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1. CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

Author

Tim Harvey-Samuel, Xuechun Feng, Emily M. Okamoto, Deepak-Kumar Purusothaman, Philip T. Leftwich, Luke Alphey, and Valentino M. Gantz

Subjects
Science
Abstract

Abstract Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus, and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes.

Published
2023
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2. Next-generation CRISPR gene-drive systems using Cas12a nuclease

Author

Sara Sanz Juste, Emily M. Okamoto, Christina Nguyen, Xuechun Feng, and Víctor López Del Amo

Subjects
Science
Abstract

Abstract One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.

Published
2023
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4. Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles

Author

Alena L. Bishop, Víctor López Del Amo, Emily M. Okamoto, Zsolt Bodai, Alexis C. Komor, and Valentino M. Gantz

Subjects
Science
Abstract

CRISPR gene drives are genetic elements capable of quickly spreading through populations and they offer promising solutions for curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations. Here the authors present a method for overcoming resistance alleles “double-tap,” that encodes additional gRNAs in the gene drive that target the most common generated resistance alleles.

Published
2022
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5. Social networks and obesity among Somali immigrants and refugees

Author

Jane W. Njeru, Mark L. Wieland, Janet M. Okamoto, Paul J. Novotny, Margaret K. Breen-Lyles, Ahmed Osman, Yahye A. Ahmed, Mohamud A. Nur, Omar Nur, and Irene G. Sia

Subjects
Community-based participatory research, Immigrants, Obesity, Refugees, Social network analysis, Somali, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Somali immigrants and refugees to the United States are at high risk for obesity and related cardiovascular risk. Social network factors influence health behaviors and are important contributors to the obesity epidemic. The objective of this study was to describe social networks and obesity-related characteristics among adult Somali immigrants in a Minnesota city in order to inform a community-based, participatory, research-derived, social network intervention to decrease obesity rates. Methods Survey data (demographics, general health measures, and sociobehavioral and network measures) and height and weight measures (for calculating body mass index) were collected from adult Somali immigrants by bilingual study team members at community locations. Descriptive statistics were used to report the survey and biometric data. Logistic regression models were used to describe the basic associations of participants and network factors. Network data were analyzed to identify nodes and ties, to visualize the network, and to identify potential interventionists for a future social network intervention. Results Of the 646 participants, 50% were overweight or affected by obesity. The network had 1703 nodes with 3583 ties between nodes, and modularity was high (0.75). Compared with respondents of normal weight, participants who were overweight or affected by obesity had more network members who were also overweight or obese (odds ratio [OR], 2.90; 95% CI, 1.11–7.56; P = .03); this was most notable for men (OR, 4.58; 95% CI, 1.22–17.22; P = .02) and suggestive for those 50 years or older (OR, 24.23; 95% CI, 1.55–377.83; P = .03). Weight loss intention among participants who were overweight or affected by obesity was associated with number of family members and friends trying to lose weight, enabling functional network factors (social norms for weight loss, social support for healthy eating, and social cohesion), and less favorable obesogenic social norms. Conclusions In this community sample of Somali immigrants, distinct social networks are clustered by weight status, and social contacts and functional network characteristics are related to individuals’ weight loss intentions. These factors should be considered in weight loss interventions and programs. A social network intervention targeting weight loss, within a community-based participatory research framework, is feasible in this vulnerable population.

Published
2020
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6. Addressing community health needs through community engagement research advisory boards

Author

Christi A. Patten, Monica L. Albertie, Chara A. Chamie, Tabetha A. Brockman, Mary Gorfine, Rosa Nicholas, Martha J. Bock, Janet M. Okamoto, Sumedha G. Penheiter, and Joyce E. Balls-Berry

Subjects
Community, research, health, needs assessment, program evaluation, Medicine
Abstract

Over 80% of CTSA programs have a community advisory board (CAB). Little is known about how research discussed with CABs aligns with community priorities (bidirectionality). This program evaluation assessed researcher presentations from 2014 to 2018 to the CABs linked to our CTSA at all three sites (Minnesota, Arizona, and Florida) for relevance to local community needs identified in 2013 and/or 2016. From content analysis, of 65 presentations total, 41 (63%) addressed ≥1 local health needs (47% Minnesota, 60% Florida, and 80% Arizona). Cross-cutting topics were cancer/cancer prevention (physical activity/obesity/nutrition) and mental health. Results could help to prioritize health outcomes of community-engaged research efforts.

Published
2019
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7. Tensile and impact properties of pulverized oil palm fiber reinforced polypropylene composites : A comparison study with wood fiber reinforced polypropylene composites

Author

M. N. A. Nordin, K. Sakamoto, H. Azhari, K. Goda, M. Okamoto, H. Ito, and T. Endo

Subjects
oil palm fiber, polypropylene, wood plastic composites (wpc), tensile strength, impact strength, size effect, failure behavior, Mechanical engineering and machinery, TJ1-1570, Mechanics of engineering. Applied mechanics, TA349-359
Abstract

In this study, the Malaysian oil palm fiber (OPF) was extracted from empty fruit bunch (EFB) and used as a reinforcement of polymer composite materials. 10 wt.% and 25 wt.% of OPF were incorporated with polypropylene (PP) and maleated polypropylene (MAPP) to produce injection-molded composite material. For comparison purpose, virgin PP and polymer composites reinforced with wood fiber (WPC) were also fabricated as benchmark samples. From the tensile test result of 25 wt.% of fiber loading, it produced higher tensile properties of the composites. Moreover, the obtained OPF/PP composites showed comparable properties with the WPC material. The second objective of this study is to investigate the effect of fiber sizes on tensile and impact properties of both WPC and OPF/PP composite. The wood fiber and OPF were mechanically classified into several size ranges by using different mesh sieves and proceeded with the kneading and injection molding. The tensile and impact tests were carried out for each type of sample in order to verify the influence of fiber size on the tensile and impact resistance behavior of the WPC and OPF/PP composites.

Published
2018
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8. Development of Rat Caries-Induced Pulpitis Model for Vital Pulp Therapy

Author

H. Huang, M. Okamoto, M. Watanabe, S. Matsumoto, K. Moriyama, S. Komichi, M. Ali, S. Matayoshi, R. Nomura, K. Nakano, Y. Takahashi, and M. Hayashi

Subjects
General Dentistry
Abstract

Rodent animal models for vital pulp therapy are commonly used in dental research because their tooth anatomy and cellular processes are similar to the anatomy and processes in humans. However, most studies have been conducted using uninfected sound teeth, which makes it difficult to adequately assess the inflammatory shift after vital pulp therapy. In the present study, we aimed to establish a caries-induced pulpitis model based on the conventional rat caries model and then evaluate inflammatory changes during the wound-healing process after pulp capping in a model of reversible pulpitis induced by carious infection. To establish the caries-induced pulpitis model, the pulpal inflammatory status was investigated at different stages of caries progression by immunostaining targeted to specific inflammatory biomarkers. Immunohistochemical staining revealed that both Toll-like receptor 2 and proliferating cell nuclear antigen were expressed in moderate and severe caries-stimulated pulp, indicating that an immune reaction occurred at both stages of caries progression. M2 macrophages were predominant in moderate caries-stimulated pulp, whereas M1 macrophages were predominant in the severe caries-stimulated pulp. Pulp capping in teeth with moderate caries (i.e., teeth with reversible pulpitis) led to complete tertiary dentin formation within 28 d after treatment. Impaired wound healing was observed in teeth with severe caries (i.e., teeth with irreversible pulpitis). During the wound-healing process in reversible pulpitis after pulp capping, M2 macrophages were predominant at all time points; their proliferative capacity was upregulated in the early stage of wound healing compared with healthy pulp. In conclusion, we successfully established a caries-induced pulpitis model for studies of vital pulp therapy. M2 macrophages have an important role in the early stages of the wound-healing process in reversible pulpitis.

Published
2023

9. Understanding American Indian Perceptions Toward Radiation Therapy

Author

Samir H. Patel MD, Sasha Ebrahimi PhD, Donald W. Northfelt MD, Timothy E. Mathews FNP-BC, Farhia M. Omar MPH, Erika D. Martinez MBA, Todd A. DeWees PhD, and Janet M. Okamoto PhD

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Many American Indian (AI) and Alaska native (AN) patients do not complete guideline-concordant cancer care for the 4 most common cancers. Our aim was to better understand AI/AN attitudes toward radiation therapy (RT). Patients eligible for this survey study were AI/AN patients with cancer at the Phoenix Indian Medical Center who either received previous RT or were recommended to receive RT. An 18-item questionnaire was administered to each of the 50 participants from October 1, 2018, through February 15, 2019. Willingness to travel for RT was compared to respondent characteristics, concerns regarding RT, and obstacles to obtain RT. Duration of RT was important to 78% of patients: 24% would consider traveling 25 miles or more for a standard course, and 48% would travel that distance for a shorter course ( P < .001). The top-ranked barriers to RT were transportation, cost of treatment, and insurance compatibility. The top-ranked concerns about RT were adverse effects, cost of treatment, and fear of RT. Concerns about adverse effects were associated with the radiation team’s inability to explain the treatment ( P = .05). Transportation concerns were significantly associated with accessibility ( P = .02), communication with the RT team ( P = .02), and fear of RT ( P = .04). AI/AN patients are concerned about the adverse effects of RT and the logistics of treatment, particularly costs, transportation, and insurance compatibility. Use of culturally specific education and hypofractionation regimens may increase acceptance of RT for AI/AN patients with cancer, and this hypothesis will be tested in a future educational intervention-based study.

