Publications by authors named "Kai Deng"

212 Publications

A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2.

Cell Rep 2021 Dec 23:110256. Epub 2021 Dec 23.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of the Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agents and Immunotechnology, Engineering Research Center of Gene Vaccine of the Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China; National Guangzhou Laboratory, Bio-Island, Guangzhou, Guangdong 510320, China. Electronic address:

Inoculation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing worldwide. However, the emergence of SARS-CoV-2 variants could cause immune evasion. We developed a bivalent nanoparticle vaccine that displays the receptor binding domains (RBDs) of the D614G and B.1.351 strains. With a prime-boost or a single-dose strategy, this vaccine elicits a robust neutralizing antibody and full protection against infection with the authentic D614G or B.1.351 strain in human angiotensin-converting enzyme 2 transgene mice. Interestingly, 8 months after inoculation with the D614G-specific vaccine, a new boost with this bivalent vaccine potently elicits cross-neutralizing antibodies for SARS-CoV-2 variants in rhesus macaques. We suggest that the D614G/B.1.351 bivalent vaccine could be used as an initial single dose or a sequential enforcement dose to prevent infection with SARS-CoV-2 and its variants.
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http://dx.doi.org/10.1016/j.celrep.2021.110256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695190PMC
December 2021

Pharmacological suppression of glycogen synthase kinase-3 reactivates HIV-1 from latency via activating Wnt/β-catenin/TCF1 axis in CD4 T cells.

Emerg Microbes Infect 2022 Jan 5:1-36. Epub 2022 Jan 5.

University of Chinese Academy of Sciences, Beijing 100039, China.

HIV-1 latency posts a major obstacle for HIV-1 eradication. Currently, no desirable latency reversing agents (LRAs) has been implicated in the "Shock and Kill" strategy to mobilize the latently infected cells to be susceptible for clearance by immune responses. Identification of key cellular pathways that modulate HIV-1 latency helps develop efficient LRAs. In this study, we demonstrate that the Wnt downstream β-catenin/TCF1 pathway is a crucial modulator for HIV-1 latency. The pharmacological activation of the β-catenin/TCF1 pathway with glycogen synthase kinase-3 (GSK3) inhibitors promoted transcription of HIV-1 proviral DNA and reactivated latency in CD4 T cells; the GSK3 kinase inhibitor 6-bromoindirubin-3'-oxime (6-BIO)- induced HIV-1 reactivation was subsequently confirmed in resting CD4 T cells from cART-suppressed patients and SIV-infected rhesus macaques. These findings advances our understanding of the mechanisms responsible for viral latency, and provides the potent LRA that can be further used in conjunction of immunotherapies to eradicate viral reservoirs.
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http://dx.doi.org/10.1080/22221751.2022.2026198DOI Listing
January 2022

Crystal structure of the chromosome partition protein MukE homodimer.

Biochem Biophys Res Commun 2022 Jan 14;589:229-233. Epub 2021 Dec 14.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

The SMC (structural maintenance of chromosomes) proteins are known to be involved in chromosome pairing or aggregation and play an important role in cell cycle and division. Different from SMC-ScpAB complex maintaining chromosome structure in most bacteria, the MukB-MukE-MukF complex is responsible for chromosome condensation in E. coli and some γ-proteobacter. Though different models were proposed to illustrate the mechanism of how the MukBEF complex worked, the assembly of the MukBEF complex is a key. The MukE dimer interacted with the middle region of one MukF molecule, and was clamped by the N- and C-terminal domain of the latter, and then was involved in the interaction with the head domain of MukB. To reveal the structural basis of MukE involved in the dynamic equilibrium of potential different MukBEF assemblies, we determined the MukE structure at 2.44 Å resolution. We found that the binding cavity for the α10, β4 and β5 of MukF (residues 296-327) in the MukE dimer has been occupied by the α9 and β7 strand of MukE. We proposed that the highly dynamic C-terminal region (173-225) was important for the MukE-F assembly and then involved in the MukBEF complex formation.
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http://dx.doi.org/10.1016/j.bbrc.2021.12.032DOI Listing
January 2022

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.

Signal Transduct Target Ther 2021 12 16;6(1):427. Epub 2021 Dec 16.

Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.
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http://dx.doi.org/10.1038/s41392-021-00822-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674414PMC
December 2021

Environmental Risk Factors for Talaromycosis Hospitalizations of HIV-Infected Patients in Guangzhou, China: Case Crossover Study.

Front Med (Lausanne) 2021 22;8:731188. Epub 2021 Nov 22.

Infectious Diseases Institute, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.

