Publications by authors named "Jin Chen"

1,485 Publications

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Genetic Polymorphisms of , , and Androgen Receptor and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Chinese Han Population.

Dis Markers 2021 4;2021:2898336. Epub 2021 Oct 4.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022 Anhui, China.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) refers to a common disorder with unclear etiology and unsatisfactory treatment, which reduces the male's quality of life.

Objective: To examine the effects of genetic polymorphisms of , , and androgen receptor () on CP/CPPS.

Methods: The single nucleotide polymorphisms (SNPs) of , , and were genotyped with the improved multiplex ligation detection reaction. The GTEx, RegulomeDB, HaploReg, and 3DSNP databases were adopted to predict the regulatory functions of the genotyped SNPs. The correlation between SNPs and CP/CPPS was analyzed with the test, logistic regression, and two genetic models (codominant and log-additive models). The nomogram was built to predict the risk of CP/CPPS occurrence.

Results: On the whole, 130 CP/CPPS patients and 125 healthy controls were recruited in the study, and 18 SNPs of , , and were genotyped. The results of functional annotation indicated that the 18 genotyped SNPs might have regulatory effects in the whole blood. The rs144488434 was correlated with the elevated CP/CPPS risk (odds ratio (OR): 2.40, 95% confidence interval (CI): 1.12-5.13, = 5.37, and = 0.021) by the test. In the built genetic models, rs10457655 was correlated with the elevated National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores (codominant model: GA/GG: crude mean difference (MD) = 0.98, 95% CI: -1.71-3.67 and AA/GG: crude MD = 9.10, 95% CI: 0.58-17.62, = 0.10). In subgroup analysis, rs2069718 was correlated with the elevated CP/CPPS risk (log-additive model: crude OR = 2.18, 95% CI: 1.03-4.64, and = 0.034) in patients ≥ 35 years. The nomogram integrating age, rs2069718, rs10457655, and rs144488434 showed good performance to predict the risk of CP/CPPS.

Conclusions: Genetic polymorphisms of , , and might act as the genetic factors for CP/CPPS susceptibility, which deserved further explorations.
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http://dx.doi.org/10.1155/2021/2898336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505099PMC
October 2021

Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis.

Theranostics 2021 27;11(19):9705-9720. Epub 2021 Sep 27.

Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.

Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival. We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features. We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis. Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.
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http://dx.doi.org/10.7150/thno.61731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490523PMC
September 2021

Proteomic Response of Rat Pituitary Under Chronic Mild Stress Reveals Insights Into Vulnerability and Resistance to Anxiety or Depression.

Front Genet 2021 17;12:751999. Epub 2021 Sep 17.

Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing, China.

Chronic stress as one of the most significant risk factor can trigger overactivity of hypothalamic-pituitary-adrenal (HPA) axis in depression as well as anxiety. Yet, the shared and unique neurobiological underpinnings underlying the pituitary abnormality in these two disorders have not been made clear. We previously have established depression-susceptible, anxiety-susceptible and insusceptible groups using a valid chronic mild stress (CMS) model. In this work, the possible protein expression changes in the rat pituitary of these three groups were continuously investigated through the use of the comparative quantitative proteomics and bioinformatics approaches. The pituitary-proteome analysis identified totally 197 differential proteins as a CMS response. These deregulated proteins were involved in diverse biological functions and significant pathways potentially connected with the three different behavioral phenotypes, likely serving as new investigative protein targets. Afterwards, parallel reaction monitoring-based independent analysis found out that expression alterations in , , , , and ; , , , , and ; , , , , and were specifically linked to depression-susceptible, anxiety-susceptible and insusceptible groups, respectively, suggesting that the same CMS had different impacts on the pituitary protein regulatory system. Collectively, the current proteomics research elucidated an important molecular basis and furnished new valuable insights into neurochemical commonalities and specificities of the pituitary dysfunctional mechanisms in HPA axis underlying vulnerability and resistance to stress-induced anxiety or depression.
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http://dx.doi.org/10.3389/fgene.2021.751999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484759PMC
September 2021

Selenium can regulate the differentiation and immune function of human dendritic cells.

Biometals 2021 Oct 2. Epub 2021 Oct 2.

School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, Guizhou, China.

