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Makito Miyake,1 Nobutaka Nishimura,1,2 Takuto Shimizu,1,3 Mikiko Ohnishi,4 Masaomi Kuwada,4 Yoshitaka Itami,5 Takeshi Inoue,5 Kenta Ohnishi,6 Yoshihiro Matsumoto,6 Takanori Yoshida,7 Yoshihiro Tatsumi,8 Masatake Shinohara,9 Shunta Hori,1 Yosuke Morizawa,1 Daisuke Gotoh,1 Yasushi Nakai,1 Satoshi Anai,1 Kazumasa Torimoto,1 Katsuya Aoki,1 Tomomi Fujii,10 Nobumichi Tanaka,1,11 Kiyohide Fujimoto1 1Department of Urology, Nara Medical University, Kashihara, Nara, 634-8522, Japan; 2Department of Urology, Okanami General Hospital, Iga, Mie, Japan; 3Department of Urology, Saiseikai Chuwa Hospital, Nara, Japan; 4Department of Urology, Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan; 5Department of Urology, Nara Prefecture General Medical Center, Nara, Japan; 6Department of Urology, Hoshigaoka Medical Center, Hirakata, Osaka, Japan; 7Department of Urology, Tane General Hospital, Osaka, Japan; 8Department of Urology, JCHO Yamato Koriyama Hospital, Koriyama, Nara, Japan; 9Department of Urology, Osaka Gyoumeikan Hospital, Osaka, Japan; 10Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, 634-8522, Japan; 11Department of Prostate Brachytherapy, Nara Medical University, Kashihara, Nara, 634-8522, JapanCorrespondence: Makito Miyake, Department of Urology, Nara Medical University, 840 Shijo-cho, Nara, 634-8522, Japan, Tel +81-744-22-3051 (ext 2338), Fax +81-744-22-9282, Email makitomiyake@yahoo.co.jpPurpose: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment.Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model.Results: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age < 70 years), those who received radical surgery, and those without visceral metastasis.Conclusion: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics.Keywords: urinary bladder neoplasms, immunotherapy, chemotherapy, survival, propensity score

Sho Okawa,1– 3 Sayo Hamatani,2,4 Yuta Hayashi,5,6 Honami Arai,2,7 Masato Nihei,2,4 Tokiko Yoshida,2 Jumpei Takahashi,1,2 Eiji Shimizu,2,3 Yoshiyuki Hirano1,2 1United Graduate School of Child Development, Osaka University, Suita, Osaka 565-0871, Japan; 2Research Center of Child Mental Development, Chiba University, Chiba-shi, Chiba 260-8670, Japan; 3Department of Cognitive Behavioral Physiology, Chiba University, Chiba-shi, Chiba 260-8670, Japan; 4Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo 102-0083, Japan; 5Department of Nursing, Graduate School of Health Sciences, Kobe University, Suma-ku, Kobe 654-0142, Japan; 6Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan; 7Faculty of Human Sciences, Tsukuba University, Bunkyo City, Tokyo 112-0012, JapanCorrespondence: Yoshiyuki HiranoResearch Center of Child Mental Development, Chiba University, 1-8-1, Inohana, Chuo Ward, Chiba-shi, Chiba 260-8670, JapanTel +81-43-226-2975Fax +81-43-226-8588Email hirano@chiba-u.jpIntroduction: Although deficits in neuropsychological functioning have been reported in social anxiety disorder (SAD), studies focusing on neuropsychological dysfunction in SAD are limited, and the evidence is still lacking. The purpose of this study was to examine the deficits in neuropsychological functioning in patients with SAD by comparing SAD patients and a healthy control (HC) group.Materials and Methods: A total of 72 participants (20 in the SAD group and 52 in the HC group) were assessed with neuropsychological tests, consisting of the Rey Complex Figure Test (RCFT) to measure central coherence and the Trail Making Test A and B (TMT-A; TMT-B) to measure visual scanning and executive functioning.Results: Analysis of covariance with depressive symptoms as a covariate revealed that central coherence (RCFT) and visual scanning (TMT-A) were significantly lower in the SAD group than in the HC group. No difference was found in executive functioning (TMT-B) when the effect of visual scanning was considered.Discussion: Our findings suggest that SAD patients have weak central coherence and deficits in visual scanning compared to healthy controls. The clinical implications of these neuropsychological functioning deficits in SAD patients are discussed.Keywords: social anxiety disorder, neuropsychological functioning, central coherence, visual scanning, executive functioning

