Publications by authors named "Sunghoon Lee"

89 Publications

Robust, self-adhesive, reinforced polymeric nanofilms enabling gas-permeable dry electrodes for long-term application.

Proc Natl Acad Sci U S A 2021 Sep;118(38)

Department of Electrical Engineering and Information Systems, The University of Tokyo, Tokyo 113-8656, Japan

Robust polymeric nanofilms can be used to construct gas-permeable soft electronics that can directly adhere to soft biological tissue for continuous, long-term biosignal monitoring. However, it is challenging to fabricate gas-permeable dry electrodes that can self-adhere to the human skin and retain their functionality for long-term (>1 d) health monitoring. We have succeeded in developing an extraordinarily robust, self-adhesive, gas-permeable nanofilm with a thickness of only 95 nm. It exhibits an extremely high skin adhesion energy per unit area of 159 μJ/cm The nanofilm can self-adhere to the human skin by van der Waals forces alone, for 1 wk, without any adhesive materials or tapes. The nanofilm is ultradurable, and it can support liquids that are 79,000 times heavier than its own weight with a tensile stress of 7.82 MPa. The advantageous features of its thinness, self-adhesiveness, and robustness enable a gas-permeable dry electrode comprising of a nanofilm and an Au layer, resulting in a continuous monitoring of electrocardiogram signals with a high signal-to-noise ratio (34 dB) for 1 wk.
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http://dx.doi.org/10.1073/pnas.2111904118DOI Listing
September 2021

Foundry-compatible high-resolution patterning of vertically phase-separated semiconducting films for ultraflexible organic electronics.

Nat Commun 2021 Aug 16;12(1):4937. Epub 2021 Aug 16.

Department of Chemistry and the Materials Research Center, Northwestern University, Evanston, IL, USA.

Solution processability of polymer semiconductors becomes an unfavorable factor during the fabrication of pixelated films since the underlying layer is vulnerable to subsequent solvent exposure. A foundry-compatible patterning process must meet requirements including high-throughput and high-resolution patternability, broad generality, ambient processability, environmentally benign solvents, and, minimal device performance degradation. However, known methodologies can only meet very few of these requirements. Here, a facile photolithographic approach is demonstrated for foundry-compatible high-resolution patterning of known p- and n-type semiconducting polymers. This process involves crosslinking a vertically phase-separated blend of the semiconducting polymer and a UV photocurable additive, and enables ambient processable photopatterning at resolutions as high as 0.5 μm in only three steps with environmentally benign solvents. The patterned semiconducting films can be integrated into thin-film transistors having excellent transport characteristics, low off-currents, and high thermal (up to 175 °C) and chemical (24 h immersion in chloroform) stability. Moreover, these patterned organic structures can also be integrated on 1.5 μm-thick parylene substrates to yield highly flexible (1 mm radius) and mechanically robust (5,000 bending cycles) thin-film transistors.
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http://dx.doi.org/10.1038/s41467-021-25059-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367968PMC
August 2021

Molecular diagnosis of McArdle disease using whole-exome sequencing.

Exp Ther Med 2021 Sep 18;22(3):1029. Epub 2021 Jul 18.

Department of Biochemistry and Molecular Biology, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea.

Whole-exome sequencing (WES) analysis has been used recently as a diagnostic tool for finding molecular defects. In the present study, researchers attempted to analyze molecular defects through WES in a 13-year-old female patient who had not been diagnosed through a conventional genetic approach. DNA was extracted and subjected to WES analysis to identify the genetic defect. A total of 106,728 exons and splicing variants were selected, and synonymous single nucleotide variants (SNVs) and general single nucleotide polymorphisms (SNPs) were filtered out. Finally, nonsynonymous SNVs (c.C415T and c.C389T) of the gene were identified in nine compound heterozygous mutations. encodes myophosphorylase and degrades glycogen in the muscle to supply energy to muscle cells. The present study revealed that the patient's father had a c.C389T mutation and the mother had a c.C415T mutation, resulting in A130V and R139W missense mutations, respectively. To the best of our knowledge, the A130V variant in has not been reported in the common variant databases. All variations of the patient's family detected using WES were verified by Sanger sequencing. Because the patient had compound heterozygous mutations in the gene, the patient was presumed to exhibit markedly decreased muscle phosphorylase activity. To assess the function of myophosphorylase, an ischemic forearm exercise test was performed. The blood ammonia level sharply increased and the lactate level maintained a flat curve shape similar to the typical pattern of McArdle disease. Therefore, the diagnosis of the patient was confirmed to be McArdle disease, a glycogen storage disease. Through WES analysis, accurate and early diagnosis could be made in the present study. This report describes a novel compound heterozygous mutation of the gene in a Korean patient.
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http://dx.doi.org/10.3892/etm.2021.10461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343624PMC
September 2021

Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

IEEE Open J Eng Med Biol 2020 7;1:243-248. Epub 2020 Aug 7.

Paolo Bonato is with the Department of Physical Medicine and RehabilitationHarvard Medical School at Spaulding Rehabilitation HospitalBostonMA02129USA.

The aim of the study herein reported was to review mobile health (mHealth) technologies and explore their use to monitor and mitigate the effects of the COVID-19 pandemic. A Task Force was assembled by recruiting individuals with expertise in electronic Patient-Reported Outcomes (ePRO), wearable sensors, and digital contact tracing technologies. Its members collected and discussed available information and summarized it in a series of reports. The Task Force identified technologies that could be deployed in response to the COVID-19 pandemic and would likely be suitable for future pandemics. Criteria for their evaluation were agreed upon and applied to these systems. mHealth technologies are viable options to monitor COVID-19 patients and be used to predict symptom escalation for earlier intervention. These technologies could also be utilized to monitor individuals who are presumed non-infected and enable prediction of exposure to SARS-CoV-2, thus facilitating the prioritization of diagnostic testing.
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http://dx.doi.org/10.1109/OJEMB.2020.3015141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023427PMC
August 2020

Development of 50 InDel-based barcode system for genetic identification of tartary buckwheat resources.

PLoS One 2021 3;16(6):e0250786. Epub 2021 Jun 3.

Highland Agriculture Research Institute, National Institute of Crop Science, Pyeongchang, Gangwon-do, Republic of Korea.

Tartary buckwheat (Fagopyrum tataricum Gartn.) is a highly functional crop that is poised to be the target of many future breeding efforts. The reliable ex situ conservation of various genetic resources is essential for the modern breeding of tartary buckwheat varieties. We developed PCR-based co-dominant insertion/deletion (InDel) markers to discriminate tartary buckwheat genetic resources. First, we obtained the whole genome from 26 accessions across a superscaffold-scale reference genome of 569.37 Mb for tartary buckwheat cv. "Daegwan 3-7." Next, 171,926 homogeneous and 53,755 heterogeneous InDels were detected by comparing 26 accessions with the "Daegwan 3-7" reference sequence. Of these, 100 candidate InDels ranging from 5-20 bp in length were chosen for validation, and 50 of them revealed polymorphisms between the 26 accessions and "Daegwan 3-7." The validated InDels were further tested through the assessment of their likelihood to give rise to a single or a few PCR products in 50 other accessions, covering most tartary buckwheat genome types. The major allele frequencies ranged from 0.5616 at the TB42 locus to 0.9863 at the TB48 locus, with the average PIC value of 0.1532 with a range of 0.0267-0.3712. To create a user-friendly system, the homology of the genotypes between and among the accessions were visualized in both one- (1D) and two-dimensional (2D) barcode types by comparing amplicon polymorphisms with the reference variety, "Daegwan 3-7." A phylogenetic tree and population structure of the 76 accessions according to amplicon polymorphisms for the 50 InDel markers corresponded to those using non-synonymous single nucleotide polymorphism variants, indicating that the barcode system based on the 50 InDels was a useful tool to improve the reliability of identification of tartary buckwheat accessions in the germplasm stocks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250786PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174720PMC
June 2021

Usefulness of Diffusion Tensor Imaging in Unexplained Ipsilateral Hemiplegia.

Korean J Neurotrauma 2021 Apr 18;17(1):61-66. Epub 2021 Mar 18.

Department of Rehabilitation Medicine, Kwangju Christian Hospital, Gwangju, Korea.

Ipsilateral hemiparesis is a rare and challenging sign in clinical neurological practice. Although the etiology of this manifestation is poorly understood, recent studies have attempted to probe the pathomechanism of this sign with advanced radiological techniques. Additional knowledge about the lesion and unraveling the pathomechanisms causing neurological impairments are important to predict the prognosis and clinical course and to aid in rehabilitation. Therefore, we present a case of a patient with a traumatic subdural hematoma on the left hemisphere and left spastic hemiparesis. Using diffusion tensor imaging (DTI), we concluded that the right corticospinal tract injury caused by compression of the cerebral peduncle accounted for the ipsilateral hemiparesis, also known as Kernohan's notch phenomenon. Thus, this case report highlights the usefulness of the newer radiological techniques, such as DTI, to identify the pathomechanisms of neurological presentations.
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http://dx.doi.org/10.13004/kjnt.2021.17.e4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093020PMC
April 2021

Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

The Research Institute, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria. cAMP stimulation also increased the movement of cholesterol from the PM compared to untreated cells, which was partially inhibited when ATPase family AAA-domain containing protein 3 A (ATAD3A), which functions in ER and mitochondria interactions, was knocked down. Mitochondria, ER, cytoplasm, PM, PM-associated membranes (PAMs), and mitochondria-associated membranes (MAMs) were isolated from control and hormone-stimulated cells. Lipidomic analyses revealed that each isolated compartment had a unique lipid composition, and the induction of steroidogenesis caused the significant remodeling of its lipidome. cAMP-induced changes in lipid composition included an increase in phosphatidylserine and cardiolipin levels in PAM and PM compartments, respectively; an increase in phosphatidylinositol in the ER, mitochondria, and MAMs; and a reorganization of phosphatidic acid, cholesterol ester, ceramide, and phosphatidylethanolamine. Abundant lipids, such as phosphatidylcholine, were not affected by hormone treatment. Our data suggested that PM-ER-mitochondria tethering may be involved in lipid trafficking between organelles and indicated that hormone-induced acute steroid production involves extensive organelle remodeling.
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http://dx.doi.org/10.3390/ijms22052554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961408PMC
March 2021

Continuous measurement of surface electrical potentials from transplanted cardiomyocyte tissue derived from human-induced pluripotent stem cells under physiological conditions in vivo.

Heart Vessels 2021 Jun 8;36(6):899-909. Epub 2021 Mar 8.

Institute of Advanced Biomedical Engineering and Science, TWIns, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Recording the electrical potentials of bioengineered cardiac tissue after transplantation would help to monitor the maturation of the tissue and detect adverse events such as arrhythmia. However, a few studies have reported the measurement of myocardial tissue potentials in vivo under physiological conditions. In this study, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSCM) sheets were stacked and ectopically transplanted into the subcutaneous tissue of rats for culture in vivo. Three months after transplantation, a flexible nanomesh sensor was implanted onto the hiPSCM tissue to record its surface electrical potentials under physiological conditions, i.e., without the need for anesthetic agents that might adversely affect cardiomyocyte function. The nanomesh sensor was able to record electrical potentials in non-sedated, ambulating animals for up to 48 h. When compared with recordings made with conventional needle electrodes in anesthetized animals, the waveforms obtained with the nanomesh sensor showed less dispersion of waveform interval and waveform duration. However, waveform amplitude tended to show greater dispersion for the nanomesh sensor than for the needle electrodes, possibly due to motion artifacts produced by movements of the animal or local tissue changes in response to surgical implantation of the sensor. The implantable nanomesh sensor utilized in this study potentially could be used for long-term monitoring of bioengineered myocardial tissue in vivo under physiological conditions.
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http://dx.doi.org/10.1007/s00380-021-01824-zDOI Listing
June 2021

Decomposition of Reaching Movements Enables Detection and Measurement of Ataxia.

Cerebellum 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 100 Cambridge St, Boston, MA, USA.

Technologies that enable frequent, objective, and precise measurement of ataxia severity would benefit clinical trials by lowering participation barriers and improving the ability to measure disease state and change. We hypothesized that analyzing characteristics of sub-second movement profiles obtained during a reaching task would be useful for objectively quantifying motor characteristics of ataxia. Participants with ataxia (N=88), participants with parkinsonism (N=44), and healthy controls (N=34) performed a computer tablet version of the finger-to-nose test while wearing inertial sensors on their wrists. Data features designed to capture signs of ataxia were extracted from participants' decomposed wrist velocity time-series. A machine learning regression model was trained to estimate overall ataxia severity, as measured by the Brief Ataxia Rating Scale (BARS). Classification models were trained to distinguish between ataxia participants and controls and between ataxia and parkinsonism phenotypes. Movement decomposition revealed expected and novel characteristics of the ataxia phenotype. The distance, speed, duration, morphology, and temporal relationships of decomposed movements exhibited strong relationships with disease severity. The regression model estimated BARS with a root mean square error of 3.6 points, r = 0.69, and moderate-to-excellent reliability. Classification models distinguished between ataxia participants and controls and ataxia and parkinsonism phenotypes with areas under the receiver-operating curve of 0.96 and 0.89, respectively. Movement decomposition captures core features of ataxia and may be useful for objective, precise, and frequent assessment of ataxia in home and clinic environments.
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http://dx.doi.org/10.1007/s12311-021-01247-6DOI Listing
March 2021

Nanomesh pressure sensor for monitoring finger manipulation without sensory interference.

Science 2020 11;370(6519):966-970

Department of Electrical Engineering and Information Systems, School of Engineering, The University of Tokyo,7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Monitoring of finger manipulation without disturbing the inherent functionalities is critical to understand the sense of natural touch. However, worn or attached sensors affect the natural feeling of the skin. We developed nanomesh pressure sensors that can monitor finger pressure without detectable effects on human sensation. The effect of the sensor on human sensation was quantitatively investigated, and the sensor-applied finger exhibits comparable grip forces with those of the bare finger, even though the attachment of a 2-micrometer-thick polymeric film results in a 14% increase in the grip force after adjusting for friction. Simultaneously, the sensor exhibits an extreme mechanical durability against cyclic shearing and friction greater than hundreds of kilopascals.
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http://dx.doi.org/10.1126/science.abc9735DOI Listing
November 2020

Circulating tumor DNA in the saliva of patients with head and neck cancer: A pilot report.

Oral Dis 2021 Sep 30;27(6):1421-1425. Epub 2020 Oct 30.

EONE-DIAGNOMICS Genome Center, Incheon, Korea.

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http://dx.doi.org/10.1111/odi.13683DOI Listing
September 2021

Enabling precision rehabilitation interventions using wearable sensors and machine learning to track motor recovery.

NPJ Digit Med 2020 21;3:121. Epub 2020 Sep 21.

Department of Physical Medicine & Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Boston, MA USA.

The need to develop patient-specific interventions is apparent when one considers that clinical studies often report satisfactory motor gains only in a portion of participants. This observation provides the foundation for "precision rehabilitation". Tracking and predicting outcomes defining the recovery trajectory is key in this context. Data collected using wearable sensors provide clinicians with the opportunity to do so with little burden on clinicians and patients. The approach proposed in this paper relies on machine learning-based algorithms to derive clinical score estimates from wearable sensor data collected during functional motor tasks. Sensor-based score estimates showed strong agreement with those generated by clinicians. Score estimates of upper-limb impairment severity and movement quality were marked by a coefficient of determination of 0.86 and 0.79, respectively. The application of the proposed approach to monitoring patients' responsiveness to rehabilitation is expected to contribute to the development of patient-specific interventions, aiming to maximize motor gains.
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http://dx.doi.org/10.1038/s41746-020-00328-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506010PMC
September 2020

Estimating Quality of Reaching Movement Using a Wrist-Worn Inertial Sensor.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3719-3722

Stroke is a major cause of long-term disability. Because patients recovering from stroke often perform differently in clinical settings than in their naturalistic environments, remote monitoring of motor performance is needed to evaluate the true impact of prescribed therapies. Wearable sensors have been considered as a technical solution to this problem, but most existing systems focus on measuring the amount of movement without considering the quality of movement. We present a novel method to seamlessly and unobtrusively measure the quality of individual reaching movements by leveraging a motor control theory that describes how the central nervous system plans and executes movements. We trained and evaluated our system on 19 stroke survivors to estimate the Functional Ability Scale (FAS) of reaching movements. The analysis showed that we can estimate the FAS scores of reaching movements, with some confusion between adjacent scores. Furthermore, we estimated the average FAS scores of subjects with a normalized root mean square error (NRMSE) of 22.5%. Though our model's high error on two severe subjects influenced our overall estimation performance, we could accurately estimate scores in most of the mild-to-moderate subjects (NRMSE of 13.1% without the outliers). With further development and testing, we believe the proposed technique can be applied to monitor patient recovery in home and community settings.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175708DOI Listing
July 2020

Predicting and Monitoring Upper-Limb Rehabilitation Outcomes Using Clinical and Wearable Sensor Data in Brain Injury Survivors.

IEEE Trans Biomed Eng 2021 06 21;68(6):1871-1881. Epub 2021 May 21.

Objective: Rehabilitation specialists have shown considerable interest for the development of models, based on clinical data, to predict the response to rehabilitation interventions in stroke and traumatic brain injury survivors. However, accurate predictions are difficult to obtain due to the variability in patients' response to rehabilitation interventions. This study aimed to investigate the use of wearable technology in combination with clinical data to predict and monitor the recovery process and assess the responsiveness to treatment on an individual basis.

Methods: Gaussian Process Regression-based algorithms were developed to estimate rehabilitation outcomes (i.e., Functional Ability Scale scores) using either clinical or wearable sensor data or a combination of the two.

Results: The algorithm based on clinical data predicted rehabilitation outcomes with a Pearson's correlation of 0.79 compared to actual clinical scores provided by clinicians but failed to model the variability in responsiveness to the intervention observed across individuals. In contrast, the algorithm based on wearable sensor data generated rehabilitation outcome estimates with a Pearson's correlation of 0.91 and modeled the individual responses to rehabilitation more accurately. Furthermore, we developed a novel approach to combine estimates derived from the clinical data and the sensor data using a constrained linear model. This approach resulted in a Pearson's correlation of 0.94 between estimated and clinician-provided scores.

Conclusion: This algorithm could enable the design of patient-specific interventions based on predictions of rehabilitation outcomes relying on clinical and wearable sensor data.

Significance: This is important in the context of developing precision rehabilitation interventions.
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http://dx.doi.org/10.1109/TBME.2020.3027853DOI Listing
June 2021

A durable nanomesh on-skin strain gauge for natural skin motion monitoring with minimum mechanical constraints.

Sci Adv 2020 Aug 12;6(33):eabb7043. Epub 2020 Aug 12.

Department of Electrical Engineering and Information Systems, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Ultraconformable strain gauge can be applied directly to human skin for continuous motion activity monitoring, which has seen widespread application in interactive robotics, human motion detection, personal health monitoring, and therapeutics. However, the development of an on-skin strain gauge that can detect human body motions over a long period of time without disturbing the natural skin movements remains a challenge. Here, we present an ultrathin and durable nanomesh strain gauge for continuous motion activity monitoring that minimizes mechanical constraints on natural skin motions. The device is made from reinforced polyurethane-polydimethylsiloxane (PU-PDMS) nanomeshes and exhibits excellent sustainability, linearity, and durability with low hysteresis. Its thinness geometry and softness provide minimum mechanical interference on natural skin deformations. During speech, the nanomesh-attached face exhibits skin strain mapping comparable to that of a face without nanomeshes. We demonstrate long-term facial stain mapping during speech and the capability for real-time stable full-range body movement detection.
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http://dx.doi.org/10.1126/sciadv.abb7043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423357PMC
August 2020

Ultraflexible organic light-emitting diodes for optogenetic nerve stimulation.

Proc Natl Acad Sci U S A 2020 09 19;117(35):21138-21146. Epub 2020 Aug 19.

Department of Electrical Engineering and Information Systems, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656 Tokyo, Japan;

Organic electronic devices implemented on flexible thin films are attracting increased attention for biomedical applications because they possess extraordinary conformity to curved surfaces. A neuronal device equipped with an organic light-emitting diode (OLED), used in combination with animals that are genetically engineered to include a light-gated ion channel, would enable cell type-specific stimulation to neurons as well as conformal contact to brain tissue and peripheral soft tissue. This potential application of the OLEDs requires strong luminescence, well over the neuronal excitation threshold in addition to flexibility. Compatibility with neuroimaging techniques such as MRI provides a method to investigate the evoked activities in the whole brain. Here, we developed an ultrathin, flexible, MRI-compatible OLED device and demonstrated the activation of channelrhodopsin-2-expressing neurons in animals. Optical stimulation from the OLED attached to nerve fibers induced contractions in the innervated muscles. Mechanical damage to the tissues was significantly reduced because of the flexibility. Owing to the MRI compatibility, neuronal activities induced by direct optical stimulation of the brain were visualized using MRI. The OLED provides an optical interface for modulating the activity of soft neuronal tissues.
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http://dx.doi.org/10.1073/pnas.2007395117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474697PMC
September 2020

Clinical Utility of Combined Circulating Tumor Cell and Circulating Tumor DNA Assays for Diagnosis of Primary Lung Cancer.

Anticancer Res 2020 Jun;40(6):3435-3444

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Background/aim: Although it has been suggested that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) might be used in a complementary manner in lung cancer diagnosis, limited confirmatory data are available. In this prospective study, we evaluated the diagnostic performance of each assay separately and in combination.

Patients And Methods: From March 2018 to January 2019, patients with suspected primary lung cancer, who underwent routine lung cancer work-up and peripheral blood sampling, were prospectively enrolled in the study. Epithelial cell adhesion molecule and cytokeratin served as markers of CTCs. In terms of ctDNA analysis, single-nucleotide variants were evaluated via next-generation sequencing.

Results: We analyzed 111 patients, including 99 with primary lung cancer and 12 with benign pulmonary disease. The median number of CTCs in 10 ml of blood was 3. The most frequently detected single nucleotide variants of ctDNA were TP53, CDKN2A, and EGFR. The diagnostic sensitivity of conventional tumor marker (combination of carcinoembryonic antigen/CYFRA 21-1/neuron-specific enolase) was 66.7%, while those of the ctDNA and CTC assays were 72.7% and 65.7%, respectively. The sensitivity of the CTC/ctDNA combination (95.0%) was significantly greater than those of the CTC (p<0.001), ctDNA (p<0.001), or conventional tumor marker (p<0.001) alone. Subgroup analysis revealed that the sensitivity of the combination assay was greater than those of the CTC or ctDNA assays alone, regardless of tumor stage or histopathology type.

Conclusion: The CTC/ctDNA combination assay enhanced the sensitivity of primary lung cancer diagnosis. The combination assay strategy may be clinically useful and could enhance the early detection of lung cancer (ClinicalTrials.gov number: NCT03479099).
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http://dx.doi.org/10.21873/anticanres.14329DOI Listing
June 2020

A Simple Low-Cost Wearable Sensor for Long-Term Ambulatory Monitoring of Knee Joint Kinematics.

IEEE Trans Biomed Eng 2020 12 19;67(12):3483-3490. Epub 2020 Nov 19.

Objective: Accurate monitoring of joint kinematics in individuals with neuromuscular and musculoskeletal disorders within ambulatory settings could provide important information about changes in disease status and the effectiveness of rehabilitation programs and/or pharmacological treatments. This paper introduces a reliable, power efficient, and low-cost wearable system designed for the long-term monitoring of joint kinematics in ambulatory settings.

Methods: Seventeen healthy subjects wore a retractable string sensor, fixed to two anchor points on the opposing segments of the knee joint, while walking at three different self-selected speeds. Joint angles were estimated from calibrated sensor values and their derivatives in a leave-one-subject-out cross validation manner using a random forest algorithm.

Results: The proposed system estimated knee flexion/extension angles with a root mean square error (RMSE) of 5.0±1.0 across the study subjects upon removal of a single outlier subject. The outlier was likely a result of sensor miscalibration.

Conclusion: The proposed wearable device can accurately estimate knee flexion/extension angles during locomotion at various walking speeds.

Significance: We believe that our novel wearable technology has great potential to enable joint kinematic monitoring in ambulatory settings and thus provide clinicians with an opportunity to closely monitor joint recovery, develop optimal, personalized rehabilitation programs, and ultimately maximize therapeutic outcomes.
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http://dx.doi.org/10.1109/TBME.2020.2988438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709863PMC
December 2020

All-nanofiber-based, ultrasensitive, gas-permeable mechanoacoustic sensors for continuous long-term heart monitoring.

Proc Natl Acad Sci U S A 2020 03 18;117(13):7063-7070. Epub 2020 Mar 18.

Department of Electrical Engineering and Information Systems, School of Engineering, The University of Tokyo, 113-8656 Bunkyo-ku, Tokyo, Japan;

The prolonged and continuous monitoring of mechanoacoustic heart signals is essential for the early diagnosis of cardiovascular diseases. These bodily acoustics have low intensity and low frequency, and measuring them continuously for long periods requires ultrasensitive, lightweight, gas-permeable mechanoacoustic sensors. Here, we present an all-nanofiber mechanoacoustic sensor, which exhibits a sensitivity as high as 10,050.6 mV Pa in the low-frequency region (<500 Hz). The high sensitivity is achieved by the use of durable and ultrathin (2.5 µm) nanofiber electrode layers enabling a large vibration of the sensor during the application of sound waves. The sensor is ultralightweight, and the overall weight is as small as 5 mg or less. The devices are mechanically robust against bending, and show no degradation in performance even after 1,000-cycle bending. Finally, we demonstrate a continuous long-term (10 h) measurement of heart signals with a signal-to-noise ratio as high as 40.9 decibels (dB).
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http://dx.doi.org/10.1073/pnas.1920911117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132136PMC
March 2020

Efficient Luminescence of SrSiN:Eu nanophosphor and its film applications to LED and Solar cell as a downconverter.

Sci Rep 2020 Jan 30;10(1):1475. Epub 2020 Jan 30.

Interdisciplinary Program of LED Convergence, Pukyong National University, Busan, 48513, Republic of Korea.

Here we present the synthesis of the efficient nanophosphor SrSiN:Eu (D = 144 nm) by a simple milling approach, its strong Rayleigh scattering, and its film applications to white LED and silicon solar cell as a downshifting medium. The final nanophosphor product showed the quantum efficiency comparable to the bulk phosphor which is, to our knowledge, the highest record of nitride nanophosphors. Especially the nanophosphor showed the more tail emission at the shorter-wavelength side of the emission spectrum and the faster thermal quenching with the more spectral broadening along with the temperature due to Rayleigh scattering. Also the lowering in the excitation spectrum was observed due to lower absorbance. Finally, the nanophosphor-dispersed polyvinyl alcohol (PVA) film was made, and its applications to white LED and silicon solar cell as a downshifting medium demonstrated that it gave the high color rendering property in white LED in spite of still lower luminous efficiency, and it caused the increase in efficiency of silicon solar cell.
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http://dx.doi.org/10.1038/s41598-020-58469-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992749PMC
January 2020

Estimating Upper-Limb Impairment Level in Stroke Survivors Using Wearable Inertial Sensors and a Minimally-Burdensome Motor Task.

IEEE Trans Neural Syst Rehabil Eng 2020 03 15;28(3):601-611. Epub 2020 Jan 15.

Upper-limb paresis is the most common motor impairment post stroke. Current solutions to automate the assessment of upper-limb impairment impose a number of critical burdens on patients and their caregivers that preclude frequent assessment. In this work, we propose an approach to estimate upper-limb impairment in stroke survivors using two wearable inertial sensors, on the wrist and the sternum, and a minimally-burdensome motor task. Twenty-three stroke survivors with no, mild, or moderate upper-limb impairment performed two repetitions of one-to-two minute-long continuous, random (i.e., patternless), voluntary upper-limb movements spanning the entire range of motion. The three-dimensional time-series of upper-limb movements were segmented into a series of one-dimensional submovements by employing a unique movement decomposition technique. An unsupervised clustering algorithm and a supervised regression model were used to estimate Fugl-Meyer Assessment (FMA) scores based on features extracted from these submovements. Our regression model estimated FMA scores with a normalized root mean square error of 18.2% ( r=0.70 ) and needed as little as one minute of movement data to yield reasonable estimation performance. These results support the possibility of frequently monitoring stroke survivors' rehabilitation outcomes, ultimately enabling the development of individually-tailored rehabilitation programs.
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http://dx.doi.org/10.1109/TNSRE.2020.2966950DOI Listing
March 2020

Highly Durable Nanofiber-Reinforced Elastic Conductors for Skin-Tight Electronic Textiles.

ACS Nano 2019 07 21;13(7):7905-7912. Epub 2019 Jun 21.

Department of Electrical Engineering and Information Systems , University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 , Japan.

Soft and stretchable electrodes are essential components for skin-tight wearable devices, which can provide comfortable, unobtrusive, and accurate physiological monitoring and physical sensing for applications such as healthcare, medical treatment, and human-machine interfaces. Metal-elastomer nanocomposites are a promising approach, enabling high conductivity and stretchability derived from metallic conduction and percolation networks of metal nano/micro fillers. However, their practical application is still limited by their inferior cyclic stability and long-term durability. Here, we report on a highly durable nanofiber-reinforced metal-elastomer composite consisting of (i) metal fillers, (ii) an elastomeric binder matrix, and (iii) electrospun polyvinylidene fluoride nanofibers for enhancing both cyclic stability and conductivity. Embedded polyvinylidene fluoride (PVDF) nanofibers enhance the toughness and suppress the crack growth by providing a fiber reinforcing effect. Furthermore, the conductivity of nanofiber-reinforced elastic conductor is four times greater than the pristine material because the silver-rich layer is self-assembled on the top surface by a filtering effect. As a result, a stretchable electrode made from nanofiber-reinforced elastic conductors and wrinkled structures has both excellent cyclic durability and high conductivity and is stretchable up to 800%. The cyclic degradation () remains at 0.56 after 5000 stretching cycles (50% strain), whereas initial conductivity and sheet resistance are 9903 S cm and 0.047 Ω sq, respectively. By utilizing a highly conductive and durable elastic conductor as sensor electrodes and wirings, a skin-tight multimodal physiological sensing suit is demonstrated. Continuous long-term monitoring of electrocardiogram, electromyogram, and motions during weight-lifting exercises are successfully demonstrated without significant degradation of signal quality.
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http://dx.doi.org/10.1021/acsnano.9b02297DOI Listing
July 2019

A novel upper-limb function measure derived from finger-worn sensor data collected in a free-living setting.

PLoS One 2019 20;14(3):e0212484. Epub 2019 Mar 20.

Department of Physical Medicine and Rehabilitation, Harvard Medical School, Spaulding Rehabilitation Hospital, Charlestown, MA, United States of America.

The use of wrist-worn accelerometers has recently gained tremendous interest among researchers and clinicians as an objective tool to quantify real-world use of the upper limbs during the performance of activities of daily living (ADLs). However, wrist-worn accelerometers have shown a number of limitations that hinder their adoption in the clinic. Among others, the inability of wrist-worn accelerometers to capture hand and finger movements is particularly relevant to monitoring the performance of ADLs. This study investigates the use of finger-worn accelerometers to capture both gross arm and fine hand movements for the assessment of real-world upper-limb use. A system of finger-worn accelerometers was utilized to monitor eighteen neurologically intact young adults while performing nine motor tasks in a laboratory setting. The system was also used to monitor eighteen subjects during the day time of a day in a free-living setting. A novel measure of real-world upper-limb function-comparing the duration of activities of the two limbs-was derived to identify which upper limb subjects predominantly used to perform ADLs. Two validated handedness self-reports, namely the Waterloo Handedness Questionnaire and the Fazio Laterality Inventory, were collected to assess convergent validity. The analysis of the data recorded in the laboratory showed that the proposed measure of upper-limb function is suitable to accurately detect unilateral vs. bilateral use of the upper limbs, including both gross arm movements and fine hand movements. When applied to recordings collected in a free-living setting, the proposed measure showed high correlation with self-reported handedness indices (i.e., ρ = 0.78 with the Waterloo Handedness Questionnaire scores and ρ = 0.77 with the Fazio Laterality Inventory scores). The results herein presented establish face and convergent validity of the proposed measure of real-world upper-limb function derived using data collected by means of finger-worn accelerometers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212484PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426183PMC
November 2019

Ultrasoft electronics to monitor dynamically pulsing cardiomyocytes.

Nat Nanotechnol 2019 02 31;14(2):156-160. Epub 2018 Dec 31.

Electrical and Electronic Engineering and Information Systems, The University of Tokyo, Tokyo, Japan.

In biointegrated electronics, the facile control of mechanical properties such as softness and stretchability in electronic devices is necessary to minimize the perturbation of motions inherent in biological systems. For in vitro studies, multielectrode-embedded dishes and other rigid devices have been widely used. Soft or flexible electronics on plastic or elastomeric substrates offer promising new advantages such as decreasing physical stress and/or applying mechanical stimuli. Recently, owing to the introduction of macroporous plastic substrates with nanofibre scaffolds, three-dimensional electrophysiological mapping of cardiomyocytes has been demonstrated. However, quantitatively monitoring cells that exhibit significant dynamical motions via electric probes over a long period without affecting their natural motion remains a challenge. Here, we present ultrasoft electronics with nanomeshes that monitor the field potential of human induced pluripotent stem cell-derived cardiomyocytes on a hydrogel, while enabling them to move dynamically without interference. Owing to the extraordinary softness of the nanomeshes, nanomesh-attached cardiomyocytes exhibit contraction and relaxation motions comparable to that of cardiomyocytes without attached nanomeshes. Our multilayered nanomesh devices maintain reliable operations in a liquid environment, enabling the recording of field potentials of the cardiomyocytes over a period of 96 h without significant degradation of the nanomesh devices or damage of the cardiomyocytes.
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http://dx.doi.org/10.1038/s41565-018-0331-8DOI Listing
February 2019

Finger-Worn Sensors for Accurate Functional Assessment of the Upper Limbs in Real-World Settings.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:4440-4443

Remote monitoring of stroke survivors' upper limb performance (stroke-affected vs. unaffected limbs) can provide clinicians with information regarding the true impact of rehabilitation in the real-world settings, which allows opportunities to administer individually tailored therapeutic interventions. In this work, we examine the use of finger-worn accelerometers, which are capable of capturing gross-arm as well as fine-hand movements, in order to quantitatively compare the performance of the upper limbs during goal-directed activities of daily living (ADLs). In this proof-of-concept study, data were collected over an eight-hour duration from ten neurologically intact individuals who wore the sensors and continued with their daily living. The sensor-based measure was compared to two clinically validated measures of handedness, i.e., Waterloo Handedness Questionnaire and Fazio Laterality Inventory, that quantity the level of preference of the limbs in performing ADLs. The results yielded statistically significant correlations to the Waterloo and Fazio scores with Pearson correlation coefficients of 0.90 and 0.87 respectively, which was substantially superior compared to the previously studied measure based on wrist-worn accelerometers. We believe this study presents an opportunity to accurately monitor the goal-directed use of the upper limbs in the real-world settings.
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http://dx.doi.org/10.1109/EMBC.2018.8513134DOI Listing
July 2018

Towards the Ambulatory Assessment of Movement Quality in Stroke Survivors using a Wrist-worn Inertial Sensor.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:2825-2828