Talaromycosis is a fatal opportunistic infection prevalent in human immunodeficiency virus (HIV)-infected patients, previous studies suggest environmental humidity is associated with monthly talaromycosis hospitalizations of HIV-infected patients, but the acute risk factor remains uncertain. In this study, we evaluated the associations between talaromycosis hospitalizations of HIV-infected patients ( = 919) and environmental factors including meteorological variables and air pollutants at the event day (assumed "lag 0" since the exact infection date is hard to ascertain) and 1-7 days prior to event day (lag 1-lag 7) in conditional logistics regression models based on a case crossover design. We found that an interquartile range (IQR) increase in temperature at lag 0-lag 7 (odds ratio [OR] [95% CI] ranged from 1.748 [1.345-2.273] to 2.184 [1.672-2.854]), and an IQR increase in humidity at lag 0 (OR [95% CI] = 1.192 [1.052-1.350]), and lag 1 (OR [95% CI] = 1.199 [1.056-1.361]) were significantly associated with talaromycosis hospitalizations of HIV-infected patients. Besides, temperature was also a common predictor for talaromycosis in patients with co-infections including candidiasis ( = 386), pneumonia ( = 183), pulmonary tuberculosis ( = 141), and chronic hepatitis ( = 158), while humidity was a specific risk factor for talaromycosis in patients with candidiasis, and an air pollutant, SO, was a specific risk factor for talaromycosis in patients with pneumonia. In an age stratified evaluation (cutoff = 50 years old), temperature was the only variable positively associated with talaromycosis in both younger and older patients. These findings broaden our understanding of the epidemiology and pathogenesis of talaromycosis in HIV-infected patients.
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http://dx.doi.org/10.3389/fmed.2021.731188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645774PMC
November 2021

Automatic Detection of Small Intestinal Hookworms in Capsule Endoscopy Images Based on a Convolutional Neural Network.

Gastroenterol Res Pract 2021 24;2021:5682288. Epub 2021 Nov 24.

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, China.

Ancylostomiasis is a fairly common small bowel parasite disease identified by capsule endoscopy (CE) for which a computer-aided clinical detection method has not been established. We sought to develop an artificial intelligence system with a convolutional neural network (CNN) to automatically detect hookworms in CE images. We trained a deep CNN system based on a YOLO-V4 (You Look Only Once-Version4) detector using 11236 CE images of hookworms. We assessed its performance by calculating the area under the receiver operating characteristic curve and its sensitivity, specificity, and accuracy using an independent test set of 10,529 small-bowel images including 531 images of hookworms. The trained CNN system required 403 seconds to evaluate 10,529 test images. The area under the curve for the detection of hookworms was 0.972 (95% confidence interval (CI), 0.967-0.978). The sensitivity, specificity, and accuracy of the CNN system were 92.2%, 91.1%, and 91.2%, respectively, at a probability score cut-off of 0.485. We developed and validated a CNN-based system for detecting hookworms in CE images. By combining this high-accuracy, high-speed, and oversight-preventing system with other CNN systems, we hope it will become an important supplement for detecting intestinal abnormalities in CE images. This trial is registered with ChiCTR2000034546 (a clinical research of artificial-intelligence-aided diagnosis for hookworms in small intestine by capsule endoscope images).
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http://dx.doi.org/10.1155/2021/5682288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635910PMC
November 2021

Progestin-primed ovarian stimulation protocol with or without letrozole for patients with normal ovarian reserve: a retrospective cohort study.

J Clin Pharm Ther 2021 Nov 18. Epub 2021 Nov 18.

Reproductive Medicine Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.

What Is Known And Objective: To compare the characteristics and efficacy of progestin-primed ovarian stimulation (PPOS) protocol plus letrozole versus PPOS protocol alone for patients with normal ovarian function who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy treatment.

Methods: From 1 October 2017 to 1 October 2019, 576 patients who underwent IVF/ICSI cycles received PPOS protocol with or without letrozole in the Center of Reproductive Medicine, Renmin Hospital of Shiyan City were included in this retrospective cohort study. The PPOS group included 249 patients who received PPOS protocol alone, and the combined treatment group included 327 patients who received PPOS protocol plus letrozole. The general data and laboratory indicators were detected and used as baseline data. In addition, evaluation of related indicators was performed, including days of gonadotropin (Gn) duration, total amount of dose of Gn and medroxyprogesterone acetate (MPA), hormone levels on the trigger day, number of oocytes retrieved and mature eggs, fertilization rate, cleavage rate, blastocyst formation rate, high-quality embryo rate, methods of endometrial preparation, stage of embryo transfer, endometrial thickness, the number of embryo transfer, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and live birth rate. The risk factors affecting clinical pregnancy rate were detected by binary Logistic regression analysis.

