Publications by authors named "Xiang Gao"

1,928 Publications

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Nomograms for predicting cancer-specific and overall survival in patients with invasive extramammary Paget's disease.

Future Oncol 2021 May 14. Epub 2021 May 14.

Department of Gastrointestinal Surgery, West China Hospital, West China School of Medicine, Sichuan University, & Institute of Digestive Surgery, Sichuan University, Chengdu, 610041, PR China.

To develop nomograms for predicting cancer-specific survival (CSS) and overall survival (OS) in patients with invasive extramammary Paget's disease (iEMPD). Retrospective data of 1955 patients with iEMPD were collected from the Surveillance, Epidemiology, and End Results database. Nomograms for predicting CSS and OS were established using competing risk regression and Cox regression, respectively, and were internally validated. Five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) clinicopathological factors were utilized to construct nomograms for predicting CSS and OS, respectively. The concordance indices of the nomograms for predicting CSS and OS were 0.78 and 0.73, respectively. The validation of the nomograms showed good calibration and discrimination. The decision curve analyses confirmed the clinical utility of these nomograms. The nomograms can be a reliable tool for treatment design and prognostic evaluation of iEMPD.
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http://dx.doi.org/10.2217/fon-2021-0372DOI Listing
May 2021

gene polymorphisms are associated with the S100B level and Alzheimer's disease risk by altering the miRNA binding capacity.

Aging (Albany NY) 2021 May 12;13. Epub 2021 May 12.

Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou, China.

To examine the role of in genetic susceptibility to Alzheimer's disease (AD), we conducted a case-control study to analyze four polymorphism loci (rs2839364, rs1051169, rs2300403, and rs9722) of the gene and AD risk. We found an independent increased risk of AD in ε4(-) subjects carrying the rs9722 AA-genotype (OR = 2.622, 95% CI = 1.399-4.915, = 0.003). Further investigation revealed the serum S100B levels to be lower in rs9722 GG carriers than in rs9722 AA carriers ( = 0.003). We identified three miRNAs (miR-340-3p, miR-593-3p, miR-6827-3p) in which the seed match region covered locus rs9722. Luciferase assays indicated that the rs9722 G allele has a higher binding affinity to miR-6827-3p than the rs9722 A allele, leading to a significantly decreased fluorescence intensity. Subsequent western blot analysis showed that the S100B protein level of SH-SY5Y cells, which carry the rs9722 G allele, decreased significantly following miR-6827-3p stimulation ( = 0.009). The present study suggests that the rs9722 polymorphism may upregulate the expression of by altering the miRNA binding capacity and may thus increase the AD risk. This finding would be of great help for the early diagnosis of AD.
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http://dx.doi.org/10.18632/aging.203005DOI Listing
May 2021

The prediction of survival in Gastric Cancer based on a Robust 13-Gene Signature.

J Cancer 2021 12;12(11):3344-3353. Epub 2021 Apr 12.

Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Gastric cancer represents a major public health problem. Owing to the great heterogeneity of GC, conventional clinical characteristics are limited in the accurate prediction of individual outcomes and survival. This study aimed to establish a robust gene signature to predict the prognosis of GC based on multiple datasets. Initially, we downloaded raw data from four independent datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and performed univariate Cox proportional hazards regression analysis to identify prognostic genes associated with overall survival (OS) from each dataset. Thirteen common genes from four datasets were screened as candidate prognostic signatures. Then, a risk score model was developed based on this 13‑gene signature and validated by four independent datasets and the entire cohort. Patients with a high-risk score had poorer OS and recurrence-free survival (RFS). Multivariate regression and stratified analysis revealed that the 13-gene signature was not only an independent predictive factor but also associated with recurrence when adjusting for other clinical factors. Furthermore, in the high-risk group, gene set enrichment analysis (GSEA) showed that the mTOR signaling pathway and MAPK signaling pathway were significantly enriched. The present study provided a robust and reliable gene signature for prognostic prediction of both OS and RFS of patients with GC, which may be useful for delivering individualized management of patients.
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http://dx.doi.org/10.7150/jca.49658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100809PMC
April 2021

EphA4 is highly expressed in the atria of heart and its deletion leads to atrial hypertrophy and electrocardiographic abnormalities in rats.

Life Sci 2021 May 8;278:119595. Epub 2021 May 8.

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing 100021, China. Electronic address:

Aims: EphA4 is a member of the Eph receptor family, and expressed mainly in central nervous system (CNS), which is involved in CNS development and multiple diseases. Due to the variability in EphA4 expression, we wondered if EphA4 is expressed in other tissues, and what role does EphA4 play?

Materials And Methods: We generated an EphA4 knockout (KO) rat line with red fluorescent marker protein encoded by the mCherry cassette inserted downstream of the EphA4 promoter as a reporter. Using this system, we observed high expression of EphA4 in the heart atria and in the brain.

