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BACKGROUND Kawasaki disease (KD) is an acute febrile illness with systemic vasculitides, mostly affecting infants and young children. The etiology of KD is still unclear; however, altered gut microbiota have been recently implicated as a contributing factor for the development of vasculitis. METHODS We conducted an age- and gender-matched case-control study on 50 patients and 200 control subjects to search for potential factors leading to intestinal dysbiosis associated with KD. Data were analyzed using conditional multivariable logistic regression. RESULTS Previous antibiotic administration was associated with the patients who developed KD (odds ratio [OR] 11.7, 95% confidence interval [CI] 4.7-29.1, P < 0.0001), but not other variables, including breastfeeding and group nursery. In subgroup analyses, cesarean birth was indicated as an associated factor in addition to previous antibiotic administration in infants under 12 months of age (OR: 8.0, 95% CI: 1.8-34.4, P = 0.005), but not in older children. CONCLUSIONS The association between previous antibiotic administration and the onset of KD was demonstrated. Antibiotics may contribute to the development of KD by affecting the intestinal microbiota in infants and young children.

Background Maxacalcitol was approved in Taiwan in 2018 as the first active vitamin D3 injection for secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis. However, no data from any clinical study with maxacalcitol in Taiwanese patients is available. Objectives This analysis aimed to evaluate the profiles of parathyroid hormone (PTH) and calcium (Ca) concentrations in Taiwanese SHPT patients on hemodialysis and maxacalcitol. Methods We developed population pharmacokinetic (PK) and pharmacodynamic (PD) models using a modeling and simulation approach. The data for these analyses were obtained from two studies: a clinical pharmacology study in Japanese patients and an ethnic comparison study in healthy Japanese and -Taiwanese volunteers. We then conducted a simulation study with a PK-PD model comprising the PK and PD models developed here. Results Serum maxacalcitol concentration profile was modeled using a two-compartment model that took into consideration the distribution of concentrations below the lower limit of quantification. An ethnic difference in clearance was included in the PK model as a covariate. A PD model that used a PTH/Ca feedback loop best described the observed data. There were no significant differences in Ca or PTH concentrations between Taiwanese and Japanese based on the simulation results from our PK-PD model, even though maxacalcitol exposure was approximately 40% higher in Taiwanese than in Japanese. Conclusions On the basis of these population PK and PD analyses and the clinical study conducted in Japan, there is no clinically relevant difference between Taiwanese and Japanese in terms of serum Ca or PTH levels.

In mismatch repair (MMR) immunohistochemistry, four MMR proteins’ staining pattern reveals which particular gene may be defective. However, in the null phenotype, four MMR proteins are lost; consequently, it will be challenging to assume the target gene by immunohistochemistry and to determine whether deficient MMR was sporadic or germline. A 70-year-old man underwent right hemicolectomy with the diagnosis of ascending colon cancer. The postoperative histopathology revealed the diagnosis of medullary carcinoma and the loss of all four MMR expressions in immunohistochemistry. The mutation analysis using a peripheral blood sample showed no germline mutations in the four genes. This clinical case presents an unusual colon carcinoma that showed a MMR protein immunohistochemistry null phenotype. The cause of expression loss of MMR proteins can be explained by the loss of MLH1 and MSH2 functions associated with somatic loss of function mutations, functional loss in all four MMR proteins associated with somatic loss of function mutations, or Lynch-like syndrome. Correct interpretation and accumulation of relevant cases are necessary to unveil unusual cases in the era of universal screening.

Security and privacy in cloud systems are critical. To address security and privacy concerns, many security patterns, privacy patterns, and non-pattern-based knowledge have been reported. However, knowing which pattern or combination of patterns to use in a specific scenario is challenging due to the sheer volume of options and the layered cloud stack. To deal with security and privacy in cloud services, this study proposes the cloud security and privacy metamodel (CSPM). CSPM uses a consistent approach to classify and handle existing security and privacy patterns. In addition, CSPM is used to develop a security and privacy awareness process to develop cloud systems. The effectiveness and practicality of CSPM is demonstrated via several case studies.