Tatsuya Yoshida,1 Takuya Miura,1 Tomoh Matsumiya,2 Hidemi Yoshida,2 Hajime Morohashi,1 Yoshiyuki Sakamoto,1 Akira Kurose,3 Tadaatsu Imaizumi,2 Kenichi Hakamada1 1Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan; 2Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan; 3Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, JapanCorrespondence: Kenichi HakamadaDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, JapanTel +81 172 39 5079Fax +81 172 39 5080Email hakamada@hirosaki-u.ac.jpPurpose: Colorectal cancer (CRC) often recurs after curative resection. Identification of major risk factors for CRC recurrence is important for effective prevention and treatment. In this study, we examined the potential relationship between CRC and TLR3 as this remains unclear.Patients and Methods: Correlations between TLR3 immunostaining and clinicopathological factors and prognosis were examined in 50 samples that were randomly extracted from 264 patients with CRC from January 2010 to December 2011. Chemokines induced by TLR3 agonist stimulation were also examined using TLR3-positive human CRC cell lines. Furthermore, the association between TLR3 and chemokine expression was assessed by analyzing the immunohistochemistry of surgical specimens.Results: Of the 50 patients, 14 (28%) were TLR3-negative. In the comparison of clinicopathological factors between the TLR3-negative and -positive groups, there were more lymph node metastasis-positive cases in the TLR3-negative group, and this difference was significant. Furthermore, there was no difference in overall survival rates between the two groups, but the 5-year recurrence-free survival (RFS) was significantly lower in the TLR3-negative group (46.2%) than in the TLR3-positive group (78.1%). Analysis of 5-year RFS using factors thought to be related to recurrence identified a high tumor budding and a TLR3-negative status as independent risk factors for recurrence. TLR3 activation of CRC cell lines induced expression of C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 5 (CCL5), and interleukin-8. The expressions of CCL2, CCL5, and IL-8 were observed in the TLR3-positive tumor cells of surgical specimens.Conclusion: Non-expression of TLR3 in CRC cells was associated with lymph node metastasis and was an independent risk factor for recurrence. These results suggest that TLR3 may not only be used as a prognostic factor and a risk factor for recurrence, but further studies on the involvement of TLR3 with tumor growth may provide new therapeutic strategies.Keywords: colorectal cancer, toll-like receptor 3, recurrence, CCL2, CCL5, IL-8

Hiroaki Kuroda,1 Yusuke Sugita,1 Yuko Ohya,2 Tatsuya Yoshida,2 Takaaki Arimura,1 Noriaki Sakakura,1 Toyoaki Hida,2 Yasushi Yatabe,3 Yukinori Sakao1 1Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; 2Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; 3Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan Introduction: The natural history of consolidation on computed tomography (CT) rarely includes invasive cancers, and evidence of the ideal timing for surgical intervention via long-term follow-up studies remains unknown. Methods: Between January 2012 and June 2017, pulmonary resection was undertaken in 293 clinical IA patients who were followed-up for > 6 months after the first detection of potential non-small-cell lung cancer (NSCLC) opacities. We evaluated the corresponding HRs and compared the recurrence risk with the CT follow-up duration. Results: HRs calculated for the longest intervals were compared between two patient subsets: a shorter-interval surgery group (SISG: 41.3%; mean follow-up interval, 13.5±5.3 months) and a longer-interval surgery group (58.7%; mean follow-up interval, 54.9±25.6 months). On Cox multivariate regression analyses, CT consolidation (ratio >0.5), an abnormal carcinoembryonic antigen and a triple-negative mutation showed an independent association with an unfavorable prognosis, as measured by disease-free survival after the first detection of potential NSCLC opacities. The longer-interval surgery group fared significantly better than the SISG in terms of 5-year overall survival after the first detection (99.3% vs 93.1%, P