Key Findings: EphaA4 KO rats (EphA4) developed obvious atrial hypertrophy with an increased atria-to-heart weight ratio and atrial cardiomyocyte cross-sectional area at six months of age. EphA4 rats had reduced atrial end diastolic volume (EDV), atrial ejection fraction (EF) and left ventricular EF. They also exhibited increased amplitude of QRS complexes and QT intervals, with invisible p waves. RNA sequencing revealed that EphA4 KO altered the transcription of multiple genes involved in regulation of transcription and translation, ion binding, metabolism and cell adhesion. Deletion of EphA4 reduced IGF1 mRNA and protein expression, which is involved in cardiac remodeling.

Significance: Our data demonstrated that EphA4 was highly expressed in the atria and its deletion caused atrial dysfunction. Our findings also suggested that the EphA4 KO rat could be a potential model for studies on atrial remodeling.
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http://dx.doi.org/10.1016/j.lfs.2021.119595DOI Listing
May 2021

Taste Masking Study Based on an Electronic Tongue: the Formulation Design of 3D Printed Levetiracetam Instant-Dissolving Tablets.

Pharm Res 2021 May 11. Epub 2021 May 11.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Haidian District, Beijing, 100850, China.

Purpose: Proper taste-masking formulation design is a critical issue for instant-dissolving tablets (IDTs). The purpose of this study is to use the electronic tongue to design the additives of the 3D printed IDTs to improve palatability.

Methods: A binder jet 3D printer was used to prepare IDTs of levetiracetam. A texture analyzer and dissolution apparatus were used to predict the oral dispersion time and in vitro drug release of IDTs, respectively. The palatability of different formulations was investigated using the ASTREE electronic tongue in combination with the design of experiment and a model for masking bitter taste. Human gustatory sensation tests were conducted to further evaluate the credibility of the results.

Results: The 3D printed tablets exhibited rapid dispersion (<30 s) and drug release (2.5 min > 90%). The electronic tongue had an excellent ability of taste discrimination, and levetiracetam had a good linear sensing performance based on a partial least square regression analysis. The principal component analysis was used to analyze the signal intensities of different formulations and showed that 2% sucralose and 0.5% spearmint flavoring masked the bitterness well and resembled the taste of corresponding placebo. The results of human gustatory sensation test were consistent with the trend of the electronic tongue evaluation.

Conclusions: Owing to its objectivity and reproducibility, this technique is suitable for the design and evaluation of palatability in 3D printed IDT development.
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http://dx.doi.org/10.1007/s11095-021-03041-9DOI Listing
May 2021

Single-Nucleus Transcriptomic Analysis Reveals Important Cell Cross-Talk in Diabetic Kidney Disease.

Front Med (Lausanne) 2021 21;8:657956. Epub 2021 Apr 21.

Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Diabetic kidney disease (DKD) leads to the loss of renal function and cell cross-talk is one of the crucial mechanisms participating in the pathogenesis of DKD. However, the mechanisms of cell communication were not fully elucidated in previous studies. In this study, we performed cell cross-talk analysis using CellPhoneDB based on a single-nucleus transcriptomic dataset (GSE131882) and revealed the associations between cell communication-related genes and renal function, providing overall insight into cell communication in DKD. In addition, this study may facilitate the discovery of novel mechanisms, promising biomarkers, and therapeutic targets that are clinically beneficial to patients.
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http://dx.doi.org/10.3389/fmed.2021.657956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097156PMC
April 2021

[Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):173-179

Department of General Surgery,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ =4.787,P=0.029).However,multivariate analysis failed to demonstrate overexpression of Cripto-1 an independent prognostic indicator in patients with pancreatic cancer(HR=1.341,95% CI=0.800-2.248,P=0.266).Conclusions Cripto-1 may play an important role in the development and progression of pancreatic cancer.It can be a potential prognostic biomarker for patients with pancreatic cancer.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12734DOI Listing
April 2021

Riding with an impaired driver and driving while impaired among adolescents: Longitudinal trajectories and their characteristics.

Traffic Inj Prev 2021 May 7:1-10. Epub 2021 May 7.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, Bethesda, Maryland.

Purpose: The purpose of this study was to identify and characterize trajectory classes of adolescents who ride with an impaired driver (RWI) and drive while impaired (DWI).

Methods: We analyzed all 7 annual assessments (Waves W1-W7) of the NEXT Generation Health Study, a nationally representative longitudinal study starting with 10th grade (2009-2010 school year). Using all 7 waves, latent class analysis was used to identify trajectory classes with dichotomized RWI (last 12 months) and DWI (last 30 days; once or more = 1 vs. none = 0). Covariates were race/ethnicity, sex, parent education, urbanicity, and family affluence.

Results: Four RWI trajectories and 4 DWI trajectories were identified: abstainer, escalator, decliner, and persister. For RWI and DWI trajectories respectively, 45.0% ( = 647) and 76.2% ( = 1,657) were abstainers, 15.6% ( = 226) and 14.2% ( = 337) were escalators, 25.0% ( = 352) and 5.4% ( = 99) were decliners, and 14.4% ( = 197) and 3.8% ( = 83) persisters. Race/ethnicity (χ = 23.93, = .004) was significantly associated with the RWI trajectory classes. Race/ethnicity (χ = 20.55, = .02), sex (χ = 13.89, = .003), parent highest education (χ = 12.49, = .05), urbanicity (χ = 9.66, = .02), and family affluence (χ = 12.88, = .05) were significantly associated with DWI trajectory classes.

