Conventionally, the effects of mean stress on fatigue strength of welded structure are regarded to be small. However, based on fatigue damage experience occurring in ship structures, it is obvious ...that the effect of mean stress on fatigue strength should be large. This relates to the large change of mean stress condition associated with the change in loading conditions during ship operations. In this study, fatigue damage experienced in the end connections of side longitudinal stiffeners of single-hull very large crude oil carriers (SHVLCC) were investigated to understand the effects of mean stress on fatigue strength. The fatigue evaluation method which considers the effect of mean stress was also examined. This method was verified by the evaluation of existing data on fatigue tests and residual stress measurements. This method was confirmed to be effective in understanding the occurrence tendency of fatigue damage in ship structures by its evaluation. This method was applied to the example of actual fatigue damage in the end connections of side longitudinal stiffeners of midsize double-hull tanker to demonstrate the effectiveness of the method.
The multi-disciplinary approach involving imaging, multi-agent chemotherapy, meticulous surgical procedures, and careful postoperative care has facilitated an increase in the use of limb-sparing ...surgery for pediatric osteosarcoma. Osteosarcoma usually occurs around the metaphysis of the distal femur or proximal tibia and needs wide excision with the adjacent joint and replacement by a megaprosthesis. The recent advancement in imaging modalities and surgical techniques supports joint-preservation surgery (JPS), involving the preservation of the adjacent epiphysis, for select patients following careful assessment of the tumor margins and precise tumor excision. An advantage of this surgery is that it maintains the adjacent joint and preserves the growth of the residual epiphysis, which provides excellent limb function. Various reconstruction options are available, including allograft, tumor-devitalized autograft, vascularized fibula graft, distraction osteogenesis, and custom-made implants. However, several complications are inevitable with these options, such as loosening, non-union at the host-graft junction, infection, fracture, implant loosening, breakage, deformity, limb-length discrepancy related to the reconstruction methods, or patient growth in pediatric osteosarcoma. Surgeons should fully understand the advantages and disadvantages of this procedure. In this review, we discuss the concept of JPS, types of reconstruction methods, and current treatment outcomes. It is our opinion that the further analysis by multi-institutional setting is necessary to clarify long-term outcomes and establish global guidelines on the indications and surgical procedure for JPS.
Osteoporosis is becoming a global health issue due to increased life expectancy. However, it is difficult to detect in its early stages owing to a lack of discernible symptoms. Hence, screening for ...osteoporosis with widely used dental panoramic radiographs would be very cost-effective and useful. In this study, we investigate the use of deep learning to classify osteoporosis from dental panoramic radiographs. In addition, the effect of adding clinical covariate data to the radiographic images on the identification performance was assessed. For objective labeling, a dataset containing 778 images was collected from patients who underwent both skeletal-bone-mineral density measurement and dental panoramic radiography at a single general hospital between 2014 and 2020. Osteoporosis was assessed from the dental panoramic radiographs using convolutional neural network (CNN) models, including EfficientNet-b0, -b3, and -b7 and ResNet-18, -50, and -152. An ensemble model was also constructed with clinical covariates added to each CNN. The ensemble model exhibited improved performance on all metrics for all CNNs, especially accuracy and AUC. The results show that deep learning using CNN can accurately classify osteoporosis from dental panoramic radiographs. Furthermore, it was shown that the accuracy can be improved using an ensemble model with patient covariates.
Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours ....
Bone defect reconstruction with artificial materials may produce good functional recovery in the short term. Over time, the durability of artificial materials becomes an issue, and therefore, ...artificial materials cannot be considered a permanent solution to reconstruction. For long-term outcomes, the goal is to regain function, permanence, and form that are as close to normal as possible. Thus, physiological materials are desirable for use in reconstruction.
Biological reconstruction involves the use of materials that are modified in vivo following reconstruction of bone defects. The goal is to achieve bone union, bone revival and remodeling, with biointegration of soft tissue and bone. Allograft use has been the mainstay of bone defect reconstruction in most parts of the world, although in some countries like Japan, allogeneic bone is difficult to obtain due to socio-religious concerns. Therefore, we developed new biological reconstruction techniques to overcome this problem.
Bone derived from distraction osteogenesis is autologous bone, which must be an ideal reconstruction material for its biological affinity, strength, resilience, and immunity to infection. When applying this method to patients with malignant disease however, it is important to preserve as much of the local soft tissue as possible, and the clinician must be especially careful of infection and callus formation. Liquid nitrogen treatment of tumor-bearing bone produces equal, if not better, bone revitalization compared to other forms of treatment to date. Reconstruction with liquid nitrogen-treated bone involves resecting the diseased bone and returning it to the body following liquid nitrogen treatment (free-freezing method). Another method involves dislocating the joint proximal to the tumor, or cutting the bone while the distal side remains attached to the body and the limb inverted and treated with liquid nitrogen (pedicle freezing method). When both methods are possible, the pedicle freezing method is preferable since it is performed with minimal osteotomy.
Our recent research has looked into the possible role of adipose-derived stem cells in promoting bone fusion and revitalization. This method has produced promising results for the future of biological reconstruction.
