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Key Clinical Message One patient with metastatic spinal tumors from colorectal cancer experienced malignant spinal cord compression (MSCC). Determining the extent of the lesion using magnetic resonance imaging is essential, even if the lesion is osteoblastic. Therefore, it is important to evaluate the risk of MSCC in patients with metastatic spinal tumors.

Abstract Aim The objective of this study was to evaluate the potential of hydrogen in preventing and treating psychiatric symptoms, particularly depressed mood and loss of interest, and to explore its underlying mechanisms. A mouse model exhibiting inflammation‐derived depressive symptoms was used for the investigation. Methods Institute of Cancer Research mice were subjected to a 7‐day intervention of either 30% hydrogen or 40 g per day of air via jelly intake. On the final day, lipopolysaccharide (LPS) was intraperitoneally administered at 5 mg/kg to induce inflammation‐related depressive symptoms. Behavioral and biochemical assessments were conducted 24 h post‐LPS administration. Results Following LPS administration, a decrease in spontaneous behavior was observed; however, this effect was mitigated in the group treated with hydrogen. The social interaction test revealed a significant reduction in interactions with unfamiliar mice in the LPS‐treated group, whereas the hydrogen‐treated group exhibited no such decrease. No significant changes were noted in the forced‐swim test for either group. Additionally, the administration of LPS in the hydrogen group did not result in a decrease in zonula occludens‐1, a biochemical marker associated with barrier function at the cerebrovascular barrier and expressed in tight junctions. Conclusion Hydrogen administration demonstrated a preventive effect against the LPS‐induced loss of interest, suggesting a potential role in symptom prevention. However, it did not exhibit a suppressive effect on depressive symptoms in this particular model. These findings highlight the nuanced impact of hydrogen in the context of inflammation‐induced psychiatric symptoms, indicating potential avenues for further exploration and research.

Abstract Objective Amyotrophic lateral sclerosis (ALS) is a devastating, incurable neurodegenerative disease. A subset of ALS patients manifests with early‐onset and complex clinical phenotypes. We aimed to elucidate the genetic basis of these cases to enhance our understanding of disease etiology and facilitate the development of targeted therapies. Methods Our research commenced with an in‐depth genetic and biochemical investigation of two specific families, each with a member diagnosed with early‐onset ALS (onset age of

Key Clinical Message In a patient with anti‐aminoacyl tRNA synthetase antibody and anti‐OJ antibody syndrome, interventions likes warming, prostaglandins, and antiplatelets failed. However, prednisolone pulse treatment rapidly halted disease progression. Patients with mild interstitial pneumonia, myositis, and extremity necrosis should be promptly considered for anti‐synthetase syndrome and receive immunosuppression after ruling out other causes. Abstract Anti‐aminoacyl tRNA synthetase (ARS) autoantibodies are myositis‐specific, and patients who test positive for ARS and have common clinical features are usually diagnosed with antisynthetase antibody syndrome (antisynthetase syndrome). Anti‐ARS antibodies include histidyl‐tRNA synthetase‐1 (Jo‐1), anti‐threonyl (PL‐7), anti‐alanyl (PL‐12), anti‐glycyl (EJ), anti‐asparaginyl (KS), anti‐tyrosyl (Ha), and anti‐phenylalanyl (Zo) tRNA synthetases. Among these, anti–isoleucyl tRNA synthetase (OJ) autoantibodies are extremely rare, and patients with these are frequently complicated by interstitial pneumonia. We report the case of an older man with ARS antibody syndrome who tested positive for anti‐OJ and anti‐Sjögren's‐syndrome‐related antigen A (Ro‐52) antibodies. He had muscle weakness due to myositis and unparalleled rapid and severe finger necrosis. Pulsed prednisolone effectively treated the myositis symptoms and terminated the progression of finger necrosis.

