Abstract: Sonothrombolysis is a technique to remove blood clot from vessels by using ultrasound waves to induce acoustic cavitation (formation of microbubbles). Recent studies have demonstrated improved sonothrombolytic efficacy when using two ultrasound waves of different frequencies (dual-frequency ultrasound). Nevertheless, our recent study [1-5] suggested that an improper selection of the ultrasound frequency, specifically when one frequency is an integer multiplier of another, can weaken the cavitation intensity and the flow-induced shear stress, leading to poor sonothrombolysis outcomes. This is due to the destructive interference at these frequencies, which reduces the pressure amplitude of the resultant waves that incident on the microbubble. In this study, we investigated the hypothesis that destructive interference due to improper frequency selection can be alleviated by shifting the phase between the two ultrasound waves. To that end, a finite element model of the microbubble undergoing ultrasound-induced oscillation was developed. When ultrasound of 0.5 MHz was paired with 1 MHz, a phase shift of 270° led to shear stress of 22.5 kPa, which was one order of magnitude higher than the case without phase shift. The results obtained showed that a correctly chosen phase shift can overcome the weakened cavitation of two ultrasound waves with frequencies being an integer multiplier of another. In contrast, non-integer multipliers of frequency pairings did not show significant influence of phase shift on cavitation and shear stress. Findings from this study provide new insights into the biomechanics behind sonothrombolysis with dual-frequency ultrasound. This allows an excellent starting point for future advancement and optimisation of this treatment.
References:
[1]. ZQ Tan, EH Ooi, YS Chiew, JJ Foo, EYK Ng, ET Ooi, “Enhancing sonothrombolysis outcomes with dual-frequency ultrasound: insights from a microbubble dynamics study”, Computers in Biology and Medicine, (2024), Vol. 181, pp. 109061 (11 pages), (IF: 7.7, Q1, Rank: 19/93 in Biology) https://doi.org/10.1016/j.compbiomed.2024.109061.
[2]. ZQ Tan, EH Ooi, YS Chiew, JJ Foo, EYK Ng, ET Ooi, “Delineating the effects of ultrasound and microbubble parameters on the outcome of sonothrombolysis: a computational analysis on the microbubble dynamics”, Biocybernetics and Biomedical Engineering, (2024), 44(2), pp. 358-368, https://doi.org/10.1016/j.bbe.2024.04.003.
[3]. Zhi Q Tan, Ean H Ooi, Yeong S Chiew, Ji J Foo, EYK Ng, ET Ooi, “A computational framework for the Multiphysics simulation of microbubble-mediated sonothrombolysis using a forward-viewing intravascular transducer”, Ultrasonics, Vol. 131, (2023), pp. 106961, (12 pages), https://doi.org/10.1016/j.ultras.2023.106961.
[4]. ZQ Tan, EH Ooi, YS Chiew, JJ Foo, EYK Ng, ET Ooi, “Competing Effect of Jetting During Microbubble-Mediated Sonothrombolysis”, M.J.M. Mokhtarudin et al. (eds.), Proceedings of the Annual Congress of the Asia-Pacific Society for Artificial Organs, Lecture Notes in Bioengineering, Springer Nature, Singapore. https://doi.org/10.1007/978-981-97-1920-4_2.
[5]. ZQ Tan, EH Ooi, YS Chiew, JJ Foo, EYK Ng, ET Ooi, “A Computational Study on the Use of Phase Shift to Improve Dual-Frequency Sonothrombolysis Outcomes”, 8th IEEE-EMBS Conference on Biomedical Engineering and Sciences (IECBES2024), 11-13th Dec 2024, Penang, Malaysia. (accepted) paper #1571061932.

Biography:
Dr. Eddie obtained Ph.D. at Cambridge Univ. with a Cambridge Commonwealth Scholarship.

