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Background: Families of critically ill patients in the intensive care unit (ICU) need a variety of information about the patient. Meeting these information needs improves the quality of communication between the family and ICU staff, as well as reduces the risk of post-intensive care syndrome-family (PICS-F). However, information needs continue to be unmet, and information regarding which specific information needs are met or unmet is insufficient. Additionally, the unmet needs that affect PICS-F are unknown. Therefore, this study aims to identify the unmet information needs of families of patients admitted to the ICU in terms of communication with ICU staff and determine their association with PICS-F., Methods: This study will be a single-center cross-sectional study using a questionnaire survey. The participants will include family members of patients admitted to the emergency ICU of the Department of Emergency and Critical Care Medicine, Nippon Medical School Hospital in Japan. Eligibility for participation will be assessed from medical records, and family members of patients who meet the eligibility criteria will be identified and sent a questionnaire. PICS-F and unmet information needs will be assessed 1 to 12 months after patients leave the ICU. PICS-F assessment will include the evaluation of anxiety, depression, post-traumatic stress disorder, and prolonged grief disorder. Univariate and multiple logistic regression analyses will be used to examine the association between PICS-F and unmet information needs., Discussion: This study will fill a research gap in communication between ICU staff and families of ICU patients by examining the information that tends not to be provided or understood by families, thereby providing an understanding of the information that is likely to be an unmet information need. Additionally, this study can contribute to the development of future communication strategies by investigating which unmet information needs are associated with PICS-F risk, thus emphasizing the information needs that should be given priority when developing effective communication strategies., Trial Registration: University Hospital Medical Information Network Center Clinical Trials Registry UMIN 000053813., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Central Ethics Committee of the Nippon Medical School Foundation (approval no. M-2023-152; approval date: February 19, 2024). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Type A insulin resistance syndrome (IRS), characterized by impaired insulin receptor function due to variants of the insulin receptor gene, manifests as severe insulin-resistant diabetes. Differentiation of type A IRS from type 2 diabetes on the basis of hyperinsulinemia can be challenging. Given the association between insulin receptor dysfunction and reduced insulin clearance, we evaluated the potential of the circulating C-peptide reactivity (CPR)/immunoreactive insulin (IRI) molar ratio, a marker of insulin clearance, for distinguishing type A IRS from type 2 diabetes., Methods: We retrospectively analyzed CPR and IRI levels measured during a 75-g oral glucose tolerance test (OGTT) in 18 individuals with type A IRS and 126 with type 2 diabetes. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performance of the CPR/IRI molar ratio and IRI levels., Results: IRI levels were significantly higher and the CPR/IRI molar ratio significantly lower in individuals with type A IRS compared with those with type 2 diabetes. The area under the ROC curve for the CPR/IRI molar ratio at baseline, 1 hour, and 2 hours after OGTT initiation was 0.997 (sensitivity 100%, specificity 99.2%), 0.999 (sensitivity 100%, specificity 97.6%), and 0.997 (sensitivity 100%, specificity 95.1%), respectively. The CPR/IRI molar ratio demonstrated robust diagnostic performance regardless of body mass index or hyperinsulinemia severity., Conclusions: The CPR/IRI molar ratio, both at baseline and during OGTT, exhibited higher sensitivity and specificity than IRI levels alone for distinguishing type A IRS from type 2 diabetes. This ratio may serve as a reliable clinical marker for early and accurate diagnosis of type A IRS., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Age-related hearing loss (ARHL) is a widespread problem in the elderly, significantly impairing their quality of life. Despite its high prevalence, no fundamental treatment for ARHL has been established. Nicotinamide adenine dinucleotide (NAD + ) is required for various biological processes and tissue levels of the coenzyme NAD + are known to decrease with age. A previous report suggested that declining NAD + levels induce age-related diseases and NAD + supplementation might be effective for treating or preventing age-related diseases. To clarify the effect of NAD + supplementation on ARHL, C57BL/6J mice used as an animal model of ARHL were treated with nicotinamide mononucleotide (NMN), a precursor of NAD + . Oral administration of NMN at 500 mg/kg/day effectively suppressed the development of ARHL in C57BL/6J mice. To elucidate the mechanism by which NMN administration suppressed the development of ARHL, NAD + -related metabolites were assessed, and a comprehensive transcriptomic analysis of the inner ear tissue was performed. NMN administration resulted in increased NAD + levels in inner ear tissues and induced changes in the transcriptome, specifically in genes related to metal ion metabolism. These findings suggest that NMN administration enhanced NAD + levels in inner ear tissues, modulating metal ion metabolism to potentially protect against oxidative stress. This study provides a novel therapeutic approach to mitigating ARHL through NAD + supplementation., (Copyright © 2025. Published by Elsevier B.V.)

Small, obligately anaerobic strains 13CB8C T , 13CB11C T , 13CB18C T and 13GAM1G T were isolated from a faecal sample in a patient with Parkinson's disease with a history of duodenal resection. After conducting a comprehensive polyphasic taxonomic analysis including genomic analysis, we propose the establishment of one new genus and four new species. The novel bacteria are Desulfovibrio falkowii sp. nov. (type strain JCM 36128 T = DSM 116810 T ), Porphyromonas miyakawae sp. nov. (type strain JCM 36129 T = DSM 116947 T ), Mediterraneibacter flintii sp. nov. (type strain JCM 36130 T = DSM 116866 T ) and Owariibacterium komagatae gen. nov. sp. nov. (type strain JCM 36131 T = DSM 116982 T ), respectively.

