Publications by authors named "Wentao Shi"

57 Publications

Bionoi: A Voronoi Diagram-Based Representation of Ligand-Binding Sites in Proteins for Machine Learning Applications.

Methods Mol Biol 2021 ;2266:299-312

Center for Computation and Technology, Louisiana State University, Baton Rouge, LA, USA.

Bionoi is a new software to generate Voronoi representations of ligand-binding sites in proteins for machine learning applications. Unlike many other deep learning models in biomedicine, Bionoi utilizes off-the-shelf convolutional neural network architectures, reducing the development work without sacrificing the performance. When initially generating images of binding sites, users have the option to color the Voronoi cells based on either one of six structural, physicochemical, and evolutionary properties, or a blend of all six individual properties. Encouragingly, after inputting images generated by Bionoi into the convolutional autoencoder, the network was able to effectively learn the most salient features of binding pockets. The accuracy of the generated model is evaluated both visually and numerically through the reconstruction of binding site images from the latent feature space. The generated feature vectors capture well various properties of binding sites and thus can be applied in a multitude of machine learning projects. As a demonstration, we trained the ResNet-18 architecture from Microsoft on Bionoi images to show that it is capable to effectively classify nucleotide- and heme-binding pockets against a large dataset of control pockets binding a variety of small molecules. Bionoi is freely available to the research community at https://github.com/CSBG-LSU/BionoiNet.
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http://dx.doi.org/10.1007/978-1-0716-1209-5_17DOI Listing
April 2021

Underdetermined DOA Estimation for Wideband Signals via Focused Atomic Norm Minimization.

Entropy (Basel) 2020 Mar 20;22(3). Epub 2020 Mar 20.

School of Marine Science and Technology, Northwestern Polytechnical University, Xi'an 710072, China.

In underwater acoustic signal processing, direction of arrival (DOA) estimation can provide important information for target tracking and localization. To address underdetermined wideband signal processing in underwater passive detection system, this paper proposes a novel underdetermined wideband DOA estimation method equipped with the nested array (NA) using focused atomic norm minimization (ANM), where the signal source number detection is accomplished by information theory criteria. In the proposed DOA estimation method, especially, after vectoring the covariance matrix of each frequency bin, each corresponding obtained vector is focused into the predefined frequency bin by focused matrix. Then, the collected averaged vector is considered as virtual array model, whose steering vector exhibits the Vandermonde structure in terms of the obtained virtual array geometries. Further, the new covariance matrix is recovered based on ANM by semi-definite programming (SDP), which utilizes the information of the Toeplitz structure. Finally, the Root-MUSIC algorithm is applied to estimate the DOAs. Simulation results show that the proposed method outperforms other underdetermined DOA estimation methods based on information theory in term of higher estimation accuracy.
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http://dx.doi.org/10.3390/e22030359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516832PMC
March 2020

Enhanced neural differentiation of neural stem cells by sustained release of Shh from TG2 gene-modified EMSC co-culture in vitro.

Amino Acids 2021 Jan 27;53(1):11-22. Epub 2020 Nov 27.

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

As a promising cell therapy, neural crest-derived ectoderm mesenchymal stem cells (EMSCs) secrete high amounts of extracellular matrix (ECM) and neurotrophic factors, promoting neural stem cell (NSC) differentiation into neuronal lineages and aiding tissue regeneration. Additionally, the forced overexpression of secreted proteins can increase the therapeutic efficacy of the secretome. Tissue transglutaminase (TG2) is a ubiquitously expressed member of the transglutaminase family of calcium-dependent crosslinking enzymes, which can stabilize the ECM, inducing smart or living biomaterial to stimulate differentiation and enhance the neurogenesis of NSCs. In this study, we examined the neuronal differentiation of NSCs induced by TG2 gene-modified EMSCs (TG2-EMSCs) in a co-culture model directly. Two weeks after initiating differentiation, levels of the neuronal markers, tubulin beta 3 class III and growth-associated protein 43, were higher in NSCs in the TG2-EMSC co-culture group and those of the astrocytic marker glial fibrillary acidic protein were lower, compared with the control group. These results were confirmed by immunofluorescence, and laminin, fibronectin and sonic hedgehog (Shh) contributed to this effect. The results of western blot analysis and the enzyme-linked immunoassay showed that after TG2-EMSCs were co-cultured for 2 weeks, they expressed much higher levels of Shh than the control group. Moreover, the sustained release of Shh was observed in the TG2-EMSC co-culture group. Overall, our findings indicate that EMSCs can induce the differentiation of NSCs, of which TG2-EMSCs can promote the differentiation of NSCs compared with EMSCs.
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http://dx.doi.org/10.1007/s00726-020-02918-0DOI Listing
January 2021

Analysis of the Incompletely Hoisted Vertebrae in the Anterior Controllable Antedisplacement and Fusion Surgery: Causes and Prevention.

Clin Spine Surg 2021 May;34(4):125-131

Department of Statistics, Second Military Medical University, Shanghai, China.