Computational screening is one of the fundamental techniques in drug discovery. Each compound in a chemical database is bound to the target protein in virtual, and candidate compounds are selected ...from the binding scores. In this work, we carried out combinational computation of docking simulation to generate binding poses and molecular mechanics calculation to estimate binding scores. The coronavirus infectious disease has spread worldwide, and effective chemotherapy is strongly required. The viral 3-chymotrypsin-like (3CL) protease is a good target of low molecular-weight inhibitors. Hence, computational screening was performed to search for inhibitory compounds acting on the 3CL protease. As a preliminary assessment of the performance of this approach, we used 51 compounds for which inhibitory activity had already been confirmed. Docking simulations and molecular mechanics calculations were performed to evaluate binding scores. The preliminary evaluation suggested that our approach successfully selected the inhibitory compounds identified by the experiments. The same approach was applied to 8820 compounds in a database consisting of approved and investigational chemicals. Hence, docking simulations, molecular mechanics calculations, and re-evaluation of binding scores including solvation effects were performed, and the top 200 poses were selected as candidates for experimental assays. Consequently, 25 compounds were chosen for in vitro measurement of the enzymatic inhibitory activity. From the enzymatic assay, 5 compounds were identified to have inhibitory activities against the 3CL protease. The present work demonstrated the feasibility of a combination of docking simulation and molecular mechanics calculation for practical use in computational virtual screening.
Recent clinical studies have suggested that inhalation of incense smoke (IS) may result in impaired lung function and asthma. However, there is little experimental evidence to link IS with airway ...hyperresponsiveness (AHR) and bronchial epithelial barrier function. Using mouse and cell culture models, we evaluated the effects of IS exposure on AHR, expression of multiple epithelial tight junction (TJ)- and adherens junction-associated mRNAs and proteins in the lungs, and the barrier function of bronchial epithelial cells assessed by transepithelial electronic resistance (TEER). Exposure of BALB/c mice to IS increased AHR and inflammatory macrophage recruitment to BALF; reduced claudin-1, -2, -3, -7, -10b, -12, -15, and -18, occludin, zonula occludens-1 ZO-1, and E-cadherin mRNA expression; and caused discontinuity of claudin-2 and ZO-1 protein immunostaining in lung tissue. IS extract dose-dependently decreased TEER and increased reactive oxygen species production in bronchial epithelial cell cultures. Treatment with N-acetyl-L-cysteine, but not glucocorticosteroids or long-acting β
-agonists, prevented the detrimental effects of IS. IS exposure can be problematic for respiratory health, as evidenced by AHR, increased recruitment of inflammatory macrophages and disruption of TJ proteins in the lung, and damage to epithelial barrier function. However, antioxidants may be useful for the treatment of IS-induced airway dysfunction.
In this study, we used panoramic X-ray images to classify and clarify the accuracy of different dental implant brands via deep convolutional neural networks (CNNs) with transfer-learning strategies. ...For objective labeling, 8859 implant images of 11 implant systems were used from digital panoramic radiographs obtained from patients who underwent dental implant treatment at Kagawa Prefectural Central Hospital, Japan, between 2005 and 2019. Five deep CNN models (specifically, a basic CNN with three convolutional layers, VGG16 and VGG19 transfer-learning models, and finely tuned VGG16 and VGG19) were evaluated for implant classification. Among the five models, the finely tuned VGG16 model exhibited the highest implant classification performance. The finely tuned VGG19 was second best, followed by the normal transfer-learning VGG16. We confirmed that the finely tuned VGG16 and VGG19 CNNs could accurately classify dental implant systems from 11 types of panoramic X-ray images.
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a high-risk infectious pathogen. In the proposed model of respiratory failure, SARS-CoV down-regulates its receptor, angiotensin-converting ...enzyme 2 (ACE2), but the mechanism involved is unknown. We found that the spike protein of SARS-CoV (SARS-S) induced TNF-α-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain. The modulation of TACE activity by SARS-S depended on the cytoplasmic domain of ACE2, because deletion mutants of ACE2 lacking the carboxyl-terminal region did not induce ACE2 shedding or TNF-α production. In contrast, the spike protein of HNL63-CoV (NL63-S), a CoV that uses ACE2 as a receptor and mainly induces the common cold, caused neither of these cellular responses. Intriguingly, viral infection, judged by real-time RT-PCR analysis of SARS-CoV mRNA expression, was significantly attenuated by deletion of the cytoplasmic tail of ACE2 or knock-down of TACE expression by siRNA. These data suggest that cellular signals triggered by the interaction of SARS-CoV with ACE2 are positively involved in viral entry but lead to tissue damage. These findings may lead to the development of anti-SARS-CoV agents.
Purpose
Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of restricting MET with ...oral-recombinant methioninase (o-rMETase) and the DNA methylation inhibitor, azacitidine (AZA) on a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model.
Methods
The osteosarcoma PDOX models were randomized into five treatment groups of six mice: control; doxorubicin (DOX) alone; AZA alone; o-rMETase alone; o-rMETase-AZA combination. Tumor size and body weight were measured during the 14 days of treatment.
Results
We found that tumor growth was arrested only by the o-rMETase–AZA combination treatment, as tumors with this treatment exhibited tumor necrosis with degenerative change.
Conclusion
This study suggests that o-rMETase-AZA combination has clinical potential for patients with chemoresistant osteosarcoma.
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