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Abstract The genome is constantly exposed to DNA damage from endogenous and exogenous sources. Fine modulation of DNA repair, chromatin remodeling, and transcription factors is necessary for protecting genome integrity, but the precise mechanisms are still largely unclear. We found that after ionizing radiation (IR), global trimethylation of histone H3 at lysine 4 (H3K4me3) was decreased at an early (5 min) post-IR phase but increased at an intermediate (180 min) post-IR phase in both human and mouse hematopoietic cells. We demonstrated that PTIP, a component of the MLL histone methyltransferase complex, is required for H3K4me3 upregulation in the intermediate post-IR phase and promotes cell cycle arrest by epigenetically inducing a cell cycle inhibitor, PRDM1. In addition, we found that PTIP expression is specifically downregulated in acute myeloid leukemia patients. These findings collectively suggest that the PTIP-PRDM1 axis plays an essential role in proper DNA damage response and its deregulation contributes to leukemogenesis.

Abstract Odours used by insects for foraging and mating are carried by the air. Insects induce airflows around them by flapping their wings, and the distribution of these airflows may strongly influence odour source localisation. The flightless silkworm moth, Bombyx mori, has been a prominent insect model for olfactory research. However, although there have been numerous studies on antenna morphology and its fluid dynamics, neurophysiology, and localisation algorithms, the airflow manipulation of the B. mori by fanning has not been thoroughly investigated. In this study, we performed computational fluid dynamics (CFD) analyses of flapping B. mori to analyse this mechanism in depth. A three-dimensional simulation using reconstructed wing kinematics was used to investigate the effects of B. mori fanning on locomotion and pheromone capture. The fanning of the B. mori was found to generate an aerodynamic force on the scale of its weight through an aerodynamic mechanism similar to that of flying insects. Our simulations further indicate that the B. mori guides particles from its anterior direction within the ~ 60° horizontally by wing fanning. Hence, if it detects pheromones during fanning, the pheromone can be concluded to originate from the direction the head is pointing. The anisotropy in the sampling volume enables the B. mori to orient to the pheromone plume direction. These results provide new insights into insect behaviour and offer design guidelines for robots for odour source localisation.

Abstract Aims Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long‐term mortality in patients with ADHF admitted to the CICU. Methods Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9 ± 12.9 years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan–Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all‐cause mortality during the observation period (1134 days). The primary endpoint of this study was all‐cause mortality. Results The Kaplan–Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log‐rank test: P = 0.016, P = 0.005 and P

The indication for surgical intervention in spontaneous intracerebral hemorrhage remains controversial. Although many clinical trials have failed to demonstrate its efficacy over medical treatment, less invasive endoscopic treatment is expected to demonstrate its superiority. A novel endoscopic system for hematoma removal consisting of a 3.1-mm-diameter 4K high-resolution rigid endoscope was used. The system was used in eight cases of spontaneous intracerebral hemorrhage. It provided improved maneuverability of the surgical instrument while maintaining satisfactory image quality. The surgical goal was achieved in all cases without any complications, including perioperative rebleeding. Endoscopic hematoma removal using the 3.1 mm high-resolution endoscope is an alternative minimally invasive approach to spontaneous intracerebral hemorrhage with improved reliability.

Abstract Objectives Poor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults. Methods 421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS. Results Results showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with ‘unfit and higher BMI’ group, ‘unfit and lower BMI’, ‘fit and higher BMI’, and ‘fit and lower BMI’ groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women. Conclusions This study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS.

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

Abstract We conducted a large-scale online survey in February 2023 to investigate the public’s perceptions of COVID-19 infection and fatality risks in Japan. We identified two key findings. First, univariate analysis comparing perceived and actual risk suggested overestimation and nonnegligible underestimation of COVID-19 risk. Second, multivariate logistic regression analyses revealed that age, income, education levels, health status, information sources, and experiences related to COVID-19 were associated with risk perceptions. Given that risk perceptions are closely correlated with daily socioeconomic activities and well-being, it is important for policy-makers and public health experts to understand how to communicate COVID-19 risk to the public effectively.

Abstract During the 3 years of the COVID-19 pandemic, Japanese children had to live with strict mitigation measures at school, such as eating school lunches silently and wearing masks during physical exercise classes, even after those mitigation measures have been relaxed worldwide. Excursions and other school events were frequently cancelled, especially in 2020 and 2021. This study conducts a retrospective survey on school experiences to understand how the strict mitigation measures were related to children's mental health and well-being. Results revealed school excursion cancellation to be associated with a higher risk of developing depressive symptoms {odds ratio [OR] 1.543 [95% confidence interval (CI) 1.109–2.148]}, and high cancellation rate of other school events to be associated with dissatisfaction in school experience [OR 1.650 (95% CI 1.222–2.228)]. In the subsample analysis, we found that girls and children with no extracurricular activities tended to exhibit depressive symptoms due to the cancellation of school excursions. Overall, the study demonstrated that persistent strict mitigation measures at schools might be a key factor in understanding children’s mental health and psychological well-being during a long-lasting pandemic.

Abstract Background 123I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts. Results We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I. Conclusions The relationship between cardiac 123I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.

Abstract Background Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt‐PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt‐PDAC. Patients and method This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt‐PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt‐PDAC prognosis were investigated. Results There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt‐PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence‐free survival (HR = 2.01, 95% CI = 1.33–3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence‐free survival. Conclusions LN dissection along the hepatic artery for Pt‐PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short‐term outcomes and preservation of pancreatic function is required.

