Publications by authors named "Sung-Won Choi"

172 Publications

Phenolic compounds in common buckwheat sprouts: composition, isolation, analysis and bioactivities.

Food Sci Biotechnol 2022 Jul 19;31(8):935-956. Epub 2022 Mar 19.

Major of Food Science and Biotechnology, Division of Bio-convergence, Kyonggi University, 154-42 Gwanggyosan-ro, Yeongtong-gu, Suwon, Gyeonggi 16227 Republic of Korea.

Phenolic compounds in common buckwheat sprouts (CBSs) have gained research interest because of their multiple health benefits. Phenolic acids, flavanones, flavonols, flavan-3-ols, and anthocyanins are important bioactive components of CBS that exhibit biological activities, including anti-inflammatory, antioxidant, anti-proliferative, and immunomodulatory effects. The isolation and quantitative and qualitative analyses of these phenolic compounds require effective and appropriate extraction and analytical methods. The most recent analytical method developed for determining the phenolic profile is HPLC coupled with a UV-visible detector and/or MS. This review highlights the extraction, purification, analysis, and bioactive properties of phenolic compounds from CBS described in the literature.
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http://dx.doi.org/10.1007/s10068-022-01056-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300812PMC
July 2022

Rapidly growing juvenile xanthogranuloma of the auricle.

Ear Nose Throat J 2022 Jul 5:1455613221113795. Epub 2022 Jul 5.

Department of Otorhinolaryngology-Head and Neck Surgery and Biomedical Research Institute, 220312Pusan National University Hospital, Busan, Korea.

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http://dx.doi.org/10.1177/01455613221113795DOI Listing
July 2022

Evaluating mobile Health technology use among cancer caregivers in the digital era.

Digit Health 2022 Jan-Dec;8:20552076221109071. Epub 2022 Jun 22.

Department of Computer Science & Data Science, School of Applied Computational Sciences, Meharry Medical College, Nashville, TN, USA.

Introduction: Digital health technology-based interventions have the potential to support cancer caregivers in caregiving responsibilities and in managing their own health and well-being. The objective of this study was to examine the association between caregiving characteristics and different types of digital health technologies used in a national sample of caregivers of patients undergoing hematopoietic cell transplantation (HCT).

Methods: We conducted an online, cross-sectional survey of 948 HCT caregivers.

Results: Spousal caregivers comprised nearly one-third of respondents (27.1%) with a median age of 59 years (range: 18-80 years), compared with parents (32.9%: 38 years), adult children (28.9%: 38 years), and other (11.1%; e.g. friend, other family member: 36 years). Almost two-thirds (65.4%) of all respondents reported using an app for fitness or step counting and 41.3% reported using a smartwatch. However, spousal caregivers were the least likely group to use mobile apps (0.72;  < 0.005) or smartwatches (OR = 0.46;  < 0.005) compared with parent caregivers in models adjusted for demographics and coping style. Caregiving for six months or greater was associated with the use of fewer apps compared with caregiving for less than six months in adjusted models (OR = 0.80,  < 0.005). Caregivers of patients receiving an allogeneic transplant (i.e. non-self-donor) used more apps on average than caregivers of patients receiving an autologous transplant (i.e. self-donor) in adjusted models (OR = 1.36,  < 0.005).

Conclusion: Digital health technologies reflect promising avenues for supporting cancer caregivers. While digital technologies are becoming increasingly pervasive, older caregivers remain an underserved population. Future research should integrate older adult caregivers in the co-design and development activities of technology-driven caregiver support products.
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http://dx.doi.org/10.1177/20552076221109071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234853PMC
June 2022

High-frequency temperature monitoring at home using a wearable device: A case series of early fever detection and antibiotic administration for febrile neutropenia with bacteremia.

Pediatr Blood Cancer 2022 09 23;69(9):e29835. Epub 2022 Jun 23.

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

We present a case series of three febrile episodes in neutropenic pediatric cancer patients who wore a Food and Drug Administration approved high-frequency temperature monitoring (HFTM) wearable device (WD) at home. The WD detected fever events when temperature monitoring by thermometer did not detect fever or was not feasible to perform. Two of the episodes were associated with bloodstream infections and the WD detected fevers 5 and 12 h prior to fevers detected by thermometer, triggering earlier medical evaluation and more prompt administration of antibiotics. These observations provide a basis for future investigation of home-based HFTM to improve infection-related outcomes in pediatric oncology.
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http://dx.doi.org/10.1002/pbc.29835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329227PMC
September 2022

Improving outcomes for care partners of persons with traumatic brain injury: Protocol for a randomized control trial of a just-in-time-adaptive self-management intervention.

PLoS One 2022 9;17(6):e0268726. Epub 2022 Jun 9.

Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, United States of America.