Abstract Introduction Nitrogen is a key nutrient for plants. Often less than 50% of the applied nitrogen fertilisers is acquired by crops and nitrogen can be easily lost into the environment causing environmental pollution. Thus, to make agriculture more sustainable, it is important to investigate which factors determine nitrogen use efficiency (NUE). We investigated whether NUE was higher in organically managed soils compared to conventionally managed soils. Materials and Methods To test this, we carried out a pot experiment in a greenhouse using soils from 16 fields. The soils were collected from conventionally (eight fields) or organically managed fields (eight fields). In addition, plants received two different 15N enriched N sources (mineral 15N or an organic fertiliser source, namely 15N enriched plant litter). Plants were harvested at three time points, and growth and nitrogen uptake were assessed at each time point. Results NUE depended on management type and harvest time and the higher NUE of organically managed soils became more evident towards the second and third harvest. The average NUE at the end of the experiment was 93% and 55% for mineral fertiliser and litter application, respectively. This indicated that mineral fertilisers were immediately acquired by the plants, while nutrients in organic amendments had a lower availability and probably would be supplied later but steadier. Further, NUE was positively linked to microbial biomass, soil organic carbon content, and aggregate size, indicating that enhanced soil quality and soil health leads to a more efficient use of fertilisers. Conclusion Our results indicate that organic management and soil health promote a more efficient use of nutrients and contribute to a more sustainable agriculture.

Abstract Aim This study aimed to clarify the abnormalities in dopamine transporter (DAT) availability in drug‐naive adult patients with attention‐deficit/hyperactivity disorder (ADHD) and the relationship between ADHD symptoms and abnormalities in DAT availability. Methods Single‐photon emission tomography (SPECT) was performed using iodine‐123‐β‐carbomethoxy‐3β‐(4‐iodophenyltropane) (I‐123 β CIT) as a tracer to measure in vivo DAT availability in 20 drug‐naive patients with ADHD [mean age ± standard deviation (SD)]: 25 ± 3.44 years; male:female = 11:9] and 20 age‐ and sex‐matched healthy controls (HCs) (mean age ± SD: 23.9 ± 2.27 years). Comparisons of DAT availability between HCs and adult patients with ADHD and the association between symptom severity and DAT availability within the ADHD group were analyzed using Statistical Parametric Mapping 12. Results Drug‐naive adults with ADHD showed significantly reduced DAT availability in the bilateral nucleus accumbens compared with HCs. Correlation analyses revealed a negative correlation between the severity of inattentive symptoms in adult patients with ADHD and DAT availability in the bilateral heads of the caudate nucleus, indicating the association between severe inattentive symptoms and lower DAT availability in the caudate nucleus. Conclusion In drug‐naive adult patients with ADHD, DAT availability was reduced in the nucleus accumbens, an important part of the reward system. This finding indicates the importance of the DAT in the reward system in the pathogenesis of ADHD. Inattentiveness was associated with DAT availability in the caudate nucleus, suggesting involvement of the cortico‐striato‐thalamo‐cortical circuit.

Key Clinical Message Recent data reveal phenotypic HoFH patients may be responsive to PCSK9 inhibitors, challenging prior assumptions. Genetic testing advancements now more accurately forecast patient responses to these therapies, improving treatment strategies.

ABSTRACT Objective Adrenoleukodystrophy (ALD) has a poor prognosis when it progresses to the cerebral form (CALD). The aim of this study is to investigate whether cerebrospinal fluid (CSF) neurofilament light chain (cNfL) is a sensitive biomarker for detecting CALD and assessing response to hematopoietic stem cell transplantation (HSCT). Methods We conducted a cross‐sectional study of 41 male ALD patients. The cNfL levels in patients with the cerebral form of ALD (CALD) or the cerebello‐brainstem form of ALD were compared with those in patients with adrenomyeloneuropathy (AMN). The correlation between cNfL levels and MRI‐based Loes severity scores was investigated. A longitudinal analysis was performed on patients who underwent multiple CSF examinations. Results The cNfL levels in 22 patients with CALD were significantly higher than those in 14 patients with AMN (median, 5545 vs. 1490 pg/mL; p