Purpose: Anterior controllable antedisplacement and fusion (ACAF) has been reported to be a safe and effective technique. However, incompletely hoisted vertebrae (IV) were found in the postoperative images. This study aims to analyze the causes and prevention of IV.

Methods: The ACAF-treated case series subjects were retrospectively reviewed. The vertebrae were separated into the IV group and completely hoisted vertebrae (CV) group according to the gap between the vertebrae and plate. The radiographic data, degree of cervical lordosis, bone mineral density, number of hoisted vertebrae, operative time, blood loss, and Japanese Orthopaedic Association score were compared between the patients with IV and the patients without IV.

Results: A total of 248 vertebrae were hoisted in the enrolled patients. Intervertebral disc height in the IV group was 3.7±0.4 mm, which is significantly lower than that in the CV group. The anterior or posterior overhanging lip, osteoporosis, and oblique osteotomy troughs and hinges existing after osteotomy were found to be impingements preventing the hoisting of the vertebrae. There were no differences in the age, sex, degree of cervical lordosis, number of hoisted vertebrae, and neurological improvement rate between the groups of patients with and without IV.

Conclusions: Lower intervertebral space height and impingements preventing hoisting were found to be possible causes of IV in ACAF. Measures to prevent the problem should be carried out.
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http://dx.doi.org/10.1097/BSD.0000000000001037DOI Listing
May 2021

Farnesoid X receptor contributes to body weight-independent improvements in glycemic control after Roux-en-Y gastric bypass surgery in diet-induced obese mice.

Mol Metab 2020 07 19;37:100980. Epub 2020 Mar 19.

Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, PR China. Electronic address:

Objective: Roux-en-Y gastric bypass surgery (RYGB) can achieve long-term remission of type 2 diabetes. However, the specific molecular mechanism through which this occurs has remained largely elusive. Bile acid signaling through the nuclear hormone receptor farnesoid X receptor (FXR) exerts beneficial effects after sleeve gastrectomy (VSG), which has similar effects to RYGB. Therefore, we investigated whether FXR signaling is necessary to mediate glycemic control after RYGB.

Methods: RYGB or sham surgery was performed in high-fat diet-induced obese FXR-/- (knockout) and FXR+/+ (wild type) littermates. Sham-operated mice were fed ad libitum (S-AL) or by weight matching (S-WM) to RYGB mice via caloric restriction. Body weight, body composition, food intake, energy expenditure, glucose tolerance tests, insulin tolerance tests, and homeostatic model assessment of insulin resistance were performed.

Results: RYGB surgery decreases body weight and fat mass in WT and FXR-KO mice. RYGB surgery has similar effects on food intake and energy expenditure independent of genotype. In addition, body weight-independent improvements in glucose control were attenuated in FXR -/- relative to FXR +/+ mice after RYGB. Furthermore, pharmacologic blockade of the glucagon-like peptide-1 receptor (GLP-1R) blunts the glucoregulatory effects of RYGB in FXR +/+ but not in FXR -/- mice at 4 weeks after surgery.

Conclusions: These results suggest that FXR signaling is not required for the weight loss up to 16 weeks after RYGB. Although most of the improvements in glucose homeostasis are secondary to RYGB-induced weight loss in wild type mice, FXR signaling contributes to glycemic control after RYGB in a body weight-independent manner, which might be mediated by an FXR-GLP-1 axis during the early postoperative period.
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http://dx.doi.org/10.1016/j.molmet.2020.100980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182762PMC
July 2020

BionoiNet: ligand-binding site classification with off-the-shelf deep neural network.

Bioinformatics 2020 05;36(10):3077-3083

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

Motivation: Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide- and heme-binding sites with a comparable accuracy to highly specialized, voxel-based methods.

Results: We developed BionoiNet, a new deep learning-based framework implementing a popular ResNet model for image classification. BionoiNet first transforms the molecular structures of ligand-binding sites to 2D Voronoi diagrams, which are then used as the input to a pretrained convolutional neural network classifier. The ResNet model generalizes well to unseen data achieving the accuracy of 85.6% for nucleotide- and 91.3% for heme-binding pockets. BionoiNet also computes significance scores of pocket atoms, called BionoiScores, to provide meaningful insights into their interactions with ligand molecules. BionoiNet is a lightweight alternative to computationally expensive 3D architectures.

Availability And Implementation: BionoiNet is implemented in Python with the source code freely available at: https://github.com/CSBG-LSU/BionoiNet.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214032PMC
May 2020

Increased Resting Energy Expenditure/Body Weight and Decreased Respiratory Quotient Correlate with Satisfactory Weight Loss After Sleeve Gastrectomy: a 6-Month Follow-Up.

Obes Surg 2020 04;30(4):1410-1416

Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, HuangPu District, Shanghai, 200011, China.

Background: Although bariatric surgery can achieve sustained weight loss, there are major differences in the magnitude of weight change post-operatively. Reduced resting energy expenditure (REE) plays an important role in unsatisfactory weight loss effect by contributing to positive energy balance.

Objectives: To identify pre- and post-surgical predictors related to satisfactory percent of total weight loss (%TWL) in Chinese individuals with obesity after laparoscopic sleeve gastrectomy (LSG).