Katsutoshi Seto,1 Hiroaki Kuroda,1 Tatsuya Yoshida,2 Shozo Sakata,1 Tetsuya Mizuno,1 Noriaki Sakakura,1 Toyoaki Hida,2 Yasushi Yatabe,3 Yukinori Sakao1 1Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; 2Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; 3Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan Objectives: There have been few studies that have fully elucidated the relationship between genomic mutations in pulmonary adenocarcinomas and occult lymph node (LN) metastases (pN1-2) despite a preoperative clinical N0 stage (cN0). It is well known that anaplastic lymphoma kinase (ALK) rearrangements are more likely to occur in younger patients with high grade tumors. The aim of this study was to investigate the genomic status, examine the clinicopathologic features, and evaluate whether ALK mutations are associated with occult LN metastases. Materials and methods: We retrospectively evaluated 459 Japanese patients who underwent pulmonary resection of cN0 adenocarcinomas between January 2012 and December 2015. The clinicopathologic characteristics, including age, sex, smoking index, tumor maximum diameter and consolidation/tumor ratio on computed tomography (CT), maximum standardized uptake value on positron emission tomography (PET) and gene mutations (epidermal growth factor receptor [EGFR], ALK, and kirsten ras genes (KRAS), were evaluated. Results: ALK and EGFR and KRAS mutations were all mutually exclusive. Among 324 patients found to have mutations, ALK was involved in 19 (5.9%), EGFR in 266 (82.1%), and KRAS in 39 (12.0%). The incidence of occult LN metastases did not differ significantly between those with or without mutations (p=0.27). On univariate and multivariate analyses, tumors with ALK were more likely to have occult LN metastases (p=0.03). In cN0 tumors with ALK, pN1 was diagnosed in 26.3% and pN2 in 10.5%, whereas pN1 or pN2 stage was found in

Yuya Watanabe,1–4,* Yosuke Yamada,2,4,* Keiichi Yokoyama,2,5,6,* Tsukasa Yoshida,2,4,7 Yasuko Yoshinaka,5,6 Mie Yoshimoto,8 Yoko Tanaka,9 Aya Itoi,10 Emi Yamagata,11 Naoyuki Ebine,1 Kazuko Ishikawa-Takata,12 Misaka Kimura2,3 1Faculty of Health and Sports Science, Doshisha University, Kyotanabe, Japan; 2Laboratory of Applied Health Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Department of Health and Sports Sciences, Kyoto Gakuen University, Kameoka, Japan; 4Section of Healthy Longevity Research, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan; 5Specified Non-profit Corporation Genki-up AGE Project, Kameoka, Japan; 6Department of Business Administration, Kyoto Gakuen University, Kyoto, Japan; 7Senior Citizen’s Welfare Section, Kameoka City Government, Kameoka, Japan; 8Corporation of Japan Dental Hygienists’ Association, Kyoto, Japan; 9Kyoto Dietetic Association, Kyoto, Japan; 10Department of Health, Sports and Nutrition, Faculty of Health and Welfare, Kobe Women’s University, Kobe, Japan; 11Faculty of Nursing, Doshisha Women’s College of Liberal Arts, Kyotanabe, Japan; 12Department of Nutrition and Metabolism, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan *These authors contributed equally to this work Objective: The number of long-term care (LTC) users and the associated expenditures in Japan are increasing dramatically. The national government recommends LTC prevention through activation of communities. However, there is no clear evidence of the effect of population-based comprehensive geriatric intervention program (CGIP) for restraints of LTC users and the associated expenditures in the future. The aims of the current paper are to describe the study protocol and progress of a cluster randomized controlled trial (RCT) with a CGIP in Kameoka City. Methods: The cluster RCT involved random allocation of regions as intervention (n=4,859) and nonintervention (n=7,195). Participants were elderly persons aged ≥65 years without LTC certification who had responded to a mailing survey. The residents living in intervention regions were invited to a physical check-up, and 1,463 people participated (30.3%). These individuals were invited to the CGIP, and 526 accepted. The CGIP comprised instructions on: 1) low-load resistance training using bodyweight, ankle weights, and elastic bands; 2) increasing daily physical activity; 3) oral motor exercise and care; and 4) a well-balanced diet based on a program from Ministry of Health, Labour and Welfare. We allocated the intervention regions randomly into home-based self-care program alone (HB group, 5 regions, n=275) and home-based program+weekly class-style session (CS group, 5 regions, n=251). We evaluated the effects of the CGIP at 12 weeks and at 12 or 15 months on physical function, and are conducting follow-up data collection for an indefinite period regarding LTC certification, medical costs, and mortality. Results and discussion: The study was launched with good response rates in each phase. Participants of both groups significantly increased their step counts by ~1,000 per day from the baseline during the CGIP. This RCT will provide valuable information and evidence about effectiveness of a community-based CGIP. Keywords: frailty, sarcopenia, long-term care, ActiveGuide, low-load resistance training, oral care, nutritional intervention, Shokuiku, physical function, physical activity monitor