Background/purpose: While there are numerous reports on surgical techniques and materials for bone grafting, limited methods are available to enhance the body's inherent capacity to heal bones. Here we investigated microRNA-199a (miR-199a), a molecular that promotes osteoblast differentiation and bone healing. Materials and methods: To construct a miR-199a delivery complex, miR-199a-5p mimics were coated with mesoporous silica nanoparticles (MSNs) following modified with polyethyleneimine (PEI) and peptide WEAKLAKALAKALAKHLAKALAKALKACEA (KALA) to obtain 199a-5p-loaded MSN-PEI-KALA. Nanoparticle complexes are assessed for particle size and zeta potential using transmission electron microscopy and dynamic light scattering. Then MC3T3-E1 cells are exposed to MSN_miR-199a-5p @PEI-KALA. The impact of MSN_miR-199a-5p@PEI-KALA at varying concentrations on cell viability is assessed using Cell Counting Kit-8. Cell uptake and distribution were analyzed by double fluorescent staining with fluorescein amidite-labeled MSN_miR-199a@PEI-KALA and lysosome labeling. On day 7 after osteogenic induction, alkaline phosphatase (ALP) staining was conducted. Results: The findings indicated that the nanoparticle complexes encapsulating PEI and peptide exhibited an augmentation in both particle size and zeta potential. At a dosage of 10 μg/mL, MSN_miR-199a@PEI-KALA displayed the lowest cytotoxicity compared to the control group. MC3T3-E1 cells treated with MSN_miR-199a-5p@PEI-KALA exhibited intensified ALP staining and elevated mRNA expression levels of ALP, runt-related transcription factor 2, and osteopontin, suggesting the involvement of miR-199a-5p-loaded MSN-PEI-KALA in osteogenic differentiation. Conclusion: The successful construction of the delivering complex MSN_miR-199a@PEI-KALA in present research highlights the promise of this biomaterial carrier for the application of miRNAs in treating bone defects.

Abstract Background The concept of ablation index (AI) was introduced to evaluate radiofrequency (RF) ablation lesions. It is calculated from power, contact force (CF), and RF duration. However, other factors may also affect the quality of ablation lesions. To examine the difference in RF lesions made during sinus rhythm (SR) and atrial fibrillation (AF). Methods Sixty patients underwent index pulmonary vein isolation during SR (n = 30, SR group) or AF (n = 30, AF group). All ablations were performed with a power of 50 W, a targeted CF of 5–15 g, and AI of 400–450 using Thermocool Smarttouch SF. The CF, AI, RF duration, temperature rise (Δtemp), impedance drop (Δimp), and the CF stability of each ablation point quantified as the standard deviation of the CF (CF‐SD) were compared between the two groups. Results A total of 3579 ablation points were analyzed, which included 1618 and 1961 points in the SR and the AF groups, respectively. Power, average CF, RF duration per point, and the resultant AI (389 ± 59 vs. 388 ± 57) were similar for the two rhythms. However, differences were seen in the CF‐SD (3.5 ± 2.2 vs. 3.8 ± 2.1 g, p

Abstract This study aimed to confirm urinary protein fragments in relation to the presence of pancreatic ductal adenocarcinoma (PDAC) via a C-terminal proteomics strategy using exploratory and validation cohorts. Urinary fragments were examined by iTRAQ-labelling of tryptic peptides and concentrations of C-terminal fragments were evaluated. Only the urinary CD276 fragment showed a fold change (FC) of > 1.5 with a significant difference of P

Abstract Background Little is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington). Findings Among 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend

Background: Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established. Hypothesis: The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair. Study design: A controlled laboratory study. Methods: In vitro: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. In vivo: An SMI model was established with Sprague–Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-β1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment. Results: In vitro: The fibroblast migration ability was suppressed by SE added at a concentration of 10⁴ μg/mL in the culture medium. In vivo: In the 1-week model, the SE group exhibited significantly lower TGFβ −1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength. Conclusion: Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair. Clinical relevance: The findings of this study may contribute to the development of an early intervention method for SMIs.

In this study, the frequency down-conversion of terahertz waves is analytically and experimentally demonstrated at the temporal boundaries within a GaAs waveguide. The temporal boundary is established by photoexciting the top surface of the waveguide, thereby instantaneously increasing its electrical conductivity. This photoexcited waveguide supports a transverse electromagnetic (TEM) mode with a frequency lower than those of the transverse magnetic (TM) modes present in the original waveguide. At the temporal boundary, the incident TM mode couples with the TEM mode, resulting in frequency down-conversion. Subtracting the propagation loss from the frequency-converted components indicates that the frequency conversion occurs with an efficiency consistent with the analytical predictions. The propagation loss is primarily due to ohmic loss, caused by the finite electrical conductivity of the photoexcited region. Given that the frequency of transverse electric modes is up-converted at the temporal boundary, our findings suggest that the direction of frequency conversion (upward or downward) can be controlled by manipulating the incident polarization. The polarization-dependent frequency conversion in waveguides holds significant potential for applications in devices designed for the interconversion of terahertz signals across various frequency channels. This capability is instrumental in the development of frequency-division-multiplexed terahertz wave communication systems, thereby enabling high data transfer rates.

Abstract HIV-1 drug resistance genotypic tests have primarily been performed by Sanger sequencing of gene segments encoding different drug target proteins. Since the number of targets has increased with the addition of a new class of antiretroviral drugs, a simple high-throughput system for assessing nucleotide sequences throughout the HIV-1 genome is required. Here, we developed a new solution using nanopore sequencing of viral pangenomes amplified by PCR. Benchmark tests using HIV-1 molecular clones demonstrated an accuracy of up to 99.9%. In addition, validation tests of our protocol in 106 clinical samples demonstrated high concordance of drug resistance and tropism genotypes (92.5% and 98.1%, respectively) between the nanopore sequencing-based results and archived clinical determinations made based on Sanger sequencing data. These results suggest that our new approach will be a powerful solution for the comprehensive survey of HIV-1 drug resistance mutations in clinical settings.

