Publications by authors named "Xiu Li"

169 Publications

F3RNet: full-resolution residual registration network for deformable image registration.

Int J Comput Assist Radiol Surg 2021 May 3. Epub 2021 May 3.

Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, USA.

Purpose: Deformable image registration (DIR) is essential for many image-guided therapies. Recently, deep learning approaches have gained substantial popularity and success in DIR. Most deep learning approaches use the so-called mono-stream high-to-low, low-to-high network structure and can achieve satisfactory overall registration results. However, accurate alignments for some severely deformed local regions, which are crucial for pinpointing surgical targets, are often overlooked. Consequently, these approaches are not sensitive to some hard-to-align regions, e.g., intra-patient registration of deformed liver lobes.

Methods: We propose a novel unsupervised registration network, namely full-resolution residual registration network (F3RNet), for deformable registration of severely deformed organs. The proposed method combines two parallel processing streams in a residual learning fashion. One stream takes advantage of the full-resolution information that facilitates accurate voxel-level registration. The other stream learns the deep multi-scale residual representations to obtain robust recognition. We also factorize the 3D convolution to reduce the training parameters and enhance network efficiency.

Results: We validate the proposed method on a clinically acquired intra-patient abdominal CT-MRI dataset and a public inspiratory and expiratory thorax CT dataset. Experiments on both multimodal and unimodal registration demonstrate promising results compared to state-of-the-art approaches.

Conclusion: By combining the high-resolution information and multi-scale representations in a highly interactive residual learning fashion, the proposed F3RNet can achieve accurate overall and local registration. The run time for registering a pair of images is less than 3 s using a GPU. In future works, we will investigate how to cost-effectively process high-resolution information and fuse multi-scale representations.
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http://dx.doi.org/10.1007/s11548-021-02359-4DOI Listing
May 2021

Correction: Lactic acid bacteria alleviate polycystic ovarian syndrome by regulating sex hormone related gut microbiota.

Food Funct 2021 Apr 21. Epub 2021 Apr 21.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. and School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, PR China and Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, PR China.

Correction for 'Lactic acid bacteria alleviate polycystic ovarian syndrome by regulating sex hormone related gut microbiota' by Yufeng He et al., Food Funct., 2020, 11, 5192-5204, DOI: 10.1039/C9FO02554E.
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http://dx.doi.org/10.1039/d1fo90033aDOI Listing
April 2021

Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

School of Life Sciences, Tianjin University, Tianjin, 300072, China;

Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP5), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Upon GTP-loading, hGBP5 forms a closed face-to-face dimer. The MD of hGBP5 undergoes a drastic movement relative to its LG domain and forms extensive interactions with the LG domain and MD of the pairing molecule. Disrupting the MD interface (for hGBP5) or mutating the hinge region (for hGBP2/5) impairs their ability to inhibit HIV-1. Our results point to a GTP-induced dimerization mode that is likely conserved among all GBP members and provide insights into the molecular determinants of their antiviral function.
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http://dx.doi.org/10.1073/pnas.2022269118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054025PMC
April 2021

Isolated from Different Hosts Modifies the Intestinal Microbiota and Displays Differential Metabolic and Immunomodulatory Properties in Mice Fed a High-Fat Diet.

Nutrients 2021 Mar 21;13(3). Epub 2021 Mar 21.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.

The incidence of obesity, which is closely associated with the gut microbiota and chronic inflammation, has rapidly increased in the past 40 years. Therefore, the probiotic-based modification of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with of various origins could alleviate obesity in mice. Male C57BL/6J mice fed a high-fat diet (HFD, 60% energy as fat) received one of the following 14-week interventions: (i) N4_N3, (ii) Z25, (iii) 17_3, (iv) 2016_7_2, and (v) phosphate-buffered saline. The metabolic parameters, thermogenesis, and immunity of all treated mice were measured. Cecal and colonic microbial profiles were determined by 16S rRNA gene sequencing. Intestinal concentrations of short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The strains isolated from the feces of elderly humans ( Z25, 17_3, and 2016_7_2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn ( N4_N3) increased the body weight of mice. The strains isolated from the elderly also increased serum leptin concentrations and induced the expression of thermogenesis- and lipid metabolism-related genes in brown adipose tissue. All the strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of and reduced the development of beta-lactam resistance. In addition, the strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as , and . We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of can alleviate obesity and modify the gut microbiota of mice. The tested strains of showed different effects on lipid metabolism and immunity regulation, with these effects related to whether they had been isolated from the feces of newborn or elderly humans. This indicates that from different sources may have disparate effects on host health possibly due to the transmission of origin-specific functions to the host.
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http://dx.doi.org/10.3390/nu13031017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004121PMC
March 2021

Neural network model assisted Fourier ptychography with Zernike aberration recovery and total variation constraint.

J Biomed Opt 2021 Mar;26(3)

Tsinghua Univ. Shenzhen International Graduate School, Tsinghua Univ., China.

Significance: Fourier ptychography (FP) is a computational imaging approach that achieves high-resolution reconstruction. Inspired by neural networks, many deep-learning-based methods are proposed to solve FP problems. However, the performance of FP still suffers from optical aberration, which needs to be considered.

Aim: We present a neural network model for FP reconstructions that can make proper estimation toward aberration and achieve artifact-free reconstruction.