Background: Fluoropyrimidine remains the key agent of adjuvant chemotherapy for stage III colorectal cancer (CRC). Western studies have shown that female sex is a favorable prognostic factor after surgery, but it is also a risk factor for adverse events (AEs) during adjuvant chemotherapy with fluoropyrimidine. However, little is known about whether sex differences in treatment outcomes exist in this setting in the Asian population., Methods: Patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy in 4 randomized controlled trials were analyzed. Incidences of AEs and survival outcomes were compared between female and male patients., Results: A total of 3170 patients (female, 1516; male, 1654) were included in this analysis. Compared with males, females were less likely to have a relative dose intensity (≥90 %: female 59.1 % vs. male 67.6 %), with a higher proportion of requiring dose reduction (28.8 % vs. 20.4 %) and a lower proportion of completing adjuvant chemotherapy (77.0 % vs. 81.7 %). Multivariable analyses demonstrated that female sex was associated with a higher incidence of grade 3-4 AEs (odds ratio 1.80 [95 % CI 1.51-2.14]). Female sex was identified as a favorable prognostic factor for overall survival (hazard ratio [HR]: 0.80 [0.65-0.97]) and relapse-free survival (HR: 0.73 [0.63-0.85]) in multivariable analyses. Female patients had fewer time-to recurrence (TTR) events than male patients (5-year TTR: 17.7 % vs. 22.3 %)., Conclusion: Sex had implications for the development of AEs and survival outcomes of Japanese patients with stage III CRC who received adjuvant fluoropyrimidine monotherapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. The authors declare the following financial interests/personal relationships that are considered potentially competing interests. H.H. has received honoraria from Bristol-Myers Squibb Japan, Chugai Pharma, Fujifilm, Novartis, Taiho Pharmaceutical, and Teijin Pharma, and has received research funding from BeiGene. A.D.W. has received payment for expert testimony from Astellas, has received support for attending meetings and/or travel from Servier, and Merck KG, has received consulting or advisory fees from MSD, Astra-Zeneca, Astellas, BMS, Pierre Fabre, and Dragonfly, and has other financial or non-financial interests. T.H. has received grands or contracts from Taiho Pharm, Chugai Pharma, Ono Pharmaceutical, BeiGene, Astellas Pharma, AstraZeneca, Pfizer, Bristol Myer Squibb, and Incyte Japan, and had received honoraria from Chugai Pharma, Merck Serono, Takeda, Taiho Pharmaceutical, Ono Pharmaceutical, Yakult Pharmaceutical, Lilly, Bristol-Myers Squibb Japan, Bayer, Daiichi-Sankyo, and Astellas. J.M. has received honoraria from Chugai pharmaceutical, Taiho pharmaceutical, his spouse is an employee of Pfizer. A.T. has received grands or contracts from Merck Sharp & Dohme, AstraZeneca, Amgen, Eisai, Bristol-Myers Squibb, and Ono Pharmaceutical, had received honoraria from Lilly, Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharma, Takeda, and Merck Serono. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this article, we investigate the encapsulation of K 2 [Ni(maleonitriledithiolate) 2 ] ( 1 ) within a host molecule, β-cyclodextrin (β-CD), via single-crystal X-ray analysis. An inclusion complex, K 2 {[Ni(maleonitriledithiolate) 2 ]@(β-CD) 2 } ( 2 ), was constructed from 1 and two β-CDs. The anion guest Ni complex included a host cavity, constructed using two β-CDs, and the Ni atom of the anion was located between the two hydrophilic primary rims. Ultraviolet-visible absorption spectroscopy revealed that inclusion complex 2 exhibited a 2:1 (host:guest) stoichiometry in the solution, which is consistent with the result obtained from X-ray crystallography. The association of the host and guest occurred in two steps, and the association constants for the first and second steps were 1.1(7) × 10 4 and 1.8(5) × 10 4 mol -1 dm 3 , respectively. The catalytic behavior of 1 and 2 was investigated for electrochemical hydrogen production in the aqueous solution of an acetate buffer (pH = 4.72). During the catalytic reaction, inclusion complex 2 was observed to have a better catalytic reaction rate than 1 . The study findings provide insights into the effects of the encapsulation of guest molecules within host structures.

Background: We recently reported that the self-care management system for heart failure (HF) decreased re-hospitalization for HF. In the present study we estimate the cost-effectiveness of this system., Methods and Results: We retrospectively enrolled 569 consecutive patients who were admitted for HF treatment at Kitano Hospital. In the present analysis, we sought to compare cardiovascular healthcare costs and the incremental cost-effective ratio (ICER), expressed as the cost per quality-adjusted life-years (QALY) gained, between patients using the self-care management system (n=153) and those not using the system (n=153) after propensity-score matching. To calculate the QALY, we used the New York Heart Association class and the corresponding scores of quality of life in every 3 months. The healthcare costs of cardiovascular disease were ¥129,747,016 in the user group and ¥156,427,032 in the non-user group, where 24 and 43 patients were hospitalized, respectively. The cost of this new system was ¥50,000 in the user group. The total costs were ¥129,797,016 in the user group and ¥156,427,032 in the non-user group. By using the system, the QALY increased from 0.653 to 0.686. The ICER was below 0 and the system was interpreted as cost-effective., Conclusions: Use of the self-care management system is likely to be a cost-effective treatment for HF with the increase in QALY and the decrease in healthcare costs., Competing Interests: E.N., M. Inoko, H.F., M.Y., Y. Yamaji, and T. Hamaguchi received a research grant from Bayer Yakuhin, Ltd, Takeda Pharmaceutical CO., Ltd, Novartis Pharma K.K., and IQVIA Services Japan G.K., and a scholarship grant from IQVIA Services Japan G.K., and Research Institute of Production Development. The other authors have no conflicts of interest., (Copyright © 2025, THE JAPANESE CIRCULATION SOCIETY.)