Introduction: We report a case of cerebral venous sinus thrombosis (CVST) that presented with bilateral optic disc swelling and diplopia in the absence of headaches. Case Presentation: A 54-year-old woman with no relevant medical history presented with a 2-week history of diplopia and no loss of visual acuity in each eye. Eye movements revealed bilateral abduction deficits, and fundoscopic examination revealed bilateral optic disc swelling. Non-contrast computed tomography of the head showed no abnormalities. Magnetic resonance venography revealed the absence of flow in the superior sagittal and left transverse sinuses as a consequence of thrombosis. The patient was diagnosed with intracranial hypertension associated with abducens nerve palsies secondary to CVST and was initiated on anticoagulant therapy. CVST can lead to stroke even in younger individuals. Conclusion: CVST should be considered in differential diagnosis when bilateral papilledema and abducens nerve palsies are present, even in the absence of headache or other neurological findings.

Abstract The westernmost Nankai Trough, southwest Japan, exhibits a rapid along-strike reduction in plate coupling in the proximity to the subducting Kyushu-Palau ridge. Yet how and to what extent the ridge subduction impacts physical properties at the megathrust have not been investigated. Here we present high-resolution seismic P-wave velocity models along the forearc wedge in the western Nankai Trough derived from full-waveform inversion analyses of seismic refraction data. The velocity models show that where the plate coupling is weak and the plate boundary presumably hosts slow earthquakes, the upper plate exhibits lower seismic velocities indicating higher degree of fracturing over a ~ 100 km length along trough. Intriguingly, the extent of the upper-plate low-velocity features is significantly larger than the surficial width of the Kyushu-Palau ridge, and this low-velocity zone is underthrust by the slab with increased crustal thickness by 2–4 km. Seismic reflection images consistently reveal that the thicker slab crust has appreciable basement roughness extending ~ 60 km from the eastern margin of the Kyushu-Palau ridge beneath the western Shikoku basin. We suggest that such a thicker and rugged slab crust, together with the main body of the Kyushu-Palau ridge, can cause significant fracture zones in the overriding plate, decrease the interplate coupling and produce preferable conditions for shallow slow earthquakes to occur when subducted. The results may also provide structural constraints on the western limit of future megathrust earthquakes in the Nankai Trough. Graphical Abstract

Abstract The 1771 Meiwa tsunami which struck the southern Ryukyu Islands (Sakishima Islands) had greater than 22 m run-up height, leaving about 12,000 casualties in its wake. At many places, the tsunami inundation or lack of inundation is well recorded in historical documents. Several tsunami source models have been proposed for this event using historical records as constraints of tsunami calculations. Nevertheless, the source model remains under discussion. This study re-evaluated the tsunami wave source model of the 1771 Meiwa tsunami using high-resolution (10 m mesh) bathymetric and topographical data for tsunami calculation, the latest historical record dataset, and seismological knowledge. Results demonstrated that a tsunami earthquake along the southern Ryukyu Trench was the likely cause of the 1771 event. However, it is noteworthy that assumption of a large slip with 30 m is necessary for a shallow and narrow region (fault depth = 5 km, fault width = 30 km, Mw = 8.49) of the plate boundary in the Ryukyu Trench, which is far larger than previously thought. This requirement of very large initial water level change at the source might involve not only the fault rupture along the plate boundary but also deformation by splay faults, inelastic deformation of unconsolidated sediments near the trench axis, and/or giant submarine landslides. Results also show that the effects of fault parameters on the run-up were quite different depending on the offshore coral reef width. This phenomenon strongly constrained the fault width to 30 km. Our tsunami ray tracing analysis further revealed the effects of bathymetry on tsunami propagation. It is noteworthy that meter-long huge tsunami boulders tend to be distributed along the specific coasts at which the tsunami was concentrated by bathymetric effects. This finding suggests that past tsunamis, including the 1771 event, might have affected the specific coral reefs on Sakishima Islands repeatedly, which is crucially important for understanding the heterogeneous distribution of tsunami boulders. This feature might also be useful to elucidate the effects of large tsunamis on the corals and reefs because a direct comparison of coral reefs that are damaged and not damaged by tsunami waves is testable in narrow areas in the case of the Sakishima Islands.

Abstract Background Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. Methods We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. Results HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. Conclusions HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.

Objectives: In the present study, we performed a detailed analysis of deglutitive dynamics during sleep in patients with obstructive sleep apnea (OSA) using a methodology developed by Sato et al. We hypothesized that the frequency of deglutition would decrease with increasing severity of OSA. The aim of this study is to clarify the involvement of deglutitive dynamics during sleep in OSA by investigating the correlations between deglutition and sleep parameters. Methods: This study included 30 adult patients with OSA. To analyze deglutition dynamics during sleep, surface electromyography recordings of the suprahyoid and thyrohyoid neck muscles, which are involved in deglutition, were performed simultaneous with conventional polysomnography. The “index of deglutition” was defined as the frequency of deglutition per hour of sleep. We examined correlations between this index and sleep parameters (apnea-hypopnea index [AHI], apnea index, hypopnea index, and lowest blood oxygen saturation). Results: By analyzing the obtained polysomnography and electromyography waveforms, we identified two deglutition patterns with and without respiratory arousal during sleep. We found a significant negative correlation between the index of deglutition in sleep stage 1 and the AHI, with a correlation coefficient of –0.48. (p=0.02) Conclusions: In the current study, we distinguished deglutition during sleep with and without arousal. In addition we discovered a significant negative correlation between the index of deglutition in sleep stage 1 and the AHI. This new finding will provide a platform for future research on OSA in aspiration pneumonia.

