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Various seismological methods are used to determine crustal stress fields, but most only provide stress changes, not absolute amounts of stress. In this study, we used Global Navigation Satellite System data to determine the spatiotemporal slip distribution of four slow slip events (SSEs) in the Bungo Channel between Shikoku and Kyushu Islands, Japan. Based on the obtained relationship between shear stress change and slip velocity, we plotted slip trajectories that were similar to theoretically stable trajectories for a spring-slider system subject to velocity weakening following a rate- and state-dependent friction law. Accordingly, we estimated the absolute values of the effective normal stress during SSE slip acceleration to have been 18–45 MPa at depths of 16.5–21.5 km. These values are very small compared to the lithostatic pressure at the depths investigated, suggesting the existence of very high pore fluid pressures at the plate boundary in the SSE source area. Our results and previous results obtained for SSEs off the Boso Peninsula, Japan, outline a positive correlation between the effective normal stress and total slip. Therefore, pore fluid pressure values at plate boundary interfaces may be an indicator of the amount of slip during SSEs. Graphical Abstract

Emergence of highly transmissible Omicron subvariants led to increased SARS-CoV-2 infection and disease in children. However, minimal knowledge exists regarding the neutralization capacity against circulating Omicron BA.4/BA.5, BA.2.75, BQ.1, BQ.1.1 and XBB.1 subvariants following SARS-CoV-2 vaccination in children versus during acute or convalescent COVID-19, or versus multisystem inflammatory syndrome (MIS-C). Here, we evaluate virus-neutralizing capacity against SARS-CoV-2 variants in 151 age-stratified children ( <5, 5–11, 12–21 years old) hospitalized with acute severe COVID-19 or MIS-C or convalescent mild (outpatient) infection compared with 62 age-stratified vaccinated children. An age-associated effect on neutralizing antibodies is observed against SARS-CoV-2 following acute COVID-19 or vaccination. The primary series BNT162b2 mRNA vaccinated adolescents show higher vaccine-homologous WA-1 neutralizing titers compared with <12 years vaccinated children. Post-infection antibodies did not neutralize BQ.1, BQ.1.1 and XBB.1 subvariants. In contrast, monovalent mRNA vaccination induces more cross-neutralizing antibodies in young children <5 years against BQ.1, BQ.1.1 and XBB.1 variants compared with ≥5 years old children. Our study demonstrates that in children, infection and monovalent vaccination-induced neutralization activity is low against BQ.1, BQ.1.1 and XBB.1 variants. These findings suggest a need for improved SARS-CoV-2 vaccines to induce durable, more cross-reactive neutralizing antibodies to provide effective protection against emerging variants in children. In this work, authors investigate the virus-neutralizing capacity in children against circulating BQ.1, BQ.1.1 and XBB.1 SARS-CoV-2 variants. Vaccination induced more neutralizing antibodies against BQ.1.1 and XBB.1 in youngest children ( < 5 years) compared with >5 years children.

We have adopted a simple and reproducible approach, “minimal manipulation approach,” since January 2021 in five patients to minimize the risk of thromboembolic events during Zone 1 and 2 thoracic endovascular aortic repair (TEVARs) with shaggy aorta. The approach consists of two parts: ① Use of a 65-cm-long sheath (dry seal) to deliver the endografts without touching the protruding atheroma. Covering the atheroma with the first endograft delivered at Zone 3 to the mid-descending aorta (paving the aorta), and second endograft insertion and deployment through the paved aorta with first endograft. ② Protection of the left subclavian artery using balloon catheter during TEVAR. No in-hospital mortality was recorded, and none of the patients had stroke, spinal cord ischemia, or distal embolic events.

Background We previously reported a phase II Kyoto trial for platinum-resistant ovarian cancer (n = 20) using nivolumab (anti-programmed cell death-1 [PD-1] antibody). We evaluated the associations between clinical outcomes and transcriptomics and T and B cell clonality from tumor and blood cells. Methods We analyzed gene expression microarray with pre- and post-treatment peripheral blood mononuclear cells, α- and β -chain of T cell receptor (TCR) repertoires, and immunoglobulin G (IgG) and M of B cell receptor (BCR) repertoires in 61 samples from 19 patients. Shannon–Weaver diversity scores of the TCR and BCR repertoires were compared between responders and non-responders. RNA sequencing analyzed gene expression and fusion genes in tumor samples (n = 17). Results BCR repertoire analyses of post-/pre-treatment ratios in four responders (two patients with complete response (CR), one with partial response, and one with stable disease near to CR) revealed significantly decreased BCR-IgG repertoires diversity versus non-responders (Shannon–Weaver index, median 0.84 vs. 1.04, p < 0.05); the diversity of BCR-IgG repertoires recovered over 100 days. More than two passenger fusion genes were detected in six of the seven responders, whereas eight of the ten non-responders lacked fusion genes. The antitumor response significantly correlated with the number of fusion genes (p = 0.0006). Pathway analyses consistently identified immune-related processes, including cytokine-cytokine receptor interactions, neutrophil degranulation, and immunoregulatory interactions in both responders and tumors with high fusion gene counts. Conclusion Transient oligoclonal expansion of B cells and passenger fusion genes might serve as predictive biomarkers of response to PD-1 blockade in ovarian cancer.

