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Abstract Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein (“spike”) as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms.

We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023–24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.

Purpose: This study examines the impact of the Association to Advance Collegiate Schools of Business (AACSB) accreditation on education quality. We discern the prospective influences of AACSB, focusing on shifts in teaching methods and content and assessment procedures. Design/methodology/approach: Using a case study approach, in-depth interviews are conducted with a Japanese-accredited business school's faculty members to understand their perceptions of the school's education-quality issues. The data were thematically analyzed. Findings: Respondents acknowledged that AACSB accreditation has positively influenced teaching, encouraging active learning and the case method. However, they also indicated that accreditation had a restrictive effect on assessment activities, pushing toward compliance rather than genuine learning evaluation. This dichotomy suggests a need for balancing standard adherence with the flexibility to maintain educational depth and assessment integrity. Research limitations/implications: Convenience sampling may introduce self-selection bias. Furthermore, the qualitative case study approach does not allow for statistical generalization. However, when combined with existing literature, the findings can be analytically generalized and transferred to other contexts. Originality/value: We provide insights regarding AACSB accreditation's impact on business education, encompassing shifts in teaching methods and content and faculty perceptions of assessment. This study enhances the scholarly understanding of business school accreditation and offers guidance to accredited or accreditation-seeking academic institutions.

Abstract Objectives This study aimed to comprehensively compare host responses of patients with bacterial sepsis and those with viral (COVID-19) sepsis by analyzing messenger RNA (mRNA) and microRNA (miRNA) profiles to shed light on their distinct pathophysiological mechanisms. Design Prospective observational study. Setting Whole blood RNA sequencing was used to analyze mRNA and miRNA profiles of patients diagnosed as having bacterial sepsis or viral (COVID-19) sepsis at the Department of Trauma and Emergency Medicine, Osaka University Graduate School of Medicine. Patients Twenty-two bacterial sepsis patients, 35 viral (COVID-19) sepsis patients, and 15 healthy subjects admitted to the department were included. We diagnosed bacterial sepsis patients according to the sepsis-3 criterion that the Sequential Organ Failure Assessment score must increase to 2 points or more among patients with suspected infections. Viral (COVID-19) sepsis patients were diagnosed using SARS-CoV-2 RT-PCR testing, and presence of pneumonia was assessed through chest computed tomography scans. Interventions None. Measurements and main results For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in the bacterial sepsis patients. Numbers of genes showing upregulated: downregulated gene expression (false discovery rate 1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in viral (COVID-19) sepsis patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated: downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. This analysis revealed significant differences in the numbers of upregulated and downregulated genes expressed and pathways between the bacterial sepsis and viral (COVID-19) sepsis patients. Bacterial sepsis patients showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway and concurrent suppression of Th1 signaling. Conclusion Our study illuminated distinct molecular variances between bacterial sepsis and viral (COVID-19) sepsis. Bacterial sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to viral (COVID-19) sepsis patients. Especially, bacterial sepsis caused more dramatic pathogenetic changes in the Th1 pathway than did viral (COVID-19) sepsis.

Abstract Resting memory B cells can be divided into classical or atypical groups, but the heterogenous marker expression on activated memory B cells makes similar classification difficult. Here, by longitudinal analysis of mass cytometry and CITE-seq data from cohorts with COVID-19, bacterial sepsis, or BNT162b2 mRNA vaccine, we observe that resting B cell memory consist of classical CD45RB+ memory and CD45RBlo memory, of which the latter contains of two distinct groups of CD11c+ atypical and CD23+ non-classical memory cells. CD45RB levels remain stable in these cells after activation, thereby enabling the tracking of activated B cells and plasmablasts derived from either CD45RB+ or CD45RBlo memory B cells. Moreover, in both COVID-19 patients and mRNA vaccination, CD45RBlo B cells formed the majority of SARS-CoV2 specific memory B cells and correlated with serum antibodies, while CD45RB+ memory are activated by bacterial sepsis. Our results thus identify that stably expressed CD45RB levels can be exploited to trace resting memory B cells and their activated progeny, and suggest that atypical and non-classical CD45RBlo memory B cells contribute to SARS-CoV-2 infection and vaccination.

Abstract Background Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. Methods This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2–4 months, 4–6 months, and 6–8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. Results In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. Conclusions The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.

