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Junna Oba,1 Masako Toriya,2 Yoshifumi Uwamino,3 Koichi Matsuo4 1Department of Extended Intelligence for Medicine, the Ishii-Ishibashi Laboratory, Keio University School of Medicine, Tokyo, Japan; 2Global Research Institute, Keio University, Tokyo, Japan; 3Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan; 4Collaborative Research Resources, Keio University School of Medicine, Tokyo, JapanCorrespondence: Masako Toriya, Global Research Institute, Keio University, 2-15-45 Mita, Minato-ku, Tokyo, 108-8345, Japan, Tel +81-3-5427-1379, Fax +81-3-5427-1703, Email masako.toriya@keio.jpBackground: During the COVID-19 pandemic, there was an increasing need to expand diagnostic testing in hospitals. At Keio University Hospital (KUH), clinical staff were concerned that the demand for PCR testing might exceed the capacity of the Clinical Laboratory. In response, basic researchers at Keio University School of Medicine (KUSM) set out to build a new, collaborative, PCR testing system. To be authorized to perform such diagnostic PCR testing, KUSM registered its core laboratory as an external clinical laboratory (ECL).Methods: In the pandemic, there was a pressure to build the PCR system quickly. Speed required discussions that developed a shared understanding of the unprecedented, new KUH/KUSM PCR system. To design, construct, and archive the new PCR testing system, we used a systems engineering (SE) approach. This included diagram visualization of functional flows and application of the Unified Architecture Framework (UAF), both of which are often used in system building. We considered daily demand for PCR testing at KUH and KUSM, and daily COVID-19 infections in Japan.Results: We operated the collaborative PCR testing system from August 2020 to June 2022. Given public health insurance reimbursement policies, KUH focused on individuals with suspicious symptoms, while the ECL at KUSM screened samples from asymptomatic individuals. KUSM performed about half as many tests as KUH. Interviewing KUH staff revealed that diagrams helped promote a better understanding of the KUH/KUSM PCR testing system.Conclusion: When designing temporary systems that may be repurposed in the future, we suggest using an SE approach with diagrams and UAF perspectives. This approach will enable stakeholders to understand what is being proposed to be built, and facilitate achieving an informed consensus on the proposed system. We suggest that SE approaches should be widely used in projects that involve building and operating complex, collaborative systems, and documenting the process. Keywords: COVID-19, PCR test, clinical laboratory, systems engineering, diagram, temporary system

Inertial confinement fusion approaches involve the creation of high-energy-density states through compression. High gain scenarios may be enabled by the beneficial heating from fast electrons produced with an intense laser and by energy containment with a high-strength magnetic field. Here, we report experimental measurements from a configuration integrating a magnetized, imploded cylindrical plasma and intense laser-driven electrons as well as multi-stage simulations that show fast electrons transport pathways at different times during the implosion and quantify their energy deposition contribution. The experiment consisted of a CH foam cylinder, inside an external coaxial magnetic field of 5 T, that was imploded using 36 OMEGA laser beams. Two-dimensional (2D) hydrodynamic modelling predicts the CH density reaches [Formula: see text], the temperature reaches 920 eV and the external B-field is amplified at maximum compression to 580 T. At pre-determined times during the compression, the intense OMEGA EP laser irradiated one end of the cylinder to accelerate relativistic electrons into the dense imploded plasma providing additional heating. The relativistic electron beam generation was simulated using a 2D particle-in-cell (PIC) code. Finally, three-dimensional hybrid-PIC simulations calculated the electron propagation and energy deposition inside the target and revealed the roles the compressed and self-generated B-fields play in transport. During a time window before the maximum compression time, the self-generated B-field on the compression front confines the injected electrons inside the target, increasing the temperature through Joule heating. For a stronger B-field seed of 20 T, the electrons are predicted to be guided into the compressed target and provide additional collisional heating. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Toshiyuki Ohtani,1– 3 Koji Matsuo,4 Chihiro Sutoh,5 Fumiyo Oshima,2,3 Yoshiyuki Hirano,2,3 Akio Wakabayashi,6 Eiji Shimizu2,3,5 1Safety and Health Organization, Chiba University, Chiba, Japan; 2Research Center for Child Mental Development, Chiba University, Chiba, Japan; 3United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan; 4Department of Psychiatry, Faculty of Medicine, Saitama Medical University, Saitama, Japan; 5Department of Cognitive Behavioral Physiology, Graduate School of Medicine and School of Medicine, Chiba University, Chiba University, Chiba, Japan; 6Department of Psychology,Graduate School of Humanities, Chiba University, Chiba, JapanCorrespondence: Toshiyuki OhtaniSafety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba, 263-8522, JapanTel/Fax +81 43 290 2216Email otanit@Chiba-u.jpPurpose: In clinical settings, diagnosing comorbid depression in individuals with autism spectrum disorder (ASD) is often difficult. Neuroimaging studies have reported reduced activation of frontal and temporal regions during emotional face recognition task (EFRT) in ASD and depression. However, to the best of our knowledge, no study has examined differences in frontotemporal activation during EFRT between ASD with and without comorbid depression. We aimed to compare the frontotemporal hemodynamic responses to the EFRT in ASD with and without depression and to find clues to help in discriminating the characteristics between them.Patients and Methods: In 24 drug-naïve young adults with ASD (12 with depression [ASD-Dep(+)] and 12 without depression [ASD-Dep(-)]) and 12 with typical development (TD), frontotemporal hemodynamic responses during an EFRT were measured using functional near-infrared spectroscopy (fNIRS).Results: The ASD groups showed reduced activation during EFRT than the TD group in the right ventrolateral prefrontal cortex (VLPFC). Moreover, the ASD-Dep(+) group showed reduced activation during EFRT than the ASD-Dep(-) group in the right anterior temporal cortex (aTC), and reduced activation than the TD group in the left VLPFC.Conclusion: The observed results might reflect reduced regional activation in ASD and ASD with comorbid depression.Keywords: autism spectrum disorder, depression comorbidity, functional near-infrared spectroscopy, emotional face recognition, social cognition, frontotemporal activation