Approach: Inspired by the iterative reconstruction of FP, we design a neural network model that mimics the forward imaging process of FP via TensorFlow. The sample and aberration are considered as learnable weights and optimized through back-propagation. Especially, we employ the Zernike terms instead of aberration to decrease the optimization freedom of pupil recovery and perform a high-accuracy estimation. Owing to the auto-differentiation capabilities of the neural network, we additionally utilize total variation regularization to improve the visual quality.

Results: We validate the performance of the reported method via both simulation and experiment. Our method exhibits higher robustness against sophisticated optical aberrations and achieves better image quality by reducing artifacts.

Conclusions: The forward neural network model can jointly recover the high-resolution sample and optical aberration in iterative FP reconstruction. We hope our method that can provide a neural-network perspective to solve iterative-based coherent or incoherent imaging problems.
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http://dx.doi.org/10.1117/1.JBO.26.3.036502DOI Listing
March 2021

Epidemic patterns of antimicrobial resistance of Salmonella enterica serovar Gallinarum biovar Pullorum isolates in China during the past half-century.

Poult Sci 2021 Mar 10;100(3):100894. Epub 2020 Dec 10.

Jiangsu Key Laboratory of Zoonosis/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agrifood Safety and Quality, Ministry of Agriculture and Rural Affairs, Yangzhou University, Yangzhou, China. Electronic address:

Pullorum is a chicken-specific systemic disease caused by Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum). This study was carried out to provide basic data for understanding the trends of S. Pullorum. A total of 652 S. Pullorum isolates collected in China during 1962-2019 were examined. Overall, 525 (80.5%) isolates were resistant to at least one antibiotic; 280 (42.9%) isolates resisted 3 or more classes of antibiotics and showed an increasing trend until 2015 and then decreased significantly. The most common multidrug-resistant pattern was ampicillin-tetracycline-nalidixic acid (13.6%). After 2008, 6 classes of antibiotic-resistant strains began to appear, and they have been prevalent ever since. In 2014, a strain resistant to 7 antibiotics (ampicillin-cefazolin-streptomycin-tetracycline-sulphonamides-nalidixic acid-nitrofurantoin) was isolated. The highest antimicrobial resistance was observed for nalidixic acid (71.9%), and the lowest was found for cefotaxime, meropenem, amikacin, gentamicin, fosfomycin, and polymyxin (0%). Our findings monitored the prevalence of the resistance of S. Pullorum during the past half-century in China. Continued surveillance of antimicrobial resistance and the rational use of antimicrobials is necessary and important to control the rapid increase in antimicrobial resistance in S. Pullorum.
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http://dx.doi.org/10.1016/j.psj.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936142PMC
March 2021

Daily intake of Lactobacillus alleviates autistic-like behaviors by ameliorating the 5-hydroxytryptamine metabolic disorder in VPA-treated rats during weaning and sexual maturation.

Food Funct 2021 Mar 25;12(6):2591-2604. Epub 2021 Feb 25.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China.

Probiotic therapy targeting gut-brain axis has been proven to be effective in treating autistic patients. The present study aimed to assess the ability of three Lactobacillus strains (L. helveticus CCFM1076, L. acidophilus La28, and L. acidophilus JCM 1132) to alleviate autistic-like behavioral symptoms in VPA-treated rats from weaning to sexual maturation. For the first time, we assessed the synthesis of 5-hydroxytryptamine (5HT) and the metabolic capacity of the 5HT system in the peripheral and central nervous systems (PNS and CNS, respectively) based on tryptophan metabolism based on VPA-induced autism model. We also assessed gut microbiota, and short-chain fatty acids (SCFAs) at the end of week 8. While improving autistic-like behavioral symptoms, we found L. helveticus CCFM1076 was more beneficial in regulating 5HT anabolism and catabolism, balancing excitatory and inhibitory neurotransmitter release in the PNS and CNS, and increasing oxytocin (OT) synthesis in the hypothalamus. A significant correlation was noted between 5HT levels and the release of GABA, glutamate (Glu), and OT, suggesting that 5HT plays a vital role in the neuroendocrine network. Analyses of the gut microbiota and SCFA levels revealed greater Turicibacter abundance and lower butyric acid levels in VPA-treated rats, which have been reported to be associated with 5HT levels. L. helveticus CCFM1076 helped reduce Turicibacter abundance and up-regulate butyric acid levels, while L. acidophilus La28 and L. acidophilus JCM 1132 did not. L. helveticus CCFM1076 restored neurotransmitter homeostasis by improving the balance of the 5HT system in the PNS and CNS, thereby ameliorating autistic-like behaviors. This finding will help in the development of bioproducts for treating autism and in the establishment of a treatment model mimicking the intestinal environment of autistic patients.
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http://dx.doi.org/10.1039/d0fo02375bDOI Listing
March 2021

Molecular cloning, expression and characterization of aspartyl protease inhibitor from Ancylostoma ceylanicum.

Vet Parasitol Reg Stud Reports 2020 12 10;22:100464. Epub 2020 Sep 10.

Guangdong Provincial Zoonosis Prevention and Control Key Laboratory, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510542, China. Electronic address:

Aspartyl protease inhibitors (APIs) from parasitic intestinal nematodes are highly immunogenic and have been suggested as potential vaccine antigens. Ac-API-1 from Ancylostoma caninum showed strong immunogenicity and its polyclonal antibodies could specifically recognize the excretory/secretory products of adult worms. However, little is known about molecular characteristics and biological function of API from Ancylostoma ceylanicum (Ace-API). In this study, the Ace-API mature peptide coding sequence was cloned and expressed, and molecular characteristics of its full length sequence were analyzed. Ace-API cDNA was 684 bp in length, which encoded 228 amino acids. The similarity of the Ace-API amino acid sequence to Ac-API-1 and Adu-API-1 was 96.93% and 96.49%, respectively, and they clustered together in the phylogenetic tree. Escheria coli-expressed recombinant protein was mainly soluble in the supernatant of bacterial cell lysate. Western blot showed that Ace-API protein had good reactivity to the serum of infected dogs. Pepsin inhibition assay revealed that the recombinant protein had inhibitory activity on pepsin. Immunofluorescence results demonstrated that Ace-API was mainly localized to the epidermis, excretory glands, and pseudocoelomic fluid of the adult. Using the quantitative real-time PCR, the expression of Ace-api mRNA in adults was significantly higher than that in the third stage (L3) larvae. Together, these data indicate that Ace-API is secreted extracellularly by the parasite, and might play a role in protecting the parasite against the proteolytic digestion by the host proteases, which stimulate further studies to explore this protein as a potential hookworm vaccine candidate.
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http://dx.doi.org/10.1016/j.vprsr.2020.100464DOI Listing
December 2020

Adversarial Uni- and Multi-modal Stream Networks for Multimodal Image Registration.

Med Image Comput Comput Assist Interv 2020 Oct 29;12263:222-232. Epub 2020 Sep 29.

Brigham and Women's Hospital, Harvard Medical School, USA.

Deformable image registration between Computed Tomography (CT) images and Magnetic Resonance (MR) imaging is essential for many image-guided therapies. In this paper, we propose a novel translation-based unsupervised deformable image registration method. Distinct from other translation-based methods that attempt to convert the multimodal problem (e.g., CT-to-MR) into a unimodal problem (e.g., MR-to-MR) via image-to-image translation, our method leverages the deformation fields estimated from both: (i) the translated MR image and (ii) the original CT image in a dual-stream fashion, and automatically learns how to fuse them to achieve better registration performance. The multimodal registration network can be effectively trained by computationally efficient similarity metrics without any ground-truth deformation. Our method has been evaluated on two clinical datasets and demonstrates promising results compared to state-of-the-art traditional and learning-based methods.
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http://dx.doi.org/10.1007/978-3-030-59716-0_22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712495PMC
October 2020

A clinically applicable deep-learning model for detecting intracranial aneurysm in computed tomography angiography images.

Nat Commun 2020 11 30;11(1):6090. Epub 2020 Nov 30.

Department of Diagnostic Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210002, P.R. China.

Intracranial aneurysm is a common life-threatening disease. Computed tomography angiography is recommended as the standard diagnosis tool; yet, interpretation can be time-consuming and challenging. We present a specific deep-learning-based model trained on 1,177 digital subtraction angiography verified bone-removal computed tomography angiography cases. The model has good tolerance to image quality and is tested with different manufacturers. Simulated real-world studies are conducted in consecutive internal and external cohorts, in which it achieves an improved patient-level sensitivity and lesion-level sensitivity compared to that of radiologists and expert neurosurgeons. A specific cohort of suspected acute ischemic stroke is employed and it is found that 99.0% predicted-negative cases can be trusted with high confidence, leading to a potential reduction in human workload. A prospective study is warranted to determine whether the algorithm could improve patients' care in comparison to clinicians' assessment.
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http://dx.doi.org/10.1038/s41467-020-19527-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705757PMC
November 2020

SE-stacking: Improving user purchase behavior prediction by information fusion and ensemble learning.

PLoS One 2020 25;15(11):e0242629. Epub 2020 Nov 25.

School of Architecture and Fine Art, Dalian University of Technology, Dalian, China.

Online shopping behavior has the characteristics of rich granularity dimension and data sparsity and presents a challenging task in e-commerce. Previous studies on user behavior prediction did not seriously discuss feature selection and ensemble design, which are important to improving the performance of machine learning algorithms. In this paper, we proposed an SE-stacking model based on information fusion and ensemble learning for user purchase behavior prediction. After successfully using the ensemble feature selection method to screen purchase-related factors, we used the stacking algorithm for user purchase behavior prediction. In our efforts to avoid the deviation of the prediction results, we optimized the model by selecting ten different types of models as base learners and modifying the relevant parameters specifically for them. Experiments conducted on a publicly available dataset show that the SE-stacking model can achieve a 98.40% F1 score, approximately 0.09% higher than the optimal base models. The SE-stacking model not only has a good application in the prediction of user purchase behavior but also has practical value when combined with the actual e-commerce scene. At the same time, this model has important significance in academic research and the development of this field.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242629PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688168PMC
January 2021

Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan.

J Cancer Educ 2020 Nov 2. Epub 2020 Nov 2.

Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.
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http://dx.doi.org/10.1007/s13187-020-01911-1DOI Listing
November 2020

Spectrometric methods of grating constants for different holographic samples.

