Improved Path Planning of the Blade for an Automatic Spinach Harvester

ArticleIFAC-PapersOnLine. 53(2): 15816-15823. (2020)journal articl

Prevalence of Takotsubo Syndrome among Patients Admitted to an Emergency Department

Article信州医学雑誌 70(1) : 39-46(2022)departmental bulletin pape

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

Background: Reward processing is fundamental for animals to survive and reproduce. Many studies have shown the importance of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons in this process, but the strongly correlative link between the activity of DRN 5-HT neurons and rewarding/aversive potency is under debate. Our primary objective was to reveal this link using two different strategies to transduce DRN 5-HT neurons. Methods: For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. For transduction in Tph2-tTA transgenic mice, AAVs bearing the tTA-dependent TetO enhancer were used. To manipulate the activity of 5-HT neurons, optogenetic actuators (CheRiff, eArchT) were expressed by AAVs. For measurement of rewarding/aversive potency, we performed a nose-poke self-stimulation test and conditioned place preference (CPP) test. Results: We found that stimulation of DRN 5-HT neurons and their projections to the ventral tegmental area (VTA) increased the number of nose-pokes in self-stimulation test and CPP scores in both targeting methods. Concomitantly, CPP scores were decreased by inhibition of DRN 5-HT neurons and their projections to VTA. Conclusion: Our findings indicate that the activity of DRN 5-HT neurons projecting to the VTA is a key modulator of balance between reward and aversion

lenvatinib in nonviral hepatocarcinoma

Aim: To investigate the therapeutic effect of lenvatinib (LEN) in liver disease etiology, especially nonviral hepatocellular carcinoma (HCC). Methods and Results: Sixty-seven patients with unresectable advanced HCC (u-HCC) treated with LEN and consisting of 26 hepatitis C virus (HCV), 19 hepatitis B virus (HBV), 11 alcohol, and 11 nonalcoholic steatohepatitis (NASH) cases were retrospectively recruited. Univariate and multivariate Cox proportional hazard models were used to determine predictive factors for survival. The objective response rate in the nonviral (alcohol and NASH) group was higher than that in the viral group (59.1% [13/22] vs. 46.7% [21/45]). Progression-free survival was significantly longer in the nonviral group than in the viral group (13.7 vs. 6.6 months; hazard ratio [HR] 0.324; 95% confidence interval [CI] 0.174–0.602; P < 0.01). Similarly, median overall survival (OS) was significantly longer in the nonviral group than in the viral group (not evaluable vs. 15.9 months; HR = 0.277; 95% CI = 0.116–0.662; P < 0.01). Multivariate analysis revealed that portal vein invasion (HR = 5.327, P = 0.0025), treatment line (HR = 0.455, P = 0.023), and etiology (HR = 0.180, P = 0.00055) were significant independent factors associated with OS in u-HCC patients treated with LEN. Conclusion: Our results suggest that LEN is more effective against nonviral u-HCC than against viral u-HCC

Lung of Fgf10-CRISPR mosaic mouse

CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known that Fibroblast growth factor 10 (Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in the Fgf10-CRISPR F0 mice. However, how the lung phenotype in the Fgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in the Fgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functional Fgf10 genotypes. Firstly, according to a previous report, Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of the Fgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 ± 6.2% in type I, 25.3 ± 2.7% in type II, and 54.3 ± 9.5% in type III (mean ± standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in the Fgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functional Fgf10 genotypes. These data suggest the Fgf10 gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, the Fgf10-CRISPR F0 mouse would present an ideal experimental system to explore it

The influence of various distractions prior to upper gastrointestinal endoscopy : a prospective randomized controlled study

