32 research outputs found

    肝癌セルラインにおける遺伝子発現プロファイルは、肝細胞様、線維芽細胞様の2つのクラスターを明らかにする

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    京都大学新制・課程博士博士(医学)甲第23409号医博第4754号新制||医||1052(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 妹尾 浩, 教授 武藤 学, 教授 小川 誠司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

    Identification of Respiratory Sounds Collected from Microphones Embedded in Mobile Phones

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    Sudden deterioration of condition in patients with various diseases, such as cardiopulmonary arrest, may result in poor outcome even after resuscitation. Early detection of deterioration is important in medical and long-term care settings, regardless of the acute or chronic phase of disease. Early detection and appropriate interventions are essential before resuscitating measures are required. Among the vital signs that indicate the general condition of a patient, respiratory rate has a greater ability to predict serious events such as thromboembolism and sepsis than heart rate and blood pressure, even in early stages. Despite its importance, however, respiratory rate is frequently overlooked and not measured, making it a neglected vital sign. To facilitate the measurement of respiratory rate, a non-invasive method of detecting respiratory sounds was developed based on deep learning technology, using a built-in microphone in a smartphone. Smartphones attached to the bed headboards of 20 participants undergoing polysomnography (PSG) at Kyoto University Hospital recorded respiratory sounds. Sound data were synchronized with overnight respiratory information. After excluding periods of abnormal breathing on the PSG report, sound data were processed for each 1-minute period. Expiration sound was determined using the pressure flow sensor signal on PSG. Finally, a model to identify the expiration section from the sound information was created using a deep learning algorithm from the convolutional Long Short Term Memory network. The accuracy of the learning model in identifying the expiratory section was 0.791, indicating that respiratory rate can be determined using the microphone in a smartphone. By collecting data from more patients and improving the accuracy of this method, respiratory rates could be more easily monitored in all situations, both inside and outside the hospital

    Macro-econometric Models and the Outline of the MEAD-RIETI Model (Japanese)

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    The global financial crisis, triggered by the subprime mortgage problem and resulting in the collapse of a major American investment bank in September 2008, has seriously affected the Japanese economy. The Japanese government has instigated certain policies in response to the global economic recession and volatility in financial markets. In formulating policies, it has become increasingly necessary to forecast different economic scenarios by taking into account the possible impact of policies and risks, including contributing factors from abroad. Using macro-econometric models is one way to respond to this. In recent years, the governments, central banks and international organizations of many nations have placed more emphasis on aligning their macro-econometric models with macroeconomic theory, in order to better respond with the "Lucas Critique." This paper will attempt to achieve two things: 1) to illustrate the macro-econometric models of foreign countries and Japan and the macroeconomic theory behind those models, and 2) to explain the "MEAD-RIETI Model" (MRM) which we have constructed. While the aim of the MRM is to evaluate quantitatively the risks and impacts of policy decisions, it is a hybrid model which attaches a high degree of importance to how it fits with empirical data considering the consistency of the model with macroeconomic theory. Although MRM comprehensively covers SNA and other key economic variables, MRM prefers simplicity over complexity with regards to model specification and avoids the use of too many variables.

    Inter-assay variability of next-generation sequencing-based gene panels

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    BACKGROUND: Tumor heterogeneity has been known to cause inter-assay discordance among next-generation sequencing (NGS) results. However, whether preclinical factors such as sample type, sample quality and analytical features of gene panel can affect the concordance between two different assays remains largely unexplored. METHODS: Replicate sets of DNA samples extracted from formalin-fixed paraffin-embedded tissues (FFPE) (n = 20) and fresh frozen (FF) tissues (n = 10) were herein analyzed using a tumor-only (TO) and paired tumor-normal (TN) gene panel in laboratories certified by the Clinical Laboratory Improvement Amendment. Reported variants from the TO and TN panels were then compared. Furthermore, additional FFPE samples were sequentially sliced from the same FFPE block and submitted to another TN panel assay. RESULTS: Substantial discordance (71.8%) was observed between the results of the two panels despite using identical DNA samples, with the discordance rate being significantly higher for FFPE samples (p < 0.05). Among the 99 variants reported only in the TO panel, 32.3% were consistent with germline variants, which were excluded in the TN panel, while 30.3% had an allele frequency of less than 5%, some of which were highly likely to be artificial calls. The comparison of two independent TN panel assay results from the same FFPE block also showed substantial discordance rate (55.3%). CONCLUSIONS: In the context of clinical settings, our comparative analysis revealed that inter-NGS assay discordance commonly occurred due to sample types and the different analytical features of each panel