Results And Discussion: In this study, we found that baseline level of Anti-Müllerian hormone (AMH) was significantly higher in combined group compared with PPOS group (p < 0.05). The days of Gn duration in combined group were significantly longer than that in PPOS group (p < 0.05), and the total amount of dose of Gn and MPA in combined group was significantly less than that in PPOS group (p < 0.05). The levels of luteinizing hormone (LH) and progesterone in combined group were significantly higher than that in PPOS group on the trigger day (p < 0.05). The number of oocytes retrieved and mature eggs in combined group was significantly more than that in PPOS group (p < 0.05). Meanwhile, the fertilization rate, cleavage rate and blastocyst formation rate in combined group were significantly higher than that in PPOS group (p < 0.05). There was no significant difference in the characteristics of endometrial preparation and embryo transfer, as well as the pregnancy outcomes. The results of logistic regression analysis showed that stage (p < 0.001) (OR = 0.281, 95% CI: 0.187, 0.422) and number (p < 0.001) (OR = 0.333, 95% CI: 0.196, 0.567) of embryos transfer were risk factors for clinical pregnancy rate.

What Is New And Conclusion: Compared with PPOS protocol alone, letrozole combined with PPOS can achieve similar embryo and pregnancy outcomes while reducing the amount of Gn and MPA, which has a higher cost performance and is worth promoting. Stage and number of embryos transfer are risk factors for clinical pregnancy rate.
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http://dx.doi.org/10.1111/jcpt.13567DOI Listing
November 2021

Trends in Tumor Site-Specific Survival of Bone Sarcomas from 1980 to 2018: A Surveillance, Epidemiology and End Results-Based Study.

Cancers (Basel) 2021 Oct 27;13(21). Epub 2021 Oct 27.

Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Objectives: As diagnosis and treatment guidelines for bone sarcomas continue updating, it is important to examine whether, when, and which kinds of patients have had a survival improvement over the last four decades.

Methods: This cohort study included 9178 patients with primary bone and joint sarcomas from 1 January 1980 to 31 December 2018 using data from Surveillance, Epidemiology and End Results (SEER)-9 Registries. The follow-up period was extended to November 2020. Patients were divided by decade into four time periods: 1980-1989, 1990-1999, 2000-2009, and 2010-2018. The primary endpoint was bone sarcomas-specific mortality (CSM). The 5-year bone sarcomas-specific survival (CSS) rate was determined stratified by demographic, neoplastic, temporal, economic, and geographic categories. The associations between time periods and CSM were examined using a multivariable Cox regression model, with reported hazard ratio (HR) and 95% confidence interval (CI).

Results: The 5-year CSS rate for bone sarcomas was 58.7%, 69.9%, 71.0%, and 69.2%, in the 1980s, 1990s, 2000s, and 2010s, respectively. Older age, male gender, tumor sites at pelvic bones, sacrum, coccyx and associated joints, as well as vertebral column, osteosarcoma and Ewing tumor, and residence in non-metropolitan areas were independently associated with higher CSM risk. After adjusting for the covariates above, patients in the 1990s (HR = 0.74, 95% CI = 0.68-0.82), 2000s (HR = 0.71, 95% CI = 0.65-0.78), and 2010s (HR = 0.68, 95% CI = 0.62-0.76) had significantly lower CSM risks than patients in the 1980s. However, patients in the 2000s and 2010s did not have lower CSM risks than those in the 1990s (both > 0.05).

Conclusions: Although bone sarcomas survival has significantly improved since 1990, it almost halted over the next three decades. Bone sarcomas survival should improve over time, similar to common cancers. New diagnostic and therapeutic strategies such as emerging immune and targeted agents are warranted to overcome this survival stalemate.
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http://dx.doi.org/10.3390/cancers13215381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582558PMC
October 2021

High-Volume Split-Dose Versus Low-Volume Split-Dose Polyethylene Glycol Preparations: Which Is a Better Choice?

Clin Gastroenterol Hepatol 2021 Oct 20. Epub 2021 Oct 20.

Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Sichuan University-Oxford University, Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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http://dx.doi.org/10.1016/j.cgh.2021.10.022DOI Listing
October 2021

Chlamydia trachomatis Stimulation Enhances HIV-1 Susceptibility through the Modulation of a Member of the Macrophage Inflammatory Proteins.

J Invest Dermatol 2021 Oct 15. Epub 2021 Oct 15.

Dermatology Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China; Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Sexually transmitted infections such as Chlamydia trachomatis can enhance HIV-1 infection. However, the molecular mechanisms modulating the enhancement of HIV-1 infectivity and replication during HIV-1/sexually transmitted infections coinfection remain elusive. In this study, we performed an ex vivo infection of HIV-1 in PBMCs of C. trachomatis‒infected patients and observed a significant increase in HIV-1 p24 levels compared with those in cells from healthy donors. Similarly, C. trachomatis‒stimulated PBMCs from healthy donors showed enhanced susceptibility to HIV-1. C. trachomatis‒stimulated CD4 T cells also harbored more HIV-1 copy numbers. RNA sequencing data revealed the upregulation of CCL3L1/CCL3L3, a paralog of CCL3 in C. trachomatis‒stimulated CD4 T cells infected with HIV-1. Furthermore, an increase in CCL3L1/CCL3L3 expression levels correlated with HIV-1 replication in C. trachomatis‒stimulated cells. However, the addition of exogenous CCL3L1 reduces HIV-1 infection of healthy cells, indicating a dual role of CCL3L1 in HIV-1 infection. Further investigation revealed that a knockout of CCL3L1/CCL3L3 in Jurkat T cells rescued the increased susceptibility of C. trachomatis‒stimulated cells to HIV-1 infection. These results reveal a role for CCL3L1/CCL3L3 in enhancing HIV-1 replication and production and highlight a mechanism for the enhanced susceptibility to HIV-1 among C. trachomatis‒infected patients.
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http://dx.doi.org/10.1016/j.jid.2021.09.020DOI Listing
October 2021

