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A 69-year-old man with refractory lung adenocarcinoma was treated with gemcitabine and vinorelbine. Dyspnea and hypertension developed after the 17th cycle of chemotherapy. Laboratory findings revealed intravascular hemolysis and renal dysfunction. Thrombotic microangiopathy (TMA) was confirmed by renal biopsy. Antihypertensive and steroid therapies were ineffective. After plasmapheresis, intravascular hemolysis and renal dysfunction gradually improved. However, the disease progressed, and he died 6 months after TMA diagnosis. Autopsy revealed similar pathological findings to those of the renal biopsy. It is important to discontinue gemcitabine at the onset of TMA and consider TMA when using gemcitabine for long periods.

Measuring the distribution, characteristics and dynamics of marine microscale plankton and other particulate matter is essential to understand the vertical flux of elements in the marine environment. Digital holographic microscopy is a powerful approach for measuring these and studying their 3-D trajectories in a relatively large observation volume. This article demonstrates a compact, in-line digital holographic microscope that allows large-volume and high-resolution recording of marine particles through combining a continuous wave laser and a short exposure CMOS camera with efficient global shutters. A resolution of better than 10 μm is demonstrated in air and the minimum distinguishable size of targets recorded in water is approximately 20 μm. The maximum volumetric throughput of the setup is 1904 mL/s. The microscope can take motion blur free holograms of particles moving at up to 490 mm/s in theory, and has been tested in the ∼200-mm/s flowing water. The orientation of the measured volume improves the ability of digital holography in profiling sinking rates and active vertical migration. The system was tested onboard a research vessel to record a range of live plankton and other particles. The motion of some samples, including the sinking motion and swimming motion, was analyzed using custom developed image processing software. The experimental results show that the combination of high resolution and a large volume over which motion of sparse-distribution particles can be tracked, can improve the ability to differentiate between different types of marine particle and identify behaviors of live plankton.

After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the EGFR and anaplastic lymphoma kinase (ALK) as well as c-ros oncogene 1 (ROS1). The mechanisms underlying this type of resistance are unknown. In this article, we report the potential role of Src homology 2 domain–containing phosphatase 2 (SHP2) in the residual cells of ALK/ROS1/EGFR-altered non–small cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells, whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo. Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC.

We report the case of a 54-year-old man who was treated with nivolumab for recurrent squamous cell lung cancer. After 7 cycles of nivolumab treatment, the patient presented to our hospital with right eye vision loss. Gadolinium-enhanced magnetic resonance imaging of the brain showed enhancement around the optic nerve sheath. This finding and his symptoms led to the diagnosis of optic perineuritis (OPN). Steroid pulse therapy was administered twice although there was no remarkable improvement in his visual field defect. The relationship between OPN and nivolumab is unclear. However, immune-related adverse events caused by immune checkpoint inhibitors should be considered.

Objectives Pembrolizumab is a standard treatment for non-small cell lung cancer (NSCLC) with high-PD-L1 expression; however, its effect is dismal in patients with poor physical condition. Additionally, the effect of immunotherapy is generally limited in NSCLC harboring driver mutations such asEGFR, ALK, or RET gene aberrations. Results We report the beneficial effect of pembrolizumab in a patient with poor performance status and PD-L1+ lung adenocarcinoma with theCCDC6–RET fusion gene and co-occurring NF1/TP53 mutations, complicated by multiple cancer-associated thrombi and respiratory failure. Conclusions Further studies are warranted to establish the role of co-occurring NF1/TP53 mutations as a positive predictive biomarker for pembrolizumab in NSCLC harboring RET fusion genes.