Conclusions: Among adolescents transitioning into emerging adulthood, race/ethnicity is a common factor associated with RWI and DWI longitudinal trajectories. Our results suggest that adolescent RWI and DWI are complex behaviors warranting further detailed investigation of the respective trajectory classes. Our study findings can inform the tailoring of prevention and intervention efforts aimed at preventing illness/injury and preserving future opportunities for adolescents to thrive in emerging adulthood.
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http://dx.doi.org/10.1080/15389588.2021.1910244DOI Listing
May 2021

Reinforcement Learning Control of Robotic Knee With Human-in-the-Loop by Flexible Policy Iteration.

IEEE Trans Neural Netw Learn Syst 2021 May 6;PP. Epub 2021 May 6.

We are motivated by the real challenges presented in a human-robot system to develop new designs that are efficient at data level and with performance guarantees, such as stability and optimality at system level. Existing approximate/adaptive dynamic programming (ADP) results that consider system performance theoretically are not readily providing practically useful learning control algorithms for this problem, and reinforcement learning (RL) algorithms that address the issue of data efficiency usually do not have performance guarantees for the controlled system. This study fills these important voids by introducing innovative features to the policy iteration algorithm. We introduce flexible policy iteration (FPI), which can flexibly and organically integrate experience replay and supplemental values from prior experience into the RL controller. We show system-level performances, including convergence of the approximate value function, (sub)optimality of the solution, and stability of the system. We demonstrate the effectiveness of the FPI via realistic simulations of the human-robot system. It is noted that the problem we face in this study may be difficult to address by design methods based on classical control theory as it is nearly impossible to obtain a customized mathematical model of a human-robot system either online or offline. The results we have obtained also indicate the great potential of RL control to solving realistic and challenging problems with high-dimensional control inputs.
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http://dx.doi.org/10.1109/TNNLS.2021.3071727DOI Listing
May 2021

TCEB3 is Regulated by Circ-0000212/miR-140-3p Axis to Promote the Progression of Cervical Cancer.

Onco Targets Ther 2021 28;14:2853-2865. Epub 2021 Apr 28.

Department of Geratology, The First Affiliated Hospital of Weifang Medical University (Weifang People's Hospital), Weifang, Shandong, 261041, People's Republic of China.

Background: Cervical cancer is a common female malignancy, which accounts for a large proportion of cancer-related mortality in the world. Therefore, exploring the mechanisms of cervical cancer progression and seeking new therapeutic targets are extraordinarily needful. The aim of this study was to explore the role of TCEB3 in cervical cancer progression.

Methods: TCEB3 expression was detected in cervical cancer tissue and adjacent normal tissues using qRT-PCR and immunohistochemistry analysis. TCEB3 expression was measured in cells using Western blot and qRT-PCR assay. Flow cytometer, CCK-8, colony formation and transwell assays were used to detect cell apoptosis, viability, colony-forming ability and invasion of cervical cancer cells. The expression of Ki-67, MMP-2, and MMP-9 was detected using Western blot. Bioinformatics analysis was used to predict circRNA-miRNA and miRNA-mRNA interactions. RIP and luciferase reporter assay were used to determine the interaction relationship.

Results: TCEB3 expression was up-regulated in both cervical cancer tissues and cells. Silencing of TCEB3 inhibited cell proliferation and invasion and promoted apoptosis of cervical cancer cells. Additionally, silencing of TCEB3 reduced the protein expression of Ki-67, MMP-2, and MMP-9 of cervical cancer cells. Mechanistically, we identified that TCEB3 was directly targeted gene of miR-140-3p, and circ-0000212 acted as a sponge of miR-140-3p. Moreover, TCEB3 was regulated by circ-0000212/miR-140-3p axis and played a tumor promotive role in cervical cancer.

Conclusion: Silencing of TCEB3 attenuated cell proliferation and invasion and promoted apoptosis of cervical cancer cells, and this effect was regulated by circ-0000212/miR-140-3p axis. Our findings may provide a novel promising target for cervical cancer treatment.
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http://dx.doi.org/10.2147/OTT.S278710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091597PMC
April 2021

ANO7: Insights into topology, function, and potential applications as a biomarker and immunotherapy target.

Tissue Cell 2021 Apr 18;72:101546. Epub 2021 Apr 18.