Informal family care partners of persons with traumatic brain injury (TBI) often experience intense stress resulting from their caregiver role. As such, there is a need for low burden, and easy to engage in interventions to improve health-related quality of life (HRQOL) for these care partners. This study is designed to evaluate the effectiveness of a personalized just-in-time adaptive intervention (JITAI) aimed at improving the HRQOL of care partners. Participants are randomized either to a control group, where they wear the Fitbit® and provide daily reports of HRQOL over a six-month (180 day) period (without the personalized feedback), or the JITAI group, where they wear the Fitbit®, provide daily reports of HRQOL and receive personalized self-management pushes for 6 months. 240 participants will be enrolled (n = 120 control group; n = 120 JITAI group). Outcomes are collected at baseline, 1-, 2-, 3-, 4-, 5- & 6-months, as well as 3- and 6-months post intervention. We hypothesize that the care partners who receive the intervention (JITAI group) will show improvements in caregiver strain (primary outcome) and mental health (depression and anxiety) after the 6-month (180 day) home monitoring period. Participant recruitment for this study started in November 2020. Data collection efforts should be completed by spring 2025; results are expected by winter 2025. At the conclusion of this randomized control trial, we will be able to identify care partners at greatest risk for negative physical and mental health outcomes, and will have demonstrated the efficacy of this JITAI intervention to improve HRQOL for these care partners. Trial registration: ClinicalTrial.gov NCT04570930; https://clinicaltrials.gov/ct2/show/NCT04570930.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268726PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182304PMC
June 2022

Patulous eustachian tube after balloon eustachian tuboplasty in a post-radiation patient.

Am J Otolaryngol 2022 Jun 2:103524. Epub 2022 Jun 2.

Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea; Department of Otorhinolaryngology, College of Medicine, Pusan National University, Busan, Republic of Korea. Electronic address:

Background: Balloon eustachian tuboplasty (BET) is a minimally invasive surgical treatment that is effective and safe for obstructive eustachian tube dysfunction. However, BET complications include excessive widening of the eustachian tube, causing a patulous eustachian tube (PET). Herein, we report a case of PET following BET in a patient who underwent radiation therapy and reviewed the literature on considerations for reducing complications after BET.

Case Presentation: A 63-year-old woman complained of bilateral ear fullness after concurrent chemoradiation therapy for nasopharyngeal lymphoma. BET was performed on the left side because the left-sided serous otitis media persisted. A left-sided PET was performed two weeks after the BET, along with eustachian tube silicone plug insertion on the left side. The patient became asymptomatic immediately after the surgery, with no recurrence reported after a 12-month follow-up period.

Conclusions: To our knowledge, there has been no report of PET following BET in a post-radiation patient, and it was successfully treated via ET silicone plug insertion.
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http://dx.doi.org/10.1016/j.amjoto.2022.103524DOI Listing
June 2022

The Optimized Protocol of Hyperbaric Oxygen Therapy For Sudden Sensorineural Hearing Loss.

Laryngoscope 2022 May 12. Epub 2022 May 12.

Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

Objective: This study aimed to determine the optimal protocol of hyperbaric oxygen therapy (HBOT) according to various treatment settings for sudden sensorineural hearing loss (SSNHL).

Methods: A 112 patients with SSNHL were enrolled in this prospective study. All patients were treated with systemic steroid therapy, intratympanic steroid therapy, and HBOT. According to the pressure and duration of HBOT (10 sessions in total), the patients were divided into three groups: group 1, 2.5 atmospheres absolute (ATA) for 1 h; group 2, 2.5 ATA for 2 h; and group 3, 1.5 ATA for 1 h. The pure-tone average (PTA), word discrimination score (WDS), and mean gain were compared.

Results: A total of 105 patients completed the 3-month follow-up, and 6 patients were excluded. Differences among groups were found in PTA, WDS, and mean gain. In the post-hoc analysis, group 3 had significantly lower WDS and mean gain than groups 1 and 2; however, group 2 showed no significant differences from group 1. The proportion of patients with hearing recovery after treatment was significantly higher in group 1 (57.6%) and group 2 (58.8%) than in group 3 (31.3%).

Conclusions: When HBOT (10 sessions) was combined with corticosteroids as the initial therapy for SSNHL, a higher pressure (1.5 ATA vs. 2.5 ATA) provided better treatment results; however, increasing the duration (1 h vs. 2 h) under 2.5 ATA did not result in a significant difference. Therefore, HBOT for SSNHL may be performed at 2.5 ATA for 1 h in 10 sessions. Laryngoscope, 2022.
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http://dx.doi.org/10.1002/lary.30181DOI Listing
May 2022

Consumer-grade wearables identify changes in multiple physiological systems during COVID-19 disease progression.

Cell Rep Med 2022 04 19;3(4):100601. Epub 2022 Apr 19.

Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA.

Consumer-grade wearables are needed to track disease, especially in the ongoing pandemic, as they can monitor patients in real time. We show that decomposing heart rate from low-cost wearable technologies into signals from different systems can give a multidimensional description of physiological changes due to COVID-19 infection. We find that the separate physiological features of basal heart rate, heart rate response to physical activity, circadian variation in heart rate, and autocorrelation of heart rate are significantly altered and can classify symptomatic versus healthy periods. Increased heart rate and autocorrelation begin at symptom onset, while the heart rate response to activity increases soon after symptom onset and increases more in individuals exhibiting cough. Symptom onset is associated with a blunting of circadian variation in heart rate, as measured by the uncertainty in the phase estimate. This work establishes an innovative data analytic approach to monitor disease progression remotely using consumer-grade wearables.
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http://dx.doi.org/10.1016/j.xcrm.2022.100601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017023PMC
April 2022

Non-surgical correction of congenital concha cavum deformity using commercial ear molding device.

Clin Exp Otorhinolaryngol 2022 Apr 8. Epub 2022 Apr 8.

Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

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http://dx.doi.org/10.21053/ceo.2021.02292DOI Listing
April 2022

Clinical features and prognosis of severe-to-profound sudden sensorineural hearing loss.

Am J Otolaryngol 2022 May-Jun;43(3):103455. Epub 2022 Apr 6.

Department of Otorhinolaryngology and Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. Electronic address:

Purpose: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency. Despite multiple efforts to clarify the factors affecting the prognosis of severe-to-profound SSNHL, various studies showed inconsistent results and lack of clinical significance. Therefore, we examined the clinical features and outcomes of severe-to-profound SSNHL.

Materials And Methods: We included patients who experienced SSNHL between 2018 and 2021 and were diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; hearing loss over 70 dB on initial pure tone audiometry (PTA) was used to define severe-to-profound SSNHL. We retrospectively examine the demographic, laboratory, radiologic, and audiometric data of SSNHL patients. We also evaluated the final hearing gain of these patients by assessing their PTA findings and word-recognition scores.

Results: Of the 178 patients, 94 (52.81%) and 84 (47.19%) showed profound (>90 dB) and severe (>70 to 90 dB) hearing loss, respectively. The presence of vertigo and hypertension differed significantly between the severe and profound groups (p < 0.001 and p = 0.012, respectively), as did the initial serum creatinine level (p = 0.043). Recovery in PTA showed a reliable correlation with the interval between onset and treatment in the severe group and periventricular white-matter findings in the profound group (p < 0.001 and p = 0.011, respectively). The presence of hypertension was related to recovery of low tone (p = 0.023 for 250 Hz; p = 0.034 for 500 Hz), while glycated hemoglobin level was related to recovery of high tone in the severe group (p = 0.049 for 4000 Hz; p = 0.047 for 8000 Hz).

Conclusions: Severe-to-profound SSNHL showed poor prognosis for hearing gain. The interval from onset to treatment was a significant prognostic factor for severe SSNHL, while the presence of vertigo, estimated glomerular filtration rate, and periventricular white-matter findings were significant prognostic factors for profound SSNHL.
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http://dx.doi.org/10.1016/j.amjoto.2022.103455DOI Listing
May 2022

Chronic Eustachian Tube Dilatory Dysfunction as a Manifestation of Meningioma.

Ear Nose Throat J 2022 Mar 10:1455613221082624. Epub 2022 Mar 10.

Department of Otorhinolaryngology-Head and Neck Surgery and Pusan National University School of Medicine, Biomedical Research Institute, 220312Pusan National University Hospital, Busan, Republic of Korea.

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http://dx.doi.org/10.1177/01455613221082624DOI Listing
March 2022

Risk Factors for COVID-19 in College Students Identified by Physical, Mental, and Social Health Reported During the Fall 2020 Semester: Observational Study Using the Roadmap App and Fitbit Wearable Sensors.

JMIR Ment Health 2022 Feb 10;9(2):e34645. Epub 2022 Feb 10.

Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, United States.

Background: The COVID-19 pandemic triggered a seismic shift in education to web-based learning. With nearly 20 million students enrolled in colleges across the United States, the long-simmering mental health crisis in college students was likely further exacerbated by the pandemic.

Objective: This study leveraged mobile health (mHealth) technology and sought to (1) characterize self-reported outcomes of physical, mental, and social health by COVID-19 status; (2) assess physical activity through consumer-grade wearable sensors (Fitbit); and (3) identify risk factors associated with COVID-19 positivity in a population of college students prior to release of the vaccine.

Methods: After completing a baseline assessment (ie, at Time 0 [T0]) of demographics, mental, and social health constructs through the Roadmap 2.0 app, participants were instructed to use the app freely, wear the Fitbit, and complete subsequent assessments at T1, T2, and T3, followed by a COVID-19 assessment of history and timing of COVID-19 testing and diagnosis (T4: ~14 days after T3). Continuous measures were described using mean (SD) values, while categorical measures were summarized as n (%) values. Formal comparisons were made on the basis of COVID-19 status. The multivariate model was determined by entering all statistically significant variables (P<.05) in univariable associations at once and then removing one variable at a time through backward selection until the optimal model was obtained.

Results: During the fall 2020 semester, 1997 participants consented, enrolled, and met criteria for data analyses. There was a high prevalence of anxiety, as assessed by the State Trait Anxiety Index, with moderate and severe levels in 465 (24%) and 970 (49%) students, respectively. Approximately one-third of students reported having a mental health disorder (n=656, 33%). The average daily steps recorded in this student population was approximately 6500 (mean 6474, SD 3371). Neither reported mental health nor step count were significant based on COVID-19 status (P=.52). Our analyses revealed significant associations of COVID-19 positivity with the use of marijuana and alcohol (P=.02 and P=.046, respectively) and with lower belief in public health measures (P=.003). In addition, graduate students were less likely and those with ≥20 roommates were more likely to report a COVID-19 diagnosis (P=.009).

Conclusions: Mental health problems were common in this student population. Several factors, including substance use, were associated with the risk of COVID-19. These data highlight important areas for further attention, such as prioritizing innovative strategies that address health and well-being, considering the potential long-term effects of COVID-19 on college students.

Trial Registration: ClinicalTrials.gov NCT04766788; https://clinicaltrials.gov/ct2/show/NCT04766788.