Coil migration can occur when coil embolization is used for treating pseudoaneurysms associated with large arteries. The double microcatheter technique is useful for preventing coil migration; the balloon catheter can reduce blood flow and active bleeding upon balloon inflation, and can also compress the bleeding point and arrest bleeding temporarily. We report a case describing the management of a pseudoaneurysm with coil embolization using double microcatheters and a balloon catheter to control blood flow and prevent coil migration. A 73-year-old male patient presented with a pseudoaneurysm of the celiac artery arising from the splenic artery stump following surgery. Coil embolization of the pseudoaneurysm using a double microcatheter embolization technique with a balloon catheter was considered. A balloon catheter was inserted into the celiac artery and active bleeding was temporarily arrested with the inflated balloon. First, a microcatheter was inserted into the balloon catheter, and another microcatheter was placed in the celiac artery. An electrical detachable coil was inserted into the proximal common hepatic artery just distal to the pseudoaneurysm. The second electrically detachable coil was inserted while the first coil remained attached. After detachment of the second coil, additional electrically detachable coils were inserted for similar embolization. The balloon was gradually deflated. Finally, the first coil was detached and we confirmed absence of the bleeding. Our case report demonstrated that a balloon catheter can control the flow vessels, and the double microcatheter embolization technique with a balloon catheter is useful for coil embolization in high-flow or large vessels.

ABSTRACT Ventricular assist device (VAD) infections are frequent causes of hospital readmission. The risk factors and optimal preventive strategies for such, including chronic suppressive antibiotics (CSA), remain uncertain. We performed a single-center, retrospective, observational cohort study assessing continuous flow VAD recipients who underwent implantation between 2008 and 2018 in Japan. From primary VAD infection (VADI), we followed the patients for recurrent infection, defined as relapsing VAD-specific (e.g., localized infections) or VAD-related (e.g., bacteremia) infections requiring hospital readmission. CSA was defined as the use of oral antimicrobial agents continued beyond initial antibiotic use until transplantation, VAD withdrawal, VADI recurrence, or death. Survival analysis was performed to identify risk factors for recurrent infection accounting for competing risks (e.g., deaths and transplants). Among 163 eligible patients, 76 patients had VADIs. The main causative organism in primary VADI was Staphylococcus aureus (63%, 48/76). Among them, 41 had recurrent infections, whereas 35 had none during the follow-up period (median, 335 days). Thirty-six patients received CSA for a median of 478 days. Although CSA was associated with a decreased risk of recurrent infection [adjusted sub-distribution hazard ratio (SHR), 0.40; 95% confidence interval (CI), 0.18–0.89; P = 0.03], this protective effect was observed only after primary VAD-specific infection (SHR, 0.28; 95% CI, 0.12–0.64; P < 0.01) but not after VAD-related infection. Surgical procedures during primary VADI were associated with an increased risk (SHR, 2.00; 95% CI, 1.10–3.66; P = 0.02). One patient had an adverse drug reaction. CSA may be an effective approach to limit relapsing VADIs following a primary VAD-specific infection with minimal adverse events.IMPORTANCEVentricular assist device infections (VADIs) are a significant complication leading to hospital readmissions. However, the risk factors and optimal preventive strategies for VADI remain unclear. This study investigated the effectiveness of chronic suppressive antibiotic therapy in patients with VADI. We found that the use of chronic suppressive antibiotic therapy was associated with a reduction in the risk of VADI recurrence with few adverse reactions. Our findings suggest the potential benefit of chronic suppressive antibiotics in preventing infections in selected cases. Our findings are relevant for the management of patients with ventricular assist devices awaiting heart transplantation, providing valuable insights for clinical practice.

Therapeutic hypothermia inhibits organ damage by suppressing metabolism, which makes it a therapy of choice for treating various diseases. Specifically, it is often used to treat conditions involving central nervous system disorders where it is expected to positively impact functional prognosis. Although keeping the body temperature at a hypothermic level has been conventionally used, how to manage the body temperature correctly remains a topic of debate. Recently, the concept of temperature management has been proposed to improve the quality of body temperature control and avoid hyperthermia. This review focuses on the effect of temperature on the central nervous system in conditions involving central nervous system disorders and the practice of temperature management in clinical situations.

Record-breaking heat waves over the past 20 years have led to a global increase in heat-related deaths, including heatstroke. Heat-related illnesses occur when the body cannot adapt to the elevated temperatures in the environment, leading to various symptoms. In severe situations, such as heatstroke, the body temperature can rise above 40°C, leading to significant injury to body systems, with particular susceptibility of the central nervous system (CNS). Neuroimaging studies conducted months or years after a heatstroke have revealed cellular damage in the cerebellum and other brain regions, including the hippocampus, midbrain, and thalamus, with the potential for long-term neurological complications in survivors of a heatstroke. This mini review aimed to describe the mechanisms and pathways underlying the development of brain injury induced by heatstroke and identify diagnostic imaging tools and biomarkers for injury to the CNS due to a heatstroke.

