Bioinspired mineralization of calcium carbonate in peptide hydrogel acting as a multifunctional three-dimensional template

Biomineralization is the process by which biominerals, minerals composed of bioinorganic matter possessing a controlled structure and orientation and a biomacromolecular assembly with an ordered structure that acts as a 3D template, are formed. In this study, we investigated the fabrication of organic/inorganic hybrid gels by bioinspired mineralization in peptide hydrogels. An Ac-(VHVEVS)3-CONH2 peptide was used as a multifunctional template with a mineral source supply capability and structural controllability that facilitates the formation of hydrogels via self-assembly. Hydrogels with varying viscoelastic strengths were prepared from the designed peptide by controlling the concentration of calcium ions added as cross-linking agents. The peptide hydrogel supplied carbonate anions as the mineral source through the hydrolysis of urea and mineralized CaCO3 with controlled morphology on the peptide network. With increases in the concentration of calcium ions added, the morphology of the mineralized CaCO3 changed from a fibrous structure to a thin film. This implies that the nucleation and growth mechanisms of CaCO3 formed by bioinspired mineralization were affected not only by the morphology and supply rate of the mineral source by the peptide network acting as a multifunctional template, but also by the viscoelastic strength of the hydrogel that served as a 3D reaction field

Partial arch replacement of type A aortic dissection after thoracic endovascular aortic repair for type B dissection

Abstract Background Stent graft-induced new entry (SINE), defined as the stent graft-induced formation of a new entry point for blood to enter an area, is increasingly being observed after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection worldwide. We herein describe a case of Stanford type A aortic dissection due to proximal SINE after TEVAR for Stanford type B dissection. Case presentation This case involved a 58-year-old man with type A aortic dissection due to SINE. Six years previously, he had developed severe back pain and was diagnosed with type B aortic dissection after computed tomography examination. Because the primary entry was positioned at the descending aorta, we conducted TEVAR for exclusion of the entry with a GORE TAG conformable thoracic aortic graft. He was thereafter followed by our hospital. Six years later, he developed jaw pain and was examined at another hospital. He was transferred to our hospital because of the possibility of type A dissection. Computed tomography revealed type A aortic dissection with proximal site SINE. Emergency partial arch replacement was conducted, and he was discharged on postoperative day 27. Because the entry was at the lesser curve of the arch, we excluded the entry and conducted partial arch replacement. Conclusions In this case, proximal SINE occurred 6 years after TEVAR. Because SINE may occur even in the long term after TEVAR, careful follow-up is necessary

Total thoracoscopic lung segmentectomy of anterior basal segment of the right lower lobe (RS8) for NSCLC stage IA (case report)

Abstract A 69-year-old woman with a pulmonary nodule in anterior basal segment of the right lower lobe (RS8) was referred to our department. The diameter of the tumor was 12 mm, and it had increased over a few months. First, video-assisted thoracoscopic lung surgery (VATS) biopsy of the pulmonary nodule was carried out. Frozen section examination of this nodule confirmed the diagnosis of bronchioloalveolar carcinoma (BAC). Segmentectomy of RS8 with lower mediastinal node dissection (ND2a-1) was performed. The intersegmental plane was identified using the intersegmental veins as landmarks and the demarcation between the resected (inflated) and preserved (collapsed) lungs. Electrocautery at 70 watts was used to divide the intersegmental plane. A vessel sealing system was used to seal and cut the pulmonary arteries. Postoperative histopathological examination revealed that the tumor was T1aN0M0 BAC, and the minimal distance between the surgical margin and the tumor edge was 15 mm. The patient was discharged from hospital on postoperative day 5 without any complications.</p

Morphological changes in functional tricuspid regurgitation on contrast-enhanced computed tomography correlates to tricuspid regurgitation grade

PURPOSE: To examine the relationship between each severity of functional tricuspid regurgitation (FTR) and morphological evaluation on contrast-enhanced computed tomography (CT). METHODS: Forty-five patients underwent contrast-enhanced CT. Tricuspid annulus area (TAA), tricuspid annulus circumference (TAC), right ventricular volume (RVV), and the distances between the tips and bases of the papillary muscles were measured on contrast-enhanced CT in diastole and systole. The patients were classified organized into 4 groups by TR grade measured by transthoracic echocardiography (none+trivial: 26, mild: 6, moderate: 6, severe: 7), and the data were compared among the groups. RESULTS: In parameters measured on contrast-enhanced CT images, TAA, TAC, and the distances between the tips of the anterior and posterior papillary muscles in both diastole and systole and RVV in diastole were significantly different among the groups (p0.40). The septal papillary muscle could not be identified in about 1/3 (35.6%) of cases. CONCLUSIONS: TAA, TAC, RVV, and the distance between the tips of the anterior and posterior papillary muscles measured on contrast-enhanced CT images had relatively positive correlations with TR grade

Evaluating Cellularity Estimation Methods: Comparing AI Counting with Pathologists’ Visual Estimates

The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurate genetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a “gold standard” TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist’s visual assessment (p0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smaller than that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy

Abstract While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately. Clinical Trial Registration: UMIN000009322

Zebrafish and Mouse α2,3-Sialyltransferases Responsible for Synthesizing GM4 Ganglioside*

We have previously reported that fish pathogens causing vibriosis specifically adhere to GM4 on the epithelial cells of fish intestinal tracts (Chisada, S., Horibata, Y., Hama, Y., Inagaki, M., Furuya, N., Okino, N., and Ito, M. (2005) Biochem. Biophys. Res. Commun. 333, 367–373). To identify the gene encoding the enzyme for GM4 synthesis in the fish intestinal tract, a phylogenetic tree of vertebrate ST3GalVs, including Danio rerio and Oryzias latipes, was generated in which two putative subfamilies of fish ST3GalVs were found. Two putative ST3GalVs of zebrafish (zST3GalV-1 and -2), each belonging to different subfamilies, were cloned from the zebrafish cDNA library. Interestingly, zST3GalV-1 synthesized GM3 (NeuAcα2–3Galβ1–4Glcβ1-1′Cer) but not GM4, whereas zSTGalV-2 synthesized both gangliosides in vitro when expressed in CHO-K1 and RPMI1846 cells. Flow cytometric analysis using anti-GM4 antibody revealed that the transformation of RPMI1846 cells with zST3GalV-2 but not zST3GalV-1 cDNA increased the cell-surface expression of GM4. Whole mount in situ hybridization showed that the zST3GalV-2 transcript was strongly expressed in the gastrointestinal tract, whereas zST3GalV-1 was expressed in the brain and esophagus but not gastrointestinal tract in 3-day post-fertilization embryos. It has long been a matter of controversy which enzyme is responsible for the synthesis of GM4 in mammals. We found that three isoforms of mouse ST3GalV (mST3GalV) having different N-terminal sequences can synthesize GM4 as well as GM3 when expressed in RPMI1846 and CHO-K1 cells. Furthermore, mST3GalV knock-out mice were found to lack GM4 synthase activity and GM4 in contrast to wild-type mice. These results clearly indicate that zST3GalV-2 and mST3GalV are the enzymes responsible for the synthesis of GM4 in zebrafish and mice, respectively