International Registered Report Identifier (irrid): RR2-10.2196/29561.
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http://dx.doi.org/10.2196/34645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834863PMC
February 2022

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Lancet Child Adolesc Health 2022 02 9;6(2):116-128. Epub 2021 Dec 9.

Congenital Heart Center, University of Florida, Gainesville, FL, USA.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.
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http://dx.doi.org/10.1016/S2352-4642(21)00336-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372796PMC
February 2022

An App-Based Just-in-Time Adaptive Self-management Intervention for Care Partners (CareQOL): Protocol for a Pilot Trial.

JMIR Res Protoc 2021 Dec 9;10(12):e32842. Epub 2021 Dec 9.

Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.

Background: Care partners (ie, informal family caregivers) of individuals with health problems face considerable physical and emotional stress, often with a substantial negative impact on the health-related quality of life (HRQOL) of both care partners and care recipients. Given that these individuals are often overwhelmed by their caregiving responsibilities, low-burden self-management interventions are needed to support care partners to ensure better patient outcomes.

Objective: The primary objective of this study is to describe an intensive data collection protocol that involves the delivery of a personalized just-in-time adaptive intervention that incorporates passive mobile sensor data feedback (sleep and activity data from a Fitbit [Fitbit LLC]) and real time self-reporting of HRQOL via a study-specific app called CareQOL (University of Michigan) to provide personalized feedback via app alerts.

Methods: Participants from 3 diverse care partner groups will be enrolled (care partners of persons with spinal cord injury, care partners of persons with Huntington disease, and care partners of persons with hematopoietic cell transplantation). Participants will be randomized to either a control group, where they will wear the Fitbit and provide daily reports of HRQOL over a 3-month (ie, 90 days) period (without personalized feedback), or the just-in-time adaptive intervention group, where they will wear the Fitbit, provide daily reports of HRQOL, and receive personalized push notifications for 3 months. At the end of the study, participants will complete a feasibility and acceptability questionnaire, and metrics regarding adherence and attrition will be calculated.

Results: This trial opened for recruitment in November 2020. Data collection was completed in June 2021, and the primary results are expected to be published in 2022.

Conclusions: This trial will determine the feasibility and acceptability of an intensive app-based intervention in 3 distinct care partner groups: care partners for persons with a chronic condition that was caused by a traumatic event (ie, spinal cord injury); care partners for persons with a progressive, fatal neurodegenerative disease (ie, Huntington disease); and care partners for persons with episodic cancer conditions that require intense, prolonged inpatient and outpatient treatment (persons with hematopoietic cell transplantation).

Trial Registration: ClinicalTrials.gov NCT04556591; https://clinicaltrials.gov/ct2/show/NCT04556591.

International Registered Report Identifier (irrid): DERR1-10.2196/32842.
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http://dx.doi.org/10.2196/32842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704108PMC
December 2021

A multicenter, randomized, active-controlled, clinical trial study to evaluate the efficacy and safety of navigation guided balloon Eustachian tuboplasty.

Sci Rep 2021 12 2;11(1):23296. Epub 2021 Dec 2.

Department of Otorhinolaryngology-Head and Neck Surgery, Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Gudeok-ro 179, Seo-Gu, Busan, 49241, Republic of Korea.

To assess the safety and efficacy of navigation-guided balloon Eustachian tuboplasty (BET) compared to medical management (MM) alone in patients with chronic Eustachian tube dilatory dysfunction (ETD). This is a prospective, multicenter, 1:1 parallel-group, randomized controlled trial (RCT). It aims to assess the efficacy of navigation-guided BET compared to MM alone in patients with chronic ETD. The primary outcome measure was an improvement in the Eustachian tube dysfunction questionnaire (ETDQ)-7 score at the 6-week follow-up compared with baseline. Secondary outcome measures included changes in the signs and symptoms during the follow-up, changes in the score for each subcategory of ETDQ-7, type of tympanometry, pure tone audiometry, and the availability of a positive modified Valsalva maneuver. Navigation-guided BET was safely performed in all patients. A total of 38 ears of 31 patients (19 ears of 16 patients in the BET group and 19 ears of 15 patients in the control group) completed the planned treatment and 6 weeks of follow-up. More patients in the BET group (1.99 ± 0.85) had less symptomatic dysfunction than in the control group (3.40 ± 1.29) at 6 weeks post-procedure (P = 0.001). More patients experienced tympanogram improvement in the BET group at 6 weeks compared to the control group (36.5% vs. 15.8%) with a positive modified Valsalva maneuver (36.6% vs. 15.8%, P = 0.014). Additionally, air-bone gap change was significantly decreased in the BET group compared to the control group at the 6-week follow-up visit (P = 0.037). This prospective, multicenter, RCT study suggests that navigation-guided BET is a safe and superior treatment option compared to MM alone in patients with chronic ETD.
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http://dx.doi.org/10.1038/s41598-021-02848-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639820PMC
December 2021

Comparison of non-surgical correction of a neonatal ear anomaly using two different commercial ear molding devices.

J Plast Reconstr Aesthet Surg 2022 Jan 3;75(1):439-488. Epub 2021 Oct 3.

Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea; Department of Otorhinolaryngology, College of Medicine, Pusan National University, Busan, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.bjps.2021.08.032DOI Listing
January 2022

Immune Suppression in Allogeneic Hematopoietic Stem Cell Transplantation.

Handb Exp Pharmacol 2022 ;272:209-243

Division of Hematology/Oncology, Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for high-risk hematologic disorders. There are multiple immune-mediated complications following allo-HSCT that are prevented and/or treated by immunosuppressive agents. Principal among these immune-mediated complications is acute graft-versus-host disease (aGVHD), which occurs when the new donor immune system targets host tissue antigens. The immunobiology of aGVHD is complex and involves all aspects of the immune system. Due to the risk of aGVHD, immunosuppressive aGVHD prophylaxis is required for nearly all allogeneic HSCT recipients. Despite prophylaxis, aGVHD remains a major cause of nonrelapse mortality. Here, we discuss the clinical features of aGVHD, the immunobiology of aGVHD, the immunosuppressive therapies used to prevent and treat aGVHD, how to mitigate the side effects of these immunosuppressive therapies, and what additional immune-mediated post-allo-HSCT complications are also treated with immunosuppression.
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http://dx.doi.org/10.1007/164_2021_544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055779PMC
July 2022

Effects of cigarette smoke on Haemophilus influenzae-induced otitis media in a rat model.

Sci Rep 2021 10 5;11(1):19729. Epub 2021 Oct 5.

Department of Otorhinolaryngology and Pusan National University School of Medicine, Biomedical Research Institute, Pusan National University Hospital, Gudeok-ro 179, Seo-Gu, Busan, 49241, Republic of Korea.

Exposure to cigarette smoke (CS) is a factor that could delay or worsen the recovery of otitis media (OM) by causing inflammatory swelling of the Eustachian tube (ET). However, despite the suggested relationship, little is known about the association between OM and CS. Therefore, we aimed to evaluate the effects of CS on the development, progression, and recovery of OM, as well as the histological and molecular changes caused by CS exposure, by using a rat model of OM infected with non-typeable Haemophilus influenzae (NTHi). Eighty Sprague-Dawley rats with normal middle ears (MEs) were divided into four groups (n = 20 rats/group): control, CS, OM, and CS + OM. The CS and CS + OM groups were exposed to CS for 2 weeks. The inflammatory reaction to NTHi was more intense and lasted longer in the CS + OM group than in the other groups. Goblet cell proliferation and mucus secretion in the ET were more significant in the CS and CS + OM groups than in the other groups. These findings suggested that because CS directly affects the ET and ME mucosa, bacterial OM can become more severe and may resolve more slowly in the presence of CS exposure rather than in its absence.
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http://dx.doi.org/10.1038/s41598-021-99367-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492685PMC
October 2021

Type 1 interferon to prevent leukemia relapse after allogeneic transplantation.

Blood Adv 2021 12;5(23):5047-5056

Transplantation and Cell Therapy Program, University of Michigan Rogel Cancer Center, Ann Arbor, MI.

A potent graft-versus-leukemia (GVL) response is crucial in preventing relapse, the major impediment to successful allogeneic hematopoietic cell transplantation (HCT). In preclinical studies, type 1 interferon (IFN-α) enhanced cross-presentation of leukemia-specific antigens by CD8α dendritic cells (DCs) and amplified GVL. This observation was translated into a proof-of-concept phase 1/2 clinical trial with long-acting IFN-α (pegylated IFN-α [pegIFNα]) in patients undergoing HCT for high-risk acute myeloid leukemia (AML). Patients with treatment-resistant AML not in remission or those with poor-risk leukemia were administered 4 dosages of pegIFNα every 14 days beginning at day -1 before HCT. Dose selection was established by adaptive design that continuously assessed the probability of dose-limiting toxicities throughout the trial. Efficacy was evaluated by determining the 6-month incidence of relapse at the maximum tolerated dose (MTD). Thirty-six patients (median age, 60 years) received pegIFNα treatment. Grade 3 or greater severe adverse events occurred in 25% of patients, establishing 180 μg as the MTD. In phase 2, the incidence of relapse was 39% at 6 months, which was sustained through 1-year post-HCT. The incidence of transplant-related mortality was 13%, and severe grade III-IV acute graft-versus-host disease (GVHD) occurred in 11%. Paired blood samples from donors and recipients after HCT revealed elevated levels of type 1 IFN with cellular response, the persistence of cross-presenting DCs, and circulating leukemia antigen-specific T cells. These data suggest that prophylactic administration of pegIFNα is feasible in the peri-HCT period. In high-risk AML, increased toxicity was not observed with preliminary evidence for reduction in leukemia relapse after HCT. This trial was registered at www.clinicaltrials.gov as #NCT02328755.
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http://dx.doi.org/10.1182/bloodadvances.2021004908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152997PMC
December 2021

Return-to-School Practices for Pediatric Hematopoietic Cell Transplantation Recipients during the COVID-19 Pandemic.

Transplant Cell Ther 2022 01 17;28(1):54.e1-54.e4. Epub 2021 Sep 17.

Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for International Blood and Marrow Transplant Research, Milwaukee, Wisconsin.