Appl Opt 2020 Oct;59(28):8976-8986

In order to measure the grating constants of different types of holographic samples efficiently and conveniently, we use spectrophotometers and the macro angle-resolved spectrum system to measure spectral information from six different holographic samples with three types, including rainbow holographic samples with light pillars, plain rainbow holographic samples, and matte holographic samples with light pillars. The information obtained from the instruments was used to investigate their grating constants by the grating equation. It was found that for the grating constant calculation, compared with the values measured using a light optical microscope, the angle-resolved spectrum system and the 45/0 spectrophotometers were applicable to the samples with rainbow effects. For the matte holographic samples, the angle-resolved spectrum system, which was mainly used to distinguish the differences between different matte samples, was necessary. The results from the spectrometric methods were similar to those from the light optical microscope.
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http://dx.doi.org/10.1364/AO.399250DOI Listing
October 2020

A High-Fat Diet Increases Gut Microbiota Biodiversity and Energy Expenditure Due to Nutrient Difference.

Nutrients 2020 Oct 20;12(10). Epub 2020 Oct 20.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have drawn inconsistent results. In this study, the unexpected results showed that the refined HFD increased gut microbiota diversity and short-chain fatty acids (SCFAs), causing an increase in energy metabolism. Further analysis revealed these changes were caused by the different fiber content in these two diets. Male C57BL/6J mice (4-5 weeks old) were fed either HFD or refined low-fat diet (LFD) for 14 weeks. The metabolic rates, thermogenesis, gut microbiome, and intestinal SCFAs were tested. The HFD triggered obesity and disturbed glucose homeostasis. Mice fed HFD ingested more fiber than mice fed LFD ( < 0.0001), causing higher intestinal SCFA concentrations related to the increased abundances of specific bacteria in the HFD group. Also, the HFD increased metabolic heat and up-regulated thermogenesis genes uncoupling protein 1(), peroxisome proliferator-activated receptor-γ coactivator-1α () expression in the brown adipose tissue (BAT). It was revealed by 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Desulfovibrionaceae, , and , meanwhile, reduced the abundance of , , , , and . The predicted metabolic pathways indicated HFD increased the gene expression of non-absorbed carbohydrate metabolism pathways, as well as the risks of colonization of intestinal pathogens and inflammation. In conclusion, the HFD was obesogenic in male C57BL/6J mice, and increased fiber intake from the HFD drove an increase in gut microbiota diversity, SCFAs, and energy expenditure. Meanwhile, the differences in specific nutrient intake can dissociate broad changes in energy expenditure, gut microbiota, and its metabolites from obesity, raising doubts in the previous studies. Therefore, it is necessary to consider whether differences in specific nutrient intake will interfere with the results of the experiments.
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http://dx.doi.org/10.3390/nu12103197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589760PMC
October 2020

Prevalence and multilocus sequence typing of Clostridium perfringens isolated from 4 duck farms in Shandong province, China.

Poult Sci 2020 Oct 8;99(10):5105-5117. Epub 2020 Jul 8.

Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an 271018, China. Electronic address:

Clostridium perfringens is an important zoonotic microorganism. The present study was undertaken to investigate prevalence, serotype distribution, antibiotic resistance, and genetic diversity of C. perfringens isolates from 4 duck farms in Shandong, China. In total, 424 samples of cloacal swabs and environment were collected from 3 commercial meat-type duck farms in Tai'an, Liaocheng, and Weifang and one breeder duck farm in Liaocheng between December 2018 and June 2019, of which, 207 (48.82%) samples were determined to be positive for C. perfringens; a total of 402 isolates of C. perfringens were recovered, all of which were identified as type A; 30.85% of the isolates were positive for cpb2 gene; and cpe gene was found in 0.5% of the isolates. Antimicrobial susceptibility testing revealed that some of the isolates exhibited high antibiotic resistance, and 39.14% of the isolates were resistant to at least 5 classes of commonly used antibiotics. Multilocus sequence typing analysis showed that 85 representative isolates encompassed 54 different sequences types (STs), clustered in 5 clonal complexes (CCs) and 40 singletons. ST3, the most common ST in 54 STs, constituting 15.29% of all isolates, was also the most prevalent ST of isolates from the Liaocheng breeder duck farm (farm 3). CC1, the most prolific CC, containing 15.29% of the analyzed isolates, was the popular subtype of isolates from Liaocheng meat duck farm (farm 2). Although all the isolates belong to type A, the genetic diversity varied greatly in different regions; the Simpson's Diversity Index of STs for Liaocheng, Tai'an, and Weifang were 0.5941, 0.9198, and 0.9627, respectively. Some of cloacal isolates and environmental isolates were distributed in the same ST or CC, indicating close genetic relationship between cloacal isolates and environmental isolates. A portion of the strains from humans and ducks was found to be phylogenetically close. The close relationship between strains from humans and ducks, the high antibiotic resistance of C. perfringens, and the cpe-positive isolates indicated potential public health risks.
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http://dx.doi.org/10.1016/j.psj.2020.06.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598333PMC
October 2020

Neural Architecture Search for compressed sensing Magnetic Resonance image reconstruction.

Comput Med Imaging Graph 2020 Oct 21;85:101784. Epub 2020 Aug 21.

Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China. Electronic address:

Recent works have demonstrated that deep learning (DL) based compressed sensing (CS) implementation can accelerate Magnetic Resonance (MR) Imaging by reconstructing MR images from sub-sampled k-space data. However, network architectures adopted in previous methods are all designed by handcraft. Neural Architecture Search (NAS) algorithms can automatically build neural network architectures which have outperformed human designed ones in several vision tasks. Inspired by this, here we proposed a novel and efficient network for the MR image reconstruction problem via NAS instead of manual attempts. Particularly, a specific cell structure, which was integrated into the model-driven MR reconstruction pipeline, was automatically searched from a flexible pre-defined operation search space in a differentiable manner. Experimental results show that our searched network can produce better reconstruction results compared to previous state-of-the-art methods in terms of PSNR and SSIM with 4∼6 times fewer computation resources. Extensive experiments were conducted to analyze how hyper-parameters affect reconstruction performance and the searched structures. The generalizability of the searched architecture was also evaluated on different organ MR datasets. Our proposed method can reach a better trade-off between computation cost and reconstruction performance for MR reconstruction problem with good generalizability and offer insights to design neural networks for other medical image applications. The evaluation code will be available at https://github.com/yjump/NAS-for-CSMRI.
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http://dx.doi.org/10.1016/j.compmedimag.2020.101784DOI Listing
October 2020

Effect of Bushen Jianpi formula on survival of patients with moderate and advanced hepatocellular carcinoma: a retrospective study.

J Tradit Chin Med 2020 08;40(4):683-689

School of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: To investigate the effect of Bushen Jianpi formula (BSJP) therapy on survival of the patients with moderate and advanced hepatocellular carcinoma (HCC).

Methods: This was a five-year retrospective study, enrolling 209 adult patients with moderate and advanced HCC patients. Log-rank test, Cox regression analysis and Kaplan-Meier analysis was applied to analyze the data.

Results: The outcome of single-factor Kaplan-Meier analysis and Log-rank test showed that stage of Barcelona-clinic liver cancer (BCLC), locoregional therapy and BSJP therapy were three factors that dominantly influenced the survival of moderate and advanced HCC patients (P < 0.05). In Cox multiple-factor regression analysis, lower BCLC staging (RR = 2.016; P = 0.000), locoregional therapy (RR = 0.611; P = 0.011) and BSJP therapy (RR = 0.684; P = 0.044) were the independent protective factors affecting survival of patients, and BSJP exerted a more significant effect on patients at BCLC-C stage (RR = 0.513; P = 0.002).

Conclusion: BSJP therapy and locoregional therapy both contributed to prolonged survival for moderate and advanced HCC patients.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.04.018DOI Listing
August 2020

Flavor Components Comparison between the Neck Meat of Donkey, Swine, Bovine, and Sheep.

Food Sci Anim Resour 2020 Jul 1;40(4):527-540. Epub 2020 Jul 1.

School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.

Donkey in China is well known for its draft purpose and transportation; however, donkey meat has attracted more and more consumers in recent years, yet it lacks sufficient information on its flavor components compared to other main meats. Therefore, in this study, volatile flavor compounds in neck meat of donkey, swine, bovine, and sheep were classified by electronic nose, then confirmed and quantified by gas chromatography-mass spectrometry. High-performance liquid chromatography (HPLC) and gas chromatography were used to quantify free fatty acid, amino acid, and flavor nucleotide. A total of 73 volatile compounds were identified, and aldehydes were identified as the characteristic flavor compounds in neck meat of donkey, bovine, swine and sheep in proportion of 76.39%, 46.62%, 31.64%, and 35.83%, respectively. Particularly, hexanal was the most abundant volatile flavor. Compared with other neck meat, much higher unsaturated free fatty acids were present in donkeys. Furthermore, neck meat of donkeys showed essential amino acid with highest content. Thus, special flavor and nutrition in donkey neck meat make it probably a candidate for consumers in other regions besides Asia.
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http://dx.doi.org/10.5851/kosfa.2020.e30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372983PMC
July 2020

Comparative Genomic Analysis Reveals the Metabolism and Evolution of the Thermophilic Archaeal Genus .

Front Microbiol 2020 19;11:1192. Epub 2020 Jun 19.

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Members of the genus are widely found in sulfur-rich and metal-laden environments, but their physiological and ecological roles remain poorly understood. Here, we sequenced Ric-A, a strain isolated from the Tengchong hot spring in Yunnan Province, China, and performed a comparative genome analysis with other genomes. The genome of had an average nucleotide identity (ANI) of approximately 70% to that of . Genes , , , , , , , and associated with sulfur oxidation, and gene clusters and involved in iron oxidation existed in all genomes. However, the adenosine-5'-phosphosulfate (APS) pathway was only detected in and , and several subunits of cluster were lost in . The complete 3-hydroxypropionate/4-hydroxybutyrate cycle and dicarboxylate/4-hydroxybutyrate cycle involved in carbon fixation were found in all genomes. A large number of gene family gain events occurred in and , whereas gene family loss events occurred frequently in Pervasive strong purifying selection was found acting on the gene families of , of which transcription-related genes underwent the strongest purifying selection. In contrast, genes related to prophages, transposons, and defense mechanisms were under weaker purifying pressure. Taken together, this study expands knowledge of the genomic traits of species and sheds light on their evolution.
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http://dx.doi.org/10.3389/fmicb.2020.01192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325606PMC
June 2020

Ammonia induce lung tissue injury in broilers by activating NLRP3 inflammasome via Escherichia/Shigella.