Objectives: The aim of this study was to evaluate the safety and efficacy of microdebrider adenoidectomy on sleep-disordered breathing among pediatric patients with OSA. Methods: In the microdebrider group (Group I), there were 30 Japanese OSA patients consisting of 26 boys and 4 girls. For comparison, we had 15 children (13 boys and 2 girls) who underwent classical adenoidectomy (Group II). Patients in Group I were selected from a pool of 95 pediatric Japanese OSA patients and were matched by age, preoperative AHI, and Kaup index with those in Group II. Parameters such as the amount of residual adenoid tissue, bleeding, duration of the procedure, and sleep-related metrics were compared between the two groups. Results: A significant improvement in postoperative AHI was observed in Group I (p

Objective: To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea–hypopnea index (AHI) and to determine whether each parameter separately (pharyngeal tonsil grade and palatine tonsil grade) results in differences in severe obstructive sleep apnea (OSA). Methods: This cross-sectional study involved 107 children (mean age, 7.2 years; range, 4–12 years) suspected of having OSA because of snoring or sleep-related complaints. The patients underwent polysomnography, and their palatine and pharyngeal tonsils were graded. Results: In examining whether the palatine tonsils and pharyngeal tonsils could be risk factors for severe OSA, the adjusted odds ratios were 4.42 for palatine tonsil grade 4 versus 1–3 and 10.40 for pharyngeal tonsil grade 4 versus 1–3; both were highly statistically significant. We also found that the AHI when both the pharyngeal and palatine tonsils were grade 4 was higher than the AHI expected for the pharyngeal and palatine tonsils alone. Conclusions: The combination of grade 4 pharyngeal tonsils and grade 4 palatine tonsils resulted in an AHI much higher than the AHI of other combinations (pharyngeal tonsils grades 1–3 and 4, palatine tonsils grades 1–3 and 4). We believe that grade 4 pharyngeal tonsils and grade 4 palatine tonsils have a great influence on severe OSA and that grade 4 pharyngeal tonsils increase the AHI.

Background: Combined knee valgus and tibial internal rotation (VL + IR) moments have been shown to stress the anterior cruciate ligament (ACL) in several in vitro cadaveric studies. To utilize this knowledge for non-contact ACL injury prevention in sports, it is necessary to elucidate how the ground reaction force (GRF) acting point (center of pressure (CoP)) in the stance foot produces combined knee VL + IR moments in risky maneuvers, such as cuttings. However, the effects of the GRF acting point on the development of the combined knee VL + IR moment in cutting are still unknown. Methods: We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector's directional probability for developing the combined knee VL + IR moment, and theoretically predicted that when the CoP is posterior to the tibial rotational axis, the GRF vector is more likely to produce the combined knee VL + IR moment than when the CoP is anterior to the tibial rotational axis. Then, we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment. Fourteen females performed 60° cutting under forefoot/rearfoot strike conditions (10 trials each). The positions of lower limb markers and GRF data were measured, and the knee moment due to GRF vector was calculated. The trials were divided into anterior- and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike, and the occurrence rate of the combined knee VL + IR moment was compared between trial groups. Results: The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL + IR moment (maximum of 82.8%) at every time point than those of the anterior-CoP trials, as theoretically predicted by the deterministic mechanical condition. Conclusion: The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL + IR stress.

Abstract: Objectives: This study aimed to analyze Japanese youth athletes’ mental health and resilience during the COVID-19 pandemic, as well as the potential correlations between their demographic factors and mental health outcomes. Methods: Participants were recruited from a single high school with a student population encompassing national-level competitors (NCs), local-level competitors (LCs), and general students (i.e., others; OTs), aiming to reduce the impact of differences in environmental conditions affecting pandemic-related stress. In March 2021, the students completed an anonymous online survey comprising questions on demographics and COVID-19, as well as the following scales: Kessler 6 (K6), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and the Resilience Scale. Differences and correlations among these groups’ scores were analyzed while controlling for covariates. Results: Of 1,022 students (51.3% girls), 22.3% were NCs, 38.6% were LCs, and 39.0% were OTs. NCs reported significantly lower scores on the K6, PHQ-9, and GAD-7, as well as significantly higher resilience scores, compared with LCs and OTs. Resilience scores had a significantly negative correlation with the K6, PHQ-9, and GAD-7 scores. Female gender, participation in cultural clubs, and indoor sports were factors associated with scores above the cut-off on each scale. COVID-19 testing, history of illness, and family history were not associated with any of the psychological evaluation measures. Conclusion: Based on responses to the self-reported questionnaires, NCs appear to have better mental health than their peers, while resilience has a potential association with improved mental health during the COVID-19 pandemic.

Abstract Uniaxial pressure provides an efficient approach to control charge density waves in YBa2Cu3Oy. It can enhance the correlation volume of ubiquitous short-range two-dimensional charge-density-wave correlations, and induces a long-range three-dimensional charge density wave, otherwise only accessible at large magnetic fields. Here, we use x-ray diffraction to study the strain dependence of these charge density waves and uncover direct evidence for a form of competition between them. We show that this interplay is qualitatively described by including strain effects in a nonlinear sigma model of competing superconducting and charge-density-wave orders. Our analysis suggests that strain stabilizes the 3D charge density wave in the regions between disorder-pinned domains of 2D charge density waves, and that the two orders compete at the boundaries of these domains. No signatures of discommensurations nor of pair density waves are observed. From a broader perspective, our results underscore the potential of strain tuning as a powerful tool for probing competing orders in quantum materials.