College of Laboratory Medicine, Jilin Medical University, Jilin, 132013, China. Electronic address:

Anoctamin 7 (ANO7) is a member of the transmembrane protein TMEM16 family. It has a conservative topology similar to other members in this family, such as the typical eight-transmembrane domain, but it also has unique features. Although the ion channel role of ANO7 has been well accepted, evolutionary analyses and relevant studies suggest that ANO7 may be a multi-facet protein in function. Studies have shown that ANO7 may also function as a scramblase. ANO7 is highly expressed in prostate cancer as well as normal prostate tissues. A considerable amount of evidence has confirmed that ANO7 is associated with human physiology and pathology, particularly with the development of prostate cancer, which makes ANO7 a good candidate as a diagnostic and prognostic biomarker. In addition, ANO7 may be a potential target for prostate cancer immunotherapy. Antibody-based or T cell-mediated immunotherapies against prostate cancer by targeting ANO7 have been highly anticipated. ANO7 may also correlate with several other types of cancers or diseases, where further studies are warranted.
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http://dx.doi.org/10.1016/j.tice.2021.101546DOI Listing
April 2021

Non-Motor Features of Parkinson's Disease in Women.

J Parkinsons Dis 2021 Apr 28. Epub 2021 Apr 28.

Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.

Background: Non-motor symptoms are common in Parkinson's disease (PD) and some, including hyposmia, constipation, and REM sleep behavior disorder, often precede the clinical diagnosis.

Objective: To assess the relation between combinations of non-motor features and presence of PD among women.

Methods: A nested case-control study was conducted among women in the Nurses' Health Study. Women were eligible if they responded to screening questions for constipation and probable REM sleep behavior disorder (pRBD) on a 2012 questionnaire and were under age 85 on January 1, 2012. 87 women with confirmed PD and 14,170 women without PD agreed to participate and completed in 2015 the Brief Smell Identification Test to assess hyposmia, as well as a questionnaire to assess parkinsonism and other non-motor PD features, including depressive symptoms, excessive daytime sleepiness, impaired color vision, and body pain.

Results: In age-adjusted logistic models, each non-motor feature was significantly associated with PD, and the odds of PD increased exponentially with the number of features. Women with constipation, pRBD, and hyposmia had an age-adjusted OR for PD of 211 (95%CI 84.2-529) compared to women with none of these features. The odds of having PD rose further with the presence of additional non-motor signs. Comparing women with at least 6 of the 7 features assessed in this study to women with one or none, the age-adjusted OR for PD was 356 (95%CI 113-1126).

Conclusion: Results suggest that these non-motor features could be useful in discriminating PD patients from controls in women, and since they often appear during the prodromal period of PD, their combinations may prove useful for identifying populations at high risk of developing PD.
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http://dx.doi.org/10.3233/JPD-202409DOI Listing
April 2021

Restless legs syndrome and perceived olfactory and taste dysfunction: a community-based study.

Eur J Neurol 2021 May 1. Epub 2021 May 1.

Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.

Background: Restless legs syndrome (RLS) was suggested as a prodromal symptom of Parkinson's disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction.

Methods: We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history.

Results: RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio =5.92; 95% confidence interval, 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio =5.55; 95% confidence interval, 2.37-13.0) or when excluding participants with major chronic diseases.

Conclusion: RLS was associated with increased odds of perceived olfactory and taste dysfunction.
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http://dx.doi.org/10.1111/ene.14890DOI Listing
May 2021

Strain-Induced Atomic-Scale Building Blocks for Ferromagnetism in Epitaxial LaCoO.

Nano Lett 2021 May 30;21(9):4006-4012. Epub 2021 Apr 30.

Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.

The origin of strain-induced ferromagnetism, which is robust regardless of the type and degree of strain in LaCoO (LCO) thin films, is enigmatic despite intensive research efforts over the past decade. Here, by combining scanning transmission electron microscopy with density functional theory calculations, we report that the ferromagnetism does not emerge directly from the strain itself but rather from the creation of compressed structural units within ferroelastically formed twin-wall domains. The compressed structural units are magnetically active with the rocksalt-type high-spin/low-spin order. Our study highlights that the ferroelastic nature of ferromagnetic structural units is important for understanding the intriguing ferromagnetic properties in LCO thin films.
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http://dx.doi.org/10.1021/acs.nanolett.1c00756DOI Listing
May 2021

Identification and Amino Acid Analysis of Allergenic Epitopes of a Novel Allergen Paramyosin (Rap v 2) from .

J Agric Food Chem 2021 May 30;69(18):5381-5391. Epub 2021 Apr 30.

College of Food Science and Engineering, Ocean University of China, No. 5, Yushan Road, Qingdao, Shandong Province 266003, P.R. China.

Besides tropomyosin (TM) that is widely recognized as a major allergen in molluscs, a 99-kDa novel allergen (Rap v 2) was recently found in the sea snail and identified as paramyosin (PM). However, the allergenic epitopes of PM in any molluscs have not been identified yet. In the present study, seven allergenic epitopes of Rap v 2 were identified by immunoinformatics tools, dot-blot inhibition assay, and basophil degranulation assay. Based on the analysis of PM and allergenic epitope amino acids, it was found that highly hydrophobic and positively charged amino acid residues play an important role in the formation of Rap v 2 epitopes. In addition, three potential critical amino acids that may account for TM and PM cross-reactivity in molluscs were found by sequence- and structure-based methods. These findings could be of major importance for improving the understanding of relevant paramyosin epitopes and the prevention and therapy of mollusc allergy.
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http://dx.doi.org/10.1021/acs.jafc.1c00775DOI Listing
May 2021

Insights into the Li Diffusion Mechanism in Si/C Composite Anodes for Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2021 May 30;13(18):21362-21370. Epub 2021 Apr 30.

