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"Suzuki, Takashi"
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Noncontact Visualization of Respiration and Vital Sign Monitoring Using a Single Mid-Wave Infrared Thermal Camera: Preliminary Proof-of-Concept
Infrared thermal cameras can noninvasively measure the surface temperatures of objects and are widely used as fever-screening systems for infectious diseases. However, body temperature measurements alone are often insufficient for identifying people with infections. To address the inherent limitations of fever-based screening, this study aimed to develop analytical methods that enable multi-vital sensing alongside body temperature measurement using a single mid-wave infrared (MWIR) camera. Respiratory parameters were assessed by visualizing exhaled airflow based on MWIR absorption by carbon dioxide, whereas the heart rate was estimated from subtle temperature fluctuations captured using high thermal resolution. The experimental results validated the proposed method, showing that the developed system achieved good agreement with reference measurements; the respiratory rate, heart rate, and body temperature showed strong correlations (r = 0.864–0.987) and acceptable limits of agreement in Bland–Altman analyses. The exhalation volume was quantified from the visualized airflow and was found to align with the expected physiological ranges. These results demonstrate that noncontact multi-vital sensing can be achieved using a single MWIR camera, without the need for complex instrumentation. The proposed method holds promise for high-precision infection screening, remote health monitoring, and in-home physiological assessment.
Journal Article
Preface to Special Issue “Mathematical Modeling and Data Science for Biology and Medicine”
This Special Issue, titled “Mathematical Modeling and Data Science for Biology and Medicine”, aims to highlight the development and growing application of mathematical models and data science in medicine, as well as their role in enhancing the understanding and clinical management of various diseases [...]
Journal Article
RNA‐binding protein NONO promotes breast cancer proliferation by post‐transcriptional regulation of SKP2 and E2F8
The majority of breast cancers are primarily hormone‐sensitive and can be managed by endocrine therapy, although therapy‐resistant or hormone‐refractory cancers need alternative treatments. Recently, increasing attention is being paid to RNA‐binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified. We herein show that an RBP non‐POU domain‐containing octamer binding (NONO) plays a critical role in the pathophysiology of breast cancers regardless of their hormone dependency. Clinicopathological and immunohistochemical study of 127 breast cancer cases showed that NONO is a significant independent prognostic factor for breast cancer patients. Notably, siRNA‐mediated NONO knockdown substantially repressed the proliferation of both hormone‐sensitive MCF‐7 and hormone‐refractory MB‐MDA‐231 breast cancer cells. Integrative analysis combined with expression microarray and RIP‐sequencing (RNA immunoprecipitation‐sequencing) showed that NONO post‐transcriptionally regulates the expression of cell proliferation‐related genes by binding to their mRNAs, as exemplified by S‐phase‐associated kinase 2 and E2F transcription factor 8. Overall, these results suggest that NONO is a key regulator for breast cancer proliferation through the pre‐mRNA splicing of cell proliferation‐related genes and could be a potential new diagnostic and therapeutic target for advanced disease. The present study shows that Drosophila behavior human splicing family RNA‐binding protein NONO plays a critical role in breast cancer tumorigenesis. Clinicopathological study defines that NONO immunoreactivity significantly correlates with poor overall and distant disease‐free survival of breast cancer patients. Cell‐based experiments show that NONO contributes to breast cancer proliferation by regulating SKP2 and E2F8 expression at the post‐transcriptional level. Our findings provide a new cancer strategy by applying NONO as a potential diagnostic and therapeutic target for breast cancer.
Journal Article
Prognostic factors of second-line nivolumab monotherapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study for 184 cases
BackgroundThe real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated.MethodsThis multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors.ResultsAmong 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1 months and overall survival was 14 months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4 months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7 months.ConclusionsOur study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding.
Journal Article
Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF
Developing therapeutic approaches are necessary for treating hormone-refractory prostate cancer. Activation of androgen receptor (AR) and its variants’ expression along with the downstream signals are mostly important for disease progression. However, the mechanism for marked increases of AR signals and its expression is still unclear. Here, we revealed that various spliceosome genes are aberrantly induced by RNA-binding protein PSF, leading to enhancement of the splicing activities for AR expression. Our high-speed sequence analyses identified global PSF-binding transcripts. PSF was shown to stabilize and activate key long noncoding RNAs and AR-regulated gene expressions in prostate cancer cells. Interestingly, mRNAs of spliceosome-related genes are putative primary targets of PSF. Their gene expressions are up-regulated by PSF in hormone-refractory prostate cancer. Moreover, PSF coordinated these spliceosome proteins to form a complex to promote AR splicing and expression. Thus, targeting PSF and its related pathways implicates the therapeutic possibility for hormone-refractory prostate cancer.