    Prevalence of pathogenic germline variants in the circulating tumor DNA testing

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    BACKGROUND: Somatic and germline variants are not distinguishable by circulating tumor DNA (ctDNA) testing without analyzing non-tumor samples. Although confirmatory germline testing is clinically relevant, the criteria for selecting presumed germline variants have not been established in ctDNA testing. In the present study, we aimed to evaluate the prevalence of pathogenic germline variants in clinical ctDNA testing through their variant allele fractions (VAFs). METHODS: A total of consecutive 106 patients with advanced solid tumors who underwent ctDNA testing (Guardant360®) between January 2018 and March 2020 were eligible for this study. To verify the origin of pathogenic variants reported in ctDNA testing, germline sequencing was performed using peripheral blood DNA samples archived in the Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan) under clinical research settings. RESULTS: Among 223 pathogenic variants reported in ctDNA testing, the median VAF was 0.9% (0.02-81.8%), and 88 variants with ≥ 1% VAFs were analyzed in germline sequencing. Among 25 variants with ≥ 30% VAFs, seven were found in peripheral blood DNA (BRCA2: n = 6, JAK2: n = 1). In contrast, among the 63 variants with VAFs ranging from 1 to < 30%, only one variant was found in peripheral blood DNA (TP53: n = 1). Eventually, this variant with 15.6% VAF was defined to be an acquired variant, because its allelic distribution did not completely link to those of neighboring germline polymorphisms. CONCLUSION: Our current study demonstrated that VAFs values are helpful for selecting presumed germline variants in clinical ctDNA testing

    Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect

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    Radiotherapy (RT) is the primary treatment for cancer. Ionizing radiation from RT induces tumor damage at the irradiated site, and, although clinically infrequent, may cause regression of tumors distant from the irradiated site-a phenomenon known as the abscopal effect. Recently, the abscopal effect has been related to prolongation of overall survival time in cancer patients, though the factors that influence the abscopal effect are not well understood. The aim of this study is to clarify the factors influencing on abscopal effect. Here, we established a mouse model in which we induced the abscopal effect. We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT

    Microrna-9-5p-CDX2 axis: A useful prognostic biomarker for patients with stage II/III colorectal cancer

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    A lack of caudal-type homeobox transcription factor 2 (CDX2) protein expression has been proposed as a prognostic biomarker for colorectal cancer (CRC). However, the relationship between CDX2 levels and the survival of patients with stage II/III CRC along with the relationship between microRNAs (miRs) and CDX2 expression are unclear. Tissue samples were collected from patients with stage II/III CRC surgically treated at Kyoto University Hospital. CDX2 expression was semi-quantitatively evaluated by immunohistochemistry (IHC). The prognostic impacts of CDX2 expression on overall survival (OS) and relapse-free survival (RFS) were evaluated by multivariable statistical analysis. The expression of miRs regulating CDX2 expression and their prognostic impacts were analyzed using The Cancer Genome Atlas Program for CRC (TCGA-CRC). Eleven of 174 CRC tissues lacked CDX2 expression. The five-year OS and RFS rates of patients with CDX2-negative CRC were significantly lower than those of CDX2-positive patients. Multivariate analysis of clinicopathological features revealed that CDX2-negative status is an independent marker of poor prognosis in stage II/III CRC. miR-9-5p was shown to regulate CDX2 expression. TCGA-CRC analysis showed that high miR-9-5p expression was significantly associated with poor patient prognosis in stage II/III CRC. In conclusion, CDX2, the post-transcriptional target of microRNA-9-5p, is a useful prognostic biomarker in patients with stage II/III CRC

    Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

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    [Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years

    Comprehensive genomic profiling for patients with chemotherapy‐naïve advanced cancer

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    Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular-based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10-329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular-based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first-line chemotherapy
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