Abstract Background Very large chest wall resections can lead to acute thoracic insufficiency syndrome due to the interdependence of lung expansion and thoracic volume. Chest wall tumor surgeries often encounter complications, with the size of the chest wall defect being a significant predictor. Several methods for large chest wall reconstruction have been described, aiming to provide stability, prevent flail chest, and ensure airtight closure. However, no single method fulfills all requirements. Composite chest wall reconstruction using titanium plates and Gore-Tex patches has shown the potential to minimize physiologic abnormalities caused by extensive defects. Case presentation A 42-year-old man with myxofibrosarcoma underwent multiple surgeries, chemotherapies, and radiation therapies due to repeated local recurrences. After right arm amputation and resection of the right third to fifth ribs, a local recurrence was detected. A 30 × 40 cm chest wall defect was resected en bloc, and a titanium plate was used for three-dimensional formability, preventing flail chest and volume loss. The Gore-Tex patch was then reconstructed into an arch shape, allowing lateral thoracic mobility. The patient recovered well and did not experience respiratory dysfunction or local recurrence but later succumbed to distant metastasis. Conclusions In this case, the combination of a titanium plate and a Gore-Tex patch proved effective for reconstructing massive lateral chest wall defects. The approach provided stability, preserved thoracic volume, and allowed for lateral mobility. While the patient achieved a successful outcome in terms of local recurrence and respiratory function, distant metastasis remained a challenge for myxofibrosarcoma patients, and its impact on long-term prognosis requires further investigation. Nevertheless, the described procedure offers promise for managing extensive chest wall defects.

Background/purpose: Porcine collagen is widely used in regenerative therapies to generate membranes for bone augmentation. However, porcine or bovine gelatin or collagen is often not appropriate for patients with creed and religious beliefs or for allergic reasons. In this study, we evaluated the potential of fish gelatin to generate membranes. Materials and methods: Fish gelatin and hydroxyapatite (HAp) were used at three different ratios (2:0, 2:1, 2:1.5, and 2:2) to prepare gelatin-hydroxyapatite (G-HAp) membranes via freeze-drying and heat-crosslinking. The surface morphology and cell attachment of G-HAp membranes were observed using scanning electron microscopy and confocal laser microscopy. G-HAp membrane was placed at the bottom of a well plate, and MC3T3-E1 cells were seeded on it. Cell viability and cytotoxicity were tested after 1 and 3 days of culture. Alkaline phosphatase (ALP) and alizarin red staining was performed at 10 and 21 days, respectively. Results: Viability of cells on G-HAp membrane with the gelatin:HAp ratio of 2:1.5 was significantly higher than that on membranes with other gelatin:HAp ratios. ALP and alizarin red staining showed that ALP-positive areas and calcium deposition were the highest on G-HAp membrane with the gelatin:HAp ratio of 2:1. These membranes showed negligible cytotoxicity. Conclusion: Fish-derived G-HAp membranes have the potential to promote osteogenic differentiation of MC3T3-E1 cells with negligible cytotoxicity.

Epiphyseal injury, particular on femoral side, is a major concern in pediatric anterior cruciate ligament (ACL) reconstruction. Therefore, the over-the-top route (OTTR) method has frequently been selected in pediatric ACL reconstruction, with good clinical results reported. However, a cadaver study reported the inferior rotational stability of the OTTR method to that of anatomical single bundle reconstruction. In recent years, a new method of reconstruction, which involves the remnant being detached, re-tensioned, and re-attached, achieved good short-term results. We developed a surgical method to restore the remnant to the posterolateral (PL) bundle footprint and obtain rotational stability in patients, thereby preserving the remnant. We hypothesized that repairing the residual remnant to the PL bundle footprint in pediatric ACL reconstruction could achieve rotational stability. This report offers the surgical techniques for PL bundle tensioning repair using remnants in the pediatric ACL OTTR procedure.

Objectives: To clarify the infection route in maternal death due to invasive group A streptococcal (GAS) infection and toxic shock syndrome (TSS). Methods: A retrospective study was conducted on maternal deaths due to GAS-TSS in Japan between January 2010 and March 2024. The final causal diagnosis of maternal death and the infection routes of GAS were analysed using medical records, laboratory data and autopsy findings. Results: Among the 616 maternal deaths during the study period, 48 (8%) involved infectious diseases. The most common infection was invasive GAS (56%, n = 27), 21 (78%) and six cases occurred during the antepartum and puerperium periods, respectively. In the GAS-TSS group, 71% (15/21) infections were originated the upper respiratory tract. However, in the puerperium cases, 67% (4/6) were infected from the genital tract. In addition, no maternal deaths due to GAS-TSS were reported during the COVID-19 pandemic period in Japan from 2020 to 2023. Conclusion: Most antepartum GAS infections were from the upper respiratory tract. They may be reduced by preventive measures, including frequent disinfection, wearing masks and isolation from persons at high risk of carrying GAS, such as symptomatic children. On the other hand, GAS-TSS during puerperium infection via the genital tract.

Background: Morton neuroma is a common cause of forefoot pain and sensory disturbances, but it is difficult to identify on magnetic resonance imaging (MRI). The aim of this study was to verify the usefulness of a characteristic MRI finding (slug sign) for identifying Morton neuroma and to clarify the relationship between excised neuroma characteristics and preoperative MRI findings. Methods: Twenty-two web spaces were retrospectively assessed from the second and third intermetatarsal spaces of 11 feet of 10 patients (7 women and 3 men, aged average 59.5 years) who underwent surgical excision of Morton neuroma between 2017 and 2022. Asymptomatic web spaces were used as control. Neuromas with 2 branches of the plantar digital nerves on axial T1-weighted MRI (MRI-T1WI) were considered the slug sign. We investigated the preoperative presence of the slug sign in Morton neuroma and asymptomatic control web spaces. We also investigated the relationship between the maximum transverse diameter of the excised specimen and that estimated on coronal MRI-T1WI. Results: A total of 15 Morton neuromas were excised and assessed. The slug signs were present in 10 intermetatarsal spaces in 15 web spaces with Morton neuroma whereas the sign was found in 1 intermetatarsal space in 7 asymptomatic web spaces. The sensitivity and specificity for the slug sign to diagnose Morton neuroma was 66.7% and 85.7%, respectively. The positive and negative predictive values were 90.9% and 54.5%, respectively. The mean maximum transverse diameter of excised neuromas was 4.7 mm. The mean maximum transverse diameter of neuromas on coronal MRI-T1WI was 3.4 mm. A significant positive correlation was found between the maximum transverse diameters of excised specimens and diameters estimated on coronal MRI-T1WI ( r = 0.799, P

