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Driving simulators (DSs) have been widely used to develop advanced driver assistance systems to improve driving safety in vehicles. A major drawback of using DSs is the lack of speed perception while driving. Hence, improvements to speed perception have been recognized as a major priority for enhancing DSs. One approach for achieving better speed perception is to manipulate the human visual space using distorted images in DSs. A previous study revealed that the visual space was distorted subjecting to a visual distance towards an object in a virtual space. Thus, this study aims to obtain optimized image distortions and to evaluate their ability to allow drivers to perceive speed more accurately. A set of computer graphic images representing driving in a straight rural-like road was generated by applying distortions to the original image. The first experiment was conducted to determine the participants’ perceived speeds when viewing the images. Four levels of image distortion were used on seven images representing different speeds. The perceived speed increased with the image distortion, and an equation defining the perceived speed as a function of both image speed and distortion was derived. Another experiment was then conducted to verify whether the images generated using the derived equation could allow drivers to accurately perceive speed. As a result, the optimized image distortion allowed the DS users to accurately determine the image speeds, with an average difference between the perceived and the image speed of 2.7%.

Objectives: Dissection of the No. 11p lymph nodes is technically challenging because of variations in anatomical landmarks. This study aimed to determine the accuracy and efficacy of predicting the dorsal landmark of No. 11p lymph node using three-dimensional computed tomography simulation. Methods: Laparoscopic gastrectomy with No. 11p lymph node dissection with preoperative simulation using three-dimensional computed tomography was performed in 24 patients at our institution from October 2016 to May 2018. Initially, preoperative three-dimensional computed tomography findings with operative videos in these 24 patients were compared. The dorsal landmark was defined as an anatomical structure behind the splenic artery on preoperative three-dimensional computed tomography and operative videos. The dorsal landmark of No. 11p lymph node was divided into four types: (1) splenic vein type, (2) splenic vein and pancreas type, (3) pancreas type, and (4) unclear type. Then, to investigate the efficacy of three-dimensional computed tomography, we compared the clinical and pathological features and surgical outcomes of nine patients who underwent preoperative three-dimensional computed tomography simulation (three-dimensional computed tomography group) and 23 patients who did not undergo three-dimensional computed tomography simulation from August 2014 to September 2016 (non-three-dimensional computed tomography group). All procedures were performed by one surgeon certified by the Endoscopic Surgical Skill Qualification System in Japan. Results: The concordance rate between three-dimensional computed tomography and operative videos of the dorsal landmark using three-dimensional computed tomography was 79% (19/24). The operative time of No. 11p lymph node dissection was significantly shorter in the three-dimensional computed tomography group than in the non-three-dimensional computed tomography group (7.7 versus 15.8 min, P = 0.044). Conclusion: The accuracy of predicting the dorsal landmark of No. 11p lymph node using three-dimensional computed tomography was extremely high. Preoperative simulation with three-dimensional computed tomography was useful in shortening the operative time of No. 11p lymph node dissection.

Inflammatory myofibroblastic tumor (IMT) is a rare but benign entity masquerading as a malignant tumor. We herein report an 18-month-old boy with small bowel wall IMT who presented with intussusception. He was transferred to our hospital with a complaint of abdominal pain and diagnosed with intussusception. On laparotomy, the small bowel wall mass consisted of solid tissue measuring 2.5 × 3.0 cm. The postoperative pathology examination revealed numerous spindle cells arranged in dense bundles with diffuse infiltration of inflammatory cells and tumor involvement of the mucosa and serosa. As the postoperative pathology examination resulted in a diagnosis of IMT and suspected partial resection, small bowel resection and mesenteric lymph node resection were performed two months after the first operation. A pathology examination after the second surgery revealed no evidence of residual IMT and negative findings for metastasis in the regional lymph nodes. IMT is a locally aggressive lesion. The immunophenotypic feature of ALK-1 in particular is associated with a high recurrence rate. Long-term follow-up is absolutely needed. Keywords: Inflammatory myofibroblastic tumour, Small intestine, Child, Intussusception, Anaplastic lymphoma kinase

The beneficial effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on major depressive disorder have been actively studied, but the underlying mechanism remains unknown. The present study examined the involvement of the nucleus accumbens (NAc) dopaminergic systems in behavioral changes in mice fed a diet high in ω-3 PUFAs. Mice fed a diet containing about double the amount of ω-3 PUFAs (krill oil (KO) diet) exerted shorter immobility times in the forced swim test (FST) than mice fed a control diet, containing only α-linolenic acid (ALA) as ω-3 PUFAs. The shorter immobility times were observed in both male and female mice. A dopamine metabolite, 3,4-dihydroxyphenylacetic acid, increased in the NAc in male mice fed the KO diet when compared with those fed the control diet. In addition, dopamine, 3-methoxytyramine, and homovanillic acid increased in the NAc in female mice fed the KO diet. Notably, the effects of the KO diet on the immobility time in the FST were abolished by microinjection of sulpiride, an antagonist of D2-like receptors, into the NAc. A similar microinjection of an antagonist selective for D1-like receptors, SKF83566, also abolished the reduction in immobility in the FST. Moreover, we found that tyrosine hydroxylase-positive cells increased in the ventral tegmental area (VTA) in mice fed the KO diet. These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which a KO diet rich in ω-3 PUFAs reduces the immobility behavior in the mouse FST.

AimsThe prognostic impact of worsening renal function (WRF) in patients with acute heart failure (AHF) remains under debate. Successful decongestion might offset the negative impact of WRF, but little is known about indicators of successful decongestion in the very acute phase of AHF. We hypothesized that decongestion as evaluated by the percent reduction in brain natriuretic peptide (BNP) could identify relevant prognostic implications of WRF in the very acute phase of AHF.Methods and resultsData on 907 consecutive hospitalized patients with AHF in the REALITY-AHF study (age: 78±12 years; 55.1% male) were analyzed. Creatinine and BNP were measured at baseline and 48 hours from admission. WRF was defined as an increase in creatinine >0.3 mg at 48 hours from admission. The primary endpoint was 1-year all-cause mortality. Patients were divided into four groups according to the presence/absence of WRF and a BNP reduction higher/lower than the median: no-WRF/higher-BNP-reduction (n = 390), no-WRF/lower-BNP-reduction (n = 397), WRF/higher-BNP-reduction (n = 63), and WRF/lower-BNP-reduction groups (n = 57). Kaplan-Meier curve analysis showed that the WRF/lower-BNP-reduction group had a worse prognosis than the other groups. In a Cox regression analysis, only the WRF/lower-BNP-reduction group had higher mortality compared to the no-WRF/higher-BNP-reduction group (hazard ratio: 3.34, pConclusionIn the very acute phase of AHF, BNP reduction may aid in identifying relevant prognostic significance of WRF.

Recently, a new rapid assay for the detection of tcdB gene of Clostridioides difficile was developed using the GENECUBE. The assay can directly detect the tcdB gene from stool samples without a purification in approximately 35 minutes with a few minutes of preparation process. We performed a prospective comparative study of the performance of the assay at eight institutions in Japan. Fresh residual stool samples (Bristol stool scale ≥5) were used and comparisons were performed with the BD MAX Cdiff assay and toxigenic cultures. For the evaluation of 383 stool samples compared with the BD MAX Cdiff assay, the sensitivity, and specificity of the two assays was 99.0% (379/383), 98.1% (52/53), 99.1% (327/330), respectively. In the comparison with toxigenic culture, the total, sensitivity, and specificity were 96.6% (370/383), 85.0% (51/60), and 98.8% (319/323), respectively. The current investigation indicated the GENECUBE Clostridioides difficile assay has equivalent performance with the BD MAX Cdiff assay for the detection of tcdB gene of C. difficile.

The drug-coated balloon (DCB) angioplasty is considered a standard therapeutic option for in-stent restenosis. In the present case, we observed high-intensity spots on optical coherence tomography (OCT) and bright spots on coronary angioplasty (CAS) immediately after DCB angioplasty. The superficial high-intensity area on OCT presumably corresponded with the bright spots on CAS. The high-intensity superficial regions were thought to represent an iopromide/paclitaxel mixture. The present serial observation demonstrated that the eluted drugs remained for at least 2 months but disappeared within 6 months. At the site where we observed the drugs, neointimal growth was successfully inhibited and stabilized at the 6-month follow-up. The association of eluted drugs after DCB angioplasty with consequent neointimal growth is of scientific interest. Further prospective imaging studies with a large sample size are warranted to clarify this association.