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value

BackgroundObservational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer.MethodsWe used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype.ResultsOverall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant.ConclusionsHigher BMI is associated with adverse survival among the majority of women with ovarian cancer.

BackgroundEvidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited.MethodsWe used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake.ResultsIntake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Toshinobu Hayashi,1,2 Mototsugu Shimokawa,3 Koichi Matsuo,2 Takanori Miyoshi,4 Yoko Toriyama,4 Chiaki Yokota,5 Jun Taniguchi,6 Kiyonori Hanada,7 Kyouichi Tsumagari,8 Noriko Okubo,9 Yoshimichi Koutake,10 Kohei Sakata,11 Yosei Kawamata,12 Takashi Goto,13 Yasufumi Tsurusaki,14 Makiko Koyabu1 1Department of Pharmacy, Clinical Research Institute, National Kyushu Medical Center, Fukuoka, Japan; 2Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; 3Cancer Biostatistics Laboratory, Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan; 4Department of Pharmacy, National Hospital Organization Beppu Medical Center, Oita, Japan; 5Department of Pharmacy, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan; 6Department of Pharmacy, National Hospital Organization Ureshino Medical Center, Saga, Japan; 7Department of Pharmacy, National Hospital Organization Kumamoto Saishunso National Hospital, Kumamoto, Japan; 8Department of Pharmacy, National Hospital Organization Miyakonojo Medical Center, Miyazaki, Japan; 9Department of Pharmacy, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan; 10Department of Pharmacy, National Hospital Organization Fukuoka National Hospital, Japan; 11Department of Pharmacy, National Hospital Organization Kumamoto South National Hospital, Kumamoto, Japan; 12Department of Pharmacy, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan; 13Department of Pharmacy, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan; 14Department of Pharmacy, National Hospital Organization Saga National Hospital, Saga, Japan Purpose: Improvement in the control of delayed chemotherapy-induced nausea and vomiting (CINV) is needed. There is limited information on antiemetic prophylaxis for patients undergoing low-emetic-risk chemotherapy (LEC), and the optimal antiemetic treatment is not well understood. Therefore, we analyzed the risk factors for delayed CINV to aid in the development of individualized treatments. Patients and methods: This prospective multicenter study was conducted in 13 hospitals and included patients with solid cancers undergoing LEC. A total of 222 patients were enrolled between September 2013 and November 2014. The participants completed a daily diary for 5 days after the commencement of the first cycle of LEC to describe the daily incidence of CINV (yes/no). Furthermore, the participants described the severity of nausea and the amount of food intake with the help of VAS. Results: Two hundred and ten patients provided their data that were analyzed using multivariate logistic regression to examine the risk factors for delayed CINV. History of CINV, Eastern Cooperative Oncology Group performance status score ≥1, acute CINV, and single-day antiemetic prophylaxis were identified as independent risk factors for delayed CINV. Conclusion: The current use of antiemetic prophylaxis according to the recommended guideline appears to effectively control delayed CINV in patients undergoing LEC. Therefore, patients with the abovementioned risk factors should be carefully observed, and their treatment should be adjusted according to their symptoms. The use of multiple-day dexamethasone may be beneficial for those patients who develop acute CINV, especially when it is accompanied by anorexia. Keywords: adverse effects, antiemetics, prophylaxis, quality of life