Objectives Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. Methods We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. Results Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0–1) vs. 3.2 months (performance status 2) (P Conclusions In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Newborn screening of inborn errors of metabolism using tandem mass spectrometry has become a public health strategy in many developed countries. Retrospective analyses using stored dried blood specimens have been limited, mainly due to a lack of biochemical information on the long-term stability of acylcarnitines and amino acids in stored specimens. We studied the characteristic profiles of the stability of amino acid, free carnitine, and acyl carnitines in dried blood specimens stored in a refrigerator after newborn screening.Dried blood specimens from 198 healthy newborns, which had been stored in a refrigerator at 5 °C after newborn screening, were prospectively subjected to tandem mass spectrometry analyses after 1, 3, 6 months, 1 and 2 years of storage. We also retrospectively re-analyzed the stored samples from 90 newborns, which had been analyzed and stored at 5 °C for 4 years.We found that proline (Pro) and tyrosine (Tyr) were stable for 2 years, and that alanine (Ala), arginine (Arg), and phenylalanine (Phe) decayed with linear regression. The C0 increased during the time-course of 2 years, whereas most acylcarnitines gradually decayed and some showed a linear correlation. The retrospective analysis of samples stored for 4 years revealed that Ala, Phe, Pro and Tyr were almost stable, leucine (Leu), valine (Val) decayed with linear regression, C0 increased, and C10, C12, C14, C14:1, C16, C18, C18:1 decreased, while maintaining a linear correlation.These data suggested that some metabolic parameters from refrigerator-stored dried blood specimens were applicable for the detection of inborn errors of metabolism.

Increasing research has been conducted about patients’ preferences for their role in treatment decision making. Nowadays, a patient-centred approach, so-called ‘shared decision making,’ emphasises ...

Introduction The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. Methods Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. Results ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs invivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth invitro and invivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. Conclusions High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.

Anti-programmed cell death 1 (PD-1) antibodies have poor efficacy in epidermal growth factor receptor (EGFR)-mutated lung cancer. We herein report a 72-year-old man with programmed cell death-ligand 1 (PD-L1)-negative lung adenocarcinoma harboring an EGFR mutation that responded to nivolumab for more than 2 years. A pathological examination revealed infiltration of CD8-positive lymphocytes and macrophages expressing CD68, CD206, and PD-L1 into the PD-L1-negative tumor; CD206 expression is a marker of immunosuppressive tumor-associated macrophages (TAMs). The presence of PD-L1-positive TAMs in the tumor environment might be a predictor of a positive response to anti-PD-1 antibodies.

This paper describes an evaluation method of shot peened surface using image processing. Shot peening is a process that applies compressive residual stress to the product surface, and its evaluation is performed visually by an expert. If visual inspection can be replaced with image processing, the inspection of the entire product will be easier. Therefore, first reference samples that experts evaluate are prepared, next these samples are evaluated by image processing. relationship between expert evaluations and image processing evaluations are compared and the estimation function is defined using gausian distribution. Unknown processed surfaces are evaluated as a classification problem. For image processing, after binarization and labeling, the number of labels and the area ratio of binarization are used.

Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression-free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-α (TGF-α) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF-α attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF-1α/TGF-α.

Molecular agents targeting the epidermal growth factor receptor (EGFR)‐, anaplastic lymphoma kinase (ALK)‐ or c‐ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene‐driven non‐small‐cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti‐vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti‐tumor effects of these agents in xenograft mouse models of EGFR‐, ALK‐, or ROS1‐altered NSCLC. The numbers of CD31‐positive blood vessels were significantly lower in the tumors of mice treated with an anti‐VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR‐, ALK‐, or ROS1‐altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti‐tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti‐tumor effects of molecular targeted agents in various oncogene‐driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti‐VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene‐driven NSCLC., We found that VEGFR2 blockade augmented the anti‐tumor effects of molecular targeted agents in oncogene‐driven NSCLC, particularly in EGFR/ALK/ROS1‐driven NSCLC. We also identified 2 mechanisms underlying the synergistic effects of anti‐VEGFR2 therapy with molecular targeted agents. VEGFR2 blockade not only inhibited tumor angiogenesis but also exerted direct antiproliferative effects on cancer cells.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the standard therapy for non-small cell lung cancer (NSCLC) harboring EGFR mutations, but the resistance is inevitable. The drug-tolerant persister cancer cells are thought to be involved in the resistance. We recently reported that HER2 expression had a negative impact on time-to-treatment-failure in patients with EGFR mutant NSCLC. In this study, we hypothesized that HER2 might be a potential target for alternative combination therapy in NSCLC harboring EGFR mutations. In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11–18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11–18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11–18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations.

Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.

It is important to the Japanese economy to increase the amount of exported agricultural products. However, agricultural products such as peaches, strawberries, and grapes are sometimes damaged during shipping. As proper packing is critical to minimize shipping damage, a special shaped soft sheet is proposed. Herein the principle and automatic sheet generating system are described. This system consists of equipment to bend a non-woven cloth and a robot arm to bond the cloths. The robot arm for bonding is newly developed. An experiment demonstrates that bending and bonding can be conducted in sequence, confirming that the bonding motion is realized automatically after bending the cloth.

Background Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%. Methods This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months. Results 45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib. Conclusions Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment.

Aim Evidence is lacking on the best standard method for forced diuresis to prevent cisplatin-induced nephrotoxicity. We compared the cisplatin-induced nephrotoxicity prevention effect of furosemide or mannitol in patients with advanced non-small cell lung cancer. Methods Patients with advanced non-small cell lung cancer suitable to receive cisplatin-containing regimen were randomly assigned to receive furosemide or mannitol with appropriate hydration. The primary endpoint was the proportion of ≥ grade 1 serum creatinine elevation in the first cycle. Results The trial was terminated early with 44 (22 per arm) of the planned 66 patients because of slow accrual. Patients' characteristics were well balanced with median baseline creatinine clearance of 98.0 and 95.1 mL/min in the furosemide and mannitol arms, respectively. In the first cycle, two (9%) and four (18%) patients developed grade 1 creatinine elevation (P = .66), respectively, despite no ≥ grade 2 toxicity. The median times to develop the worst creatinine score were 10 and 8 days, respectively. For all cycles, median times to recover to grade 0 were 56 and 20 days, respectively. The furosemide arm was characterized by relatively high urine output after cisplatin administration (900 vs 550 mL/h), low frequency of unplanned additional hydration (14% vs 32%), and high incidence of hyponatremia (18% and 5%) compared with the mannitol arm. Both arms showed similar progression-free survival and overall survival. Conclusion The preventive effect of the two forced diuretics on cisplatin-induced nephrotoxicity was not significantly different. However, the two diuretics have some distinct types of clinical presentations.

This paper presents the proto-flight model test results of X band synthetic aperture radar for small satellites with 130kg mass. The specification of SAR performance is single polarization SAR with 3m ground resolution for strip map mode. Optional 1 m ground resolution can be achieved with sliding spot light mode under condition of limited valus of NESZ. The paper describes the unique antenna system, the RF power amplifier, high speed data storage/transmission system, and the ground SAR response test results.

Background Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline. Methods This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled. Results We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009). Conclusions We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.

The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non‑small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube™ method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC‑ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54‑81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post‑operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC‑ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC‑ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC‑ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult.

Pulmonary pleomorphic carcinoma (PPC) is a rare very aggressive subtype of non-small cell lung cancer. We herein report a case of PPC that showed a rapid response to nivolumab. The patient, whose multiple tumors had progressed very aggressively, was treated with nivolumab, an anti-programmed cell death-1 (PD-1) antibody. The tumors dramatically shrank after one cycle of nivolumab. The tumors were positive for programmed cell death ligand 1 (PD-L1). An immunohistochemical analysis revealed numerous PD-1+, CD68+ and CD206+ macrophages. This PD-1 antibody may be a good treatment option, especially in tumors that express PD-L1 and which show PD-1+ macrophage infiltration.

We herein report a case of congestive heart failure which developed during osimertinib treatment. A 78-year-old woman presented with mild exertional dyspnea three weeks after starting osimertinib for the treatment of epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer. She was diagnosed with congestive heart failure caused by the osimertinib. In contrast to trastuzumab, a human epidermal growth factor receptor 2 (HER2) monoclonal antibody that often causes cardiac dysfunction, the causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear. However, it inhibits HER2 in addition to mutant EGFR, thereby potentially causing cardiotoxicity.