Abstract Background Bone and soft tissue sarcomas are rare tumors and extremely rarely metastasize to the brain. Previous studies have examined the characteristics and poor prognostic factors in cases of sarcoma brain metastasis (BM). Due to the rarity of cases of BM from sarcoma, limited data exist concerning the prognostic factors and treatment strategies. Methods A retrospective single‐center study was performed on sarcoma patients with BM. The clinicopathological characteristics and treatment options for BM of sarcoma were investigated to identify predictive prognostic factors. Results Between 2006 and 2021, 32 patients treated for newly diagnosed BM at our hospital were retrieved among 3133 bone and soft tissue sarcoma patients via our database. The most common symptom was headache (34%), and the most common histological subtypes were alveolar soft part sarcoma (ASPS) and undifferentiated pleomorphic sarcoma (25%). Non‐ASPS (p = 0.022), presence of lung metastasis (p = 0.046), a short duration between initial metastasis, and the diagnosis of brain metastasis (p = 0.020), and the absence of stereotactic radiosurgery for BM (p = 0.0094) were significantly correlated with a poor prognosis. Conclusions In conclusion, the prognosis of patients with brain metastases of sarcomas is still dismal, but it is necessary to be aware of the factors associated with a relatively favorable prognosis and to select treatment options appropriately.

Abstract Aims/Introduction We previously showed that upregulation of myocardial adenosine monophosphate deaminase (AMPD) is associated with pressure overload‐induced diastolic dysfunction in type 2 diabetes hearts. Here, we examined involvement of AMPD localized in the endoplasmic reticulum–mitochondria interface in mitochondrial Ca2+ overload and its pathological significance. Materials and Methods We used type 2 diabetes Otsuka Long–Evans Tokushima Fatty rats (OLETF) and non‐diabetes Long–Evans Tokushima Otsuka Fatty rats (LETO) as well as AMPD3‐overexpressing H9c2 cells and human embryonic kidney 293 cells. Results OLETF, but not LETO, showed diastolic dysfunction under the condition of phenylephrine‐induced pressure overload. The levels of 90‐kDa AMPD3 in outer mitochondrial membranes/endoplasmic reticulum and mitochondria‐associated endoplasmic reticulum membrane (MAM) fractions were significantly higher in OLETF than in LETO. The area of the MAM quantified by electron microscopic analysis was 57% larger, mitochondrial Ca2+ level under the condition of pressure overload was 47% higher and Ca2+ retention capacity in MAM‐containing crude mitochondria isolated before the pressure overloading was 21% lower in OLETF than in LETO (all P‐values

Abstract Aims Anti‐mitochondrial antibody (AMA)‐positive myositis is frequently associated with various cardiac involvements, such as arrhythmia and left ventricular (LV) dysfunction. However, the efficacy of immunosuppressive therapy in these complications remains unknown. This study aimed to investigate the cardiac response to immunosuppressive therapy in patients with AMA‐positive myositis. Methods and results The clinical data of 15 AMA‐positive myositis patients with cardiac involvement were retrospectively collected at our centre. To evaluate the effects of immunosuppressive therapy, echocardiographic and laboratory data of patients who received glucocorticoid therapy with additional immunosuppressants (n = 6) and those who did not (n = 6) were compared. Also, the characteristics of patients with or without >5% LV ejection fraction (LVEF) decline during the follow‐up period (n = 5 vs. n = 7) were compared. Thirteen patients (87%) had arrhythmias, and eight patients (53%) had LV wall motion abnormalities. Although arrhythmias decreased after treatment, reduced LVEF and LV wall motion abnormalities persisted. Further investigation revealed an increased LV end‐systolic dimension and reduced LVEF in patients without additional immunosuppressive therapy, while those in patients with additional immunosuppressive therapy were maintained. Six of seven patients (86%) without LVEF decline received additional immunosuppressive therapy, whereas no patients with LVEF decline had additional immunosuppressive therapy. Conclusions Cardiac involvement in AMA‐positive myositis may worsen even with glucocorticoid monotherapy, and there might be some associations between the change of LV function and additional immunosuppressive therapy.