He is elected as:
• Fellow (inaugural) for National Academy of Technology (USA);
• Academician for European Academy of Sciences and Arts (EU-Austria);
• Academician for European Academy of Sciences (EU-Greece);
• Fellow (Life) of the American Society of Mechanical Engineers (USA);
• Fellow of Institute of Engineering and Technology (United Kingdom);
• Fellow of Industry Academy: International Artificial Intelligence Industry Alliance (HK),
• Fellow of International Engineering and Technology Institute (Hong Kong),
• Fellow of Asia-Pacific Technological Sciences Academy (Hong Kong),
• Distinguished Fellow for Institute of Data Science and Artificial Intelligence, (China), and,
• Fellow of the American Institute for Medical and Biological Engineering (USA) with his citation reads: "For outstanding contributions in non-contact, early detection of human-health abnormality non-invasively with infrared-physics-technology".
Eddie received 2022 Alumni Highly Commended Award from the VC of Newcastle University, UK for his contributions to the society and achievements as academia. Winner of the 2024 2nd IETI (International Engineering and Technology Institute) Ramesh Agarwal Lifetime Achievement Award in Science, Engineering or Technology. This award honors individuals with lifetime achievements in research, education, and service towards the advancement of any discipline of engineering and technology.

Since 1992, he works as Faculty in the School of Mechanical & Aerospace Engineering in Nanyang Technological University, Singapore. He is the: Lead Editor-in-Chief for the ISI Journal of Mechanics in Medicine and Biology for dissemination of original research in all fields of mechanics in medicine and biology since 2000; & Lead Editor-in-Chief for the ISI Journal of IET - AI in Surgery for dissemination of original research in integrating of artificial intelligence, surgery, and biomedical engineering, since 2024; https://www.worldscientific.com/page/iet/ai-surgery

He is included in the Stanford list of the World’s top 2% Scientists since 2019 (ranked <80 out of 64,425 as 0.001% in the field of Biomedical Engineering). The ranking method is calculated by removing the self-citation of the literature. His Google Scholar (h-index: 73+) can be found in: [http://scholar.google.com.sg/citations?user=9QW1LYAAAAAJ].

Biography: Dr. Liu received his B.S. and Ph.D. degrees in Biomedical Engineering from Shandong University, China, in 2005 and 2010 respectively. Dr. Liu has completed the Postdoctoral trainings at Shandong University, Newcastle University in UK (2013-2014) and Emory University in USA (2015-2017). He is now the Dean of the School of Instrument Science and Engineering in Southeast University, a Professor of the State Key Laboratory of Digital Medical Engineering, and the founding Director of Wearable Heart-Sleep-Emotion Intelligent Monitoring Lab in Southeast University, leading the research works on medical big-data processing, medical device development and clinical applications. He is now a member of Federation Journal Committee of International Federation for Medical and Biological Engineering (IFMBE), a Council member of Chinese Society of Biomedical Engineering (CSBME), and serve as an Executive Editorial Board member for Physiological Measurement, an Deputy Editor for Medical & Biological Engineering & Computing, an International Advisory Editorial Board member for Journal of Medical and Biological Engineering, an Associate Editor for IEEE Transactions on Instrumentation and Measurement, etc. He has published more than 300 original Journal/Conference papers, and holds more than 30 patents as an inventor. His research topics include: mHealth and intelligent monitoring, machine learning and big data processing for physiological signals, early detection and device development for cardiovascular diseases, sleep quality and emotion status monitoring.

Abstract: Cancer continues to be a major global health concern, affecting millions of lives worldwide. However, translational cancer research has emerged as a crucial approach in the fight against cancer, bridging the gap between laboratory discoveries and clinical applications. This presentation begins by introducing precision medicine and emphasizing the role of cancer biomarkers. The use of proteomic and genomic profiling, along with molecular diagnostics, is essential for identifying cancer subtypes, predicting treatment response, and determining personalized strategies.

Liquid biopsies, which involve the analysis of circulating tumor DNA and other biomarkers in liquid samples, have shown promise for non-invasive cancer detection, monitoring treatment response, and identifying resistance mechanisms. This approach has the potential to revolutionize cancer diagnosis and monitoring.

Despite significant advancements, challenges such as resistance and tumor heterogeneity pose obstacles to long-term treatment success. This presentation will cover research topics such as drug repurposing, artificial intelligence, and the utilization of Chinese medicine in cancer treatment.