BackgroundHealth information seeking via the internet among patients with cancer in disaster-affected areas is underresearched. ObjectiveThis study aims not only to assess the extent and means of web-based health information seeking among patients with cancer living in the disaster-affected area of the 2011 Fukushima triple disaster but also to compare these patterns with those without cancer, identifying distinct and shared factors influencing their web-based health information behaviors. MethodsWe surveyed 404 patients (263 with and 141 without cancer) from the surgery department outpatient office at Minamisoma Municipal General Hospital, from October 2016 to January 2017. The survey included self-administered questions on internet and digital device use. Descriptive analyses were performed to examine the use patterns of digital devices and the internet and their impact on health information seeking across different age groups of patients with and without cancer. Multivariable logistic regression was used to examine factors associated with web-based health information seeking, stratifying by cancer diagnosis. ResultsThe proportion of participants who sought health information on the internet was comparable between patients with cancer and patients without cancer (19% vs 17.4%; P=.71). Digital device use varied significantly with age, with peak smartphone use occurring among the youngest cohorts for both groups. Multivariable logistic regression revealed that patients with cancer using smartphones or tablets daily were significantly more likely to gather web-based health information (odds ratio [OR] for smartphones 3.73, 95% CI 1.58-8.80; OR for tablets 5.08, 95% CI 1.27-20.35). Trust in institutional websites also significantly influenced web-based health information gathering among patients with cancer (OR 2.87, 95% CI 1.13-7.25). Conversely, among patients without cancer, unemployment was associated with a lower likelihood of seeking web-based health information (OR 0.26, 95% CI 0.08-0.85), whereas trust in both institutional and personal websites significantly increased this likelihood (OR for institutional websites 6.76, 95% CI 2.19-20.88; OR for personal websites 6.97, 95% CI 1.49-32.58). ConclusionsThis study reveals that a small proportion of both patients with cancer and patients without cancer engage in health information seeking via the internet, influenced by age, digital device use, and trust in institutional websites. Given the growing prevalence of digital literacy, strategies to enhance accessible and reliable web-based health information should be developed, particularly for patients with cancer in postdisaster settings. Future efforts should focus on tailored health communication strategies that address the unique needs of these populations.

We are pleased to bring you Volume 53 Issue 1 of The Australian Journal of Indigenous Education. We wish to thank the authors, reviewers, and editorial board members for their contributions to this volume. Thanks also to the Indigenous Engagement Division at The University of Queensland and Informit for their financial support of the journal. We hope you enjoy this volume of AJIE.

Introduction: This study aimed to clarify the relationship between psychological factors (goal orientation and desire for approval from others) and the severity of sports injuries experienced by young Japanese athletes. Methods: A total of 560 young Japanese athletes (328 males and 232 females) aged 18–24 years completed an online survey in 2022–2023. A web questionnaire was used to investigate participants’ task and ego orientations, desire for approval from others (e.g., coaches and friends/families), and history of injury. The samples were then split into 3 groups on the basis of the rest duration due to the injury: noninjury group (0 days), mild-to-moderate injury group (1–27 days), and severe injury group (>28 days). Spearman's test examined a correlation between task and ego orientation scores among all samples. The Mann–Whitney U test was used to compare the scores between the severe injury and noninjury groups. Result: A significant positive correlation was found between task and ego orientation scores from all samples (ρ=0.27, p4 weeks to return to sports. The goal orientation profiles should be interpreted with caution. Future research should examine contextual effects such as the perceived motivational climate, in addition to the goal orientation profiles.

Background. The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function. We hypothesized that the administration of the fibrinolytic enzyme plasmin to the donor organ during the cold storage period would reduce the thrombotic burden and improve DCD liver graft function. Methods. In 2 separate cohorts, 32 syngeneic orthotopic rat liver transplants were performed in Lewis rats. Livers were procured from donors with 45 min of warm ischemic injury. Liver grafts were flushed with histidine-tryptophan-ketoglutarate preservation solution mixed with either plasmin (experimental group) or albumin (control group). All investigators were blinded to treatment group. After preparing the liver for implant using a modified cuff technique, the liver was stored for 1 h by static cold storage at 4 °C. Immediately before implantation, the liver graft was flushed, and this effluent was analyzed for fibrin degradation products to determine graft clot burden. Twenty-four hours following transplantation, animals were euthanized, and samples were collected. Results. Recipient survival was significantly higher for DCD liver grafts treated with plasmin compared with control. Moreover, histology of liver graft tissue immediately before implant reflected significantly reduced congestion in plasmin-treated livers (score, mean ± SD: 0.73 ± 0.59 versus 1.12 ± 0.48; P = 0.0456). The concentration of fibrin degradation products in the final flush before implantation was significantly reduced in plasmin-treated livers (743 ± 136 versus 10 919 ± 4642 pg/mL; P = 0.0001), reflecting decreased clot burden in the graft. Conclusions. The present study demonstrates that plasmin improves survival and may reduce thrombotic burden in DCD liver grafts with prolonged warm ischemic injury, meriting further study.