Selenium is an essential trace element that can regulate the function of immnue cells via selenoproteins. However, the effects of selenium on human dendritic cell (DCs) remain unclear. Thus, selenoprotein levels in monocytes, immature DCs (imDCs) and mature DCs (mDCs) treated with or without NaSeO were evaluated using RT-PCR, and then the immune function of imDCs and mDCs was detected by flow cytometry, cell counting and the CCK8 assay. In addition, the effects of Se on cytokine and surface marker expression were investigated by RT-PCR. The results revealed different expression levels of selenoprotein in monocytes, imDCs and mDCs, and selenoproeins could be regulated by Se. Moreover, it was indicated that anti-phagocytic activity was improved by 0.1 µM Se, whereas it was suppressed by 0.2 µM Se in imDCs; The migration of imDCs and mDCs was improved by 0.1 µM Se, whereas their migration was inhibited by treatment with 0.05 or 0.2 µM Se; The mixed lymphocyte reaction of mDCs was improved by 0.1 µM Se, and it was inhibited by 0.05 and 0.2 µM Se. In addition, 0.1 µM Se improved the immune function of DCs through the regulation of CD80, CD86, IL12-p35 and IL12-p40. Wheres 0.05 and 0.2 µM Se impaired immune function of DCs by up-regulation of interleukin (IL-10) in imDCs and down-regulation of CD80, CD86, IL12-p35 and IL12-p40 in mDCs. In conclusion, 0.1 µM Se might improve the immune function of human DCs through selenoproteins.
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http://dx.doi.org/10.1007/s10534-021-00347-4DOI Listing
October 2021

Ca sensor-mediated ROS scavenging suppresses rice immunity and is exploited by a fungal effector.

Cell 2021 Oct 30;184(21):5391-5404.e17. Epub 2021 Sep 30.

National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address:

Plant immunity is activated upon pathogen perception and often affects growth and yield when it is constitutively active. How plants fine-tune immune homeostasis in their natural habitats remains elusive. Here, we discover a conserved immune suppression network in cereals that orchestrates immune homeostasis, centering on a Ca-sensor, RESISTANCE OF RICE TO DISEASES1 (ROD1). ROD1 promotes reactive oxygen species (ROS) scavenging by stimulating catalase activity, and its protein stability is regulated by ubiquitination. ROD1 disruption confers resistance to multiple pathogens, whereas a natural ROD1 allele prevalent in indica rice with agroecology-specific distribution enhances resistance without yield penalty. The fungal effector AvrPiz-t structurally mimics ROD1 and activates the same ROS-scavenging cascade to suppress host immunity and promote virulence. We thus reveal a molecular framework adopted by both host and pathogen that integrates Ca sensing and ROS homeostasis to suppress plant immunity, suggesting a principle for breeding disease-resistant, high-yield crops.
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http://dx.doi.org/10.1016/j.cell.2021.09.009DOI Listing
October 2021

Neurodevelopmental toxicity of alumina nanoparticles to zebrafish larvae: Toxic effects of particle sizes and ions.

Food Chem Toxicol 2021 Sep 27:112587. Epub 2021 Sep 27.

Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China. Electronic address:

The aim of this study was to explore the mechanism of neurodevelopmental toxicity of alumina nanoparticles (AlNPs) on zebrafish larvae, specifically, the toxic effects of AlNPs of different particle sizes and of dissolved aluminum ions. AlNPs with sizes of 13 nm (13 nm-Al) and 50 nm (50 nm-Al) were used as the main research objects; while nanocarbon particles with sizes of 13 nm (13 nm-C) and 50 nm (50 nm-C) as particle-size controls; and an aluminum chloride solution (Al) as an ion control. Zebrafish embryos were exposed to different treatments from 6 h post-fertilization (hpf) to 168 hpf. Deformities were observed at different time points. Neurodevelopmental behavior tests were carried out, and oxidative stress responses and transcriptional alterations in autophagy-related genes were assessed. Malformations occurred in the 13 nm-Al, 50 nm-Al, and Al treated groups at different developmental stages of zebrafish larval, but no malformations were observed in the 13 nm-C or 50 nm-C groups. In addition, the average speed, distance travelled and thigmotaxis in zebrafish larvae decreased in the AlNPs treated group, and the effects were related to the particle sizes. Furthermore, increases in the oxidative stress response and autophagy-related genes expression were also related to the particle sizes of AlNPs as well. In conclusion, the mechanism underlying the neurodevelopmental toxicity of AlNPs on zebrafish larvae mainly depended on the size of the nanoparticles, and dissolved Al also contributes to the toxic effects.
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http://dx.doi.org/10.1016/j.fct.2021.112587DOI Listing
September 2021

Efficacy and safety evaluation of low-intensity extracorporeal shock wave therapy on prostatitis-like symptoms: An open-label, single-arm trial.