Key Clinical Message Prompt recognition and accurate diagnosis of seatbelt‐related injuries such as Chance fractures are crucial for pediatric patients. Clinicians should be aware of the unique characteristics of children, including the presence of growth plates, and use advanced imaging techniques such as magnetic resonance imaging to guide appropriate treatment and minimize complications. Abstract Seatbelt‐related injuries, known as the “seatbelt syndrome,” encompass various injuries resulting from automobile accidents, including vertebral fractures, abdominal injuries, and great vessel traumas. Seatbelt signs include bruising or peeling of the anterior chest or abdominal wall, indicating abdominal pressure against the seatbelt. Chance fractures are a type of vertebral fracture characterized by fracture lines through multiple vertebral structures and are often associated with seatbelt injuries in adults. However, the unique features of Chance fractures in pediatric patients, such as the presence of growth plates, require a comprehensive diagnostic approach using advanced imaging techniques, including magnetic resonance imaging (MRI). This case report highlights the complexity of seatbelt‐related injuries in children and emphasizes the importance of accurate diagnosis and multidisciplinary management. Understanding these factors can improve clinical knowledge and outcomes in children with seatbelt‐related injuries.

Abstract Glioblastoma is characterized by diffuse infiltration into the normal brain. Invasive glioma stem cells (GSCs) are an underlying cause of treatment failure. Despite the use of multimodal therapies, the prognosis remains dismal. New therapeutic approach targeting invasive GSCs is required. Here, we show that neural stem cells (NSCs) derived from CRISRP/Cas9‐edited human‐induced pluripotent stem cell (hiPSC) expressing a suicide gene had higher tumor‐trophic migratory capacity compared with mesenchymal stem cells (MSCs), leading to marked in vivo antitumor effects. High migratory capacity in iPSC‐NSCs was related to self‐repulsive action and pathotropism involved in EphB‐ephrinB and CXCL12‐CXCR4 signaling. The gene insertion to ACTB provided higher and stable transgene expression than other common insertion sites, such as GAPDH or AAVS1. Ferroptosis was associated with enhanced antitumor immune responses. The thymidylate synthase and dihydroprimidine dehydrogenase expressions predicted the treatment efficacy of therapeutic hiPSC‐NSCs. Our results indicate the potential benefit of genome‐edited iPS cells based gene therapy for invasive GSCs. Furthermore, the present research concept may become a platform to promote clinical studies using hiPSC.

Background In patients with cardiogenic shock (CS), acute myocardial infarction (AMI) is the most common cause, and a percutaneous microaxial ventricular assist device (Impella, Abiomed, Danvers, MA) is a choice for temporary mechanical circulatory support. However, data are limited on complications and outcomes of Impella treatment in patients with CS with and without AMI. Methods and Results Using nationwide prospective registry data in Japan, we included a total of 2047 patients with CS in whom the Impella devices were successfully placed between February 2020 and December 2021. Patients were divided into 2 groups according to the primary indication for the Impella use: AMI versus non‐AMI. The primary end point was a composite of in‐hospital all‐cause death and major complications. Of the 2047 patients, the Impella was indicated for AMI in 1337 (65.3%). In the group without AMI, myocarditis was the leading cause of CS. Patients with AMI‐CS were older and more likely to have cardiovascular risk factors than those with non‐AMI‐CS. The rates of in‐hospital mortality (46.0% versus 43.9%, P=0.38) and major complications (35.2% versus 34.7%, P=0.85) were similar between the 2 groups. Overall, multivariable analysis identified older age, higher body mass index, previous transient ischemic attack or stroke, out‐of‐hospital cardiac arrest, and the Impella 5.0 as factors significantly associated with the primary end point. Conclusions The use of Impella in patients with and without AMI was related to similar clinical outcomes with high mortality and complication rates. Further studies are needed to identify patients who may benefit from the Impella devices in CS. Registration URL: https://www.umin.ac.jp/english. Identifier: UMIN000033603.

Abstract Aim Bipolar disorder is a leading disorder contributing to global disease burden, and bipolar depression often becomes severe and refractory. Therefore, clarifying the pathophysiology of bipolar disorder is an urgent issue. Previous reports suggested that factors, such as affective temperaments and childhood maltreatment, aggravate bipolar depression severity. However, to our knowledge, no reports to date have clarified the interrelationship between the above factors and bipolar depression severity. We here hypothesized that childhood maltreatment worsens bipolar depression severity via increasing affective temperaments. To test this hypothesis, a covariance structural analysis was conducted. Methods The following information was evaluated for a total of 75 people with bipolar disorder using self‐administered questionnaires: demographic characteristics, depressive symptoms (Patient Health Questionnaire‐9), history of childhood maltreatment (Child Abuse and Trauma Scale), and affective temperaments (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire). The results were analyzed using covariance structure analysis. Results A significant indirect effect of childhood maltreatment on bipolar depression severity via increasing affective temperaments was identified, whereas the direct effect of childhood maltreatment was not significant. Conclusion Our results reveal that affective temperaments can mediate the adverse effects of childhood maltreatment on the severity of bipolar depression.

