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Very-low-birth-weight infants (VLBWIs) are at high risk for neurodevelopmental problems after age 3 years. We investigated the association between the developmental quotient (DQ) of VLBWIs and their growth profiles during 6 years after birth. Participants were VLBWIs born at Kokura Medical Center (the first cohort) and Kyushu University Hospital (the second cohort) between 2012 and 2017. Recorded charts were used to collect growth profiles and developmental quotients (DQ) of the participants until age 6 years. In the first cohort (n = 64), the DQ values at age 6 years were correlated with those at age 3 years. VLBWIs with DQ ≥ 85 at age 6 years had a higher body weight and height at age 3 years than those with DQ < 85. The second cohort (n = 69) validated these findings. A comparative analysis of the two cohorts revealed that the DQ of VLBWIs was dissociated from their growth profiles after age 3 years. Clustering analyses indicated that DQ values at age 3 years predicted better the prognosis of VLBWIs with DQ ≥ 85 at age 6 years than their growth profiles. This study demonstrates that VLBWIs gain divergent profiles in growth, development, and growth-and-development correlation during postnatal 6 years., Competing Interests: Competing interests: The authors declare no competing interests. Ethics: The present study was conducted in accordance with institutional guidelines for clinical studies using human samples. Both NHO Kokura Medical Center and Kyushu University started a prospective observational study for VLBWIs organized by the Neonatal Research Network, Japan in 2003 (Tokyo Women’s University: UMIN000008763; Kyushu University: #29-628 and #29-635). The specific aim of this study was approved by the research committees at both institutes as a retrospective analysis of participants during the observation period (REC2021-024). The parents of the participants gave their written informed consent for a prospective study of their developmental outcomes. Consent statement: Written informed consent was obtained from the parents of the participants at birth for the long-term observation of neurological development. Consent was not required for the retrospective analysis of their growth and development., (© 2025. The Author(s).)

Background: This report investigates the applicability of nursing support for patients with cancer with a prognosis of months and weeks, and their families., Objectives: To evaluate the applicability of nursing support for five symptoms (dyspnea, pain, nausea/vomiting, constipation, and delirium) in patients with cancer during the last weeks of life, and the caregiver burden on their families., Design Setting: A Delphi study was used to determine the applicability of nursing support for patients with terminal cancer and their families. Eight experts in symptom palliation in Japan who have direct care or research experience with these populations were included. The Delphi method was used to assess nursing support types for prognoses of months and weeks. Consensus was defined as ≥70% agreement for either "high applicability" or "low applicability" of each support type., Results: A total of 50 nursing support types for 5 symptoms were evaluated as highly applicable for 92% ( n = 46) of patients with cancer with a prognosis of months. For patients with cancer with a prognosis of weeks, 78% ( n = 39) of the nursing support was rated as highly applicable. For both prognosis groups, all nursing support (n = 6) for caregiver burden was highly applicable., Conclusion: Applicability ratings of nursing support may be influenced by a high degree of invasiveness, accessibility of knowledge and information, and high expectations of effectiveness. Future studies are needed to verify the effectiveness of nursing support evaluated as highly applicable to patients with cancer during the last few months and weeks of life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose In recent years, research on caregivers has highlighted the importance of integrating advanced technologies, such as wearable devices. Furthermore, when investigating the characteristics of persons with dementia (PWD), comparative analyses should be conducted based on the presence or absence of the condition. We aimed to elucidate the relationship between caregivers' subjective burdens, tasks, and heart rate (HR) using wearable sensors to objectively assess the health status of caregivers of PWD and older adults requiring long-term care. Methods The study recruited 21 caregivers of PWDs and older adults requiring long-term care between September 2022 and December 2024 from one hospital, two care plan centers, and visiting nursing stations in Fukuoka Prefecture, Japan. We collected the participants' sociodemographic data using a questionnaire survey for caregivers. We also measured the caregiver's HR, walking steps, and total sleep time using a wearable sensor. Results Data from 17 participants with no missing values were included in this analysis among the 21 caregivers who provided consent to participate in this study. The demographic variables of the caregivers and care recipients revealed that the caregivers were predominantly female (typical spouses). Most PWDs were diagnosed with atopic disease. No significant correlations were found between the short Japanese version of the Zarit Burden Interview (J-ZBI&#95;8) and the following measures: caregiving years, activities of daily living (ADL), the 14-item Short-Memory Questionnaire (SMQ), caregiving time, the Caregiving Gratification Scale (CGS), total caregiving tasks, sleep time, walking steps, or conversation time. Caregiver burden was significantly associated with caregiving experience and continued caregiving. We observed no significant differences in the average HR for pre- and post-caregiving tasks. Significant differences were found in the maximum pre- and post-caregiving HR. While caregiver burden showed a high-scoring trend and positive perception showed a low-scoring trend, none of the variables differed according to the presence or absence of PWDs. Conclusions These results indicate that subjective appraisal of caregiver burden was not significantly associated with HR change during caregiving tasks. No differences were observed in the behaviors of caregivers with or without dementia. It is necessary to measure subjective and objective appraisals using wearable sensors to better understand caregivers' situations., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Ethics Committee of the Japanese Red Cross Kyushu International College of Nursing issued approval 22-017. 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: This study was supported by the JSPS KAKENHI (Grant Number JP 21K11073). The funders played no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Kajiwara et al.)