Proximal junctional failure (PJF) is one of the most devastating complications that develop after adult spinal deformity (ASD) surgery. Here, we report 2 rare cases of PJF accompanied by delayed infection after ASD surgery with a review of the relevant literatures. Late-onset infection is an infrequent complication despite acute postoperative infection is common after posterior spinal instrumentation and fusion. Among them, delayed onset pyogenic spondylitis of the adjacent vertebra to the instrumented vertebrae is an extremely rare phenomenon. We do not have a clear explanation for this pathology. Since the delayed infections developed not in the fused segments but in the adjacent vertebra, the cause of the first case can be speculated as stimulation of low-virulent organisms to fester and hematogenous seeding and that of the second case as metal fretting and a sterile inflammatory response causing hematogenous microbial seeding, respectively. Additional studies on this phenomenon are warranted to elucidate the pathogenesis of this complication.

Abstract Background Corticosteroids are widely used to reduce the urine protein levels of patients with immunoglobulin A nephropathy (IgAN). However, their potential preventive effects on end-stage kidney disease (ESKD) are unclear. Methods We previously performed a large-scale, long-term multicenter cohort study of patients with biopsy-proven IgAN treated between 1981 and 2013 (n = 1923). Based on the results, we reported that corticosteroids pulse therapy was potentially effective for the treatment of patients with an eGFR ≥30 ml/min/1.73m2 and a urine protein amount of ≥1 g/gCr. In the present study, we extracted 766 patients with chronic kidney disease (CKD), stage G3–G4 (15 ≤ estimated glomerular filtration rate [eGFR]

Insertional mutagenesis is an important risk with all genetically modified cell therapies, including chimeric antigen receptor (CAR)-T cell therapy used for hematological malignancies. Here we describe a new tagmentation-assisted PCR (tag-PCR) system that can determine the integration sites of transgenes without using restriction enzyme digestion (which can potentially bias the detection) and allows library preparation in fewer steps than with other methods. Using this system, we compared the integration sites of CD19-specific CAR genes in final T cell products generated by retrovirus-based and lentivirus-based gene transfer and by the piggyBac transposon system. The piggyBac system demonstrated lower preference than the retroviral system for integration near transcriptional start sites and CpG islands and higher preference than the lentiviral system for integration into genomic safe harbors. Integration into or near proto-oncogenes was similar in all three systems. Tag-PCR mapping is a useful technique for assessing the risk of insertional mutagenesis. Keywords: CD19 CAR-T cell, piggyBac transposon, Integration site mapping, Tag-PCR

Adoptive T cell therapy using chimeric antigen receptor (CAR)-modified T cells is a promising cancer immunotherapy. We previously developed a non-viral method of gene transfer into T cells using a piggyBac transposon system to improve the cost-effectiveness of CAR-T cell therapy. Here, we have further improved our technology by a novel culture strategy to increase the transfection efficiency and to reduce the time of T cell manufacturing. Using a CH2CH3-free CD19-specific CAR transposon vector and combining irradiated activated T cells (ATCs) as feeder cells and virus-specific T cell receptor (TCR) stimulation, we achieved 51.4% ± 14% CAR+ T cells and 2.8-fold expansion after 14 culture days. Expanded CD19.CAR-T cells maintained a significant fraction of CD45RA+CCR7+ T cells and demonstrated potent antitumor activity against CD19+ leukemic cells both in vitro and in vivo. Therefore, piggyBac-based gene transfer may provide an alternative to viral gene transfer for CAR-T cell therapy.