Department of Mechanical Engineering and Engineering Science, The University of North Carolina at Charlotte, Charlotte, North Carolina 28223, United States.

Recently, Si/C composite materials have attracted enormous research interest as the most promising candidates for the anodes of next-generation lithium-ion batteries, owing to their high energy density and mechanical buffering property. However, the fundamental mechanism of Li diffusion behavior in various Si/C composite materials remains unclear, with our understanding limited by experimental techniques and continuum modeling methodologies. Herein, the atomic behavior of Li diffusion in the Si/C composite material is studied within the framework of density functional theory. Two representative structural mixing formats, that is, simple mixture mode and core-shell mode, are modeled and compared. We discover that the carbon material increases Li diffusion in silicon from 7.75 × 10 to 2.097 × 10 cm/s. The boost is about 50% more obvious in the mixture mode, while the core-shell structure shows more dependence on the atomic structures of the carbon layer. These results offer new insights into Li diffusion behavior in Si/C composites and unlock the enhancing mechanism for Li diffusion in Si/C. This understanding facilitates the modeling of batteries with composite anodes and will guide the corresponding structure designs for robust and high-energy-density batteries.
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http://dx.doi.org/10.1021/acsami.1c03366DOI Listing
May 2021

Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients.

Pharmacol Res Perspect 2021 May;9(3):e00764

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.

Xanthine oxidase (XO) competes with thiopurine S-methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6-mercaptopurine (6-MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine-induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6-MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu-like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu-like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine-induced toxicity.
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http://dx.doi.org/10.1002/prp2.764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085934PMC
May 2021

The Association between Poor Diet Quality, Physical Fatigability and Physical Function in the Oldest-Old from the Geisinger Rural Aging Study.

Geriatrics (Basel) 2021 Apr 15;6(2). Epub 2021 Apr 15.

Department of Kinesiology, Louisiana State University, Baton Rouge, LA 70803, USA.

More perceived physical fatigability and poor diet quality are associated with impairments in physical function in older adults. However, the degree to which more perceived fatigability explains the association between poor diet quality and low physical function is unknown. We examined this relationship in 122 (66F, 56M) of the oldest-old participants from the Geisinger Rural Aging Study (GRAS). We used 24-h dietary recalls to assess the Healthy Eating Index (HEI), the Pittsburgh Fatigability Scale (PFS, 0-50) to assess perceived physical fatigability, and the PROMIS Physical Function 20a* to assess physical function. We grouped participants into three age categories: 80-84 ( = 51), 85-89 ( = 51), and 90+ ( = 20) years. Multiple linear regression revealed that a lower HEI was associated with higher PFS Physical score after adjusting for age group, sex, body mass index, and the number of medical conditions ( = 0.001). Several macro- and micro-nutrient intakes were also lower in those reporting more (≥15) compared to less (<15) perceived physical fatigability. Mediation analysis revealed that PFS Physical scores explained ~65% ( = 0.001) of the association between HEI total score and PROMIS19 Physical Function score. Poor diet quality may contribute to more perceived physical fatigability, which could exacerbate impairments in the oldest-old's physical function.
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http://dx.doi.org/10.3390/geriatrics6020041DOI Listing
April 2021

Are Essential Women's Healthcare Services Fully Covered? A Comparative Analysis of Policy Documents in Shanghai and New York City from 1978-2017.

Int J Environ Res Public Health 2021 Apr 17;18(8). Epub 2021 Apr 17.

Research Institute of Health Development Strategies, Fudan University, Shanghai 200032, China.

This study aimed to analyze the changes in the 10 major categories of women's healthcare services (WHSs) in Shanghai (SH) and New York City (NYC) from 1978 to 2017, and examine the relationship between these changes and maternal mortality ratio (MMR). Content analysis of available public policy documents concerning women's health was conducted. Two indicators were designed to represent the delivery of WHSs: The essential women's healthcare service coverage rate (ESCR) and the assessable essential healthcare service coverage rate (AESCR). Spearman correlation was used to analyze the relationship between the two indicators and MMR. In SH, the ESCR increased from 10% to 90%, AESCR increased from 0% to 90%, and MMR decreased from 24.0/100,000 to 1.01/100,000. In NYC, the ESCR increased from 0% to 80%, the AESCR increased from 0% to 60%, and the MMR decreased from 24.7/100,000 to 21.4/100,000. The MMR significantly decreased as both indicators increased ( < 0.01). Major advances have been made in women's healthcare in both cities, with SH having a better improvement effect. A common shortcoming for both was the lack of menopausal health service provision. The promotion of women's health still needs to receive continuous attention from governments of SH and NYC. The experiences of the two cities showed that placing WHSs among policy priorities is effective in improving service status.
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http://dx.doi.org/10.3390/ijerph18084261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072775PMC
April 2021

[Mirror-type rehabilitation training with dynamic adjustment and assistance for shoulder joint].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Apr;38(2):351-360

Institute of Robot Information Perception and Control, Nanjing University of Posts and Telecommunications, Nanjing 210023, P.R.China.

