研究者詳細 - 大場　純奈

Using a Systems Engineering Approach to Build a PCR Testing System at a Medical School During the COVID-19 Pandemic

Oba J., Toriya M., Uwamino Y., Matsuo K.

Risk Management and Healthcare Policy 17 649 - 662 2024年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 1179-1594

　概要を見る

Background: 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.
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Building a versatile medical test system in a pandemic

J Oba, M Toriya, K Matsuo

Impact 2023 (2), 42-44 （Science Impact Ltd）（ 2 ） 42 - 44 2023年04月

共著, 筆頭著者

　概要を見る

The COVID-19 pandemic was unprecedented and forced countries to organise and combine resources and develop coordinated responses. Temporary systems were established with the support of researchers and other stakeholders. Dr Junna Oba, Assistant Professor at the Department of Extended Intelligence for Medicine at Keio University School of Medicine (KUSM) is devising methodologies for developing adjustable temporary systems that are quick and efficient to build, apply and dissemble when emergency situations have passed. KUSM helped to respond to the COVID-19 crisis by collaborating with basic science researches to reinforce the PCR testing system in hospitals. Among those involved in this effort were Professor Masako Toriya of Keio University Global Research Institute (KGRI) and Professor Koichi Matsuo from the KUSM's Collaborative Research Resources group. The researchers built from scratch a workflow for effective testing and information sharing. Since this time, the team has been working to build a cooperative network, developing a novel approach to planning, analysing and recording various processes and strategies to address emergency situations that will be shared with the wider healthcare community and policy makers. The researchers used systems engineering methods to launch an unprecedented collaborative system that offers the ability to gain an overall picture of the interrelationships between departments that are working together on the diagnosis, treatment and management of COVID-19.

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Multi-modal molecular programs regulate melanoma cell state

Andrews M.C., Oba J., Wu C.J., Zhu H., Karpinets T., Creasy C.A., Forget M.A., Yu X., Song X., Mao X., Robertson A.G., Romano G., Li P., Burton E.M., Lu Y., Sloane R.S., Wani K.M., Rai K., Lazar A.J., Haydu L.E., Bustos M.A., Shen J., Chen Y., Morgan M.B., Wargo J.A., Kwong L.N., Haymaker C.L., Grimm E.A., Hwu P., Hoon D.S.B., Zhang J., Gershenwald J.E., Davies M.A., Futreal P.A., Bernatchez C., Woodman S.E.

Nature Communications （Nature Communications） 13 （ 1 ） 4000 2022年07月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

　概要を見る

Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states. These findings have implications for cancer biology and the identification of new therapeutic strategies. Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field.
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SARS-CoV-2 RT-qPCR testing of pooled saliva samples: A case study of 824 asymptomatic individuals and a questionnaire survey in Japan

Oba J., Taniguchi H., Sato M., Takanashi M., Yokemura M., Sato Y., Nishihara H.

PLoS ONE （PLoS ONE） 17 （ 5 May ） e0263700 2022年05月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

　概要を見る

From the beginning of the COVID-19 pandemic, the demand for diagnostic and screening tests has exceeded supply. Although the proportion of vaccinated people has increased in wealthier countries, breakthrough infections have occurred amid the emergence of new variants. Pooled-sample COVID-19 testing using saliva has been proposed as an efficient, inexpensive, and non-invasive method to allow larger-scale testing, especially in a screening setting. In this study, we aimed to evaluate pooled RT-qPCR saliva testing and to compare the results with individual tests. Employees of Philips Japan, Ltd. were recruited to participate in COVID-19 screening from October to December 2020. Asymptomatic individuals (n = 824) submitted self-collected saliva samples. Samples were tested for the presence of SARS-CoV-2 by RT-qPCR in both 10-sample pools and individual tests. We also surveyed participants regarding their thoughts and behaviors after the PCR screening project. Two of the 824 individuals were positive by RT-qPCR. In the pooled testing, one of these two had no measurable Ct value, but showed an amplification trend at the end of the PCR cycle. Both positive individuals developed cold-like symptoms, but neither required hospitalization. Of the 824 participants, 471 responded to our online questionnaire. Overall, while respondents agreed that PCR screening should be performed regularly, the majority were willing to undergo PCR testing only when it was provided for free or at low cost. In conclusion, pooled testing of saliva samples can support frequent large-scale screening that is rapid, efficient, and inexpensive.
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Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy

Terranova C.J., Tang M., Maitituoheti M., Raman A.T., Ghosh A.K., Schulz J., Amin S.B., Orouji E., Tomczak K., Sarkar S., Oba J., Creasy C., Wu C.J., Khan S., Lazcano R., Wani K., Singh A., Barrodia P., Zhao D., Chen K., Haydu L.E., Wang W.L., Lazar A.J., Woodman S.E., Bernatchez C., Rai K.

Cell Reports （Cell Reports） 36 （ 3 ） 109410 2021年07月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2211-1247

　概要を見る

The dynamic evolution of chromatin state patterns during metastasis, their relationship with bona fide genetic drivers, and their therapeutic vulnerabilities are not completely understood. Combinatorial chromatin state profiling of 46 melanoma samples reveals an association of NRAS mutants with bivalent histone H3 lysine 27 trimethylation (H3K27me3) and Polycomb repressive complex 2. Reprogramming of bivalent domains during metastasis occurs on master transcription factors of a mesenchymal phenotype, including ZEB1, TWIST1, and CDH1. Resolution of bivalency using pharmacological inhibition of EZH2 decreases invasive capacity of melanoma cells and markedly reduces tumor burden in vivo, specifically in NRAS mutants. Coincident with bivalent reprogramming, the increased expression of pro-metastatic and melanocyte-specific cell-identity genes is associated with exceptionally wide H3K4me3 domains, suggesting a role for this epigenetic element. Overall, we demonstrate that reprogramming of bivalent and broad domains represents key epigenetic alterations in metastatic melanoma and that EZH2 plus MEK inhibition may provide a promising therapeutic strategy for NRAS mutant melanoma patients.
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パンデミック状況下における可塑的対応を可能とする検査システムモデルの構築

2021年04月

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2024年03月

文部科学省・日本学術振興会, 科学研究費助成事業, 大場純奈, 基盤研究(C), 補助金, 研究代表者

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