Methods: A retrospective cohort study was conducted in 97 ethnic Chinese with mean body mass index (BMI) of 37.2 kg/m, focusing on body composition, anthropometric and metabolic energy expenditure parameters, and %TWL before and 6 months after LSG. Patients were divided post-operatively into those with or without satisfactory %TWL (%TWL ≥ 20%). Multiple stepwise logistic regression analysis was used to identify predictors.

Results: Satisfactory %TWL was achieved in 53 (54.6%) patients 6 months after surgery. The univariate analysis of post-operative variables showed that patients with satisfactory %TWL had significantly higher resting energy expenditure/body weight (REE/BW) and lower respiratory quotient (RQ) than those who did not (P < 0.001). Multiple stepwise logistic regression analysis indicated that REE/BW and RQ were closely associated with satisfactory %TWL (P = 0.004, P = 0.023, respectively). %TWL was positively correlated with changes in BMI, percent of fat-free mass (FFM%), REE/BW, and RQ.

Conclusions: Higher REE/BW and lower RQ resulting from LSG correlated with satisfactory %TWL in Chinese patients with obesity. The maintenance of FFM might be an important factor linking %TWL and REE/BW.
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http://dx.doi.org/10.1007/s11695-019-04308-2DOI Listing
April 2020

Infection Regulates Thioredoxin-Interacting Protein Expression to Facilitate Intracellular Survival by Reducing the Production of Nitric Oxide and Reactive Oxygen Species.

J Immunol 2020 02 18;204(3):632-643. Epub 2019 Dec 18.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 201100, People's Republic of China; and

Thioredoxin-interacting protein (TXNIP) is a multifunctional protein that functions in tumor suppression, oxidative stress, and inflammatory responses. However, how TXNIP functions during microbial infections is rarely reported. In this study, we demonstrate that infection decreased TXNIP expression to promote its intracellular growth in macrophages by decreasing the production of NO and reactive oxygen species (ROS). Following infection, TXNIP knockout RAW264.7 cells produced significantly lower levels of NO and ROS, compared with wild-type RAW264.7 cells. Inducible NO synthase (iNOS) inhibitor treatment reduced NO levels, which resulted in a dose-dependent restoration of TXNIP expression, demonstrating that the expression of TXNIP is regulated by NO. In addition, the expression of iNOS and the production of NO were dependent on the type IV secretion system of Moreover, infection reduced TXNIP expression in bone marrow-derived macrophages and mouse lung and spleen. Knocked down of the TXNIP expression in bone marrow-derived macrophages increased intracellular survival of These findings revealed the following: 1) TXNIP is a novel molecule to promote intracellular survival by reducing the production of NO and ROS; 2) a negative feedback-regulation system of NO confers protection against iNOS-mediated antibacterial effects. The elucidation of this mechanism may reveal a novel host surveillance pathway for bacterial intracellular survival.
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http://dx.doi.org/10.4049/jimmunol.1801550DOI Listing
February 2020

Birth, expansion, and death of VCY-containing palindromes on the human Y chromosome.

Genome Biol 2019 10 14;20(1):207. Epub 2019 Oct 14.

The Wellcome Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK.

Background: Large palindromes (inverted repeats) make up substantial proportions of mammalian sex chromosomes, often contain genes, and have high rates of structural variation arising via ectopic recombination. As a result, they underlie many genomic disorders. Maintenance of the palindromic structure by gene conversion between the arms has been documented, but over longer time periods, palindromes are remarkably labile. Mechanisms of origin and loss of palindromes have, however, received little attention.

Results: Here, we use fiber-FISH, 10x Genomics Linked-Read sequencing, and breakpoint PCR sequencing to characterize the structural variation of the P8 palindrome on the human Y chromosome, which contains two copies of the VCY (Variable Charge Y) gene. We find a deletion of almost an entire arm of the palindrome, leading to death of the palindrome, a size increase by recruitment of adjacent sequence, and other complex changes including the formation of an entire new palindrome nearby. Together, these changes are found in ~ 1% of men, and we can assign likely molecular mechanisms to these mutational events. As a result, healthy men can have 1-4 copies of VCY.

Conclusions: Gross changes, especially duplications, in palindrome structure can be relatively frequent and facilitate the evolution of sex chromosomes in humans, and potentially also in other mammalian species.
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http://dx.doi.org/10.1186/s13059-019-1816-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790999PMC
October 2019

Bi-layer blood vessel mimicking microfluidic platform for antitumor drug screening based on co-culturing 3D tumor spheroids and endothelial layers.

Biomicrofluidics 2019 Jul 31;13(4):044108. Epub 2019 Jul 31.

Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, Pennsylvania 18015, USA.