Hiroaki Kuroda,1 Hitomi Mizuno,2 Hitoshi Dejima,1 Kiyoe Watanabe,2 Tatsuya Yoshida,3 Yumiko Naito,2 Yukinori Sakao1 1Department of Thoracic Surgery, 2Department of Nursing, 3Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan Background: Thoracoscopic surgery (TS) has been performed as a minimally invasive procedure since the beginning of the 1990s. This has led to a dramatic change in the postoperative condition of these patients, facilitating early ambulation and easier management of postoperative pain. However, empirical evidence on postoperative pain management after TS is limited. The aims of this study were to determine the efficacy and adequacy of postoperative analgesic medications and to simplify the choice of additional drugs based on a numerical rating scale (NRS).Materials and methods: A retrospective study of patients who underwent TS was performed to evaluate postoperative pain, analgesia requirements, and the number of drugs needed during the perioperative period based on the NRS score.Results: Of the 524 patients, mild pain was noted in 87% patients on the day of the operation and in 75.6% patients on ambulation. The mean NRS score was 1.83±1.49 on the day of the operation and 2.73±1.75 on ambulation. An NRS score of 3 on both the day of operation and on ambulation was defined as the necessary condition for improved pain management. Multivariate analysis showed that high surgical stress significantly influenced pain scores. Reduction in pain with an NRS score of ≥1 was significant with the addition of pentazocine hydrochloride (p3 on ambulation.Conclusion: A small number of patients have moderate-to-severe pain after TS. Tramadol demonstrated borderline efficacy in controlling postoperative intense pain with an NRS score of ≥3. Keywords: tramadol, thoracoscopic surgery, ambulation, NRS, postoperative pain

Kenya Yuki,1 Toru Nakazawa,2 Daijiro Kurosaka,3 Tsunehiko Yoshida,4–6 Eduardo C Alfonso,7 Richard K Lee,7 Shigeru Takano,8 Kazuo Tsubota1 1Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; 3Department of Ophthalmology, Iwate Medical University, Iwate, Japan; 4The House of Representatives of Japan, Tokyo, Japan; 5Nagoya University Hospital, Aichi, Japan; 6Aichi Medical University Hospital, Aichi, Japan; 7Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 8Japan Ophthalmological Association, Tokyo, Japan Purpose: The Great East Japan Earthquake of March 11, 2011 triggered powerful tsunami waves off the northeastern Pacific coast of Japan that destroyed almost all of the built-up areas along the coast. The study reported here examined the role played by the Vision Van, a mobile outpatient ophthalmological clinic, in providing eye care to disaster evacuees. Methods: This was a retrospective case-series study of 2,070 victims (male: 732, female: 1,338) who visited the Vision Van. The subjects' medical records were examined retrospectively and analyzed in terms of age, sex, and date of visit to the Vision Van. Information regarding each patient's chief complaint, diagnosis, medication(s) prescribed, and eyeglasses and contact lenses provided, was also examined. Results: The Vision Van was used to conduct medical examinations on 39 days between April 23 and June 29, 2011. The average number of subjects visiting the Vision Van each day was 53±31 (range: 7–135), with examinations carried out in Miyagi Prefecture and Iwate Prefecture. The most frequent complaint was a need for eye drops (871/2,070 [42.1%]). The second and third most frequent complaints, respectively, were the need for contact lenses (294/2,070 [14.2%]) and eyeglasses (280/2,070 [13.5%]). The most frequent ocular disease diagnosis was cataract (497/2,070 [24.0%]). Eye drops were prescribed to 74.1% of the subjects. Conclusion: Mobile clinics such as the Vision Van provide valuable care, in this case, particularly to individuals who lost or left behind eyeglasses or contact lenses while escaping a natural disaster, and to subjects with chronic eye disease. Keywords: natural disaster, disaster relief, eye care, mobile medical services

