Publications by authors named "Quynh Nguyen"

249 Publications

Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.

Immunity 2021 Apr 28. Epub 2021 Apr 28.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA. Electronic address:

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/β-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs) . Activation of β-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, β-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted β-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This β-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by β-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.
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http://dx.doi.org/10.1016/j.immuni.2021.04.001DOI Listing
April 2021

Irreducible Traumatic Radial Head Dislocation Due to Annular Ligament Interposition in a Child with Ulnar Plastic Deformation: A Case Report.

Orthop Surg 2021 May 4. Epub 2021 May 4.

VietDuc University Hospital, Hanoi, Vietnam.

Background: The traumatic dislocation of the radial head in children is commonly treated by closed reduction. Sometimes, however, this strategy of treatment may not be effective due to the location of soft tissues in the radio-shoulder joint. The literature presents a few cases of the irreducible radial head dislocation with ulnar plastic deformation. Because it is a relatively rare condition, such a traumatic dislocation can be easily missed. Neglected injuries can lead to unwanted complications and unpredictable surgical outcomes.

Case Presentation: This study presents a relatively rare case of traumatic radial head dislocation with ulnar plastic deformation in a 3-year-old child, which was successfully treated by open reduction. The examined case did not require osteotomy and ligamentous reconstruction. The initial attempt of closed reduction failed due to annular ligament interposition, which has been detected on MRI. After 3 months of treatment, the range of motion of the operated arm gradually improved. At the 6-month follow-up, the Mayo elbow-performance score indicated an excellent treatment outcome.

Conclusions: The delayed treatment of radial head dislocation with ulnar plastic deformation can hinder the supination and pronation of the forearm, resulting in elbow/forearm deformity. The earlier this condition is detected, the easier it will be to treat it and the better the treatment outcome will be. The examined case of irreversible traumatic dislocation, successfully treated by open reduction, may help to treat radial head dislocation better.
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http://dx.doi.org/10.1111/os.12981DOI Listing
May 2021

Resistance of Winter Spelt Wheat [ subsp. (L.) Thell.] to Fusarium Head Blight.

Front Plant Sci 2021 7;12:661484. Epub 2021 Apr 7.

Crop Research Institute, Prague, Czechia.

Resistance to Fusarium head blight (FHB) of spelt wheat was investigated in field trials carried out at three European locations between 2016 and 2018. Resistance was assessed after artificial inoculation by visual scoring of symptoms and the determination of the contamination of grains and glumes with the mycotoxin deoxynivalenol (DON). It was found that typical spelt traits such as tall plant height, lax spikes, and tough glumes play a role as passive resistance factors. Across all test environments, modern spelt varieties with a significantly reduced plant height showed a significantly higher susceptibility to FHB and a higher contamination of the grains with DON compared to old landraces/varieties and plant genetic resources. Similarly, the lowest mycotoxin levels in grains were found only in old landraces and varieties, while the highest DON concentration was observed mainly in modern varieties. The results obtained can be used for the selection of suitable parental material for breeding spelt with improved FHB resistance.
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http://dx.doi.org/10.3389/fpls.2021.661484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058439PMC
April 2021

Preoperative anemia and transfusion in cardiac surgery: a single-centre retrospective study.

J Cardiothorac Surg 2021 Apr 23;16(1):109. Epub 2021 Apr 23.

Division of Anesthesiology & Pain Medicine, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada.

Background: Preoperative anemia and transfusion are associated with worse outcomes. This study aims to identify the prevalence of preoperative anemia, transfusion rates on surgery day, and predictors of transfusion in elective cardiac surgery patients at our centre. We also aim to evaluate our preoperative intervention program, and examine the intervention window for anemia before surgery.

Methods: This study included 797 adult patients who underwent elective cardiac surgery at a tertiary hospital. Multivariable logistic regression analysis was used to identify predictors of transfusion on surgery day.

Results: Preoperative anemia was present in 15% of patients. Anemic patients had a significantly higher transfusion rate at 53% compared to 10% in non-anemic patients. Hemoglobin concentration, estimated glomerular filtration rate (eGFR), body surface area (BSA), and total cardiopulmonary bypass time were predictive of transfusion on surgery day. Patients had a median of 7 days between initial visit and surgery day, however, referral to the blood conservation clinic was only done for 8% of anemic patients and treatment was initiated in 3% of anemic patients. Among the 3 anemic patients who received treatment, 2 did not require blood transfusion on surgery day.

Conclusions: Preoperative anemia is present in 15% of patients at our centre and these patients have 53% transfusion rates on surgery day. Hemoglobin concentration, eGFR, BSA, and total cardiopulmonary bypass time were predictors of transfusion on surgery day. Patients had a median of 7 days between initial visit and surgery day. Referral and anemia treatment were infrequently initiated in preoperative anemic patient.
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http://dx.doi.org/10.1186/s13019-021-01493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063400PMC
April 2021

Immediate allograft reconstruction of the infraorbital nerve following resection of polyostotic fibrous dysplasia lesion.

Case Reports Plast Surg Hand Surg 2021 Feb 5;8(1):12-17. Epub 2021 Feb 5.

Department of Oral Maxillofacial Surgery and Pathology, School of Dentistry - University of Mississippi Medical Center, Jackson, MS, USA.