Abstract Accurate cup placement is critical to ensure satisfactory outcomes after total hip arthroplasty. Portable hip navigation systems are novel intraoperative guidance tools that achieve accurate cup placement in the supine position; however, accuracy in the lateral decubitus position is under debate. A new inertial portable navigation system has recently become available. The present study investigated the accuracy of measurements of the cup position in 54 patients in the lateral decubitus position using this system and compared it with that by a goniometer. After cup placement, cup abduction and anteversion were measured using the system and by the goniometer, and were then compared with postoperatively measured angles. Absolute measurement errors with the system were 2.8° ± 2.6° for cup abduction and 3.9° ± 2.9° for anteversion. The system achieved 98 and 96% measurement accuracies within 10° for cup abduction and anteversion, respectively. The system was more accurate than the goniometer for cup anteversion (p

Surgical resection is recommended for advanced-stage, resectable glottic cancer. However, total laryngectomy results in the loss of vocal function and reduces patients’ quality of life. At our institution, patients with cT3N0M0 stage III resectable glottic cancer who wish to preserve their larynx are treated with super-selective cisplatin infusion with concomitant radiotherapy (RADPLAT) to improve local control over systemic chemotherapy. Herein, we present 4 patients with glottic cancer who underwent biweekly intra-arterial infusion chemotherapy combined with radiation therapy 3 times. For intra-arterial infusion chemotherapy, 100 mg cis-diaminodichloroplatinum was infused into the superior thyroid artery, including the superior laryngeal artery branch. Thereafter, intensity-modulated radiation therapy was administered at doses of 70 Gy in 35 fractions for 3 patients and 66 Gy in 33 fractions for 1 patient. These patients showed complete response after chemoradiotherapy with no recurrence or metastases during the follow-up period to date (mean follow-up period: 56 months, range: 39-76 months).

ABSTRACTAlthough the coronavirus disease of 2019 arguably changed citizens’ transportation mode choices, how these choices changed and what factors influenced them, especially during the soft intervention period, remains ambiguous. To clarify this phenomenon, this study examined how citizens’ socio-demographic and psychological factors contributed to their transportation mode changes (public transportation, active transportation: walking and cycling, and cars) between 2019 and 2020. We employed the extended theory of the norm activation model and the value–attitude–behaviour hierarchy, surveyed 973 citizens in Toyama City, Japan, and applied a confirmatory factor analysis and a multinomial logistic regression model. Regarding psychological characteristics, the findings showed that those with positive attitudes toward public transportation tended to shift to public transportation; those with high personal norms for car use tended to shift to public transportation; those with perceived behavioural control over car use tended not to change to public transportation; and those with positive attitudes toward car use tended not to shift to active transportation. Socio-demographically, respondents who were female, highly educated and/or whose income decreased from the previous year tended to shift to active transportation. Age was not significantly associated with transportation mode changes. No significant variable was found between respondents’ shift to cars and socio-demographic and psychological factors. Our study provides implications, suggesting that policymakers focus on adopting measures to retain female or highly educated individuals in the active transportation mode use even beyond the pandemic period, while raising awareness among men, informing them of the health benefits of the active transportation mode and establishing active transportation mode-friendly infrastructure.

ABSTRACTThis study analyses the knowledge-sharing process and its outcomes among stakeholders (i.e., academia, industry, government and civil society) in the context of a regional sustainability-oriented project held in Ena City, central Japan, by using the Quadruple Helix (QH) framework. We collected data through interviews with the stakeholders and related documents and employed qualitative content analysis to analyse the data. Our findings imply that there is a gap between the theoretical understanding and practical application of sustainability practices at the initial stage of interaction. However, the project facilitated inter-exchanges of knowledge among stakeholders in the respective helices that could address this gap. Our research suggested the roles of stakeholders in a sustainability-driven collaboration as bridging academics, resource-providing industry, observant government and boundary-spanning civil society which represent the balanced QH model. The current study contributes to the existing literature three-fold. First, few existing studies have employed the QH model in the context of sustainability. Second, most previous studies on the QH model have focused on macro-perspectives. Third, the study clarifies the roles of the stakeholders, which extends the understanding of the QH model. This study suggests a regional sustainability policy that encourages more bottom-up initiatives, in line with the balanced helix model.

Objectives This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity.Design Retrospective observational study of a nationwide database.Setting The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint.Participants This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018.Main outcome measure The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis.Results The median time to surgery was 9 months (IQR 4–22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p

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.

Abstract In summer, the survival zones of cold‐water species are predicted to narrow by both increasing water temperatures from the surface and by expanding hypoxic zones from the lake bottom. To examine how the abundance of cold‐water fishes changes along environmental gradients, we assessed the vertical environmental DNA (eDNA) distributions of three salmonid species which may have different water temperature tolerances during both stratification and turnover periods using quantitative PCR (qPCR). In addition, we examined on the vertical distribution of diverse fish fauna using an eDNA metabarcoding assay. The results suggested that the kokanee salmon (Oncorhynchus nerka) eDNA were abundant in deep, cold waters. On the other hand, rainbow trout (O. mykiss) eDNA were distributed uniformly throughout the water column, suggesting that they may have high water‐temperature tolerance compared with kokanee salmon. The eDNA concentrations of masu salmon (O. masou) were below the detection limit (i.e.,