Minoru Tomizawa,1 Fuminobu Shinozaki,2 Aika Ozaki,2 Akira Baba,2 Yoshiya Fukamizu,2 Futoshi Matsunaga,2 Takao Sugiyama,3 Shigenori Yamamoto,4 Makoto Sueishi,3 Takanobu Yoshida51Department of Gastroenterology, 2Department of Radiology, 3Department of Rheumatology, 4Department of Pediatrics, 5Department of Internal Medicine, National Hospital Organization Shimoshizu Hospital, Yotsukaido City, JapanPurpose: Information on the extent or structure of esophageal cancer (ESC) is necessary for identifying whether the carcinoma is localized or resectable. Diffusion-weighted imaging (DWI) and diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) are useful for this purpose.Patients and methods: One case of ESC with dysphagia presented at our hospital. Endoscopic examination revealed an elevated lesion with an ulcer, and stenosis was detected. DWI showed a high-intensity signal extending from the proximal to the distal ends of the carcinoma and extending to the tunica adventitia. A strong signal was also observed using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). DWIBS clearly revealed ESC, and these findings, along with those from DWI, suggested that our case had stage-T3 ESC. FDG-PET did not reveal the detailed structure of the ESC. DWIBS, on the other hand, showed that the signal extended to the tunica adventitia and the lumen of the esophagus.Conclusion: These findings suggest that DWI and DWIBS are useful for the detection and assessment of ESC.Keywords: positron emission tomography, endoscopy, computed tomography, cross section, squamous cell carcinoma

Al-Zn-Mg alloy has been known as one of the aluminum alloys with the good age-hardening ability and the high strength among commercial aluminum alloys. The mechanical property of the limited ductility, however, is required to further improvement. In this work, three alloys, which were added Cu or Ag into the Al-Zn-Mg alloy, were prepared to compare the effect of the additional elements on the aging behavior. The content of Ag and Cu were 0.2at.% and the same as, respectively. Ag or Cu added alloy showed higher maximum hardness than base alloy. The particle shape and rod shape precipitates were observed in all alloys peak-aged at 423K. According to addition of Ag or Cu, the number density of the precipitates increased higher than that of base alloy.

Yuya Watanabe,1 Yosuke Yamada,1,2 Yoshihiro Fukumoto,3 Tatsuro Ishihara,4 Keiichi Yokoyama,1 Tsukasa Yoshida,1 Motoko Miyake,1 Emi Yamagata,5 Misaka Kimura1 1Laboratory of Sports and Health Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan; 3Faculty of Rehabilitation, Kobe Gakuin University, Kobe, Japan; 4Faculty of Health and Sports Science, Doshisha University, Kyoto, Japan; 5Laboratory of Gerontological Nursing, Kyoto Prefectural University of Medicine, Kyoto, Japan Background: It is well known that loss of muscle mass (quantitative change) is a major change that occurs with aging. Qualitative changes in skeletal muscle, such as increased intramuscular fat, also occur as one ages. Enhanced echo intensity (EI) on ultrasonography images of skeletal muscle is believed to reflect muscle quality. Recent studies evaluating the quality of skeletal muscle using computer-aided gray scale analysis showed that EI is associated with muscle strength independently of age or muscle size in middle-aged and elderly women. The aim of the present study was to investigate whether muscle quality based on EI is associated with muscle strength independently of muscle size for elderly men. Methods: A total of 184 elderly men (65–91 years) living independently in Kyoto, Japan, participated in this study. The EI, muscle thickness (MT), and subcutaneous fat thickness (FT) of the anterior compartment of the right thigh were determined by assessing ultrasonography images. The maximum isometric torque of knee extension at a knee angle of 90° was measured. Results: The EI showed a significant negative correlation with muscle strength (r = -0.333, P < 0.001). Multivariate regression analysis revealed that the MT and EI of the knee extensor muscle were independently associated with maximum isometric knee extension strength. Even when partial correlation analysis was performed with age, height, weight, and FT as control variables, EI was still significantly correlated with muscle strength. Conclusion: The results of this study indicate that aging-related changes in muscle quality contribute to diminishing muscle strength. Ultrasonography is a low-cost, easily accessible, and safe method suitable for the assessment of EI as an index of muscle quality. Keywords: echogenicity, sarcopenia, ultrasound imaging