Processed nerve allografts (PNA) have increasingly been used as alternative to autogenous nerve grafts to repair nerve injuries in oral-maxillofacial surgeries. This case report describes an immediate PNA reconstruction of infraorbital nerve injury sustained during the ablation of a large expansile polyostotic fibrous dysplasia centered in the left maxilla.
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http://dx.doi.org/10.1080/23320885.2021.1883435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015865PMC
February 2021

Surgical management for unruptured sinus of Valsalva aneurysms: a narrative review of the literature.

J Thorac Dis 2021 Mar;13(3):1833-1850

Division of Cardiovascular Surgery, Department of Surgery, University of British Columbia, Vancouver, BC, Canada.

Unruptured sinus of Valsalva aneurysms (SVAs) are rare cardiac lesions that arise due to congenital or acquired etiologies. They could be asymptomatic or cause various clinical manifestations as a consequence of their mass effect on the coronary arteries, heart valves, and other adjacent structures. While the factors predicting SVA rupture are not fully understood, ruptured SVAs carry a high complication and mortality rate, highlighting the need for early recognition and management of unruptured SVAs. Imaging modalities such as echocardiography, computed tomography (CT), angiography, and magnetic resonance imaging (MRI) are essential in identifying and characterizing the aneurysm as well as associated cardiac anomalies. However, there are no specific guidelines for the diagnosis and management of SVAs. Herein, we performed a contemporary systematic review to examine the presentation, diagnostic tests and findings, as well as outcomes for surgical intervention of unruptured SVAs. We demonstrate that surgical repair remains the preferred method of treatment in order to prevent complications such as rupture or thrombus formation. Surgery should be prompted in patients with symptomatic, large, or rapidly expanding unruptured SVAs, as well as those unruptured SVAs that contain intraluminal thrombi, have a mass effect on surrounding structures, or are recurrent. Surgical outcomes are generally good with favourable prognosis and minimal recurrence.
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http://dx.doi.org/10.21037/jtd-20-2682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024852PMC
March 2021

Flow Rectification in Loopy Network Models of Bird Lungs.

Phys Rev Lett 2021 Mar;126(11):114501

Applied Math Lab, Courant Institute, New York University, New York, New York 10012, USA.

We demonstrate flow rectification, valveless pumping, or alternating to direct current (AC-to-DC) conversion in macroscale fluidic networks with loops. Inspired by the unique anatomy of bird lungs and the phenomenon of directed airflow throughout the respiration cycle, we hypothesize, test, and validate that multiloop networks exhibit persistent circulation or DC flows when subject to oscillatory or AC forcing at high Reynolds numbers. Experiments reveal that disproportionately stronger circulation is generated for higher frequencies and amplitudes of the imposed oscillations, and this nonlinear response is corroborated by numerical simulations. Visualizations show that flow separation and vortex shedding at network junctions serve the valving function of directing current with appropriate timing in the oscillation cycle. These findings suggest strategies for controlling inertial flows through network topology and junction connectivity.
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http://dx.doi.org/10.1103/PhysRevLett.126.114501DOI Listing
March 2021

Prognosis of severe lymphopenia after postoperative radiotherapy in non-small cell lung cancer: Results of a long-term follow up study.

Clin Transl Radiat Oncol 2021 May 12;28:54-61. Epub 2021 Mar 12.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Purpose: To investigate the incidence and prognosis of severe radiation-induced lymphopenia (sRIL) after postoperative radiotherapy (PORT) for resected NSCLC.

Patients And Methods: Between 1998 and 2017, 170 patients treated with PORT for NSCLC were retrospectively reviewed. Lymphopenia was divided into tertiles with severe lymphopenia defined as absolute lymphocyte counts (ALC) < 0.37 × 10/ul.

Results: sRIL was observed in 32.3% of patients. Multivariable logistic regression analysis indicated sRIL was associated with planning target volume radiation fraction numbers (OR 1.09,  = 0.005) and total lung mean dose (OR 1.12,  = 0.006). With a median follow-up time of 12.2 years, the median progression-free survival and overall survival were 14.8 months and 28.4 months respectively in patients with sRIL, vs. 21.7 months ( = 0.008) and 48.3 months ( = 0.01) respectively in patients without sRIL. Multivariable analyses indicated sRIL significantly decreased OS (HR 1.95,  < 0.01). Since PORT for stage I-II NSCLC was done largely for positive margins, which may confound the contribution of severe RIL, we analyzed stage III separately and found that sRIL also significantly decreased OS (HR 1.88,  = 0.004) in multivariable analysis.

Conclusion: For this long-term outcome study, severe RIL correlated with total lung mean dose and radiation fractionation numbers, and was a strong prognostic factor for poor survival in PORT patients, particularly in patients with stage III NSCLC, highlighting the importance of an intact immune system for post-radiation immunologic disease surveillance.
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http://dx.doi.org/10.1016/j.ctro.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985216PMC
May 2021

Electrochemical Sensor Based on Reduced Graphene Oxide/Double-Walled Carbon Nanotubes/Octahedral FeO/Chitosan Composite for Glyphosate Detection.

Bull Environ Contam Toxicol 2021 Mar 20. Epub 2021 Mar 20.

Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.

In this work, reduced graphene oxide/double-walled carbon nanotubes/octahedral-FeO/chitosan composite material modified screen-printed gold electrodes (rGO/DWCNTs/Oct-FeO/Cs/SPAuE) under inhibition of urease enzyme was developed for the determination of glyphosate (GLY). The electrochemical behaviors of GLY on these electrodes were evaluated by square wave voltammetry (SWV). With the electroactive surface area is 1.7 times higher than that of bare SPAuE, the rGO/DWCNTs/Oct-FeO/Cs/SPAuE for detection of GLY shows a low detection limit (LOD) of ~ 0.08 ppb in a large concentration range of 0.1-1000 ppb. Moreover, it is also successfully applied to the determination of GLY in river water samples with recoveries and relative standard deviations (RSDs) from 98.7% to 106.9% and from 0.79% to 0.87%, respectively. The developed composite will probably provide an universal electrochemical sensing platform that is very promising for environmental monitoring.
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http://dx.doi.org/10.1007/s00128-021-03179-7DOI Listing
March 2021

Evaluating associations between area-level Twitter-expressed negative racial sentiment, hate crimes, and residents' racial prejudice in the United States.

SSM Popul Health 2021 Mar 6;13:100750. Epub 2021 Feb 6.

Department of Epidemiology & Biostatistics, University of Maryland School of Public Health, College Park, MD, 20742, USA.

Background: The objective of the current study is to investigate whether an area-level measure of racial sentiment derived from Twitter data is associated with state-level hate crimes and existing measures of racial prejudice at the individual-level.

Methods: We collected 30,977,757 tweets from June 2015-July 2018 containing at least one keyword pertaining to specific groups (Asians, Arabs, Blacks, Latinos, Whites). We characterized sentiment of each tweet (negative vs all other) and averaged at the state-level. These racial sentiment measures were merged with other measures based on: hate crime data from the FBI Uniform Crime Reporting Program; implicit and explicit racial bias indicators from Project Implicit; and racial attitudes questions from General Social Survey (GSS).

Results: Living in a state with 10% higher negative sentiment in tweets referencing Blacks was associated with 0.57 times the odds of endorsing a GSS question that Black-White disparities in jobs, income, and housing were due to discrimination (95% CI: 0.40, 0.83); 1.64 times the odds of endorsing the belief that disparities were due to lack to will (95% CI: 0.95, 2.84); higher explicit racial bias (β: 0.11; 95% CI: 0.04, 0.18); and higher implicit racial bias (β: 0.09; 95% CI: 0.04, 0.14). Twitter-expressed racial sentiment was not statistically-significantly associated with incidence of state-level hate crimes against Blacks (IRR: 0.99; 95% CI: 0.52, 1.90), but this analysis was likely underpowered due to rarity of reported hate crimes.

Conclusion: Leveraging timely data sources for measuring area-level racial sentiment can provide new opportunities for investigating the impact of racial bias on society and health.
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http://dx.doi.org/10.1016/j.ssmph.2021.100750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901034PMC
March 2021

Job satisfaction and turnover intention of preventive medicine workers in northern Vietnam: Is there any relationship?

Health Serv Insights 2021 17;14:1178632921995172. Epub 2021 Feb 17.

Ministry of Health, Hanoi, Vietnam.

To access the relationship between job satisfaction and turnover intention of preventive medicine workers in Vietnam, we conducted a cross-sectional study using a purposive convenience sample of 12 preventive medicine centers in 3 provinces of northern Vietnam (Hai Duong, a plain province, Yen Bai, a mountainous province, and Hanoi, the capital of Vietnam). Overall, 400 preventive medicine staff were invited to participate, and 383 questionnaires were analyzed (153 from 3 provincial centers and 230 from 9 district centers). All eligible participants completed the questionnaire, which included questions relating to general information, job satisfaction, intention to quit. We identified significant associations between turnover intention and personal factors, including age, marital status, education level, professional degree, and length of employment at the current center. The bivariate analysis also indicated that job satisfaction had an inverse relationship with turnover intention, as expected. The correlations varied between facets and overall job satisfaction, from -0.19 for community support to -0.37 for overall job satisfaction. These correlations remained significant after controlling for personal factors using hierarchical multiple regressions. The results indicated that facet and overall job satisfaction were significant predictors of turnover intention, while overall job satisfaction was the strongest predictor (β = 0.37,  < .001). This study could contribute to local system development and the international understanding of job satisfaction and turnover intention among preventive medicine workers. Addressing the aspects of job satisfaction that were found to have the lowest scores may help the preventive medicine system to retain staff.
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http://dx.doi.org/10.1177/1178632921995172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894696PMC
February 2021

Effects of Smartphone-Based Stress Management on Improving Work Engagement Among Nurses in Vietnam: Secondary Analysis of a Three-Arm Randomized Controlled Trial.

J Med Internet Res 2021 02 23;23(2):e20445. Epub 2021 Feb 23.

Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Work engagement is important for employee well-being and work performance. However, no intervention study has investigated the effect of an eMental Health intervention on work engagement among workers in low- and middle-income countries (LMICs).

Objective: The aim of the study was to examine the effects of a newly developed smartphone-based stress management program (ABC Stress Management) on improving work engagement among hospital nurses in Vietnam, an LMIC.

Methods: Full-time registered nurses (n=949) were randomly assigned to one of 2 intervention groups or a control group. The intervention groups were a 6-week, 6-lesson program offering basic cognitive behavioral therapy (CBT-based stress management skills), provided in either free-choice (program A) or fixed order (program B). Work engagement was assessed at baseline and 3-month and 7-month follow-ups in each of the 3 groups.

Results: The scores of work engagement in both intervention groups improved from baseline to 3-month follow-up, and then decreased at the 7-month follow-up, while the score steadily increased from baseline to 7-month follow-up in the control group. Program B showed a significant intervention effect on improving work engagement at the 3-month follow-up (P=.049) with a small effect size (Cohen d= 0.16; 95% CI 0.001 to 0.43]). Program A showed nonsignificant trend (d=0.13; 95% CI -0.014 to 0.41; P=.07) toward improved engagement at 3 months. Neither program achieved effectiveness at the 7-month follow-up.

Conclusions: The study demonstrated that a fixed order (program B) delivery of a smartphone-based stress management program was effective in improving work engagement in nurses in Vietnam. However, the effect was small and only temporary. Further improvement of this program is required to achieve a greater effect size and more sustained, longer lasting impact on work engagement.

Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000033139; tinyurl.com/55gxo253.

International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2018-025138.
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http://dx.doi.org/10.2196/20445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943341PMC
February 2021

Fish sauce fermentation using SPQ isolate as a starter culture.

Food Sci Nutr 2021 Feb 30;9(2):651-661. Epub 2020 Dec 30.

Division of Bioindustry The University of Suwon Hwaseong Korea.

A total of 344 halophilic bacteria were isolated from fish fermentation broths, solar salt crystals, seawater, and muds from ponds of salt pans in Vietnam and subjected to aroma evaluation using fish broth containing 29 ~ 30% (w/v) NaCl. One isolate from a salt crystal with the highest aroma score was selected, identified by using 16S rDNA sequence, and named SPQ. The GC-MS results of the fish broth fermented by SPQ revealed elevated concentrations of several aroma compounds such as ethyl alcohol, 1-propanol, 1-butyl alcohol, 1-amyl alcohol, and methionol. During the validation tests for SPQ, using 2 kg of anchovy fish in 30% (w/v) NaCl at pH 5.78, the total and amino nitrogen values in the broth increased over time from 15.2 g/L at the beginning to 26.3 g/L at 6th month, with these values being comparable to those of the control. The ammoniacal nitrogen value (2.52 g/L) in the inoculated broth at 6th month was slightly higher than that (2.21 g/L) of control. The histamine content of the fish broth inoculated with SPQ after 6 months was 110.12 mg/L, less than the maximum permitted safety limit of 200 mg/L, indicating it to be safe. Physical parameters, such as the total, amino, ammoniacal nitrogens, and histamine content of fish broth fermented by MPQ met the standards for Vietnamese fish sauces. Two important umami amino acids, aspartic and glutamic acid, were seen to significantly increase, by 23.5% and 35.1%, respectively, even in the extremely harsh fermentation conditions posed by 30% (w/v) NaCl. The color, odor, and taste of the fish sauce fermented by SPQ elicited the highest preference score accorded by the panelists. Taken together, SPQ is a promising starter culture strain for fish sauce fermentation.
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http://dx.doi.org/10.1002/fsn3.2024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866574PMC
February 2021

Preventive Effects of Anthraquinones Isolated from an Endophytic Fungus, sp. JS-0367 in Tumor Necrosis Factor-α-Stimulated Damage of Human Dermal Fibroblasts.

Antioxidants (Basel) 2021 Jan 30;10(2). Epub 2021 Jan 30.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Reactive oxygen species (ROS) are a major causative factor of inflammatory responses and extracellular matrix degradation. ROS also cause skin aging and diverse cutaneous lesions. Therefore, antioxidants that inhibit the generation of ROS may be beneficial in the relief of skin aging and diseases. We investigated the anti-skin aging effect of anthraquinones from cultures of sp., an endophytic fungus isolated from L. using human dermal fibroblasts (HDFs). We preferentially evaluated the preventive effects of anti-oxidative anthraquinones (, ) against the generation of ROS, nitric oxide (NO), and prostaglandins-E (PGE). Among them, 1,3-dihydroxy-2,8-dimethoxy-6-methylanthraquinone () suppressed the generation of ROS, NO, and PGE in tumor necrosis factor-alpha (TNF-α)-stimulated HDFs. Compound reversed the TNF-induced increase in matrix metalloproteinase (MMP)-1 and a decrease in procollagen I α1 (COLIA1). It also suppressed inducible NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8, which upregulate inflammatory reactions. Mechanistically, compound suppressed nuclear factor-κB, activator protein 1, and mitogen-activated protein kinases in TNF-α-stimulated HDFs. These results suggest that compound may be beneficial for improving skin aging and diverse cutaneous lesions.
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http://dx.doi.org/10.3390/antiox10020200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910856PMC
January 2021

Emerging carbapenem-resistant sequence type 16 causing multiple outbreaks in a tertiary hospital in southern Vietnam.

Microb Genom 2021 03 10;7(3). Epub 2021 Feb 10.

Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.

The emergence of carbapenem resistance in represents a major global public health concern. Nosocomial outbreaks caused by multidrug-resistant are commonly reported to result in high morbidity and mortality due to limited treatment options. Between October 2019 and January 2020, two concurrent high-mortality nosocomial outbreaks occurred in a referral hospital in Ho Chi Minh City, Vietnam. We performed genome sequencing and phylogenetic analysis of eight isolates from infected patients and two environmental isolates for outbreak investigation. We identified two outbreaks caused by two distinct lineages of the international sequence type (ST) 16 clone, which displayed extensive drug resistance, including resistance to carbapenem and colistin. Carbapenem-resistant ST16 outbreak strains clustered tightly with previously described ST16 from other hospitals in Vietnam, suggesting local persistence and transmission of this particular clone in this setting. We found environmental isolates from a hospital bed and blood pressure cuff that were genetically linked to an outbreak case cluster, confirming the potential of high-touch surfaces as sources for nosocomial spread of . Further, we found colistin resistance caused by disruption of the gene by an IS-like element, and carbapenem resistance mediated by a transferable IncF/ plasmid carrying the IS-like element. Our study highlights the importance of coordinated efforts between clinical and molecular microbiologists and infection control teams to rapidly identify, investigate and contain nosocomial outbreaks. Routine surveillance with advanced sequencing technology should be implemented to strengthen hospital infection control and prevention measures.
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http://dx.doi.org/10.1099/mgen.0.000519DOI Listing
March 2021

Suppresses LPS-Induced Oxidative Stress during Inflammatory Response in Human Keratinocytes by Regulating the MAPKs/AP-1, NFκB, and NFAT Signaling Pathways.

Molecules 2021 Feb 6;26(4). Epub 2021 Feb 6.

College of Life Sciences, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Korea.

belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol berry extract (CLE) was investigated on lipopolysaccharide (LPS)-stimulated keratinocytes. The LPS-induced overproduction of reactive oxygen species (ROS) was suppressed by the treatment with CLE. In response to ROS induction, the overexpression of inflammatory regulating signaling molecules including mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and nuclear factor of activated T-cells (NFAT) were reduced in CLE-treated human keratinocytes. Consequently, CLE significantly suppressed the mRNA levels of pro-inflammatory chemokines and interleukins in LPS-stimulated cells. Our results indicated that CLE has protective effects against LPS-induced injury in an in vitro model and is a potential alternative agent for inflammatory treatment.
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http://dx.doi.org/10.3390/molecules26040869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914440PMC
February 2021

Online Tuning of PID Controller Using a Multilayer Fuzzy Neural Network Design for Quadcopter Attitude Tracking Control.

Front Neurorobot 2020 18;14:619350. Epub 2021 Jan 18.

Faculty of Mechanical and Aerospace, Sejong University, Seoul, South Korea.

This study presents an online tuning proportional-integral-derivative (PID) controller using a multilayer fuzzy neural network design for quadcopter attitude control. PID controllers are simple but effective control methods. However, finding the suitable gain of a model-based controller is relatively complicated and time-consuming because it depends on external disturbances and the dynamic modeling of plants. Therefore, the development of a method for online tuning of quadcopter PID parameters may save time and effort, and better control performance can be achieved. In our controller design, a multilayer structure was provided to improve the learning ability and flexibility of a fuzzy neural network. Adaptation laws to update network parameters online were derived using the gradient descent method. Also, a Lyapunov analysis was provided to guarantee system stability. Finally, simulations concerning quadcopter attitude control were performed using a Gazebo robotics simulator in addition to a robot operating system (ROS), and their results were demonstrated.
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http://dx.doi.org/10.3389/fnbot.2020.619350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847850PMC
January 2021

Using Reduction Kinetics to Control and Predict the Outcome of a Colloidal Synthesis of Noble-Metal Nanocrystals.

Inorg Chem 2021 Feb 1. Epub 2021 Feb 1.

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.

Improving the performance of noble-metal nanocrystals in various applications critically depends on our ability to manipulate their synthesis in a rational, robust, and controllable fashion. Different from a conventional trial-and-error approach, the reduction kinetics of a colloidal synthesis has recently been demonstrated as a reliable knob for controlling the synthesis of noble-metal nanocrystals in a deterministic and predictable manner. Here we present a brief Viewpoint on the recent progress in leveraging reduction kinetics for controlling and predicting the outcome of a synthesis of noble-metal nanocrystals. With a focus on Pd nanocrystals, we first offer a discussion on the correlation between the initial reduction rate and the internal structure of the resultant seeds. The kinetic approaches for controlling both nucleation and growth in a one-pot setting are then introduced with an emphasis on manipulation of the reduction pathways taken by the precursor. We then illustrate how to extend the strategy into a bimetallic system for the preparation of nanocrystals with different shapes and elemental distributions. Finally, the influence of speciation of the precursor on reduction kinetics is highlighted, followed by our perspectives on the challenges and future endeavors in achieving a controllable and predictable synthesis of noble-metal nanocrystals.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03576DOI Listing
February 2021

Colloidal Metal Nanocrystals with Metastable Crystal Structures.

Angew Chem Int Ed Engl 2021 Jan 21. Epub 2021 Jan 21.

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA.

In addition to the conventional knobs such as composition, size, shape, and defect structure, the crystal structure (or phase) of metal nanocrystals offers a new avenue for engineering their properties. Various strategies have recently been developed for the fabrication of colloidal metal nanocrystals in metastable phases different from their bulk counterparts. With a focus on noble metals, we begin with a brief introduction to their atomic packing, followed by a discussion about five major synthetic approaches to their colloidal nanocrystals in unconventional phases. We then highlight the success of synthesis in terms of mechanistic insights and experimental controls, as well as the enhanced catalytic properties. We end this Minireview with perspectives on the remaining issues and future opportunities.
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http://dx.doi.org/10.1002/anie.202017076DOI Listing
January 2021

Factors Associated With Early Extubation After Cardiac Surgery: A Retrospective Single-Center Experience.