The real physical image of the affected limb, which is difficult to move in the traditional mirror training, can be realized easily by the rehabilitation robots. During this training, the affected limb is often in a passive state. However, with the gradual recovery of the movement ability, active mirror training becomes a better choice. Consequently, this paper took the self-developed shoulder joint rehabilitation robot with an adjustable structure as an experimental platform, and proposed a mirror training system completed by next four parts. First, the motion trajectory of the healthy limb was obtained by the Inertial Measurement Units (IMU). Then the variable universe fuzzy adaptive proportion differentiation (PD) control was adopted for inner loop, meanwhile, the muscle strength of the affected limb was estimated by the surface electromyography (sEMG). The compensation force for an assisted limb of outer loop was calculated. According to the experimental results, the control system can provide real-time assistance compensation according to the recovery of the affected limb, fully exert the training initiative of the affected limb, and make the affected limb achieve better rehabilitation training effect.
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http://dx.doi.org/10.7507/1001-5515.202001053DOI Listing
April 2021

Strain-driven autonomous control of cation distribution for artificial ferroelectrics.

Sci Adv 2021 Apr 28;7(18). Epub 2021 Apr 28.

Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.

In past few decades, there have been substantial advances in theoretical material design and experimental synthesis, which play a key role in the steep ascent of developing functional materials with unprecedented properties useful for next-generation technologies. However, the ultimate goal of synthesis science, i.e., how to locate atoms in a specific position of matter, has not been achieved. Here, we demonstrate a unique way to inject elements in a specific crystallographic position in a composite material by strain engineering. While the use of strain so far has been limited for only mechanical deformation of structures or creation of elemental defects, we show another powerful way of using strain to autonomously control the atomic position for the synthesis of new materials and structures. We believe that our synthesis methodology can be applied to wide ranges of systems, thereby providing a new route to functional materials.
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http://dx.doi.org/10.1126/sciadv.abd7394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081366PMC
April 2021

Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer.

Bioact Mater 2021 Nov 6;6(11):3678-3691. Epub 2021 Apr 6.

Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.

The immunosuppressive tumor microenvironment (TME) of cancer strongly hinders the anti-tumor immune responses, thereby resulting in disappointing responses to immunotherapy. Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME. In this study, a folic acid (FA) -modified gene delivery system based on the self-assembly of DOTAP, MPEG-PCL-MPEG, and FA-PEG-PCL-PEG-FA, namely F-PPPD, was developed to deliver plasmids encoding the immunostimulating chemokine CKb11. The delivery of plasmid CKb11 (pCKb11) by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells, which successfully activated T cells, suppressed the M2 polarization of macrophages, promoted the maturation of dendritic cells (DCs), facilitated the infiltration of natural killer (NK) cells and inhibited the infiltration of immunosuppressive cells in tumor tissues. Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression. Our study demonstrated a nanotechnology-enabled delivery of pCKb11, that remodeled the immunosuppressive TME, for cancer treatment.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056185PMC
November 2021

Correction to: Maternal and fetal outcomes of patients with liver cirrhosis: a case-control study.

BMC Pregnancy Childbirth 2021 Apr 24;21(1):325. Epub 2021 Apr 24.

Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Qihelou street No.17, Dongcheng District, Beijing, 100006, China.

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http://dx.doi.org/10.1186/s12884-021-03823-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070274PMC
April 2021

Association of mushroom consumption with all-cause and cause-specific mortality among American adults: prospective cohort study findings from NHANES III.

Nutr J 2021 04 22;20(1):38. Epub 2021 Apr 22.

Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.

Background: Whether mushroom consumption, which is rich in several bioactive compounds, including the crucial antioxidants ergothioneine and glutathione, is inversely associated with low all-cause and cause-specific mortality remains uncertain. This study aimed to prospectively investigate the association between mushroom consumption and all-cause and cause-specific mortality risk.

Methods: Longitudinal analyses of participants from the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988-1994). Mushroom intake was assessed by a single 24-h dietary recall using the US Department of Agriculture food codes for recipe foods. All-cause and cause-specific mortality were assessed in all participants linked to the National Death Index mortality data (1988-2015). We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cause-specific mortality.

Results: Among 15,546 participants included in the current analysis, the mean (SE) age was  44.3 (0.5) years. During a mean (SD) follow-up duration of 19.5 (7.4) years , a total of 5826 deaths were documented. Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73-0.98) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy. When cause-specific mortality was examined, we did not observe any statistically significant associations with mushroom consumption. Consuming 1-serving of mushrooms per day instead of 1-serving of processed or red meats was associated with lower risk of all-cause mortality (adjusted HR = 0.65; 95% CI: 0.50-0.84). We also observed a dose-response relationship between higher mushroom consumption and lower risk of all-cause mortality (P-trend = 0.03).