Hiroyasu Kaneda,1 Takeshi Yoshida,1 Isamu Okamoto2 1Department of Medical Oncology, Kinki University, Osakasayama, Japan; 2Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan Abstract: The discovery of activating mutations in the epidermal growth-factor receptor (EGFR) gene in 2004 opened a new era of personalized treatment for non-small-cell lung cancer (NSCLC). EGFR mutations are associated with a high sensitivity to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib. Treatment with these agents in EGFR-mutant NSCLC patients results in dramatically high response rates and prolonged progression-free survival compared with conventional standard chemotherapy. Subsequently, echinoderm microtubule-associated protein-like 4 (EML4)–anaplastic lymphoma kinase (ALK), a novel driver oncogene, has been found in 2007. Crizotinib, the first clinically available ALK tyrosine kinase inhibitor, appeared more effective compared with standard chemotherapy in NSCLC patients harboring EML4-ALK. The identification of EGFR mutations and ALK rearrangement in NSCLC has further accelerated the shift to personalized treatment based on the appropriate patient selection according to detailed molecular genetic characterization. This review summarizes these genetic biomarker-based approaches to NSCLC, which allow the instigation of individualized therapy to provide the desired clinical outcome. Keywords: non-small-cell lung cancer, epidermal growth factor receptor, ALK rearrangement, gefitinib, erlotinib, crizotinib

Motonori Okabe,1 Kiyotaka Kitagawa,2 Toshiko Yoshida,1 Chika Koike,1 Takeshi Katsumoto,2 Etsuko Fujihara,2 Toshio Nikaido1 1Department of Regenerative Medicine, University of Toyama, Graduate School of Medicine and Pharmaceutical Sciences, Toyama, 2Division of Ophthalmology, Matsue Red Cross Hospital, Japanese Red Cross Society, Shimane, Japan Background: This paper reports on the efficacy of a tissue adhesive, 2-octyl-cyanoacrylate, in the treatment of corneal perforation and glaucoma filtering bleb leak. Methods: Two eyes from two patients with corneal perforation or laceration and two eyes from two patients with bleb leak were included. The patients underwent application of 2-octyl-cyanoacrylate onto the perforated or leaking site, and a hydrogel contact lens was applied as a bandage. We also evaluated the in vitro cell toxicity of 2-octyl-cyanoacrylate in HeLa cells. Results: The two cases of corneal perforation were repaired within 22 days with one application of the tissue adhesive. The two cases of bleb leak were repaired with 2–4 applications of the tissue adhesive over 134 (range 17–134) days). There were no recurrences or adverse effects during a mean follow-up period of 12.7 months. In vitro testing revealed that 2-octyl-cyanoacrylate was markedly toxic to HeLa cells. Conclusion: Four patients with corneal perforation or bleb leak were successfully managed using 2-octyl-cyanoacrylate tissue adhesive. This simple and easy surgical technique may become an alternative therapeutic option for corneal perforation or bleb leak, although several applications of this tissue adhesive may be required. Although 2-octyl-cyanoacrylate was toxic to HeLa cells, no adverse clinical effects were noted using this adhesive. Keywords: corneal perforation, bleb leak, tissue adhesive, 2-octyl-cyanoacrylate

Haruka Yamamoto,1 Hideto Tsuchida,1 Takashi Nakamae,1 Seiji Nishida,1 Yuki Sakai,1 Akihito Fujimori,1 Jin Narumoto,1 Yoshihisa Wada,1 Takafumi Yoshida,2 Chiaki Taga,3 Kenji Fukui11Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Kyoto Cognitive Behavior Therapy Counseling Room, Kyoto, Japan; 3Department of Psychiatry, Kyoto Second Red Cross Hospital, Kyoto, JapanPurpose: Obsessive-compulsive disorder (OCD) patients exhibit a noninhibition response pattern very similar to that observed in schizotypy patients in cognitive tasks. It has been suggested that the reduced cognitive inhibition observed in both schizotypy and OCD may result in the frequent entry into awareness of unacceptable urges and intrusive thoughts. The aim of this study was to investigate the relationship between the severity of obsession or compulsion and schizotypy in OCD.Patients and methods: Sixty subjects (25 males and 35 females) who were OCD outpatients in the University Hospital at the Kyoto Prefectural University of Medicine during the period 2008–2010 were enrolled in the study. Assessments of these patients were made using the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), the Schizotypal Personality Questionnaire (SPQ), the Hamilton Depression Rating Scale (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). The Pearson correlation coefficients between Y-BOCS and SPQ scores were calculated. Furthermore, hierarchical multiple linear regression analyses were conducted to assess whether schizotypy predicted the severity of obsession and compulsion.Results: By calculating the Pearson correlation coefficient, it was found that the Y-BOCS obsession score, not the Y-BOCS compulsion score, was correlated with the SPQ total score. Results of the hierarchical multiple linear regression analysis showed that SPQ total score was a significant predictor of the Y-BOCS obsession score, after accounting for control variables (ie, HAM-D and HAM-A).Conclusion: Results of this study showed that the Y-BOCS obsession score, not the Y-BOCS compulsion score, was correlated with the SPQ total score. This finding suggests that OCD patients with an elevated SPQ total score experience a reduction of cognitive inhibition, resulting in the frequent entry into obsession. Future longitudinal studies are recommended to clarify the effect of schizotypy on the clinical course of OCD. Keywords: Y-BOCS, obsession, compulsion, severity