Background: Diabetes treatments by the control of sodium-glucose cotransporter 2 (SGLT2) is commonly conducted while there are still uncertainties about the mechanisms for the SGLT2 overexpression in kidneys with diabetes. Previously, we have reported that glomeruli and proximal tubules with diabetic nephropathy express toll-like receptor TLR2/4, and that the TLR ligand lipopolysaccharide (LPS) of periodontal pathogens have caused nephropathy in diabetic model mice. Recently, many researchers suggested that the periodontal pathogenic bacteria Fusobacterium (F.) nucleatum has the TLR4-associated strong activator of the colorectal inflammation and cancer. The present study aimed to investigate the possibility of F. nucleatum as an exacerbation factor of diabetes through the renal SGLT2 induction., Methods: The induction of the SGLT2 by F. nucleatum LPS (Fn-LPS) were investigated in the streptozotocin-induced diabetic mouse renal tissue and cultured renal proximal epithelial cells. The changes of blood glucose levels and survival curves in diabetic mice with Fn-LPS were analyzed. The Fn-LPS-induced SGLT2 production in the diabetic mouse renal tissue and in the cultured proximal epithelial cells was examined by ELISA, quantitative RT-PCR, and immunohistochemical analysis., Results: The SGLT2 expression in the cultured mouse tubular epithelial cells was significantly increased by TNF- or co-culture with Fn-LPS-supplemented J774.1 cells. The period to reach diabetic condition was significantly shorter in Fn-LPS-administered diabetic mice than in diabetic mice. All Fn-LPS-administered-diabetic mice reached humane endpoints during the healthy period of all of the mice administered Fn-LPS only. The promotion of the SGLT2 expression at the inner lumen of proximal tubules were stronger in the Fn-LPS-administered-diabetic mice than in diabetic mice. The renal tissue SGLT2 mRNA amounts and the number of renal proximal tubules with overexpressed SGLT2 in the lumen were more in the Fn-LPS-administered-diabetic mice than in diabetic mice., Conclusions: This study suggests that F. nucleatum causes the promotion of diabetes through the overexpression of SGLT2 in proximal tubules under the diabetic condition. Periodontitis with F. nucleatum may be a diabetic exacerbating factor., Competing Interests: Declarations. Ethical approval: All methods were performed in accordance with the relevant guidelines and regulations. The animal experimental procedures were prepared following the ARRIVE guidelines. The protocol of the experiments for animal use was approved by the Animal Experiment Committee of Fukuoka Dental College (No. 19010). For studies with human subjects, include the statement “All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and/or with the Helsinki Declaration of 1964 and later versions. Consent to participate: Not applicable. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Delirium is a condition characterized by an acute and transient disturbance in attention, cognition, and consciousness. It is increasingly prevalent at the end of life in patients with cancer. While non-pharmacological nursing interventions are essential for delirium prevention, their effectiveness in terminally ill patients with cancer remains unclear., Objectives: This study examined the nursing support practices employed to prevent delirium in terminally ill patients with cancer in palliative care units (PCUs) in Japan., Methods: This cross-sectional study administered an online survey to 2448 nurses from 162 institutions with PCUs in Japan., Results: Regarding nursing practices with patients with a prognosis of months and weeks, multi-component intervention, family support, and dehydration prevention were practiced frequently, whereas bright light therapy was practiced less frequently. The specialist team approach was practiced by approximately 50% of participants. Regarding multicomponent intervention in cases with a prognosis of months and weeks, adjustments in the sleep environment and pain management were practiced by more than 90% of the participants, whereas early exercise, vision or hearing assistance, and patient education on delirium were implemented by less than 50%. The management of intravenous injection routes and catheters was implemented by participants approximately 20% more frequently in cases with a prognosis of weeks than those with a prognosis of months., Conclusion: The primary methods of nursing support for preventing delirium in patients with terminal cancer were multicomponent intervention, family support, and dehydration prevention. Further research is necessary to develop and implement appropriate nursing support strategies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Catalytic subunit of DNA polymerase ζ (REV3), involved in translesion-replication is evolutionarily conserved from yeast and plants to higher eukaryotes. However, a large intermediate domain is inserted in REV3 of humans and mice. The domain has "DUF4683" region, which is significantly similar to human neurite extension and migration factor (NEXMIF). This region was also found in REV3 of invertebrates such as Ciona intestinalis (sea squirt) … and Lingula anatina (Brachiopoda). We hypothesize foreign sequences were introduced into the Rev3 genes in the ancestral species of L. anatina, which would have gradually evolved into the DUF4683 region through overly complicated processes. Besides DUF4683, various exogenous sequences would have been inserted during the REV3 evolution. Therefore, insertion events of foreign sequences are all products of "necessity". tBLASTn analysis of the Callorhinchus milii (elephant shark) genome with the C. milii REV3 sequence identified three neural factors (NEXMIF, NEXMIF-like and AHDC1) in distinct positions of the genome. These factors may have differentiated from the Rev3 gene in Chondrichthyes, which had experienced two rounds of whole-genome duplication, and may have evolved into neurite-forming proteins in vertebrates. L. anatina has the DUF4683 C-terminal proximal consensus (SPPRA/CWSP) in REV3. However, the consensus was not necessarily maintained in Mollusca, the closely related animal phylum of L. anatina. Just as written by Jacques Monod, we assume "chance" (mutation in DNA) and "necessity" (selection at the "organism" population level) were frequently repeated on the Rev3 in Cambrian ancestors. As a result, certain species developed the DUF4683 consensus of a neurite extension activity., (© 2025 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: Constipation is an uncomfortable symptom experienced by many patients with advanced cancer, and it decreases the quality of life. Several studies have advised pharmacological therapies for constipation management, whereas others have promoted nonpharmacological approaches that promote changes in the patient's lifestyle. However, constipation management by nurses has not yet been systematically reviewed in patients with cancer. Therefore, this study conducted a scoping review of nursing support focused on nonpharmacological therapies offered to relieve constipation in patients with cancer. Methods: The review was guided by Arksey and O'Malley's five-stage scoping review framework. We searched the databases of PubMed, Cumulative Index to Nursing and Allied Health Literature, CENTRAL in the Cochrane Library, and Ichushi-Web of the Japan Medical Abstract Society from the databases' inceptions to August 31, 2023, using various search terms such as "cancer," "constipation," and "nursing care." Results: A total of 1501 articles that met the eligibility criteria were identified; of these, 5 articles were selected, and 1 additional article was found via handsearching. The final sample included six articles. We categorized the articles into three major nursing support types: acupressure, aroma massage to the abdomen, and self-management education. Five studies used a randomized controlled trial (RCT) design, including one with a randomized, waiting-list controlled trial, and one used a non-RCT design. All included studies showed the effectiveness of nonpharmacological interventions to improve constipation. Conclusion: This study also identified three types of nursing support for patients with cancer to relieve constipation. However, because of the small sample size, further evidence is required.