Krabbe disease involves the accumulation of neurotoxic metabolites due to lysosomal galactocerebrosidase enzyme deficiency, which results in widespread demyelination of central and peripheral nerves. Generally, Krabbe disease presents as spastic paraplegia with a slow progressive course; however, some cases may show clinical symptoms similar to those of chronic inflammatory demyelinating polyneuropathy (CIDP). No previously reported studies have investigated the efficacy of intravenous immunoglobulin (IVIg) for treating Krabbe disease, and reporting a case involving IVIg treatment may be informative in the clinical setting. A 14-year-old girl who developed Guillain-Barré syndrome-like limb weakness was administered IVIg, and her limb weakness improved. At 16 years old, she developed abnormal sensory perception and weakness of both upper limbs. A nerve conduction study revealed demyelination, which led us to suspect CIDP. IVIg was administered, and her symptoms gradually improved. A nerve biopsy, enzyme activity, and genetic test results indicated adult Krabbe disease. In some cases, IVIg may be an effective treatment for Krabbe disease.

Background A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this “DNA adductome approach” in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. Aim Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. Materials and methods From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. Results Seven DNA adducts, including modified bases, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. Conclusions We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

This study aimed to identify factors that influence the decision to take safety regulatory actions in routine signal management based on spontaneous reports. For this purpose, we analyzed the safety signals identified from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and related information. From the signals that the FDA identified in the FAERS between 2008 1Q and 2014 4Q, we selected 216 signals for which regulatory action was or was not taken. Characteristics of the signals were extracted from the FAERS quarterly reports that give information about what signals were identified from the FAERS and what actions were taken for them, and the FAERS data released in the same quarter when the signal was published. Univariate and multivariable logistic regression analysis was used to assess the relationship between the characteristics of each of the signals and the decision on regulatory action. As a result of the univariate logistic regression analysis, we selected 5 factors (positive rechallenge, number of cases accumulated in the last one-year period before the signal indication, previous awareness, serious outcome, risk for special populations) to include in the multivariable logistic regression model (p

Objective To study the efficacy of phosphodiesterase-5 inhibitor tadalafil in attenuating adverse events after low-dose-rate brachytherapy for prostate cancer. Methods This was a randomized open-label trial, conducted at two institutions. Prostate cancer patients undergoing low-dose-rate brachytherapy were randomly assigned to receive tadalafil (study group) or tamsulosin (control group). The primary endpoint was International Prostate Symptom Score for subjective evaluation of lower urinary tract symptoms. Uroflowmetry, postvoid residual urine volume, and Sexual Health Inventory for Men score were the secondary endpoints. Each clinical variable was evaluated during a follow-up period of 1 year after low-dose-rate brachytherapy. Results A total of 107 patients were enrolled in this study, with a final total of 96 patients analyzed. The mean total International Prostate Symptom Score changes at 1, 3, 6, 9, and 12 months after low-dose-rate brachytherapy were +7.4, +7.1, +4.7, +1.5, and +0.8, respectively, in the tamsulosin group, and +8.5, +9.2, +6.4, +4.1, and +1.6, respectively, in the tadalafil group. There were no statistically significant differences in International Prostate Symptom Score with the exception of the score at 9-month follow-up. Moreover, there were no statistically significant differences in any of the uroflowmetry or postvoid residual urine volume findings. The Sexual Health Inventory for Men score in the tadalafil group was significantly higher than that in the tamsulosin group at 6, 9, and 12 months after low-dose-rate brachytherapy. Conclusions Tadalafil could be an effective option for the management of lower urinary tract symptoms after low-dose-rate brachytherapy.

Endurance exercise training enhances muscle fat oxidation while concomitantly reducing carbohydrate (glycogen) utilization during exercise, thereby delaying the onset of fatigue. This study examined the effects of dietary fat restriction on endurance training-induced metabolic adaptations in rat skeletal muscle. Male Sprague-Dawley rats were placed on either a control diet (CON: 19.2% protein, 21.6% fat, and 59.2% carbohydrate as a percentage of total energy) or a fat-restricted diet (FR: 21.5% protein, 2.4% fat, and 76.1% carbohydrate as a percentage of total energy) for 4 wks. Half the rats in each dietary group performed daily 6-h swimming exercise (two 3-h sessions separated by 45 min of rest) on 5 days each wk. Endurance training significantly increased the expression of β-hydroxyacyl CoA dehydrogenase (βHAD), a key enzyme of fat oxidation, and pyruvate dehydrogenase kinase 4 (PDK4), an inhibitory regulator of glycolytic flux, in the skeletal muscle of rats fed the CON diet. However, such endurance training-induced increases in muscle βHAD and PDK4 were partially suppressed by the FR diet, suggesting that a FR diet may diminish the endurance training-induced enhancement of fat oxidation and reduction in glycogen utilization during exercise. We then assessed the muscle glycogen utilization rate during an acute bout of swimming exercise in the trained rats fed either the CON or the FR diet and consequently found that rats fed the FR diet had a significantly higher muscle glycogen utilization rate during exercise compared with rats fed the CON diet. In conclusion, dietary fat restriction may attenuate the endurance training-induced metabolic adaptations in skeletal muscle.