Poult Sci 2020 Jul 15;99(7):3402-3410. Epub 2020 Apr 15.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, State Key Laboratory of Animal Nutrition, Beijing 100193, China. Electronic address:

Respiratory tract diseases are closely related to atmosphere pollution. Ammonia is one of the harmful pollutants in the atmosphere environment, which has a great threat to human and animal respiratory tract health, but the mechanism of causing diseases is not clear. In this study, broiler lung tissue was used as a model to study the effect of high ammonia on respiratory tract diseases through the relationship between respiratory microflora, NLRP3 inflammasome, and inflammatory factors. For this, we validated the occurrence of lung tissue inflammation under ammonia exposure and detected the lung tissue microbial constituent by 16S rDNA sequencing. Moreover, the relative expression levels of NLRP3 and caspase-1 mRNA and the content of IL-1β and IL-6 were measured. After 7-D ammonia exposure, the proportion of the phylum Proteobacteria and the genus Escherichia/Shigella in lung tissue was significantly increased, the expression levels of NLRP3 and caspase-1 mRNA were significantly increased, and the content of IL-1β in lung tissue and serum was higher than that in the control group. In conclusion, high ammonia induced lung tissue inflammation via increasing the proportion of Escherichia/Shigella, activating NLRP3 inflammasome, and promoting IL-1β release. These findings provided a reference for the prevention and control of respiratory tract diseases in humans and animals caused by ammonia pollution.
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http://dx.doi.org/10.1016/j.psj.2020.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597683PMC
July 2020

Lactic acid bacteria reduce diabetes symptoms in mice by alleviating gut microbiota dysbiosis and inflammation in different manners.

Food Funct 2020 Jul 23;11(7):5898-5914. Epub 2020 Jun 23.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China.

The prevalence of diabetes mellitus is increasing worldwide. Lactic acid bacteria have shown efficacy in alleviating diabetes. We studied the remission effect of nine strains of lactic acid bacteria on the symptoms of high-fat diet- and streptozotocin-induced type 2 diabetes and its mechanism in mice. The oral administration of Bifidobacterium adolescentis, B. bifidum or Lactobacillus rhamnosus to mice every day for more than 12 weeks showed that the individual strains could reduce the fasting and postprandial blood sugar levels, improve glucose tolerance and prevent pancreatic damage. However, L. rhamnosus strains showed greater efficacy than Bifidobacterium strains in the regulation of blood lipid levels. The effects of lactic acid bacteria on the recovery of glycolipid metabolism disorder and gut microbiota dysbiosis showed inter- and intraspecific differences. In addition, the strains that exhibited hypoglycaemic effects played a beneficial role in reducing insulin resistance by contributing to the production of short-chain fatty acids and alleviation of inflammation. The ability of lactic acid bacteria to reduce inflammation was found to be closely related to their ability to alleviate diabetes mellitus.
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http://dx.doi.org/10.1039/c9fo02761kDOI Listing
July 2020

Preventive and Control Measures for the Coronavirus Pandemic in Clinical Dentistry.

Chin J Dent Res 2020 ;23(2):99-104

A severe public health crisis has been declared worldwide since coronavirus disease 2019 (COVID-19) was classified as a pandemic of acute respiratory infectious disease by the World Health Organisation (WHO). China has taken strict measures to curb the spread of the disease to save lives, and has managed to control the outbreak. COVID-19 is mainly transmitted through respiratory droplets and close physical contact, so it is challenging to prevent nosocomial infection and possible spread during dental treatment. Since the initial phase of the COVID-19 outbreak, a disease prevention and control strategy based on the new concept of population risk classification and rational use of personal protective equipment has been implemented by the Peking University Hospital of Stomatology. Nosocomial infection prevention and control concepts and measures relating to dental diagnosis and treatment are critically checked in the hospital. Our experiences in handling this situation are shared here and may have wide-ranging implications for infection prevention and control (IPC) for COVID-19 in dental practices worldwide.
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http://dx.doi.org/10.3290/j.cjdr.a44745DOI Listing
June 2020

and Efficacies of the EGFR/MEK/ERK Signaling Inhibitors in the Treatment of Alveolar Echinococcosis.

Antimicrob Agents Chemother 2020 07 22;64(8). Epub 2020 Jul 22.

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China

Alveolar echinococcosis (AE), caused by the larval stage of the cestode , is a lethal disease in humans. Novel therapeutic options are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. In this study, we assessed the and effects of the epidermal growth factor receptor (EGFR)/MEK/extracellular signal-regulated kinase (ERK) signaling inhibitors, including BIBW2992, CI-1033, and U0126, on Our data showed that BIBW2992, CI-1033, and U0126 all displayed effects on the viability of the metacestode. These inhibitors also showed protoscolicidal activities and caused severe ultrastructural alterations in the parasite. Moreover, BIBW2992 and CI-1033 exhibited potent proapoptotic effects on metacestodes. Strikingly, a large portion of the apoptotic cells were found to be the germinative cells. studies showed that BIBW2992 and U0126 significantly reduced parasite burden, and the parasite obtained from BIBW2992-treated mice displayed impaired structural integrity of the germinal layer. In conclusion, these findings demonstrate the potential of EGFR-mediated signaling as a target for the development of novel anti-AE agents. The EGFR inhibitor BIBW2992 represents a promising drug candidate and/or a lead compound for anti-AE chemotherapy.
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http://dx.doi.org/10.1128/AAC.00341-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526812PMC
July 2020

The potential role of clock genes in children attention-deficit/hyperactivity disorder.