Two-dimensional (2D) cell culture is not ideal for traditional drug screening, because 2D culture does not accurately mimic the physiological microenvironment of tumor cells. Thus, a drug-screening system which more closely mimics the microenvironment of tumors is necessary. Here, we present a biomimicking bilayer microfluidic device that can facilitate antitumor drug screening. The microfluidic device consists of two polydimethylsiloxane (PDMS) pieces with channels which are separated by a semipermeable membrane to allow water, oxygen, and nutrition supply, while preventing cell migration. The channels embedded on the two PDMS pieces overlap each other over a long distance to ensure a larger exchange area to mimic the blood vessel-tumor model. High concentrations of endothelial cells (EC) are first seeded onto the membrane through the apical channel, and after a two-day culture, a confluent EC monolayer forms. Tumor spheroid-laden Matrigel is then seeded into the basal channel. After the Matrigel is cured, the device is ready for drug testing. Paclitaxel is used as the model drug for testing. Confocal microscopy and ImageJ are used to assess the efficacy of different concentrations of paclitaxel, and optical coherence tomography (OCT) is employed to determine the tumor volumetric change after the drug treatment. The results indicate that the proposed bilayer microfluidic device in combination with confocal and OCT optical characterization provide an efficient platform for antitumor drug testing.
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http://dx.doi.org/10.1063/1.5108681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669041PMC
July 2019

Clobetasol propionate enhances neural stem cell and oligodendrocyte differentiation.

Exp Ther Med 2019 Aug 19;18(2):1258-1266. Epub 2019 Jun 19.

Department of Embryology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.

Clobetasol propionate (Clo) is a potent topical glucocorticoid and a potential remyelinating agent that has been approved by the U.S. Food and Drug Administration. However, the effect of Clo on neural stem cells (NSCs) remains largely unknown. The aim of the present study was to investigate the effect of Clo on the differentiation of NSCs . NSCs were isolated from mouse embryonic brain tissues and expanded . The effect of Clo on NSC viability was examined using an MTT assay. Differentiating NSCs were treated with 5 or 10 µM Clo, or with DMSO control, and the degree of differentiation was examined following culture in stem cell differentiation induction medium for 7 days. The effect of Clo on NSC differentiation was assessed using immunocytochemistry and western blot analyses. The results revealed that Clo significantly increased NSC viability compared with the DMSO control group. Treatment with Clo also significantly increased the number of NSCs that differentiated into growth associated protein 43 positive neurons and corresponding axon lengths were also significantly increased. In addition, treatment with Clo significantly increased the number of myelin basic protein positive oligodendrocytes and decreased the number of glial fibrillary acidic protein positive astrocytes. Furthermore, inhibition of the sonic hedgehog and AMP-activated protein kinase signaling pathways inhibited Clo-induced NSC differentiation, and treatment with Clo upregulated the expression of several neurotrophic factors. In conclusion, the results of the current study suggest that Clo may have a potential therapeutic benefit in neurological disorders affecting oligodendrocytes and neurons.
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http://dx.doi.org/10.3892/etm.2019.7692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614724PMC
August 2019

Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuron‑like cells and promotes functional recovery in adult rats following spinal cord injury.

Mol Med Rep 2019 Sep 15;20(3):2763-2773. Epub 2019 Jul 15.

Department of Embryology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.

Ectomesenchymal stem cells (EMSCs) represent a type of adult stem cells derived from the cranial neural crest. These cells are capable of self‑renewal and have the potential for multidirectional differentiation. Tissue transglutaminase type 2 (TG2) is a ubiquitously expressed member of the transglutaminase family of Ca2+‑dependent crosslinking enzymes. However, the effect of TG2 on neural differentiation and proliferation of EMSCs remains unknown. To determine whether TG2 improves EMSC proliferation and neurogenesis, a stable TG2‑overexpressing EMSC cell line (TG2‑EMSCs) was established by using an adenovirus system. Immunofluorescence staining and western blot analyses demonstrated that TG2 overexpression had beneficial effects on the rate of EMSC neurogenesis, and that the proliferative capacity of TG2‑EMSCs was higher than that of controls. Furthermore, the results of western blotting revealed that extracellular matrix (ECM) and neurotrophic factors were upregulated during the differentiation of TG2‑EMSCs. Notably, TG2‑EMSC transplantation in an animal model of spinal cord injury (SCI), TG2‑EMSCs differentiated into neuron‑like cells and enhanced the repair of SCI. Taken together, these results demonstrated that TG2 gene transfection may offer a novel strategy to enhance EMSC proliferation and neurogenesis in vivo and in vitro, which may ultimately facilitate EMSC‑based transplantation therapy in patients with SCI.
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http://dx.doi.org/10.3892/mmr.2019.10502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691247PMC
September 2019

Unique gelation and rheological properties of the cellulose/CO-based reversible ionic liquid/DMSO solutions.

Carbohydr Polym 2019 Oct 25;222:115024. Epub 2019 Jun 25.

Zhejiang Key Laboratory of Bio-Based Polymeric Materials Technology and Application, Ningbo Key Laboratory of Polymer Materials, Ningbo Institute of Materials Technology and Engineering (NIMTE), CAS, Ningbo, 315201, China. Electronic address:

Gelation and rheological behaviors of cellulose/CO-based reversible ionic liquid (RIL)/DMSO solutions were investigated. The exponents of specific viscosity η versus concentration c were determined for wood pulp (WP) and microcrystalline cellulose (MCC) solutions. The complex viscosity acquired using oscillatory shear closely follows the steady shear viscosity, thus revealing the applicability of Cox-Merz rule. The influence of RIL content in the solvent on apparent viscosities, activation energy, intrinsic viscosities, specific viscosity-c[η] master curve, and relaxation time were also investigated. Gelation occurred in this cellulose solution system due to thermal-induced CO release from the decomposition of the CO-based reversible ionic liquid. The formed gel was stable in air, but re-dissolved when exposed to CO, indicating the switch-on and switch-off effects of CO in cellulose dissolution and gelation.
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http://dx.doi.org/10.1016/j.carbpol.2019.115024DOI Listing
October 2019

Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome.

Hum Mol Genet 2019 08;28(16):2785-2798

Wellcome Genome Campus, Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10-3 (95% CI 1.94 × 10-3 to 2.48 × 10-3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.
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http://dx.doi.org/10.1093/hmg/ddz101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687947PMC
August 2019

Changes in Energy Expenditure of Patients with Obesity Following Bariatric Surgery: a Systematic Review of Prospective Studies and Meta-analysis.

Obes Surg 2019 07;29(7):2318-2337

Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, HuangPu District, Shanghai, 200011, People's Republic of China.

We herein summarize the available literature on the effects of bariatric surgery (BS) on energy expenditure in individuals with obesity. We conducted a systematic literature review, and 35 prospective studies met our inclusion criteria. The findings indicate that BS contributes to increased diet-induced thermogenesis (DIT) and decreased total energy expenditure (TEE) and resting energy expenditure (REE) in patients with obesity. The meta-analysis demonstrated a significant decrease in TEE and REE within 6 months following BS. With the sustained decrease in REE, there was no further decrease in TEE between the 6- and 12-month follow-up. Increased DIT might explain the variance between the patterns of REE and TEE change. The postoperative decrease in REE/FFM and increase in REE/BW were observed. The changes in substrate utilization might be consistent with the change in the respiration quotient postoperatively.
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http://dx.doi.org/10.1007/s11695-019-03851-2DOI Listing
July 2019

Longitudinal Morphological and Physiological Monitoring of Three-dimensional Tumor Spheroids Using Optical Coherence Tomography.

J Vis Exp 2019 02 9(144). Epub 2019 Feb 9.

Department of Electrical and Computer Engineering, Lehigh University; Department of Bioengineering, Lehigh University; Center for Photonics and Nanoelectronics, Lehigh University;

Tumor spheroids have been developed as a three-dimensional (3D) cell culture model in cancer research and anti-cancer drug discovery. However, currently, high-throughput imaging modalities utilizing bright field or fluorescence detection, are unable to resolve the overall 3D structure of the tumor spheroid due to limited light penetration, diffusion of fluorescent dyes and depth-resolvability. Recently, our lab demonstrated the use of optical coherence tomography (OCT), a label-free and non-destructive 3D imaging modality, to perform longitudinal characterization of multicellular tumor spheroids in a 96-well plate. OCT was capable of obtaining 3D morphological and physiological information of tumor spheroids growing up to about 600 µm in height. In this article, we demonstrate a high-throughput OCT (HT-OCT) imaging system that scans the whole multi-well plate and obtains 3D OCT data of tumor spheroids automatically. We describe the details of the HT-OCT system and construction guidelines in the protocol. From the 3D OCT data, one can visualize the overall structure of the spheroid with 3D rendered and orthogonal slices, characterize the longitudinal growth curve of the tumor spheroid based on the morphological information of size and volume, and monitor the growth of the dead-cell regions in the tumor spheroid based on optical intrinsic attenuation contrast. We show that HT-OCT can be used as a high-throughput imaging modality for drug screening as well as characterizing biofabricated samples.
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http://dx.doi.org/10.3791/59020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681648PMC
February 2019

EMSCs Build an All-in-One Niche via Cell-Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells.

Adv Mater 2019 Mar 11;31(10):e1806861. Epub 2019 Jan 11.

School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, 212001, P. R. China.

The therapeutic efficiency of allogenic/intrinsic neural stem cells (NSCs) after spinal cord injury is severely compromised because the hostile niche at the lesion site incurs massive astroglial but not neuronal differentiation of NSCs. Although many attempts are made to reconstruct a permissive niche for nerve regeneration, solely using a living cell material to build an all-in-one, multifunctional, permissive niche for promoting neuronal while inhibiting astroglial differentiation of NSCs is not reported. Here, ectomesenchymal stem cells (EMSCs) are reported to serve as a living, smart material that creates a permissive, all-in-one niche which provides neurotrophic factors, extracellular matrix molecules, cell-cell contact, and favorable substrate stiffness for directing NSC differentiation. Interestingly, in this all-in-one niche, a corresponding all-in-one signal-sensing platform is assembled through recruiting various niche signaling molecules into lipid rafts for promoting neuronal differentiation of NSCs, and meanwhile, inhibiting astrocyte overproliferation through the connexin43/YAP/14-3-3θ pathway. In vivo studies confirm that EMSCs can promote intrinsic NSC neuronal differentiation and domesticating astrocyte behaviors for nerve regeneration. Collectively, this study represents an all-in-one niche created by a single-cell material-EMSCs for directing NSC differentiation.
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http://dx.doi.org/10.1002/adma.201806861DOI Listing
March 2019

Y Chromosome Sequences Reveal a Short Beringian Standstill, Rapid Expansion, and early Population structure of Native American Founders.