BackgroundHand washing instructions for children have been implemented in school education to establish good lifestyle habits. However, repeated hand washing through education from early childhood was common for both teachers and children. If this continues, children might assume they already know how to wash their hands, stop taking handwashing instructions seriously, and become increasingly lax about washing their hands.PurposeThis study aimed to develop a new handwashing education method for children.MethodsWe applied the adenosine triphosphate (ATP) test to health education on hand washing in elementary schools. This study was conducted as part of a class for elementary school students in October 2023, in Hokkaido, Japan. The subjects were 157 third-grade (9–10 years old) elementary school students. After excluding absent pupils, 147 were included in the analysis.ResultsBoth pre- and post-education, ATP values after handwashing were lower than those before handwashing. Following the education, children’s handwashing behavior improved, with an increase in the number of point washed and appropriate timing of handwashing.ConclusionThe new handwashing education program utilizing the ATP-test succeeded in promoting handwashing behavior among many children. Visualizing handwashing using ATP values was effective in motivating children.

Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.

In the 2010s, several unusual rotavirus strains emerged, causing epidemics worldwide. This study reports a comprehensive molecular epidemiological study of rotaviruses in Japan based on full-genome analysis. From 2014 to 2019, a total of 489 rotavirus-positive stool specimens were identified, and the associated viral genomes were analyzed by next-generation sequencing. The genotype constellations of those strains were classified into nine patterns (G1P[8] (Wa), G1P[8]-E2, G1P[8] (DS-1), G2P[4] (DS-1), G3P[8] (Wa), G3P[8] (DS-1), G8P[8] (DS-1), G9P[8] (Wa), and G9P[8]-E2). The major prevalent genotype differed by year, comprising G8P[8] (DS-1) (37% of that year’s isolates) in 2014, G1P[8] (DS-1) (65%) in 2015, G9P[8] (Wa) (72%) in 2016, G3P[8] (DS-1) (66%) in 2017, G1P[8]-E2 (53%) in 2018, and G9P[8] (Wa) (26%) in 2019. The G1P[8]-E2 strains (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1) isolated from a total of 42 specimens in discontinuous years (2015 and 2018), which were the newly-emerged NSP4 mono-reassortant strains. Based on the results of the Bayesian evolutionary analyses, G1P[8]-E2 and G9P[8]-E2 were hypothesized to have been generated from distinct independent inter-genogroup reassortment events. The G1 strains detected in this study were classified into multiple clusters, depending on the year of detection. A comparison of the predicted amino acid sequences of the VP7 epitopes revealed that the G1 strains detected in different years encoded VP7 epitopes harboring distinct mutations. These mutations may be responsible for immune escape and annual changes in the prevalent strains.

Summary: Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.

We report a patient with hemophilia A who underwent partial splenic embolization (PSE) for severe thrombocytopenia secondary to portal hypertension-induced splenomegaly, resulting in a stable long-term quality of life. The patient was diagnosed with hemophilia A and unfortunately contracted human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) from blood products. He subsequently developed progressive splenomegaly due to portal hypertension from chronic HCV, resulting in severe thrombocytopenia. PSE was performed because he had occasional subcutaneous bleeding and needed to start interferon (IFN) and ribavirin (RBV) treatment for curing his HCV infection at that time. His platelet counts increased, and no serious adverse events were observed. Currently, he continues to receive outpatient treatment, regular factor VIII (FVIII) replacement therapy for hemophilia A, and antiretroviral therapy for HIV infection. Vascular embolization has been reported to be an effective and minimally invasive treatment for bleeding in hemophilia patients. PSE also provided him with a stable quality of life without the side effects of serious infections and thrombocytopenia relapses. We conclude that PSE is a promising therapeutic option for patients with hemophilia A.

Abstract Background Predicting time to renal replacement therapy (RRT) is important in patients at high risk for end-stage kidney disease. We developed and validated machine learning models for predicting the time to RRT and compared its accuracy with conventional prediction methods that uses the rate of estimated glomerular filtration rate (eGFR) decline. Methods Data of adult chronic kidney disease (CKD) patients who underwent hemodialysis at Oita University Hospital from April 2016 to March 2021 were extracted from electronic medical records (N = 135). A new machine learning predictor was compared with the established prediction method that uses the eGFR decline rate and the accuracy of the prediction models was determined using the coefficient of determination (R2). The data were preprocessed and split into training and validation datasets. We created multiple machine learning models using the training data and evaluated their accuracy using validation data. Furthermore, we predicted the time to RRT using a conventional prediction method that uses the eGFR decline rate for patients who had measured eGFR three or more times in two years and evaluated its accuracy. Results The least absolute shrinkage and selection operator regression model exhibited moderate accuracy with an R2 of 0.60. By contrast, the conventional prediction method was found to be extremely low with an R2 of -17.1. Conclusions The significance of this study is that it shows that machine learning can predict time to RRT moderately well with continuous values from data at a single time point. This approach outperforms the conventional prediction method that uses eGFR time series data and presents new avenues for CKD treatment.

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

Abstract In the field of expensive optimization, numerous papers have proposed surrogate-assisted evolutionary algorithms (SAEAs) for a few thousand or even hundreds of function evaluations. However, in reality, low-cost simulations suffice for a lot of real-world problems, in which the number of function evaluations is moderately restricted, e.g., to several thousands. In such moderately restricted scenario, SAEAs become unnecessarily time-consuming and tend to struggle with premature convergence. In addition, tuning the SAEA parameters becomes impractical under the restricted budgets of function evaluations—in some cases, inadequate configuration may degrade performance instead. In this context, this paper presents a fast and auto-tunable evolutionary algorithm for solving moderately restricted expensive optimization problems. The presented algorithm is a variant of adaptive differential evolution (DE) algorithms, and is called emulation-based adaptive DE or EBADE. The primary aim of EBADE is to emulate the principle of sample-efficient optimization, such as that in SAEAs, by adaptively tuning the DE parameter configurations. Specifically, similar to Expected Improvement-based sampling, EBADE identifies parameter configurations that may produce expected-to-improve solutions, without using function evaluations. Further, EBADE incepts a multi-population mechanism and assigns a parameter configuration to each subpopulation to estimate the effectiveness of parameter configurations with multiple samples carefully. This subpopulation-based adaptation can help improve the selection accuracy of promising parameter configurations, even when using an expected-to-improve indicator with high uncertainty, by validating with respect to multiple samples. The experimental results demonstrate that EBADE outperforms modern adaptive DEs and is highly competitive compared to SAEAs with a much shorter runtime.