J Cardiothorac Vasc Anesth 2020 Nov 28. Epub 2020 Nov 28.

Mazankowski Alberta Heart Institute, Edmonton, Canada; Division of Anesthesiology and Pain Medicine, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. Electronic address:

Objectives: To identify factors associated with early extubation in cardiac surgery patients.

Design: Single center, retrospective.

Setting: Tertiary university hospital.

Participants: The study comprised 8,872 adult patients who underwent cardiothoracic surgery from 2011-2019.

Interventions: None.

Measurements And Main Results: Of the 8,872 patients, 2,950 (33%) were extubated within six hours after surgery. Early extubated patients were younger, had a higher body mass index (BMI), were more likely to be male, and were fast-track designated. These patients more frequently underwent isolated coronary artery bypass graft, isolated valve, or adult congenital surgeries than did late extubated patients. Early extubated patients had a greater incidence of coronary artery disease (CAD) and anxiety and a higher left ventricular ejection fraction. They also were less likely to have difficult intubation or require mechanical circulatory support, reintubation, or readmission. Analysis of the 8,872 patients showed that male sex (odds ratio [OR] 1.222, 95% confidence interval [CI] 1.096-1.363), a BMI >30 kg/m (OR 1.702, 95% CI 1.475-1.965), undergoing isolated valve surgery (OR 1.187, 95% CI 1.060-1.328), and having a fast-track designation (OR 1.455, 95% CI 1.208-1.751) and CAD (OR 1.122, 95% CI 1.005-1.253) were associated with early extubation. Data on intensive care unit (ICU) admission after surgery were available only from 2014-2018. Within this subgroup of 5,977 patients, variables associated with early extubation included male sex (OR 1.356, 95% CI 1.193-1.541), BMI >30 kg/m (OR 1.267, 95% CI 1.084-1.480), daytime admission to the ICU (OR 1.712, 95% CI 1.527-1.919), and fast-track designation (OR 1.423, 95% CI 1.123-1.802).

Conclusions: Male sex; a BMI >30 kg/m; undergoing isolated valve surgery; and having a fast-track designation, CAD, and daytime admission to the ICU are associated with early extubation.
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http://dx.doi.org/10.1053/j.jvca.2020.11.051DOI Listing
November 2020

Diagnostic Practices and Treatment for in the InterEthnic Therapeutic Encounter of South-Central Vietnam: A Mixed-Methods Study.

Pathogens 2020 Dec 31;10(1). Epub 2020 Dec 31.

Medical Anthropology Unit, Department of Public Health, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium.

Malaria elimination in the Greater Mekong Sub-Region is challenged by a rising proportion of malaria attributable to Primaquine (PQ) is effective in eliminating the parasite's dormant liver stages and can prevent relapsing infections, but it induces severe haemolysis in patients with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency, highlighting the importance of testing enzyme activity prior to treatment. A mixed-method study was conducted in south-central Vietnam to explore the factors that affect acceptability of G6PD testing, treatment-seeking behaviors, and adherence to current regimens. The majority of respondents (75.7%) were unaware of the different parasite species and rather differentiated malaria by perceived severity. People sought a diagnosis if suspected of malaria fever but not if they perceived their fevers as mild. Most respondents agreed to take prescribed medication to treat asymptomatic infection (94.1%) and to continue medication even if they felt better (91.5%). Health professionals did not have G6PD diagnostic tools nor the means to prescribe PQ safely. Adherence to treatment was linked to trust in public providers, who were perceived to make therapeutic decisions in the interest of the patient. Greater focus on providing acceptable ways of assessing G6PD deficiency will be needed to ensure the timely elimination of malaria in Vietnam.
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http://dx.doi.org/10.3390/pathogens10010026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824694PMC
December 2020

No time for change? Impact of contextual factors on the effect of training primary care healthcare workers in Kyrgyzstan and Vietnam on how to manage asthma in children - A FRESH AIR implementation study.

BMC Health Serv Res 2020 Dec 10;20(1):1137. Epub 2020 Dec 10.

Global Health Unit, Department of Paediatrics and Adolescent Medicine, Juliane Marie Center, Copenhagen University Hospital "Rigshospitalet", Copenhagen, Denmark.

Background: Training is a common and cost-effective way of trying to improve quality of care in low- and middle-income countries but studies of contextual factors for the successful translation of increased knowledge into clinical change are lacking, especially in primary care. The purpose of this study was to assess the impact of contextual factors on the effect of training rural healthcare workers in Kyrgyzstan and Vietnam on their knowledge and clinical performance in managing pediatric patients with respiratory symptoms.

Methods: Primary care health workers in Kyrgyzstan and Vietnam underwent a one-day training session on asthma in children under five. The effect of training was measured on knowledge and clinical performance using a validated questionnaire, and by direct clinical observations.

Results: Eighty-one healthcare workers participated in the training. Their knowledge increased by 1.1 Cohen's d (CI: 0.7 to 1.4) in Kyrgyzstan where baseline performance was lower and 1.5 Cohen's d (CI: 0.5 to 2.5) in Vietnam. Consultations were performed by different types of health care workers in Kyrgyzstan and there was a 79.1% (CI 73.9 to 84.3%) increase in consultations where at least one core symptom of respiratory illness was asked. Only medical doctors participated in Vietnam, where the increase was 25.0% (CI 15.1 to 34.9%). Clinical examination improved significantly after training in Kyrgyzstan. In Vietnam, the number of actions performed generally declined. The most pronounced difference in contextual factors was consultation time, which was median 15 min in Kyrgyzstan and 2 min in Vietnam.

Discussion And Conclusion: The effects on knowledge of training primary care health workers in lower middle-income countries in diagnosis and management of asthma in children under five only translated into changes in clinical performance where consultation time allowed for changes to clinical practice, emphasizing the importance of considering contextual factors in order to succeed in behavioral change after training.
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http://dx.doi.org/10.1186/s12913-020-05984-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730734PMC
December 2020

Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults.

Sci Rep 2020 12 3;10(1):21154. Epub 2020 Dec 3.

Institute of Chemistry, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.

Obesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R = 0.1384, P = 0.01) and diastolic BP (R = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R = 0.1232, P = 0.02) and partially correlated to urine protein (R = 0.047, P = 0.12) and FBG (R = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.
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http://dx.doi.org/10.1038/s41598-020-78382-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713175PMC
December 2020

Protective Effect of Shikimic Acid against Cisplatin-Induced Renal Injury: In Vitro and In Vivo Studies.

Plants (Basel) 2020 Dec 1;9(12). Epub 2020 Dec 1.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of extract and its mechanism of action against cisplatin-induced renal injury.
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http://dx.doi.org/10.3390/plants9121681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759863PMC
December 2020

Quantized thermoelectric Hall effect induces giant power factor in a topological semimetal.

Nat Commun 2020 Dec 2;11(1):6167. Epub 2020 Dec 2.

Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Thermoelectrics are promising by directly generating electricity from waste heat. However, (sub-)room-temperature thermoelectrics have been a long-standing challenge due to vanishing electronic entropy at low temperatures. Topological materials offer a new avenue for energy harvesting applications. Recent theories predicted that topological semimetals at the quantum limit can lead to a large, non-saturating thermopower and a quantized thermoelectric Hall conductivity approaching a universal value. Here, we experimentally demonstrate the non-saturating thermopower and quantized thermoelectric Hall effect in the topological Weyl semimetal (WSM) tantalum phosphide (TaP). An ultrahigh longitudinal thermopower [Formula: see text] and giant power factor [Formula: see text] are observed at ~40 K, which is largely attributed to the quantized thermoelectric Hall effect. Our work highlights the unique quantized thermoelectric Hall effect realized in a WSM toward low-temperature energy harvesting applications.
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http://dx.doi.org/10.1038/s41467-020-19850-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710760PMC
December 2020

Genotype-Phenotype Correlations in Duchenne and Becker Muscular Dystrophy Patients from the Canadian Neuromuscular Disease Registry.

J Pers Med 2020 Nov 23;10(4). Epub 2020 Nov 23.

Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada.

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder generally caused by out-of-frame mutations in the gene. In contrast, in-frame mutations usually give rise to the milder Becker muscular dystrophy (BMD). However, this reading frame rule does not always hold true. Therefore, an understanding of the relationships between genotype and phenotype is important for informing diagnosis and disease management, as well as the development of genetic therapies. Here, we evaluated genotype-phenotype correlations in DMD and BMD patients enrolled in the Canadian Neuromuscular Disease Registry from 2012 to 2019. Data from 342 DMD and 60 BMD patients with genetic test results were analyzed. The majority of patients had deletions (71%), followed by small mutations (17%) and duplications (10%); 2% had negative results. Two deletion hotspots were identified, exons 3-20 and exons 45-55, harboring 86% of deletions. Exceptions to the reading frame rule were found in 13% of patients with deletions. Surprisingly, C-terminal domain mutations were associated with decreased wheelchair use and increased forced vital capacity. Dp116 and Dp71 mutations were also linked with decreased wheelchair use, while Dp140 mutations significantly predicted cardiomyopathy. Finally, we found that 12.3% and 7% of DMD patients in the registry could be treated with FDA-approved exon 51- and 53-skipping therapies, respectively.
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http://dx.doi.org/10.3390/jpm10040241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712074PMC
November 2020

Coadaptation of the chemosensory system with voluntary exercise behavior in mice.

PLoS One 2020 25;15(11):e0241758. Epub 2020 Nov 25.

Neuroscience Graduate Program, University of California Riverside, Riverside, California, United States of America.

Ethologically relevant chemical senses and behavioral habits are likely to coadapt in response to selection. As olfaction is involved in intrinsically motivated behaviors in mice, we hypothesized that selective breeding for a voluntary behavior would enable us to identify novel roles of the chemosensory system. Voluntary wheel running (VWR) is an intrinsically motivated and naturally rewarding behavior, and even wild mice run on a wheel placed in nature. We have established 4 independent, artificially evolved mouse lines by selectively breeding individuals showing high VWR activity (High Runners; HRs), together with 4 non-selected Control lines, over 88 generations. We found that several sensory receptors in specific receptor clusters were differentially expressed between the vomeronasal organ (VNO) of HRs and Controls. Moreover, one of those clusters contains multiple single-nucleotide polymorphism loci for which the allele frequencies were significantly divergent between the HR and Control lines, i.e., loci that were affected by the selective breeding protocol. These results indicate that the VNO has become genetically differentiated between HR and Control lines during the selective breeding process. Although the role of the vomeronasal chemosensory receptors in VWR activity remains to be determined, the current results suggest that these vomeronasal chemosensory receptors are important quantitative trait loci for voluntary exercise in mice. We propose that olfaction may play an important role in motivation for voluntary exercise in mammals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241758PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688120PMC
December 2020

Leveraging 31 Million Google Street View Images to Characterize Built Environments and Examine County Health Outcomes.