After the adoption of the Aichi Target, data accumulation and evaluation regarding biodiversity have progressed rapidly. The use of ecologically and biologically significant areas (EBSAs) criteria to evaluate important areas enables the identification of effective and prioritized areas for ecosystem management. This includes strategic environmental assessment and discussions aimed at establishing protected marine areas based on scientific data. This paper reviews previous and current ideas as well as the methods used, for the identification of EBSAs. In particular, the following issues are addressed: problems associated with different types of marine ecosystems in the Japanese Archipelago, such as seagrass and seaweed beds, coral reefs, offshore pelagic plankton, and deep-sea benthic ecosystems; and problems associated with the integration of multiple criteria that are not totally exclusive. Several candidate variables accounting for each of the 7 criteria used to identify ecologically important areas are presented. Data availability is the most important criterion that allowed for the comprehensive evaluation of different types of ecosystems in the same localities. In particular, for coastal ecosystems such as seagrass, seaweed beds, and coral reefs, it is possible to carry out broad spatial comparisons using variables representing most of these 7 criteria. Regarding methods for the quantitative evaluation of each criterion and their integration, application of these methods to kelp forest ecosystems in Hokkaido, Northern Japan is presented as a case study.

X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23) levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets:PHEX,FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novelPHEXexon 9 mutation (c.947G>T; p.Gly316Val) inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting thatin silicoanalysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novelPHEXmutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia.

Background: Non-small cell lung cancers (NSCLCs) harboring driver oncogene such as epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement are sensitive to the corresponding molecular targeted tyrosine kinase inhibitors (TKIs). However, acquired resistance inevitably develops, and more effective treatment strategies are needed. Anti-vascular endothelial growth factor (VEGF) antibody bevacizumab significantly prolongs progression free survival when added to first-generation EGFR TKIs in EGFR mutant NSCLC. However, it remains unknown whether anti-VEGF receptor (VEGFR) antibody enhances the efficacy of molecular targeted agents as well. In this study, we investigated combinations with an anti-VEGFR antibody and EGFR or ALK TKIs in preclinical models Materials and Methods: We treated mice bearing subcutaneous tumor cell lines harboring EGFR mutation (PC-9, H3255) or ALK rearrangement (ABC-11, H3122) using combinations of anti-mouse VEGFR antibody DC101 and erlotinib (EGFR TKI) /alectinib (ALK TKI). Neovascularization of the tumors were determined by CD31 immunostaining. To determine the effects of VEGFR antibody on cancer cell itself, we also examined the efficacy of the combinations in vitro. Results: Combination therapy demonstrated significantly better tumor inhibition compared to erlotinib or alectinib alone in all the examined xenograft tumors. CD31 positive blood vessel staining was significantly reduced in the tumors treated with combination therapy. Mutant EGFR transfection in HEK293T cells increased VEGF expression in the cell culture supernatant. Furthermore, MTT assay showed significantly enhanced cell growth inhibition when anti-human VEGFR antibody ramucirumab combined with erlotinib (against PC-9 or H3255 cells) or alectinib (against ABC-11 or H3122 cells) suggesting that anti-VEGFR antibody affects not only on tumor vasculature but cancer cell itself. Consistent with this finding, combination with siVEGFR and erlotinib also inhibited the cell proliferation significantly better than erlotinib alone in PC-9 cells. Conclusion: A significant combination benefit was observed with anti-VEGFR2 antibody and EGFR or ALK TKI both in vivo and in vitro, suggesting anti-VEGFR antibody inhibits not only the blood vessels but may also exert direct anticancer effects. Combination therapy of erlotinib or alectinib and anti-VEGFR2 antibody could be a promising treatment strategy for oncogene addicted NSCLC. Citation Format: Hiromi Watanabe, Eiki Ichihara, Hiroe Kayatani, Hisao Higo, Go Makimoto, Hirohisa Kano, Kazuya Nishii, Naofumi Hara, Kiichiro Ninomiya, Toshio Kubo, Kadoaki Ohashi, Kammei Rai, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura. Significant combination benefit of anti-VEGFR antibody and oncogene-targeted agents in EGFR or ALK mutant NSCLC cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2131.