Although organizations such as Centers for Disease Control and Prevention and American Academy of Pediatrics have published guidelines favoring the resumption of in-person schooling during the coronavirus disease 19 (COVID-19) pandemic, there is no specific guidance on hematopoietic cell transplantation (HCT) recipients' safe return to school. We conducted a cross-sectional survey of pediatric HCT physician members of the Pediatric Transplantation and Cellular Therapy Consortium practicing in the United States to describe current return-to-school practices during the COVID-19 pandemic for HCT recipients. A total of 122 respondents (response rate, 30.6%) from 60 transplant centers in 32 US states completed the survey. Most of the respondents (76%) recommended that HCT recipients consider a remote or hybrid school option at this time if possible. If not possible, the respondents recommended a return to in-person school if the patient is at least 12 months post-transplantation or off immune suppression, while taking school safety measures and local COVID-19 cases into account. These results provide valuable guidance for the HCT community, patients, and caregivers on important topics to consider while making return-to-school decisions.
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http://dx.doi.org/10.1016/j.jtct.2021.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447546PMC
January 2022

Device failure caused by the dissociation of floating mass transducer in Vibrant SoundBridge®.

Am J Otolaryngol 2022 Jan-Feb;43(1):103222. Epub 2021 Sep 11.

Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 49241, Republic of Korea; Department of Otorhinolaryngology, College of Medicine, Pusan National University, 2 Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Republic of Korea. Electronic address:

Background: Vibrant SoundBridge® (VSB), a semi-implantable middle ear device, is one of the treatment options for patients with mild-to-severe sensorineural hearing loss or mixed hearing loss. Herein, we report delayed device failure after VSB surgery in two patients.

Case Presentation: In both cases, a revision surgery was performed for the removal of the device; dissociation of the floating mass transducer (FMT) and coupler was noticed in one patient, and dissociation of the FMT-coupler complex from the short process of the incus in the other. In Case 1, the vibration-like sounds disappeared after the surgery. In Case 2, wearing bilateral hearing aids improved hearing after removal surgery, but complaints regarding speech discrimination persisted. Both cases show the importance of not loosening the connectivity between the FMT, coupler, and short process of the incus during VSB surgery.

Conclusions: To our knowledge, there has been no report of dissociation from the short process of the incus or the dissociation between an FMT and the coupler.
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http://dx.doi.org/10.1016/j.amjoto.2021.103222DOI Listing
January 2022

Metabolomic identification of α-ketoglutaric acid elevation in pediatric chronic graft-versus-host disease.

Blood 2022 01;139(2):287-299

Michael Cuccione Childhood Cancer Research Program and.

Chronic graft-versus-host disease (cGVHD) is the most common cause for non-relapse mortality postallogeneic hematopoietic stem cell transplant (HSCT). However, there are no well-defined biomarkers for cGVHD or late acute GVHD (aGVHD). This study is a longitudinal evaluation of metabolomic patterns of cGVHD and late aGVHD in pediatric HSCT recipients. A quantitative analysis of plasma metabolites was performed on 222 evaluable pediatric subjects from the ABLE/PBMTC1202 study. We performed a risk-assignment analysis at day + 100 (D100) on subjects who later developed either cGVHD or late aGVHD after day 114 to non-cGVHD controls. A second analysis at diagnosis used fixed and mixed multiple regression to compare cGVHD at onset to time-matched non-cGVHD controls. A metabolomic biomarker was considered biologically relevant only if it met all 3 selection criteria: (1) P ≤ .05; (2) effect ratio of ≥1.3 or ≤0.75; and (3) receiver operator characteristic AUC ≥0.60. We found a consistent elevation in plasma α-ketoglutaric acid before (D100) and at the onset of cGVHD, not impacted by cGVHD severity, pubertal status, or previous aGVHD. In addition, late aGVHD had a unique metabolomic pattern at D100 compared with cGVHD. Additional metabolomic correlation patterns were seen with the clinical presentation of pulmonary, de novo, and progressive cGVHD. α-ketoglutaric acid emerged as the single most significant metabolite associated with cGVHD, both in the D100 risk-assignment and later diagnostic onset analysis. These distinctive metabolic patterns may lead to improved subclassification of cGVHD. Future validation of these exploratory results is needed. This trial was registered at www.clinicaltrials.gov as #NCT02067832.
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http://dx.doi.org/10.1182/blood.2021013244DOI Listing
January 2022

High-frequency temperature monitoring for early detection of febrile adverse events in patients with cancer.

Cancer Cell 2021 09 12;39(9):1167-1168. Epub 2021 Aug 12.

Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ccell.2021.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982843PMC
September 2021

Monitoring beliefs and physiological measures in students at risk for COVID-19 using wearable sensors and smartphone technology: Protocol for a mobile health study.

JMIR Res Protoc 2021 Jun 4. Epub 2021 Jun 4.

Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Michigan, 1500 E. Medical Center DrD4118 Medical Professional Building, Ann Arbor, US.

Background: The COVID-19 pandemic has impacted lives significantly and greatly affected an already vulnerable population, college students, in relation to mental health and public safety. Social distancing and isolation have brought about challenges to student's mental health. Mobile health apps and wearable sensors may help to monitor students at risk for COVID-19 and support their mental well-being.

Objective: Through the use of a wearable sensor and smartphone-based survey completion, this study aimed to monitor students at risk for COVID-19.