Curr Biol 2019 01 20;29(1):149-157.e3. Epub 2018 Dec 20.

The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. Electronic address:

The Americas were the last inhabitable continents to be occupied by humans, with a growing multidisciplinary consensus for entry 15-25 thousand years ago (kya) from northeast Asia via the former Beringia land bridge [1-4]. Autosomal DNA analyses have dated the separation of Native American ancestors from the Asian gene pool to 23 kya or later [5, 6] and mtDNA analyses to ∼25 kya [7], followed by isolation ("Beringian Standstill" [8, 9]) for 2.4-9 ky and then a rapid expansion throughout the Americas. Here, we present a calibrated sequence-based analysis of 222 Native American and relevant Eurasian Y chromosomes (24 new) from haplogroups Q and C [10], with four major conclusions. First, we identify three to four independent lineages as autochthonous and likely founders: the major Q-M3 and rarer Q-CTS1780 present throughout the Americas, the very rare C3-MPB373 in South America, and possibly the C3-P39/Z30536 in North America. Second, from the divergence times and Eurasian/American distribution of lineages, we estimate a Beringian Standstill duration of 2.7 ky or 4.6 ky, according to alternative models, and entry south of the ice sheet after 19.5 kya. Third, we describe the star-like expansion of Q-M848 (within Q-M3) starting at 15 kya [11] in the Americas, followed by establishment of substantial spatial structure in South America by 12 kya. Fourth, the deep branches of the Q-CTS1780 lineage present at low frequencies throughout the Americas today [12] may reflect a separate out-of-Beringia dispersal after the melting of the glaciers at the end of the Pleistocene.
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http://dx.doi.org/10.1016/j.cub.2018.11.029DOI Listing
January 2019

Short fiber reinforced 3d printed ceramic composite with shear induced alignment.

Ceram Int 2017 Oct;43(15):11766-11772

Department of Mechanical Engineering & Mechanics, Lehigh University, Bethlehem, PA 18015, USA.

This paper accounts for utilization of shear induced alignment method during ceramic stereolithography. Lateral oscillation mechanism, combined with 3d printed wall pattern, was employed to generate necessary shear to align fiber in desired direction. First, semicircular channel pattern was printed to assess the effect of difference between wall direction and oscillation direction on the fiber alignment. Then, flexural strength of ceramic matrix was tested with nickel coated carbon fiber and ceramic fiber reinforcements. The results demonstrated that the shear induced alignment further improves the flexural strength compare to randomly distributed samples. Flexural strength of aligned samples with 1.0 wt% carbon fiber loading was improved by ~90% compared to randomly orientated samples and by ~333% compared to unreinforced samples. Finally, fracture surface morphology of the flexural strength test specimens was evaluated. The main fracture mechanism was observed as fiber pull-out.
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http://dx.doi.org/10.1016/j.ceramint.2017.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191193PMC
October 2017

Application of biclustering algorithm in adverse drug reaction monitoring system of China.

Pharmacoepidemiol Drug Saf 2018 11 19;27(11):1257-1264. Epub 2018 Sep 19.

Department of Health Statistics, Second Military Medical University, Shanghai, China.

Purpose: Signal evaluation is considered to be a tedious process owing to the large number of disproportional signals detected. This study aimed to apply a biclustering algorithm in the spontaneous reporting system of China and to obtain the optimal parameters. The biclustering algorithm is expected to improve the efficiency of signal evaluation by identifying similar signal groups.

Methods: Information component (IC) was the method used for disproportionality analysis. By using IC thresholds of various strengths (0.05-4.00), the original quantitative data matrix was transformed into 80 different binary data matrices, where each cell contained either a 1 or 0. The biclustering results were obtained using a total of 720 Bimax algorithm parameters (minimal number of columns and rows was 3, 4, or 5). Next, the optimal parameters were determined through the comprehensive evaluation of the rank sum ration. Finally, we examined the biclustering results under the optimal parameters and evaluated the effect of biclustering analysis on adverse drug reaction (ADR) data in China.

Results: The optimal strength of the IC threshold was 0.80, and the minimum number of rows and columns was 3. After taxonomic evaluation, we also found that 1836 biclusters (42.8%) contained similar drugs or similar ADRs, which accounted for 72.3% of signals unevaluated.

Conclusions: Applying biclustering analysis in spontaneous reporting system could provide support in confirming unrecognized ADRs, identifying rare ADRs, and screening drug-ADR pairs, which need more attention. Biclustering algorithm could improve the efficiency of signal detection and evaluation in China.
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http://dx.doi.org/10.1002/pds.4661DOI Listing
November 2018

[Identify Sudden Cardiac Death Based on Cyclostationary Characteristics of ECG Signal].