Public Health Rep 2021 Mar-Apr;136(2):201-211. Epub 2020 Nov 19.

14434 Department of Electrical and Computer Engineering, Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA.

Objectives: Built environments can affect health, but data in many geographic areas are limited. We used a big data source to create national indicators of neighborhood quality and assess their associations with health.

Methods: We leveraged computer vision and Google Street View images accessed from December 15, 2017, through July 17, 2018, to detect features of the built environment (presence of a crosswalk, non-single-family home, single-lane roads, and visible utility wires) for 2916 US counties. We used multivariate linear regression models to determine associations between features of the built environment and county-level health outcomes (prevalence of adult obesity, prevalence of diabetes, physical inactivity, frequent physical and mental distress, poor or fair self-rated health, and premature death [in years of potential life lost]).

Results: Compared with counties with the least number of crosswalks, counties with the most crosswalks were associated with decreases of 1.3%, 2.7%, and 1.3% of adult obesity, physical inactivity, and fair or poor self-rated health, respectively, and 477 fewer years of potential life lost before age 75 (per 100 000 population). The presence of non-single-family homes was associated with lower levels of all health outcomes except for premature death. The presence of single-lane roads was associated with an increase in physical inactivity, frequent physical distress, and fair or poor self-rated health. Visible utility wires were associated with increases in adult obesity, diabetes, physical and mental distress, and fair or poor self-rated health.

Conclusions: The use of computer vision and big data image sources makes possible national studies of the built environment's effects on health, producing data and results that may inform national and local decision-making.
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http://dx.doi.org/10.1177/0033354920968799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093841PMC
November 2020

Anxiety and Depression Among People Under the Nationwide Partial Lockdown in Vietnam.

Front Public Health 2020 29;8:589359. Epub 2020 Oct 29.

Department of Psychological Medicine, National University Hospital, Singapore, Singapore.

This study aimed to evaluate the psychological effects of the partial lockdown on the people in Vietnam during the COVID-19 pandemic. An online questionnaire regarding attitudes toward COVID-19 along with psychological parameters, including the Impact of Event Scale-Revised (IES-R) Depression, Anxiety, Stress Scale-21 (DASS-21) was conducted. From a total of 1,382 questionnaires, the respondents reported low prevalence of depression (4.9%), anxiety (7.0%), and stress (3.4%). The mean DASS-21 scores recorded were also markedly lower compared to similar studies conducted in China, Italy, and Iran. Respondents who reported severe PTSD had significantly higher depression, anxiety, and stress levels. Factors that were associated with an increased level of depression, stress, and anxiety were being single, separated, or widowed, a higher education level, a larger family size, loss of jobs and being in contact with potential COVID-19 patients. Contrary to expectations, the level of depression, stress, and anxiety observed has been low. Our findings can aid in future research on the impact of a partial lockdown and guide mental health professionals in Vietnam and other countries in the preparation of better care for populations under such circumstances.
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http://dx.doi.org/10.3389/fpubh.2020.589359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658379PMC
May 2021

Perceptions and Attitudes Toward COVID-19-Related National Response Measures of Vietnamese: Implications for Pandemic Prevention and Control.

Front Public Health 2020 9;8:589053. Epub 2020 Oct 9.

Department of Psychological Medicine, National University Hospital, Singapore, Singapore.

Public perceptions and attitudes toward preventive and control measures are vital to ensure the success of national response strategies in combating COVID-19. This study assessed perceptions and attitudes via the importance of national response measures to COVID-19 among people under the nationwide partial lockdown of Vietnam. An online cross-sectional survey was conducted on 1382 people in Vietnam mainly public administration and health workers with relatives. Perceptions and attitudes toward seven national response measures to COVID-19 epidemics were assessed. Multivariable Tobit regression models were employed to identify factors associated with the perceptions. The proportion of participants strongly agreeing with the measure "Isolate people from abroad and people in contact with people infected with COVID 19" was the highest (96.9%), following by the measure "Obligatory to wear face masks in public places" (96.8%), and "Blockade of places having new cases" (92.9%). Living in the Southern region, having a family with more than 5 people, and having post-graduate education were negatively correlated to the levels of perceived importance of "Social distancing and community screening" measures. Meanwhile, having post-graduate education (Coef. = -0.04; 95%CI: -0.07; -0.01), working as white-collar workers (Coef. = -0.04; 95%CI: -0.08; -0.01), and having fixed-term, full-time employment (Coef. = -0.07; 95%CI: -0.10; -0.03) were inversely associated with the levels of perceived importance of the "Mandatory quarantine and personal protective equipment" measures. This study informed highly positive perceptions and attitudes toward the national response measure to combat the COVID-19 in Vietnam. Contextualized strategies to maintain and improve these perceptions are warranted to ensure the success of preventive measures in the future.
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http://dx.doi.org/10.3389/fpubh.2020.589053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581721PMC
May 2021