Video plethysmogram (VPG) can easily be obtained from video images taken by ordinary video cameras that are installed in personal computers or smartphones. In this article, the wide application possibilities of the VPG, its problems and limitations will be discussed after introducing basic characteristics and methods of extracting the VPG signals.

We introduce our skin component analysis method based on physical characteristics and physiology in consideration of melanin pigment, hemoglobin pigment an shading component. First of all, removal of the influence of shading on the face is realized by vector analysis in a simple color space based on the knowledge of imaging optics. The de-shaded image is separated into hemoglobin component and melanin component by pigment component separation method with independent component analysis. The analysis of the time axis of total extracted hemoglobin has realized to show the hemoglobin signal that is highly correlated with pulse wave from the heart beats. This method can make it possible to monitor affectiveness and emotions from live facial video.

Image PPG has attracted a great deal of research interest in the recent few years in healthcare applications. Since the image PPG extracts a change in blood flow as a waveform, it is considered that the image PPG is also related to the skin condition. In this study, we report the results of basic examination of skin condition diagnosis using image PPG.

The video plethysmogram (VPG) has the advantage of not only non-contact measurement but also simultaneous multi-point measurement. Therefore, if VPG contains the hemodynamic information as well as photo-plethysmogram (PPG), it may be possible to obtain the multi-point pulse wave at various regions as if many PPG sensors are attached to body surfaces. However, it is difficult to extract valid pulse waveform at the skin surface with a few capillary vessels. We have proposed VPG extraction algorithm based on repetitive periodic component analysis (rPiCA) and VPG could be extracted from the region other than face. Furthermore, the several hemodynamic indices which were calculated by same signal processing as PPG analysis had characteristic changes relating to hemodynamic change such as the blood pressure and peripheral vascular resistance. However, the instantaneous heart rate from VPG did not have sufficient accuracy for the heart rate variability analysis.

Research on biological information using a video image has been actively conducted in recent years. In particular, a technique to obtain pulse wave information from a video image (video plethysmography) allows us to monitor our biological condition in a non-contact manner. Pulse wave extraction using three channel (RGB) signals of a visible light video is useful to suppress noise such as body motion. On the other hand, in the case of a near-infrared video image that has a single channel signal and has a different light absorption characteristic from visible light, a new approach is needed to obtain a video plethysmography stably. In this talk, we describe the basic characteristics of video plethysmography using near-infrared light and show the result of applying our proposed method on near-infrared video images.

[Background] The mortality rate varies depending on the temperature, and the risk increases in both heat and cold. However, the detailed mechanism is unknown. [Purpose] The purpose of this study was to investigate the effects of temperature on heart rate and heart rate variability, including regional differences. [Methods] The data of RR intervals (sinus rhythm) obtained by 24-hour Holter ECG was analyzed by the methods of time domain, frequency domain, and non-linear index. The cases of Tokyo and Hokkaido were compared after extraction from the Holter ECG database. [Results] MeanNN showed M-shaped change in both regions. In Hokkaido, the curve shifted toward lower temperatures compared to Tokyo. The standard deviation of NN interval (SDNN) and the power of high frequency range (HF) showed the same changes as MeanNN. [Conclusions] The 24-hour mean heart rate was fluctuated depending on the temperature. Regional variations in heart rate variability were recognized.

Cortical potential imaging has been proposed as a method of visualizing brain electrical activity with high spatial resolution. In cortical potential imaging, the potential on the brain surface is estimated from a scalp-recorded electroencephalogram by solving an inverse problem. In order to visualize the brain electrical activity with high accuracy, we proposed a spatial inverse filter with an optimal filter property that considers the transfer matrix error. Moreover, the spatial inverse filter was expanded into a spatiotemporal filter to visualize time-varying brain activity dynamically. The inverse filter was stabilized by limiting the time-varying parameters according to the time-varying noise involved in the EEG. The proposed method was applied to actual human visually-evoked potentials of pattern reversal stimulus and visual motion stimulus. We confirmed that the visual pathways of ventral and dorsal streams consistent with physiological findings. The proposed method is expected to be a non-invasive spatiotemporal analysis of brain function.