The DOPA-decarboxylase (DDC) gene is crucial for dopamine synthesis and influences various biological functions in insects, including body coloration, behavior, learning, and sleep. However, its evolutionary impact remains largely unexplored. This study reports on the tandem duplication of two bona fide ddc genes (ddc1 and ddc2) in the Gryllidae cricket family. We herein investigated the function of ddc1 and ddc2 using Gryllus bimaculatus (Gb) as a model. Our results revealed that Gb'ddc1 was expressed systemically, with its expression being higher immediately after molting compared to the stage following melanin pigmentation. In homozygous knockout mutants of Gb'ddc1, generated via CRISPR/Cas9, reduced body color pigmentation and had translucent cuticles, decreased dopamine levels, and over-accumulated DOPA. These mutants died shortly after hatching, likely due to cuticle defects, underscoring the essential role of dopamine, produced by Gb'ddc1, in melanin synthesis. Conversely, Gb'ddc2 expression was confined to the ovary and was not up-regulated after molting. Homozygous knockout mutants of Gb'ddc2 exhibited no body color defects, whereas hatchability and embryonic development rates were significantly reduced. Interestingly, dopamine levels in the ovaries were significantly elevated in Gb'ddc2 mutants. This suggests that normal ovarian dopamine levels, modulated by Gb'ddc2, are vital for fertility maintenance. The function of Gb'ddc2 differs from that of typical ddc, indicating neofunctionalization through evolutionary duplication. Overall, Gb'ddc1 and Gb'ddc2 have distinct functions, and precise regulation of ovarian dopamine levels using these two ddc genes may have enhanced cricket fertility., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dry mouth results from decreased saliva secretion due to aging or drug side effects. Decreased saliva secretion causes dryness in the oral cavity that makes swallowing difficult and increases the risk of aspiration pneumonia. There are few fundamental treatments for dry mouth. Here we investigated whether treatment of old mice with nicotinamide mononucleotide (NMN) improved factors associated with dry mouth. Young (16-week-old) and old (113-week-old) male mice were treated subcutaneously with saline or NMN (300 mg/kg) once every two days for four weeks and saliva secretion was measured. The amount of nicotinamide adenine dinucleotide (NAD + ) in salivary gland tissues was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene expression in the intestinal tract and salivary glands was measured by real-time PCR. The population of cells with acetylation in the submandibular gland was quantified by immunohistological staining. SA-β-gal activity in the submandibular gland was measured to assess cell senescence. Statistical analysis was performed by one-way analysis of variance with Tukey post hoc analysis. The submandibular glands from old mice treated with NMN exhibited increased saliva secretion and NAD + levels, which both decrease with aging. In addition, the submandibular glands from NMN-treated old mice had decreased acetylation, numbers of senescent cells, and levels of senescence-associated secretory phenotype (SASP) factors, which all increase with aging, as well as increased aquaporin5 (AQP5) mRNA expression. NMN administration may improve dry mouth by regulating cellular senescence in the submandibular gland and increasing expression of AQP5, a water channel involved in saliva secretion, to inhibit age-related decreases in saliva secretion. It is necessary to elucidate further mechanism and confirm its effectiveness in humans., Competing Interests: Declarations. Conflict of interest: This study is fully funded by Meiji Holdings Co., Ltd. JW, TH, MM, and NM are employees of Meiji Holding Co., Ltd., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Colonoscopy is widely performed. However, reports of colonoscopic incarceration within inguinal hernias are rare. Incarceration during colonoscopy is a critical condition, and attempting forced reduction may exacerbate complications; therefore, a careful approach is required. Here, we present a case of colonoscopic incarceration of a left inguinal hernia that was successfully reduced under fluoroscopic guidance, followed by elective endoscopic surgery., Case Presentation: A 74-year-old man presented for colonoscopy at a primary care clinic and was referred to our hospital for the incarceration of the colonoscope within the inguinal hernia. On arrival, the colonoscope remained in situ through the anus. Laboratory tests and imaging studies confirmed the absence of perforation. Manual pressure was applied under fluoroscopic guidance to successfully reduce the hernia and allow for scope extraction. No evidence of perforation was revealed in the follow-up fluoroscopic examination using a gastrografin enema. Six weeks later, the patient underwent definitive surgery for total extraperitoneal hernia repair., Conclusions: A complication of colonoscopy is the incarceration of the colonoscope within the inguinal hernia, particularly in older men. Therefore, inquiring about the patient's history of inguinal hernia, particularly those accompanied by scrotal swelling, besides assessing the surgical history before performing a colonoscopy, is critical. Furthermore, recent trends include attempts at incarceration reduction under fluoroscopic guidance, with emergency surgery reserved for irreducible cases., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for publication of this report. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Purpose: Doublet chemotherapy with fluoropyrimidine (FP) and oxaliplatin (OX) plus bevacizumab (BEV) is a standard regimen for unresectable metastatic colorectal cancer (MCRC). However, the efficacy of adding OX to FP plus BEV (FP + BEV) remains unclear for older patients, a population for whom FP + BEV is standard. We aimed to confirm the superiority of adding OX to FP + BEV for this population., Methods: This open-label, randomized, phase III trial was conducted at 42 institutions in Japan. Patients with unresectable MCRC age 70-74 years with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 and those 75 years and older with ECOG-PS 0-2 were randomly assigned (1:1) to an FP + BEV arm or an OX addition (FP + BEV + OX) arm. Fluorouracil plus levofolinate calcium or capecitabine was declared before enrollment. The primary end point was progression-free survival (PFS). The study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031180145)., Results: Between September 2012 and March 2019, 251 patients were randomly assigned to the FP + BEV arm (n = 125) and the FP + BEV + OX arm (n = 126). The median age was 80 and 79 years in the respective arm. The median PFS was 9.4 months (95% CI, 8.3 to 10.3) in the FP + BEV arm and 10.0 months (9.0 to 11.2) in the FP + BEV + OX arm (hazard ratio [HR], 0.84 [90.5% CI, 0.67 to 1.04]; one-sided P = .086). The median overall survival was 21.3 months (18.7 to 24.3) in the FP + BEV arm and 19.7 months (15.5 to 25.5) in the FP + BEV + OX arm (HR, 1.05 [0.81 to 1.37]). The proportion of any grade ≥3 adverse events was higher in the FP + BEV + OX arm (52% v 69%). There was one treatment-related death in the FP + BEV arm and three in the FP + BEV + OX arm., Conclusion: No benefit of adding OX to FP + BEV as first-line treatment was demonstrated in older patients with MCRC. FP + BEV is recommended for this population.

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

Background/objectives: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann's criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan., Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann's criteria were calculated by comparing diagnoses with those made by the JPDS Committee., Results: Of the 786 included cases, Hermann's criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann's criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as "definite" by both criteria., Conclusions: The findings suggest that Hermann's criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.

Background: The Japan Clinical Oncology Group (JCOG) 1006 was a phase III trial of patients with clinical T3/T4 colon cancer comparing the no-touch isolation technique ('No Touch') with the conventional technique ('Conventional'). The planned primary analysis at 3 years failed to confirm the superiority of the No Touch over the 'Conventional'. The present study aimed to compare the 'No Touch' and 'Conventional' using long-term (6-year) follow-up data., Methods: Patients aged 20-80 years who had a clinical classification of T3-4, N0-2, and M0 with histologically proven colon cancer were randomly assigned (1 : 1) to undergo open surgery using 'Conventional' or 'No Touch' techniques. The primary endpoint was disease-free survival., Results: In total, 853 patients from 30 institutions were assigned to the 'Conventional' (427) or 'No Touch' (426) groups between June 2011 and November 2015. The 6-year disease-free survival was 70.3% and 69.4% for 'Conventional' and 'No Touch' arms respectively (HR 1.030; 95% c.i. 0.813 to 1.304; one-sided P = 0.60). The 6-year overall survival was 89.4% and 86.6% respectively (HR 1.276; 95% c.i. 0.902 to 1.807). The 6-year relapse-free survival was 78.9% and 75.0% respectively (HR 1.209; 95% c.i. 0.920 to 1.589). The 6-year liver relapse-free survival was 85.1% and 80.2% respectively (HR 1.311; 95% c.i. 0.961 to 1.787)., Conclusion: Long-term follow-up data did not support the superiority of 'No Touch' over 'Conventional' technique in patients with stages II and III colon cancer. These study findings indicate that the conventional technique is still standard surgery for managing colon cancers., Trial Registration Number: UMIN000004957., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Objective: Prolonged immobilization of joints after distal radius fracture (DRF) causes cerebral disuse-dependent plasticity (DDP) and deterioration of upper extremity function. Action observation therapy (AOT) can improve DDP., Trial Design: This nonrandomized controlled trial (UMIN 000039973) tested the hypothesis that AOT improves hand-use difficulties during activities of daily living in patients with DRF., Method: Right-handed women with volar locking plate fixation for DRF were divided into AOT and Non-AOT groups for a 12-week intervention. The primary outcome was difficulty in using the fractured hand, assessed with the Japanese version of the Patient-related Wrist Evaluation (PRWE). The secondary outcomes were range of motion (ROM) of the injured side and gap between measured ROM and patient-estimated ROM. The survey was administered immediately post operation and at postoperative weeks 4, 8, and 12. The AOT group used a head-mounted display and three-dimensional video during ROM exercises. The Non-AOT group used active ROM exercises alone. A generalized linear model (GLM) was used to confirm interactions and main effects by group and time period, and multiple comparisons were performed., Results: Thirty-five patients were assigned to the AOT group (n = 18, median age, 74 years) or the Non-AOT group (n = 17, median age, 70 years). In the GLM, PRWE Total, PRWE Specific, and PRWE Usual scores revealed interactions between groups and periods. The post-hoc test revealed that the PRWE Specific scores (z = 3.43, p = 0.02) and PRWE Usual scores (z = 7.53, p<0.01) were significantly lower in the AOT group than in the Non-AOT group at 4 weeks postoperatively, whereas PRWE Total scores (z = 3.29, p = 0.04) were lower at 8 weeks postoperatively., Conclusions: These results suggested that AOT can improve hand-use difficulties in right-handed women after DRF surgery. AOT positively affects the motor imagery of patients with DRF and can reverse the patient's perceived difficulty in using the fractured hand during rehabilitation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Usuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Endothelin type B receptor (ET B R) plays a crucial role in regulating blood pressure and humoral homeostasis, making it an important therapeutic target for related diseases. ET B R activation by the endogenous peptide hormones endothelin (ET)-1-3 stimulates several signaling pathways, including G s , G i/o , G q/11 , G 12/13 , and β-arrestin. Although the conserved NPxxY motif in transmembrane helix 7 (TM7) is important during GPCR activation, ET B R possesses the lesser known NPxxL motif. In this study, we present the cryo-EM structure of the ET B R-G i complex, complemented by MD simulations and functional studies. These investigations reveal an unusual movement of TM7 to the intracellular side during ET B R activation and the essential roles of the diverse NPxxL motif in stabilizing the active conformation of ET B R and organizing the assembly of the binding pocket for the α5 helix of G i protein. These findings enhance our understanding of the interactions between GPCRs and G proteins, thereby advancing the development of therapeutic strategies., (© 2024. The Author(s).)