We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF) injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

The lithium-ion secondary batteries have been widely used for the space programs, today. Among them, REIMEI was one of the first satellites using lithium-ion secondary battery. In 2005, the satellite was launched, and injected into the low earth polar orbit. Eleven years has passed since the launch and over 60,000 cycles of charge and discharge was experienced in space. The lithium-ion secondary cell of the REIMEI battery was designed using spinel manganese oxide type material for the positive electrode, and the graphitized type carbon for the negative electrode. The cell case was made of aluminium laminated film and the structure was reinforced by the epoxy resin and aluminium housing. After the operation of eleven years, the cells still maintain the appropriate uniform balance and operative. In order to identify the internal condition of the battery/cell, we calculated the ac impedance by the pulse duration to the on-board battery.

An intrahepatic portosystemic venous shunt is a relatively rare abnormality that can cause encephalopathy owing to hyperammonaemia. Two patients with encephalopathy owing to intrahepatic portosystemic venous shunts were treated with transcatheter emboli sation using the AMPLATZER Vascular Plug II. Both patients achieved complete obliteration, which was confirmed on dynamic CT. Their symptoms that had been related to portalsystemic encephalopathy subsequently improved after the intervention. No short-term complications were observed in either patient. We recommend that the AMPLATZER Vascular Plug II be used for embolis ation owing to its superior safety and utility when compared with metallic coils or other liquid embolic materials.

Objective Although sedation with fentanyl and midazolam during bronchoscopic examination is widely accepted in the USA and Europe, it is not routine practice in Japan. The objective of the present study was to evaluate sedation with fentanyl and midazolam during bronchoscopy. Methods Thirty-seven patients were enrolled prospectively between November 2014 and July 2015 at Okayama University Hospital. Fentanyl (20 μg) was administered to the patients just before the examination, and fentanyl (10 μg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire was administered 2 hours after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: great (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also used. Predefined matters for investigation (e.g. blood pressure, heart rate, oxygen saturation and complications) were recorded. Results The enrolled patients included 13 males and 24 females; the median age was 67 (range: 31-87) years. The patients received a median dose of fentanyl of 45.4 μg (range: 30-100 μg) and midazolam of 2.56 mg (range: 1-10 mg). Twenty-six patients (70.2%) agreed to undergo a second bronchoscopic examination, and the average levels of discomfort and re-examination were 2.02 points for each. Only 37.8% of the patients remembered the bronchoscopic examination. No severe complications were reported. Conclusions Sedation with fentanyl and midazolam during bronchoscopic examination should be recommended for use in Japan.

A wearable walking navigation system without any special infrastructures has been developed to guide visually impaired. It is important to estimate a position correctly so that safe navigation can be realized. In our system, different sensor data are fused to estimate a pedestrian's position. An image processing system and a laser range finder were used to estimate the positions indoors. In this paper, we introduce the concept of “similarity” between map information and sensor data. This similarity is used to estimate the positions. Experimental results show that highly accurate position estimation can be achieved by sensor fusion. The positions in a linear passage were estimated using image processing data, and when the passage turns, the positions were estimated using LRF data.

e21147Background: Several kinds of immune checkpoint inhibitors (ICIs) have demonstrated longer survival compared with chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the effe...

e21034Background: Immune checkpoint inhibitors (ICIs) offer longer survival than chemotherapy in advanced non-small cell lung cancer (NSCLC). In subset analyses, ICIs extended survival compared to ...

Hyperventilation (HV) is widely used to induce EEG abnormalities and epileptic seizures. However, it is still controversial how long it should be done in routine EEG. We analyzed 1,184 routine EEG data recorded in our institution between October, 2016 and September, 2017. Among them, 970 patients tried to perform HV lasting 4 min, and 949 patients completed it age mean, range. During HV, interictal epileptiform discharges (IED) were induced in 82 patients (9%). Generalized IED were seen in 70 patients, focal IED in eight, bi-temporal slow wave in three, and rhythmic theta activity (focal) in one. IED appeared only after 3-min HV in 11 patients (13%) out of 82. Epileptic seizures were induced by HV in 25 patients (3%). Absence seizures occurred in 23 patients, and focal seizures in two. Two patients (12%) had seizures after 3-min HV. No adverse event occurred during 4-min HV, not only during this study period, but also more than 40 years of our practice. We concluded that 4-min HV is effective and safe for epilepsy patients.