Published
2020
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10. Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory

Author

Sabrina A. Gardner, Katelyn S. Weymouth, Wei S. Kelly, Ekaterina Bogdanova, Wenjie Chen, Daniel Lupu, Joshua Suhl, Qiandong Zeng, Ute Geigenmüller, Debbie Boles, Patricia M. Okamoto, Geraldine McDowell, Melissa A. Hayden, and Narasimhan Nagan

Subjects
Inherited cancer panel, VUS, HBOC, Lynch syndrome, CMMRD, Variant classification, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470
Abstract

Abstract Background Extensive clinical and genetic heterogeneity of inherited cancers has allowed multi-gene panel testing to become an efficient means for identification of patients with an inherited predisposition to a broad spectrum of syndromic and nonsyndromic forms of cancer. This study reports our experience with a 27-gene inherited cancer panel on a cohort of 630 consecutive individuals referred for testing at our laboratory with the following objectives: 1. Determine the rates for positive cases and those with variants of uncertain clinical significance (VUS) relative to data published in the recent literature, 2. Examine heterogeneity among the constituent genes on the panel, and 3. Review test uptake in the cohort relative to other reports describing outcomes for expanded panel testing. Methods Clinical and genomic data were reviewed on 630 individuals tested on a panel of 27 genes selected on the basis of high (≥ 40%) or moderate to low (≤ 40%) lifetime risk of hereditary cancer. These patients were not enriched for adherence to the National Comprehensive Cancer Network (NCCN) criteria for Hereditary Breast and Ovarian Cancer (HBOC) or Lynch Syndrome (LS) and constitute a referral laboratory cohort. Results Sixty-five individuals with variants classified as pathogenic or likely pathogenic across 14 genes were identified for an overall positive rate of 10.3%. Although a family history of cancer constituted a major reason for referral, accounting for 84% of our cohort, excluding patients with a known familial variant did not have a significant impact on the observed positive rate (9% vs 10.3%). More than half (58%) of the pathogenic or likely pathogenic variants were observed in high or moderate to low risk genes on the panel, while only 42% occurred in classic HBOC or LS-associated genes. Conclusion These results provide the actual percentage of family or personal history of cancer that can be attributed to pathogenic or likely pathogenic variants in one or more of the genes on our panel and corroborate the utility of multi-gene panels over sequential testing to identify individuals with an inherited predisposition to cancer.

Published
2018
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12. Finances and Fate: Parent Financial Socialization, Locus of Control, and Mental Health in Emerging Adulthood

Author

Ashley B. LeBaron-Black, Xiaomin Li, Rachel M. Okamoto, Matthew T. Saxey, and Toby M. Driggs

Subjects
Developmental and Educational Psychology, Experimental and Cognitive Psychology, Life-span and Life-course Studies
Abstract

Utilizing a sample of 4182 U.S. emerging adults and structural equation modeling, we examined how parent financial socialization received during childhood and adolescence is associated with mental health in emerging adulthood and whether locus of control is an intervening variable. Financial socialization was negatively associated with anxiety and depressive symptoms, and positively associated with life satisfaction. Indirect pathways were found through locus of control. That is, emerging adults who had received better financial socialization were more likely to report an internal locus of control and thus were less likely to be experiencing anxiety and depressive symptoms and more likely to be satisfied with life. These findings provide educators with further evidence of the importance of parent financial socialization, being associated with not only financial health but also mental health. Clinicians of emerging adults may consider financial education and internal locus of control development as intervention points for mental health improvement.

Published
2022

14. Applying Social Network Analysis to Evaluate Implementation of a Multisector Population Health Collaborative That Uses a Bridging Hub Organization

Author

Aaron L. Leppin, Janet M. Okamoto, Paige W. Organick, Anjali D. Thota, Francisco J. Barrera-Flores, Mark L. Wieland, Rozalina G. McCoy, Robert P. Bonacci, and Victor M. Montori

Subjects
social network analysis, population health, health promotion, community based programs, partnerships, Public aspects of medicine, RA1-1270
Abstract

Background: Multisector collaboratives are increasingly popular strategies for improving population health. To be comprehensive, collaboratives must coordinate the activities of many organizations across a geographic region. Many policy-relevant models encourage creation and use of centralized hub organizations to do this work, yet there is little guidance on how to evaluate implementation of such hubs and track their network reach. We sought to demonstrate how social network analysis (SNA) could be used for this purpose.Methods: Through formative research, we defined and conceptualized key characteristics of a bridging hub network and identified a set of candidate measures—(1) network membership, (2) network interaction, (3) role and reach of the bridging hub, and (4) network collaboration—to evaluate its implementation within a pre-determined geographic region of Southeast Minnesota, USA. We then developed and administered a survey to assess outcomes as part of a SNA. We commented on the feasibility and usefulness of the methods.Results: The initial surveyed network consisted of 50 healthcare organizational sites and 50 community organizations representing sectors of public health, education, research, health promotion, social services, and long-term care and supports. Fifty-three of these organizations responded to the survey. The network's level of collaboration was “Cooperation” (level 2 of 5) and reported levels of collaboration varied by organization. Thirty-eight additional, unsurveyed organizations were identified as collaborators by respondents, pushing the theoretical network denominator up to 138 organizations. These additional organizations included grocery stores, ambulance services, and smaller, independent healthcare and community-based services focused on meeting the needs of underserved populations. The bridging hub organization had the highest betweenness centrality and was in good position to bridge healthcare and the community, although its organizational reach was estimated at only 51%. The SNA methods were feasible and useful for identifying opportunities and guiding implementation.Conclusions: Bridging hub organizations are not likely to link—or even be aware of—all relevant organizations in a geographic region at initial implementation. SNA may be a useful method for evaluating the value and reach of a bridging hub organization and guiding ongoing implementation efforts.Trial registration: http://ClinicalTrials.gov; #NCT03046498

Published
2018
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15. Novel Functional Peptide for Next-Generation Vital Pulp Therapy

Author

M. Watanabe, M. Okamoto, S. Komichi, H. Huang, S. Matsumoto, K. Moriyama, J. Ohshima, S. Abe, M. Morita, M. Ali, K. Takebe, I. Kozaki, A. Fujimoto, K. Kanie, R. Kato, K. Uto, M. Ebara, A. Yamawaki-Ogata, Y. Narita, Y. Takahashi, and M. Hayashi

Subjects
General Dentistry
Abstract

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography–tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Published
2022

19. 追悼文

Author

K. Koyama, M. Takahashi, T. Takigawa, H. Watanabe, T. Shikata, M. Okamoto, and O. Urakawa

Subjects
Mechanics of Materials, Mechanical Engineering, General Materials Science, Condensed Matter Physics
Published
2021

21. 3007 Addressing Community Health Needs through Community Engagement Research Advisory Boards

Author

Christi Patten, Monica L. Albertie, Chara A. Chamie, Tabetha A. Brockman, Mary Gorfine, Rosa Nicholas, Martha J. Bock, Janet M. Okamoto, Sumedha G. Penheiter, and Joyce E. Balls-Berry

Subjects
Medicine
Abstract

OBJECTIVES/SPECIFIC AIMS: Over 80% of CTSA programs have a community advisory board (CAB), an effective strategy to increase community engagement (CE) in research. Little is known about how the research discussed with CABs aligns with community priorities (i.e., bi-directionality). This program evaluation assessed the health topics presented by researchers to the CABs linked to our CE Program at all three Mayo Clinic sites (MN, AZ, and FL) for relevance to local community needs. METHODS/STUDY POPULATION: Two coders classified Mayo researcher presentations to our CABs from 2014-2018 for relevance to needs identified in the local 2013 and/or 2016 County Health Needs Assessments and specific topic(s); with high levels of agreement (Kappa=0.90). RESULTS/ANTICIPATED RESULTS: Overall, of the 65 presentations 41 (63%) addressed one or more local health needs (47% MN, 60% FL, 80% AZ). Cross-cutting health topics addressed at 2 sites were physical activity/obesity/nutrition and mental health. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings were shared with our CABs to obtain input on future directions. The FL and AZ CABs are systematic in seeking out or initiating research projects that address local health needs, an approach the MN site is interested in adopting. Ultimately, it is important to demonstrate improved health outcomes with CTSA-based CE research strategies. Understanding community health needs and depth of researchers in those areas may help to focus priorities for demonstrating such outcomes.