Conclusion: Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.
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http://dx.doi.org/10.1186/s12937-021-00691-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061446PMC
April 2021

Prospective assessment of breast cancer risk from multimodal multiview ultrasound images via clinically applicable deep learning.

Nat Biomed Eng 2021 Apr 19. Epub 2021 Apr 19.

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.

The clinical application of breast ultrasound for the assessment of cancer risk and of deep learning for the classification of breast-ultrasound images has been hindered by inter-grader variability and high false positive rates and by deep-learning models that do not follow Breast Imaging Reporting and Data System (BI-RADS) standards, lack explainability features and have not been tested prospectively. Here, we show that an explainable deep-learning system trained on 10,815 multimodal breast-ultrasound images of 721 biopsy-confirmed lesions from 634 patients across two hospitals and prospectively tested on 912 additional images of 152 lesions from 141 patients predicts BI-RADS scores for breast cancer as accurately as experienced radiologists, with areas under the receiver operating curve of 0.922 (95% confidence interval (CI) = 0.868-0.959) for bimodal images and 0.955 (95% CI = 0.909-0.982) for multimodal images. Multimodal multiview breast-ultrasound images augmented with heatmaps for malignancy risk predicted via deep learning may facilitate the adoption of ultrasound imaging in screening mammography workflows.
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http://dx.doi.org/10.1038/s41551-021-00711-2DOI Listing
April 2021

Acinar cell NLRP3 inflammasome and GSDMD activation mediates pyroptosis and systemic inflammation in acute pancreatitis.

Br J Pharmacol 2021 Apr 19. Epub 2021 Apr 19.

Center of Severe Acute Pancreatitis (CASP), Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background And Purpose: Pyroptosis is a lytic form of proinflammatory cell death characterised as caspase-1-dependent with canonical NLRP3 inflammasome-induced gasdermin D (GSDMD) activation. We aimed to investigate the role of acinar pyroptotic cell death in pancreatic injury and systemic inflammation in acute pancreatitis (AP).

Experimental Approach: Pancreatic acinar pyroptotic cell death pathway activation upon pancreatic toxin stimulation in vitro and in vivo were investigated. Effects of pharmacological (NLRP3 and caspase-1 inhibitors), constitutive (Nlrp3 , Caspase-1 and Gsdmd ) and acinar cell conditional (Pdx1 Nlrp3 and Pdx1 Gsdmd ) genetic inhibition on pyroptotic acinar cell death, pancreatic necrosis and systemic inflammation were assessed using mouse AP models (caerulein, sodium taurocholate, L-arginine). Effects of Pdx1 Gsdmd vs myeloid conditional knockout (Lyz2 Gsdmd ) and Gsdmd vs receptor interacting protein 3 (RIP3) inhibitor were compared in caerulein-induced AP (CER-AP).

Key Results: There was consistent pyroptotic acinar cell death upon pancreatic toxin stimulation both in vitro and in vivo which was significantly reduced by pharmacological or genetic pyroptosis inhibition. Pdx1 Gsdmd but not Lyz2 Gsdmd mice significantly reduced pyroptotic acinar cell death, pancreatic necrosis and systemic inflammation in CER-AP. Co-application of RIP3 inhibitor on Gsdmd mice further increased protection on CER-AP.

Conclusion And Implications: This work demonstrates a critical role for NLRP3 inflammasome and GSDMD activation-mediated pyroptosis in acinar cells, linking pancreatic necrosis and systemic inflammation in AP. Targeting pyroptosis signalling pathways holds promise for specific AP therapy.
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http://dx.doi.org/10.1111/bph.15499DOI Listing
April 2021

Siomycin A induces reactive oxygen species-mediated cytotoxicity in ovarian cancer cells.

Oncol Lett 2021 Jun 31;21(6):431. Epub 2021 Mar 31.

Department of Obstetrics and Gynecology, The Hospital of Tinglin, Shanghai 201505, P.R. China.

Ovarian cancer is one of the leading causes of cancer-related death among women worldwide and accounts for 4% of all cancer cases in female patients. To date, ovarian cancer has the poorest prognosis among all types of gynecological cancer; thus, it is necessary to identify prospective therapeutic options. Previous studies have demonstrated the involvement of reactive oxygen species (ROS) in the cytotoxicity of various anticancer drugs against several types of carcinoma, including ovarian cancer. The present study aimed to investigate the anticancer effects of Siomycin A, a thiopeptide antibiotic, on the ovarian cancer cell lines PA1 and OVCAR3. To determine the viability of these cells following exposure to Siomycin A, the MTT assay was used, and apoptosis was determined by ELISA. In addition, mitochondrial membrane potential was determined by JC1 staining, and cellular ROS levels were assessed by dichlorodihydrofluorescein diacetate staining in the presence and absence of antioxidant NAC. The subsequent levels of antioxidant enzymes and glutathione were also determined following Siomycin A treatment in the two cell lines. A combination study with Siomycin A and cisplatin indicated enhanced efficiency of the drugs on ovarian cancer cell viability. The results of the present study also demonstrated that Siomycin A induced ROS production, inhibited the major antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and intracellular GSH in PA1 and OVCAR3 cells, and inhibited the cell viability with an IC of ~5.0 and 2.5 µM after 72 h respectively compared with the untreated controls. Additionally, the Siomycin A-induced ROS production further targeted apoptotic cell death by impairing the mitochondrial membrane potential and modulating the levels of pro- and antiapoptotic proteins compared with those in the corresponding control groups. The administration of the antioxidant N-acetylcysteine significantly abrogated the cytotoxic effects of Siomycin A. In conclusion, the results of the present study demonstrated the role of ROS in Siomycin A-mediated cytotoxicity in ovarian cancer cells.
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http://dx.doi.org/10.3892/ol.2021.12692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045165PMC
June 2021