Business-to-Business (B-to-B) software development companies develop services to satisfy their customers’ requirements. Developers should prioritize customer satisfaction because customers greatly influence agile software development. However, satisfying current customer’s requirements may not fulfill actual users or future customers’ requirements because customers’ requirements are not always derived from actual users. To reconcile these differences, developers should identify conflicts in their strategic plan. This plan should consider current commitments to end users and their intentions as well as employ a data-driven approach to adapt to rapid market changes. A persona models an end user representation in human-centered design. Although previous works have applied personas to software development and proposed data-driven software engineering frameworks with gap analysis between the effectiveness of commitments and expectations, the significance of developers’ commitment and quantitative decision-making are not considered. Developers often do not achieve their business goal due to conflicts. Hence, the target of commitments should be validated. To address these issues, we propose Data-Driven Persona Retrospective (DDR) to help developers plan future releases. DDR, which includes the Persona Significance Index (PerSI) to reflect developers’ commitments to end users’ personas, helps developers identify a gap between developers’ commitments to personas and expectations. In addition, DDR identifies release situations with conflicts based on PerSI. Specifically, we define four release cases, which include different situations and issues, and provide a method to determine the release case based on PerSI. Then we validate the release cases and their determinations through a case study involving a Japanese cloud application and discuss the effectiveness of DDR.

Purpose Bioelectrical impedance analysis (BIA) has been used recently to measure the body water of patients with acute heart failure. We used BIA in this study to better understand, and possibly identify a predictive marker for, perioperative water behavior in cardiac surgery patients. Methods We measured body water and studied its behavior in 44 patients undergoing surgery for cardiac valvular disease at our hospital. Measurements included the levels of extracellular water (ECW), intracellular water (ICW), and total body water, the edema index (EI), and the ratio of ECW to total body water. The first measured EI was defined as the “preoperative EI” and the maximum as the “peak EI”. Results A negative correlation was found between the preoperative EI and the preoperative estimated glomerular filtration rate (eGFR) (R = 0.644, p R = 0.625, p R = 0.366, p R = 0.464, p = 0.026). Conclusion The EI is possibly a predictive marker for perioperative water management in cardiac surgery.

TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1–5 and 8–12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

The third-generation meteorological satellites equipped with highly-improved imagers provide a huge amount of Earth observation data. Himawari-8 is the first unit of the Japan Meteorological Agency’s third generation of geostationary satellites. After its starting operation in 2015, there are several websites that provide remotely sensed images in real time. However, it is hard to develop a real-time and full-resolution website, due to the large amount of data to be handled. Himawari-8 real-time web is only one website that provides full-resolution remotely sensed images in real time. To reduce network traffic and increase the access speed of it from other countries out of Japan, mirror websites of each country are needed. In this paper, we propose a cost-effective mirroring system for the Himawari-8 real-time web. A mirroring model is introduced to avoid the problem of big data processing in the mirror websites. We adopt a file copy tool based on high-performance and flexible protocol (HpFP) to transfer meteorological satellite data from the Himawari-8 real-time web to the mirror websites. Our first target is Thailand, one of the most disaster-prone countries in South-East Asia. The mirror website is set up at an institution in Thailand connected via collaborative international networks, e.g., Japan Gigabit Network (JGN) and Asia Pacific Advanced Network (APAN). The results show that the proposed mirroring system is able to overcome the big data issue by reducing the central processing unit (CPU) usage in the mirror website and transferring remotely sensed image files at high speed over international networks even under packet loss conditions. This suggests that our mirroring system has a potential for deployment in other Asian and Oceanian countries.

The 79 years old man was referred to our department due to high value of serum prostate specific antigen (39.54 ng/ml). The magnetic resonance imaging demonstrated diffuse low signal at his prostate. Bone scintigraphy revealed multiple metastatic lesion. Needle biopsy was performed for definite diagnosis. Systemic purpura showed after prostate needle biopsy although he had noticed local purpura at his back before the examination. He was diagnosed as disseminated intravascular coagulation (DIC) syndrome due to advanced prostate cancer. Treatment with anti-DIC therapy, blood transfusion, subcutaneous injection of degarelix acetate settled the DIC. Abiraterone hydrochloride and prednisolone was added as we confirmed Gleason score5+4 in the pathological examination. He has been alive for 15 months after diagnosis without desease progression.