Even when the eye gazes at a certain point of view, the eye moves involuntarily and constantly, which is called fixation eye movement. The fixation eye movement is mainly composed of three components, microsaccade, drift, and tremor. In recent years, there have been many reports showing that the fixation eye motion is under the influence of cognitive mechanisms such as attention. Therefore it is an important index for knowing human cognitive mechanisms. In this research, we propose a new method that tracks the fixation eye movement by using a state space model. The model can separate the fixation eye movement into three components, microsaccade, drift, and tremor. As a result, it was possible to accurately track the fixation eye movement even including the overshoot and undershoot of the microsaccade. In addition, we proposed a new method for microsaccade detection using the median prediction and the Bayesian prediction interval of the fixation eye motion tracking. Compared with conventional methods that detect micro saccades using smoothing differentiation and thresholds, the proposed method can detect microsaccades with high accuracy with taking into account overshoots and undershoots that appear in micro saccades, and the detection rate was also high.

Snore sound, as a common symptom among adults (more than 30%), has been increasingly studied during the past three decades. Particularly, an in-depth analysis of snore sound can benefit a targeted surgical plan for both the subjects suffering from primary snoring and Obstructive Sleep Apnoea snoring. In this presentation, we will firstly introduce the history of using snore sound analysis for localising the snore site in the upper airway. We will compare the early works focused on acoustic parameter analysis and the machine learning (including the cutting-edge deep learning approaches) based studies by a comprehensive review on literature. Then, we indicate the findings and limitations in current research work. Finally, we conclude the studies and give our future perspectives.

Recent development of sleep monitoring technologies, such as wearable sleep trackers, and the pervasive of sleep monitoring services using them enable us to obtain continuous and large-scale sleep data in our daily life. Beyond the measurement in conventional laboratory environments, analyses of habitual sleep big-data provide sleep epidemiological findings with ecological validity. Recently, we obtained objective epidemiological findings on habitual sleep of Japanese residents using a large-scale trunk acceleration database (approximately 80,000 individuals, 24-hour data including sleep periods) collected from all over Japan. In this presentation, we report our findings, especially, effects of aging, gender, and biometeorological factors on habitual sleep.

We have been developing BioValve as an artificial hearts valve by using iBTA. Because atrioventricular valve has a complicated structure consisting of both leaflet and tendinous cords, and its performance is affected by the cord length, BioValve have not been applied to atrioventricular valve. The purpose of this study is a simple shape artificial atrioventricular valve developing. Newly developed valve consists of a metal annulus and a BioSheet. Because a BioSheet is fixed on a beam of the annulus, the sheet can open and close with flow change like a mechanical butterfly-valve. The valve performance, such as regurgitation-ratio, EOA and pressure-drop was measured by using arterial circulation simulator under the typical physiological conditions. To apply to optimal design, we had fabricated a valve model by using polyurethane sheet, of which mechanical bending properties were same as the BioSheet, and the influence of shape change of the leaflet was investigated.

Control of blood flow rate is vital in prevention of thrombogenesis in extracorporeal circulation. Electrical capacitance tomography was used to visualize permittivity distribution to enhance precision in control flow rates thrombus prevention. An ECT sensor was made to measure blood capacitance at flow rates Q from Q = 0 to 2.6 L/min using impedance analyzer at current I =1 mA and at frequency from f = 1 kHz to 3 MHz. The flow dependent cell distribution images were reconstructed based on Linear back projection while simulations and modified Hanai formula were used as a post-evaluation of methods used in main experiments. Under the images at f = 430, 550 and 758 kHz showed significant increase in permittivity with increase in Q. Results correlated well with the simulation results showing flow dependent permittivity distribution. This adds a medical dimension to application of ECT to visualize permittivity distributions in proactive prevention thrombogenesis

On the photo-aging skin by ultraviolet exposure, it is well known that epidermal thickness grows due to a vital self-protective barrier against light. The biomechanical characteristics of skin tissue, e.g. viscoelasticity and micro-circulation, could be also changed corresponding to the epidermal barrier. In this study, Photo-Thermal Optical Coherence Doppler Velocigraphy is applied to visualize micro-circulating function of lymph flow inside skin tissue of mice. This can micro-tomographically visualize leaking plasma of from capillaries by means of the photo-thermal effect as well as optical absorption of Indocyanine Green. In addition, the comparative evaluation is carried out to the dynamical characteristic measurement using the cute meter.

According to the "Science and Technology Research Survey" (2019), the current number of Japanese researchers is 874,800, of which 155,000 are women. The percentage of women among researchers is a record high of 16.6%, but it is still low compared to the advanced countries in Europe and the United States. The period from graduate school to post-doctoral period coincides with the period of marriage for both men and women and the establishment of a family. In particular, young female researchers tend to choose between "research and childbirth" or "research or childbirth", and it is also a time of strong conflict and pressure. Since 2018, the conference in Sapporo has been set up to provide a nursery room and gender equality / diversity sessions with the support of the event chair. In this session, I would like to discuss what a research environment that allows young researchers.