Accessible water jet system modified from the infusion set with ideal visibility during emergency bedside endoscopy.

Dig Endosc 2022 Jan 15;34(1):e7-e8. Epub 2021 Oct 15.

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1111/den.14156DOI Listing
January 2022

Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody.

Front Immunol 2021 23;12:751584. Epub 2021 Sep 23.

Institute of Immunology, Third Military Medical University, Chongqing, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.
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http://dx.doi.org/10.3389/fimmu.2021.751584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495157PMC
October 2021

MAT2A-Mediated S-Adenosylmethionine Level in CD4 T Cells Regulates HIV-1 Latent Infection.

Front Immunol 2021 20;12:745784. Epub 2021 Sep 20.

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Antiretroviral drugs effectively halt HIV-1 replication and disease progression, however, due to the presence of a stable viral latent reservoir, the infection cannot be cured by antiretroviral drugs alone. Elucidating the molecular mechanisms underlying HIV-1 latent infection remains a critical hurdle that precludes the development of novel therapeutic strategies aiming for a potential functional cure. Cellular metabolism has been reported to affect HIV-1 replication in CD4 T cells, but it remains largely unclear whether it is involved in the regulation of HIV-1 latency. Here, we performed a sub-pooled CRISPR library knockout screen targeting 1773 metabolic-related genes in a cell model of HIV-1 latent infection and found that Methionine Adenosyltransferase 2A (MAT2A) contributes to HIV-1 latency. MAT2A knockout enhanced the reactivation of latent HIV-1 while MAT2A overexpression did the opposite. Mechanistically, MAT2A modulates HIV-1 latency through S-Adenosylmethionine (SAM)-mediated one-carbon flux. MAT2A knockout resulted in a significant downregulation of DNA and histone methylation at the HIV-1 5'-LTR. Importantly, we found that the plasma level of SAM is positively correlated with HIV-1 DNA in PBMCs from ART-treated infected individuals, suggesting SAM could serve as a potential biomarker for the latent viral reservoir. Overall, this study reveals an important role of MAT2A-mediated one-carbon metabolism in regulating HIV-1 latency and provides a promising target for the development of new strategies for a functional cure of HIV-1.
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http://dx.doi.org/10.3389/fimmu.2021.745784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488394PMC
January 2022

Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China.

EClinicalMedicine 2021 Oct 12;40:101129. Epub 2021 Sep 12.

Guangzhou Eighth People's Hospital , Guangzhou Medical University, Guangzhou, 510060, China.

Background: A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China.

Methods: We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital.

Findings: There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%,  = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86];  = 0.01).

Interpretation: Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks.

Funding: National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory.
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http://dx.doi.org/10.1016/j.eclinm.2021.101129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435265PMC
October 2021

Improved colorimetric analysis for subtle changes of powdered anthocyanins extracted from Lycium ruthenicum Murr.

Food Chem 2022 Mar 8;371:131080. Epub 2021 Sep 8.

Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, PR China; Huzhou China-Science Innovation Centre of Plateau Biology, Huzhou 313000, PR China. Electronic address:

Anthocyanins of Lycium ruthenicum (LR) are valuable, whereas stabilities, especially colour stabilities, constrain development. This study investigates stored temperature effects on the stability of powdered anthocyanin extracts of LR in anaerobic conditions and colour changes in simulated applications. We found that temperature had limited effects on anthocyanin contents but negative effects on colour. Colour differences (ΔE) were amplified in simulated applications, 4 °C had the most changes in ΔE in simulated applications, 37 °C caused shrinkage of the colour range towards the yellow area, and changes in ΔE at pH 7 and 9 were summarized by models. In conclusion, during anaerobic storage of powdered anthocyanins, asynchronous changes occur between anthocyanin contents and colour. High storage temperature attenuates colour intensity, but low storage temperature causes more ΔE in applications. Established models are beneficial for decreasing the visual differences in products, deepening the understanding, and offering a new perspective on colour analysis.
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http://dx.doi.org/10.1016/j.foodchem.2021.131080DOI Listing
March 2022

Synergism of Interfaces and Defects: Cu/Oxygen Vacancy-Rich Cu-MnO Heterostructured Ultrathin Nanosheet Arrays for Selective Nitrate Electroreduction to Ammonia.