Sleep Med 2020 07 5;71:18-27. Epub 2020 Mar 5.

Department of Maternal, Child and Adolescent Health, School of Public Health, Lanzhou University, Lanzhou, Gansu, PR China.

Background: Attention deficit/ hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder and is thought to be associated with circadian system.

Methods: We performed a pathway-based study to test individual single nucleotide polymorphisms (SNPs) and the overall evidence of genetic polymorphisms involved in the circadian pathway in association with children ADHD susceptibility among a Chinese population. A community-based case-control study was conducted among Chinese children, and 168 ADHD patients and 233 controls were recruited using a combination diagnosis based on the diagnostic and statistical manual of mental disorders iv (DSM-IV) ADHD rating scale, Swanson, Nolan, and Pelham rating scale (SNAP-IV) rating scale, and semi-structured clinical interview.

Results: The results of single-loci analyses identified that PER1 rs2518023 and ARNTL2 rs2306074 were nominally association with ADHD susceptibility (P < 0.05). Next, we applied multifactor dimensionality reduction (MDR), and classification and regression tree (CART) analyses to explore high-order gene-gene interactions among the functional SNPs to ADHD risks. The results indicated that interactions among the PER1 rs2518023, ARNTL2 rs2306074 and NR1D1 rs939347 were associated with the risk of ADHD in children. Individuals carrying the combination genotypes of the PER1 rs2518023 GG or GT, ARNTL2 rs2306074 TC or TT and NR1D1 rs939347 GA or AA displayed a significantly higher risk for ADHD than who carry the PER1 rs2518023 TT and CRY2 rs2292910 CA/CC genotypes (adjusted OR = 4.37, 95% CI = 2.16-8.85, P < 0.001).

Conclusions: These findings revealed the importance of genetic variations related to the circadian clock system to the susceptibility of children ADHD.
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http://dx.doi.org/10.1016/j.sleep.2020.02.021DOI Listing
July 2020

Lactic acid bacteria alleviate polycystic ovarian syndrome by regulating sex hormone related gut microbiota.

Food Funct 2020 Jun;11(6):5192-5204

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. and School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China and National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, PR China and Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, PR China.

Polycystic ovarian syndrome (PCOS) is a common endocrine disease across the world. Because gut microbiota play a key role in the pathogenesis of PCOS, probiotics may alleviate PCOS symptoms through the regulation of intestinal flora. The effects of 8 lactic acid bacterial strains on PCOS were investigated. Letrozole was used to produce a PCOS rat model and a 4-week-strain-intervention was performed. Diane-35, as a clinical PCOS treatment medicine, was effective in attenuating rats' reproductive disorders. Lactobacillus plantarum HL2 was protective against ovary pathological changes and restored luteinizing hormone, follicle stimulating hormone and testosterone levels. Bifidobacterium longum HB3 also alleviated ovary abnormalities and decreased testosterone levels. Administration of lactic acid bacteria up-regulated short-chain fatty acid levels. Based on 16S rRNA sequencing, lactic acid bacteria improved letrozole induced gut microbiota dysbiosis with different degrees. Akkermansia, Roseburia, Prevotella, Staphylococcus and Lactobacillus genera were correlated with sex hormone levels. Some of the sex hormone-related gut microbiota were restored by treatment with the strains. These results demonstrated that lactic acid bacteria alleviated PCOS in a rat model by regulating sex hormone related gut microbiota. Modifying gut microbiota by probiotic interventions may thus be a promising therapeutic option for PCOS.
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http://dx.doi.org/10.1039/c9fo02554eDOI Listing
June 2020

Effects of ammonia exposure on growth performance and cytokines in the serum, trachea, and ileum of broilers.

Poult Sci 2020 May 19;99(5):2485-2493. Epub 2020 Mar 19.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address:

This study investigated the effects of ammonia (NH) exposure (0, 15, 25, and 35 ppm) on growth performance and cytokines in the serum, trachea, and ileum of broilers. A total of 288 22-day-old male broiler chickens were assigned to 4 treatment groups with 6 replicates of 12 chickens for a 21-D trial period. Growth performance and cytokines (IL-1β, IL-6, and IL-10) concentrations in the serum, trachea, and ileum were measured in response to 3, 7, 14, or 21 D of exposure to NH. Correlations between cytokines in the serum, trachea, and ileum and growth performance, and between tracheal and ileal cytokines, were also analyzed. Results showed that exposure to 15 ppm NH did not influence the growth performance, but exposure to both 25 ppm and 35 ppm NH decreased the growth performance compared to that of the control group. Exposure to 15 ppm NH for 3 D increased IL-6 concentrations and induced an inflammatory response in the trachea and ileum, whereas exposure to 15 ppm NH for 7 D increased IL-10 concentrations and induced an anti-inflammatory response in the ileum. Exposure to 25 ppm NH induced an inflammatory response in the serum, trachea, and ileum after 3 D and induced an anti-inflammatory response in the ileum after 7 D. Exposure to 35 ppm NH for 3 D induced both inflammatory and anti-inflammatory responses in the trachea and ileum. Furthermore, increases in cytokines in the serum, trachea, or ileum were accompanied by a decrease in BW, ADFI, ADG, and an increase of feed/gain (F/G) from 7 D to 21 D. In addition, tracheal cytokine, especially IL-1β, was positively correlated with ileal cytokine IL-1β. These results indicated that the low growth performance associated with NH exposure may be due in part to an increase in cytokines, and the inflammatory response in the trachea and ileum may be related to cross-talk by cytokines such as IL-6, IL-10, and, in particular, IL-1β.
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http://dx.doi.org/10.1016/j.psj.2019.12.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597540PMC
May 2020