Periodontal diseases are well-known background for infective endocarditis. Here, we show that pericardial effusion or pericarditis might have origin also in periodontal diseases. An 86-year-old man with well-controlled hypertension and diabetes mellitus developed asymptomatic increase in pericardial effusion. Two weeks previously, he took oral new quinolone antibiotics for a week because he had painful periodontitis along a dental bridge in the mandibular teeth on the right side and presented cheek swelling. The sputum was positive for Streptococcus species. He was healthy and had a small volume of pericardial effusion for the previous 5 years after drug-eluting coronary stents were inserted at the left anterior descending branch 10 years previously. The differential diagnoses listed for pericardial effusion were infection including tuberculosis, autoimmune diseases, and metastatic malignancy. Thoracic to pelvic computed tomographic scan demonstrated no mass lesions, except for pericardial effusion and a small volume of pleural effusion on the left side. Fluorodeoxyglucose positron emission tomography disclosed many spotty uptakes in the pericardial effusion. The patient denied pericardiocentesis, based on his evaluation of the risk of the procedure. He was thus discharged in several days and followed at outpatient clinic. He underwent dental treatment and pericardial effusion resolved completely in a month. He was healthy in 6 years until the last follow-up at the age of 92 years. We also reviewed 8 patients with pericarditis in association with periodontal diseases in the literature to reveal that periodontal diseases would be the background for developing infective pericarditis and also mediastinitis on some occasions.

BackgroundAcute respiratory distress syndrome (ARDS) is respiratory failure that commonly occurs in critically ill patients, and the molecular mechanisms underlying its pathogenesis and severity are poorly understood. We evaluated mRNA and miRNA in patients with ARDS and elucidated the pathogenesis of ARDS after performing mRNA and miRNA integration analysis.MethodsIn this single-center, prospective, observational clinical study of patients with ARDS, peripheral blood of each patient was collected within 24 hours of admission. Sequencing of mRNA and miRNA was performed using whole blood from the ARDS patients and healthy donors.ResultsThirty-four ARDS patients were compared with 15 healthy donors. Compared with the healthy donors, 1233 mRNAs and 6 miRNAs were upregulated and 1580 mRNAs and 13 miRNAs were downregulated in the ARDS patients. For both mRNA and miRNA-targeted mRNA, canonical pathway analysis showed that programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) cancer immunotherapy pathway was most activated and the Th2 pathway was most suppressed. For mRNA, the Th1 pathway was most suppressed. miR-149-3p and several miRNAs were identified as upstream regulators.ConclusionmiRNAs regulated the PD-1 and PD-L1 cancer immunotherapy pathway and Th2 pathway through miRNA interference action of mRNA. Integrated analysis of mRNAs and miRNAs showed that T cells were dysfunctional in ARDS patients.

Background: The double D technique (DDT) is a method of parallel placement of the left and right legs of the same diameter in patients with anatomically incompatible commercially available bifurcated stent grafts in endovascular aortic repair (EVAR). It is indicated for cases such as aortic dissection and isolated common iliac aneurysm, in which the working space is small when inserting the lateral leg and contralateral gate insertion is difficult. Herein, we report a case in which EVAR with DDT was used to treat a ruptured isolated common iliac aneurysm with a narrow terminal aorta. Case: A 46-year-old man was transferred to the emergency room because of loss of consciousness. On arrival, he was in shock (systolic blood pressure: 48 mmHg; heart rate: 112 bpm). Contrast-enhanced computed tomography supported a diagnosis of ruptured right common iliac artery aneurysm and underwent emergency EVAR. The distance from the aortic bifurcation to the right common iliac artery aneurysm was 10 mm, and hemostasis was expected to be difficult with unilateral leg placement. Additionally, the terminal aortic diameter was 17 mm, and a bifurcated device that could be used in an emergency could not be applied. Therefore, EVAR (Excluder) with DDT was performed. The patient was discharged home on postoperative day 7. The patient had no endoleaks 6 months postoperatively. Conclusion: EVAR is the first choice for ruptured abdominal aortic aneurysms and common iliac aneurysms because of its minimal invasiveness and rapidity, if the anatomical requirements are met. Using DDT, EVAR can be performed in emergencies in patients with anatomical restrictions, such as those with a narrow terminal aorta, thus enabling minimally invasive and rapid treatment.

Bamboo fiber was extracted after alkaline treatment, and the mechanical properties of fibers and polymer composites were measured. The results showed that the strength of bamboo fiber was higher when the diameter was smaller. Smaller diameter bamboo fibers were dense, while larger diameter ones were composed of vascular bundles, which contained inside voids and outside parts having insufficient lignification. Tensile tests were conducted on bamboo fibers after heating at constant temperatures, and a significant decrease in mechanical properties was observed at heating temperatures above 250 °C. Bamboo fibers were compounded with PE, PA12, ABS, PA6, and biobased PC (Durabio), and injection-molded to prepare the composite specimens for flexural testing. The composite of polyethylene with 30 wt% bamboo exhibited considerably high flexural modulus compared to pure PE. Nevertheless, a large plastic deformation, which was equivalent to that of pure PE was observed. In other polymer composites, those flexural moduli increased, and degree of plastic deformation decreased dramatically, leading to brittleness. For PA6, which was molded above 250 °C, the increment in flexural modulus by fibers was less than the other composites due to the thermal decomposition of the fibers.