This study explored the use of virtual reality (VR) in disaster preparedness education, focusing on VR scenarios, disaster types, and user interactivity to identify gaps in existing research. A scoping review methodology, based on the Arksey and O'Malley framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Reviews (PRISMA-ScR) guidelines, was used, and the protocols were registered in the UMIN Clinical Trials Registry (UMIN000052800). The review included PubMed, CINAHL, the Cochrane Central Register of Controlled Trials in the Cochrane Library, and Ichushi-Web of the Japan Medical Abstract Society, with data up to January 31, 2024. Studies on disaster preparedness and mitigation education using VR were included, without restrictions on study design, country, or language. We excluded studies utilizing non-immersive VR, as well as non-academic letters to the editor, editorials, commentaries, review articles, conference abstracts, and non-academic manuscripts. In the first screening phase, 2 researchers independently reviewed the titles and abstracts of 516 articles and conducted the screening. A total of 17 articles were selected. In cases where there were differing opinions on inclusion or exclusion, the two researchers discussed the matter together. In the second screening phase, the 17 selected articles underwent full-text screening. Three articles were excluded because their outcomes did not align with our research. Eight articles were excluded based on our predefined criteria, which included commentaries, editorials, and review articles. Ultimately, six articles were included in the meta-analysis. Of these, three studies were from East Asia, one from Australia, one from North America, and one from an unspecified region. Disaster types included chemical, radiation, explosion, fire, and earthquake events. The VR training scenarios covered evacuation, first aid, patient transport, triage, decontamination, and other skills. Five of the studies emphasized user interactivity and were primarily aimed at professionals such as medical staff and nursing students. Current VR disaster response training primarily targets professionals, demonstrating its effectiveness and importance; however, there is a lack of studies focusing on training for the general public, especially in the least developed countries. Extending VR-based training programs to the general public is critical to improving countries' disaster response capabilities., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This research was funded by the Japanese Red Cross Kyushu International College of Nursing Incentive Research (Task No. 23-3). Funding for this study was provided by unrestricted grants from NEW NURSING, Inc. (grant number: N/A). The funding source had no role in the design, practice, or analysis of this study. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kimura et al.)

Dural arteriovenous fistula (DAVF) represents a pathological group of intracranial shunts arising from the dural artery to venous sinus and veins. Childhood-onset DAVF is generally considered to be poor in prognosis, whereas only limited information is available for the onset and long-term outcomes. We herein report a Japanese girl with trisomy 21, large ventricular septal defects, and pulmonary vein stenosis, for which a transcatheter stent had been placed after birth. At age 6 years, she developed bacterial meningitis due to S. pneumoniae, leading to the diagnosis of venous sinus thrombosis and multiple intracranial shunts. Cerebral angiography identified multiple shunts arising from the middle meningeal arteries to the superior sagittal sinus and a concurrent reflux to cortical vein. Endovascular embolization successfully occluded the shunts without neurovascular complications over 24 months. This report first demonstrates the favorable outcome of DAVF in a pediatric patient with trisomy 21 after the catheter intervention. For children at a risk for intracranial thrombosis, preemptive neurovascular evaluation and transcatheter intervention provide a chance of early diagnosis of DAVF to improve their survival and neurologic outcome., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective Our previous study indicated that the efficacy of metformin in lowering glycated hemoglobin (HbA1c) levels may be influenced by the pretreatment frequency of defecation (FD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to further examine how FD and the metformin dose may affect HbA1c changes (ΔHbA1c) in T2DM patients. Methods A retrospective analysis was conducted on inpatients who received antidiabetic treatment without altering dosages for six months post-discharge, except for minor insulin adjustments. For new patients, FD was assessed before (pretreatment FD) and after the initiation of antidiabetic therapy (posttreatment FD). For patients already on treatment, FD was evaluated during hospitalization (posttreatment FD). Patients were categorized based on their metformin use, and the relationship between FD and ΔHbA1c was assessed 1.5-6 months post-discharge. The impact of the metformin dose and posttreatment FD on the ΔHbA1c level was analyzed, along with other factors affecting posttreatment FD. Results The analysis included 89 patients (41 on metformin, 21 newly treated; 48 not on metformin, 17 newly treated). Both pre- and posttreatment FD were linked to ΔHbA1c levels in the metformin group. The metformin dose correlated with posttreatment FD but not with pretreatment FD. A significant relationship was observed between ΔHbA1c and the metformin dose. A multiple regression analysis identified posttreatment FD and metformin dose as significant independent factors influencing ΔHbA1c levels. Additionally, diabetic peripheral neuropathy and diabetes duration were found to diminish the effectiveness of metformin, likely due to decreased posttreatment FD. Conclusion FD may independently contribute to the dose-dependent HbA1c-lowering effects of metformin.