Aim Ample evidence indicates that gastrin‐releasing peptide receptor (GRPR)–expressing neurons play a critical role in the transmission of acute itch. However, the pathophysiology of spinal mechanisms underlying intractable itch such as psoriasis remains unclear. In this study, we aimed to determine whether itch‐responsive GRPR+ neurons contribute to the spinal transmission of imiquimod (IMQ)‐induced psoriatic itch. Methods To generate a psoriasis model, C57BL/6J mice received a daily topical application of 5% IMQ cream on their shaved back skin for 7‐10 consecutive days. GRP+ neurons were inhibited using Cre‐dependent expression of Gi‐designer receptors exclusively activated by designer drugs (DREADDs), while GRPR+ neurons were ablated by intrathecal administration of bombesin‐saporin. Results Repeated topical application of IMQ elicited psoriasis‐like dermatitis and scratching behaviors. The mRNA expression levels of GRP and GRPR were upregulated in the cervical spinal dorsal horn (SDH) on days 7 and 10 after IMQ application. Either chemogenetic silencing of GRP+ neurons by Gi‐DREADD or ablation of GRPR+ neurons significantly attenuated IMQ‐induced scratching behaviors. Conclusion The GRP‐GRPR system might be enhanced in the SDH, and itch‐responsive GRPR+ neurons largely contribute to intractable itch in a mouse model of psoriasis., The aim of this study was to determine whether itch‐responsive gastrin‐releasing peptide receptor (GRPR)–expressing neurons contribute to the spinal transmission of imiquimod (IMQ)‐induced psoriatic itch. We found that mRNA expression of GRP and GRPR was upregulated in the cervical spinal dorsal horn after IMQ application, and IMQ‐induced psoriatic itch was suppressed by either chemogenetic inhibition of GRP+ neurons or ablation of GRPR+ neurons.

Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2-weeks of cast immobilization in chronic post-cast pain (CPCP) rat model. In the present study, we also demonstrated dystrophy-like changes, both peripheral nociceptive signals and activation of the central pain pathway in CPCP rats. This was done by the following methods: (1) vascular permeability (Evans blue dye) and inflammatory- and oxidative stress-related messenger RNA (mRNA) changes (real-time quantitative polymerase chain reaction); (2) immunofluorescence of pERK and/or c-Fos expression in the spino-parabrachio-amygdaloid pathway; and (3) blockade of nociceptive-related signals using sciatic nerve block (SNB). Furthermore, we demonstrated tactile allodynia using an optogenetic method in a transgenic rat line (W-TChR2V4), cold allodynia using the acetone test, and activation of dorsal horn neurons in the chronic phase associated with chronic mechanical hyperalgesia using c-Fos immunofluorescence. In addition, we showed that nociceptive signals in the acute phase are involved in chronic pathological pain-like behaviors by studying the effects of SNB. Thus, we conclude that physical disuse contributes to dystrophy-like changes, spontaneous pain-like behavior, and chronic widespread pathological pain-like behaviors in CPCP rats after 2 weeks of cast immobilization.

BACKGROUND Intraoperative cardiac arrest (ICA) has a reported frequency of 1 in 10,000 anesthetics but has a much higher estimated incidence in orthotopic liver transplantation (OLT). Single-center studies of ICA in OLT are limited by small sample size that prohibits multivariable regression analysis of risks. METHODS Utilizing data from 7 academic medical centers, we performed a retrospective, observational study of 5296 adult liver transplant recipients (18-80 years old) between 2000 and 2017 to identify the rate of ICA, associated risk factors, and outcomes. RESULTS ICA occurred in 196 cases (3.7% 95% confidence interval [CI], 3.2-4.2) and mortality occurred in 62 patients (1.2%). The intraoperative mortality rate was 31.6% in patients who experienced ICA. In a multivariable generalized linear mixed model, ICA was associated with body mass index (BMI)

Endovascular therapy is developing, but not all aneurysms are completely obliterated even by using the techniques such as stent-assisted coiling or a flow diverter. To predict the aneurysm-occlusion status after stent-assisted coiling, the authors applied computational fluid dynamics (CFD) using porous media modeling to propose a new technique with the double porous media settings, one of which is a porous media setting for a coiled aneurysm and another of which is that for an intracranial stent. CFD with double porous media settings using preoperative aneurysm geometry may be useful for simulating the hemodynamic changes in intracranial aneurysms after stent-assisted coiling.