Background Although many patients still have anxiety about upper gastrointestinal (GI) endoscopy, there have been few reports on the influence of distractions for a person who is going to undergo upper GI endoscopy soon. This study was a prospective randomized controlled study investigating the influence of distractions, such as auditive and visual distractions using subjective and objective assessments including autonomic nervous function prior to upper GI endoscopy. Methods 206 subjects who underwent upper GI endoscopy as regular health check-ups were divided randomly into 4 groups prior to upper GI endoscopy; group 1 (control group), group 2 (auditive group), group 3 (visual group), and group 4 (combination group). We measured vital signs, autonomic nervous function, profile of mood state (POMS), and the impression for upper GI endoscopy pre- and post-distraction in the 4 groups. Results There was no significant difference in vital signs between 5 and 15 min after sitting in group 1, however, several vital signs in all distraction groups improved significantly after distraction (Pulse rate (P): p <  0.001 in group 4; blood pressure: p <  0.05 in group 2, 3, 4) and the rate of decrease in P and diastolic blood pressure was highest in group 4 (p <  0.001). Several scores of POMS and the impression for upper GI endoscopy post-distraction improved significantly compared to pre-distraction between distraction groups and the satisfaction for distraction was highest in group 4 (p <  0.01). Regarding autonomic nerve function, the low- frequency power/ high- frequency power ratio post-distraction was significantly lower than that pre-distraction in all distraction groups (p <  0.001). Conclusions Although auditive distraction alone and visual distraction alone were effective, a combination distraction was more effective than any other distraction by subjective and objective assessments. These distractions, which were simple and safe, may play an assistive role in the stability of physical and psychological conditions prior to upper GI endoscopy. Trial registration This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000022801 ( https://www.umin.ac.jp/ctr/ ). Registered on 10 July 2016

Fgf10-CRISPR mosaic mutants demonstrate the gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung

CRISPR/Cas9-mediated gene editing often generates founder generation (F0) mice that exhibit somatic mosaicism in the targeted gene(s). It has been known thatFibroblast growth factor 10(Fgf10)-null mice exhibit limbless and lungless phenotypes, while intermediate limb phenotypes (variable defective limbs) are observed in theFgf10-CRISPR F0 mice. However, how the lung phenotype in theFgf10-mosaic mutants is related to the limb phenotype and genotype has not been investigated. In this study, we examined variable lung phenotypes in theFgf10-targeted F0 mice to determine if the lung phenotype was correlated with percentage of functionalFgf10genotypes. Firstly, according to a previous report,Fgf10-CRISPR F0 embryos on embryonic day 16.5 (E16.5) were classified into three types: type I, no limb; type II, limb defect; and type III, normal limbs. Cartilage and bone staining showed that limb truncations were observed in the girdle, (type I), stylopodial, or zeugopodial region (type II). Deep sequencing of theFgf10-mutant genomes revealed that the mean proportion of codons that encode putative functional FGF10 was 8.3 +/- 6.2% in type I, 25.3 +/- 2.7% in type II, and 54.3 +/- 9.5% in type III (mean +/- standard error of the mean) mutants at E16.5. Histological studies showed that almost all lung lobes were absent in type I embryos. The accessory lung lobe was often absent in type II embryos with other lobes dysplastic. All lung lobes formed in type III embryos. The number of terminal tubules was significantly lower in type I and II embryos, but unchanged in type III embryos. To identify alveolar type 2 epithelial (AECII) cells, known to be reduced in theFgf10-heterozygous mutant, immunostaining using anti-surfactant protein C (SPC) antibody was performed: In the E18.5 lungs, the number of AECII was correlated to the percentage of functionalFgf10genotypes. These data suggest theFgf10gene dose-related loss of the accessory lobe and decrease in the number of alveolar type 2 epithelial cells in mouse lung. Since dysfunction of AECII cells has been implicated in the pathogenesis of parenchymal lung diseases, theFgf10-CRISPR F0 mouse would present an ideal experimental system to explore it

NAFLD with elevation of alanine aminotransferase levels at various stages of metabolic syndrome

Background The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. Objective To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. Methods Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. Results The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl- L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). Conclusions Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells