CASS FRACTURE TESTS USING FLAT PLATE SPECIMENS WITH A SURFACE FLAW

ABSTRACT JSME rules for fitness for service have flaw acceptance rules for cast austenitic stainless steel (CASS) pipes. They allow applying two-parameter and elastic-plastic fracture mechanics methods using Z-factor. However they do not clearly describe whether limit load method is applicable for the case of no or low thermal aging condition. The authors performed tensile fracture tests using flat plate specimens with a surface flaw and confirmed that limit load method is applicable in the conditions of no thermal aging and even fully saturated thermal aging with high ferrite number. Also the plate with a shallow flaw ruptured at the critical stress defined by nominal stress at rupture-flaw depth curve in the code case which was determined by the similar flat plate tests of stainless steel or nickel alloy specimens. These results will be reflected to the revision of the code

Machine learning methods can more efficiently predict prostate cancer compared with prostate-specific antigen density and prostate-specific antigen velocity

BackgroundProstate-specific antigen (PSA)–based screening for prostate cancer has been widely performed, but its accuracy is unsatisfactory. To improve accuracy, building an effective statistical model using machine learning methods (MLMs) is a promising approach.MethodsData on continuous changes in the PSA level over the past 2 years were accumulated from 512 patients who underwent prostate biopsy after PSA screening. The age of the patients, PSA level, prostate volumes, and white blood cell count in urinalysis were used as input data for the MLMs. As MLMs, we evaluated the efficacy of three different techniques: artificial neural networks (ANNs), random forest, and support vector machine. Model performance was evaluated using area under the receiver operating characteristic curve (AUC) and compared with the PSA level and the conventional PSA–based parameters: PSA density and PSA velocity.ResultsWhen using two annual PSA testing, all receiver operating characteristic curves of the three MLMs were above the curve for the PSA level, PSA density, and PSA velocity. The AUCs of ANNs, random forest, and support vector machine were 0.69, 0.64, and 0.63, respectively. Those values were higher than the AUCs of the PSA level, PSA density, and PSA velocity, 0.53, 0.41, and 0.55, respectively. The accuracies of the MLMs (71.6% to 72.1%) were also superior to those of the PSA level (39.1%), PSA density (49.7%), and PSA velocity (54.9%). Among the MLMs, ANNs showed the most favorable AUC. The MLMs showed higher sensitivity and specificity than conventional PSA–based parameters. The model performance did not improve when using three annual PSA testing.ConclusionThe present retrospective study results indicate that machine learning techniques can predict prostate cancer with significantly better AUCs than those of PSA density and PSA velocity

Quantification of (–)-Epigallocatechin-3-gallate Inhibition of Anaplastic Thyroid Cancer Cell Line Adhesion and Proliferation Using Real-time Cell Analysis

Anaplastic thyroid cancer (ATC) has a poor prognosis because of immediate metastasis. Several studies in humans and animals have suggested that the ingestion of green tea or its active ingredient (–)-epigallocatechin-3-gallate (EGCG) may decrease the risk of cancer. Using a recently developed real-time cell analysis (RTCA) system, we have shown previously that EGCG inhibits cell migration and the invasion of oral cavity cancers by suppressing matrix metalloproteinases. In the present study we used RTCA to investigate the effects of EGCG on cell adhesion to fibronectin-coated plates using three cancer cell lines: one ATC cell line (TCO-1) and two poorly differentiated oral squamous cell carcinomas (OSCCs) cell lines (SAS and HO-1-u-1; originating from the tongue and floor of the mouth, respectively). EGCG (50µM) inhibited the adhesion of all three cell lines. In addition to its effects on cell adhesion, 50µM EGCG inhibited the cell proliferation of TCO-1 cells. Furthermore, EGCG decreased αV integrin (ITGAV) mRNA levels in all three cell lines, suggesting that EGCG inhibits the cell adhesion and proliferation of OSCC and ATC cells via suppression of integrin expression. Therefore, EGCG represents a useful dietary constituent or a lead compound for counteracting metastasis of oral cavity cancers and thyroid cancers

A Study on In-Service Training for Improving the Professional Development of Teaching Physical Education in Elementary Schools

First this study aims to clarify how elementary school teachers of B Prefecture informed their learning outcomes by in-service training of physical activities to their school colleagues. Secondary this study aims to clarify how in-service training of physical activities at D Elementary School in C City influenced improving school teachers' teaching in physical education. The results are summarized as following points. 1. Elementary school teachers of B Prefecture informed their learning outcomes to their school colleagues through 'in-service training meetings within their schools' or 'their daily job'. 2. D Elementary School Teachers have taught new teaching materials as learning outcomes from ‘in-service training meetings of physical activities'. 3. Teacher X and Teacher Y learned teaching method and subject knowledge of physical education by team teaching experiences with PE coordinators as 'their daily job'. Teacher L learned the way of making unit plan, modification of activities and management of his class from his elder colleague K by dialogues about teaching in physical education as 'their daily job'. 4. It seems that it is important we make mentors' daily supports to mentees between PE coordinators and other school teachers.本研究の一部は,科学研究費補助金(基盤B)課題研究番号24300212の補助によ

Downregulation of Neuronal and Dendritic Connexin36-Made Electrical Synapses Without Glutamatergic Axon Terminals in Spinal Anterior Horn Cells From the Early Stage of Amyotrophic Lateral Sclerosis

Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1G93A) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases. We found that in the lamina IX of the lumbar spinal cord from wild type mice, about half of the Cx36 puncta existed independently of chemical synapse markers, while the rest coexisted with chemical synapse markers, such as vesicular glutamate transporter 1 (VGLUT1), which is a glutamatergic axon terminal marker, and/or glutamate decarboxylase 65 (GAD65), which is a GABAergic axon terminal marker. Cx36 single or Cx36/GAD65 double positive puncta, but not VGLUT1-containing puncta, were preferentially decreased on neuronal and dendritic surfaces of the anterior horn cells in the early stage of SOD1G93A ALS mice. Moreover, in five human autopsied sporadic ALS cases with bulbar or upper limb onset, Cx36 immunoreactivity was diminished in the proximal dendrites and neuropils of well-preserved large motor neurons in the lumbar anterior horns. These findings suggest that downregulation of neuronal and dendritic Cx36 in the spinal anterior horns commonly occurs from the early stage of hereditary and sporadic ALS. Cx36-made electrical synapses without glutamatergic signaling appear to be more vulnerable than other chemical synapses and electrical synapses with glutamatergic signaling in the early stage of motor neuron degeneration, suggesting involvement of Cx36-made electrical synapses in the pathogenesis of human ALS

Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study

Risk stratification for the prognosis of patients with chemoresistant urothelial cancer treated with pembrolizumab

The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil-to-lymphocyte ratio. The median OS times (95% confidence intervals [CIs]) for the low-, intermediate-, and high-risk groups (discovery cohort) were not yet reached (NYR) (NYR–19.1), 6.8 mo (5.8-8.9), and 2.3 mo (1.2-2.6), respectively. The HRs (95% CI) for OS in the low- and intermediate-risk groups vs the high-risk group were 0.07 (0.04-0.11) and 0.23 (0.15-0.37), respectively. The objective response rates for in the low-, intermediate-, and high-risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first-line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab-treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design

Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

OBJECTIVES: This multicentre retrospective study in Japan aimed to assess the retention of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors (JAKi), and to clarify the factors affecting their retention in a real-world cohort of patients with rheumatoid arthritis. METHODS: The study included 6666 treatment courses (bDMARD-naïve or JAKi-naïve cases, 55.4%; tumour necrosis factor inhibitors (TNFi) = 3577; anti-interleukin-6 receptor antibodies (aIL-6R) = 1497; cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) = 1139; JAKi=453 cases). The reasons for discontinuation were divided into four categories (ineffectiveness, toxic adverse events, non-toxic reasons and remission); multivariate Cox proportional hazards modelling by potential confounders was used to analyse the HRs of treatment discontinuation. RESULTS: TNFi (HR=1.93, 95% CI: 1.69 to 2.19), CTLA4-Ig (HR=1.42, 95% CI: 1.20 to 1.67) and JAKi (HR=1.29, 95% CI: 1.03 to 1.63) showed a higher discontinuation rate due to ineffectiveness than aIL-6R. TNFi (HR=1.28, 95% CI: 1.05 to 1.56) and aIL-6R (HR=1.27, 95% CI: 1.03 to 1.57) showed a higher discontinuation rate due to toxic adverse events than CTLA4-Ig. Concomitant use of oral glucocorticoids (GCs) at baseline was associated with higher discontinuation rate due to ineffectiveness in TNFi (HR=1.24, 95% CI: 1.09 to 1.41), as well as toxic adverse events in JAKi (HR=2.30, 95% CI: 1.23 to 4.28) and TNFi (HR=1.29, 95%CI: 1.07 to 1.55). CONCLUSIONS: TNFi (HR=1.52, 95% CI: 1.37 to 1.68) and CTLA4-Ig (HR=1.14, 95% CI: 1.00 to 1.30) showed a higher overall drug discontinuation rate, excluding non-toxicity and remission, than aIL-6R.Ebina K., Etani Y., Maeda Y., et al. Drug retention of biologics and Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. RMD open 9, (2023); https://doi.org/10.1136/rmdopen-2023-003160

EMPRESS. III. Morphology, Stellar Population, and Dynamics of Extremely Metal Poor Galaxies (EMPGs): Are EMPGs Local Analogs of High-zz Young Galaxies?

We present the morphology and stellar population of 27 extremely metal poor galaxies (EMPGs) at $z\sim0$ with metallicities of 0.01--0.1 Z$_{\odot}$. We conduct multi-component surface brightness (SB) profile fitting for the deep Subaru/HSC $i$-band images of the EMPGs with the {\sc Galfit} software, carefully removing the SB contributions of tails. We find that the EMPGs with a median stellar mass of $\log(M_{*}/{\rm M}_{\odot})=6.0$ have a median S{\'e}rsic index of $n=1.1$ and a median effective radius of $r_{\rm e}=200$ pc, suggesting that typical EMPGs have very compact disk. We compare the EMPGs with $z\sim6$ galaxies and local galaxies on the size-mass ($r_{\rm e}$-$M_*$) diagram, and identify that the majority of the EMPGs have a $r_{\rm e}$-$M_*$ relation similar to $z\sim0$ star-forming galaxies rather than $z\sim6$ galaxies. Not every EMPG is a local analog of high-$z$ young galaxies in the $r_{\rm e}$-$M_*$ relation. A spectrum of one pair of EMPG and tail, so far available, indicates that the tail is dynamically related to the EMPG with a median velocity difference of $\Delta V=101\pm32$ km s$^{-1}$. This moderately-large $\Delta V$ cannot be explained by the dynamics of the tail, but likely by the infall on the tail. For the first time, we may identify the metal-poor star-forming system just now infalling into the tail.Comment: ApJ in Pres

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals