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Is it Time for Single-Pill Combinations in Dyslipidemia?

Am J Cardiovasc Drugs 2021 Sep 22. Epub 2021 Sep 22.

First Department of Cardiology, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Despite the availability of lipid-lowering therapies (LLTs) that are safe and effective, the overall rate of low-density lipoprotein cholesterol (LDL-C) control at a population level in real-life studies is low. Higher-intensity treatment, earlier intervention, and longer-term treatment have all been shown to improve outcomes. However, in clinical practice, actual exposure to LLT is a product of the duration and intensity of, and adherence to, the treatment. Read More

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September 2021

Implementation of robotic-assisted total knee arthroplasty in the public health system: a comparative cost analysis.

Int Orthop 2021 Sep 22. Epub 2021 Sep 22.

Department of Orthopaedic Surgery, Royal Prince Alfred Hospital (RPAH), Sydney, NSW, Australia.

Purpose: Robotic-assisted total knee arthroplasty (TKA) may improve the precision of bone preparation and component alignment when compared to the conventional surgical approach; however, the detailed cost analysis of robotic-assisted TKA is lacking. This study aims to compare in-hospital costs between robotic-assisted and computer-navigated TKA.

Methods: Patients undergoing primary TKA at a public hospital in Sydney between October 2018 and June 2019 were included. Read More

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September 2021

Status of N-of-1 Trials in Chronic Pain Management: A Narrative Review.

Pain Ther 2021 Sep 16. Epub 2021 Sep 16.

Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Gongye Road, Guangzhou, 510282, China.

N-of-1 trials are randomized controlled clinical trials conducted exclusively on a single patient. The ultimate aim of N-of-1 trials is to optimize a strategy in a particular individual. Chronic pain is a common but refractory clinical problem. Read More

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September 2021

Clinical impact of detecting low-frequency variants in cell-free DNA on treatment of castration-resistant prostate cancer.

Clin Cancer Res 2021 Sep 15. Epub 2021 Sep 15.

Department of Urology, Hirosaki University Graduate School of Medicine.

Purpose: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from CRPC patients and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%.

Experimental Design: This prospective, multicenter cohort study enrolled CRPC patients eligible for treatment with abiraterone or enzalutamide. Read More

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September 2021

The Neutrophil-to-Lymphocyte Ratio (NLR) Predicts the Prognosis of Unresectable Intermediate and Advanced Hepatocellular Carcinoma Treated with Apatinib.

Cancer Manag Res 2021 7;13:6989-6998. Epub 2021 Sep 7.

Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.

Purpose: Patients with hepatocellular carcinoma (HCC) who might benefit most from anti-angiogenesis therapy remain unknown. In recent years, neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammatory response, has received particular attention in HCC. Herein, we explored the prognostic value of pre-treatment NLR in individuals with unresectable intermediate and advanced hepatocellular carcinoma treated with apatinib, a second-line angiogenesis inhibitor. Read More

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September 2021

Diffraction-Unlimited Photomanipulation at the Plasma Membrane via Specifically Targeted Upconversion Nanoparticles.

Nano Lett 2021 Sep 14. Epub 2021 Sep 14.

Department of Biology/Chemistry and Center of Cellular Nanoanalytics (CellNanOs), Osnabrück University, 49076 Osnabrück, Germany.

Engineered UCNP are used to trigger rapid photoconversion of the fluorescent protein Dendra2 with nanoscopic precision and over longer distances in mammalian cells. By exploiting the synergy of high-level thulium doping with core-shell design and elevated excitation intensities, intense UCNP emission is achieved, allowing fast photoconversion of Dendra2 with <10 nm resolution. A tailored biocompatible surface coating and functionalization with a derivate of green fluorescent protein (GFP) for recognition of antiGFP nanobodies are developed. Read More

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September 2021

Innovative radiation oncology Together - Precise, Personalized, Human : Vision 2030 for radiotherapy & radiation oncology in Germany.

Strahlenther Onkol 2021 Sep 13. Epub 2021 Sep 13.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Purpose: Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. Read More

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September 2021

Integrative analysis reveals clinically relevant molecular fingerprints in pancreatic cancer.

Mol Ther Nucleic Acids 2021 Dec 2;26:11-21. Epub 2021 Jul 2.

Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 201620, China.