Stroke is a leading cause of long-term disability that may lead to significant functional motor impairments in the upper limb (UL). Wrist-worn inertial sensors have emerged as an objective, minimally-obtrusive tool to monitor UL motor function in the real-world setting, such that rehabilitation interventions can be individually tailored to maximize functional performance. However, current wearable solutions focus on capturing the quantity of movement without considering the quality of movement. This paper introduces a novel approach to unobtrusively estimate the quality of UL movements in stroke survivors using a single wrist-worn inertial sensor during any type of voluntary UL movements. The proposed method exploits kinematic characteristics of voluntary limb movements that are optimized by the central nervous system during motor control. This work demonstrates that the proposed method could extract clinically important information during random UL movements in 16 stroke survivors, showing a statistically significant correlation to the Functional Ability Scale - a clinically validated score for movement quality.
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http://dx.doi.org/10.1109/EMBC.2018.8512845DOI Listing
July 2018

Effectiveness of the RAPAEL Smart Board for Upper Limb Therapy in Stroke Survivors: A Pilot Controlled Trial.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:2466-2469

We aim to assess the effectiveness of using the RAPAEL Smart Board as an assistive tool for therapists in clinical rehabilitation therapy settings and to investigate if it can be used to improve the motor recovery rate of stroke survivors. The RAPAEL Smart Board is a therapy tool where therapists actively engage patients, giving necessary verbal and physical interventions as in traditional treatment sessions. We conducted a randomized controlled study with 17 stroke survivors. An experimental group received therapy using the RAPAEL Smart Board for 30 minutes a day, 5 days per week, for 4 weeks in addition to their traditional treatments (i.e., 30 minutes of functional arm movement therapy). A control group received two 30-minute sessions of traditional treatment 5 days per week, for 4 weeks. The upper-extremity function was measured using the Wolf Motor Function Test before and after the 4-week interventions. Our results demonstrate that using the RAPAEL Smart Board, in combination with traditional treatment, significantly improves motor recovery when compared to traditional treatments alone.
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http://dx.doi.org/10.1109/EMBC.2018.8512813DOI Listing
July 2018

Estimating Mini Mental State Examination Scores using Game-Specific Performance Values: A Preliminary Study.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:1518-1521

Individuals with permanent cognitive impairment need to be evaluated and monitored. There exists a number of clinically validated cognitive assessment tools, but they often need to be administered by trained therapists in clinical settings. This serves as a major barrier for frequent, longitudinal monitoring of cognitive function. In this work, we introduce Neuro-World, a collection of innovative 3D mobile games, that allows one to self-administer the assessment of his/her cognitive function. The game performance is analyzed and converted into a clinically-accepted measure of cognitive function, specifically the Mini Mental State Examination (MMSE) score, improving the translational impact of the system in real-world clinical settings. To validate the feasibility of our approach, we collected game-specific performance data from 12 post-stroke patients, which was used to train a supervised machine learning model to estimate the corresponding MMSE score. Our experiment results showed a normalized root mean square error of 5.3% between the actual and estimated MMSE scores. This study enables new clinical and research opportunities for accurate longitudinal assessment of cognitive function via an interactive means of playing mobile games.
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http://dx.doi.org/10.1109/EMBC.2018.8512516DOI Listing
July 2018

Erratum: Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube.

J Gynecol Oncol 2018 09 20;29(5):e80. Epub 2018 Jun 20.

Hereditary Gynecologic Cancer Clinic, Precision Medicine Center, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

This corrects the article on p. e43 in vol. 29, PMID: 29770616.
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http://dx.doi.org/10.3802/jgo.2018.29.e80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078884PMC
September 2018

The Use of a Finger-Worn Accelerometer for Monitoring of Hand Use in Ambulatory Settings.

IEEE J Biomed Health Inform 2019 03 30;23(2):599-606. Epub 2018 Mar 30.

Objective assessment of stroke survivors' upper limb movements in ambulatory settings can provide clinicians with important information regarding the real impact of rehabilitation outside the clinic and help to establish individually-tailored therapeutic programs. This paper explores a novel approach to monitor the amount of hand use, which is relevant to the purposeful, goal-directed use of the limbs, based on a body networked sensor system composed of miniaturized finger- and wrist-worn accelerometers. The main contributions of this paper are twofold. First, this paper introduces and validates a new benchmark measurement of the amount of hand use based on data recorded by a motion capture system, the gold standard for human movement analysis. Second, this paper introduces a machine learning-based analytic pipeline that estimates the amount of hand use using data obtained from the wearable sensors and validates its estimation performance against the aforementioned benchmark measurement. Based on data collected from 18 neurologically intact individuals performing 11 motor tasks resembling various activities of daily living, the analytic results presented herein show that our new benchmark measure is reliable and responsive, and that the proposed wearable system can yield an accurate estimation of the amount of hand use (normalized root mean square error of 0.11 and average Pearson correlation of 0.78). This study has the potential to open up new research and clinical opportunities for monitoring hand function in ambulatory settings, ultimately enabling evidence-based, patient-centered rehabilitation and healthcare.
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http://dx.doi.org/10.1109/JBHI.2018.2821136DOI Listing
March 2019
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