The long-term outcomes of patients with disorders of consciousness after traumatic brain injury (TBI) is unclear. We investigated the long-term outcomes over 20 years in patients who were in a persistent vegetative state (VS). We conducted a retrospective cohort study using a review of medical records and collected data by telephone and written interviews with patients and their families. We included patients who were treated for TBI at our hospital, between October 1996 and January 2003 and who were in a persistent VS, defined as a Disability Rating Scale (DRS) score of ?22 at 1 month after TBI. The DRS was administered at 1 month, 6 months, 1 year, and then annually out to 20 years. We evaluated their clinical course until July 2021 with the DRS. We analyzed 35 patients in a persistent VS attributable to TBI. We were able to confirm the 20-year outcomes for 26 of the 35 patients (74%); at 20 years post-TBI, 19 (54%) patients were found to be deceased and 7 (20%) were alive. Over the 20-year study period, 23 of the 35 patients (65.7%) emerged from a persistent VS. Among the 35 patients in a persistent VS at 1 month post-TBI, 20 (57%) emerged from a persistent VS within 1 year, and 3 patients (8.6%) emerged from a persistent VS after more than a year after injury. DRS scores improved up to 9 years post-injury, whereas the change in DRS scores from 10 to 20 years post-injury was within ?1 point in all patients. We found that patients with persistent VS attributable to TBI may show improvement in functional disability up to 10 years post-injury. On the other hand, no substantial improvement in functional disability was observed after the 10th year.

Abstract The regional differences in cerebral oxygen extraction fraction (OEF) in brain were investigated using positron emission tomography (PET) in detail with consideration of systemic errors in PET measurement estimated by simulation studies. The cerebral blood flow (CBF), cerebral blood volume (CBV), OEF, and cerebral metabolic rate of oxygen (CMRO2) were measured on healthy men by PET with 15O-labeled gases. The OEF values in the pons and the parahippocampal gyrus were significantly smaller than in the other brain regions. The OEF value in the lateral side of the occipital cortex was largest among the cerebral cortical regions. Simulation studies have revealed that errors in OEF caused by regional differences in the distribution volume of 15O-labeled water, as well as errors in OEF caused by a mixture of gray and white matter, must be negligible. The regional differences in OEF in brain must exist which might be related to physiological meanings.Article title: Kindly check and confirm the edit made in the article title.I have checked the article title and it is OK as is. Trial registration: The UMIN clinical trial number: UMIN000033382, https://www.umin.ac.jp/ctr/index.htm

Microplastics’ spreading in the ocean is currently causing significant damage to organisms and ecosystems around the world. To address this oceanic issue, there is a current focus on marine degradable plastics. Polycaprolactone (PCL) is a marine degradable plastic that is attracting attention. To further improve the biodegradability of PCL, we selected a completely new protein that has not been used before as a functional filler to incorporate it into PCL, aiming to develop an environmentally friendly biocomposite material. This novel protein is derived from the mucus bubbles of the violet sea snail (VSS, Janthina globosa), which is a strong bio-derived material that is 100% degradable in the sea environment by microorganisms. Two types of PCL/bubble composites, PCL/b1 and PCL/b5, were prepared with mass ratios of PCL to bubble powder of 99:1 and 95:5, respectively. We investigated the thermal properties, mechanical properties, biodegradability, surface structure, and crystal structure of the developed PCL/bubble composites. The maximum biochemical oxygen demand (BOD) degradation for PCL/b5 reached 96%, 1.74 times that of pure PCL (≈55%), clearly indicating that the addition of protein fillers significantly enhanced the biodegradability of PCL. The surface morphology observation results through scanning electron microscopy (SEM) definitely confirmed the occurrence of degradation, and it was found that PCL/b5 underwent more significant degradation compared to pure PCL. The water contact angle measurement results exhibited that all sheets were hydrophobic (water contact angle > 90°) before the BOD test and showed the changes in surface structure after the BOD test due to the newly generated indentations on the surface, which led to an increase in surface toughness and, consequently, an increase in surface hydrophobility. A crystal structure analysis by wide-angle X-ray scattering (WAXS) discovered that the amorphous regions were decomposed first during the BOD test, and more amorphous regions were decomposed in PCL/b5 than in PCL, owing to the addition of the bubble protein fillers from the VSS. The differential scanning calorimeter (DSC) and thermal gravimetric analysis (TGA) results suggested that the addition of mucus bubble protein fillers had only a slight impact on the thermal properties of PCL. In terms of mechanical properties, compared to pure PCL, the mucus-bubble-filler-added composites PCL/b1 and PCL/b5 exhibited slightly decreased values. Although the biodegradability of PCL was significantly improved by adding the protein fillers from mucus bubbles of the VSS, enhancing the mechanical properties at the same time poses the next challenging issue.