Published
2019
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22. DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy

Author

M. E. Fenstermacher, J. Abbate, S. Abe, T. Abrams, M. Adams, B. Adamson, N. Aiba, T. Akiyama, P. Aleynikov, E. Allen, S. Allen, H. Anand, J. Anderson, Y. Andrew, T. Andrews, D. Appelt, R. Arbon, N. Ashikawa, A. Ashourvan, M. Aslin, Y. Asnis, M. Austin, D. Ayala, J. Bak, I. Bandyopadhyay, S. Banerjee, K. Barada, L. Bardoczi, J. Barr, E. Bass, D. Battaglia, A. Battey, W. Baumgartner, L. Baylor, J. Beckers, M. Beidler, E. Belli, J. Berkery, T. Bernard, N. Bertelli, M. Beurskens, R. Bielajew, S. Bilgili, B. Biswas, S. Blondel, J. Boedo, I. Bogatu, R. Boivin, T. Bolzonella, M. Bongard, X. Bonnin, P. Bonoli, M. Bonotto, A. Bortolon, S. Bose, N. Bosviel, S. Bouwmans, M. Boyer, W. Boyes, L. Bradley, R. Brambila, D. Brennan, S. Bringuier, L. Brodsky, M. Brookman, J. Brooks, D. Brower, G. Brown, W. Brown, M. Burke, K. Burrell, K. Butler, R. Buttery, I. Bykov, P. Byrne, A. Cacheris, K. Callahan, J. Callen, G. Campbell, J. Candy, J. Canik, P. Cano-Megias, N. Cao, L. Carayannopoulos, T. Carlstrom, W. Carrig, T. Carter, W. Cary, L. Casali, M. Cengher, G. Cespedes Paz, R. Chaban, V. Chan, B. Chapman, I. Char, A. Chattopadhyay, R. Chen, J. Chen, X. Chen, M. Chen, Z. Chen, M. Choi, W. Choi, G. Choi, L. Chousal, C. Chrobak, C. Chrystal, Y. Chung, R. Churchill, M. Cianciosa, J. Clark, M. Clement, S. Coda, A. Cole, C. Collins, W. Conlin, A. Cooper, J. Cordell, B. Coriton, T. Cote, J. Cothran, A. Creely, N. Crocker, C. Crowe, B. Crowley, T. Crowley, D. Cruz-Zabala, D. Cummings, M. Curie, D. Curreli, A. Dal Molin, B. Dannels, A. Dautt-Silva, K. Davda, G. De Tommasi, P. De Vries, G. Degrandchamp, J. Degrassie, D. Demers, S. Denk, S. Depasquale, E. Deshazer, A. Diallo, S. Diem, A. Dimits, R. Ding, S. Ding, W. Ding, T. Do, J. Doane, G. Dong, D. Donovan, J. Drake, W. Drews, J. Drobny, X. Du, H. Du, V. Duarte, D. Dudt, C. Dunn, J. Duran, A. Dvorak, F. Effenberg, N. Eidietis, D. Elder, D. Eldon, R. Ellis, W. Elwasif, D. Ennis, K. Erickson, D. Ernst, M. Fasciana, D. Fedorov, E. Feibush, N. Ferraro, J. Ferreira, J. Ferron, P. Fimognari, D. Finkenthal, R. Fitzpatrick, P. Fox, W. Fox, L. Frassinetti, H. Frerichs, H. Frye, Y. Fu, K. Gage, J. Galdon Quiroga, A. Gallo, Q. Gao, A. Garcia, M. Garcia Munoz, D. Garnier, A. Garofalo, A. Gattuso, D. Geng, K. Gentle, D. Ghosh, L. Giacomelli, S. Gibson, E. Gilson, C. Giroud, F. Glass, A. Glasser, D. Glibert, P. Gohil, R. Gomez, S. Gomez, X. Gong, E. Gonzales, A. Goodman, Y. Gorelov, V. Graber, R. Granetz, T. Gray, D. Green, C. Greenfield, M. Greenwald, B. Grierson, R. Groebner, W. Grosnickle, M. Groth, H. Grunloh, S. Gu, W. Guo, H. Guo, P. Gupta, J. Guterl, W. Guttenfelder, T. Guzman, S. Haar, R. Hager, S. Hahn, M. Halfmoon, T. Hall, K. Hallatschek, F. Halpern, G. Hammett, H. Han, E. Hansen, C. Hansen, M. Hansink, J. Hanson, M. Hanson, G. Hao, A. Harris, R. Harvey, S. Haskey, E. Hassan, A. Hassanein, D. Hatch, R. Hawryluk, W. Hayashi, W. Heidbrink, J. Herfindal, J. Hicok, D. Hill, E. Hinson, C. Holcomb, L. Holland, C. Holland, E. Hollmann, J. Hollocombe, A. Holm, I. Holmes, K. Holtrop, M. Honda, R. Hong, R. Hood, A. Horton, L. Horvath, M. Hosokawa, S. Houshmandyar, N. Howard, E. Howell, D. Hoyt, W. Hu, Y. Hu, Q. Hu, J. Huang, Y. Huang, J. Hughes, T. Human, D. Humphreys, P. Huynh, A. Hyatt, C. Ibanez, L. Ibarra, R. Icasas, K. Ida, V. Igochine, Y. In, S. Inoue, A. Isayama, O. Izacard, V. Izzo, A. Jackson, G. Jacobsen, A. Jaervinen, A. Jalalvand, J. Janhunen, S. Jardin, H. Jarleblad, Y. Jeon, H. Ji, X. Jian, E. Joffrin, A. Johansen, C. Johnson, T. Johnson, C. Jones, I. Joseph, D. Jubas, B. Junge, W. Kalb, R. Kalling, C. Kamath, J. Kang, D. Kaplan, A. Kaptanoglu, S. Kasdorf, J. Kates-Harbeck, P. Kazantzidis, A. Kellman, D. Kellman, C. Kessel, K. Khumthong, E. Kim, H. Kim, J. Kim, S. Kim, K. Kim, C. Kim, W. Kimura, M. King, J. King, J. Kinsey, A. Kirk, B. Kiyan, A. Kleiner, V. Klevarova, R. Knapp, M. Knolker, W. Ko, T. Kobayashi, E. Koch, M. Kochan, B. Koel, M. Koepke, A. Kohn, R. Kolasinski, E. Kolemen, E. Kostadinova, M. Kostuk, G. Kramer, D. Kriete, L. Kripner, S. Kubota, J. Kulchar, K. Kwon, R. La Haye, F. Laggner, H. Lan, R. Lantsov, L. Lao, A. Lasa Esquisabel, C. Lasnier, C. Lau, B. Leard, J. Lee, R. Lee, M. Lee, Y. Lee, C. Lee, S. Lee, M. Lehnen, A. Leonard, E. Leppink, M. Lesher, J. Lestz, J. Leuer, N. Leuthold, X. Li, K. Li, E. Li, G. Li, L. Li, Z. Li, J. Li, Y. Li, Z. Lin, D. Lin, X. Liu, J. Liu, Y. Liu, T. Liu, C. Liu, Z. Liu, D. Liu, A. Liu, A. Loarte-Prieto, L. Lodestro, N. Logan, J. Lohr, B. Lombardo, J. Lore, Q. Luan, T. Luce, T. Luda Di Cortemiglia, N. Luhmann, R. Lunsford, Z. Luo, A. Lvovskiy, B. Lyons, X. Ma, M. Madruga, B. Madsen, C. Maggi, K. Maheshwari, A. Mail, J. Mailloux, R. Maingi, M. Major, M. Makowski, R. Manchanda, C. Marini, A. Marinoni, A. Maris, T. Markovic, L. Marrelli, E. Martin, J. Mateja, G. Matsunaga, R. Maurizio, P. Mauzey, D. Mauzey, G. Mcardle, J. Mcclenaghan, K. Mccollam, C. Mcdevitt, K. Mckay, G. Mckee, A. Mclean, V. Mehta, E. 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P, Finkenthal, D, Fitzpatrick, R, Fox, P, Fox, W, Frassinetti, L, Frerichs, H, Frye, H, Fu, Y, Gage, K, Quiroga, J, Gallo, A, Gao, Q, Garcia, A, Munoz, M, Garnier, D, Garofalo, A, Gattuso, A, Geng, D, Gentle, K, Ghosh, D, Giacomelli, L, Gibson, S, Gilson, E, Giroud, C, Glass, F, Glasser, A, Glibert, D, Gohil, P, Gomez, R, Gomez, S, Gong, X, Gonzales, E, Goodman, A, Gorelov, Y, Graber, V, Granetz, R, Gray, T, Green, D, Greenfield, C, Greenwald, M, Grierson, B, Groebner, R, Grosnickle, W, Groth, M, Grunloh, H, Gu, S, Guo, W, Guo, H, Gupta, P, Guterl, J, Guttenfelder, W, Guzman, T, Haar, S, Hager, R, Hahn, S, Halfmoon, M, Hall, T, Hallatschek, K, Halpern, F, Hammett, G, Han, H, Hansen, E, Hansen, C, Hansink, M, Hanson, J, Hanson, M, Hao, G, Harris, A, Harvey, R, Haskey, S, Hassan, E, Hassanein, A, Hatch, D, Hawryluk, R, Hayashi, W, Heidbrink, W, Herfindal, J, Hicok, J, Hill, D, Hinson, E, Holcomb, C, Holland, L, Holland, C, Hollmann, E, Hollocombe, J, Holm, A, Holmes, I, Holtrop, K, Honda, M, Hong, R, Hood, R, Horton, A, Horvath, L, Hosokawa, M, Houshmandyar, S, Howard, N, Howell, E, Hoyt, D, Hu, W, Hu, Y, Hu, Q, Huang, J, Huang, Y, Hughes, J, Human, T, Humphreys, D, Huynh, P, Hyatt, A, Ibanez, C, Ibarra, L, Icasas, R, Ida, K, Igochine, V, In, Y, Inoue, S, Isayama, A, Izacard, O, Izzo, V, Jackson, A, Jacobsen, G, Jaervinen, A, Jalalvand, A, Janhunen, J, Jardin, S, Jarleblad, H, Jeon, Y, Ji, H, Jian, X, Joffrin, E, Johansen, A, Johnson, C, Johnson, T, Jones, C, Joseph, I, Jubas, D, Junge, B, Kalb, W, Kalling, R, Kamath, C, Kang, J, Kaplan, D, Kaptanoglu, A, Kasdorf, S, Kates-Harbeck, J, Kazantzidis, P, Kellman, A, Kellman, D, Kessel, C, Khumthong, K, Kim, E, Kim, H, Kim, J, Kim, S, Kim, K, Kim, C, Kimura, W, King, M, King, J, Kinsey, J, Kirk, A, Kiyan, B, Kleiner, A, Klevarova, V, Knapp, R, Knolker, M, Ko, W, Kobayashi, T, Koch, E, Kochan, M, Koel, B, Koepke, M, Kohn, A, Kolasinski, R, Kolemen, E, Kostadinova, E, Kostuk, M, Kramer, G, Kriete, D, Kripner, L, Kubota, S, Kulchar, J, Kwon, K, La Haye, R, Laggner, F, Lan, H, Lantsov, R, Lao, L, Esquisabel, A, Lasnier, C, Lau, C, Leard, B, Lee, J, Lee, R, Lee, M, Lee, Y, Lee, C, Lee, S, Lehnen, M, Leonard, A, Leppink, E, Lesher, M, Lestz, J, Leuer, J, Leuthold, N, Li, X, Li, K, Li, E, Li, G, Li, L, Li, Z, Li, J, Li, Y, Lin, Z, Lin, D, Liu, X, Liu, J, Liu, Y, Liu, T, Liu, C, Liu, Z, Liu, D, Liu, A, Loarte-Prieto, A, Lodestro, L, Logan, N, Lohr, J, Lombardo, B, Lore, J, Luan, Q, Luce, T, Di