Pancreatic cancer is a highly aggressive cancer with an exceedingly low rate of response to treatments, which calls for comprehensive molecular characterization of pancreatic cancer cell lines (PCCLs). We screened multi-layer molecular data of 36 PCCLs, including gene mutation, gene expression, microRNA (miRNA) expression, and protein profiles. Our comparative analysis of genomic mutations found that PCCLs recapitulated genomic alterations of the primary tumor and suggested potential therapeutic strategies for clinical interventions. Read More

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December 2021

Molecular View on the Dissociation Pathways and Transactivation Regulation Mechanism of Nonsteroidal GR Ligands.

J Chem Inf Model 2021 Sep 10. Epub 2021 Sep 10.

Innovation Institute for Artificial Intelligence in Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 Zhejiang, China.

As a major drug target for anti-inflammatory therapy, the glucocorticoid receptor (GR) regulates a wide range of physiological processes through transactivation (TA) or transrepression. GR TA is involved in many adverse effects of GR-targeting drugs, and therefore, the discovery of novel GR ligands with lower TA activity and longer residence time is quite urgent. Undoubtedly, understanding the ligand dissociation mechanisms and the structural basis of the TA regulation is crucial for the development of novel GR-targeting drugs. Read More

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September 2021

Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region.

Eur Heart J 2021 Sep 10. Epub 2021 Sep 10.

Department of Cardiology, CARIM, Maastricht University Medical Center, PO Box 5800, 6202 Maastricht, The Netherlands.

Aims: Mutation type, location, dominant-negative IKs reduction, and possibly loss of cyclic adenosine monophosphate (cAMP)-dependent IKs stimulation via protein kinase A (PKA) influence the clinical severity of long QT syndrome type 1 (LQT1). Given the malignancy of KCNQ1-p.A341V, we assessed whether mutations neighbouring p. Read More

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September 2021

Hierarchical Learning of Statistical Regularities over Multiple Timescales of Sound Sequence Processing: A Dynamic Causal Modeling Study.

J Cogn Neurosci 2021 Jul;33(8):1549-1562

University of Newcastle, Callaghan, Australia.

Our understanding of the sensory environment is contextualized on the basis of prior experience. Measurement of auditory ERPs provides insight into automatic processes that contextualize the relevance of sound as a function of how sequences change over time. However, task-independent exposure to sound has revealed that strong first impressions exert a lasting impact on how the relevance of sound is contextualized. Read More

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Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study.

Br J Cancer 2021 Sep 7. Epub 2021 Sep 7.

CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.

Introduction: Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution.

Methods: Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. Read More

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September 2021

Elucidating the Mechanisms Underlying the Signal Drift of Electrochemical Aptamer-Based Sensors in Whole Blood.

ACS Sens 2021 Sep 7. Epub 2021 Sep 7.

Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, United States.

The ability to monitor drugs, metabolites, hormones, and other biomarkers in situ in the body would greatly advance both clinical practice and biomedical research. To this end, we are developing electrochemical aptamer-based (EAB) sensors, a platform technology able to perform real-time, in vivo monitoring of specific molecules irrespective of their chemical or enzymatic reactivity. An important obstacle to the deployment of EAB sensors in the challenging environments found in the living body is signal drift, whereby the sensor signal decreases over time. Read More

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September 2021

Accurate detection of typical absence seizures in adults and children using a two-channel electroencephalographic wearable behind the ears.

Epilepsia 2021 Sep 7. Epub 2021 Sep 7.

Laboratory for Epilepsy Research, KU Leuven and Department of Neurology, University Hospitals, Leuven, Belgium.

Objective: Patients with absence epilepsy sensitivity <10% of their absences. The clinical gold standard to assess absence epilepsy is a 24-h electroencephalographic (EEG) recording, which is expensive, obtrusive, and time-consuming to review. We aimed to (1) investigate the performance of an unobtrusive, two-channel behind-the-ear EEG-based wearable, the Sensor Dot (SD), to detect typical absences in adults and children; and (2) develop a sensitive patient-specific absence seizure detection algorithm to reduce the review time of the recordings. Read More

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September 2021

Psychodynamic Psychiatry and the Therapeutic Space in the Era of COVID-19.

Douglas H Ingram

Psychodyn Psychiatry 2021 ;49(3):441-452

Clinical Professor of Psychiatry and Behavioral Sciences at New York Medical College.