Andrologia 2021 Sep 28:e14260. Epub 2021 Sep 28.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.

The present work aims to evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (Li-ESWT) on patients with prostatitis-like symptoms (PLS). Patients with PLS were recruited and received four-week Li-ESWT (once per week), which was conducted at a frequency of 3 Hz with a preferred energy flow density of 0.25 mJ/mm . The scores of the National Institute of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and Visual Analogue Scale (VAS) were recorded to assess the remission of disease in the 0, 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks. A decrease of the NIH-CPSI score ≥6 was regarded as the effectiveness standard of Li-ESWT. Among 91 enrolled patients, the scores of all validated questionnaires presented significant improvements in the 4th week (p < .05) compared with that in baseline, except for IIEF-5. The treatment effective rates in the 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks were 28.57%, 38.46%, 47.25%, 51.65%, 57.30%, 68.18% and 69.44%, respectively. No pronounced undesirable side effect has occurred. Li-ESWT is effective and safe in treating PLS. The efficacy can be maintained within three months.
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http://dx.doi.org/10.1111/and.14260DOI Listing
September 2021

Alcohol consumption and the risk of rosacea: A systematic review and meta-analysis.

J Cosmet Dermatol 2021 Sep 28. Epub 2021 Sep 28.

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Rosacea is a chronic inflammatory skin disease that affects people's life quality. It has been found to be related to many detrimental factors including ultraviolet exposure. However, the association between alcohol consumption and rosacea has long been debated.

Aims: To elucidate this association, we conducted a systematic review and meta-analysis.

Methods: We performed a systematic search of the literature published before February 16, 2021 on PubMed, Embase, and the Cochrane database and used a meta-analytic approach to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs).

Results: Finally, 14 eligible studies were identified, and alcohol consumption was not found to be a risk factor for rosacea. However, in subgroup analysis, alcohol consumption increased the risk of phymatous rosacea (PhR) and the pooled OR was 4.17 (95% CI = 1.76-9.91).

Conclusion: Overall, our study showed that alcohol consumption was a risk factor in phymatous rosacea (PhR). More studies of rosacea investigating sex distribution, alcohol intake levels, and types of alcoholic beverages consumed are needed in the future.
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http://dx.doi.org/10.1111/jocd.14483DOI Listing
September 2021

Chemical components change along the ontogeny of a bat fruit (Neolamarckia cadamba) with ripening asynchrony in favour of its fruit selection and seed dispersal.

Naturwissenschaften 2021 Sep 28;108(5):46. Epub 2021 Sep 28.

Department of Zoology, School of Life Sciences, Periyar University, Salem, Tamil Nadu, 636011, India.

An asynchronous fruit-ripening strategy can enhance the chance of seed dispersal by providing ripe fruits for an extended period to foragers. However, mechanisms associated with this strategy that can facilitate seed dispersal are understudied. This study aimed to investigate whether the chemical components (minerals and secondary metabolites) of a bat fruit with ripening asynchrony change along its ontogeny (Rubiaceae: Neolamarckia cadamba). We predicted that the seed-to-pulp ratio would increase along with fruit ripeness. The chemical components of the fruit were also predicted to change along their ontogenesis in favour of fruit selection and seed dispersal by fruit bats. Our study shows that the asynchronous fruiting strategy limited the number of ripe fruits daily so that fruits were available at a steady rate. As predicted, the seed-to-pulp ratio of each fruit increased along with fruit development. A fruit's mineral concentration also increased as fruit developed, with a sharp jump at full ripeness, when fruit colour also changed. In contrast, the concentration of secondary metabolite compositions decreased gradually during the process of ontogeny. Fruit bats (Pteropodidae: Pteropus giganteus and Cynopterus sphinx) were the only nocturnal frugivore visitors of these trees and their fruit selection was driven by fruit size and colour. Both bats preferably consumed ripe fruits, which had a higher concentration of attractants (essential minerals) and a lower concentration of deterrents (secondary metabolites), supplemented with a higher seed-to-pulp ratio. The bats exhibited different foraging patterns and home ranges resulting in dispersal (as measured by feeding roost location) occurring across different spatial scales. Our study shows that the chemical components involved in an asynchronous fruit-ripening process could select for extended fruit availability by intensifying the demand for each ripe fruit among legitimate seed dispersers, which increases the likelihood of fruits being dispersed away from parent crowns.
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http://dx.doi.org/10.1007/s00114-021-01756-8DOI Listing
September 2021