Cortemiglia, T, Luhmann, N, Lunsford, R, Luo, Z, Lvovskiy, A, Lyons, B, Ma, X, Madruga, M, Madsen, B, Maggi, C, Maheshwari, K, Mail, A, Mailloux, J, Maingi, R, Major, M, Makowski, M, Manchanda, R, Marini, C, Marinoni, A, Maris, A, Markovic, T, Marrelli, L, Martin, E, Mateja, J, Matsunaga, G, Maurizio, R, Mauzey, P, Mauzey, D, Mcardle, G, Mcclenaghan, J, Mccollam, K, Mcdevitt, C, Mckay, K, Mckee, G, Mclean, A, Mehta, V, Meier, E, Menard, J, Meneghini, O, Merlo, G, Messer, S, Meyer, W, Michael, C, Michoski, C, Milne, P, Minet, G, Misleh, A, Mitrishkin, Y, Moeller, C, Montes, K, Morales, M, Mordijck, S, Moreau, D, Morosohk, S, Morris, P, Morton, L, Moser, A, Moyer, R, Moynihan, C, Mrazkova, T, Mueller, D, Munaretto, S, Burgos, J, Murphy, C, Murphy, K, Muscatello, C, Myers, C, Nagy, A, Nandipati, G, Navarro, M, Nave, F, Navratil, G, Nazikian, R, Neff, A, Neilson, G, Neiser, T, Neiswanger, W, Nelson, D, Nelson, A, Nespoli, F, Nguyen, R, Nguyen, L, Nguyen, X, Nichols, J, Nocente, M, Nogami, S, Noraky, S, Norausky, N, Nornberg, M, Nygren, R, Odstrcil, T, Ogas, D, Ogorman, T, Ohdachi, S, Ohtani, Y, Okabayashi, M, Okamoto, M, Olavson, L, Olofsson, E, Omullane, M, Oneill, R, Orlov, D, Orvis, W, Osborne, T, Pace, D, Canal, G, Martinez, A, Palacios, L, Pan, C, Pan, Q, Pandit, R, Pandya, M, Pankin, A, Park, Y, Park, J, Parker, S, Parks, P, Parsons, M, Patel, B, Pawley, C, Paz-Soldan, C, Peebles, W, Pelton, S, Perillo, R, Petty, C, Peysson, Y, Pierce, D, Pigarov, A, Pigatto, L, Piglowski, D, Pinches, S, Pinsker, R, Piovesan, P, Piper, N, Pironti, A, Pitts, R, Pizzo, J, Plank, U, Podesta, M, Poli, E, Poli, F, Ponce, D, Popovic, Z, Porkolab, M, Porter, G, Powers, C, Powers, S, Prater, R, Pratt, Q, Pusztai, I, Qian, J, Qin, X, Ra, O, Rafiq, T, Raines, T, Raman, R, Rauch, J, Raymond, A, Rea, C, Reich, M, Reiman, A, Reinhold, S, Reinke, M, Reksoatmodjo, R, Ren, Q, Ren, Y, Ren, J, Rensink, M, Renteria, J, Rhodes, T, Rice, J, Roberts, R, Robinson, J, Fernandez, P, Rognlien, T, Rosenthal, A, Rosiello, S, Rost, J, Roveto, J, Rowan, W, Rozenblat, R, Ruane, J, Rudakov, D, Ruiz, J, Rupani, R, Saarelma, S, Sabbagh, S, Sachdev, J, Saenz, J, Saib, S, Salewski, M, Salmi, A, Sammuli, B, Samuell, C, Sandorfi, A, Sang, C, Sarff, J, Sauter, O, Schaubel, K, Schmitz, L, Schmitz, O, Schneider, J, Schroeder, P, Schultz, K, Schuster, E, Schwartz, J, Sciortino, F, Scotti, F, Scoville, J, Seltzman, A, Seol, S, Sfiligoi, I, Shafer, M, Sharapov, S, Shen, H, Sheng, Z, Shepard, T, Shi, S, Shibata, Y, Shin, G, Shiraki, D, Shousha, R, Si, H, Simmerling, P, Sinclair, G, Sinha, J, Sinha, P, Sips, G, Sizyuk, T, Skinner, C, Sladkomedova, A, Slendebroek, T, Slief, J, Smirnov, R, Smith, J, Smith, S, Smith, D, Snipes, J, Snoep, G, Snyder, A, Snyder, P, Solano, E, Solomon, W, Song, J, Sontag, A, Soukhanovskii, V, Spendlove, J, Spong, D, Squire, J, Srinivasan, C, Stacey, W, Staebler, G, Stagner, L, Stange, T, Stangeby, P, Stefan, R, Stemprok, R, Stephan, D, Stillerman, J, Stoltzfus-Dueck, T, Stonecipher, W, Storment, S, Strait, E, Su, D, Sugiyama, L, Sun, Y, Sun, P, Sun, Z, Sun, A, Sundstrom, D, Sung, C, Sungcoco, J, Suttrop, W, Suzuki, Y, Suzuki, T, Svyatkovskiy, A, Swee, C, Sweeney, R, Sweetnam, C, Szepesi, G, Takechi, M, Tala, T, Tanaka, K, Tang, X, Tang, S, Tao, Y, Tao, R, Taussig, D, Taylor, T, Teixeira, K, Teo, K, Theodorsen, A, Thomas, D, Thome, K, Thorman, A, Thornton, A, Ti, A, Tillack, M, Timchenko, N, Tinguely, R, Tompkins, R, Tooker, J, De Sousa, A, Trevisan, G, Tripathi, S, Ochoa, A, Truong, D, Tsui, C, Turco, F, Turnbull, A, Umansky, M, Unterberg, E, Vaezi, P, Vail, P, Valdez, J, Valkis, W, Van Compernolle, B, Van Galen, J, Van Kampen, R, Van Zeeland, M, Verdoolaege, G, Vianello, N, Victor, B, Viezzer, E, Vincena, S, Wade, M, Waelbroeck, F, Wai, J, Wakatsuki, T, Walker, M, Wallace, G, Waltz, R, Wampler, W, Wang, L, Wang, H, Wang, Y, Wang, Z, Wang, G, Ward, S, Watkins, M, Watkins, J, Wehner, W, Wei, Y, Weiland, M, Weisberg, D, Welander, A, White, A, White, R, Wiesen, S, Wilcox, R, Wilks, T, Willensdorfer, M, Wilson, H, Wingen, A, Wolde, M, Wolff, M, Woller, K, Wolz, A, Wong, H, Woodruff, S, Wu, M, Wu, Y, Wukitch, S, Wurden, G, Xiao, W, Xie, R, Xing, Z, Xu, X, Xu, C, Xu, G, Yan, Z, Yang, X, Yang, S, Yokoyama, T, Yoneda, R, Yoshida, M, You, K, Younkin, T, Yu, J, Yu, M, Yu, G, Yuan, Q, Zaidenberg, L, Zakharov, L, Zamengo, A, Zamperini, S, Zarnstorff, M, Zeger, E, Zeller, K, Zeng, L, Zerbini, M, Zhang, L, Zhang, X, Zhang, R, Zhang, B, Zhang, J, Zhao, L, Zhao, B, Zheng, Y, Zheng, L, Zhu, B, Zhu, J, Zhu, Y, Zsutty, M, Zuin, M, Lawrence Livermore National Laboratory, Princeton Plasma Physics Laboratory, Princeton University, General Atomics, Max-Planck-Institut für Plasmaphysik, Imperial College London, National Institute for Fusion Science, Universidade de São Paulo, University of Texas at Austin, ITER, College of William and Mary, University of California Los Angeles, University of California San Diego, Columbia University, Massachusetts Institute of Technology, Oak Ridge National Laboratory, Eindhoven University of Technology, Oak Ridge Associated Universities, West Virginia University, University of Tennessee, Knoxville, National Research Council of Italy, Stony Brook University, Purdue University, University of Seville, University of Science and Technology of China, Carnegie Mellon University, Institute for Plasma Research, Peking University, University of California Davis, University of California Irvine, Commonwealth Fusion Systems, University of Liverpool, University of Illinois at Urbana-Champaign, University of Milan - Bicocca, Georgia Institute of Technology, Southwestern Institute of Physics, University of Toronto, Auburn University, Polytechnic University of Turin, Universidade Lisboa, Association CCFE, KTH Royal Institute of Technology, San Diego State University, Durham University, Lehigh University, Fusion and Plasma Physics, University of Washington, Department of Applied Physics, Sandia National Laboratories, Ghent University, Technical University of Denmark, CEA, University of Colorado Boulder, Harvard University, National Technical University of Athens, Coventry University, University of Stuttgart, Czech Academy of Sciences, Harvey Mudd College, Seoul National University, Donghua University, University of York, Dalian University of Technology, University of California Berkeley, Los Alamos National Laboratory, United States Department of Energy, University of British Columbia, Pacific Northwest National Laboratory, University of Wisconsin, Michigan State University, University of Strathclyde, Pennsylvania State University, Rensselaer Polytechnic Institute, University of Southern California, Chalmers University of Technology, University of Virginia, University of Naples Federico II, University of Oxford, VTT Technical Research Centre of Finland, National Institute of Technology, University of Connecticut, DIFFER, CIEMAT, Hanyang University, Brigham Young University, UiT The Arctic University of Norway, Australian National University, Russian Research Centre Kurchatov Institute, Forschungszentrum Jülich, Zhejiang University, The University of Tokyo, University of Michigan, Agenzia nazionale per le nuove tecnologie, l'energia e lo sviluppo economico sostenibile, Aalto-yliopisto, Aalto University, DIII-D Team, Complex Ionized Media, Elementary Processes in Gas Discharges, Applied Physics and Science Education, Science and Technology of Nuclear Fusion, and Control Systems Technology