Background and Purpose: Dyspnea in patients with terminal cancer worsens near death, necessitating effective nonpharmacological management. Despite guideline recommendations, detailed studies on nonpharmacological nursing practices are scarce. This study aimed to elucidate nursing practices for dyspnea in patients with cancer based on monthly and weekly prognoses., Methods: A multi-site cross-sectional study was conducted among nurses in 389 palliative care units in Japan. The study surveyed the frequency of direct care practices for dyspnea management (nurse-led intervention, multidisciplinary intervention, psychoeducational programs, breathing techniques, walking therapy, inspiratory muscle training, respiratory rehabilitation, yoga, acupressure, fan therapy, guided imagery, abdominal massage, aromatherapy, and a reduction in room temperature and humidity) in patients with cancer with monthly and weekly prognoses., Results: Of the 389 invited units, 162 participated. From these, 2448 registered nurses were invited and 539 (22.3%) responded. Almost similar nursing practices were provided regardless of patient prognosis. Nurse-led intervention was the most frequently practiced, followed by room temperature and humidity reduction, multidisciplinary intervention, and fan therapy. Yoga, respiratory rehabilitation, and acupressure were rarely practiced., Conclusion: Nursing practices for dyspnea are similar, irrespective of prognosis. Nurse-led interventions, reducing room temperature and humidity, multidisciplinary intervention, and fan therapy are frequently used for dyspnea in patients with cancer. Future studies should evaluate the effectiveness of these nursing practices., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Purpose: This study explores the use of nursing support among nurses for caregiver burden in family caregivers of terminally ill patients with cancer in palliative care units (PCUs)., Methods: Requests were sent to 389 institutions, and cooperation was received from 162 PCUs. Nurses at 162 PCUs were asked to participate in an Internet survey regarding nursing practices for caregiver burden in Japan. The frequency of six nursing support practices (extracted in a scoping review) was reported using a 5-point Likert scale., Results: The response rate was 22.3% (539/2448). Support for reducing caregiver stress was the most frequently provided nursing support (mean Likert score: 2.41 for monthly prognosis and 2.42 for weekly prognosis). Psychological and educational support was mainly provided via non-face-to-face (telephone) (mean Likert score: 2.26 for monthly prognosis and 2.21 for weekly prognosis) and face-to-face methods (mean Likert score: 2.32 for monthly prognosis and 2.29 for weekly prognosis)., Conclusion: Nursing support was provided through telephone support and face-to-face interactions and aimed at reducing caregiver stress among nurses and family caregivers of patients with terminal cancer in PCUs. In this study, the trends in nursing support were similar for patients with a prognosis of weeks or months., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Purpose: To identify nursing support for caregiver burden in family caregivers of patients with cancer. Methods: This scoping review was guided by Arksey and O'Malley's six-stage scoping review framework. All available published articles from database inception to July 31, 2023 were systematically searched through PubMed, CINAHL, CENTRAL, and Ichushi-Web of the Japan Medical Abstract Society databases with additional relevant studies from the article list. Each key journal was manually searched. Results: Overall, 502 articles were screened, and 34 were finally included. The results of the qualitative thematic analysis were categorized into 7 components of nursing support: psychological and educational support, psychological and educational support using mainly non-face-to-face (Information and Communication Technology), psychological and educational support mainly using non-face-to-face (telephone) methods, mindfulness to support, support aimed at reducing caregiver stress, support for both patients and caregivers, and others. Of the 34 studies, 23 were randomized controlled trials (RCT), and the remaining 11 were non-RCTs. Conclusion: The results of the scoping review categorized nursing support for caregiver burden in the family caregivers of patients with cancer into 7 components. Future research should examine the feasibility of implementing these components., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: A subpopulation of Japanese patients with type 2 diabetes mellitus (T2DM) who have elevated insulin clearance (IC) exists. We tested our hypothesis that it is possible to estimate IC using common and simple test results collected in routine clinical practice., Methods: We recruited patients with newly diagnosed, treatment-naïve T2DM and measured the metabolic clearance rate of insulin (MCRI) determined by a hyperinsulinemic-euglycemic clamp examination. Multivariable regression analysis was performed with body mass index (BMI), serum uric acid (UA), and fasting plasma insulin (F-IRI) which were independently associated with IC increase in our previous reports as explanatory variables to calculate a prediction equation for MCRI., Results: We enrolled 101 patients in this study. Because MCRI is not normally distributed, we calculated the logarithmically transformed estimated Log 10 MCRI as a prediction formula for IC. Multivariable regression analysis showed that Log 10 BMI (β =  - 0.3257, P  < 0.001), UA (β =  - 0.1834, P  = 0.0081), and Log 10 F-IRI (β =  - 0.4367, P  < 0.001) were significant independent factors for Log 10 MCRI. The regression equation was as follows: estimated Log 10 MCRI =  - 0.5421 × Log 10 BMI - 0.0167 × UA - 0.1792 × Log 10 F-IRI + 3.8251 ( r  = 0.7677, R 2  = 0.5894, P  < 0.001)., Conclusion: IC can easily be predicted using BMI, UA, and F-IRI which are common and simple test results collected in routine clinical practice., Competing Interests: Conflict of interestHJ has received honoraria from Novo Nordisk, Sanofi, AstraZeneca Pharmaceuticals, Astellas Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Takeda, and Novartis Pharmaceuticals. SS has received honoraria from AstraZeneca Pharmaceuticals and Ono Pharmaceutical. The authors declare that no other potential conflicts of interest exist related to this study., (© The Japan Diabetes Society 2024.)