Abstract Aims Heart failure with a preserved ejection fraction (HFpEF) is associated with chronic inflammation. We aimed to investigate the association between pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography as a novel noninvasive marker of pericoronary inflammation and the presence of HFpEF. Methods and results This retrospective study included 607 outpatients (median age, 65 years; 50% male) who underwent both echocardiography and coronary computed tomography angiography. Patients with obstructive coronary artery disease were excluded from this study. PCATA was compared between patients with and without HFpEF, which was diagnosed according to the Heart Failure Association (HFA)‐PEFF score. PCATA was assessed at the proximal 40‐mm segments of all three major coronary arteries on coronary computed tomography angiography. Patients with HFpEF had higher PCATA in all coronary arteries compared to the control participants: left anterior descending artery (LAD), −65.2 ± 6.9 Hounsfield units (HU) vs. −68.1 ± 6.7 HU; left circumflex artery (LCX), −62.7 ± 6.8 HU vs. −65.4 ± 6.6 HU; and right coronary artery (RCA), −63.6 ± 8.5 HU vs. −65.5 ± 7.7 HU (P

Abstract Background Little is known about the association between liver indicators (The FIB‐4 index, nonalcoholic fatty liver disease fibrosis score (NFS), and fatty liver index (FLI)) and cancer development in patients without preexisting liver disease. Methods We conducted a retrospective cohort study with participants who underwent voluntary health checkups and without fatty liver between 2005 and 2018. Our primary outcome was the development of any type of cancer, and its association with each liver indicator was evaluated. Results A total of 69,592 participants (mean age: 43.9 years, 29,984 (43.1%) were men) were included. During a median follow‐up of 5.1 years, 3779 (5.4%) patients developed cancer. Compared to participants with a low NFS, those with a medium NFS had a higher risk of developing any type of cancer (adjusted hazard ratio [HR]: 1.18, 95% confidence interval [CI]: 1.07–1.31), whereas those with a medium FIB‐4 index had a decreased risk of developing any type of cancer compared to those with a low FIB‐4 index (adjusted HR: 0.91, 95% CI: 0.83–0.99). Patients with higher scores tended to have a higher risk of digestive organ cancer, regardless of the indicator. A high FLI was also associated with an increased risk of breast cancer (adjusted HR: 2.42, 95% CI: 1.24–4.71); however, those with a medium FIB‐4 index (adjusted HR: 0.65, 95% CI: 0.52–0.81) and NFS (adjusted HR: 0.50, 95% CI: 0.35–0.72) had decreased risks of developing breast cancer compared to those with a high FIB‐4 index and NFS, respectively. Conclusion Among patients without fatty liver, a higher liver indicator score was associated with an increased risk of cancer in the digestive organs, regardless of the indicator. Notably, those with a medium FIB‐4 index or NFS had a lower risk of developing breast cancer, whereas those with a medium FLI had an increased risk.

Abstract Introduction Methemoglobinemia is a condition in which methemoglobin is increased and the oxygen carrying capacity of tissues is decreased, causing a lack of oxygen to the whole body. RNA (ribonucleic acid) sequencing technologies have made it possible to systematically examine how the human transcriptome responds to invasive pathologies. To our knowledge, no previous studies have reported the results of RNA sequencing in a patient with methemoglobinemia. We describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. Case presentation A 31-year-old Japanese man was brought to our hospital with symptoms of dyspnea due to inhalation of gas from an acetic acid phosphonitrate storage tank at a factory. The nitrogen oxide concentration measured around the storage tank was over 2500 ppm, and he witnessed orange–brown smoke at that time. After entering the area and taking a few breaths, he suddenly became unwell, with dyspnea and numbness in his extremities. He was evacuated from the area within a few minutes, at which time he was suffering from whole-body cyanosis and was still aware of the above symptoms. On arrival at the hospital, his respiration rate was 18 breaths/minute, and his SpO2 ranged from 80% to 85% on 15 L/minute of oxygen by mask (2.5 hours postexposure). Arterial blood gas testing revealed a methemoglobin level of 23.1%. After the administration of methylene blue, the patient’s methemoglobin level normalized and his symptoms improved. Chest X-ray and chest computed tomography showed no evidence of pulmonary edema or interstitial pneumonia, and no other abnormal findings were observed. RNA sequencing was performed on the blood samples obtained at the time of the visit, with the blood sample collected on day 5 used as a control. To our knowledge, the present study is the first to describe the analysis of RNAs from the whole blood of a patient with methemoglobinemia. The RNA sequencing analysis showed that an activated “hydrogen peroxide catabolic process” may be associated with the pathogenesis of methemoglobinemia. Conclusion The results reported in the present study may explain the pathogenesis of methemoglobinemia.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR‐CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non‐invasive diagnosis using 99mTechnetium (Tc)‐pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR‐CM. The aim of this study was to clarify the prevalence and characteristics of ATTR‐CM among Japanese patients with HFpEF. Methods and results This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A 99mTc‐PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac 99mTc‐PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate‐to‐severe 99mTc‐PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR‐CM and non‐ATTR‐CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc‐PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on 99mTc‐PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR‐CM, n = 53 vs. non‐ATTR‐CM, n = 320). Patients in the ATTR‐CM group had a higher N‐terminal pro‐brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P

BackgroundPheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells.MethodsWe are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211At] MABG is 0.65 MBq/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123I] MIBG scintigraphy on reducing tumor accumulation, and quality of life.Trials registrationjRCT2021220012 registered on 17 June 2022.

IntroductionSpeaker recognition has been performed by considering individual variations in the power spectrograms of speech, which reflect the resonance phenomena in the speaker's vocal tract filter. In recent years, phase-based features have been used for speaker recognition. However, the phase-based features are not in a raw form of the phase but are crafted by humans, suggesting that the role of the raw phase is less interpretable. This study used phase spectrograms, which are calculated by subtracting the phase in the time-frequency domain of the electroglottograph signal from that of speech. The phase spectrograms represent the non-modified phase characteristics of the vocal tract filter.MethodsThe phase spectrograms were obtained from five Japanese participants. Phase spectrograms corresponding to vowels, called phase spectra, were then extracted and circular-averaged for each vowel. The speakers were determined based on the degree of similarity of the averaged spectra.ResultsThe accuracy of discriminating speakers using the averaged phase spectra was observed to be high although speakers were discriminated using only phase information without power. In particular, the averaged phase spectra showed different shapes for different speakers, resulting in the similarity between the different speaker spectrum pairs being lower. Therefore, the speakers were distinguished by using phase spectra.DiscussionThis predominance of phase spectra suggested that the phase characteristics of the vocal tract filter reflect the individuality of speakers.

Abstract Background Although thiamine deficiency (TD) can lead to Wernicke encephalopathy, the characteristics associated with TD in the elderly have not yet been clarified. We sought to clarify the frequency of TD among an institutionalized elderly population with a controlled dietary intake and to identify possible factors related to TD. Method We undertook a cross‐sectional study of residents in three nursing homes for the elderly as of June 2020. Blood thiamine concentrations were measured using a high‐performance liquid chromatography method, with TD defined as a concentration of

The goal of this study is to perform correlation analysis of Computed tomography (CT) and magnetic resonance imaging (MRI) results in posterior ligament complex (PLC) injury and define the morphological traits of thoracolumbar (TL) burst fractures connected to PLC injury. Forty patients with surgically repaired TL burst fractures between January 2013 and December 2020 were retrospectively analyzed. The patients were split into two groups for comparison based on MRI (Group P: patients with a confirmed or suspected PLC injury; Group N: patients with PLC injury denied). The radiographic morphological examination based on CT scans and clinical evaluation was performed and compared between two groups. The thoracolumbar injury classification and severity score (TLICS), the load sharing classification (LSC) scores, and the number of patients with neurological impairments were considerably greater in Group P. Loss of height of the fracture (loss height), local kyphosis of the fracture (local kyphosis), and supraspinous distance were significantly higher in Group P and significantly associated with PLC injuries indicating severe vertebral body destruction and traumatic kyphosis in multivariate logistic analysis [odds ratio: 1.90, 1.06, and 1.13, respectively]. Cutoff value for local kyphosis obtained from the receiver operating characteristic curve was 18.8. If local kyphosis is greater than 18.8 degrees on CT scans, we should take into account the probability of the highly damaged burst fracture associated with PLC injury. In this situation, we should carefully assess MRI to identify the spinal cord injury or spinal cord compression in addition to PLC injury because these instances likely present with neurological abnormalities.

Background: Standard methods for deriving Centiloid scales from amyloid PET images are time-consuming and require considerable expert knowledge. We aimed to develop a deep learning method of automating Centiloid scale calculations from amyloid PET images with 11C-Pittsburgh Compound-B (PiB) tracer and assess its applicability to 18F-labeled tracers without retraining. Methods: We trained models on 231 11C-PiB amyloid PET images using a 50-layer 3D ResNet architecture. The models predicted the Centiloid scale, and accuracy was assessed using mean absolute error (MAE), linear regression analysis, and Bland–Altman plots. Results: The MAEs for Alzheimer’s disease (AD) and young controls (YC) were 8.54 and 2.61, respectively, using 11C-PiB, and 8.66 and 3.56, respectively, using 18F-NAV4694. The MAEs for AD and YC were higher with 18F-florbetaben (39.8 and 7.13, respectively) and 18F-florbetapir (40.5 and 12.4, respectively), and the error rate was moderate for 18F-flutemetamol (21.3 and 4.03, respectively). Linear regression yielded a slope of 1.00, intercept of 1.26, and R2 of 0.956, with a mean bias of −1.31 in the Centiloid scale prediction. Conclusions: We propose a deep learning means of directly predicting the Centiloid scale from amyloid PET images in a native space. Transferring the model trained on 11C-PiB directly to 18F-NAV4694 without retraining was feasible.