Journal Article
Molecular dynamics simulations of a multicellular model with cell-cell interactions and Hippo signaling pathway
The transcriptional coactivator Yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) induces cell proliferation through nuclear localization at low cell density. Conversely, at extremely high cell density, the Hippo pathway, which regulates YAP/TAZ, is activated. This activation leads to the translocation of YAP/TAZ into the cytoplasm, resulting in cell cycle arrest. Various cancer cells have several times more YAP/TAZ than normal cells. However, it is not entirely clear whether this several-fold increase in YAP/TAZ alone is sufficient to overcome proliferation inhibition (contact inhibition) under high-density conditions, thereby allowing continuous proliferation. In this study, we construct a three-dimensional (3D) mathematical model of cell proliferation incorporating the Hippo-YAP/TAZ pathway. Herein, a significant innovation in our approach is the introduction of a novel modeling component that inputs cell density, which reflects cell dynamics, into the Hippo pathway and enables the simulation of cell proliferation as the output response. We assume such 3D model with cell-cell interactions by solving reaction and molecular dynamics (MD) equations by applying adhesion and repulsive forces that act between cells and frictional forces acting on each cell. We assume Lennard-Jones (12-6) potential with a softcore character so that each cell secures its exclusive domain. We set cell cycles composed of mitotic and cell growth phases in which cells divide and grow under the influence of cell kinetics. We perform mathematical simulations at various YAP/TAZ levels to investigate the extent of YAP/TAZ increase required for sustained proliferation at high density. The results show that a twofold increase in YAP/TAZ levels of cancer cells was sufficient to evade cell cycle arrest compared to normal cells, enabling cells to continue proliferating even under high-density conditions. Finally, this mathematical model, which incorporates cell-cell interactions and the Hippo-YAP/TAZ pathway, may be applicable for evaluating cancer malignancy based on YAP/TAZ levels, developing drugs to suppress the abnormal proliferation of cancer cells, and determining appropriate drug dosages. The source codes are freely available.
Journal Article
Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance
Recent advance in cancer research sheds light on the contribution of mitochondrial respiration in tumorigenesis, as they efficiently produce ATP and oncogenic metabolites that will facilitate cancer cell growth. Here we show that a stabilizing factor for mitochondrial supercomplex assembly, COX7RP/COX7A2L/SCAF1, is abundantly expressed in clinical breast and endometrial cancers. Moreover, COX7RP overexpression associates with prognosis of breast cancer patients. We demonstrate that COX7RP overexpression in breast and endometrial cancer cells promotes in vitro and in vivo growth, stabilizes mitochondrial supercomplex assembly even in hypoxic states, and increases hypoxia tolerance. Metabolomic analyses reveal that COX7RP overexpression modulates the metabolic profile of cancer cells, particularly the steady-state levels of tricarboxylic acid cycle intermediates. Notably, silencing of each subunit of the 2-oxoglutarate dehydrogenase complex decreases the COX7RP-stimulated cancer cell growth. Our results indicate that COX7RP is a growth-regulatory factor for breast and endometrial cancer cells by regulating metabolic pathways and energy production.
Cancer cells rely on mitochondrial respiration to satisfy their metabolic demands. Here the authors show that the mitochondrial supercomplex assembly factor COX7RP is abundantly expressed in breast and endometrial cancer cells and promotes tumor growth and hypoxia tolerance partially by altering levels of the tricarboxylic acid cycle intermediates.
Journal Article
Association between mask-associated dry eye (MADE) and corneal sensations
To determine the risk of mask-associated dry eye (MADE), we investigated the fluorescein tear break-up time (FBUT), ocular surface temperature and blood flow, along with corneal sensitivity, in mask wearers. We enrolled 60 mask wearers (mean age, 27.1 ± 5.2 years) and then measured FBUT, corneal temperature and conjunctival blood flow without wearing masks (no mask), with masks, and with taped masks. We defined MADE as the condition in which dry eye symptoms appeared and the FBUT with mask was less than 5 s. The FBUT with a mask was significantly shorter compared to the no mask and taped mask groups (
P
< 0.01 and
P
< 0.05). The corneal temperature difference and conjunctival blood flow difference were significantly higher after wearing a mask than after wearing a taped mask (
P
< 0.01). Of the 60 subjects, 13 were diagnosed with MADE. Pain sensitivity and the Ocular Surface Disease Index (
P
< 0.05 and
P
< 0.01) were significantly higher in the MADE group, with the FBUT without masks (
P
< 0.05) significantly shorter than in the non-MADE group. MADE may be associated with corneal hypersensitivity. Wearing masks decreased FBUT and increased ocular surface temperature and blood flow. Taping the top edge of masks prevented these changes. Fitting masks properly may reduce MADE risk.
Journal Article
Improving the differentiation potential of pluripotent stem cells by optimizing culture conditions
Embryoid cells and induced pluripotent stem cells (iPSCs) are pluripotent stem cells (PSCs). They retain differentiation and self-renewal potential. However, the differentiation potential of PSCs can be changed by the culture medium. PSCs retain their differentiation potential when cultured with medium that supports the glycolytic pathway, showing high expression of chromodomain-helicase-DNA-binding protein 7 (CHD7), but lose their differentiation potential with medium that supports mitochondrial function, showing reduced levels of CHD7. Labeling cells by their copy number variant profile revealed that genetically different PSC populations can be cultured by medium selection. Another factor that defines the self-renewal potential of PSCs is culture condition. PSCs form colonies as they grow, and spontaneous differentiation inevitably occurs along the rim of these colonies in areas that lack cell-to-cell contact; because of this, undifferentiated cell populations would diminish if differentiated cells are not removed properly. Seeding cells on a less potent cell-binding material may minimize the inclusion of differentiated cells, exploiting the reduced adhesive properties of differentiated cells. Culturing cells with medium that supports the glycolytic pathway, using CHD7 as a biomarker for differentiation potential, and culturing cells on less sticky material can improve the differentiation potential of already established PSC clones.
Journal Article