Introduction: This study aimed to explore the association between ferroptosis, a newly identified type of cell death, and the role of retinoic acid in developing pregnancy complications. Therefore, the effects of all-trans retinoic acid (ATRA) on ferroptosis susceptibility in BeWo cells were assessed to understand abnormal placental development., Methods: BeWo cells were used as surrogates for cytotrophoblasts. The effect of ATRA on ferroptosis sensitivity was assessed on BeWo cells pretreated with ATRA or dimethyl sulfoxide (DMSO; control), following which the LDH-releasing assay was performed. The effects of ATRA pretreatment on the antioxidant defense system (including glutathione [GSH], mitochondrial membrane potential, and heme oxygenase-1 [HMOX1]) in BeWo cells were assessed using assay kits, RT-qPCR, and HMOX1 immunostaining. To evaluate the effect of ATRA on BeWo cells, HMOX1 was silenced in BeWo cells using shRNA., Results: ATRA pretreatment increased ferroptosis resistance in BeWo cells. Although with pretreatment, qPCR indicated upregulation of HMOX1, no significant change was observed in the GSH levels or mitochondrial membrane potential. This was corroborated by intensified immunostaining for heme oxygenase-1 protein (HO-1). Notably, the protective effect of ATRA against ferroptosis was negated when HO-1 was inhibited. Although HMOX1-silenced BeWo cells exhibited heightened ferroptosis sensitivity compared with controls, ATRA pretreatment counteracted ferroptosis in these cells., Discussion: ATRA pretreatment promotes BeWo cell viability by suppressing ferroptosis and upregulating HMOX1 and this can be used as a potential therapeutic strategy for addressing placental complications associated with ferroptosis., 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 article., (Copyright © 2024. Published by Elsevier Ltd.)

While the incidence and prevalence of non-tuberculous mycobacterial-pulmonary disease (NTM-PD) are increasing and microscopic polyangiitis (MPA) is common in East Asian countries, case reports of MPA associated with NTM-PD are limited. A 72-year-old male receiving treatment for NTM-PD with antibiotics was referred to our hospital with fever and arthralgia that developed a few months previously. A blood test revealed the presence of the myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) and renal impairment. Based on a pathological examination of renal tissue, which showed crescentic glomerulonephritis, the patient was diagnosed with MPA. Due to acute kidney injury and strongly positive MPO-ANCA, pulse steroid therapy was initiated followed by intravenous rituximab (RTX). The patient also received plasmapheresis (14 sessions). Renal dysfunction was reversed. MPA associated with NTM-PD is extremely rare and, thus, there is currently no established treatment. Our patient was diagnosed with MPA based on the findings of renal biopsy while receiving treatment for NTM-PD. RTX and plasmapheresis combined with systemic glucocorticoid therapy were initiated before these clinical conditions had fully recovered. Although MPA secondary to NTM-PD may be more refractory to treatment than primary MPA in the presence of a very low interferon-gamma (IFN-γ) level, this case was successfully treated with steroids, RTX, and plasmapheresis., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Adverse childhood experiences (ACEs) of mothers have been shown to be associated with children's mental health and behavior problems. It is important to identify effective intervention points to prevent negative consequences among children. This study aimed to investigate whether mothers' education is protective against children's depressive symptoms in families with mothers who experienced parental divorce in childhood., Methods: Data from a cross-sectional study of 5th and 8th grade children and their caregivers in a prefecture in Japan were used. Final analytic sample consisted of 9666 child-caregiver pairs. Mediation analyses using inverse odds weighting were performed where the exposure was maternal experience of parental divorce in childhood, outcome was child depressive symptoms, and potential mediators were maternal education beyond high school, maternal mental health, and household income., Results: Maternal experience of parental divorce was associated with an elevated risk of child depressive symptoms (risk ratio: 1.22, 95 % confidence interval (CI): 1.07-1.39). Mediation analyses indicated that the combination of maternal education, maternal depression and household income mediated about half of the total effect. In the model where maternal education was the sole mediator, maternal education mediated nearly half of the total effect (risk ratio: 1.10, 95 % CI: 1.01-1.20)., Limitations: Results should be cautiously interpreted given observational and cross-sectional nature of the data., Conclusions: Maternal education beyond high school may be protective against negative mental health consequences among children due to mothers' experience of parental divorce. Further studies are needed regarding potential mechanisms and the roles of other potential mediators., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The xerogel pill has been developed as a novel dosage form with dose-adjusting and swallow-assisting functions by using drop freeze-drying (DFD) technique. It was double-structured small sphere composed of an inner drug core and an outer dried-gel layer, however, had problem of insufficient physical strength. In this study, it was attempted to use dextrin (DEX), one of oligosaccharides, to strengthen the xerogel pill. DEX was co-dissolved in the dropping fluid in the DFD process and co-loaded in the conventional pill, which was mainly composed of mannitol (MNT) as a filler, to prepare the rigid body. DEX-loaded pill could be successfully prepared with high recovery (>90 %) by optimizing the ratio of DEX and MNT. Further, the representative pills with and without DEX (P-DEX and P-MNT, respectively) were hardening-processed under humidification. The physical strength of P-DEX pill was significantly increased when humidified under severe condition, resulting in enough hardness (>5N) and friability (<1.0 %). Processed P-DEX was found to have dense structure covered with a thick outer shell, which would be formed by interparticle bridge of DEX. It was also found that processed P-DEX pill suppressed initial drug dissolution significantly and exhibited sustained dissolution behavior, suggesting the potential function of bitter taste masking. Processed P-DEX pill had excellent sliding behavior with low friction forces as a result of lubricant effect of xanthan gum (XG) surrounding the pills. Furthermore, the sliding test also suggested that processed P-DEX pill had hard candy-like texture, in contrast unprocessed P-DEX pill had orally disintegrating (OD) tablet-like texture. Various xerogel pills with such different swallowing texture would have a potential to accommodate the children's preferences when taking medication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Hayashi et al.)