Competing Interests: Disclosure: Y.K. received a consulting or advisory role from Covidien, and honoraria from Chugai Pharma, Johnson and Johnson KK, Covidien, and Intuitive Surgical. S.T. received honoraria from Johnson and Johnson KK, Covidien, and Intuitive Surgical. Y.S. received honoraria from Ono Pharmaceutical, Novartis, Yakult Honsha, and Daiichi Sankyo/UCB Japan. T.H. received honoraria from Chugai Pharma, Merck Serono, Takeda, Taiho Pharmaceutical, Ono Pharmaceutical, Yakult Pharmaceutical, Lilly, Bristol-Myers Squibb Japan, Bayer, and Daiichi Sankyo/UCB Japan, and research funding from Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharma, BeiGene, Astellas Pharma, AstraZeneca, and Pfizer. The remaining authors declare that they have nothing to disclose. This study was supported in part by the National Cancer Center Research and Development Funds (23-A-16, 23-A-19, 26-A-4, 29-A-3, 2020-J-3, and 2023-J-03), Grants-in-Aid for Clinical Cancer Research (11S-4, 14S-3, 14S-4, 17S-3, 17S-5, 20S-3, and 20S-5), and Health Sciences Research Grants (H13-21Century-15, H14Gann-015, H16Gann-031, H19Gann-021, H21Gann-027, Hl5-018, H18-013, H21-017, H24-005, H19-021, and H22-027) from the Ministry of Health, Labour, and Welfare of Japan.

Tissue-specific deficiency of nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD + )-salvage pathway, causes a decrease of NAD + in the tissue, resulting in functional abnormalities. The NAD + -salvage pathway is drastically activated in the mammary gland during lactation, but the significance of this has not been established. To investigate the impact of NAD + perturbation in the mammary gland, we generated two new lines of mammary gland epithelial-cell-specific Nampt-knockout mice (MGKO). LC-MS/MS analyses confirmed that the levels of NAD + and its precursor nicotinamide mononucleotide (NMN) were significantly increased in lactating mammary glands. We found that murine milk contained a remarkably high level of NMN. MGKO exhibited a significant decrease in tissue NAD + and milk NMN levels in the mammary gland during lactation periods. Despite the decline in NAD + levels, the mammary glands of MGKO appeared to develop normally. Transcriptome analysis revealed that the gene profiles of MGKO were indistinguishable from those of their wild-type counterparts, except for Nampt. Although the NMN levels in milk from MGKO were decreased, the metabolomic profile of milk was otherwise unaltered. The mammary gland also contains adipocytes, but adipocyte-specific deficiency of Nampt did not affect mammary gland NAD +  metabolism or mammary gland development. These results demonstrate that the NAD +  -salvage pathway is activated in mammary epithelial cells during lactation and suggest that this activation is required for production of milk NMN rather than mammary gland development. Our MGKO mice could be a suitable model for exploring the potential roles of NMN in milk., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yo-ichi Nabeshima reports financial support was provided by Meiji Holdings Co Ltd. Kouya Hattori, Rika Azuma-Suzuki, Seiichiro Higashi, Takashige Hamaguchi, Yoshie Saito, Masashi Morifuji reports a relationship with Meiji Holdings Co Ltd that includes: employment. The Department of Aging Science and Medicine is endowed by Meiji Holdings Co., Ltd. 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 Elsevier Inc. All rights reserved.)

Background: Although treatment outcomes for metastatic colorectal cancer (mCRC) have dramatically improved over the past few decades, drug costs have also significantly increased. This study aimed to investigate which first-line treatment regimens for mCRC are actually used (frequency) in Japanese practice and at what cost., Methods: We collected data on patients with mCRC who received first-line treatment at 37 institutions of the Japan Clinical Oncology Group Colorectal Cancer Study Group from July 2021 to June 2022, and calculated the cost of regimens. The cost per month of each regimen was estimated based on standard usage, assuming a patient with a weight of 70 kg and a body surface area of 1.8 m2. We categorized the regimens into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month), and others (<500 000 JPY/month)., Results: The study included 1880 participants, 24% of whom were ≥ 75 years. Molecular targeted containing regimens were received by 78% of the patients. The most frequently used regimen was the doublet regimen (fluoropyrimidine with either oxaliplatin or irinotecan) plus bevacizumab (43%), followed by doublet plus cetuximab or panitumumab (21%). The cost of molecular targeted drugs-containing regimens (ranging from 85 406 to 843 602 JPY/month) is much higher than that of only cytotoxic drug regimens (ranging from 17 672 to 51 004 JPY/month). About 16% received high-cost treatments that included panitumumab-containing regimens and pembrolizumab (17% of patients aged ≤74 years and 11% of patients aged ≥75 years)., Conclusion: About 16% of mCRC patients received first-line treatment with regimens costing >500 000JPY/month, and molecular targeted drugs being the main drivers of cost., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We report the case of a 46-year-old female patient who developed a subacute progression of axial and proximal muscle weakness. Laboratory findings revealed mildly elevated serum creatine kinase levels. No monoclonal gammopathy was detected. A muscle biopsy revealed that she had nemaline myopathy. Serological tests and a lip biopsy revealed Sjögren's syndrome (SjS). We diagnosed her as having sporadic late-onset nemaline myopathy without monoclonal gammopathy of undetermined significance associated with SjS. Her symptoms improved after methylprednisolone pulse therapy followed by intravenous immunoglobulin therapy. A good response to immunotherapy demonstrates the necessity of making a correct diagnosis, for which a muscle biopsy is required.