Lenvatinib is an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, as well as platelet-derived growth factor receptor α, RET, and KIT. At present, lenvatinib is used in the treatment of thyroid cancer and renal cell carcinoma. We herein report a case of a 67-year-old patient with squamous cell carcinoma of unknown primary who was effectively treated with lenvatinib. The patient was initially diagnosed as having undifferentiated thyroid cancer, and after total thyroidectomy and bilateral lymph node dissection, lenvatinib was administered for the treatment of residual lymph node metastasis. A computed tomography scan after 1 month of lenvatinib administration showed marked regression of the lymph nodes, but interstitial pneumonia was also detected. Because the drug lymphocyte stimulation test for lenvatinib was strongly positive, we concluded that the interstitial pneumonia was induced by lenvatinib. The interstitial pneumonia only improved by the withdrawal of lenvatinib. Finally, his thyroid tumor was diagnosed as a metastasis of squamous cell carcinoma; however, we were unable to identify the primary lesion. This is the first reported case of interstitial pneumonia induced by lenvatinib.

Abstract Background Atrial fibrillation (AF) is common in patients with heart failure and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in out-patients with AF, it remains unclear whether DOACs reduce mortality in hospitalized heart failure (HHF) patients with AF. Therefore, we examined the impact of DOACs on mortality in this group of patients. Methods Consecutive 497 HHF patients with AF were retrospectively registered and divided into three groups on the basis of the presence of anticoagulant therapy: non-anticoagulant group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n = 150). We followed up all the patients for mortality. Results In the Kaplan-Meier analysis (mean follow-up of 1093 days), all-cause mortality was significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and 15.3% vs. 43.3%, log-rank P

Abstract Background The interest in perioperative lung protective ventilation has been increasing. However, optimal management during one-lung ventilation (OLV) remains undetermined, which not only includes tidal volume (VT) and positive end-expiratory pressure (PEEP) but also inspired oxygen fraction (FIO2). We aimed to investigate current practice of intraoperative ventilation during OLV, and analyze whether the intraoperative ventilator settings are associated with postoperative pulmonary complications (PPCs) after thoracic surgery. Methods We performed a prospective observational two-center study in Japan. Patients scheduled for thoracic surgery with OLV from April to October 2014 were eligible. We recorded ventilator settings (FIO2, VT, driving pressure (ΔP), and PEEP) and calculated the time-weighted average (TWA) of ventilator settings for the first 2 h of OLV. PPCs occurring within 7 days of thoracotomy were investigated. Associations between ventilator settings and the incidence of PPCs were examined by multivariate logistic regression. Results We analyzed perioperative information, including preoperative characteristics, ventilator settings, and details of surgery and anesthesia in 197 patients. Pressure control ventilation was utilized in most cases (92%). As an initial setting for OLV, an FIO2 of 1.0 was selected for more than 60% of all patients. Throughout OLV, the median TWA FIO2 of 0.8 (0.65-0.94), VT of 6.1 (5.3-7.0) ml/kg, ΔP of 17 (15-20) cm H2O, and PEEP of 4 (4-5) cm H2O was applied. Incidence rate of PPCs was 25.9%, and FIO2 was independently associated with the occurrence of PPCs in multivariate logistic regression. The adjusted odds ratio per FIO2 increase of 0.1 was 1.30 (95% confidence interval: 1.04-1.65, P = 0.0195). Conclusions High FIO2 was applied to the majority of patients during OLV, whereas low VT and slight degree of PEEP were commonly used in our survey. Our findings suggested that a higher FIO2 during OLV could be associated with increased incidence of PPCs.

Abstract Background Breath acetone is a noninvasive biomarker of heart failure; however, its significance in heart failure patients with diabetes mellitus has yet to be clarified. The objective of this study is to investigate whether exhaled acetone concentration is a noninvasive biomarker in heart failure patients with diabetes mellitus. Methods This study prospectively included 35 diabetic patients with stage C heart failure and 20 diabetic patients with or at risk of heart failure (stage A or B). Exhaled breath was collected after an overnight fast. Results The stage C group had significantly higher brain natriuretic peptide levels, larger left ventricular diameter, lower left ventricular ejection fraction, and more frequent use of β-blocker, compared with the stage A or B group. The stage C group had higher exhaled acetone concentrations than the stage A or B group (p = 0.013). Exhaled acetone concentration was correlated with total ketone bodies (r = 0.588, p

The olfactory bulb is arranged in glomeruli defined by their olfactory receptor expression. The authors identify an olfactory receptor for fox odour, TMT, and show that activation of the glomerulus expressing that receptor in mice leads to immobility, but does not lead to other fear behaviours.