Objective: This study aimed to investigate the relationship between plasma glucose profiles and periodontal disease (PD) severity in men and women., Methods: We conducted a cross-sectional cohort study, enrolling all eligible patients with type 2 diabetes mellitus (T2DM) who regularly visited the outpatient department., Results: Patients were divided into severe and non-severe PD groups. The severe PD group showed a male predominance and significantly higher hemoglobin A1c (HbA1c) levels than the non-severe PD group. The optimal HbA1c cutoff value on the receiver operating characteristic curve for predicting severe PD was 7.3% [56 mmol/mol] (sensitivity, 52%; specificity, 73%; P = 0.01). Multivariate logistic regression revealed that male sex (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.19-6.34; P = 0.01) and higher HbA1c levels (OR, 3.09; 95% CI, 1.42-6.70; P < 0 .01) were independently and significantly associated with the presence of severe PD. The prevalence rates of severe PD in patients with HbA1c levels < 7.3% [56 mmol/mol] and HbA1c levels ≥ 7.3% [56 mmol/mol] were 17.4% and 53.3% in women, and 50.0% and 66.7% in men, respectively., Conclusions: Men with T2DM had a high risk of severe PD independent of HbA1c levels. Plasma glucose management may be crucial for maintaining periodontal health in T2DM patients, particularly in women., Competing Interests: Conflict of interestHJ has received honoraria from Novo Nordisk, Sanofi, AstraZeneca Pharmaceuticals, Astellas Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Takeda, and Novartis Pharmaceuticals. SS has received honoraria from AstraZeneca Pharmaceuticals and Ono Pharmaceutical. The authors declare no other potential conflicts of interest relevant to this study., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: This study aimed to assess the conclusiveness of Cochrane Reviews (CRs) in oncology nursing., Methods: We searched systematically for all CRs published in the Cochrane Library in the oncology nursing field between January 2014 and April 2023. We analyzed the difference between conclusive and inconclusive outcomes using the χ 2 and Mann-Whitney U -tests and identified 430 articles. However, we excluded 385 articles after reviewing their titles and abstracts. We assessed 45 full-text articles for eligibility and identified 32 articles. Of the 32 articles, we extracted 19 interventions., Results: The overall outcomes were 182 cases, with 51.6% (n = 94) and 48.4% (n = 88) demonstrating conclusiveness and inconclusiveness, respectively. Regarding conclusiveness, 28.0% (n = 51) and 23.6% (n = 43) reported that the studied interventions were effective and ineffective, respectively. We found that studies on interventions related to physical activity and yoga had significantly high rates of conclusive. Compared with inconclusiveness outcomes, conclusive outcomes involved significantly more studies ( p < 0.001) and patients ( p < 0.001)., Conclusions: Ultimately, these findings reveal that in the oncology nursing field, only 51% of the main outcomes of each nursing intervention in CRs were conclusive., Competing Interests: None, (Copyright © Japan Medical Association.)

Background: Area postrema syndrome (APS), a rare childhood condition, manifests as intractable nausea and hiccups. APS has high diagnostic significance in neuromyelitis optica syndrome spectrum disorders (NMOSD) and can be the initial presentation of other critical diseases, including brainstem glioma., Methods: We described two representative cases of unrelated Japanese patients with APS. An etiologic evaluation, including a detailed intracranial neuroradiological examination and autoantibodies assessment, was performed. We also reviewed the literature focusing on the prognosis of pediatric APS symptoms., Results: A 14-year-old girl with aquaporin-4 antibody-positive NMOSD showed a good prognosis with immunotherapy, whereas another nine-year-old girl with irresectable medullary low-grade glioma had persistent symptoms for more than 10 years. All reported children aged >12 years were diagnosed with NMOSD, and patients aged <13 years showed heterogeneous etiologies., Conclusions: Distinctive time courses and neuroimaging features were key clinical findings for the diagnostic and therapeutic processes in these patients. This literature review highlights the wide spectrum and prognosis of pediatric-onset APS., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to determine the effect of proximal splenic artery embolization (SAE) in cirrhotic patients with splenomegaly who underwent surgical laparotomy., Material and Methods: This retrospective observational study included 8 cirrhotic patients with splenomegaly. They underwent proximal SAE before- ( n  = 6) or after ( n  = 2) laparotomy. Vascular plugs or coils were placed in the proximal splenic artery. The diameter of the portal vein and the splenic volume were recorded. Clinical outcome assessments included platelet counts, the model for end-stage liver disease (MELD) score, and complications., Results: After embolization, the portal venous diameter was significantly smaller (pre: 13.6 ± 2.7 mm, post: 12.5 ± 2.3 mm, p  = 0.023), the splenic volume was significantly decreased (pre: 463.2 ± 145.7 ml, post: 373.3 ± 108.5 ml, p  = 0.008) and the platelet count was significantly higher (pre: 69.6 ± 30.8 × 10 3/ μl, post: 86.8 ± 27.7 × 10 3/ μl, p  = 0.035). Before embolization, the median MELD score was 12; after embolization, it was 11 ( p  = 0.026). No patient developed post-treatment complications after embolization., Conclusions: The reduction of hypersplenism by perioperative proximal SAE may be safe and reduce the surgical risk in cirrhotic patients with splenomegaly.