Zhongguo Yi Liao Qi Xie Za Zhi 2017 Sep;41(5):322-326

College of Electrical and Information Engineering, Lanzhou University of Technology, Lanzhou, 730050.

Aiming at sudden cardiac death diseases identification accuracy is not high, a new method is proposed to extract the cyclostationary characteristics of ECG signal. We denoise ECG signal through the wavelet transform. Based on the cyclostationary features of ECG signal, we adopt the method of cyclic spectrum estimation in cyclic frequencey domain to extract cyclostationary characteristics. Support vector machine is used to identify the sudden cardiac death. The results show that cyclic frequence average can especially reflect the cyclostationary characteristics of ECG signal and accurately identify the sudden cardiac death. Sudden death of ECG signal recognition accuracy up to reach 97.50%.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2017.05.003DOI Listing
September 2017

Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity.

Sci Rep 2018 05 1;8(1):6837. Epub 2018 May 1.

Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania, 18015, USA.

A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.
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http://dx.doi.org/10.1038/s41598-018-25203-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931581PMC
May 2018

A Facile Way to Fabricate Transparent Superhydrophobic Surfaces.

J Nanosci Nanotechnol 2018 Jul;18(7):5082-5087

Department of BioEngineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.

A fast, easy, and low-cost way to fabricate transparent superhydrophobic (SHP) surfaces is developed. By simply mixing silica nanoparticles (SiNPs), polydimethylsiloxane (PDMS) and heptane to form a suspension, dip- or drop-coating the suspension onto different surfaces, transparent SHP surfaces can be obtained. By tuning the ratio of the three components above, transparency of the coating can reach more than 90% transmittance in the visible region, while static water contact angle of the coating can reach as high as 162°. Dynamic contact angle study shows the advancing contact angle and receding contact angle of water can be as high as 168° and 161°, and the resulting contact angle hysteresis can be as low as 7°. The reported facile way of fabricating transparent superhydrophobic (SHP) surfaces is potential for applications which need both optical transparency and self-cleaning capability, such as solar cells, optical equipment, and visible microfluidic chips.
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http://dx.doi.org/10.1166/jnn.2018.15329DOI Listing
July 2018

Copy number variation arising from gene conversion on the human Y chromosome.

Hum Genet 2018 Jan 5;137(1):73-83. Epub 2017 Dec 5.

Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.

We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0-3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0-2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.
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http://dx.doi.org/10.1007/s00439-017-1857-9DOI Listing
January 2018

Higher triglyceride level predicts hyperuricemia: A prospective study of 6-year follow-up.

J Clin Lipidol 2018 Jan - Feb;12(1):185-192. Epub 2017 Nov 7.

Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, P.R. China. Electronic address:

Background: Despite abundant evidence indicating that higher triglyceride (TG) levels are associated with increased risks of hyperuricemia (HUA), it is unclear whether TG levels can independently predict the incidence of HUA.

Objective: The aim of the study was to investigate whether TG is an independent risk factor of HUA in a cohort study.

Methods: We explored the relationship between TG levels and HUA in a dynamic cohort established in 2009. During the 6 years of follow-up, 5442 subjects without HUA were studied. We divided subjects into 4 groups based on baseline TG levels and used the Cox hazard regression model to estimate HUA risk by TG quartile, after adjustment for potential confounding factors. Kaplan-Meier survival analysis compared the risk of HUA incidence among individuals in each TG quartile.

Results: The incidence of HUA in this cohort was 25.9%. The hazard ratios (95% confidence intervals) for HUA in the second, third, and fourth TG quartiles, compared with the first quartile, were 1.19 (1.01-1.40), 1.33 (1.13-1.57), and 1.62 (1.37-1.92), respectively. The Kaplan-Meier survival analysis suggested that higher TG levels predicted higher incidences of HUA in a dose-dependent relationship. Stratification analyses showed that the association between TG levels and the presence of HUA was more pronounced in individuals aged <50 years, of obese, with normal estimated glomerular filtration rate, and with hypertension.

Conclusion: Our findings suggest that TG level is a significant and independent risk factor for HUA.
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http://dx.doi.org/10.1016/j.jacl.2017.10.009DOI Listing
July 2019

Magnetic particles assisted capture and release of rare circulating tumor cells using wavy-herringbone structured microfluidic devices.

Lab Chip 2017 09;17(19):3291-3299

Department of BioEngineering, Lehigh University, Bethlehem, Pennsylvania 18015, USA.

A wavy-herringbone (wavy-HB) structured microfluidic device was used to effectively and selectively capture and release circulating tumor cells (CTCs) by using immunoaffinity and magnetic force. This device was designed to create passive turbulence and increase the possibility of tumor cells colliding with the device wall. Under an external magnetic field, magnetic particles (MPs) coated with anti-EpCAM against a tumor cell surface protein (EpCAM) were immobilized over the wavy-HB surface to capture tumor cells. After removing the magnetic field, the captured cells with surplus MPs were released from the device and collected; thus, these cells could be re-cultured for further analysis. Under optimized conditions, the capture efficiency of the tumor cells can be as high as 92% ± 2.8%. Capture experiments were also performed on whole blood samples, and the capture efficiency was in a high range of 81-95%, at different tumor cell concentrations. Such a method can potentially be used for CTC sorting from patient blood samples, CTC concentration monitoring, therapeutic guidance and drug dosage choice, and further study of tumors, such as drug screening and tumor mutations.
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http://dx.doi.org/10.1039/c7lc00333aDOI Listing
September 2017

Structure of a pectic polysaccharide from Pseudostellaria heterophylla and stimulating insulin secretion of INS-1 cell and distributing in rats by oral.