A full-HD (1080p30) 500 MHz mobile application processor with an H.264 HP/MPEG-2/MPEG-4 video codec is integrated on a 6.4 × 6.5 mm2 die in 65 nm low-power CMOS. With two parallel pipelines for macroblock processing and tile-based address translation circuits, the processor consumes 342 mW in real-time playback of a full-HD H.264 stream from a 64 b width low-power DDR-SDRAM at an operating frequency of 166 MHz at 1.2 V.

A full high-definition (full HD) video codec includes a high-performance stream processing unit to support multiple standards in mobile application processors. The unit performs at 40 Mbps when operated at a 162-MHz clock rate. Implemented in 65-nm CMOS technology, the proposed video codec consumes 176 mW in real-time decoding of H.264 full HD video.

A video-size-scalable H.264 high-profile codec including 19 application-specific CPUs for extensibility to multiple standards has been fabricated in 65 nm CMOS. With two parallel pipelines for macroblock processing, the codec consumed 256 mW in real-time encoding of 40 Mbp full-HDs (1080p30) video at an operating frequency of 162 MHz.

In the autonomous mobile robot using ultrasonic range finders, especially in outdoor environment, the ultrasonic range finder is required to detect the object frequently at the short distance for driving control and obstacle avoidance, and to find the landmark object at a long distance for navigation system. However the frequency and the long rang measurement at same time are incompatible in the conventional ultrasonic range finder. The aim of this paper is describe about the ultrasonic range finder that processes these two opposite functions in parallel. This ultrasonic range finder transmits wave coded the pattern that is composed in transmitting patterns of each functions, then calculates cross-correlation between transmitted pattern and received signal at each functions. The experimental results show the ultrasonic range finder measures distance to the short range object frequently and the long range object at same time.

We have developed an H.264/MPEG-4 dual video codec IP for mobile applications such as digital still cameras (DSCs), digital video cameras (DVCs), and mobile phones. The codec is capable of encoding and decoding HD-sized moving pictures (1280 pixels by 720 lines at 30 fps) in real-time at an operating frequency of 144 MHz, and SD-sized pictures at 54 MHz. We have implemented our original architecture based on a macroblock-level pipeline method and encoding algorithms suitable for the architecture in the codec, which enable low power of 64 mW for HD encoding with high picture quality equivalent to that of the H.264 reference encoder ldquoJM (Joint Model)rdquo.

A wearable electronic travel aid to guide visually impaired has been developed. Visually impaired are at risk of a lot of accidents on a solo walking. Therefore, it is necessary to support safety walking with the electronic travel aids. The detection of the obstacles is one important factor for the safety. In this paper, the method of detection of the obstacles is proposed. Descending down steps like the platform and down stairs are very dangerous places. Therefore, the obstacles to detect are walls, upstairs, descending down steps and downstairs. An IR range finder and the fuzzy reasoning are used to detect these objects. The production rules used for the fuzzy reasoning are made based on using human being's sense. The experimental results show that the obstacles could be detected and distinguish a type by the coverage of 100% at 750mm in front of the obstacles. The results showed this device is effective as the detection device of the obstacle to support the visually impaired. The researched and developed device was practicable and suitable for the life environment.

During a disaster, it may be difficult for the visually impaired to use infrastructure or to obtain care worker's support. To support the independence of the visually impaired, we have developed a wearable travel aid that assists in safe travel, including navigating stairs, without special infrastructure. Because safe navigation requires accurate position estimation, our system fuses data from different sensors to estimate a pedestrian's position. In this paper, we propose a floor estimation method based on fuzzy inference with a laser range finder (LRF). When walking on a floor, an image processing system and a LRF are used together to estimate the position, but when walking on stairs, a second LRF is used to estimate the floor and detect obstacles. The experimental results show that our floor estimation is also useful for position estimation.