Background Coronary artery evaluation by virtual histological intravascular ultrasonography (VH-IVUS) late in Kawasaki disease (KD) shows intimal thickening, calcification, fatty components, and necrosis of regressed coronary artery lesions (CALs). However, it is not clear when these VH-IVUS findings start to occur. Therefore, we evaluated coronary arteries using VH-IVUS in patients with early-stage KD and tried to determine whether these atherosclerotic findings on VH-IVUS were different from that in patients with late-stage KD. Methods Eighteen patients with KD aged between 1 and 32 years who had CALs and underwent cardiac catheterization between January 1, 2008 and December 31, 2014 were included. They were divided into 2 groups—those with the disease for 10 years (group B). VH-IVUS findings were compared between the groups. The coronary arteries were divided based on coronary angiography findings into normal, regressed (dilated CALs regressed to a normal size), and aneurysmal lesions. The Wilcoxon signed-rank test was used in the statistical analysis. Results In both regressed and aneurysmal lesions, marked intimal proliferation and atherosclerotic findings (fibro-fatty and necrotic core lesions) were observed. In addition, there was no difference in the area percentage of atherosclerosis between the groups. Conclusions VH-IVUS revealed that atherosclerotic-like findings exist in CALs in patients with KD, even within a year of onset. The findings were almost the same in those with the disease for >10 years. Because there is no histological evidence of atherosclerosis in KD, these VH-IVUS findings may indicate complex histological findings of KD. Nevertheless, early interventions to help reduce the risk factors of atherosclerosis may be required in these patients.

Aim/Purpose: Although many computer science measures have been proposed, visualizing individual students’ capabilities is difficult, as those measures often rely on specific tools and methods or are not graded. To solve these problems, we propose a rubric for measuring and visualizing the effects of learning computer programming for elementary school students enrolled in computer science education (CSE), which is independent of the programming language being used. Background: In this research, we proposed a rubric based on existing CSE standards and criteria having a programming education-learning goal. We then applied this rubric to actual lessons to visualize the educational effects. Methodology: The proposed new rubric for teaching computer programming, based on existing standards and criteria, was applied to fourth- and sixth-grade students in Japan. We assessed which skills were cultivated through quizzes before and after the teaching. Contribution: This paper contributes on how to make and utilize a rubric for programming education in computer science. We evaluated and visualized the proposed rubric’s learning effects on children and found that our proposed rubrics are independent of any particular method or tool. Findings: The results of this survey are twofold: (1) we proposed a rubric of programming education in computer science, independent of the programming tools used and (2) we succeeded in visualizing students’ learning stages by applying the proposed rubric to programming education conducted in a Japanese elementary school. Recommendations for Practitioners: Evaluating educational effects in CSE is important. In particular, graded assessments of learner abilities can reveal individual characteristics. This research is useful for assessing CSE because it focuses specifically on programming education. Recommendation for Researchers: The rubric’s suggestions and quality improvements in CSE help learners assess their learning progress and will clarify the cultivated computer science skills. Impact on Society: This research evaluates CSE based on a rubric in the programming education field. Future Research: Future work is needed to improve the proposed rubric’s quality and relevance. Also, this rubric should be applied to many classes to increase the number of evaluations and analyses.

BACKGROUND Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. METHODS Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. RESULTS The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17, RANTES, INF-γ, and TNF-α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. CONCLUSIONS These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.

Traditional recommendation algorithms based on collaborative filtering suffer from a data sparsity problem. The emergence of online social network has enriched the user's information, realizing a new way to solve recommendation tasks. Social-aware recommendation algorithms can effectively alleviate the data sparsity problem and improve the performance of recommendation systems. Despite the success of these algorithms, they have some common limitations. Most algorithms assume that social networks are homogeneous, with similar preferences among connected users. However, users may only share similar preferences in some aspects. Besides, different friends affect the user's preference in different levels. And this influence of friends on users' preference should be adaptive. Even close friends may have different influences in different decision-making processes. For example, a user may trust a friend in “travel” but distrust this friend in “music” because this friend had more travel experiences. Motivated by the above limitations, we designed a neural network model called adaptive attention neural network for social recommendation (ANSR) to study the interaction between a user and his or her social friends as well as infer the complex influence of the user's social relationships on the user's preferences. By utilizing the co-attention mechanism, we can not only extract the user's special attention to certain aspects of their friends but also determine the adaptive influences of different friends on the user. When the user interacts with different items, different attention weights will be assigned to the user and his or her friends, respectively. In addition, we also utilize network embedding to learn more efficient features of each user and incorporate these features into the ANSR to enhance the recommendation results. Moreover, we also conduct extensive experiments on four different real-world datasets and demonstrate that our proposed method performs better on all datasets compared with the state-of-the-art baseline methods.

Objective Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in a subset of malignant cells. However, it remains unknown whether ROR1 is targetable in malignant mesothelioma (MM). Therefore, in this study, we investigated the effects of ROR1 inhibition in mesothelioma cells. Materials and methods Growth inhibition, colony formation, apoptosis, and mRNA/protein levels using siRNA-transfected MM cells were evaluated. Cluster analysis using Gene Expression Omnibus repository of transcriptomic information was also performed. Results Our results indicated that in three (H2052, H2452, and MESO-1) among four MM cell lines, ROR1 inhibition had anti-proliferative and apoptotic effects and suppressed the activation of AKT and STAT3. Although growth inhibition by siROR1 was minimal in another mesothelioma cell line (H28), colony formation was significantly suppressed. Microarray, quantitative polymerase chain reaction, and Western blot analyses showed that there were differences in the suppression of mRNA and proteins between H2452 and H28 cells transfected with siROR1 compared with those transfected with control siRNA. Cluster analysis further showed that MM tumors had relatively high ROR1 expression, although the cluster in them was different from that in MM cell lines. Thymidylate synthase, a target of pemetrexed, was downregulated in H2452 cells transfected with siROR1. Accordingly, a combination of pemetrexed with siROR1 was found to be effective in the three MM cell lines we studied. Conclusion Our findings may provide novel therapeutic insight into the treatment of advanced MM.

Software reliability is an essential characteristic for ensuring the qualities of software products. Predicting the potential number of bugs from the beginning of a development project allows practitioners to make the appropriate decisions regarding testing activities. In the initial development phases, applying traditional software reliability growth models (SRGMs) with limited past data does not always provide reliable prediction result for decision making. To overcome this, herein, we propose a new software reliability modeling method called a deep cross-project software reliability growth model (DC-SRGM). DC-SRGM is a cross-project prediction method that uses features of previous projects’ data through project similarity. Specifically, the proposed method applies cluster-based project selection for the training data source and modeling by a deep learning method. Experiments involving 15 real datasets from a company and 11 open source software datasets show that DC-SRGM can more precisely describe the reliability of ongoing development projects than existing traditional SRGMs and the LSTM model.

An 84-year-old woman was referred for lower abdominal pain lasting more than six months. Computed tomography showed a left ovarian varicose vein and a peri-uterine venous plexus. Due to suspected pelvic congestion syndrome, left ovarian venography and left ovarian embolization were performed. Blood flowed back through the dilated left ovarian vein and through the uterine venous plexus to the right ovarian vein. Embolization of the left ovarian vein with a sclerosing agent resulted in the disappearance of the venous congestion. Preoperative Visual Analogue Scale was 7, which decreased to 3 after the operation. As a result, improvements in QOL were recognized. Although pelvic congestion syndrome is a treatable disease, its recognition as a urological disease is low. Here, we have reported a case of pelvic congestion syndrome in which symptoms improved with treatment and have discussed its pathophysiology and treatment.

Software reliability is an important characteristic for ensuring the qualities of software products. Predicting the potential number of bugs from the beginning of a development project allows practitioners to make the appropriate decisions regarding testing activities. In the initial development phases, applying traditional software reliability growth models (SRGMs) with limited past data does not always provide reliable prediction result for decision making. To overcome this, herein we propose a new software reliability modeling method called deep cross-project software reliability growth model (DC-SRGM). DC-SRGM is a cross-project prediction method that uses features of previous projects’ data through project similarity. Specifically, the proposed method applies cluster-based project selection for training data source and modeling by a deep learning method. Experiments involving 15 real datasets from a company and 11 open source software datasets show that DC-SRGM can more precisely describe the reliability of ongoing development projects than existing traditional SRGMs and the LSTM model.

The aging population problem is growing worldwide and physical therapists must be able to care for the elderly and injured efficiently. One burden facing physical therapists is determining the Functional Independence Measure (FIM), which measures the level of independence in activities of daily living for the elderly and injured. This measure is used in designing rehabilitation programs. Determining the FIM is a time-consuming task for both physical therapists and rehabilitation patients because it requires an interview. Some researchers have explored estimating FIM using wearable devices; however, it is burdensome for patients to wear such devices continuously. Therefore, we propose a method to estimate FIM motor items automatically using machine learning and sleep sensors. The proposed method classifies patients into three levels of FIM values that are referred to as s-FIM using vital data acquired through sleep sensors, personal data (age, gender, and Body Mass Index), and s-FIM values from the previous day. The results of a one-week study based on 19 patients showed that the proposed method had a mean accuracy of 0.87 for s-FIM motor items. The results were more accurate than continuing to use the s-FIM values determined by the physical therapist without updating them for one week.