Subjects
Nuclear and High Energy Physics, Tokamak, Technology and Engineering, DIII-D, Nuclear engineering, TOKAMAKS, MITIGATION, law.invention, Plasma physics, mitigation, law, plasma physic, tokamak, Physics, Core-edge integration, Basis (linear algebra), plasma physics, core-edge integration, scenarios, Fusion power, Condensed Matter Physics, SCENARIOS, fusion energy, Fusion energy
Abstract

Funding Information: This material is based upon work supported by the US Department of Energy, Office of Science, Office of Fusion Energy Sciences, using the DIII-D National Fusion Facility, a DOE Office of Science user facility, under Awards DE-FC02-04ER54698 and DE-AC52-07NA27344. Publisher Copyright: © 2022 IAEA, Vienna. DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.

Published
2022

23. Arrhythmogenic right ventricular cardiomyopathy patients with a markedly enlarged RV compressing LV to left side have an atypical distribution of epsilon waves and elevated plasma BNP

Author

N Funabashi, M Okamoto, K Nakamura, T Sasaki, S Naito, and Y Kobayashi

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Funding Acknowledgements Type of funding sources: None. Background Epsilon waves on V1-3 leads are specific ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) suggesting RV conduction delay. Four dimensional (4D) cardiac CT visualizes ARVC characteristics, such as fibro-fatty invasion into RV and left ventricular (LV) myocardium (RVM, LVM), an enlarged RV, reduced RV motion, and bulging. Purpose We hypothesize that Epsilon waves in V4-6 leads suggest LV invasion in ARVC. Alternatively, extreme RV enlargement may compress the LV and cause clockwise rotation; an enlarged RV may itself cause epsilon waves in V4-6 leads. Methods Retrospective analysis of 17 patients (11 males, 57 ± 17 yrs) with suspected ARVC undergoing cardiac CT and ECG, 9 of whom met 2010 ARVC task force criteria. Results All 9 patients had epsilon waves on ECG; 5 had fibro-fatty invasion into the LVM. We divided the 9 into 5 groups by CT: 1) markedly enlarged RV compressing the LV to the left side with fibro-fatty changes exclusively in RVM (N = 1); 2) similar findings in both RVM and LVM (N = 2); 3) moderately enlarged RV without compression of the LV to the left side and fibro-fatty changes exclusively in RVM (N = 3); 4) the same in both RVM and LVM (N = 2); 5) severe mitral valve regurgitation, a markedly enlarged LV, and a fibro-fatty change in both RVM and LVM (N = 1). The patient in group (gp) 1 showed epsilon waves in V1-6 leads, patients in gp 2 had epsilon waves in V1-6 (N = 1), and V3-5 (N = 1) leads; patients in gp 3 had epsilon waves in V1-4 (N = 2), and V1-3 (N = 1) leads, patients in gp 4 had epsilon waves in V1-3 (N = 1), and V1, 2 (N = 1) leads; finally, the patient in gp 5 had epsilon waves in V4-6 leads. Plasma brain natriuretic peptide (BNP) levels were significantly greater in patients in gp 1 & 2 than gp 3 & 4 (1255 ± 838 vs 80 ± 52 pg/ml, P = 0.016). Conclusions ARVC patients with a markedly enlarged RV compressing the LV to the left side (gp 1,2) had a broad (V1-6) or different range (V3-5) distribution of epsilon waves and significantly elevated plasma BNP independent of fibro-fatty invasion of the LV, different from typical ARVC (gp 3,4). Additionally, structural change due to complicated heart disease, such as valvular disease (gp5), may also influence the distribution of epsilon waves in ARVC. Abstract Figure. CT and ECG in ARVC group 1

Published
2022

24. Allergen immunotherapy in MASK-air users in real-life: Results of a Bayesian mixed-effects model

Author

Sousa-Pinto, B. Azevedo, L.F. Sá-Sousa, A. Vieira, R.J. Amaral, R. Klimek, L. Czarlewski, W. Anto, J.M. Bedbrook, A. Kvedariene, V. Ventura, M.T. Ansotegui, I.J. Bergmann, K.-C. Brussino, L. Canonica, G.W. Cardona, V. Carreiro-Martins, P. Casale, T. Cecchi, L. Chivato, T. Chu, D.K. Cingi, C. Costa, E.M. Cruz, A.A. De Feo, G. Devillier, P. Fokkens, W.J. Gaga, M. Gemicioğlu, B. Haahtela, T. Ivancevich, J.C. Ispayeva, Z. Jutel, M. Kuna, P. Kaidashev, I. Kraxner, H. Larenas-Linnemann, D.E. Laune, D. Lipworth, B. Louis, R. Makris, M. Monti, R. Morais-Almeida, M. Mösges, R. Mullol, J. Odemyr, M. Okamoto, Y. Papadopoulos, N.G. Patella, V. Pham-Thi, N. Regateiro, F.S. Reitsma, S. Rouadi, P.W. Samolinski, B. Sova, M. Todo-Bom, A. Taborda-Barata, L. Tomazic, P.V. Toppila-Salmi, S. Sastre, J. Tsiligianni, I. Valiulis, A. Wallace, D. Waserman, S. Yorgancioglu, A. Zidarn, M. Zuberbier, T. Fonseca, J.A. Bousquet, J. Pfaar, O.

Abstract

Background: Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. Objective: To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods: We assessed the MASK-air® data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. Results: We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2). Conclusion: In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its ‘real-world’ effectiveness. © 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

Published
2022

26. Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air® real-world data

Author

Sousa-Pinto, B. Sá-Sousa, A. Vieira, R.J. Amaral, R. Klimek, L. Czarlewski, W. Antó, J.M. Pfaar, O. Bedbrook, A. Kvedariene, V. Ventura, M.T. Ansotegui, I.J. Bergmann, K.-C. Brussino, L. Canonica, G.W. Cardona, V. Carreiro-Martins, P. Casale, T. Cecchi, L. Chivato, T. Chu, D.K. Cingi, C. Costa, E.M. Cruz, A.A. De Feo, G. Devillier, P. Fokkens, W.J. Gaga, M. Gemicioğlu, B. Haahtela, T. Ivancevich, J.C. Ispayeva, Z. Jutel, M. Kuna, P. Kaidashev, I. Kraxner, H. Larenas-Linnemann, D.E. Laune, D. Lipworth, B. Louis, R. Makris, M. Monti, R. Morais-Almeida, M. Mösges, R. Mullol, J. Odemyr, M. Okamoto, Y. Papadopoulos, N.G. Patella, V. Pham-Thi, N. Regateiro, F.S. Reitsma, S. Rouadi, P.W. Samolinski, B. Sova, M. Todo-Bom, A. Taborda-Barata, L. Tomazic, P.V. Toppila-Salmi, S. Sastre, J. Tsiligianni, I. Valiulis, A. Vandenplas, O. Wallace, D. Waserman, S. Yorgancioglu, A. Zidarn, M. Zuberbier, T. Fonseca, J.A. Bousquet, J.