Individuals often imitate the postures or gestures of others in everyday life, without even being aware. This behavioral tendency is known as “automatic imitation” in laboratory settings and is thought to play a crucial role in social interactions. Previous studies have shown that the perception of a simple finger movement activates a shared representation of the observed and executed movements, which then elicits automatic imitation. However, relatively few studies have examined whether automatic imitation is limited to simple single-finger movements or whether it can be produced using a different automatic imitation paradigm with more complex sequential movements. Therefore, this study conducted three experiments in which participants observed the sequential movements of a model and then executed a compatible (similar) action or an incompatible (different) action involving the hand or foot in response to number cues that indicated the sequence for moving their hands or feet. The delay to onset of participants’ initial hand or foot movements was calculated. Participants consistently executed compatible actions faster than incompatible actions. In particular, the results showed an imitative compatibility effect with a human stimulus but not an inanimate stimulus. These results demonstrate that automatic imitation occurs during more complex movements that require memory.

IntroductionTransplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.MethodsIn this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4−), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.ResultsTo evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4− single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4− SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.DiscussionSuch functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

Extravascular leakage on computed tomography (CT) angiography in patients with traumatic brain injury (TBI) is associated with hematoma expansion, functional prognosis, subsequent surgery, and death. Fresh frozen plasma (FFP) administration is often necessary to treat coagulation disorders associated with TBI. This study aimed to determine the relationship between the presence of extravascular leakage on contrast-enhanced head CT, fibrinogen level at admission, and FFP administration in patients with TBI. The medical records of patients with TBI ?18 years of age referred to our hospital between January 2010 and December 2020 were examined retrospectively. Patients who underwent contrast-enhanced CT immediately after admission were selected, and the presence or absence of extravascular leakage, fibrinogen level at admission, and percentage of patients who required FFP administration within 24?h of admission were examined; 172 patients were included. Multi-variable linear regression analysis was performed to determine the effects of contrast extravasation on fibrinogen levels at admission and was adjusted for age, sex, systolic blood pressure, time from injury to admission, Marshall CT score, Glasgow Coma Scale score at admission, Injury Severity Score, and need for emergency surgery; the regression coefficient was ?19.8. The effect of extravasation on FFP administration within 24?h of admission was analyzed using logistic regression while adjusting for age, systolic blood pressure, Marshall CT score, need for emergency surgery, and fibrinogen level at admission. The odds ratio of contrast extravasation was 7.08 after adjustment. Extravascular leakage is associated with fibrinogen levels at admission and FFP administration within 24?h of admission.

Abstract The circadian rhythm is a fundamental physiological function for a wide range of organisms. The molecular machinery for generating rhythms has been elucidated over the last few decades. Nevertheless, the mechanism for temperature compensation of the oscillation period, which is a prominent property of the circadian rhythm, is still controversial. In this study, we propose a new mechanism through a chemically synthetic approach (i.e., we realized temperature compensation by the Belousov–Zhabotinsky (BZ) gels). The BZ gels are prepared by embedding a metal catalyst of the BZ reaction into the gel polymer. We made the body of BZ gels using a temperature-sensitive polymer gel, which enabled temperature compensation of the oscillation by using temperature dependence of volume. Moreover, we constructed a simple mathematical model for the BZ oscillation in temperature-sensitive gels. The model can reproduce temperature compensation of BZ gels, even though all reactions are temperature sensitive according to the Arrhenius rule. Our finding hints that a soft body coupling may be underlying temperature-compensated biological functions, including circadian rhythms.

ABSTRACTCities worldwide have introduced or revived light rail transit (LRT) to develop compact city strategies and help address environmental issues, such as increasing CO2 emissions or air pollution. Toyama is such a city that has addressed these issues by establishing a compact city rooted in transportation policies, notably the LRT established in 2006. Although there appears to be a consensus that the LRT contributes to establishing a compact city, contributing factors to ridership remain unclear. This study attempts to identify these factors, using the norm-activation model and theory of planned behaviour as a theoretical grounding, questionnaires for a data collection method and structural equation modelling for data analysis. The findings suggest that attitudes, perceived behavioural control and behavioural norms are significantly associated with the intention to use the LRT, which is, along with age, associated with its actual use. Based on these findings, this study provides theoretical and practical insights for cities wanting to pursue establishing or developing an LRT system.