This study established the clinical conclusiveness of Cochrane reviews (CRs) in family nursing. We extracted relevant characteristics of CRs to determine the methods of obtaining high-level evidence for family nursing. We performed a systematic search of all CRs on family nursing published in the Cochrane Library between January 2014 and April 2023. After screening 1212 titles and abstracts, we identified seven potentially relevant articles. Upon reviewing their full texts, we included six CRs with a total of 34 interventions. Of these, 22 (64.7%) interventions were conclusive and 12 (55%) were inconclusive. Thus, the number and percentage of conclusive CRs is lower in family nursing versus other fields., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hydrodynamic cavitation is useful in many processing applications, for example, in chemical reactors, water treatment and biochemical engineering. An important type of hydrodynamic cavitation that occurs in a Venturi tube is vortex cavitation known to cause luminescence whose intensity is closely related to the size and number of cavitation events. However, the mechanistic origins of bubbles constituting vortex cavitation remains unclear, although it has been concluded that the pressure fields generated by the cavitation collapse strongly depends on the bubble geometry. The common view is that vortex cavitation consists of numerous small spherical bubbles. In the present paper, aspects of vortex cavitation arising in a Venturi tube were visualized using high-speed X-ray imaging at SPring-8 and European XFEL. It was discovered that vortex cavitation in a Venturi tube consisted of angulated rather than spherical bubbles. The tangential velocity of the surface of vortex cavitation was assessed considering the Rankine vortex model., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pain is subjective, warranting tailored responses in pharmacotherapy and nursing support. Despite this, the evidence for suitable nursing support for pain is not well established in terminally ill patients such as those with cancer; therefore, it is necessary to provide support in consideration of changes in physical symptoms and quality of life. However, interventional studies for such patients are often difficult. There have been no comprehensive studies to date on non-pharmacological support that can be implemented by nurses. Therefore, with the aim of examining nursing support applicable at the end of life, this scoping review comprehensively mapped nursing support for pain in cancer patients at all stages of the disease. This study complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Arksey and O'Malley framework. All available published articles from the time of database establishment to January 31, 2022, were systematically searched for in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), CENTRAL, and the Ichushi Web database of the Japanese Society of Medical Abstracts. Overall, 10,385 articles were screened, and 72 were finally included. Both randomized controlled trials (RCTs) (n = 62) and non-RCTs (n = 10) were included. Twenty-two types of nursing support were identified. Eighteen of them showed positive results; five of them were provided only to terminally ill patients, three of which were effective, namely, comfort care, foot bath, and combined therapy. It is important to examine the applicability of types of nursing support in clinical practice in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Morikawa et al.)

Nausea and vomiting are symptoms commonly experienced by patients with advanced cancer and have a wide range of causes, including pharmacological interventions. Additionally, multiple factors often simultaneously cause nausea and vomiting. These highly distressing symptoms may be directly or indirectly related to the disease and can significantly impact both the physical and psychological well-being of patients. This study aims to identify the nursing support provided to reduce nausea and vomiting experienced by patients with cancer. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist and Arksey and O'Malley's framework. We searched the PubMed, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials in the Cochrane Library, and the Ichushi-Web of the Japan Medical Abstract Society databases for all content published from the inception of each database through July 31, 2023. A total of 4,625 scientific articles were identified after literature screening. In total, 58 articles were included for full-text review, and 10 articles were finally selected for review. The types of study designs comprised six randomized controlled trials, three prospective observational studies, and one before-after study with no controls. The types of cancers included in the articles were colorectal, breast, lung, pancreatic, gynecological, stomach, and sarcoma. The total sample size of the study population was 793 patients (range = 12-281) for intervention studies and 4,333 patients (range = 20-4,197) for observational studies. Nursing support, extracted from the 10 articles, was classified into the following six types: massage therapy, acupressure, early palliative care, psychosocial support, self-symptom monitoring, and coordinated care. The review yielded six classifications of nursing support for nausea and vomiting in cancer patients. Future research should examine the feasibility of providing nursing support for nausea and vomiting in cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kobayashi et al.)

