Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity

Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan

Kogetsu A., Isono M., Aikyo T., et al. Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan. Research Involvement and Engagement 9, 107 (2023); https://doi.org/10.1186/s40900-023-00515-5.Background: Although stakeholder involvement in policymaking is attracting attention in the fields of medicine and healthcare, a practical methodology has not yet been established. Rare-disease policy, specifically research priority setting for the allocation of limited research resources, is an area where evidence generation through stakeholder involvement is expected to be effective. We generated evidence for rare-disease policymaking through stakeholder involvement and explored effective collaboration among stakeholders. Methods: We constructed a space called ‘Evidence-generating Commons’, where patients, family members, researchers, and former policymakers can share their knowledge and experiences and engage in continual deliberations on evidence generation. Ten rare diseases were consequently represented. In the ‘Commons’, 25 consecutive workshops were held predominantly online, from 2019 to 2021. These workshops focused on (1) clarification of difficulties faced by rare-disease patients, (2) development and selection of criteria for priority setting, and (3) priority setting through the application of the criteria. For the first step, an on-site workshop using sticky notes was held. The data were analysed based on KJ method. For the second and third steps, workshops on specific themes were held to build consensus. The workshop agendas and methods were modified based on participants’ feedback. Results: The ‘Commons’ was established with 43 participants, resulting in positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants. The difficulties faced by patients with rare diseases were classified into 10 categories. Seven research topics were identified as priority issues to be addressed including ‘impediments to daily life’, ‘financial burden’, ‘anxiety’, and ‘burden of hospital visits’. This was performed by synthesising the results of the application of the two criteria that were particularly important to strengthen future research on rare diseases. We also clarified high-priority research topics by using criteria valued more by patients and family members than by researchers and former policymakers, and criteria with specific perspectives. Conclusion: We generated evidence for policymaking in the field of rare diseases. This study’s insights into stakeholder involvement can enhance evidence-informed policymaking. We engaged in comprehensive discussions with policymakers regarding policy implementation and planned analysis of the participants’ experiences in this project

Integrating UAV-SfM and Airborne Lidar Point Cloud Data to Plantation Forest Feature Extraction

A low-cost but accurate remote-sensing-based forest-monitoring tool is necessary for regularly inventorying tree-level parameters and stand-level attributes to achieve sustainable management of timber production forests. Lidar technology is precise for multi-temporal data collection but expensive. A low-cost UAV-based optical sensing method is an economical and flexible alternative for collecting high-resolution images for generating point cloud data and orthophotos for mapping but lacks height accuracy. This study proposes a protocol of integrating a UAV equipped without an RTK instrument and airborne lidar sensors (ALS) for characterizing tree parameters and stand attributes for use in plantation forest management. The proposed method primarily relies on the ALS-based digital elevation model data (ALS-DEM), UAV-based structure-from-motion technique generated digital surface model data (UAV-SfM-DSM), and their derivative canopy height model data (UAV-SfM-CHM). Following traditional forest inventory approaches, a few middle-aged and mature stands of Hinoki cypress (Chamaecyparis obtusa) plantation forests were used to investigate the performance of characterizing forest parameters via the canopy height model. Results show that the proposed method can improve UAV-SfM point cloud referencing transformation accuracy. With the derived CHM data, this method can estimate tree height with an RMSE ranging from 0.43 m to 1.65 m, equivalent to a PRMSE of 2.40&ndash;7.84%. The tree height estimates between UAV-based and ALS-based approaches are highly correlated (R2 = 0.98, p &lt; 0.0001), similarly, the height annual growth rate (HAGR) is also significantly correlated (R2 = 0.78, p &lt; 0.0001). The percentage HAGR of Hinoki trees behaves as an exponential decay function of the tree height over an 8-year management period. The stand-level parameters stand density, stand volume stocks, stand basal area, and relative spacing are with an error rate of less than 20% for both UAV-based and ALS-based approaches. Intensive management with regular thinning helps the plantation forests retain a clear crown shape feature, therefore, benefitting tree segmentation for deriving tree parameters and stand attributes

Integrating UAV-SfM and Airborne Lidar Point Cloud Data to Plantation Forest Feature Extraction