Photoautotrophic production of renewable ethylene by engineered cyanobacteria: Steering the cell metabolism towards biotechnological use.

Physiol Plant 2021 Apr 17. Epub 2021 Apr 17.

Microbial Chemistry, Department of Chemistry-Ångström, Uppsala University, Uppsala, Sweden.

Ethylene is a volatile hydrocarbon with a massive global market in the plastic industry. The ethylene now used for commercial applications is produced exclusively from nonrenewable petroleum sources, while competitive biotechnological production systems do not yet exist. This review focuses on the currently developed photoautotrophic bioproduction strategies that enable direct solar-driven conversion of CO into ethylene, based on the use of genetically engineered photosynthetic cyanobacteria expressing heterologous ethylene forming enzyme (EFE) from Pseudomonas syringae. The emphasis is on the different engineering strategies to express EFE and to direct the cellular carbon flux towards the primary metabolite 2-oxoglutarate, highlighting associated metabolic constraints, and technical considerations on cultivation strategies and conditional parameters. While the research field has progressed towards more robust strains with better production profiles, and deeper understanding of the associated metabolic limitations, it is clear that there is room for significant improvement to reach industrial relevance. At the same time, existing information and the development of synthetic biology tools for engineering cyanobacteria open new possibilities for improving the prospects for the sustainable production of renewable ethylene.
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http://dx.doi.org/10.1111/ppl.13430DOI Listing
April 2021

Carbon quantum dots modified AgS/CS nanocomposite as effective antibacterial agents.

J Inorg Biochem 2021 Apr 8;220:111456. Epub 2021 Apr 8.

College of Petrochemical Technology, Lanzhou University of Technology, Lanzhou, 730050, China. Electronic address:

The present study attempted to synthesize carbon quantum dots (CQDs) through Aldol polymerization reaction, wherein acetone was used as the carbon source. A nano composite CQDs/AgS/CS was developed by loading as prepared CQDs and AgS nanoparticles on a chitosan substrate (CS). An in-situation growth of nanocomposites was adopted to study their antibacterial properties. Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and methicillin-resistant Staphylococcus aureus were selected as the model bacteria. The CQDs/AgS/CS nanocomposites exhibited excellent inhibition not only against common pathogenic bacteria, but also those well-known drug-resistant bacteria. Moreover, compared to traditional antibiotics, the as prepared nanocomposites in the present work do not likely cause bacterial drug resistance, which make them a potential candidate for a new type of clinically applicable antibiotics.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111456DOI Listing
April 2021

Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6.

J Immunol Res 2021 26;2021:8875450. Epub 2021 Mar 26.

The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510500, China.

RIPK4 has been implicated in multiple cancer types, but its role in ovarian cancer (OC) has not been clearly elucidated. Our data from Gene Expression Profiling Interactive Analysis, RT-PCR, and immunohistochemical analysis showed that RIPK4 was expressed at higher levels in OC tissues and cells than in normal ovarian tissues and cells. Increased RIPK4 expression in OC markedly correlated with a worse overall survival than lower RIPK4 expression levels (hazard rate (HR) 1.5 (1.45-1.87); = 0.001). In functional experiments, RIPK4 downregulation significantly inhibited metastatic behaviours in OC cells. Subsequently, based on data from 593 OC patients in the TCGA database, gene set enrichment analysis revealed that RIPK4 was involved in epithelial-mesenchymal transition (EMT) in OC. At the molecular level, silencing RIPK4 significantly downregulated vimentin, N-cadherin, and Twist expression but induced an increase in the protein level of E-cadherin and inhibited the IL-6 and STAT3 levels. Moreover, IL-6 levels were significantly decreased in RIPK4-silenced OC cells ( < 0.05). The addition of IL-6 to OC cells rescued the suppressive effect of RIPK4 knockdown on EMT. Thus, our data illustrate that downregulation of RIPK4 expression can restrain EMT in OC by inhibiting IL-6. This finding may provide a novel diagnostic and therapeutic target for improving the poor prognoses of OC patients.
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http://dx.doi.org/10.1155/2021/8875450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019379PMC
March 2021