We applied the gross theory of β-decay to calculate the reactor electron and antineutrino ( ν¯e${{\rm{\bar \nu }}_{\rm{e}}}$) spectra emitted from 235,238U and 239,241Pu by summing up all the contributions from a large number of decaying fission-products (FPs). We make it clear what kinds of transition types and FP nuclides are important to shape the lepton spectra. After taking the ambiguity in the current data for fission yields and Qβ-values into account, we suggested a possibility that the high-energy part of the widely referred electron-spectra by Schreckenbach et al., almost only one experimental data set available now, might possibly be too low. Arguments on a special role of the odd(Z)-odd(N) nuclides and on the consistency between U-238 and other fissiles in the experimental data lead to the importance of a new and independent measurement of electron energy spectra which could be converted into the reactor ν¯e${{\rm{\bar \nu }}_{\rm{e}}}$ spectra.

We studied Nd3-XBiXFe4GaO12 films to obtain perpendicular magnetic anisotropy as well as large Faraday effect. NdBi2Fe4GaO12 (Bi2:NIGG) and Nd0.5Bi2.5Fe4GaO12 (Bi2.5:NIGG) films were obtained on Nd2BiFe4GaO12 (Bi1:NIGG) layer prepared on glass substrates by metal-organic decomposition (MOD) method. Bi2:NIGG and Bi2.5:NIGG films showed large Faraday rotation angles of 7.5 and 10.5 degree/µm, at a wavelength of 520 nm, respectively. Those films have perpendicular magnetic anisotropy with a coercivity of 350 Oe and a saturation magnetic field of 730 Oe.

The wave functions of the ground states for 8,10Be which are obtained from the Monte Carlo shell model (MCSM) are investigated. A method to define an intrinsic state in the MCSM is discussed. The appearance of two-α-cluster structure in 8Be and the property of the valence neutrons in 10Be are also discussed.

Background: Thousands of units of whole blood (WB) and blood components are transfused daily to treat trauma patients. Improved methods for blood storage are critical to support trauma‐related care. The Hemanext ONE® system offers a unique method for hypoxic storage of WB, with successfully demonstrated storage of clinically viable RBCs. This work evaluated the system for the storage of WB, focusing on platelet health and function. Study Design and Methods: WB was collected from healthy donors and processed through the Hemanext ONE® system. Hemoglobin oxygen saturation (HbSO2) levels of WB were depleted to 10%, 20%, or 30% of total HbSO2 and then stored in PVC bags sealed in oxygen‐impermeable bags (except for normoxic control) with samples collected on days 1, 7, and 14 post‐processing. Flow cytometry assessed the activation and apoptosis of platelets. Clot dynamics were assessed based on aggregometry and thromboelastography assays, as well as thrombin generation using a calibrated‐automated thrombogram method. Results: Hypoxic storage conditions were maintained throughout the storage period. Hypoxia triggered increased lactate production, but pH changes were negligible compared to normoxic control. Storage at 10% HbSO2 had a significant impact on platelet function, resulting in increased activation and reduced clot formation and aggregation. These effects were less significant at 20% and 30% HbSO2. Discussion: This study indicates that platelets are sensitive to hypoxic storage and suffer significant metabolic and functional deterioration when stored at or below 10% HbSO2. [ABSTRACT FROM AUTHOR]