A low-cost but accurate remote-sensing-based forest-monitoring tool is necessary for regularly inventorying tree-level parameters and stand-level attributes to achieve sustainable management of timber production forests. Lidar technology is precise for multi-temporal data collection but expensive. A low-cost UAV-based optical sensing method is an economical and flexible alternative for collecting high-resolution images for generating point cloud data and orthophotos for mapping but lacks height accuracy. This study proposes a protocol of integrating a UAV equipped without an RTK instrument and airborne lidar sensors (ALS) for characterizing tree parameters and stand attributes for use in plantation forest management. The proposed method primarily relies on the ALS-based digital elevation model data (ALS-DEM), UAV-based structure-from-motion technique generated digital surface model data (UAV-SfM-DSM), and their derivative canopy height model data (UAV-SfM-CHM). Following traditional forest inventory approaches, a few middle-aged and mature stands of Hinoki cypress (Chamaecyparis obtusa) plantation forests were used to investigate the performance of characterizing forest parameters via the canopy height model. Results show that the proposed method can improve UAV-SfM point cloud referencing transformation accuracy. With the derived CHM data, this method can estimate tree height with an RMSE ranging from 0.43 m to 1.65 m, equivalent to a PRMSE of 2.40–7.84%. The tree height estimates between UAV-based and ALS-based approaches are highly correlated (R2 = 0.98, p 2 = 0.78, p < 0.0001). The percentage HAGR of Hinoki trees behaves as an exponential decay function of the tree height over an 8-year management period. The stand-level parameters stand density, stand volume stocks, stand basal area, and relative spacing are with an error rate of less than 20% for both UAV-based and ALS-based approaches. Intensive management with regular thinning helps the plantation forests retain a clear crown shape feature, therefore, benefitting tree segmentation for deriving tree parameters and stand attributes

Joining of alumina with an alumina–zirconia insert under low mechanical pressure

Two alumina pipes were joined with an alumina–20 mass% zirconia composite insert for 4 and 8 h at 1650 °C and 1700 °C under a low mechanical pressure of 0.05 MPa. Although plate-like voids were observed along the interfaces in the specimens joined at 1650 °C, such voids were replaced with smaller round pores in specimens bonded at 1700 °C owing to local plastic deformation of the insert at the joint interfaces. In addition, the zirconia grains of the insert were deeply incorporated into alumina grains in the parent alumina at the interfaces at 1700 °C. Because of these microstructural effects, the specimens joined at 1700 °C showed relatively high flexural strengths both at room temperature and at 1200 °C that were close to that of the parent alumina, and most of the specimens were fractured from the parent alumina

A case of resected hepatocellular carcinoma with gallbladder metastasis

Abstract Background Advanced hepatocellular carcinoma (HCC) can often spread as intrahepatic metastases. Extrahepatic metastasis (e.g., lung, lymph nodes, and bones) is rare, and gallbladder metastasis from HCC is extremely rare. Case presentation A 66-year-old woman who presented with right hypochondrial pain was referred to our hospital for further examination of a liver tumor. The blood chemistry data showed elevated levels of serum α-fetoprotein (AFP) (3730 ng/mL), protein induced by vitamin K absence or antagonist II (PIVKA-II) (130 mAU/mL), and carcinoembryonic antigen (CEA) (358.6 ng/mL). Hepatitis B surface antigen and hepatitis C virus antibody were negative. Dynamic computed tomography (CT) showed a tumor measuring 12 × 7 cm in the right lobe of the liver. This tumor was contrast-enhanced in the hepatic arterial phase and then became less dense than the liver parenchyma in the portal phase. A well-enhanced tumor was found in the gallbladder. No regional lymph nodes were enlarged. Contrast-enhanced magnetic resonance imaging (MRI) demonstrated that the liver tumor showed a pattern of early enhancement and washout. The gallbladder tumor was also detected as an enhanced mass. Endoscopic retrograde cholangiography (ERC) showed compression of the left hepatic duct due to the liver tumor. The patient was diagnosed with simultaneous HCC and gallbladder cancer. Right hepatic trisectionectomy and caudate lobectomy with extrahepatic bile duct resection were performed. Histopathological examination of the resected liver specimen showed a poorly differentiated HCC cell component with a trabecular and solid growth, and diffuse invasion of the portal vein. The same tumor cells were found in the gallbladder, but no continuity with the liver tumor was identified. Immunohistochemistry of the liver tumor and gallbladder was positive for AFP, Glypican 3, and CK7, and negative for CK19. The final pathological diagnosis was the gallbladder metastasis from HCC. A follow-up diagnostic image 33 months after surgery showed a mass in the upper lobe of the left lung. The patient underwent left upper lobectomy. Postoperative pathology revealed that the lung lesion was a metastasis of HCC. The patient was still alive with lung metastasis and was being treated with a molecular-targeting drug in good health 42 months after the initial surgery. Conclusions The standard treatment for advanced HCC with extrahepatic metastases is molecularly targeted drugs, but surgery is also an option if the lesion can be resected en bloc without remnants