Both of the authors are biomedical engineers raising two elementary school children. Here we would like to share our experiences of balancing work and life, looking at both success and failure, and focusing on how a male researcher's work benefits from contributing to housework and childcare. We think doing housework strengthened the ability to do multiple tasks simultaneously, which helped us take a comprehensive view of our research groups and manage their activities. Giving easy-to-follow explanations to children and exciting them through science were beneficial to the improvement of researcher's skills of presentation, acquiring budgets, and educating students. Playing scientific tools such as microcomputer with children gave us some inspiration related to biomedical engineering. Though housework and childcare should be shared among husbands and wives even without these viewpoints, we hope that our presentation and subsequent discussion motivate researchers balancing work and life.

The author and his wife are working as a university professor and a hospital doctor, respectively. We are a dual-career couple with two children, and have been trying to keep a good balance between work and family, however, life is not so easy. In this paper, we would like to share our experiences related to keeping work-life balance and building the careers.

When a young researcher leaves the laboratory with a proven track record and becomes independent, it is necessary to seek a new industry-academia collaboration system. However, science and technology universities often offer lectures on development and research, but not on business and management. Therefore, industry-academia collaboration can be said to be unknown science for young researchers. According to the author's experience, the role that universities actually play in industry-academia collaboration was not only pure research and development. Therefore, we clarify the strengths that universities should have and the roles that companies are unlikely to have, and propose a new industry-academia collaboration system.

The presenter has been conducting research on basics and applications of haptics, and has collaborated with industry companies on haptic design of products and development of haptic devices. Haptic sensations have not been computerized compared to visual and auditory sense, and evaluation and design methods have not been established. Therefore, possible applications and effects are often unknown for using haptic devices such as sensors and displays. Industry-academia collaborations in haptics might rarely take the simple aspect of matching industry needs with university technology seeds. It is important to set co-creative issues toward good results. Here, I believe that basic knowledge, original perspective, and backcasting might be applied from academia. In industry-academia collaborations on medical and biological engineering, there could be common issues and approach. I would like to introduce my experience to discuss co-creative industry-academia collaboration.

In the past, there has been an increasing movement from "different industries" to enter the medical devices and healthcare industries. The large-scale R&D in the Late Phase of AMED cannot be applied unless companies and universities/hospitals are collaborated. So "Industry-Academia Collaboration" are increasing.In general, although the development of medical devices requires a very long-term perspective, there are not many cases where this is a long-term effort in the industry-academia collaboration. For this reason, it may not work well in the case of industry-academia collaboration.The author has consulted in various industrial fields and has seen examples of industry-academia collaboration and cross-industry collaboration. Many causes are due to lack of mutual understanding. We identify pitfalls in industry-academia collaboration and processes suitable for avoiding them, and propose measures to facilitate the output of young researchers and new entrants aiming at medical device development.

Recent progress in understanding the essential roles of mechanical forces in regulating various cellular functions expands the field of biology to one where interdisciplinary approaches with mechanical engineering techniques become indispensable. Cellular traction forces (CTF) - that are present in proliferative cells including cancer cells due to the activity of ubiquitous nonmuscle myosin II (NMII) - are one of such mechanical forces (or signal regulators), but because NMII works downstream of diverse signaling pathways, it is often difficult to predict how the CTF changes upon perturbations to particular molecules such as gene mutations and drugs. Here I will talk about our unique bioengineering technology with a high-throughput data analysis capability to determine whether the endogenous CTF is upregulated or downregulated.

Atomic force microscopy (AFM) is a powerful technique for quantifying mechanical properties of single cells [1]. Recent AFM studies revealed the cell-to-cell [2] and temporal [3] variations of single-cell mechanical properties. Furthermore, AFM allowed us to measure the mechanical properties of multicellular system [4], combined with high-speed [5] and precise [6] measurement techniques. The applicability and limitations of single-cell mechanical assay and of probing tissue mechanics by AFM will be presented.[1] Y. M. Efremov et al. Soft Matter 16, 64 (2020). [2] P.G. Cai et al., Biophys. J. 105, 1093 (2013) . [3] P.G. Cai, R. Takahashi et al. Biophys. J. 113, 671 (2017). [4] Y. Fujii, T. Okajima, AIP Advances 9, 015028 (2019). [5] R. Takahashi, T. Okajima, Appl. Phys. Lett. 107, 173702 (2015). [6] Y. Fujii et al., Biophys. J. 116, 1152 (2019).

Periodontal ligament (PDL) and articular cartilage are always exposed to mechanical stress such as occlusion and walking. However, the effect of pressure on cells at a molecular level is poorly understood due to the lack of methods that directly observe cell motility under high pressure condition. Here we used hydrostatic pressure system to apply mechanical stress to cells in vitro and investigated cell morphology, molecules, and gene expression levels under mechanical stress conditions. We observe fork head protein O (FOXO), one of the transcription factor, translocates to nucleus from cytosol in a PDL cell under the high pressure condition. We also observe high pressure induces nucleus translocation of smad, one of the TGF-beta signaling pathway-related proteins, in a chondrocyte. Our systems directly show translocation of transcription factor and give us new pressure-sensing mechanism of PDL and cartilage tissue.

Glioma is a highly invasive brain tumor resulting in poor prognosis. Glioma stem cells generate heterogeneous cell populations composed of glioma stem cells and their differentiated progeny, which makes glioma treatment difficult. Here, we performed an in vitro three-dimensional invasion assay of glioma stem cells in interstitial flow. Cells were cultured in a microfluidic device, which allows to monitor cellular invasion process within gel. First, we found that invasion process of glioma stem cells in interstitial flow was depending on their differentiation. In addition, we investigated cellular distribution in the invasion process, revealing predominant existence of stem cells at the invasion front. Next, we focused on the magnitude of interstitial flow, because it is known that interstitial flow in tumor tissues is higher than that in normal tissues. We found that invasion and proliferation of glioma stem cells varied depending the magnitude of interstitial flow.

The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

Skeletal muscle has the capacity to regenerate myofibers after muscle injury. Upon a variety of stimuli including mechanical stretch, muscle-resident stem cells called muscle satellite cells (MuSCs) are committed to become myoblasts that can fuse with each other to generated multinucleated myofibers. We have focused on the role of mechanosensing machinery that is activated by membrane tension in myofiber regeneration. In this session, we will present our recent data showing that PIEZO1, one of mechanosensitive ion channels play crucial roles in activation of MuSCs. Piezo1 deficiency in MuSCs causes delayed regeneration of myofibers at least in part due to the defect of cell division in MuSCs. Moreover, in silico analysis demonstrates that at least three mechanosensitive ion channels including PIEZO1 are predominantly expressed in MuSCs, implying that cell fate of MuSC is largely dependent on mechanosensation through a triad of mechanosensitive ion channels.

It is known that atrophy of skeletal muscle progresses in a state where weightless stress is applied to the body such as bedridden and space flight. In our previous work, we have shown that weightless stress increases the expression of the ubiquitin ligase Cbl-b, which induces ubiquitination and degradation of IRS-1 and inhibits IGF-1 signaling, resulting in muscle atrophy. However, it remains unclear how cells sense weightless stress and enhance Cbl-b expression. Therefore, to clarify the mechanism of gravity sensing of myocytes, we conducted "Myolab" and "Cell-Mechanosensing" space experiments, and a study using 3D-Clinorotation, a simulated microgravity culture device on the ground. First, in the Myolab space experiment, metabolome analysis was performed on a space sample cultured in zero-gravity space for one week. Changes in the expression of proteins localized in mitochondria related to oxidative stress accumulation in cells and energy metabolism were observed. 3D-Clinorotation also shows an increase in intracellular oxidative stress as in the space sample, and this increased oxidative stress decreases the avtivity of the enzyme aconitase, which is important for energy production in mitochondria. Furthermore, it became clear that mitochondrial abnormalities were caused in the morphology. In the aconitase knockdown experiment using siRNA, mitochondrial morphological changes similar to those in3D-Clinorotation were caused. These results suggest that mitochondrial components such as aconitase play an important role in the initial response of cells to gravity sensing.

To understand the morphogenesis and homeostasis of muscles, tendons, skeletons and joints, we created a transcription factor expression database EMBRYS. Using this database, Mkx was identified as tendon/ligament specific gene and its critical functions in tendon development and homeostasis were elucidated by generating knockout mice and rats. In cartilage development, we identified Sox9 distal enhancers in cartilage and contributed to the understanding of congenital skeletal system diseases. In addition, as a Sox9 downstream target, we showed the critical role of miR-140 in cartilage. miR-140 is encoded in an intron of WWP2. Interestingly, we observed the distinct and cooperative function of miR-140 and WWP2 in cartilage development and homeostasis. Based on these finding, we further examine the miRNA dependent molecular network in musculoskeletal system by creating a target identification system for miRNA.

We use 3D foot type measuring device and foot pressure measuring device for more than 10 years, and for shoes that were sold only with experience, select shoes based on numerical and orthopedic theory, insole production, order I have been making shoes. In this lecture, we will present the voice of "now" for feet and shoes of customers visiting our company, shoes selection according to each symptom, and examples of insole production. Finally, he will present his attempt to make lasts using a 3D printer in collaboration with the medical field and future challenges.

Hallux valgus is a common disease of the foot in females that is treated with various surgical procedures. To prevent the recurrence, I think the ideal correction is three-dimensional correction considering the postoperative weight-bearing position. I have performed proximal oblique metatarsal osteotomy combined with distal soft tissue treatment using a plantar locking plate for moderate to severe hallux valgus since November 2013. I introduce the concept of the three-dimensional correction and this operative technique.The results of the clinical evaluation are satisfactory (JSSF scale, intermetatarsal angle, hallux valgus angle, the sesamoid position, Inclination angle, SAFE-Q). Recurrence of hallux valgus deformity was found in about 5%. Use of a plantar locking plate provides sufficient maintenance of the correction and complications associated with hardware are rare. We need to study the biomechanical effectiveness of the locked fixation from the tension side of the construct.

The foot is an important part of the body, because it is the only part of the body that normally makes contact with the ground. Hallux valgus(HV) is conditions that occur in many people, from the young to the elderly, and these conditions are causes of knee osteoarthritis. While it is thought that the skeletal structure of the foot has an influence on issues such as these, quantitative evaluations of the skeletal structure of the foot are not practiced.In this study, to evaluate the skeletal structure of the foot quantitatively, a 3D foot scanner that utilizes a smartphone was developed. The measuring precision of this system is as follows: a distance of 1.7mm and an angle 0.1 degrees. In this study, measurements were performed on people ranging in age from children to the elderly, and the risk of HV was evaluated based on the skeletal structure of the foot.

Respiratory organs experience repetitive and wide-ranging mechanical forces during breathing. Some of those mechanical signals are transduced by airway-innervating sensory neurons and control respiration; however, the physiological significance and molecular mechanisms of these signals remained obscure. PIEZO2, a mechanically activated cation channel, is the principal mechanotransducer in low-threshold cutaneous mechanoreceptors and skeletal-muscle-innervating proprioceptors in mice. We found that global and sensory neuron-specific ablation of PIEZO2 causes respiratory distress and death in newborn mice. Optogenetic activation of PIEZO2 expressing vagal sensory neurons causes apnoea in adult mice. Moreover, induced ablation of PIEZO2 in nodose sensory neurons of adult mice causes decreased neuronal responses to lung inflation, an impaired Hering-Breuer mechanoreflex, and increased tidal volume under normal conditions. Our data suggest that PIEZO2 is an airway stretch sensor and that PIEZO2-mediated mechanotransduction within airway-innervating sensory neurons is critical for establishing efficient respiration at birth and maintaining normal breathing in adults.

Chronic obstructive pulmonary disease (COPD) is characterized as progressive airflow limitation caused by pathologies in airway and lung parenchyma. Whereas airflow limitation may occur due to simple airway diseases, physiological and mechanical interaction between airway and parenchyma may be important pathophysiological features of COPD. Such interaction may exist in various level of airways, and consequently, static and/or dynamic hyperinflation may occur in COPD lungs. These pathophysiological features may serve as major source of severe breathlessness, excise intolerance and restricted activities in daily life. To evaluate these pathophysiological features of COPD, several modalities, such as pulmonary function tests, quantitative imaging techniques, and other objective measurements are conducted in clinical settings. However, radical interventions to treat COPD lungs are not achieved yet. Recent progress in techniques of quantitative measurements, and physiological investigations of COPD lungs may contribute deepened understandings of COPD pathophysiology and development of significant intervention of patients with COPD.

Introduction: Emphysema is a progressive disease that gradually destroys alveolar tissue leading to airspace enlargement. CT imaging have demonstrated that tissue density decreases in a heterogeneous manner producing a distribution of clusters of low attenuation areas (LAA). Although computational models have been proposed to understand the process via mechanical failure, they lack patient specificity. The aim of this work was to develop a computational model that allows spatiotemporal simulations of patient specific tissue loss on CT images.

Materials and Methods: We created a large 2-dimensional hexagonal elastic network to recapitulate the alveolar geometry. Initially, the network had a rectangular boundary. The CT image of a patient was thresholded and the boundary of the lung field was approximated with a closed polygon. The coordinates of the vertices were mapped onto the network and nodes outside the polygon were set to be fixed whereas nodes inside the polygon were allowed move in subsequent optimization procedures. The line elements were linear springs with their initial length smaller than the distance between their nodes creating a prestress. The equilibrium configuration was solved and an apparent CT image was created by placing a square grid on the network and within each square, the number of springs were counted which was set to be proportional to CT density. From the network, a stress map can be computed by averaging the network forces within a pixel. To mimic emphysema progression, first a set of initial holes was created in the network by cutting springs in a random fashion. Next, the internal node positions were found that minimized the total elastic energy of the network. The forces on all springs were computed and 10 springs carrying the largest force were cut followed by another optimization. These steps were then repeated 5 times where each iteration represents the progression of emphysema.