ACS Appl Mater Interfaces 2021 Sep 9;13(37):44733-44741. Epub 2021 Sep 9.

State Key Laboratory Breeding Base of Green-Chemical Synthesis Technology, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Achieving high efficiency in nitrate (NO) to ammonia (NH) electrocatalysis requires the exploration of advanced electrocatalysts with a well-designed composition and architecture. In this work, a facile one-step hydrothermal approach was developed for the construction of novel Cu/oxygen vacancy-rich Cu-MnO heterostructured ultrathin nanosheet arrays on Cu foam (Cu/Cu-MnO NSAs/CF). Two-dimensional ultrathin nanosheet arrays could increase the exposure of catalytically active centers, and the heterogeneous nanointerface and oxygen vacancies synergistically improve the nitrate-to-ammonia activity over the active centers. Due to the desirable compositional and structural advantages, the Cu/Cu-MnO NSAs/CF demonstrated excellent performance for the electrocatalytic nitrate reduction to ammonia with high ammonia selectivity (87.6%) and Faradic efficiency (92.4%).
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http://dx.doi.org/10.1021/acsami.1c11249DOI Listing
September 2021

Combination of graphene oxide and platelet-rich plasma improves tendon-bone healing in a rabbit model of supraspinatus tendon reconstruction.

Regen Biomater 2021 Oct 4;8(6):rbab045. Epub 2021 Aug 4.

Department of Orthopedics, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, PR China.

The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons. The key to treatment is the reconstruction of the tendon-bone interface (TBI). Autologous platelet-rich plasma (PRP) is used as a therapeutic agent to accelerate the healing of tendons, as it contains a variety of growth factors and is easy to prepare. Graphene oxide (GO) is known to improve the physical properties of biomaterials and promote tissue repair. In this study, PRP gels containing various concentrations of GO were prepared to promote TBI healing and supraspinatus tendon reconstruction in a rabbit model. The incorporation of GO improved the ultrastructure and mechanical properties of the PRP gels. The gels containing 0.5 mg/ml GO (0.5 GO/PRP) continuously released transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF)-AB, and the released TGF-β1 and PDGF-AB were still at high concentrations, ∼1063.451 pg/ml and ∼814.217 pg/ml, respectively, on the 14th day. assays showed that the 0.5 GO/PRP gels had good biocompatibility and promoted bone marrow mesenchymal stem cells proliferation and osteogenic and chondrogenic differentiation. After 12 weeks of implantation, the magnetic resonance imaging, micro-computed tomography and histological results indicated that the newly regenerated tendons in the 0.5 GO/PRP group had a similar structure to natural tendons. Moreover, the biomechanical results showed that the newly formed tendons in the 0.5 GO/PRP group had better biomechanical properties compared to those in the other groups, and had more stable TBI tissue. Therefore, the combination of PRP and GO has the potential to be a powerful advancement in the treatment of rotator cuff injuries.
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http://dx.doi.org/10.1093/rb/rbab045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411035PMC
October 2021

Application of a novel phage vB_SalS-LPSTLL for the biological control of Salmonella in foods.

Food Res Int 2021 09 4;147:110492. Epub 2021 Jun 4.

Key Laboratory of Environment Correlative Dietology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY, USA. Electronic address:

Salmonella is one of the most common foodborne pathogens around the world. Phages are envisioned as a new strategy to control foodborne pathogenic bacteria and food safety. A Salmonella specific lytic phage vB_SalS-LPSTLL (LPSTLL) was selected for food applications on the basis of lytic range, lytic efficiency, functional stability and characteristics. Phage LPSTLL was able to lyse 11 Salmonella serotypes, which represents the broadest range reported Salmonella phages, and was able to suppress the growth of Salmonella enterica in liquid culture over nine hours. LPSTLL exhibited rapid reproductive activity with a short latent period and a large burst size in one-step growth experiment. LPSTLL remained active over a pH range of 3.0 to 12.0, and at incubation temperatures up to 60 °C for 60 min, indicating wide applicability for food processing and storage. Significant reductions of viable Salmonella were observed in diverse foods (milk, apple juice, chicken and lettuce) with reductions up to 2.8 log CFU/mL recorded for milk. Sensory evaluation indicated that treatment with phage LPSTLL did not alter the visual or tactile quality of food matrices. Genome analysis of LPSTLL indicated the absence of any virulence or antimicrobial resistance genes. Genomic comparisons suggest phage LPSTLL constitutes a novel member of a new genus, the LPSTLLvirus with the potential for Salmonella biocontrol in the food industry.
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http://dx.doi.org/10.1016/j.foodres.2021.110492DOI Listing
September 2021

Letter to the Editor: Unanswered questions about hepatitis B virus infection in patients with COVID-19.