Biography: Dr William Cho primarily focused on cancer studies with the aim of identifying biomarkers for cancer diagnosis, treatment prediction, and prognosis. As a seasoned researcher, Dr Cho has contributed over 600 peer-reviewed papers to reputable journals including Lancet, Lancet Oncology, Annals of Oncology, Advanced Science, Journal of Thoracic Oncology, Nature Communications, Cancer Communications, PNAS, Science Advances, Journal of the National Cancer Institute, Journal of Extracellular Vesicles, Clinical Cancer Research, Molecular Cancer, and Theranostics, among others. These publications cover a wide range of topics including cancer biomarkers, non-coding RNAs, extracellular vesicles, drug repurposing and Chinese medicine. Additionally, Dr Cho has crafted over three dozen books, including "MicroRNAs in Cancer Translational Research", "An Omics Perspective on Cancer Research", "Supportive Cancer Care with Chinese Medicine", "Drug Repurposing in Cancer Therapy: Approaches and Applications", “Resistance to Anti-CD20 Antibodies and Approaches for Their Reversal”, and “Biochemical and Molecular Pharmacology in Drug Discovery” to name a few.
Dr Cho published papers have garnered more than 30,000 citations and Dr Cho is being listed in the top 2% most influential scientists in the world since 2017. Recently, Dr Cho is also listed in the Highly Cited Researchers in 2023 by Clarivate.

Abstract: Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a risk factor for insulin resistance/type 2 diabetes, hypertension, and cardiovascular diseases. However, the mechanisms linking IH and the diseases remain elusive. We used in vitro IH system to expose pancreatic β-cells, adipocytes, hepatocytes, skeletal muscle cells, neuronal cells, enteroendocrine cells, vascular smooth muscle cells, vascular endothelial cells, juxtaglomerular cells, cardiomyocytes to IH or normoxia for analyzing changes of gene expression and the mechanisms. We found that IH induced (1) attenuation of glucose-induced insulin secretion via downregulation CD38, (2) upregulation of adipokines via downregulation of microRNA (miR)-452, (3) upregulation of hepatokine via downregulation of miR-203, (4) upregulation of myokines via OCT1- and NRF2-mediated mechanism, (5) vascular smooth muscle cell proliferation via upregulation of EGF family, (6) upregulation of ESM1 and ICAM-1 in vascular endothelial cells via downregulation of miR-181a1, (7) upregulation of renin in juxtaglomerular cells via downregulation of miR-203, (8) upregulation of catecholamine-metabolizing enzymes in catecholamine synthesizing neuronal cells via downregulation of miR-375, and (9) downregulation of components for the CD38-cyclic ADP-ribose signal system in cardiomyocytes via upregulation of Pten. In SAS, cells throughout the body are exposed to IH, which affects various cells related to diabetes, hypertension, and heart disease, which are complications frequently seen in SAS. We have clarified the effects of IH exposure through molecular biological methods. In the future, it will be important to develop good animal models and use them to develop treatment and prevention methods.
Keywords: diabetes, hypertension, SAS, IH, CD38-cADPR signal system, Reg-Reg receptor system

Biography: Shin Takasawa was born in 1958 in Kashiwazaki, Nigata, Japan. He qualified as a medical doctor at the age of 25 years in Yamagata University and has completed his PhD at the age of 30 years from Tohoku University School of Medicine. He has been engaged in biochemical and molecular biological research on diseases such as diabetes in Tohoku University Graduate School of Medicine as a staff of Department of Biochemistry. In the process, he found cyclic ADP-ribose as a second messenger in glucose-induced insulin secretion from pancreatic β-cells and Reg (regenerating gene)-Reg receptor system in β-cell regeneration. In 2007, he moved to professor & chairman of Department of Biochemistry, Nara Medical University and performed molecular research concerning sleep apnea syndrome (SAS)/intermittent hypoxia (IH). He has published more than 200 papers in reputed journals and has been serving as an editorial board member of Life Sci. & Int. J. Mol. Sci.