Psychodynamic psychiatric practice during the COVID-19 pandemic has required most clinicians to conduct treatment online or by telephone. The result is a natural experiment that appears to endorse the efficacy of distance therapy. Consequently, the brick-and-mortar consulting room is no longer the presumptive therapeutic space for the conduct of psychodynamic psychiatric or other treatment approaches. Read More

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September 2021

Molecular Understanding of the Catalytic Consequence of Ketene Intermediates under Confinement.

J Am Chem Soc 2021 Sep 3;143(37):15440-15452. Epub 2021 Sep 3.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, P. R. China.

Neutral ketene is a crucial intermediate during zeolite carbonylation reactions. In this work, the roles of ketene and its derivates (viz., acylium ion and surface acetyl) associated with direct C-C bond coupling during the carbonylation reaction have been theoretically investigated under realistic reaction conditions and further validated by synchrotron radiation X-ray diffraction (SR-XRD) and Fourier transformed infrared (FT-IR) studies. Read More

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September 2021

Association of Sleep Duration With All- and Major-Cause Mortality Among Adults in Japan, China, Singapore, and Korea.

JAMA Netw Open 2021 Sep 1;4(9):e2122837. Epub 2021 Sep 1.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan.

Importance: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations.

Objectives: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index.

Design, Setting, And Participants: This cohort study of individual-level data from 9 cohorts in the Asia Cohort Consortium was performed from January 1, 1984, to December 31, 2002. Read More

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September 2021

Mechanical activation of spike fosters SARS-CoV-2 viral infection.

Cell Res 2021 Aug 31. Epub 2021 Aug 31.

Department of Cardiology of the Second Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike's S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Read More

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The Effects and Patterns among Mobile Health, Social Determinants, and Physical Activity: A Nationally Representative Cross-Sectional Study.

AMIA Annu Symp Proc 2021 17;2021:653-662. Epub 2021 May 17.

Department of Public Health Sciences, University of Chicago, Chicago, USA.

Mobile health (mHealth) technologies and applications are becoming more and more accessible. The increased prevalence of wearable and embeddable sensors has opened up new opportunities to collect health data continuously outside of the clinical environment. Meanwhile, wearable devices and smartphone health apps are useful to address the issues of health disparities and inequities. Read More

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September 2021

Predicting change in symptoms and function in patients with persistent shoulder pain: a prognostic model development study.

BMC Musculoskelet Disord 2021 Aug 27;22(1):732. Epub 2021 Aug 27.

Department of Occupational Medicine, University Research Clinic, Regional Hospital West Jutland, Gl. Landevej 61, 7400, Herning, Denmark.

Background: Persistent shoulder pain causes considerable disruption of the individual's life and imposes high costs on healthcare and society. Well-informed treatment and referral pathways are crucial as unsuccessful interventions and longer duration of symptoms minimizes the likelihood of success in future interventions. Although physiotherapy is generally recommended as first line treatment, no prognostic model or clinical prediction rules exists to help guide the treatment of patients with persistent shoulder pain undergoing physiotherapy. Read More

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The Time-Dependence of Three Different Modes of ELF-EMF Stimulation on LTP at Schaffer Collateral-CA1 Synapses.

Bioelectromagnetics 2021 Oct 27;42(7):538-549. Epub 2021 Aug 27.

School of Life Sciences, Tiangong University, Tianjin, China.

Long-term potentiation (LTP) is considered the cellular basis of learning and memory. Extremely low-frequency electromagnetic fields (ELF-EMFs) are neuromodulation tools for regulating LTP. However, the temporal effects of short-term ELF-EMF stimulation on LTP are not yet known. Read More

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October 2021

Fiber Optic Pressure Measurements Open Up New Experimental Possibilities in Hydrogeology.

Ground Water 2021 Aug 27. Epub 2021 Aug 27.

Department of Geosciences, Boise State University, Boise, ID, USA.

Fiber-optic (FO) technology is being used increasingly for measurement methods in a variety of environmental applications. However, FO pressure transducers are rarely used in hydrogeological applications. We review the current state of Fabry-Pérot interferometry-based FO pressure transducers, including their advantages and limitations, as another option for high-resolution pressure- or head-change measurements in conventional or advanced aquifer testing. Read More

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Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells.