A 31-year-old Japanese man presented with cerebral and pulmonary cryptococcosis. Cryptococcus gattii (C. gattii) genotype VGIIb was detected in the patient's sputum and cerebrospinal fluid specimens. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were elevated in this patient, which has been associated with pulmonary alveolar proteinosis and is considered a risk factor for C. gattii infection. After undergoing >12 months of antifungal treatments, the patient showed improvements in symptoms and findings on brain and lung imaging. Several Japanese patients who develop C. gattii infection have also been reported; however, most of these patients have been infected outside Japan, as C. gattii infection is rare in Japan. Only one patient with C. gattii genotype VGIIb infection has been reported in Japan, and it is believed that this patient contracted the infection in China. In the present case, our patient has never been outside Japan, indicating that the infection originated in Japan. Our findings suggest that C. gattii might be spreading in Japan. Therefore, patients with positive serum anti-GM-CSF antibodies should be thoroughly monitored for C. gattii infection, even those living in Japan., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC)., Methods: In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes., Findings: Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%)., Conclusion: CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC., Funding: Chugai Pharmaceutical Co., Ltd., Competing Interests: Declaration of interests H.B. received grants from Ono Pharmaceutical. H.B. also reports honoraria for lectures from Ono Pharmaceutical, Eli Lilly Japan, and Taiho Pharmaceutical. D.K. reports honoraria from Takeda Pharmaceutical, Chugai Pharmaceutical, Novartis, Eli Lilly, Seagen, MSD, Ono Pharmaceutical, Eisai, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi-Sankyo, Pfizer, Merck Biopharma, and Sysmex and research funding from Ono Pharmaceutical, MSD, Novartis, Servier, Janssen, IQVIA, Syneoshealth, CIMIC, and Cimic Shift Zero. H.S. received grants from Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, and Sanofi and reports honoraria from Bayer, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Bio Pharma, MSD, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. T.H. reports honoraria for lectures from Chugai Pharmaceutical. M.S. is on the speakers’ bureau at Johnson & Johnson, Kaken Pharmaceutical, Eli Lilly Japan, Merck Serono, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. M.K. reports honoraria for lectures from Chugai Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Yakult Honsha, and Taiho Pharmaceutical. T. Masuishi reports honoraria from Bayer Yakuhin, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck Serono, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha and reports research funding from Amgen (Inst), Boehringer Ingelheim (Inst), CMIC (Inst), Daiichi Sankyo (Inst), Eli Lilly Japan (Inst), MSD (Inst), Novartis (Inst), Ono Pharmaceutical (Inst), Pfizer (Inst), and Syneos Health (Inst). H.Y. reports honoraria from Chugai Pharmaceutical and Yakult Honsha. Y. Kagawa reports honoraria from Chugai Pharmaceutical and Yakult Honsha. Y. Komatsu received grants from Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi, Nippon Zoki Pharmaceutical, Asahi Kasei Pharma Corporation, Nippon Kayaku, Daichi Sankyo, IQVIA Services Japan, MSD, Astellas Pharma, Incyte Corporation, Eisai, National Cancer Center Japan, Syneos Health Clinical, Shift Zero, PARAXEL International, Japan Clinical Cancer Research Organization, EPS Holdings, SYSMEX Corporation, Public Health Research Foundation, Aichi Cancer Center, and the Kyushu Study group of Clinical Cancer and reports honoraria for lectures from Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly and Company, Alfresa Pharma Corporation, Astellas Pharma, EA Pharma, Nippon Kayaku, Pfizer, Nippon Zoki Pharmaceutical, Sanofi, NIPRO, MOROO, Boehringer lngelheim, Hakodate National Hospital, Asahi Kasei Pharma Corporation, MSD, Zeria Pharmaceutical, Bayer Yakuhin, Yakult Honsha, Sumitomo Dainippon Pharma, Incyte Corporation, Merck Biopharma, The Japanese Gastroenterological Association, Sapporo Minami Tokushukai Hospital, and Pancan Japan. E.O. is on the speakers’ bureau at Bristol-Myers Squibb Japan, Chugai Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical and received research funding from Guardant Health. Y.Y. reports honoraria for lectures from Ono Pharmaceutical, Bristol Myers Squibb, Yakult, Chugai Pharmaceutical, Eli Lily, Bayer, Taiho Pharmaceutical, Servier, Takeda Pharmaceutical, Daiichi Sankyo, Teijin, and Insight. H.K. received grants or contracts from Chugai Pharmaceutical, Taiho Pharmaceutical, and Eisai and received consulting fees from BMS, Eli Lilly Japan, Ono Pharmaceutical, Daiichi Sankyo, and Taiho Pharmaceutical; and has received honoraria from BMS, Bayer Yakuhin, Eli Lilly Japan, MSD, Ono Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, and Taiho Pharmaceutical. T. Misumi reports honoraria from Chugai Pharmaceutical, AstraZeneca, and Miyarisan. H.T. received lecture fees from Takeda Pharmaceutical, Ono Pharmaceutical, Eli Lilly, Merck Biopharma, and Chugai Pharmaceutical and received research funds from Takeda Pharmaceutical, Daiichi Sankyo, and Ono Pharmaceutical. K.Y. reports honoraria for lectures from Chugai Pharmaceutical, Yakult, Daiichi Sankyo, Merk Serono, Sanofi, MSD, Takeda Pharmaceutical, Taiho Pharmaceutical, Bayer, Eli Lily, Ono Pharmaceutical, and Bristol-Myers Squibb. K.M. reports honoraria from Bristol-Myers Squibb, Daiichi Sankyo, MSD, Eli Lilly, Ono Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical; reports a consulting or advisory role at Amgen, Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, and Ono Pharmaceutical; and received research funding from Amgen (Inst), Astellas Pharma (Inst), Chugai Pharmaceutical (Inst), Eisai (Inst), MSD (Inst), Novartis (Inst), Ono Pharmaceutical (Inst), Sanofi (Inst), and Taiho Pharmaceutical (Inst). T.Y. received consulting fees Sumitomo Corporation; received grants from Amgen, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, FALCO biosystems, Genomedia, Molecular Health GmbH, MSD, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan, Roche Diagnostics, Sanofi, Sysmex, and Taiho Pharmaceutical; and reports honoraria for presentations from Bayer Yakuhin, Chugai Pharmaceutical, Merck Biopharma, MSD, Ono Pharmaceutical, and Takeda Pharmaceutical. T.K. reports honoraria for lectures from Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, and Eli Lilly and Company. A.T. is on the speakers' bureau at Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, Merck Serono, Sanofi, Taiho Pharmaceutical, and Takeda Pharmaceutical and reports research funding from Ono Pharmaceutical (Inst), Sanofi (Inst), and Taiho Pharmaceutical (Inst)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The eukaryotic nucleus has a highly organized structure. Although the spatiotemporal arrangement of spliceosomes on nascent RNA drives splicing, the nuclear architecture that directly supports this process remains unclear. Here, we show that RNA-binding proteins (RBPs) assembled on RNA form meshworks in human and mouse cells. Core and accessory RBPs in RNA splicing make two distinct meshworks adjacently but distinctly distributed throughout the nucleus. This is achieved by mutual exclusion dynamics between the charged and uncharged intrinsically disordered regions (IDRs) of RBPs. These two types of meshworks compete for spatial occupancy on pre-mRNA to regulate splicing. Furthermore, the optogenetic enhancement of the RBP meshwork causes aberrant splicing, particularly of genes involved in neurodegeneration. Genetic mutations associated with neurodegenerative diseases are often found in the IDRs of RBPs, and cells harboring these mutations exhibit impaired meshwork formation. Our results uncovered the spatial organization of RBP networks to drive RNA splicing., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Physicians, physical therapists, and occupational therapists have traditionally assessed hand motor function in hemiplegic patients but often struggle to evaluate complex hand movements. To address this issue, in 2019, we developed Fahrenheit, a device and algorithm that uses infrared camera image processing to estimate hand paralysis. However, due to Fahrenheit's dependency on specialized equipment, we conceived a simpler solution: developing a smartphone app that integrates MediaPipe. The objective of this study was to measure hand movements in stroke patients using both MediaPipe and Fahrenheit and to assess their criterion-related validity. The analysis revealed moderate-to-high correlations between the two methods. Consistent results were also observed in the peak angle and velocity comparisons across the severity stages. Because Fahrenheit determines finger recovery status based on these measures, it has the potential to transfer this function to MediaPipe. This study highlighted the potential use of MediaPipe in paralysis estimation applications.