Preparation and Properties of 3D Printing Light-Curable Resin Modified with Hyperbranched Polysiloxane.

ACS Omega 2021 Sep 9;6(37):23683-23690. Epub 2021 Sep 9.

College of Material Science and Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.

A novel, hyperbranched polysiloxane (HBPSi) is successfully synthesized via hydrolysis using γ-methacryloxypropyl trimethoxysilane (A174) and deionized water, under catalyst-free conditions. Then, for the first time, the HBPSis are used to modify a 3D printing light-curing epoxy resin. Thermogravimetry results showed that the addition of HBPSi improved the heat resistance of the epoxy resin. Experimental results also show that the addition of HBPSi simultaneously improves tensile strength, elongation at break, and impact strength. In particular, a great increase in the toughness of 3D printing light-curing epoxy resin is observed, with 5 wt % HBPSi loading. These results indicate that the HBPSi containg OH- and Si-O-Si can be potentially effective at improving the performance of the 3D printing light-curing epoxy resin. This investigation suggests that the method proposed herein is a new approach to develop the performance of 3D printing light-curing epoxy resin for cutting-edge industries, especially those that simultaneously have outstanding thermal resistance and toughness.
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http://dx.doi.org/10.1021/acsomega.1c01232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459355PMC
September 2021

Assessing Clinical Effects of Traditional Chinese Medicine Interventions: Moving Beyond Randomized Controlled Trials.

Front Pharmacol 2021 7;12:713071. Epub 2021 Sep 7.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

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http://dx.doi.org/10.3389/fphar.2021.713071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452912PMC
September 2021

Association of CNVs with methylation variation.

NPJ Genom Med 2020 Sep 24;5(1):41. Epub 2020 Sep 24.

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA.

Germline copy number variants (CNVs) and single-nucleotide polymorphisms (SNPs) form the basis of inter-individual genetic variation. Although the phenotypic effects of SNPs have been extensively investigated, the effects of CNVs is relatively less understood. To better characterize mechanisms by which CNVs affect cellular phenotype, we tested their association with variable CpG methylation in a genome-wide manner. Using paired CNV and methylation data from the 1000 genomes and HapMap projects, we identified genome-wide associations by methylation quantitative trait locus (mQTL) analysis. We found individual CNVs being associated with methylation of multiple CpGs and vice versa. CNV-associated methylation changes were correlated with gene expression. CNV-mQTLs were enriched for regulatory regions, transcription factor-binding sites (TFBSs), and were involved in long-range physical interactions with associated CpGs. Some CNV-mQTLs were associated with methylation of imprinted genes. Several CNV-mQTLs and/or associated genes were among those previously reported by genome-wide association studies (GWASs). We demonstrate that germline CNVs in the genome are associated with CpG methylation. Our findings suggest that structural variation together with methylation may affect cellular phenotype.
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http://dx.doi.org/10.1038/s41525-020-00145-wDOI Listing
September 2020

High-Efficiency Classification of White Blood Cells Based on Object Detection.

J Healthc Eng 2021 13;2021:1615192. Epub 2021 Sep 13.

Key Laboratory of RF Circuits and Systems, Ministry of Education, Hangzhou Dianzi University, Hangzhou 310018, China.