Naoko Okamoto,1 Kaori Umehara,1 Junko Sonoda,1 Mitsuyuki Hotta,2 Hiroki Mizushima,1 Yutaka Takagi,1 Keiko Matsuo,3 Naoko Baba4 1Skin Care Products Research Laboratories, Kao Corporation, Tokyo, 2Biological Science Research Laboratories, Kao Corporation, Tochigi, 3Office of the President, Kao Corporation, Tokyo, 4Department of Dermatology, Kanagawa Children’s Medical Center, Yokohama, Japan Objective: Despite the application of skin care treatments, many infants have skin problems such as dryness and erythema. We proposed a new combination skin care for infants which consisted of a foaming cleanser with lower surfactant activity and moisturizers that contained pseudo-ceramide. Subjects and methods: A total of 50 infants (age: 3–24 months) with insignificant levels of dry skin were enrolled in this usage trial. The parents washed the infants with the test cleanser while bathing and then applied the moisturizer (lotion or cream) containing pseudo-ceramide. Prior to and following the 4-week usage period, visual evaluation of the skin condition was conducted by a dermatologist, in addition to instrumental analysis. Results: Erythema and papule, accompanied by dryness, were commonly observed at week 0. However, by week 4, these symptoms significantly improved; the condition of none of the subjects deteriorated. The number of infants with lower cutaneous barrier function and higher skin pH decreased. The parents of the infants recognized improvements in the skin symptoms and were appreciative of the test materials. Conclusion: The combined usage of the foaming cleanser with lower surfactant activity and a moisturizer containing pseudo-ceramide may be effective in maintaining healthy infant skin and ameliorating the skin symptoms. Keywords: infant, cleanser, lotion, cream, dryness

Mariko Kitano,1 Shingo Iwano,1 Naozumi Hashimoto,2 Keiji Matsuo,3 Yoshinori Hasegawa,2 Shinji Naganawa1 1Department of Radiology, 2Department of Respiratory Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan; 3Department of Radiology, Ichinomiya Municipal Hospital, Ichinomiya, Aichi, Japan Background: We investigated correlations between lung volume collapsibility indices and pulmonary function test (PFT) results and assessed lobar differences in chronic obstructive pulmonary disease (COPD) patients, using paired inspiratory and expiratory three dimensional (3D) computed tomography (CT) images. Methods: We retrospectively assessed 28 COPD patients who underwent paired inspiratory and expiratory CT and PFT exams on the same day. A computer-aided diagnostic system calculated total lobar volume and emphysematous lobar volume (ELV). Normal lobar volume (NLV) was determined by subtracting ELV from total lobar volume, both for inspiratory phase (NLVI) and for expiratory phase (NLVE). We also determined lobar collapsibility indices: NLV collapsibility ratio (NLVCR) (%) = (1 - NLVE/NLVI) × 100%. Associations between lobar volumes and PFT results, and collapsibility indices and PFT results were determined by Pearson correlation analysis. Results: NLVCR values were significantly correlated with PFT results. Forced expiratory volume in 1 second, measured as percent of predicted results (FEV1%P) was significantly correlated with NLVCR values for the lower lobes (P

Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th) and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B) of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B administration. The results of this study provide evidence for the potential utility of Ag85B DNA inoculation as a novel approach for the treatment of asthma.Keywords: immunotherapy, asthma, Ag85B, mycobacteria, allergy

Yohei Tanaka1,2, Kiyoshi Matsuo1, Shunsuke Yuzuriha11Department of Plastic and Reconstructive Surgery, Shinshu University School of Medicine, Matsumoto, Japan; 2Clinica Tanaka Plastic and Reconstructive Surgery and Anti-aging Center, Matsumoto, JapanBackground: We reported previously that near-infrared (NIR) irradiation provides long-lasting stimulation of elastin, and is efficient for skin rejuvenation. Many studies have indicated the efficacy of various types of laser, but did not include sufficiently objective evaluation. Therefore, we evaluated the efficacy of NIR laser treatment not only subjectively but also objectively.Methods: Fifty Japanese patients were treated with a NIR 1064-nm neodymium: YAG laser. Objective computer assessments were performed by Canfield VISIA Complexion Analysis for improvement of dilated pores, skin texture, and wrinkles. The volunteers then provided subjective assessments. Histological evaluations of elastin were performed by Victoria blue staining up to 90 days post-treatment in four Japanese volunteers.Results: Mean pretreatment percentiles of dilated pores, skin texture, and wrinkles were 51.08 ± 24.82, 54.7 ± 26.33, and 58.02 ± 28.61, respectively. Mean post-treatment percentiles of dilated pores, skin texture, and wrinkles were 53.58 ± 23.89, 58.58 ± 24.44, and 62.2 ± 25.39, respectively. All objective computer assessments evaluated by percentiles in dilated pores, skin texture, and wrinkles showed significant improvement after NIR laser treatment. Ninety-six percent, 100%, and 98% of volunteers reported satisfaction with the improvement of dilated pores, skin texture, and wrinkles, respectively. NIR laser treatment appeared to increase the amount of elastin at day 30, which then decreased slightly but was still elevated at day 90 compared with nonirradiated controls on day 0. Thickening of the epidermis was detected on day 30, and epidermal smoothness persisted for up to 90 days. No treatment-related adverse events were observed.Conclusions: NIR irradiation increased elastin in the dermis, and achieved skin rejuvenation. The results indicated that NIR irradiation provides safe and effective long-term stimulation of elastin, which is beneficial for improving dilated pores, skin texture, and wrinkles.Keywords: near-infrared laser, elastin, skin rejuvenation, objective assessment