Int J Biol Macromol 2018 Jan 7;106:456-463. Epub 2017 Aug 7.

The Institute of Drug Research, Fujian Academy of Traditional Chinese Medicine, Fuzhou, 350003, PR China; The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address:

A water-soluble, pectic polysaccharide named as 0.5MSC-F isolated from Pseudostellaria Heterophylla with a molecular weight of 4.8×10Da that was composed of rhamnose, galactose, arabinose, and galacturonic acid which the major monosaccharide contents range up to 63.20%. Where the main chain was consists of 1,4-linked galacturonic acid and a small amount of 1,2-linked rhamnose was embedded into backbone to connect alternative galacturonic acid in the form of Rhamnogalacturonan I (RG-I) structure. 1, 5-linked arabinose through C-4 of 1, 2-linked rhamnose, another 1, 3 or 1,6-linked galactose through C-4 of 1, 2-linked rhamnose, was interconnected to branch chain. 0.5MSC-F could obviously stimulated insulin secretion of islet cells cultured in high glucose are of potential practical value in the hypoglycemic action. Radioisotopes Tc-labeled-0.5MSC-F was analyzed by SPECT/CT image after oral in rats. At 2h post ingestion, above 40% of the radioactivity was observed in the intestine, but no found in the heart, liver, and kidney. Conjecturing absorption of Tc-labeled 0.5MSC-F might via intestinal mucosa absorption into the systemic circulation.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.08.034DOI Listing
January 2018

Single Carrier with Frequency Domain Equalization for Synthetic Aperture Underwater Acoustic Communications.

Sensors (Basel) 2017 Jul 6;17(7). Epub 2017 Jul 6.

School of Marine Science and Technology, Northwestern Polytechnical University, Xi'an 710072, China.

Phase-coherent underwater acoustic (UWA) communication systems typically employ multiple hydrophones in the receiver to achieve spatial diversity gain. However, small underwater platforms can only carry a single transducer which can not provide spatial diversity gain. In this paper, we propose single-carrier with frequency domain equalization (SC-FDE) for phase-coherent synthetic aperture acoustic communications in which a virtual array is generated by the relative motion between the transmitter and the receiver. This paper presents synthetic aperture acoustic communication results using SC-FDE through data collected during a lake experiment in January 2016. The performance of two receiver algorithms is analyzed and compared, including the frequency domain equalizer (FDE) and the hybrid time frequency domain equalizer (HTFDE). The distances between the transmitter and the receiver in the experiment were about 5 km. The bit error rate (BER) and output signal-to-noise ratio (SNR) performances with different receiver elements and transmission numbers were presented. After combining multiple transmissions, error-free reception using a convolution code with a data rate of 8 kbps was demonstrated.
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http://dx.doi.org/10.3390/s17071584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539470PMC
July 2017

Space-frequency coded orthogonal signal-division multiplexing over underwater acoustic channels.

J Acoust Soc Am 2017 06;141(6):EL513

Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology, 2826 CD Delft, The Netherlands

Orthogonal signal-division multiplexing (OSDM) is a newly emerged modulation scheme which provides a generalized framework unifying conventional orthogonal frequency-division multiplexing (OFDM) and single-carrier frequency domain equalization. In this letter, a space-frequency block coding (SFBC) scheme based on OSDM is proposed for time-varying underwater acoustic channels. The receiver processing includes Doppler compensation, channel estimation, space-frequency decoding, and equalization. Simulation and experimental results demonstrate its superiority over the existing SFBC-OFDM counterpart.
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http://dx.doi.org/10.1121/1.4983632DOI Listing
June 2017

Acoustic Patterning for 3D Embedded Electrically Conductive Wire in Stereolithography.

J Micromech Microeng 2017 Apr 14;27(4). Epub 2017 Mar 14.

Department of Mechanical Engineering & Mechanics, Lehigh University, Bethlehem, PA 18015, USA.

In this paper, we reported a new approach for particle assembly with acoustic tweezer during three-dimensional (3D) printing for the fabrication of embedded conductive wire with 3D structures. A hexagon shaped acoustic tweezer was incorporated with Digital Light Processing (DLP) based stereolithography (SLA) printer to pattern conductive lines via aligning and condensing conductive nanoparticles. The effect of filler content on electrical resistivity and pattern thickness were studied for copper, magnetite nanoparticles, and carbon nanofiber reinforced nanocomposite samples. The obtained data was later used to produce examples of conductive 3D microstructures and embedded electronic components by using the suggested method.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195324PMC
April 2017