Purpose A narrow terminal aorta is a risk factor for endograft occlusion after endovascular aneurysm repair. To minimize limb complications, we used Gore Excluder legs positioned side-by-side at the terminal aorta. We investigated the outcomes of our strategy for endovascular aneurysm repair in patients with a narrow terminal aorta. Methods We enrolled 61 patients who underwent endovascular aneurysm repair with a narrow terminal aorta (defined as < 18 mm in diameter) from April 2013 to October 2021. The standard procedure involves complete treatment with the Gore Excluder device. When other types of main body endografts were used, they were deployed proximal to the terminal aorta, and we used the Gore Excluder leg device in the bilateral limbs. Postoperatively, the intraluminal diameter of the legs at the terminal aorta was measured to assess the configuration. Results During the follow-up period (mean: 2.7 ± 2.0 years), there were no aorta-related deaths, endograft occlusions, or leg-related re-interventions. There were no significant differences between the pre- and postoperative ankle-brachial pressure index values in the dominant and non-dominant legs ( p  = 0.44 and p  = 0.17, respectively). Postoperatively, the mean difference rate (defined as [dominant leg diameter–non-dominant leg diameter]/terminal aorta diameter) was 7.5 ± 7.1%. The difference rate was not significantly correlated with the terminal aortic diameter, calcification thickness, or circumferential calcification ( r  = 0.16, p  = 0.22; r  = 0.07, p  = 0.59; and r  = − 0.07, p  = 0.61, respectively). Conclusions Side-by-side deployment of Gore Excluder legs produces acceptable outcomes for endovascular aneurysm repair with a narrow terminal aorta. The endograft expansion at the terminal aorta is tolerable without influencing calcification distribution.

We hypothesized that deep learning-based post hoc denoising could improve the quality of cardiac CT for the 3D volume-rendered (VR) imaging of mitral valve (MV) prolapse. We aimed to evaluate the quality of denoised 3D VR images for visualizing MV prolapse and assess their diagnostic performance and efficiency. We retrospectively reviewed the cardiac CTs of consecutive patients who underwent MV repair in 2023. The original images were iteratively reconstructed and denoised with a residual dense network. 3DVR images of the “surgeon’s view” were created with blood chamber transparency to display the MV leaflets. We compared the 3DVR image quality between the original and denoised images with a 100-point scoring system. Diagnostic confidence for prolapse was evaluated across eight MV segments: A1-3, P1-3, and the anterior and posterior commissures. Surgical findings were used as the reference to assess diagnostic ability with the area under curve (AUC). The interpretation time for the denoised 3DVR images was compared with that for multiplanar reformat images. For fifty patients (median age 64 years, 30 males), denoising the 3DVR images significantly improved their image quality scores from 50 to 76 ( P  <.001). The AUC in identifying MV prolapse improved from 0.91 (95% CI 0.87–0.95) to 0.94 (95% CI 0.91–0.98) ( P  =.009). The denoised 3DVR images were interpreted five-times faster than the multiplanar reformat images ( P  <.001). Deep learning-based denoising enhanced the quality of 3DVR imaging of the MV, improving the performance and efficiency in detecting MV prolapse on cardiac CT. Graphical Abstract Deep learning-based post hoc denoising improved 3D cardiac CT imaging of the mitral valve, enhancing performance and efficiency in detecting prolapse

This study investigated a method for improving the quality of images with a low number of excitations (NEXs) based on deep learning using T2-weighted magnetic resonance imaging (MRI) of the heads of normal Wistar rats to achieve higher image quality and a shorter acquisition time. A 7T MRI was used to acquire T2-weighted images of the whole brain with NEXs = 2, 4, 8, and 12. As a preprocessing step, non-rigid registration of the acquired low NEX images (NEXs = 2, 4, 8) and NEXs = 12 images was performed. A residual dense network (RDN) was used for training. A low NEX image was used as the input to the RDN, and the NEX12 image was used as the correct image. For quantitative evaluation, we measured the signal-to-noise ratio (SNR), peak SNR, and structural similarity index measure of the original image and the image obtained by RDN. The NEX2 results are presented as an example. The SNR of the cortex was 10.4 for NEX2, whereas the SNR of the image reconstructed with RDN for NEX2 was 32.1. (The SNR NEX12 was 19.6) In addition, the PSNR in NEX2 was significantly increased to 35.4 ± 2.0 compared to the input image and to 37.6 ± 2.9 compared to the reconstructed image (p = 0.05). The SSIM in NEX2 was 0.78 ± 0.05 compared to the input image and 0.91 ± 0.05 compared to the reconstructed image (p = 0.0003). Furthermore, NEX2 succeeded in reducing the shooting time by 83%. Therefore, in preclinical 7T MRI, supervised learning between the NEXs using RDNs can potentially improve the image quality of low NEX images and shorten the acquisition time.

Objectives Endoscopic balloon dilation (EBD) is an effective treatment for intestinal strictures in Crohn's disease (CD). However, restenosis often occurs and requires repeat EBD or surgery. Previous studies have seldom examined restenosis with respect to stricture diameter, leaving the factors contributing to post‐EBD restenosis unclear. Our retrospective study indicated that complete mucosal healing significantly reduces restenosis after EBD in CD‐related small intestinal strictures. This prospective study aimed to validate these findings by accurately measuring stricture diameters in patients with CD. Methods We conducted a single‐center prospective study of patients with CD and small intestinal strictures. The patients underwent an EBD session between June 2022 and December 2023. Stricture diameters were measured using a calibrated small‐caliber‐tip transparent hood. Multivariate analysis was performed to identify factors influencing stricture progression. Results This study included 41 patients (33 men). The number of strictures detected between sessions increased from 159 to 170. The average diameter of all strictures and the narrowest stricture per patient showed slight increases. However, 73% of patients experienced stricture progression. The presence of ulcers between sessions was identified as a significant risk factor for stricture progression (odds ratio 7.59, p = 0.031). Patients achieving complete mucosal healing demonstrated a significant increase in the narrowest stricture diameter (+1.5 mm, p = 0.00089). Conclusions Complete mucosal healing is crucial for preventing stricture progression after EBD in patients with CD‐related small intestinal strictures.

Wearable technologies for functional whole brain imaging in freely moving animals would advance our understanding of cognitive processing and adaptive behavior. Fluorescence imaging can visualize the activity of individual neurons in real time, but conventional microscopes have limited sample coverage in both the width and depth of view. Here we developed a novel head-mounted laser camera (HLC) with macro and deep-focus lenses that enable fluorescence imaging at cellular resolution for comprehensive imaging in mice expressing a layer- and cell type-specific calcium probe. We visualized orientation selectivity in individual excitatory neurons across the whole visual cortex of one hemisphere, and cell assembly expressing the premotor activity that precedes voluntary movement across the motor cortex of both hemispheres. Including options for multiplex and wireless interfaces, our wearable, wide- and deep-imaging HLC technology could enable simple and economical mapping of neuronal populations underlying cognition and behavior.

Background: Biliary tract cancer (BTC) is an aggressive malignancy with limited therapeutic options and a poor prognosis. CD73 is upregulated under hypoxic conditions and promotes tumor progression. However, its clinical role in BTC and interaction with tumor-infiltrating lymphocytes (TILs) remain unclear. This study aimed to elucidate the association between CD73 expression and prognosis in BTC, as well as its impact on the tumor microenvironment (TME) and TILs. Methods: This retrospective study included 100 patients who underwent curative BTC surgery at Hokkaido University Hospital between 2018 and 2023. Formalin-fixed tumor specimens were analyzed using DeepPathFinder™ (biomy Inc., Tokyo, Japan), an AI-based digital pathology platform enabling objective quantification of CD73 expression and lymphocyte infiltration within tumoral (T) and stromal (S) compartments. Immunohistochemistry for CD3, CD8, Foxp3, and CD163 was used to identify T-cell subsets and macrophages. Associations between CD73, TIL subsets, and overall survival (OS) were assessed using the Kaplan–Meier, Cox regression, and Spearman correlation analyses. Results: High T-CD73 expression was associated with shorter OS (hazard ratio [HR] = 1.97, p = 0.041), whereas S-CD73 showed no prognostic relevance. Conversely, high S-TIL density was correlated with improved survival (HR = 0.49, p = 0.032). T-CD73 expression was negatively correlated with stromal CD3+ and CD8+ T-cell densities, indicating selective suppression of stromal cytotoxic T-lymphocyte (CTL) infiltration. No significant correlations were observed between Foxp3+ T cells and CD163+ M2 macrophages. Conclusions: CD73 upregulation in tumor cells impairs stromal CTL and TIL activity, leading to a poor prognosis. Spatial distribution, rather than total TIL number, better reflects effective anti-tumor immunity.