Although phase III randomized controlled trials (RCTs) represent the most robust statistical approach for answering clinical questions, they require massive expenditures in terms of time, labor, and funding. Ancillary and supplementary analyses using RCTs are sometimes conducted as alternative approaches to answering clinical questions, but the available integrated databases of RCTs are limited. In this background, the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG) established a database of ancillary studies integrating four phase III RCTs (JCOG0212, JCOG0404, JCOG0910 and JCOG1006) conducted by the CCSG to investigate specific clinicopathological factors in pStage II/III colorectal cancer (JCOG2310A). This database will be updated by adding another clinical trial data and accelerating several analyses that are clinically relevant in the management of localized colorectal cancer. This study describes the details of this database and planned and ongoing analyses as an initiative of JCOG cOlorectal Young investigators (JOY)., Competing Interests: Declaration of competing interest None declared., (© 2024 Published by Elsevier Ltd.)

The reaching motion to the back of the head with the hand is an important movement for daily living. The scores of upper limb function tests used in clinical practice alone are difficult to use as a reference when planning exercises for movement improvements. This cross-sectional study aimed to clarify in patients with mild hemiplegia the kinematic characteristics of paralyzed and non-paralyzed upper limbs reaching the occiput. Ten patients with post-stroke hemiplegia who attended the Department of Rehabilitation Medicine of the Jikei University Hospital and met the eligibility criteria were included. Reaching motion to the back of the head by the participants' paralyzed and non-paralyzed upper limbs was measured using three-dimensional motion analysis, and the motor time, joint angles, and angular velocities were calculated. Repeated measures multivariate analysis of covariance was performed on these data. After confirming the fit to the binomial logistic regression model, the cutoff values were calculated using receiver operating characteristic curves. Pattern identification using random forest clustering was performed to analyze the pattern of motor time and joint angles. The cutoff values for the movement until the hand reached the back of the head were 1.6 s for the motor time, 55° for the maximum shoulder joint flexion angle, and 145° for the maximum elbow joint flexion angle. The cutoff values for the movement from the back of the head to the hand being returned to its original position were 1.6 s for the motor time, 145° for the maximum elbow joint flexion angle, 53°/s for the maximum angular velocity of shoulder joint abduction, and 62°/s for the maximum angular velocity of elbow joint flexion. The numbers of clusters were three, four, and four for the outward non-paralyzed side, outward and return paralyzed side, and return non-paralyzed side, respectively. The findings obtained by this study can be used for practice planning in patients with mild hemiplegia who aim to improve the reaching motion to the occiput., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sakamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We aimed to identify gut microbial features in Parkinson's disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls in Japan with five previously reported datasets from USA, Germany, China1, China2, and Taiwan. GC-MS and LC-MS/MS assays were established to quantify fecal short-chain fatty acids (SCFAs) and fecal polyamines, respectively. α-Diversity was increased in PD across six datasets. Taxonomic analysis showed that species Akkermansia muciniphila was increased in PD, while species Roseburia intestinalis and Faecalibacterium prausnitzii were decreased in PD. Pathway analysis showed that genes in the biosyntheses of riboflavin and biotin were markedly decreased in PD after adjusting for confounding factors. Five out of six categories in carbohydrate-active enzymes (CAZymes) were decreased in PD. Metabolomic analysis of our fecal samples revealed that fecal SCFAs and polyamines were significantly decreased in PD. Genes in the riboflavin and biotin biosyntheses were positively correlated with the fecal concentrations of SCFAs and polyamines. Bacteria that accounted for the decreased riboflavin biosynthesis in Japan, the USA, and Germany were different from those in China1, China2, and Taiwan. Similarly, different bacteria accounted for decreased biotin biosynthesis in the two country groups. We postulate that decreased SCFAs and polyamines reduce the intestinal mucus layer, which subsequently facilitates the formation of abnormal α-synuclein fibrils in the intestinal neural plexus in PD, and also cause neuroinflammation in PD., (© 2024. The Author(s).)

Background/Objectives : Population aging is rapidly increasing, and the importance of preventive medicine has been stressed. Health checkups, diet, and exercise are of paramount importance. This study aimed to evaluate the effectiveness of a personalized dual-task intervention that combined exercise with cognitive tasks in improving physical and cognitive functions among independently living older individuals. Methods : Participants aged >65 years who were mostly independent in their activities of daily living were divided into two groups. The group receiving the 20 min robot-assisted session was compared with the group receiving traditional functional restoration training. This randomized trial assessed the impact of this intervention on the 30 s chair stand test score and Montreal Cognitive Assessment-Japanese version score of the participants. Results : Both scores significantly improved in the intervention group, indicating enhanced lower-limb function and cognitive capabilities. Conclusions : These findings suggest that integrating cognitive tasks with physical exercise can stand as an effective strategy to improve overall well-being in older people, offering valuable insights for designing comprehensive preventive health programs tailored to this demographic.

