Black-Box Test Case Generation from TFM Module Interface Specications and Usage Statistics

In this thesis, we propose a black-box testing method that derives important test cases by including usage statistics, and enables a product manager to make a release decision with the rationale, the important use cases specified in the usage statistics are tested and have no error. First, we propose a method to specify components with Trace Function Method (TFM) module interface specifications. Then, we propose a way to associate module usage statistics with the TFM module interface specification. Finally, we propose a method to generate a prioritized list of black-box test cases for component testing and integration testing from the TFM module interface specification with usage statistics

スイ カセイ ノウホウ ニ タイスル フククウキョウカ ノホウ イ フンゴウジュツ : イヘキ トノ ユチャク オ ゼンテイ ト シナイ アンゼンナ ジュツシキ

A forty seven-year-old male who had been in clinical follow-up for a pancreatic pseudocystunderwent a laparoscopic cystogastrostomy through the lesser peritoneal sac in 1996. Thisprocedure is performed by creating a cystotomy and posterior gastrotomy through whichan Endo GIATM is applied. The mouth of cystogastrostomy is closed using continuous suturesby Endo STITCHTM. This approach does not rely on adhesions between the pseudocyst andposterior wall of the stomach, and offers clear advantages over previously described techniquesin the management of pancreatic pseudocyst

Safety and Utility of Endoscopic Removal of Common Bile Duct Stones in the Elderly

We investigated the safety and utility of endoscopic removal of common　bile duct stones (CBDS) in the elderly. In all, 253 patients with CBDS who　underwent endoscopic retrograde cholangiopancreatography (ERCP) between January　2007 and December 2011 at Showa University Hospital were evaluated retorspectively. The median age of the patients was 75 years ; thus, we divided patients　into two groups, those aged ≥ 75 years (Group A ; n ＝ 134) and those aged ＜75 years (Group B ; n ＝ 119). Patients in Group A had significantly higher rates　of endoscopic sphincterotomy in palliative ERCP (24.8% vs. 10.7%; p ＝ 0.008) and　palliative removal of CBDS (34.8% vs. 20.9%; p ＝ 0.015) than patients in Group　B. However, the median dose of flunitrazepam was significantly lower for patients　in Group A than Group B (1 vs. 1.4 mg, respectively ; p ＜ 0.001). The rate of use　of pentazocine (18.5% vs. 54.7%; p ＜ 0.001) and scopolamine butylbromide (6.2%　vs. 23.9%; p ＜ 0.01) was significantly lower in Group A patients, whereas the use　of glucagon was significantly higher in this group (43.8 vs. 15.4%; p ＜ 0.001).　There were no significant differences in the rate of successful endoscopic removal　of CBDS, treatment time, complications, and the recurrence of CBDS between the　two groups. Endoscopic removal of CBDS in the elderly is a safe procedure with　good outcomes if the appropriate treatment is selected

Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors

Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs). Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo. Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody. Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

Doripenem (DRPM) is a relatively new drug belonging to the carbapenem antibiotic group. We hypothesized that the pharmacological characteristics of DRPM could make it useful in the treatment of severe acute pancreatitis (SAP). We investigated the usefulness of continuous regional arterial infusion (CRAI) with DRPM and protease inhibitors for SAP. Two hundred and forty-two patients with SAP were admitted to Showa University Hospital between November 2002 and June 2013. Of these, 53 patients were treated with CRAI with carbapenem antibiotics and nafamostat mesilate (NM), a serine protease inhibitor, via the celiac and superior mesenteric arteries. Clinical outcomes were evaluated retrospectively in 34 patients treated with DRPM and 19 patients undergoing non-DRPM therapy (meropenem n=11, imipenem n=6; biapenem n=2). The median time to commencement of oral intake was significantly shorter in the DRPM than non-DRPM group (9 vs 14 hospital days, respectively; P<0.01). In addition, the rate of walled-off necrosis in the DRPM group tended to be lower than in the non-DRPM group (37.5 vs 64.7%, respectively, P=0.069). The results of the present study suggest that CRAI with DRPM and NM for SAP could have equivalent therapeutic effects to CRAI with other carbapenem antibiotics and NM

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.Oyama S., Ebina K., Etani Y., et al. A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. Scientific Reports 12, 18102 (2022); https://doi.org/10.1038/s41598-022-23152-6

Features of and Mechanisms Underlying Insulitis In aly/aly Male Mice as an Animal Model of Autoimmune Pancreatitis: Activation of CD11c+, CD4+, and Th2 Cells and Predominant Destruction of β-cells

Diabetes mellitus (DM) is observed in patients with autoimmune pancreatitis (AIP). The development of DM in AIP is believed to be due to blood flow obstruction of the endocrine gland that accompanies pancreatitis, as well as injury to the islets caused by inflammation. The latter is called insulitis and the detailed mechanisms underlying its development are not yet clear. The aim of the present study was to elucidate the mechanisms involved in the development of insulitis in AIP using aly mice as an animal model of AIP: results in aly/aly male mice, as the AIP group, were compared with those inaly/+ male mice as a control group. Mice in both groups were killed between 16 and 48 weeks of age, and pancreatitis and insulitis were evaluated histologically. Inflammatory and endocrine cells were evaluated by immunofluorescence staining with anti-CD4, anti-CD8, anti-CD11b, and anti-CD11c antibodies, as well as immunohistochemical analyses using insulin and glucagon antibodies. Plasma levels and the pancreatic content of interferon (IFN)-γ (as a Th1-secreted cytokine) and interleukin (IL)-4 (as a Th2-secreted cytokine) were determined. Pancreatitis was seen in aly/aly mice from 16 weeks of age and it developed gradually thereafter. Insulitis also developed gradually and was seen in mice after 24 weeks of age in association with a decrease in the number of islets. CD11c+ cells and CD4+ T cells were seen to infiltrate into the islets. Although the number of β-cells decreased with time, the number of α-cells was maintained until mice were 48 weeks of age. IFN-γ content peaked in mice at 16 weeks of age and declined rapidly from 20 weeks. There were two peaks in IL-4 content, one at 16 weeks and the other at 32 weeks, suggesting an association between IL-4 content and advanced insulitis after 32 weeks. In conclusion, the results suggest that insulitis in AIP is induced predominantly by the infiltration of CD11c+ cells and CD4+ T cells into the islets, and progression is facilitated by the imbalance of the activation of Th2 rather than Th1. Furthermore, insulitis in AIP predominantly involves β-cells rather than α-cells

Scan-less confocal phase imaging based on dual-comb microscopy

Confocal laser microscopy (CLM) is a powerful tool in life science research and industrial inspection because it offers two-dimensional optical sectioning or three-dimensional imaging capability with micrometer depth selectivity. Furthermore, scan-less imaging modality enables rapid image acquisition and high robustness against surrounding external disturbances in CLM. However, the objects to be measured must be reflective, absorptive, scattering, or fluorescent because the image contrast is given by the optical intensity. If a new image contrast can be provided by the optical phase, scan-less CLMcan be further applied for transparent non-fluorescent objects or reflective objects with nanometer unevenness by providing information on refractive index, optical thickness, or geometrical shape. Here, we report scan-less confocal dual-comb microscopy offering a phase image in addition to an amplitude image with depth selectivity by using an optical frequency comb as an optical carrier of amplitude and phase with discrete ultra-multichannels. Our technique encodes confocal amplitude and phase images of a sample onto a series of discrete modes in the optical frequency comb with well-defined amplitude and phase to establish a one-to-one correspondence between image pixels and comb modes. The technique then decodes these images from comb modes with amplitude and phase. We demonstrate confocal phase imaging with milliradian phase resolution under micrometer depth selectivity on the millisecond timescale. As a proof of concept, we demonstrate the quantitative phase imaging of standing culture fixed cells and the surface topography of nanometer-scale step structures. Our technique for confocal phase imaging will find applications in three-dimensional visualization of stacked living cells in culture and nanometer surface topography of semiconductor objects

ジュニア期スポーツにおけるサプリメント摂取の現状とその影響

近年、多種類のサプリメントが簡単に入手できる時代となり、子どもたちも自由に気軽に購入できる状況におかれている。また、スポーツ界ではアンチ・ドーピング活動が盛んとなっているが、サプリメント摂取はアスリートにとってドーピング的意味合いを持つことを忘れてはならない。そこで、我々は、まず子どものサプリメントの摂取状況を文献的に考察し、次いで全国の日本スポーツ少年団に登録する子どもを対象としたサプリメント等に関するアンケート調査を実施した結果を踏まえて、子どもたちのサプリメント摂取やドーピングに関する今後の課題を検討した。その結果、サプリメント摂取はスポーツに対する効果だけでなく、ドーピング問題も含めた教育をジュニア期から行い、専門家による早急な対応の必要性が明らかとなった

Black-Box Test Case Generation from TFM Module Interface Specications and Usage Statistics

In this thesis, we propose a black-box testing method that derives important test cases by including usage statistics, and enables a product manager to make a release decision with the rationale, "the important use cases specified in the usage statistics are tested and have no error." First, we propose a method to specify components with Trace Function Method (TFM) module interface specifications. Then, we propose a way to associate module usage statistics with the TFM module interface specification. Finally, we propose a method to generate a prioritized list of black-box test cases for component testing and integration testing from the TFM module interface specification with usage statistics.</p