Hepatology 2022 01 7;75(1):229. Epub 2021 Dec 7.

Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1002/hep.32098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426842PMC
January 2022

Acquisition of the L452R Mutation in the ACE2-Binding Interface of Spike Protein Triggers Recent Massive Expansion of SARS-CoV-2 Variants.

J Clin Microbiol 2021 10 11;59(11):e0092121. Epub 2021 Aug 11.

University of Washingtongrid.34477.33, Seattle, Washington, USA.

We report that there is a recent global expansion of numerous independent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutation L452R in the receptor-binding domain (RBD) of the spike protein. The massive emergence of L452R variants was first linked to lineage B.1.427/B.1.429 (clade 21C) that has been spreading in California since November and December 2020, originally named CAL.20C and currently variant of interest epsilon. By PCR amplification and Sanger sequencing of a 541-base fragment coding for amino acids 414 to 583 of the RBD from a collection of clinical specimens, we identified a separate L452R variant that also recently emerged in California but derives from the lineage B.1.232, clade 20A (named CAL.20A). Notably, CAL.20A caused an infection in gorillas in the San Diego Zoo, reported in January 2021. Unlike the epsilon variant that carries two additional mutations in the N-terminal domain of spike protein, L452R is the only mutation found in the spike proteins of CAL.20A. Based on genome-wide phylogenetic analysis, emergence of both viral variants was specifically triggered by acquisition of L452R, suggesting a strong positive selection for this mutation. Global analysis revealed that L452R is nearly omnipresent in a dozen independently emerged lineages, including the most recent variants of concern/interest delta, kappa, epsilon and iota, with the lambda variant carrying L452Q. L452 is in immediate proximity to the angiotensin-converting enzyme 2 (ACE2) interaction interface of RBD. It was reported that the L452R mutation is associated with immune escape and could result in a stronger cell attachment of the virus, with both factors likely increasing viral transmissibility, infectivity, and pathogenicity.
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http://dx.doi.org/10.1128/JCM.00921-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525575PMC
October 2021

Retracted: Management of Infected Bone Defects of the Lower Extremities by Three-Stage Induced Membrane Technique.

Med Sci Monit 2021 Aug 6;27:e934259. Epub 2021 Aug 6.

Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China (mainland).

Retraction requested by the author due to an admission of research fraud. Reference: Chong Zhang, Chunquan Zhu, Guorong Yu, Kai Deng, Li Yu. Management of Infected Bone Defects of the Lower Extremities by Three-Stage Induced Membrane Technique. Med Sci Monit 2020; 26: e919925. 10.12659/MSM.919925.
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http://dx.doi.org/10.12659/MSM.934259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354000PMC
August 2021

Duality of the association between COVID-19 and acute pancreatitis.

Gut 2022 01 15;71(1):229. Epub 2021 Jun 15.

Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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http://dx.doi.org/10.1136/gutjnl-2021-325221DOI Listing
January 2022

Research on the distribution spectrum of atherosclerotic plaques in patients with suspected coronary artery disease and the noninvasive screening model for coronary atherosclerosis burden.

Quant Imaging Med Surg 2021 Jul;11(7):3274-3285

Department of Radiology, the First Affiliated Hospital of Shandong First Medical University, Jinan, China.

Background: This study aimed to establish a non-invasive and simple screening model of coronary atherosclerosis burden based on the associations between multiple blood parameters and total plaque score (TPS), segment-stenosis score (SSS), coronary artery disease severity (CADS) in coronary artery disease (CAD) and thus reduce unnecessary coronary angiography (CAG).

Methods: A total of 1,366 patients with suspected CAD who underwent CAG were included in this study. The clinical risk factors [age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG), low-density lipoprotein (LDL), fasting plasma glucose (FPG), and glycated hemoglobin (GHB)] were collected. The presence of plaques and lumen stenosis was assessed based on CAG imaging. The TPS, SSS, and CADS were calculated, and the distribution spectrum of atherosclerotic plaques was described. Kruskal-Wallis test for multiple comparison tests was performed to analyze the differences in groups of different risk factors. The selected independent predictors were put into a multivariate logistic model, and the variables were further screened by stepwise regression to establish a screening model. Finally, the receiver operating characteristic (ROC) curve was used to evaluate the selected model's discriminant effect.

Results: The distributions of TPS and SSS scores were both right-skewed. Among males, both TPS and SSS scores were higher than in females (χ=46.7659, P<0.0001, χ=51.6603, P<0.0001). Both TPS and SSS scores increased with age (χ=123.4456, P<0.0001, χ=123.4456, P<0.0001). For TPS, the most common position was proximal left anterior descending artery (P-LAD, 51.39%). In SSS, the P-LAD plaque was highest: 0: 48.61%, 1: 10.32%, 2: 9.15%, and 3: 31.92%. The TPS score >5, SSS score >5, and CAD >0 were valuable indicators for SBP, FPG, TG, HDL, and GHB. In the model, TPS score >5, SSS score >5, and CADS >0, the area under ROC curve (AUC) was 0.753 [95% confidence interval (CI): 0.713 to 0.789], 0.728 (95% CI: 0.687 to 0.766), and 0.756 (95% CI: 0.717 to 0.793), respectively.

