magnetic nanoparticles., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)