Abstract

Background: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. Methods: We analysed 2015–2020 MASK-air® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms (‘VAS Global Symptoms’) and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. Results: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median ‘VAS Global Symptoms’ was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p

Published
2022

28. Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats

Author

M.S. Souza, U.F. Machado, M. Okamoto, M.C. Bertoluci, C. Ponpermeyer, N. Leguisamo, F. Azambuja, M.C. Irigoyen, and B.D. Schaan

Subjects
Angiotensin-converting enzyme inhibition, Diabetes mellitus, Diabetic nephropathy, Glucose transporter proteins, Hypertension, Streptozotocin, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Diabetes in spontaneously hypertensive rats is associated with cortical renal GLUT1 and GLUT2 overexpression. Our objective was to evaluate the effect of the angiotensin-converting enzyme blockade on cortical renal GLUT1 and GLUT2 expression, urinary albumin and urinary TGF-β1. Streptozotocin, 50 mg/kg, or citrate buffer (N = 16) was administered as a single injection into the tail vein in adult spontaneously hypertensive rats (~260 g). Thirty days later, these diabetic spontaneously hypertensive rats received ramipril by gavage: 0.01 mg·kg-1·day-1 (D0.01, N = 14), 1 mg·kg-1·day-1 (D1, N = 9) or water (D, N = 11) for 15 days. Albumin and TGF-β1 (24-h urine), direct arterial pressure, renal tissue angiotensin-converting enzyme activity (fluorometric assay), and GLUT1 and GLUT2 protein levels (Western blot, renal cortex) were determined. Glycemia and glycosuria were higher (P < 0.05) in the diabetic rats compared with controls, but similar between the diabetic groups. Diabetes in spontaneously hypertensive rats lowered renal tissue angiotensin-converting enzyme activity (40%), which was reduced further when higher ramipril doses were used. Diabetes associated with hypertension raised GLUT1 by 28% (P < 0.0001) and GLUT2 by 76% (P = 0.01), and both doses of ramipril equally reduced cortical GLUT1 (D vs D1 and vs D0.01, P ≤ 0.001). GLUT2 levels were reduced in D0.01 (P < 0.05 vs D). Diabetes increased urinary albumin and TGF-β1 urinary excretion, but the 15-day ramipril treatment (with either dose) did not reduce them. In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy.

Published
2008

29. Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles

Author

Alena L. Bishop, Víctor López Del Amo, Emily M. Okamoto, Zsolt Bodai, Alexis C. Komor, and Valentino M. Gantz

Subjects
Mammals, Multidisciplinary, Gene Drive Technology, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Mice, Germ Cells, Genetics, RNA, Animals, Kinetoplastida, CRISPR-Cas Systems, Guide, Alleles, Biotechnology, RNA, Guide, Kinetoplastida
Abstract

Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the drive-induced DNA break is repaired by error-prone pathways, which creates mutations that disrupt the gRNA recognition sequence and prevent further gene-drive propagation. Here, we attempt to counteract this by encoding additional gRNAs that target the most commonly generated resistance alleles into the gene drive, allowing a second opportunity at gene-drive conversion. Our presented “double-tap” strategy improved drive efficiency by recycling resistance alleles. The double-tap drive also efficiently spreads in caged populations, outperforming the control drive. Overall, this double-tap strategy can be readily implemented in any CRISPR-based gene drive to improve performance, and similar approaches could benefit other systems suffering from low HDR frequencies, such as mammalian cells or mouse germline transformations.

Published
2021

30. The ABC-X’s of Stress among U.S. Emerging Adults during the COVID-19 Pandemic: Relationship Quality, Financial Distress, and Mental Health

Author

Ashley B. LeBaron-Black, Jeremy B. Yorgason, Melissa A. Curran, Matthew T. Saxey, and Rachel M. Okamoto

Subjects
Adult, Mental Health, Depression, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Humans, COVID-19, COVID-19 pandemic, financial distress, mental health, relationship quality, ABC-X Model, moderated mediation, emerging adults, structural equation modeling (SEM), Anxiety, Pandemics
Abstract

Many emerging adults have experienced increased financial distress and mental health problems during the COVID-19 pandemic, and isolation may have amplified the importance of close relationships (especially as parents’ influence diminishes during this developmental stage). Using the ABC-X Model to frame our model, we tested whether financial distress (C) mediates the associations between COVID-19 impact (A) and anxiety and depressive symptoms (X), and whether or not romantic relationship quality (B) moderates these indirect associations. Our sample comprised of 1950 U.S. emerging adults in a romantic relationship. Mediation and first-stage moderated mediation were tested using structural equation modeling. Financial distress partially mediated the association between COVID-19 impact and anxiety symptoms and fully mediated the association between COVID-19 impact and depressive symptoms. Strong evidence of moderated mediation was found but in the opposite direction expected: the indirect associations of COVID-19 impact with anxiety and depressive symptoms (through financial distress) were stronger for those in high-quality romantic relationships. The findings may inform policy and practice aimed at optimizing the mental health of emerging adults, especially in light of the ongoing COVID-19 pandemic: specifically, alleviating financial distress may improve the mental health of emerging adults, while focusing on the quality of their romantic relationships may not.

Published
2022

31. Gastrointestinal helminths and Taenia spp. in parenteral tissues of free-roaming pigs (Sus scrofa indicus) from hilltribe village at the western border of Thailand

Author

K, Chaisiri, S, Aueawiboonsri, T, Kusolsuk, P, Dekumyoy, S, Sanguankiat, N, Homsuwan, G, Peunpipoom, M, Okamoto, T, Yanagida, Y, Sako, and A, Ito

Abstract

A serological survey of pig cysticercosis was conducted in a hill-tribe village at Thai-Myanmar border, Tak province of Thailand in 2012. Sixteen backyard pigs were examined for pig cysticercosis and gastrointestinal helminth infection. In addition to cysticerci of Taenia solium and Taenia hydatigena found outside the gut, nine other helminth species were found in guts: Echinostoma malayanum, Pseudanoplocephala crawfordi, Ascarops dentata, Physocephalus sexalatus, Gnathostoma doloresi, Ascaris suum, Globocephalus sp., Oesophagostomum dentatum and Bourgelatia diducta. The study presents a report for the first time of adult tapeworm, P. crawfordi infection in pigs from Thailand. For medical importance, E. malayanum, P. crawfordi, G. doloresi and A. suum have been confirmed as potentially zoonotic helminths and pigs may act as one of the reservoir hosts for human helminthiases. Pigs of both gender and all ages appeared to be exposed to the parasites equally and did not show any significant difference to these helminth species in richness and total intensity.

Published
2021

32. A customized scaffolds approach for the detection and phasing of complex variants by next-generation sequencing

Author

Lynne S Rosenblum, Stanley Letovsky, Patricia M. Okamoto, Ruth A Heim, Qiandong Zeng, Natalia T Leach, Jean A Smith, Zhaoqing Zhou, Angela Kenyon, Hui Zhu, and Marcia Eisenberg

Subjects
Genetic testing, Computer science, lcsh:Medicine, Cystathionine beta-Synthase, Homocystinuria, Computational biology, medicine.disease_cause, Genome, Polymorphism, Single Nucleotide, DNA sequencing, Article, Homologous chromosome, medicine, Humans, Nucleotide, 1000 Genomes Project, lcsh:Science, Gene, chemistry.chemical_classification, Mutation, Multidisciplinary, medicine.diagnostic_test, Alternative splicing, lcsh:R, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, medicine.disease, Phaser, Alternative Splicing, chemistry, Mutation (genetic algorithm), Next-generation sequencing, lcsh:Q, Genome-Wide Association Study
Abstract

Next-generation sequencing (NGS) is widely used in genetic testing for the highly sensitive detection of single nucleotide changes and small insertions or deletions. However, detection and phasing of structural variants, especially in repetitive or homologous regions, can be problematic due to uneven read coverage or genome reference bias, resulting in false calls. To circumvent this challenge, a computational approach utilizing customized scaffolds as supplementary reference sequences for read alignment was developed, and its effectiveness demonstrated with two CBS gene variants: NM_000071.2:c.833T>C and NM_000071.2:c.[833T>C; 844_845ins68]. Variant c.833T>C is a known causative mutation for homocystinuria, but is not pathogenic when in cis with the insertion, c.844_845ins68, because of alternative splicing. Using simulated reads, the custom scaffolds method resolved all possible combinations with 100% accuracy and, based on > 60,000 clinical specimens, exceeded the performance of current approaches that only align reads to GRCh37/hg19 for the detection of c.833T>C alone or in cis with c.844_845ins68. Furthermore, analysis of two 1000 Genomes Project trios revealed that the c.[833T>C; 844_845ins68] complex variant had previously been undetected in these datasets, likely due to the alignment method used. This approach can be configured for existing workflows to detect other challenging and potentially underrepresented variants, thereby augmenting accurate variant calling in clinical NGS testing.