Methods: We conducted a prospective study of students, undergraduate and graduate, at a public university in the Midwest. Students were instructed to download the Fitbit, Social Rhythms, and Roadmap 2.0 apps onto their personal mobile devices (Android or iOS). Subjects consented to provide up to 10 saliva samples during the study period. Surveys were administered through the Roadmap 2.0 app at five timepoints - at baseline, 1-month later, 2-months later, 3-months later, and at study completion. The surveys gathered information regarding demographics, COVID-19 diagnoses and symptoms, and mental health resilience, with the aim of documenting the impact of COVID-19 on the college student population.

Results: This study enrolled 2,158 college students between September 2020 and January 2021. Subjects are currently being followed on-study for one academic year. Data collection and analysis are ongoing.

Conclusions: This study examined student health and well-being during the COVID-19 pandemic. It also assessed the feasibility of wearable sensor use and survey completion in a college student population, which may inform the role of our mobile health tools on student health and well-being. Finally, using wearable sensor data, biospecimen collection, and self-reported COVID-19 diagnosis, our results may provide key data towards the development of a model for the early prediction and detection of COVID-19.

Clinicaltrial: ClinicalTrials.gov NCT04766788.
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http://dx.doi.org/10.2196/29561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386373PMC
June 2021

The Clinical Value of Periventricular White Matter Hyperintensity on MRI in Sudden Sensorineural Hearing Loss.

Ann Otol Rhinol Laryngol 2022 Mar 25;131(3):244-251. Epub 2021 May 25.

Department of Otorhinolaryngology-Head and Neck Surgery and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

Objectives: To assess the clinical value of periventricular white matter hyperintensity (PWMH) found on brain magnetic resonance imaging (MRI) in patients with sudden sensorineural hearing loss (SSNHL).

Methods: In this prospective study, 115 patients who were diagnosed with SSNHL aged between 55 and 75 years were analyzed. All subjects underwent brain MRI and were divided into a PWMH and control groups, depending on the presence of PWMH on MRI. PWMH was subdivided into 3 groups according to severity. Pure-tone average results and hearing gain were compared between the 2 groups before treatment and 2 months after treatment. Hearing improvement was assessed using Sigel's criteria.

Results: A total of 106 patients (43 in the PWMH group and 63 in the control group) finally completed the 2-month follow-up. Average hearing gain in the PWMH group was significantly higher than in the control group (34.8 ± 20.3 and 25.9 ± 20.3, respectively,  = .029). PWMH score 1 showed significantly better hearing levels and hearing gain compared to PWMH score 3 and the control group. Multivariate analysis revealed that younger age, better initial hearing level, and the presence of PVWM score 1 were associated with good recovery.

Conclusions: The presence of PWMH score 1 on brain MRI in patients with SSNHL was associated with better treatment response and was a good prognostic factor in a multivariate analysis while the hearing recovery in more severe PWMH (scores 2, 3) was not different from the control group.
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http://dx.doi.org/10.1177/00034894211018925DOI Listing
March 2022

Evaluating health technology engagement among family caregivers of patients undergoing hematopoietic cell transplantation.

Res Sq 2021 May 14. Epub 2021 May 14.

University of Michigan Medicine: University of Michigan Michigan Medicine.

Digital health technology-based interventions have the potential to support caregivers in their caregiving responsibilities and in managing their own health and well-being. Designing digital health technologies to support caregivers of patients undergoing hematopoietic cell transplantation requires evaluating their engagement with these technologies. The objective of this study was to examine the association between caregiving characteristics and different types of digital health technologies used. We conducted an online cross-sectional, national survey of 948 unpaid family caregivers of patients undergoing hematopoietic cell transplantation. Almost two-thirds (65.4%) of respondents reported using an app for fitness or step counting, while 41.3% reported using a smartwatch. The average number of apps used was 3.3 (range 0-9). In adjusted models, adult children who were caregivers (OR=5.82, p<0.005) and caregivers of another relative (OR=2.51, p<0.005) were significantly more likely to use a fitness tracker than caregivers of a child. Caregiving for six months or greater was associated with use of fewer apps compared with caregiving for less than six months in adjusted models (OR=0.80, p<0.005). Caregivers of patients receiving an allogeneic transplant used more apps on average than caregivers of patients receiving an autologous transplant, in adjusted (OR=1.36, p<0.005) models. Digital health technologies may reflect promising avenues for supporting caregivers of patients undergoing HCT. The rapid insurgence of telehealth, propelled by the current COVID-19 pandemic, emphasizes the need for a better understanding of digital health technology for future study design.
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http://dx.doi.org/10.21203/rs.3.rs-427058/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132239PMC
May 2021

A longitudinal study of changes of congenital auricular deformity regarding self-correction.

J Plast Reconstr Aesthet Surg 2021 Oct 28;74(10):2705-2711. Epub 2021 Mar 28.