Int J Mol Sci 2021 Aug 10;22(16). Epub 2021 Aug 10.

Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy.

Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. Read More

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Bonding Performance of Universal Adhesives Applied to Nano-Hydroxyapatite Desensitized Dentin Using Etch-and-Rinse or Self-Etch Mode.

Materials (Basel) 2021 Aug 22;14(16). Epub 2021 Aug 22.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, China.

The study assessed the bonding performance of three universal adhesives on desensitized dentin with etch-and-rinse mode or self-etch mode after nano-hydroxyapatite (nHAp)-based desensitizers application. Simulated sensitive dentin specimens were prepared and separated into four groups: no treatment as the negative control, groups desensitized by Biorepair toothpaste, Dontodent toothpaste, or nHAp paste. Three universal adhesives of All-Bond Universal, Single Bond Universal, and Clearfil Universal Bond with etch-and-rinse or self-etch mode were bonded to the desensitized dentin specimens separately, followed by resin composite build-ups. Read More

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Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021.

MMWR Morb Mortal Wkly Rep 2021 Aug 27;70(34):1156-1162. Epub 2021 Aug 27.

Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48. Read More

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Nonadiabatic Dynamics Mechanism of Chalcone Analogue Sunscreen FPPO-HBr: Excited State Intramolecular Proton Transfer Followed by Conformation Twisting.

J Phys Chem B 2021 Aug 16;125(33):9572-9578. Epub 2021 Aug 16.

MeChem Group, Molecular Dynamic Chemistry Center, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, National Demonstration Center for Experimental Chemistry & Chemical engineering Education, School of Science, Tianjin University, Tianjin 300354, China.

Nowadays, traditional sunscreen molecules face many adverse problems: single energy relaxation pathway, lack of adequate UVA light protection, and therefore no longer meeting the growing demand for UVA protection. In this work, we reported a novel sunscreen molecule ()-3-(5-bromofuran-2-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one (hereinafter referred to as FPPO-HBr) which tackled adverse problems of traditional sunscreen molecules as single energy relaxation pathway, lacking effective UVA light protection. Various nonradiative pathways were proposed and verified by combining the steady-state and femtosecond transient absorption (FTA) spectroscopy and theoretical calculation. Read More

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Clinical Profiles of Childhood Astrovirus-, Sapovirus-, and Norovirus-Associated Acute Gastroenteritis in Pediatric Emergency Departments in Alberta, 2014-2018.

J Infect Dis 2021 Aug 25. Epub 2021 Aug 25.

Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: Infections by previously under-diagnosed viruses astrovirus and sapovirus are poorly characterized compared to norovirus, the most common cause of acute gastroenteritis.

Methods: Children <18-years-old with acute gastroenteritis were recruited from pediatric emergency departments in Alberta, Canada, 2014-2018. We described and compared the clinical course of acute gastroenteritis in children with astrovirus, sapovirus, and norovirus. Read More

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YouTube Is a Poor-Quality Source for Patient Information on Rehabilitation and Return to Sports After Hip Arthroscopy.

Arthrosc Sports Med Rehabil 2021 Aug 14;3(4):e1055-e1063. Epub 2021 May 14.

Department of Orthopedic Surgery, Mayo Clinic, Minneapolis, Minnesota, U.S.A.

Purpose: To investigate the information quality on YouTube regarding rehabilitation and return to sport (RTS) after hip arthroscopy.

Methods: By use of private browsing and predefined search terms, 217 unique videos regarding RTS and rehabilitation after hip arthroscopy were included and systematically reviewed. A total of 164 videos were included in the final analysis. Read More

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The landscape of alternative polyadenylation in single cells of the developing mouse embryo.

Nat Commun 2021 08 24;12(1):5101. Epub 2021 Aug 24.

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

3' untranslated regions (3' UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3'-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9. Read More

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Oxford's clinical experience in the development of high intensity focused ultrasound therapy.

Int J Hyperthermia 2021 09;38(2):81-88

Green Templeton College, University of Oxford, Oxford, UK.

High Intensity Focused Ultrasound (HIFU) capably bridges the disciplines of surgery, oncology and biomedical engineering science. It provides the precision associated with a surgical tool whilst remaining a truly non-invasive technique. Oxford has been a centre for both clinical and preclinical research in HIFU over the last twenty years. Read More

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September 2021