Results and Discussion: The original CT image and the LAA cluster structure created by the model were similar and the corresponding network also predicted the LAA clusters and a stress map. The model captured the large and medium sized LAA clusters but not the smallest clusters. The model was then applied to predict a patient's CT image 1 or 2 year after the first image was taken by advancing the progression of emphysema on the images obtained at time 0. Despite some differences, the model was able to capture major trends in structural alterations. The stress map predicted by the model can then be used as a patient and location specific risk predictor.

Conclusions: We have introduced a personalized network model approach to convert a CT image to a stress map which allows predicting the spatial location of tissue deterioration. Our approach may find implications for predicting the personalized rate of decline of lung structure and function in response to interventions such as drug treatment or lung volume reduction.

Acknowledgements: This study was funded by NIH grant U01 HL-139466.

Mechanical cues such as stretch, shear stress and matrix stiffness are considered to be involved in the mechanisms underlying the pathogenesis of pulmonary diseases. Because the elastic modulus of solid tumors (20-30 kPa) is much stiffer than that of normal lung parenchyma (0.5-5 kPa), the increased rigidity of the extracellular matrix (ECM) is one of characteristics of malignant phenotypes in solid tumors including lung cancer. Expression of programmed death-ligand 1 (PD-L1) in lung cancer cells regulates evasion of an immune check point system. We evaluated the effects of substrate stiffness on PD-L1 expression by using polyacrylamide hydrogels with different stiffnesses. We demonstrated that a stiff substrate enhanced PD-L1 expression via actin-dependent mechanisms in lung cancer cells. It is suggested that stiff substrates corresponding to pathologically cancer-related fibrotic tissues as a tumor environment regulates PD-L1 expression, which leads to evasion of the immune system and tumor growth.

Electromagnetic Compatibility Conference Japan (EMCC) was founded in 1987. The main contents of activity are as follows.- Collecting and exchanging information about unnecessary electromagnetic waves- Studying limits and measurement methods for unnecessary electromagnetic waves to create a sound electromagnetic environment- Providing technical information to deliberative bodies tackling electromagnetic compatibility problems- Providing information to the public about electromagnetic compatibility EMCC has five committees. One of them is the "committee for radio use promotion in medical institution". This committee discusses policies and guidelines for safe and secure use of radio waves at medical institutions. This presentation mainly explains the subject of a guideline and the present condition as contents of activity of a committee.

Recently, we are considering the utilization smartphones for their work-style innovation in hospitals. So far Nurse Call system is consisted of PHS communication, but smartphone is going to take the place of it, and some hospitals have already replaced and in use.This session we show the next generation nurse call system by smartphone, and explain the use case and system components, and effectiveness for work flow.Additionally, we need to emphasize on the security approach to use smartphone in hospitals.

The use of electronic information, such as electronic medical records, is expanding at medical sites.In addition, the use of wireless communication as data transmission has increased due to the use of ICT in medical devices.As for vital sign devices and sensors, those that support wireless communication as IoT devices are also expanding.Utilization of sensor data from IoT devices has also begun for medical safety and monitoring purposes.For these reasons, the wireless communication environment has become an important infrastructure.Another challenge is to share radio waves not only in wireless LANs but also in many types of wireless communications.Since many radio waves are used, it is important to prevent radio interference.Therefore, radio wave management in medical institutions is a very important action.

Electrical excitation conduction abnormalities at the right ventricular outflow tract (RVOT) are one of the arrhythmogenic substrates despite normal heart. However, how much delay at the RVOT develops ventricular arrhythmias is not quantitatively investigated. In this study, we constructed a three-dimensional human ventricular model including 20 million myocardial units to investigate the role of conduction delay in the RVOT on initiation and maintenance of the ventricular arrhythmias. Electrical coupling conductance between two units in the conduction delay zone and size of conduction delay zone could be freely changed. Ventricular arrhythmia inducibility in the heart with conduction delay zone around the RVOT was higher compared with the heart with conduction delay the right ventricular free wall. Anatomical complexities and electrophysiological heterogeneity around the RVOT might act as important role in induction spiral wave reentry to transfer to ventricular arrhythmia.