EDAG mediates Hsp70 nuclear localization in erythroblasts and rescues dyserythropoiesis in myelodysplastic syndrome.

FASEB J 2020 06 29;34(6):8416-8427. Epub 2020 Apr 29.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, China.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.
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http://dx.doi.org/10.1096/fj.201902946RDOI Listing
June 2020

Development and validation of machine learning prediction model based on computed tomography angiography-derived hemodynamics for rupture status of intracranial aneurysms: a Chinese multicenter study.

Eur Radiol 2020 Sep 29;30(9):5170-5182. Epub 2020 Apr 29.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China.

Objectives: To build models based on conventional logistic regression (LR) and machine learning (ML) algorithms combining clinical, morphological, and hemodynamic information to predict individual rupture status of unruptured intracranial aneurysms (UIAs), afterwards tested in internal and external validation datasets.

Methods: Patients with intracranial aneurysms diagnosed by computed tomography angiography and confirmed by invasive cerebral angiograph or clipping surgery were included. The prediction models were developed based on clinical, aneurysm morphological, and hemodynamic parameters by conventional LR and ML methods.

Results: The training, internal validation, and external validation cohorts were composed of 807 patients, 200 patients, and 108 patients, respectively. The area under curves (AUCs) of conventional LR models 1 (clinical), 2 (clinical and aneurysm morphological), and 3 (clinical, aneurysm morphological and hemodynamic characteristics) were 0.608, 0.765, and 0.886, respectively (all p < 0.05). The AUCs of ML models using random forest (RF), multilayer perceptron (MLP), and support vector machine (SVM) were 0.871, 0.851, and 0.863, respectively. There were no difference among AUCs of conventional LR, RF, and SVM (all p > 0.05/6), while the AUC of MLP was lower than that of conventional LR (p = 0.0055).

Conclusion: Hemodynamic parameters play an important role in the prediction performance of the models. ML methods cannot outperform conventional LR in prediction models for rupture status of UIAs integrating clinical, aneurysm morphological, and hemodynamic parameters.

Key Points: • The addition of hemodynamic parameters can improve prediction performance for rupture status of unruptured intracranial aneurysms. • Machine learning algorithms cannot outperform conventional logistic regression in prediction models for rupture status integrating clinical, aneurysm morphological, and hemodynamic parameters. • Models integrating clinical, aneurysm morphological, and hemodynamic parameters may help choose the optimal management.
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http://dx.doi.org/10.1007/s00330-020-06886-7DOI Listing
September 2020

Outcomes of Adding Induction Chemotherapy to Concurrent Chemotherapy for Nasopharyngeal Carcinoma Patients with Moderate-Risk in the Intensity-Modulated Radiotherapy Era.

Ther Clin Risk Manag 2020 26;16:201-211. Epub 2020 Mar 26.

Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.

Background: The aim of this study was to evaluate the efficacy of induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients with moderate-risk treated with intensity-modulated radiotherapy (IMRT).

Methods: We retrospectively assessed 506 patients with T1-2N1M0 or T3-4N0-1M0 NPC (according to the 2010 UICC/AJCC staging system) who received concurrent chemoradiotherapy (CCRT) with or without IC at a single center in China between 2005 and 2010. Survival outcomes were compared between the IC + CCRT and CCRT groups using the Kaplan-Meier method, Log-rank test and a Cox regression model.

Results: Among the 506 patients, CCRT alone resulted in equivalent overall survival (86.8% vs 88.5%, =0.661), progression-free survival (79.6% vs 79.6%, =0.756), locoregional relapse-free survival (90.2% vs 87.0%, =0.364) and distant metastasis-free survival (88.0% vs 89.8%, 0.407) to IC plus CCRT. In multivariate analysis, IC did not lower the risk of death (HR 0.76, 95% CI 0.46-1.25, 0.278), progression (HR 0.78, 95% CI 0.51-1.19, 0.244), locoregional relapse (HR 1.06, 95% CI 0.81-1.42, 0.651) or distant metastasis (HR 0.66, 95% CI 0.38-1.15, 0.140) in the entire cohort; similar results were obtained in stratified analysis based on N category (N0 vs N1) and EBV DNA (< vs ≥4000 copies/mL).

Conclusion: Addition of IC to CCRT does not improve survival outcomes in moderate-risk NPC; the use of IC should be carefully considered in these patients, though additional prospective trials are warranted to confirm the conclusions of this study.
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http://dx.doi.org/10.2147/TCRM.S241216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7130107PMC
March 2020