Abstract Background Minimally invasive distal pancreatectomy (MIDP), including laparoscopic and robotic distal pancreatectomy, has gained widespread acceptance over the last decade owing to its favorable short-term outcomes. However, evidence regarding its oncologic safety is insufficient. In March 2023, a randomized phase III study was launched in Japan to confirm the non-inferiority of overall survival in patients with resectable pancreatic cancer undergoing MIDP compared with that of patients undergoing open distal pancreatectomy (ODP). Methods This is a multi-institutional, randomized, phase III study. A total of 370 patients will be enrolled from 40 institutions within 4 years. The primary endpoint of this study is overall survival, and the secondary endpoints include relapse-free survival, proportion of patients undergoing radical resection, proportion of patients undergoing complete laparoscopic surgery, incidence of adverse surgical events, and length of postoperative hospital stay. Only a credentialed surgeon is eligible to perform both ODP and MIDP. All ODP and MIDP procedures will undergo centralized review using intraoperative photographs. The non-inferiority of MIDP to ODP in terms of overall survival will be statistically analyzed. Only if non-inferiority is confirmed will the analysis assess the superiority of MIDP over ODP. Discussion If our study demonstrates the non-inferiority of MIDP in terms of overall survival, it would validate its short-term advantages and establish its long-term clinical efficacy. Trial registration This trial is registered with the Japan Registry of Clinical Trials as jRCT 1,031,220,705 [ https://jrct.niph.go.jp/en-latest-detail/jRCT1031220705 ].

Abstract Owing to their remarkable properties, gold nanoparticles are applied in diverse fields, including catalysis, electronics, energy conversion and sensors. However, for catalytic applications of colloidal gold nanoparticles, the trade-off between their reactivity and stability is a significant concern. Here we report a universal approach for preparing stable and reactive colloidal small (~3 nm) gold nanoparticles by using multi-dentate polyoxometalates as protecting agents in non-polar solvents. These nanoparticles exhibit exceptional stability even under conditions of high concentration, long-term storage, heating and addition of bases. Moreover, they display excellent catalytic performance in various oxidation reactions of organic substrates using molecular oxygen as the sole oxidant. Our findings highlight the ability of inorganic multi-dentate ligands with structural stability and robust steric and electronic effects to confer stability and reactivity upon gold nanoparticles. This approach can be extended to prepare metal nanoparticles other than gold, enabling the design of novel nanomaterials with promising applications.

Abstract Menkes disease is an X-linked disorder of copper metabolism caused by mutations in the ATP7A gene, and female carriers are usually asymptomatic. We describe a 7-month-old female patient with severe intellectual disability, epilepsy, and low levels of serum copper and ceruloplasmin. While heterozygous deletion of exons 16 and 17 of the ATP7A gene was detected in the proband, her mother, and her grandmother, only the proband suffered from Menkes disease clinically. Intriguingly, X chromosome inactivation (XCI) analysis demonstrated that the grandmother and the mother showed skewing of XCI toward the allele with the ATP7A deletion and that the proband had extremely skewed XCI toward the normal allele, resulting in exclusive expression of the pathogenic ATP7A mRNA transcripts. Expression bias analysis and recombination mapping of the X chromosome by the combination of whole genome and RNA sequencing demonstrated that meiotic recombination occurred at Xp21-p22 and Xq26-q28. Assuming that a genetic factor on the X chromosome enhanced or suppressed XCI of its allele, the factor must be on either of the two distal regions derived from her grandfather. Although we were unable to fully uncover the molecular mechanism, we concluded that unfavorable switching of skewed XCI caused Menkes disease in the proband.

Abstract Tennis is a popular leisure sport, and studies have indicated that playing tennis regularly provides many health benefits. We aimed to clarify the characteristics of physical activity during beginner-level group tennis lessons and daily physical activity of the participants. Physical activity was measured using an accelerometer sensor device for four weeks, including the 80-min duration tennis lessons held twice a week. Valid data were categorized for tennis and non-tennis days. The mean physical activity intensity during the tennis lesson was 3.37 METs. The mean ratio of short-bout rest periods to the tennis lesson time in 90 and 120 s was 7% and 4%, respectively. The mean physical activity intensity was significantly higher (p

The Japanese space mission JAXA/ Global Change Observation Mission-Climate (GCOM-C) launched in 2017 carries a second-generation global imager (SGLI). The SGLI contains 19 channels from near-UV to thermal infrared (IR), including red (674 nm named PL1 band) and near-IR (869 nm; PL2 band) polarization channels. The SGLI's spatial resolution is fine as the instantaneous field-of-view is 250 m from the near-UV to short-IR wavelength range for radiometry and 1 km for the polarization measurements. This work presents the retrieval algorithms for biomass burning aerosol (BBA) using the advantages of the SGLI features. The BBA generated by wildfires causes long-range advection migration. Severe wildfires, which now frequently occur around the world, have become a major environmental problem. Using as an example the large scale wildfires in September of 2020 around western North America, we show that the SGLI's simultaneous observation of radiance and polarization is useful for the characterization of BBA. Furthermore, a regional numerical model scalable computing for advanced library and environment is used to consider meteorological conditions and/or topography. The objective of this study is to better understand the BBA events through the integration of space-borne and ground-based measurements as well as the regional meteorological model.