Published
2020

33. Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial

Author

Rainer Georg Goeldner, S. Abe, Dirk Skowasch, Romain Kessler, S. Izumi, A. Barczyk, E. Belloli, J. S. Park, H. Takaya, C. Marquette, Neil Ettinger, Krishna Thavarajah, Nina Patel, Manuel Quaresma, Yasuhiko Nishioka, D Koschel, Silvia Quadrelli, M. A. Bergna, J. Sauleda, M. Salinas Fénero, J. Kang, G. Giessel, Oksana A. Shlobin, Kevin K. Brown, T. Kawamura, Ketan P. Buch, W. Randerath, O. Acosta, A. Silva Orellana, L. Wemeau, N. Sakamoto, Bruno Crestani, Sonye K. Danoff, Shane Shapera, S. Stieglitz, M. Reynaud-Gaubert, Tejaswini Kulkarni, P. Elias, Leslie Tolle, Lake Morrison, C. Glazer, Yoshikazu Inoue, Rozsa Schlenker-Herceg, Yolanda Mageto, Anand Devaraj, Zeenat Safdar, H. Hayashi, Y. Kim, Nik Hirani, Srihari Veeraraghavan, Sylvain Marchand-Adam, S. Cerri, J. Golden, D. Hotchkin, Rebecca Bascom, K. Ichikado, Martin Kolb, Nazia Chaudhuri, H. Cai, B. Crestani, J. W. Song, V. Yakusevich, Anoop M. Nambiar, Sergey Moiseev, Y. Kondoh, F. Lebargy, Wim A. Wuyts, Maria Padilla, A. Gamez-Dubuis, Sergey Avdeev, A. León Jiménez, R. Martinez, Luca Richeldi, J. Dematte D'Amico, Teng Moua, E. Bergot, J. Falk, Benjamin Bondue, K. Kishi, Danielle Antin-Ozerkis, L. Gómez Carrera, Francesco Bonella, Vincent Cottin, T. Moua, A. Villar, Stéphane Jouneau, Z. Xu, R. Hallowell, Mary E. Strek, H. Takahashi, Antje Prasse, A. Cantin, M. Okamoto, G. Criner, M. Rossman, M. Schwartz, R. Refini, Myriam Aburto, S. Makino, Y. Inoue, L. Jones, J. Burk, L. Morrow, Shelley L. Schmidt, S. Chaaban, M. Ilkovich, J. A. Rodríguez Portal, Athol U. Wells, S. Blaas, C. Andrews, D. M. Castillo Villegas, Caroline Dahlqvist, Q. Luo, H. Yamauchi, Justin M. Oldham, Julien Guiot, M. Kolb, Nitin Y. Bhatt, Y. Yamada, Maria Otaola, Alberto Pesci, E. Britt, W. Wuyts, E. Jassem, Daniel F. Dilling, Kevin R. Flaherty, H. Kitamura, H. Poonyagariyagorn, Y. Miyazaki, Robert J. Kaner, L. Pitts, Toby M. Maher, Marilyn K. Glassberg, G. Arce, J. Kus, S. Weigt, E. R. Fernández Pérez, Ivan O. Rosas, Michael Kreuter, Claudia Valenzuela, S. Tomassetti, Susanne Stowasser, K. Tomii, C. Kono, Ben Hope-Gill, D. Ziora, B. Sigal, E. Bazdyrev, R. Maturana Rozas, Paul Beirne, T. Saito, F. Varone, T. Suda, M. Arias, A. Cazaux, J. Hetzel, Helen Stone, Maria Molina-Molina, F. Riviere, L. Homik, Mary Beth Scholand, A. Gifford, W. Piotrowski, Carlo Vancheri, T. Takeuchi, H. Sugiura, M. Martínez, and Hilario Nunes

Subjects
Diarrhea, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Indoles, Vital Capacity, Population, nintedanib, idiopathic pulmonary fibrosis, Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO, behavioral disciplines and activities, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Idiopathic pulmonary fibrosis, FEV1/FVC ratio, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, nintedanib, medicine, Humans, 030212 general & internal medicine, education, Protein Kinase Inhibitors, Idiopathic interstitial pneumonia, Aged, education.field_of_study, business.industry, Interstitial lung disease, Nausea, Middle Aged, respiratory system, Sciences bio-médicales et agricoles, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, body regions, 030228 respiratory system, chemistry, Disease Progression, Female, Nintedanib, business, Hypersensitivity pneumonitis
Abstract

The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis., info:eu-repo/semantics/published

Published
2020

34. Billet flow formation of discontinuous carbon fiber ribbed square panels from continuous carbon fibers

Author

Daichi Tatsuno, T. Sekido, M. Okamoto, K. Kawamoto, and Takeshi Yoneyama

Subjects
chemistry.chemical_classification, 0209 industrial biotechnology, Thermoplastic, business.product_category, Materials science, Flow (psychology), Rigidity (psychology), 02 engineering and technology, Deformation (meteorology), 020303 mechanical engineering & transports, 020901 industrial engineering & automation, 0203 mechanical engineering, chemistry, Cushion, Ultimate tensile strength, Die (manufacturing), General Materials Science, Fiber, Composite material, business
Abstract

This paper presents a newly-developed billet flow formation method, which produces discontinuous carbon fiber thermoplastic ribbed panels by using the die cushion motion of a press. Billets of discontinuous fiber reinforced thermoplastic were extruded into rib cavities by die cushion motion while press-forming a panel of continuous fiber reinforced thermoplastic. Using billet flow formation, 200 mm long, 46 mm high, 1.4 mm thick ribs comprised of 30 mm long discontinuous fibers were formed on 400 mm wide, 300 mm depth, 50 mm high panels. The rigidity of a ribbed panel was five times greater than a panel without ribs. The tensile strength of the formed ribs was approximately 250 MPa, the same strength of the material before forming. Material behavior such as fiber flow and billet deformation during formation is discussed. This study has shown that the billet flow formation can create ribs with high mechanical strength using only a press with a die cushion.

Published
2018

35. Gastric inhibitory polypeptide receptor antagonist, SKL-14959, suppressed body weight gain on diet-induced obesity mice

Author

M. Okamoto, H. Tanimoto, Y. Tsubamoto, H. Noda, T. Nakamura, Y. Mizuno, and M. Takeuchi

Subjects
0301 basic medicine, medicine.medical_specialty, Nutrition and Dietetics, business.industry, Endocrinology, Diabetes and Metabolism, Fatty liver, Adipose tissue, 030209 endocrinology & metabolism, Lipid metabolism, Metabolism, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Gastric inhibitory polypeptide, Insulin resistance, Internal medicine, medicine, Gastric inhibitory polypeptide receptor, medicine.symptom, business, Weight gain
Abstract

Objective Gastric inhibitory polypeptide plays a role in glucose and lipid metabolism and is associated with obesity and insulin resistance. The objective of this study is to confirm the anti-obesity effects of the gastric inhibitory polypeptide receptor antagonist, SKL-14959, on diet-induced obesity mice. Method Diet-induced obesity mice at 20 weeks of age were administered with or without SKL-14959 for 96 d. Body weight and food intake were monitored throughout the experiment. Mice were sacrificed, and physiological and biochemical markers were measured, and then histochemical and gene expression analyses were also performed. In further studies, mice were orally gavaged with [14C]-oleic acid to investigate the excursion of digested lipids. Results SKL-14959 significantly suppressed weight gain without affecting food intake, decreased triacylglycerol contents in the liver and the muscle and the intensity stained with oil-red in the liver. It also improved plasma glutamic pyruvic transaminase and 3-hydroxybutyrate levels in addition to notably down-regulated relative gene expression of srebf1 and dgat1 in the liver despite not altering in the adipose tissue. Furthermore, SKL-14959 showed remarkable inhibition of lipid uptake in the adipose tissue after the oil challenge. Conclusion SKL-14959 inhibited lipids uptake and improved lipids metabolism, results in suppression of body-weight gain.

Published
2018

36. High IL-1α production was induced in the WBN/Kob-Leprfa type 2 diabetes mellitus rat model and inhibited by Syphacia muris infection

Author

R. Ito, T. Ikeda, Kensuke Taira, and M. Okamoto

Subjects
0301 basic medicine, medicine.medical_specialty, Medicine (General), syphacia muris, Lipopolysaccharide, endocrine system diseases, type 2 diabetes mellitus, wbn/kob-leprfa, medicine.medical_treatment, Agriculture (General), il-1α, Congenic, Inflammation, Stimulation, macrophage, Biology, Proinflammatory cytokine, S1-972, 03 medical and health sciences, chemistry.chemical_compound, Insulin resistance, R5-920, Internal medicine, medicine, Interleukin, medicine.disease, 030104 developmental biology, Cytokine, Endocrinology, chemistry, Animal Science and Zoology, Parasitology, medicine.symptom
Abstract

Summary The novel WBN/Kob-Leprfa (fa/fa) congenic rat strain is considered a useful rat model of type 2 diabetes mellitus (T2DM). Accumulating findings suggest that low-grade inflammation is a causative factor in T2DM and that circulating levels of inflammatory cytokines are associated with insulin resistance. However, inflammatory cytokine profiles and their correlations with T2DM development/progression in fa/fa rats have not been studied. In this study, we found that the fa/fa rats had considerably high plasma levels of interleukin (IL)-1α. Abundant cecal IL-1α mRNA expression and cecal inflammation with infiltrating IL-1α-producing macrophages was observed in fa/fa rats. Bone marrow derived macrophages from fa/fa rats expressed high levels of IL-1α upon lipopolysaccharide stimulation. Furthermore, Syphacia muris infection, which delays the onset of T2DM, reduced both plasma and cecal IL-1α levels in fa/fa rats. These results suggest that macrophage infiltration and IL-1α secretion comprise an important part of T2DM development and that S. muris infection inhibits pro-inflammatory cytokine expression in fa/fa rats.

Published
2018

38. Reverse-phase high-performance liquid chromatographic assay of phospholipases: application of spectrophotometric detection to rat phospholipase A2 isozymes

Author

H Tojo, T Ono, and M Okamoto

Subjects
Biochemistry, QD415-436
Abstract

This paper appraises an HPLC method for assaying phospholipase A2 (PLA2). The procedure is based on heptane-isopropanol-H2SO4 extraction of fatty acids released by the enzyme in the presence of margaric acid as an internal standard, and precolumn derivatization with 9-anthryldiazomethane. The derivatives of naturally occurring long-chain fatty acids were accurately determined by reverse-phase HPLC with ultraviolet detection at 254 nm; the fatty acids were identical with margaric acid in terms of their extraction efficiency in the presence or absence of a bile salt, reactivity with the labeling reagent, and molar extinction coefficients of their derivatives. HPLC conditions were optimized so as to separate the derivatives of palmitic and oleic acids completely within 7 min. The use of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol/cholate system as substrate proved useful for the sensitive detection of PLA2 activities in rat tissue homogenates. Distribution of immunoreactive pancreatic and group II phospholipases A2 was estimated from the degree of inhibition of enzyme activities by specific antibodies raised against either forms of phospholipase A2 isozymes. The results were consistent with those of immunoblot analyses.