Primary hepatic neuroendocrine tumors (PHNETs) are rare in dogs, and limited information exists about the treatment of these tumors. A 12-year-old castrated male French bulldog was presented to our clinic with gastrointestinal signs. Diagnostic tests revealed increased hepatic enzyme levels, a mass in the hepatic quadrate lobe, multiple intrahepatic nodules, and enlarged hepatic hilar lymph nodes. The liver mass was diagnosed cytologically as a malignant epithelial tumor suspected to be of neuroendocrine origin. The dog was treated with single-agent toceranib phosphate (TOC) and survived 25.1 months after the initial presentation. On necropsy, a liver mass was found and was subsequently diagnosed as a PHNET on histopathology. To the best of our knowledge, this is the first report of long-term survival in a dog with PHNET treated with TOC.

To guide practitioners and researchers to design and research Machine Learning (ML) system development processes, we conduct a preliminary literature review on ML system development practices. We identified seven papers and two other papers determined in an ad-hoc review. Our findings include emphasized phases in ML system developments, frequently described ML-specific practices, and tailored traditional practices.

XRISM is an X-ray astronomical mission by the JAXA, NASA, ESA and other international participants, that is planned for launch in 2022 (Japanese fiscal year), to quickly restore high-resolution X-ray spectroscopy of astrophysical objects. To enhance the scientific outputs of the mission, the Science Operations Team (SOT) is structured independently from the instrument teams and the Mission Operations Team. The responsibilities of the SOT are divided into four categories: 1) guest observer program and data distributions, 2) distribution of analysis software and the calibration database, 3) guest observer support activities, and 4) performance verification and optimization activities. As the first step, lessons on the science operations learned from past Japanese X-ray missions are reviewed, and 15 kinds of lessons are identified. Among them, a) the importance of early preparation of the operations from the ground stage, b) construction of an independent team for science operations separate from the instrument development, and c) operations with well-defined duties by appointed members are recognized as key lessons. Then, the team structure and the task division between the mission and science operations are defined; the tasks are shared among Japan, US, and Europe and are performed by three centers, the SOC, SDC, and ESAC, respectively. The SOC is designed to perform tasks close to the spacecraft operations, such as spacecraft planning, quick-look health checks, pre-pipeline processing, etc., and the SDC covers tasks regarding data calibration processing, maintenance of analysis tools, etc. The data-archive and user-support activities are covered both by the SOC and SDC. Finally, the science-operations tasks and tools are defined and prepared before launch., Comment: 42 pages, 7 figures, 8 table, Accepted for Publication in JATIS (SPIE)

We previously reported that consuming a ketogenic diet containing medium-chain triacylglycerols (MCTs) might be a valuable dietary strategy for endurance athletes. However, the long-term safety of the diet has not been established, and there is a concern that a higher intake of MCTs increases the liver triacylglycerol content. In this study, we found that consuming an MCT-containing ketogenic diet for 24 weeks decreased, rather than increased, the liver triacylglycerol concentration and did not aggravate safety-related blood biomarkers in male Wistar rats. Our results may therefore suggest that the long-term intake of a ketogenic diet containing MCTs may have no deleterious effects on physiological functions.

Myeloid/lymphoid neoplasms with PDGFRB rearrangement are a distinct type of myeloid neoplasms that occur in association with rearrangement of PDGFRB at 5q32. The hematological features most often show prominent eosinophilia. We herein report a patient with myeloid/lymphoid neoplasms with PDGFRB rearrangement with t (5;10) (q33;q22) who showed atypical chronic myeloid leukemia-like clinical features without eosinophilia and achieved an optimal response to imatinib. A sequence analysis showed a CCDC6-PDGFRB fusion gene with a new break point in the PDGFRB gene. This is the sixth case of myeloid/lymphoid neoplasm with PDGFRB rearrangement harboring a CCDC6-PDGFRB fusion gene, and it has a new breakpoint in the PDGFRB fusion gene.