This paper presents electrocardiogram (ECG) measurement systems that involve capacitively coupled electrodes. Two of three systems presented are non-wearable types and the other is wearable type. The non-wearable systems are in-bed and on-seat systems, respectively. Capacitive ECG (cECG) measured by these systems provided clearly visible R and T waves even in realistic measuring conditions. Moreover, the wearable-type system using elastic bandage electrodes also provided stable cECG recordings in treadmill exercise test, compared with directly measured NASA-lead ECG.

[Aims] Atrial fibrillation (AF) is known as a major cause of acute cerebral infarction. Cerebral infarction with AF could be prevented by taking oral anticoagulants. Thus, it is critically important to detect and diagnose the presence of AF. Machine learning of Lorenz plot (LP) images is recognized as a promising method for the detection of AF in long-term ECG monitoring, however, the optimal segment length of LP image is unknown. We examined the performance of AF detection by differing LP segment length using convolutional neural network (CNN).

[Methods] The datasets of 32x32-low-resolution LP images of R-R interval segments between 20 and 600 beats were created from 24-h ECG data in 52 patients with AF and 58 non-AF controls as teacher data and in 53 patients with paroxysmal AF and 52 non-AF controls as verification data.

[Results] In the verification, the positive likelihood ratio (LR) for detecting AF showed a convex parabolic curve with a peak positive LR at 100 beats, while negative LR decreased monotonously as the segment length decreased.

[Conclusions] The optimal segment length using CNN models should be 100 beats for discriminating between AF and non-AF.

【Background】Spiral Wave (SW) excitation, which is known to be a driving source of tachyarrhythmia, has been reported to move around the local cooling area of the heart. It may be possible to realize minimally invasive defibrillation, if the SW movement can be controlled by regional cooling. We proposed linear regional cooling (LRC) to stop SW excitation, and demonstrated the effectiveness of the method in in silico and ex vivo experiments.

【Methods】For the in silico experiment, we used a two-dimensional bidomain heart tissue model. Three LRC parameters were set: the angle of the cooling device with fiber orientation, the cooling device width and its cooling temperature. The dynamics of SW during LRC was simulated. We constructed a LRC system using low-temperature coolant, and ex vivo experiments were performed on extracted rabbit hearts.

【Results】As a result of the in silico experiment, effective SW movement was observed when LRC with low cooling temperature and wide cooling width was performed along the fiber orientation. In the ex vivo experiment, SW termination due to LRC was observed.

【Conclusion】It was shown that appropriate linear regional cooling could effectively terminate SW excitation.

Targeted external heavy ion beam irradiation has been shown to reduce the vulnerability of infarctionrelated ventricular tachyarrhythmia in rabbit. However, the effects of heavy ion radiation on the atrial arrhythmia are not well understood. We investigated the electrophysiological effects of heavy ion beams on the atrial arrhythmogenic substrate in aged and hypercholesterolemic rabbit. Optical action potential signals were recorded from left atrium of Langendorff-perfused rabbit hearts of young (YR: n=4), aged with hypercholesterolemia (high fat and hypercholesterolemic chow for 8 weeks, ARC: n=6) and ARC plus heavy ion irradiation group rabbit (ARC-H: n=4). In ARC-H group rabbit, single target external heavy ion irradiation (of 15Gy carbon beam) was applied on the left atrium (LA) using the Heavy Ion Medical Accelerator in Chiba, Japan. Spontaneous atrial premature complex (APC) and induced sustained atrial tachycardia and fibrillation (AT/AF) occurred in 5 out of 6 rabbit hearts of ARC group, while none (0/4) of YR group exhibited AT/AF even APC. Short- and/or long-lasting rotor was observed in the maintenance of sustained AT/AF. Heavy ion irradiation dramatically decreased incidence of atrial arrhythmia. These results indicate that heavy ion irradiation reversed atrial remodeling, thereby reducing AT/AF in aged and hypercholesterolemic rabbit.

Skeletal muscle is a dynamic tissue that routinely undergoes cell shortening and generates forces, and thus, it is required to limit mechanical cellular injury and adapt to changing workloads. Dystroglycan connects extracellular matrix and cytoskeletons across the cell membrane via sugar chain that contains a novel post-translational unit ribitol-phosphate (RboP). RboP forms a tandem repeat and functions as a scaffold for the formation of the ligand-binding moiety. Muscle cell membrane in mouse models that lack the RboP shows fragility against physical stress. These findings demonstrate that RboP-containing sugar chain plays an essential role to maintain membrane integrity and prevent physical stress-induced cell damages.In this symposium, we also introduce our current AMED-CREST project "Elucidation of membrane and sugar chain environment required for mechano-sensing/response and its application to the development of therapeutic strategy for muscle diseases" that aims at developing therapeutic and preventive strategies for muscle diseases by understanding the molecular basis of the mechano-sensing/response.