Conclusions: The most common site of lesions was P-LAD. These models can be used as non-invasive and simple initial screening tools without CAG.
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http://dx.doi.org/10.21037/qims-20-901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250030PMC
July 2021

Nitraria tangutorum Bobr.-derived polysaccharides protect against LPS-induced lung injury.

Int J Biol Macromol 2021 Sep 1;186:71-78. Epub 2021 Jul 1.

CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China; Huzhou Plateau Biological Resource Centre of Innovation, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Huzhou 313000, China. Electronic address:

Nitraria tangutorum Bobr. is suggested to be active in immunoregulation and antioxidation. However, the in vivo bioactivity of N. tangutorum Bobr.-derived polysaccharides (NTP) and their anti-inflammatory activity have not been addressed. In the present study, we extracted and purified polysaccharides from N. tangutorum Bobr. and determined their anti-inflammatory activities in vivo. HPGPC, UHPLC/DAD, and NMR analyses identified that the monosaccharide components of NTP were Man, Rha, GalUA, Glu, Gal, and Ara, with relative contents of 3.52%, 15.08%, 10.00%, 26.73%, 38.08%, and 6.59%, respectively. In mice with lipopolysaccharide (LPS)-induced Acute Lung Injury (ALI), NTP treatment attenuated tissue damage, inhibited the production of inflammatory cytokines, and promoted the anti-oxidative response. The supposed mechanism may be via suppressing the Toll-like receptor 4 (TLR4) signaling pathway. In conclusion, our study suggests a protective role of NTP in LPS-induced ALI by inhibiting inflammatory damage.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.181DOI Listing
September 2021

Dual-step irradiation strategy to sequentially destroy singlet oxygen-responsive polymeric micelles and boost photodynamic cancer therapy.

Biomaterials 2021 08 11;275:120959. Epub 2021 Jun 11.

Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, China. Electronic address:

Nanotechnology provides a powerful tool to overcome many disadvantages of small-molecule photosensitizers for photodynamic cancer therapy, such as hydrophobicity, rapid blood clearance, low accumulation in tumor tissue and low cell penetration, etc. The occurrence of quench in photosensitizer-loaded nanoparticle greatly downregulates the ability to generate singlet oxygen with light irradiation. Stimuli-responsive nanocarriers can improve the efficacy of PDT to a certain extent. However, insufficient release of photosensitizer from either endogenous or exogenous stimuli responsive nanocarriers in the short period of light irradiation restricts full usage of the photosensitizer delivered into cancer cells. We here report a dual-step light irradiation strategy to enhance the efficacy of cancer PDT. Ce6 as a photosensitizer is loaded in singlet oxygen-sensitive micelles (Ce6-M) via self-assembly of amphiphilic polymer mPEG-TK-C. After co-incubation of Ce6-M with cancer cells or i.v. injection of Ce6-M, cancer cells or tumor tissues are irradiated with light for a short time to trigger Ce6 release, and 2 h later, re-irradiated for relatively long time. The sufficient release of Ce6 in the period between twice light irradiation significantly improves the generation of singlet oxygen, leading to more efficient cancer therapeutic effects of dual-step irradiation than that of single-step irradiation for the same total irradiation time.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120959DOI Listing
August 2021

The Varying Costs of Endoscopic Surveillance May Affect the Follow-Up Endpoint Identified by Cost-Benefit Analysis in Barrett's Esophagus Patients Around the World.

Gastroenterology 2022 01 11;162(1):351. Epub 2021 Jun 11.

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Sichuan, China.

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http://dx.doi.org/10.1053/j.gastro.2021.06.010DOI Listing
January 2022

A multiplexed nanostructure-initiator mass spectrometry (NIMS) assay for simultaneously detecting glycosyl hydrolase and lignin modifying enzyme activities.

Sci Rep 2021 06 3;11(1):11803. Epub 2021 Jun 3.

Joint BioEnergy Institute, Emeryville, CA, 94608, USA.