White blood cells (WBCs) play a significant role in the human immune system, and the content of various subtypes of WBCs is usually maintained within a certain range in the human body, while deviant levels are important warning signs for diseases. Hence, the detection and classification of WBCs is an essential diagnostic technique. However, traditional WBC classification technologies based on image processing usually need to segment the collected target cell images from the background. This preprocessing operation not only increases the workload but also heavily affects the classification quality and efficiency. Therefore, we proposed one high-efficiency object detection technology that combines the segmentation and recognition of targets into one step to realize the detection and classification of WBCs in an image at the same time. Two state-of-the-art object detection models, Faster RCNN and Yolov4, were employed and comparatively studied to classify neutrophils, eosinophils, monocytes, and lymphocytes on a balanced and enhanced Blood Cell Count Dataset (BCCD). Our experimental results showed that the Faster RCNN and Yolov4 based deep transfer learning models achieved classification accuracy rates of 96.25% and 95.75%, respectively. For the one-stage model, Yolov4, while ensuring more than 95% accuracy, its detection speed could reach 60 FPS, which showed better performance compared with the two-stage model, Faster RCNN. The high-efficiency object detection network that does not require cell presegmentation can remove the difficulty of image preprocessing and greatly improve the efficiency of the entire classification task, which provides a potential solution for future real-time point-of-care diagnostic systems.
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http://dx.doi.org/10.1155/2021/1615192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452424PMC
September 2021

Enhancing discoveries of molecular QTL studies with small sample size using summary statistic imputation.

Brief Bioinform 2021 Sep 20. Epub 2021 Sep 20.

School of Computer Science, Northwestern Polytechnical University, 1 Dongxiang Rd, 710129, Xi'an, China.

Quantitative trait locus (QTL) analyses of multiomic molecular traits, such as gene transcription (eQTL), DNA methylation (mQTL) and histone modification (haQTL), have been widely used to infer the functional effects of genome variants. However, the QTL discovery is largely restricted by the limited study sample size, which demands higher threshold of minor allele frequency and then causes heavy missing molecular trait-variant associations. This happens prominently in single-cell level molecular QTL studies because of sample availability and cost. It is urgent to propose a method to solve this problem in order to enhance discoveries of current molecular QTL studies with small sample size. In this study, we presented an efficient computational framework called xQTLImp to impute missing molecular QTL associations. In the local-region imputation, xQTLImp uses multivariate Gaussian model to impute the missing associations by leveraging known association statistics of variants and the linkage disequilibrium (LD) around. In the genome-wide imputation, novel procedures are implemented to improve efficiency, including dynamically constructing a reused LD buffer, adopting multiple heuristic strategies and parallel computing. Experiments on various multiomic bulk and single-cell sequencing-based QTL datasets have demonstrated high imputation accuracy and novel QTL discovery ability of xQTLImp. Finally, a C++ software package is freely available at https://github.com/stormlovetao/QTLIMP.
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http://dx.doi.org/10.1093/bib/bbab370DOI Listing
September 2021

Traumatic cervical spinal cord injury: relationship of MRI findings to initial neurological impairment.

Eur Spine J 2021 Sep 20. Epub 2021 Sep 20.

Division of Spine Surgery, Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, No. 389 Xincun Road, Putuo District, Shanghai, China.

Purpose: To quantify the degree of available space for the cord and cord swelling in patients following traumatic cervical spinal cord injury (TCSCI), and to assess the relationship among the available space for the cord, cord swelling, and the severity of neurological impairment.

Methods: This study included 91 patients. The following indexes were measured by two blinded observers: maximum cord available area (CAA) and maximum cord swelling area (CSA). The American Spinal Injury Association (ASIA) impairment scale (AIS) grades were used to evaluate the extent of neurological injury. Relationship among CAA, CSA, and initial AIS grades was assessed via univariate and multivariate analyses.

Results: Patients who were AIS grade A (complete injury) demonstrated significantly greater median CAA and CSA than AIS grade C or D (incomplete injury) (P < 0.01). Multivariate analysis identified only CAA (OR 20.88 [95% CI 1.50-291.21]; P = 0.024) and CSA (OR 17.84 [95% CI 1.15-276.56]; P = 0.039) were identified as independently influencing the likelihood of complete injury at the initial assessment. The classification accuracy was best for CAA and CSA; areas under the curve were 0.8998 (95% CI 0.7881-1.0000) and 0.9167 (95% CI 0.8293-1.0000), respectively.