Articular cartilage is an essential tissue that support movement of articular joint, and always receives intensive mechanical loading, particularly in lower extremities. We have studied molecular pathophysiology of osteoarthritis using mouse experimental models for years, and identified NF-kappaB-HIF-2alpha pathway as a major responsible signaling for cartilage degeneration. We recently reported mechanisms in which excessive loading cause cartilage degradation through Gremlin-1 induction and the subsequent NF-kappaB activation. In this symposium, I introduce these molecular mechanisms.

The cell surface is coated with a dense layer of glycocaryx composed of glycoproteins and glycolipids and the glycan structures are altered in diseases. The majority of Federal Drug Administration (FDA)-approved tumor markers, which are clinically utilized worldwide, are either glycans or glycoproteins. In this study, we report a series of methodologies for the comprehensive glycomic analysis of various glycoconjugates using mass spectrometry and liquid chromatography. Moreover, we introduce the sialic acid linkage-specific alkylamidation method by lactone-ring opening aminolysis (aminolysis-SALSA method) for the discovery of disease-related biomarkers.

The hearts has a dynamic compensatory mechanism for hemodynamic stress. However, prolonged and abnormal hemodynamic stress induces cardiac disease. We investigated the molecular mechanism of cardiac hypertrophic response and progression of heart failure to hemodynamic stress. Transient receptor potential cation channel vanilloid-family type 2 (TRPV2) is a potential candidate as a hypotonically-activated and stretch-activated channel. Previously, we have reported that TRPV2 is crucial for the cardiac structure and function under physiological conditions. TRPV2-deficient neonatal cardiomyocytes had severely impaired functional maturation. The elimination of TRPV2 from juveniles resulted in mild chamber dilation, and defects in the compensatory hypertrophic response to pressure-overload. These results indicate that the TRPV2 signal is also required for the maturation of myocytes, and the compensatory hypertrophic response to hemodynamic stress. In addition, we show why Fktn (causative gene for Fukuyam mascular dystrophy)-deficient hearts is vulnerable to pressure-overload, and discuss the pathomolecular mechanism of muscular dystrophy-associated heart failure.

Membrane is one of the most important apparatus for living cells. Every single external matter, include mechanical stimuli, goes through the membrane. However, membrane proteins are generally tough targets to study although there is the strong demand for medicine. Here, I present one of the examples how to conduct basic and translational research of membrane transporters. Nutrient transporters play the role to allow selective permeation of nutrients. In cancer cells, nutrient transporters are constitutively upregulated to facilitate the uptake for robust cell growth. Among them, LAT1 (SLC7A5) is known as a cancer-specific amino acid transporter. LAT1 transports most of essential amino acids include leucine, a signal for cell growth via mTORC1. Thus, LAT1 has been considered as an attractive target for cancer diagnose and treatment. By using multi-disciplinary approaches from biochemistry, pharmacology and proteomics, we have been studying LAT1 and developed several of small compounds for cancer imaging or anti-cancer.

Otsuka and Proteus Digital Health developed the first digital medicine "Abilify MyCite" that can measure medication adherence. It embeds a very small sensor developed by Proteus into an antipsychotic Abilify tablet marketed by Otsuka. When a patient swallows tablets, a chip emits a signal in the stomach and it is captured by a small patch which sticks to the patient's abdomen and this is recorded. The patch transmits adherence information to the patient's smartphone as well as capturing activity and rest from sensors on the patch. The transmitted information is captured on both the patient's phone as well as shared with healthcare professionals, caregivers and families with the patients' consent. Based on this information, healthcare professionals can measure the condition of the patient and assess the risk if there is a sign of recurrence such as poor adherence or abnormal sleep pattern, then take the appropriate intervention.

The organic electronics enables flexible, large-area, and distributed sensor and/or actuator array and is suitable for the wearing-unconscious devices used in biomedical and healthcare applications. Power delivery to ultra-thin flexible devices with the thickness of 1um to 10um, however, is a challenge, because wired connections and rigid battery are not allowed. To solve the problem, novel flexible devices for wearable healthcare applications with the energy harvesting or the wireless powering using organic circuits are proposed and demonstrated. In this talk, I will show an insole pedometer with piezoelectric energy harvesters, a fever alarm armband with solar cells, and a wet sensor sheet in a diaper with wireless powering.