The incidence of neuroendocrine carcinomas arising from the bile duct is low, and that of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) is even lower; therefore, there is no standard treatment for MiNENs. Choosing the appropriate treatment in clinical practice is difficult. We herein report a case of unresectable extrahepatic bile duct MiNEN in a 66-year-old man who received curative chemoradiotherapy and achieved a complete response, remaining recurrence-free for 2.5 years. We consider the findings of this case to be valuable in selecting a treatment strategy for unresectable bile duct MiNENs.

[Purpose] Physical activity helps prevent diseases and mitigate their severity in older individuals with lifestyle-related conditions. We investigated whether seasonal factors and existing diseases affect physical activity in this demographic to identify lifestyle guidance indicators for health maintenance. [Participants and Methods] We compared the daily steps of older individuals (age of ≥65 years) by month, sex, and disease status from August to January by using three-way analysis of covariance. We evaluated a total of 115 participants (83 females and 32 males). [Results] Females with diseases had significantly fewer monthly daily steps than females without diseases in November (mean difference=1,138 ± 220) and December (mean difference=1,578 ± 239). Throughout, males with diseases completed significantly fewer monthly daily steps than did males without diseases. Furthermore, monthly daily steps never differed significantly between females with diseases and their male counterparts. [Conclusion] Compared with healthy older individuals, in older persons with diseases, physical activity was lower year-round among males and in November and December among females. Separate daily step count goals may be required for health maintenance in both sexes. It is important to determine the daily steps necessary to prevent various diseases and mitigate their severity while maintaining physical activity among older persons with diseases., Competing Interests: The authors declare that there is no conflict of interest., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background/Objectives : Upper-limb function of chronic stroke patients declined when outpatient rehabilitation was interrupted and outings restricted, owing to the novel coronavirus infection (COVID-19) pandemic. We investigated whether these patients recovered upper-limb function post-resumption of outpatient rehabilitation. Methods : In this observational study, 43 chronic stroke hemiparesis patients with impaired upper extremity function were scored for limb function via the Fugl-Meyer assessment of the upper extremity (FMA-UE) and the Action Research Arm Test (ARAT) after a structured interview, evaluation, and intervention. Scores at 6 and 3 months pre- and 3 months post-rehabilitation interruption were examined retrospectively; scores immediately and at 3 and 6 months post-resumption of care were examined prospectively. The amount of change for each time period and an analysis of covariance were performed with time as a factor, changes in the FMA-UE and the ARAT scores as dependent variables, and statistical significance at 5%. Results : The time of evaluation significantly impacted the total score, as well as part C and part D of FMA-UE and total, pinch, and gross movement of the ARAT. Post-hoc tests showed that the magnitude of change in limb-function scores from immediately to 3 months post-resumption was significantly higher than the change from 3 months pre- to immediately post-interruption for the total score and part D of the FMA-UE, as well as grip and gross movement of the ARAT ( p < 0.05). Conclusions : Upper-limb functional decline in chronic stroke patients, caused by the COVID-19 pandemic-related therapy interruption and outing restrictions, was resolved approximately 3 months post-resumption of rehabilitation therapy. Our data can serve as reference standards for planning and evaluating treatment for chronic stroke patients with inactivity-related impaired upper-limb function.

Background: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP., Materials and Methods: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response., Results: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively)., Conclusion: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A better understanding of the relative contributions of various factors to patient outcomes is essential for optimal patient selection for extracorporeal CPR (ECPR) therapy for patients with out-of-hospital cardiac arrest (OHCA). However, evidence on the prognostic comparison based on the etiologies of cardiac arrest is limited., Research Question: What is the etiology-based prognosis of patients undergoing ECPR for OHCA?, Study Design and Methods: This retrospective multicenter registry study involved 36 institutions in Japan and included all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. The primary etiology for OHCA was determined retrospectively from all hospital-based data at each institution. We performed a multivariable logistic regression model to determine the association between etiology of cardiac arrest and two outcomes: favorable neurologic outcome and survival at hospital discharge., Results: We identified 1,781 eligible patients, of whom 1,405 (78.9%) had cardiac arrest because of cardiac causes. Multivariable logistic regression analysis for favorable neurologic outcome showed that accidental hypothermia (adjusted OR, 5.12; 95% CI, 2.98-8.80; P < .001) was associated with a significantly higher rate of favorable neurologic outcome than cardiac causes. Multivariable logistic regression analysis for survival showed that accidental hypothermia (adjusted OR, 5.19; 95% CI, 3.15-8.56; P < .001) had significantly higher rates of survival than cardiac causes. Acute aortic dissection/aneurysm (adjusted OR, 0.07; 95% CI, 0.02-0.28; P < .001) and primary cerebral disorders (adjusted OR, 0.12; 95% CI, 0.03-0.50; P = .004) had significantly lower rates of survival than cardiac causes., Interpretation: In this retrospective multicenter cohort study, although most patients with OHCA underwent ECPR for cardiac causes, accidental hypothermia was associated with favorable neurologic outcome and survival; in contrast, acute aortic dissection/aneurysm and primary cerebral disorders were associated with nonsurvival compared with cardiac causes., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of β-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APP SWE ) in the neurons. Observation throughout the brain revealed APP SWE -positive somata in the broad regions. Quantitative model analysis showed that the somatic accumulation of APP SWE developed firstly in the hippocampus from a very early age (<1 month) and proceeded slower in the isocortex. In line with this, the hippocampus was the first region to form amyloid plaques at the age of 9-12 months, while amyloid plaques were rarely observed in the isocortex. Females had more APP SWE -positive somata and plaques than males. Furthermore, amyloid plaques were observed in the lateral septum and pontine grey, which did not contain APP SWE -positive somata but only the APP SWE -positive fibers. These results suggested that neuronal accumulation of APP SWE , both in somatodendritic and axonal domains, is closely related to the formation of amyloid plaques., Competing Interests: 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., (© 2024 The Author(s).)