Department of Otorhinolaryngology-Head and Neck Surgery and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Pusan National University, Busan, Republic of Korea. Electronic address:

This study aimed to investigate the factors associated with congenital auricular deformities and evaluate the long-term frequency of their self-correction. Ninety newborns were enrolled in the study, and data were collected within 2 weeks after birth and at 1 year. The shape of the auricle was classified into seven categories using a digital image. At 2 weeks after birth, several birth-related factors were evaluated in the auricular deformity and normal groups. At 1 year after birth, the images of auricles were compared with the images at birth, and the changes in the auricle shape were investigated. Congenital auricular deformities were observed in 139 out of 180 ears, and the major type noted was helix rim deformity (47 ears), followed by normal ears (41 ears), and cup ears (33 ears). Male sex was found to have a statistically significant association with the occurrence of auricular deformity. In the longitudinal study, among 43 neonates (86 ears) followed-up 12 months later, the self-correction rate was approximately 50%. The normal auricle and prominent ear increased, helix rim deformity and cup ear decreased significantly. The prognosis of deformity varied depending on the type of deformity. Considering the low self-correction rate in the prominent and cup ears, newborns with these deformities might be recommended to undergo management such as auricle molding technique, as required.
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http://dx.doi.org/10.1016/j.bjps.2021.03.023DOI Listing
October 2021

Monitoring Health Care Workers at Risk for COVID-19 Using Wearable Sensors and Smartphone Technology: Protocol for an Observational mHealth Study.

JMIR Res Protoc 2021 May 12;10(5):e29562. Epub 2021 May 12.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.

Background: Health care workers (HCWs) have been working on the front lines of the COVID-19 pandemic with high risks of viral exposure, infection, and transmission. Standard COVID-19 testing is insufficient to protect HCWs from these risks and prevent the spread of disease. Continuous monitoring of physiological data with wearable sensors, self-monitoring of symptoms, and asymptomatic COVID-19 testing may aid in the early detection of COVID-19 in HCWs and may help reduce further transmission among HCWs, patients, and families.

Objective: By using wearable sensors, smartphone-based symptom logging, and biospecimens, this project aims to assist HCWs in self-monitoring COVID-19.

Methods: We conducted a prospective, longitudinal study of HCWs at a single institution. The study duration was 1 year, wherein participants were instructed on the continuous use of two wearable sensors (Fitbit Charge 3 smartwatch and TempTraq temperature patches) for up to 30 days. Participants consented to provide biospecimens (ie, nasal swabs, saliva swabs, and blood) for up to 1 year from study entry. Using a smartphone app called Roadmap 2.0, participants entered a daily mood score, submitted daily COVID-19 symptoms, and completed demographic and health-related quality of life surveys at study entry and 30 days later. Semistructured qualitative interviews were also conducted at the end of the 30-day period, following completion of daily mood and symptoms reporting as well as continuous wearable sensor use.

Results: A total of 226 HCWs were enrolled between April 28 and December 7, 2020. The last participant completed the 30-day study procedures on January 16, 2021. Data collection will continue through January 2023, and data analyses are ongoing.

Conclusions: Using wearable sensors, smartphone-based symptom logging and survey completion, and biospecimen collections, this study will potentially provide data on the prevalence of COVID-19 infection among HCWs at a single institution. The study will also assess the feasibility of leveraging wearable sensors and self-monitoring of symptoms in an HCW population.

Trial Registration: ClinicalTrials.gov NCT04756869; https://clinicaltrials.gov/ct2/show/NCT04756869.

International Registered Report Identifier (irrid): DERR1-10.2196/29562.
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http://dx.doi.org/10.2196/29562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117956PMC
May 2021

Surgical Removal of Hearing Aid Earmold Impression Material in the Middle Ear.

Ear Nose Throat J 2021 Apr 8:1455613211009129. Epub 2021 Apr 8.

Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

When fitting hearing aids, patients are required to make an earmold impression material for device fixation. It usually causes no problems, although in rare cases, the earmold passes through the middle ear through tympanic membrane perforations.- Foreign bodies may cause a delayed inflammatory reaction and deterioration of aeration, especially in the Eustachian tube. Herein, we report a rare case of earmold impression material as a foreign body in the middle ear that required surgical removal.
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http://dx.doi.org/10.1177/01455613211009129DOI Listing
April 2021

Harnessing mobile health technology to support long-term chronic illness management: exploring family caregiver support needs in the outpatient setting.

JAMIA Open 2020 Dec 5;3(4):593-601. Epub 2020 Dec 5.

Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, Michigan, USA.

Objective: Family caregiving is an important public health issue, particularly with the aging population. In recent years, mobile health (mHealth) technology has emerged as a potential low-cost, scalable platform to address caregiver support needs, and thereby alleviate the burden on caregivers. This study sought to examine the support needs of family caregivers in their lived experiences of outpatient care to inform the development of a future mHealth intervention.

Materails And Methods: We conducted 20 semi-structured interviews in 2 outpatient hematopoietic cell transplant (HCT) clinics at a large academic medical center in the Midwestern United States. A thematic analysis was performed to define emerging themes.

Results: Qualitative data analysis identified 5 primary themes that HCT caregivers faced: (I) lifestyle restrictions due to the patient's immunocompromised state; (II) Unmet needs due to limitations in the current resources, including unfamiliar medical tasks without necessary trainings; and (III) caregivers' adaptive strategies, including reformation of social relationships with family and friends. Based on these findings, we suggest 3 design considerations to guide the development of a future mHealth intervention.

Conclusions: The findings herein captured the family caregiver's lived experiences during outpatient care. There was broad agreement that caregiving was challenging and stressful. Thus, effective and scalable interventions to support caregivers are needed. This study provided data to guide the content and design of a future mHealth intervention in the outpatient setting.
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http://dx.doi.org/10.1093/jamiaopen/ooaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969961PMC
December 2020
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