Competing Interests: None

Objective: To identify nursing support provided for the relief of breathlessness in patients with cancer., Design: A scoping review following a standard framework proposed by Arksey and O'Malley., Study Selection: Electronic databases (PubMed, CINAHL, CENTRAL and Ichushi-Web of the Japan Medical Abstract Society Databases) were searched from inception to 31 January 2022. Studies reporting on patients with cancer (aged ≥18 years), intervention for relief from breathlessness, nursing support and quantitatively assessed breathlessness using a scale were included., Results: Overall, 2629 articles were screened, and 27 were finally included. Results of the qualitative thematic analysis were categorised into 12 nursing support components: fan therapy, nurse-led intervention, multidisciplinary intervention, psychoeducational programme, breathing technique, walking therapy, inspiratory muscle training, respiratory rehabilitation, yoga, acupuncture, guided imagery and abdominal massage., Conclusions: We identified 12 components of nursing support for breathlessness in patients with cancer. The study results may be useful to understand the actual state of nursing support provided for breathlessness in patients with terminal cancer and to consider possible support that can be implemented., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The non-receptor tyrosine kinase SRC is overexpressed and/or hyperactivated in various human cancers, and facilitates cancer progression by promoting invasion and metastasis. However, the mechanisms underlying SRC upregulation are poorly understood. In this study, we demonstrate that transforming growth factor-β (TGF-β) induces SRC expression at the transcriptional level by activating an intragenic the SRC enhancer. In the human breast epithelial cell line MCF10A, TGF-β1 stimulation upregulated one of the SRC promotors, the 1A promoter, resulting in increased SRC mRNA and protein levels. Chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that the SMAD complex is recruited to three enhancer regions ∼15 kb upstream and downstream of the SRC promoter, and one of them is capable of activating the SRC promoter in response to TGF-β. JUN, a member of the activator protein (AP)-1 family, localises to the enhancer and regulates TGF-β-induced SRC expression. Furthermore, TGF-β-induced SRC upregulation plays a crucial role in epithelial-mesenchymal transition (EMT)-associated cell migration by activating the SRC-focal adhesion kinase (FAK) circuit. Overall, these results suggest that TGF-β-induced SRC upregulation promotes cancer cell invasion and metastasis in a subset of human malignancies., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Herein, we report the development of a nickel-catalyzed cross-coupling reaction of silyl difluoroenolates with aryl zinc reagents via C-F bond cleavage. Treatment of a stoichiometric amount of Ni(0)/ N -heterocyclic carbene (NHC) with silyl difluoroenolates in the presence of a lithium salt resulted in C-F bond cleavage to selectively afford the corresponding ( Z )-alkenyl Ni complexes. On the basis of the observations, we developed a catalytic cross-coupling reaction that selectively delivers a single geometric isomer of a fluoroenolate.

Background: Omalizumab, an anti-IgE antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD also present with extrarespiratory (chest, gastrointestinal, and/or cutaneous) symptoms, which are resistant to conventional treatment but can be alleviated by systemic corticosteroids., Objective: We evaluated the efficacy of omalizumab on extrarespiratory symptoms related to AERD., Methods: In study 1, a total of 27 consecutive patients with AERD initially prescribed omalizumab at Sagamihara National Hospital between July 2009 and March 2019 were retrospectively studied. Frequency of exacerbations of AERD-related extrarespiratory symptoms was compared before and after omalizumab treatment. In study 2, we reported 3 AERD cases with aspirin challenge-induced extrarespiratory symptoms among patients studied in our previous randomized trial (registration UMIN000018777), which evaluated the effects of omalizumab on hypersensitivity reactions during aspirin challenge to AERD patients. Extrarespiratory symptoms induced during the aspirin challenge were compared between placebo and omalizumab phases., Results: In study 1, omalizumab treatment was associated with decrease in frequency of exacerbation of chest pain (no. [%] of patients with exacerbation frequency ≥1 time per year, 6 [22.2%] vs 0; P < .001), gastrointestinal symptoms (9 [33.3%] vs 2 [7.4%]; P = .016), and cutaneous symptoms (16 [59.3%] vs 2 [7.4%]; P < .001), even under conditions of treatment-related reduction in systemic corticosteroid dose. Omalizumab also attenuated all the extrarespiratory symptoms during aspirin challenge in study 2., Conclusion: Omalizumab ameliorated extrarespiratory symptoms at baseline (without aspirin exposure) and during aspirin challenge., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Here, we investigated expression modules reflecting the reciprocal expression of the cancer microenvironment and immune response-related genes associated with poor prognosis in primary central nervous system lymphoma (PCNSL)., Methods: Weighted gene coexpression network analysis revealed representative modules, including neurogenesis, immune response, anti-virus, microenvironment, gene expression and translation, extracellular matrix, morphogenesis, and cell adhesion in the transcriptome data of 31 PCNSL samples. RESULTS : Gene expression networks were also reflected by protein-protein interaction networks. In particular, some of the hub genes were highly expressed in patients with PCNSL with prognoses as follows: AQP4, SLC1A3, GFAP, CXCL9, CXCL10, GBP2, IFI6, OAS2, IFIT3, DCN, LRP1, and LUM with good prognosis; and STAT1, IFITM3, GZMB, ISG15, LY6E, TGFB1, PLAUR, MMP4, FTH1, PLAU, CSF3R, FGR, POSTN, CCR7, TAS1R3, small ribosomal subunit genes, and collagen type 1/3/4/6 genes with poor prognosis. Furthermore, prognosis prediction formulae were constructed using the Cox proportional-hazards regression model, which demonstrated that the IP-10 receptor gene CXCR3 and type I interferon-induced protein gene IFI44L could predict patient survival in PCNSL., Conclusion: These results indicate that the differential expression and balance of immune response and microenvironment genes may be required for PCNSL tumor growth or prognosis prediction, which would help understanding the mechanism of tumorigenesis and potential therapeutic targets in PCNSL., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)