The relationship between certain lifestyle habits and schoolchildren’s health has previously been reported on, but the exact pathway of the effects lifestyle habits have on physical/psychosocial health (PPH) has not been investigated nor has the relative influence of different habits on schoolchildren’s health. In this study, schoolchildren were recruited from a primary school in Toyama Prefecture, Japan ( n = 576), and the relevant data were collected in June/July 2017. Path analysis was used to examine the relationships of lifestyle habits and physical fitness with PPH among schoolchildren in grades 1–4 and 5–6. Body weight and total fitness scores were found to be not related to the children’s PPH. The pathway via which lifestyle habits influenced PPH was determined successfully. Among children in grades 1–4, sex ( p < .05), age ( p < .01), and breakfast intake ( p < .05) were related to PPH. Among schoolchildren in grades 5–6, the duration of sleep ( p < .05) was related to PPH. Thus, factors related to schoolchildren’s PPH vary by school grade. The identification of the predictors of the PPH of schoolchildren should inform the design of tailored, grade-specific health promotion interventions in Japanese elementary schools.

Background Recent studies have shown that the systemic inflammatory response induced by cancer leads to cancer progression. Neutrophil-to-lymphocyte ratio (NLR) is the most reliable marker to detect systemic inflammation. In this study, we investigated the significance of NLR in patients with well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification. Methods We retrospectively collected data for patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at six institutions. Clinicopathological factors, recurrence, and immunohistochemical staining of tumor-associated macrophages (TAMs) were analyzed in a total of 55 patients in this study. Results High NLR (>3.41) in patients was significantly associated with higher white blood cell count, higher Ki-67 index, higher mitotic count, higher grade, higher incidence of lymph node metastasis, higher incidence of lymphatic and neural invasion, massive blood loss, and a large number of CD163-expressing TAMs. Recurrence-free survival of patients with high NLR was significantly poorer than that of patients with low NLR. Multivariate analysis identified high NLR, NET Grade 2 (G2) or Grade 3 (G3), and synchronous hepatic resection as independent risk factors for recurrence after curative resection. Conclusions NLR is a promising predictor of recurrence after pancreatectomy that needs to be further investigated and that accumulation of TAMs in the tumor could be one of the causes of NLR elevation.

Factors influencing fallopian tube occlusion in women with a lower genital tract infection remain incompletely elucidated. We evaluated whether a polymorphism in the mannose-binding lectin (MBL) gene at codon 54 influences the occurrence of fallopian tube blockage in relation to exposure to Chlamydia trachomatis. In a case–control study at The Hospital das Clinicas, University of Sao Paulo, Brazil, 75 women with hysterosalpingography-documented tubal occlusion and 75 women with patent fallopian tubes were analyzed for detection of single-nucleotide polymorphism in codon 54 of the MBL gene and for IgG anti-C. trachomatis antibodies in their sera. Both groups were matched for age, race, and sexual variables. Prior exposure to C. trachomatis, as evidenced by the presence of IgG antibodies, was comparable in both groups. Detection of the polymorphic MBL allele was more prevalent in women with blocked tubes (p

Background Treatment with TAS-102 has significantly improved the progression-free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC). Reportedly, the combination of TAS-102 plus bevacizumab extends the median PFS. The present study aimed to confirm the efficacy and safety of TAS-102 plus bevacizumab (biweekly administration) as third-line chemotherapy for patients with mCRC. Methods/design This is a single-arm, open-label, prospective, nonrandomized, multicenter phase II trial conducted in Japan. With a threshold and expected PFS of 2.1 and 3.5 months, respectively, the simulation results showed a sample size of 42 with α = 0.05 (both sides) for 90% power, based on the One-Arm Binomial test using the SWOG statistical tool. If the estimated dropout is 7%-8%, the target sample size is estimated to be 45. The TAS-CC4 study regimen comprised 28-day cycles with biweekly oral administration of TAS-102 (35 mg/m2 twice daily on days 1-5 and 15-19 of every 28-day cycle) and bevacizumab (5.0 mg/kg on days 1 and 15). The primary end point is the PFS; secondary end points include response rate (RR), OS, grade ≥3 neutropenia, and genetic alterations (KRAS/BRAF mutations) in the circulating cell-free DNA. Discussion The present study can contribute to the determination of the effective dosing interval of TAS-102 and bevacizumab in patients with mCRC and is thought to lead to prophylaxis of neutropenia and prolongation of the treatment period.

The internally stacked CuO/Cu2O photoactive layers were prepared by electrodeposition of the Cu2O layer followed by heating in air. The 1.4 eV-p-CuO layer was heteroepitaxially grown on the Cu2O la...