Abstract Systemic branched‐chain amino acid (BCAA) metabolism is dysregulated in cardiometabolic diseases. We previously demonstrated that upregulated AMP deaminase 3 (AMPD3) impairs cardiac energetics in a rat model of obese type 2 diabetes, Otsuka Long‐Evans‐Tokushima fatty (OLETF). Here, we hypothesized that the cardiac BCAA levels and the activity of branched‐chain α‐keto acid dehydrogenase (BCKDH), a rate‐limiting enzyme in BCAA metabolism, are altered by type 2 diabetes (T2DM), and that upregulated AMPD3 expression is involved in the alteration. Performing proteomic analysis combined with immunoblotting, we discovered that BCKDH localizes not only to mitochondria but also to the endoplasmic reticulum (ER), where it interacts with AMPD3. Knocking down AMPD3 in neonatal rat cardiomyocytes (NRCMs) increased BCKDH activity, suggesting that AMPD3 negatively regulates BCKDH. Compared with control rats (Long‐Evans Tokushima Otsuka [LETO] rats), OLETF rats exhibited 49% higher cardiac BCAA levels and 49% lower BCKDH activity. In the cardiac ER of the OLETF rats, BCKDH‐E1α subunit expression was downregulated, while AMPD3 expression was upregulated, resulting in an 80% lower AMPD3‐E1α interaction compared to LETO rats. Knocking down E1α expression in NRCMs upregulated AMPD3 expression and recapitulated the imbalanced AMPD3‐BCKDH expressions observed in OLETF rat hearts. E1α knockdown in NRCMs inhibited glucose oxidation in response to insulin, palmitate oxidation, and lipid droplet biogenesis under oleate loading. Collectively, these data revealed previously unrecognized extramitochondrial localization of BCKDH in the heart and its reciprocal regulation with AMPD3 and imbalanced AMPD3‐BCKDH interactions in OLETF. Downregulation of BCKDH in cardiomyocytes induced profound metabolic changes that are observed in OLETF hearts, providing insight into mechanisms contributing to the development of diabetic cardiomyopathy.

Abstract Aim To identify whether the coronavirus disease 2019 (COVID‐19) pandemic affects the operational efficiency of emergency medical services (EMS) and the survival rate of out‐of‐hospital cardiac arrest (OHCA) in prehospital settings. Methods We conducted a population‐based cohort study in Kobe, Japan, between March 1, 2020, and September 31, 2022. In study 1, the operational efficiency of EMS, such as the total out‐of‐service time for ambulances, the daily occupancy rate of EMS, and response time, was compared between the pandemic and nonpandemic periods. In study 2, the impacts of the changes in EMS operational efficiency were investigated among patients with OHCA, with 1‐month survival as the primary outcome and return of spontaneous circulation, 24‐h survival, 1‐week survival, and favorable neurological outcomes as the secondary outcomes. Logistic regression analysis was conducted to identify the factors associated with survival among patients with OHCA. Results The total out‐of‐service time, occupancy rate, and response time significantly increased during the pandemic period (p

Abstract The purpose of this study is to clarify the individual differences in the consciousness of the students participating in a wooden craftsmanship activity (WCA) program. Based on a study conducted in Ono, a village located in the low uplands and mountainous region of Miyama Ward, Nantan City, in the Kyoto Prefecture, we determined the three principal components in the consciousness of the participants: “Awareness to contribution to the local region,” “Awareness to forest conservation,” and “Awareness to wooden craftsmanship.” We subsequently conducted a cluster analysis using the principal component scores of the university students participating in the study and categorized them into the following four groups: “Contribution to the local region group,” “Design‐oriented group,” “Moderate group,” and “Environment conservation group,” to clarify the effects of the activity and the important themes related to design education and WCA programs.