Lignocellulosic biomass is composed of three major biopolymers: cellulose, hemicellulose and lignin. Analytical tools capable of quickly detecting both glycan and lignin deconstruction are needed to support the development and characterization of efficient enzymes/enzyme cocktails. Previously we have described nanostructure-initiator mass spectrometry-based assays for the analysis of glycosyl hydrolase and most recently an assay for lignin modifying enzymes. Here we integrate these two assays into a single multiplexed assay against both classes of enzymes and use it to characterize crude commercial enzyme mixtures. Application of our multiplexed platform based on nanostructure-initiator mass spectrometry enabled us to characterize crude mixtures of laccase enzymes from fungi Agaricus bisporus (Ab) and Myceliopthora thermophila (Mt) revealing activity on both carbohydrate and aromatic substrates. Using time-series analysis we determined that crude laccase from Ab has the higher GH activity and that laccase from Mt has the higher activity against our lignin model compound. Inhibitor studies showed a significant reduction in Mt GH activity under low oxygen conditions and increased activities in the presence of vanillin (common GH inhibitor). Ultimately, this assay can help to discover mixtures of enzymes that could be incorporated into biomass pretreatments to deconstruct diverse components of lignocellulosic biomass.
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http://dx.doi.org/10.1038/s41598-021-91181-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175421PMC
June 2021

Retroflexed view for reexamination of the right colon after forward view examination: Systematic review and meta-analysis.

Dig Endosc 2022 Jan 12;34(1):33-42. Epub 2021 Jul 12.

Department of Gastroenterology and Hepatology,, West China Hospital of Sichuan University, Chengdu, China.

Background: The effect of retroflexed view (RV) for the reexamination of the right colon after forward view (FV) examination has not been fully understood.

Methods: We searched multiple databases including PubMed, Embase, and the Cochrane Library for prospective studies exploring the role of RV for reexamination of the right colon. A meta-analysis was performed on outcomes including lesion detection rates, lesion miss rates, and withdrawal time.

Results: Four randomized controlled trials aimed to compare the impact of the second withdrawal from the right colon in RV vs. FV following a standard colonoscopy. Both the additional adenoma detection rate (AADR) and additional polyp detection rate (APDR) of the right colon were lower in the RV group compared with the FV group (risk ratio [RR] 0.73 for AADR; RR 0.76 for APDR); similar results were noted in comparisons of the adenoma miss rate and polyp miss rate. Six prospective cohort studies aimed to describe the effect of the RV examination of the right colon after one or two rounds of FV examination. Both the adenoma detection rate (ADR) and polyp detection rate (PDR) of the right colon were slightly higher in combined examinations with RV examination than single FV examination (RR 1.11 for ADR; RR 1.16 for PDR) or two FV examinations (RR 1.21 for ADR; RR 1.22 for PDR).

Conclusions: FV may detect more adenomas and polyps than RV during the second withdrawal from the right colon. RV may detect additional adenomas and polyps in the right colon after two FV examinations.
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http://dx.doi.org/10.1111/den.14052DOI Listing
January 2022

Porous PdAg alloy nanostructures with a concave surface for efficient electrocatalytic methanol oxidation.

Nanotechnology 2021 Jun 11;32(35). Epub 2021 Jun 11.

State Key Laboratory Breeding Base of Green-Chemical Synthesis Technology, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, People's Republic of China.

Tuning the composition and surface structure of the metal nanocrystals offered viable avenues for enhancing catalytic performances. Herein, we report a facile one-pot strategy for the formation of PdAg porous alloy nanostructures (PANs) with a concave surface. Due to their highly open nanostructures and tunable d-band center features, PdAg PANs exhibit superior electrocatalytic activity and long-term durability than Pd nanoparticles (NPs) and Pd/C for methanol oxidation reaction (MOR) in alkaline media. Our results provide a feasible and efficient approach for the controlled synthesis of high-performance Pd-based nanomaterials for alkaline MOR.
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http://dx.doi.org/10.1088/1361-6528/ac0471DOI Listing
June 2021

Tensor envelope mixture model for simultaneous clustering and multiway dimension reduction.

Authors:
Kai Deng Xin Zhang

Biometrics 2021 May 19. Epub 2021 May 19.

Department of Statistics, Florida State University, Tallahassee, Florida, USA.

In the form of multidimensional arrays, tensor data have become increasingly prevalent in modern scientific studies and biomedical applications such as computational biology, brain imaging analysis, and process monitoring system. These data are intrinsically heterogeneous with complex dependencies and structure. Therefore, ad-hoc dimension reduction methods on tensor data may lack statistical efficiency and can obscure essential findings. Model-based clustering is a cornerstone of multivariate statistics and unsupervised learning; however, existing methods and algorithms are not designed for tensor-variate samples. In this article, we propose a tensor envelope mixture model (TEMM) for simultaneous clustering and multiway dimension reduction of tensor data. TEMM incorporates tensor-structure-preserving dimension reduction into mixture modeling and drastically reduces the number of free parameters and estimative variability. An expectation-maximization-type algorithm is developed to obtain likelihood-based estimators of the cluster means and covariances, which are jointly parameterized and constrained onto a series of lower dimensional subspaces known as the tensor envelopes. We demonstrate the encouraging empirical performance of the proposed method in extensive simulation studies and a real data application in comparison with existing vector and tensor clustering methods.
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http://dx.doi.org/10.1111/biom.13486DOI Listing
May 2021
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