Light-harvesting complexes (LHCs) are diversified among photosynthetic organisms, and the structure of the photosystem I-LHC (PSI-LHCI) supercomplex has been shown to be variable depending on the species of organisms. However, the structural and evolutionary correlations of red-lineage LHCs are unknown. Here, we determined a 1.92-Å resolution cryoelectron microscopic structure of a PSI-LHCI supercomplex isolated from the red alga Cyanidium caldarium RK-1 (NIES-2137), which is an important taxon in the Cyanidiophyceae. We subsequently investigated the correlations of PSI-LHCIs from different organisms through structural comparisons and phylogenetic analysis. The PSI-LHCI structure obtained shows five LHCI subunits surrounding a PSI-monomer core. The five LHCIs are composed of two Lhcr1s, two Lhcr2s, and one Lhcr3. Phylogenetic analysis of LHCs bound to PSI in the red-lineage algae showed clear orthology of LHCs between C. caldarium and Cyanidioschyzon merolae , whereas no orthologous relationships were found between C. caldarium Lhcr1-3 and LHCs in other red-lineage PSI-LHCI structures. These findings provide evolutionary insights into conservation and diversity of red-lineage LHCs associated with PSI., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: In some cases of patients with out-of-hospital cardiac arrest (OHCA) who underwent extracorporeal cardiopulmonary resuscitation (ECPR), negative pupillary light reflex (PLR) and mydriasis upon hospital arrival serve as common early indicator of poor prognosis. However, in certain patients with poor prognoses inferred by pupil findings upon hospital arrival, pupillary findings improve before and after the establishment of ECPR. The association between these changes in pupillary findings and prognosis remains unclear. This study aimed to clarify the association of pupillary examinations before and after the establishment of ECPR in patients with OHCA showing poor pupillary findings upon hospital arrival with their outcomes. To this end, we analysed retrospective multicentre registry data involving 36 institutions in Japan, including all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. We selected patients with poor prognosis inferred by pupillary examinations, negative pupillary light reflex (PLR) and pupil mydriasis, upon hospital arrival. The primary outcome was favourable neurological outcome, defined as Cerebral Performance Category 1 or 2 at hospital discharge. Multivariable logistic regression analysis was performed to evaluate the association between favourable neurological outcome and pupillary examination after establishing ECPR., Results: Out of the 2,157 patients enrolled in the SAVE-J II study, 723 were analysed. Among the patients analysed, 74 (10.2%) demonstrated favourable neurological outcome at hospital discharge. Multivariable analysis revealed that a positive PLR at ICU admission (odds ration [OR] = 11.3, 95% confidence intervals [CI] = 5.17-24.7) was significantly associated with favourable neurological outcome. However, normal pupil diameter at ICU admission (OR = 1.10, 95%CI = 0.52-2.32) was not significantly associated with favourable neurological outcome., Conclusion: Among the patients with OHCA who underwent ECPR and showed poor pupillary examination findings upon hospital arrival, 10.2% had favourable neurological outcome at hospital discharge. A positive PLR after the establishment of ECPR was significantly associated with favourable neurological outcome., (© 2024. The Author(s).)

Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.

[Purpose] This study investigated the changes in caregiving risk and motor function among older adults participating in community gatherings ("Kayoinoba") in Koshigaya. [Participants and Methods] A total of 257 older participants who engaged in the Kayoinoba program for 6 months from its inception were included in the analysis. Caregiving risk and motor function were assessed twice-once at the beginning of the Kayoinoba (first assessment) and again 6 months later (second assessment). The Kihon Checklist was used to evaluate caregiving risk, and the timed up-and-go, one-leg standing, and 30-s chair-stand tests were done to evaluate motor functioning. Participants were divided into pre-frail and healthy groups, and the first and second assessments were compared. [Results] The Kihon Checklist score of the pre-frail group significantly improved from the first to the second assessment. The pre-frail group had lower composite scores for physical function, outdoor activities, and depression mood items based on the Kihon Checklist; the healthy group showed no such differences. Performance on the 30-s chair-stand test was significantly better in the second assessment than in the first assessment in both groups. [Conclusion] The findings of this study emphasize the benefits of participating in Kayoinoba among high-risk older adults and provide the knowledge for developing a healthier community-based symbiotic society., Competing Interests: The authors declare that there is no conflict of interest., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Artificial photosynthetic cells producing organic matter from CO 2 and water have been extensively studied for carbon neutrality, and the research trend is currently transitioning from proof of concept using small-sized cells to large-scale demonstrations for practical applications. We previously demonstrated a 1 m 2 size cell in which an electrochemical (EC) reactor featuring a ruthenium (Ru)-complex polymer (RuCP) cathode catalyst was integrated with photovoltaic cells. In this study, we tackled the remaining issue to improve the long-term durability of cathode electrodes used in the EC reactors, demonstrating high Faradaic efficiencies exceeding 80% and around 60% electricity-to-chemical energy-conversion efficiencies of a 75 cm 2 sized EC reactor after continuous operation for 3000 h under practical conditions. Introduction of a pyrrole derivative containing an amino group in the RuCP coupled with UV-ozone treatment to create carboxyl groups on the carbon supports effectively reduced the detachment of the RuCP catalyst by forming a strong amide linkage. A newly developed chemically resistant graphite adhesive prevented the carbon supports from peeling off of the conductive substrates. In addition, highly durable anodes composed of IrO x -TaO y /Pt-metal oxide/Ti were adopted. Even though the EC reactor was installed at an inclined angle of 30°, which is approximately the optimal angle for receiving more solar energy, the crossover reactions were sufficiently suppressed because the porous separator film impeded the transfer of oxygen gas bubbles from the anode to the cathode. The intermittent operation improved the energy-conversion efficiency because the accumulated bubbles were removed at night., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aim: To investigate the factors associated with favourable neurological outcomes in adult patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA)., Methods: This retrospective observational study used secondary analysis of the SAVE-J II multicentre registry data from 36 institutions in Japan. Between 2013 and 2018, 2157 patients with OHCA who underwent ECPR were enrolled in SAVE-J II. A total of 1823 patients met the study inclusion criteria. Adult patients (aged ≥ 18 years) with OHCA, who underwent ECPR before admission to the intensive care unit, were included in our secondary analysis. The primary outcome was a favourable neurological outcome at hospital discharge, defined as a Cerebral Performance Category score of 1 or 2. We used a multivariate logistic regression model to examine the association between factors measured at the incident scene or upon hospital arrival and favourable neurological outcomes., Results: Multivariable analysis revealed that shockable rhythm at the scene [odds ratio (OR); 2.11; 95% confidence interval (CI), 1.16-3.95] and upon hospital arrival (OR 2.59; 95% CI 1.60-4.30), bystander CPR (OR 1.63; 95% CI 1.03-1.88), body movement during resuscitation (OR 7.10; 95% CI 1.79-32.90), gasping (OR 4.33; 95% CI 2.57-7.28), pupillary reflex on arrival (OR 2.93; 95% CI 1.73-4.95), and male sex (OR 0.43; 95% CI 0.24-0.75) significantly correlated with neurological outcomes., Conclusions: Shockable rhythm, bystander CPR, body movement during resuscitation, gasping, pupillary reflex, and sex were associated with favourable neurological outcomes in patients with OHCA treated with ECPR., Competing Interests: 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., (© 2024 The Authors.)