Published
1993
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40. Blood Parameters and Rumen Wall Histology of Brahman Crossbred Steers in Response to the Administration of Rumen Mechanical Stimulating Brushes

Author

M. Okamoto, Salundik, N. Nurmeilias, Anuraga Jayanegara, Rudi Priyanto, J. Takahashi, T. Okamoto, and Dewi Apri Astuti

Subjects
0301 basic medicine, 03 medical and health sciences, Rumen, 030104 developmental biology, Nutrition and Dietetics, Animal science, Brahman, Public Health, Environmental and Occupational Health, Histology, Biology, Blood parameters, Crossbreed, Food Science
Published
2017

41. Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer

Author

K. Kataoka, Kiyotaka Hoshinaga, M. Okamoto, Naohiko Fukami, Masashi Takenaka, Taihei Ito, Takashi Kenmochi, Hitomi Sasaki, Ryoichi Shiroki, and Mamoru Kusaka

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, Population, Biology, Digestive System Neoplasms, Transcriptome, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Internal medicine, Gene expression, medicine, Cluster Analysis, Humans, education, Early Detection of Cancer, Kidney transplantation, Transplantation, education.field_of_study, Gene Expression Profiling, Cancer, Middle Aged, medicine.disease, Kidney Transplantation, Gene expression profiling, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Surgery, Pancreas
Abstract

Background Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract). Study Design and Method Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm. Results The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period. Conclusion The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system.

Published
2017

42. An Application of Architectural Precast System to Railway Viaduct Structure

Author

T. Tadokoro, M. Okamoto, N. Kita, and H. Mikura

Subjects
Engineering, business.industry, Precast concrete, 021105 building & construction, 0211 other engineering and technologies, Structure (category theory), General Materials Science, 02 engineering and technology, Structural engineering, business, 01 natural sciences, 010406 physical chemistry, 0104 chemical sciences
Published
2017

43. Group II phospholipase A2 in human gingiva with periodontal disease

Author

H. Shinohara, T. Komatsubara, H. Tojo, M. Okamoto, S. Nishikawa, T. Nagata, and H. Ishida

Subjects
Pathology, RB1-214
Abstract

Fourteen kilodalton phospholipase A2 molecules (PLA2) are classified into two groups, I- and II-PLA2, and only the latter has been considered to play a pathogenetic role in various forms of tissue inflammation. Previously we demonstrated high PLA2 activity in gingival crevicular fluid (GCF) of patients with periodontal disease, without determining the group of the enzyme involved. In this study, the activity, groups and levels of enzyme in gingiva taken from 13 sites of periodontal disease were determined using both biochemical and radioimmunological methods. A linear correlation between the activity and the level of II-PLA2 was observed. No I-PLA2 was found in any of the samples tested. These data suggest that the PLA2 activity found in the GCF of patients with periodontal disease does not belong to the I-PLA2 but to the II-PLA2 group.

Published
1995
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44. Underage JUUL Use Patterns: Content Analysis of Reddit Messages (Preprint)

Author

Yongcheng Zhan, Zhu Zhang, Janet M Okamoto, Daniel D Zeng, and Scott J Leischow

Abstract

BACKGROUND The popularity of JUUL (an e-cigarette brand) among youth has recently been reported in news media and academic papers, which has raised great public health concerns. Little research has been conducted on the age distribution, geographic distribution, approaches to buying JUUL, and flavor preferences pertaining to underage JUUL users. OBJECTIVE The aim of this study was to analyze social media data related to demographics, methods of access, product characteristics, and use patterns of underage JUUL use. METHODS We collected publicly available JUUL-related data from Reddit. We extracted and summarized the age, location, and flavor preference of subreddit UnderageJuul users. We also compared common and unique users between subreddit UnderageJuul and subreddit JUUL. The methods of purchasing JUULs were analyzed by manually examining the content of the Reddit threads. RESULTS A total of 716 threads and 2935 comments were collected from the subreddit UnderageJuul before it was shut down. Most threads did not mention a specific age, but ages ranged from 13 years to greater than 21 years in those that did. Mango, mint, and cucumber were the most popular among the 7 flavors listed on JUUL’s official website, and 336 subreddit UnderageJuul threads mentioned 7 discreet approaches to circumvent relevant legal regulations to get JUUL products, the most common of which was purchasing JUUL from other Reddit users (n=181). Almost half of the UnderageJuul users (389/844, 46.1%) also participated in discussions on the main JUUL subreddit and sought information across multiple Reddit forums. Most (64/74, 86%) posters were from large metropolitan areas. CONCLUSIONS The subreddit UnderageJuul functioned as a forum to explore methods of obtaining JUUL and to discuss and recommend specific flavors before it was shut down. About half of those using UnderageJuul also used the more general JUUL subreddit, so a forum still exists where youths can attempt to share information on how to obtain JUUL and other products. Exploration of such social media data in real time for rapid public health surveillance could provide early warning for significant health risks before they become major public health threats.

Published
2018

45. Production system to form, cut, and join by using a press machine for continuous carbon fiber-reinforced thermoplastic sheets

Author

Daichi Tatsuno, K. Kawamoto, M. Okamoto, and Takeshi Yoneyama

Subjects
chemistry.chemical_classification, Textile, Thermoplastic, Materials science, Polymers and Plastics, business.industry, Fiber orientation, Process (computing), 02 engineering and technology, General Chemistry, Welding, 021001 nanoscience & nanotechnology, law.invention, 020303 mechanical engineering & transports, 0203 mechanical engineering, chemistry, law, Materials Chemistry, Ceramics and Composites, Join (sigma algebra), Trimming, Composite material, 0210 nano-technology, business, Production system
Abstract

To build a processing method for textile carbon fiber reinforced thermoplastic (CFRTP) sheets, a production system to form, cut, and join the sheets by using a mechanical servo press machine was developed and examined. The system's problems were analyzed, and attempts were made to solve them through a series of processes. In press forming, the effects of sheet geometry, fiber orientation, and slide motion on the forming of the variant-cross-sectional-beam, which has a narrow and wide part, were investigated. In addition, the shear-cutting method was chosen trimming the unnecessary region of the variant-cross-sectional-beam. For the joining process, a thermal welding method that uses a heating-plate was chosen. The closed-sectional-beam was fabricated by thermally welding a pair of the variant-cross-sectional-beams. Finally, the potential of the production system for textile CFRTP sheets using the mechanical servo press machine was discussed. © 2016 The Authors Polymer Composites published by Wiley Periodicals, Inc. on behalf of Society of Plastics Engineers., Embargo Period 12 months

Published
2016

46. Global transcriptome dysregulation in second trimester fetuses withFMR1expansions

Author

Patricia M. Okamoto, Diana W. Bianchi, Lillian M. Zwemer, Marcia Eisenberg, Sarah L. Nolin, and Heather C. Wick

Subjects
0301 basic medicine, Genetics, Mutation, Obstetrics and Gynecology, Biology, medicine.disease_cause, Phenotype, FMR1, Transcriptome, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Gene expression, medicine, DNA microarray, Allele, Gene, 030217 neurology & neurosurgery, Genetics (clinical)
Abstract

Objective We tested the hypothesis that FMR1 expansions would result in global gene dysregulation as early as the second trimester of human fetal development. Method Using cell-free fetal RNA obtained from amniotic fluid supernatant and expression microarrays, we compared RNA levels in samples from fetuses with premutation or full mutation allele expansions with control samples. Results We found clear signals of differential gene expression relating to a variety of cellular functions, including ubiquitination, mitochondrial function, and neuronal/synaptic architecture. Additionally, among the genes showing differential gene expression, we saw links to related diseases of intellectual disability and motor function. Finally, within the unique molecular phenotypes established for each mutation set, we saw clear signatures of mitochondrial dysfunction and disrupted neurological function. Patterns of differential gene expression were very different in male and female fetuses with premutation alleles. Conclusion These results support a model for which genetic misregulation during fetal development may set the stage for late clinical manifestations of FMR1-related disorders. © 2016 John Wiley & Sons, Ltd.

Published
2016

49. Effect of lattice-frame reinforced geosynthetics on seismic stability improvement of embankment on loose sand deposit

Author

Y. Kitamoto, M. Okamoto, Y. Nakajima, T. Yoshida, Hiroyuki Kyokawa, T. Obara, Yasuyuki Sawada, and Fujisaki Katsutoshi

Subjects
Centrifuge, geography, Seismic stability, geography.geographical_feature_category, 010102 general mathematics, 0211 other engineering and technologies, Liquefaction, 02 engineering and technology, 01 natural sciences, Lattice (order), Geotechnical engineering, 0101 mathematics, Geosynthetics, Levee, Geology, 021101 geological & geomatics engineering
Published
2016

50. A study of autorotating plant seeds

Author

Shigeru Sunada, A. Ide, M. Okamoto, and Y. Hoshino

Subjects
Statistics and Probability, Physics, Airfoil, Lift-to-drag ratio, Rotation, General Immunology and Microbiology, Applied Mathematics, Leading edge vortex, General Medicine, Mechanics, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Biomechanical Phenomena, Trees, Vortex, Aerodynamic force, Classical mechanics, Modeling and Simulation, Seeds, Descent (aeronautics), Rheology, General Agricultural and Biological Sciences, Falling (sensation), Algorithms
Abstract

A leading edge vortex exists on the upper surface of an autorotating plant seed. The vortex enhances the vertical aerodynamic force acting on the seed and decreases the rate of descent. We analyzed the flight data of rotary seeds and revealed that the lift-drag ratio affects the descent factor more strongly than the vertical force coefficient. This has also been confirmed by falling tests of model rotors, which have various aspect ratios, airfoil shapes and total masses.

Published
2015

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