Conclusion: The present study provides a novel radiologic method for identifying the severity of TCSCI with T2-weighted MRI findings. Greater available space for the cord (CAA > 38%) and cord swelling (CSA > 29%) can be used to identify patients at risk for TCSCI and both imaging characteristics are associated with an increased likelihood of severe neurological deficits.

Level Of Evidence: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
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http://dx.doi.org/10.1007/s00586-021-06996-wDOI Listing
September 2021

KGDAL: Knowledge Graph Guided Double Attention LSTM for Rolling Mortality Prediction for AKI-D Patients.

ACM BCB 2021 Aug;2021

Department of Internal Medicine, Department of Computer Science, University of Kentucky, Lexington, Kentucky, USA.

With the rapid accumulation of electronic health record (EHR) data, deep learning (DL) models have exhibited promising performance on patient risk prediction. Recent advances have also demonstrated the effectiveness of knowledge graphs (KG) in providing valuable prior knowledge for further improving DL model performance. However, it is still unclear how KG can be utilized to encode high-order relations among clinical concepts and how DL models can make full use of the encoded concept relations to solve real-world healthcare problems and to interpret the outcomes. We propose a novel knowledge graph guided double attention LSTM model named KGDAL for rolling mortality prediction for critically ill patients with acute kidney injury requiring dialysis (AKI-D). KGDAL constructs a KG-based two-dimension attention in both time and feature spaces. In the experiment with two large healthcare datasets, we compared KGDAL with a variety of rolling mortality prediction models and conducted an ablation study to test the effectiveness, efficacy, and contribution of different attention mechanisms. The results showed that KGDAL clearly outperformed all the compared models. Also, KGDAL-derived patient risk trajectories may assist healthcare providers to make timely decisions and actions. The source code, sample data, and manual of KGDAL are available at https://github.com/lucasliu0928/KGDAL.
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http://dx.doi.org/10.1145/3459930.3469513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445228PMC
August 2021

Transcription factor SOX2 contributes to nonalcoholic fatty liver disease development by regulating the expression of the fatty acid transporter CD36.

FEBS Lett 2021 10 27;595(19):2493-2503. Epub 2021 Sep 27.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.

Nonalcoholic fatty liver disease (NAFLD) can lead to hepatocellular carcinoma (HCC). The level of the transcription factor SOX2 correlates with HCC progression, but its role in fat accumulation remains unclear. Here, a high-fat diet, with and without fructose, significantly upregulated SOX2 in murine liver tissue. Treatment with free fatty acids (FFAs) and fructose upregulated SOX2 in murine FL83B hepatocytes. SOX2 overexpression or knockdown regulated triglyceride synthesis and lipid accumulation after FFA stimulation. CD36, a fatty acid transporter, and Yes-associated protein (YAP), a downstream molecule of the Hippo signaling pathway, were upregulated by FFA/fructose in vivo and in vitro. Transcriptional regulation of CD36 by SOX2 suggested the involvement of CD36 in SOX2-mediated hepatic steatosis. Thus, SOX2 may be a target to prevent NAFLD development.
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http://dx.doi.org/10.1002/1873-3468.14193DOI Listing
October 2021

Two orders of magnitude extra SERS enhancement on silver nanoparticle-based substrate induced by laser irradiation in nitrogen ambient.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Sep 8;265:120372. Epub 2021 Sep 8.

National Laboratory of Solid State Microstructures, College of Engineering and Applied Sciences, and Collaborative Innovation Centre of Advanced Microstructures, Nanjing University, Nanjing 210093, China. Electronic address:

Photo-reduction of silver oxide and light-induced Ag nanoparticle (NP) generations have been applied for Surface-enhanced Raman spectroscopy (SERS) substrate fabricated for years. In this paper, we demonstrate a general method to enhance the SERS activity of conventional Ag NPs-based SERS substrates by performing Raman scattering measurement in a nitrogen ambient after a period of laser irradiation (photoactivation). The Raman characteristic peak intensity of carbonaceous impurities adsorbed on the surfaces of Ag NPs display an additional enhancement of 93 times after photoactivation in nitrogen ambient. A 3-fold extra Raman gain enhancement is also observed in the nitrogen-protected SERS measurement of R6G molecules. The extra SERS enhancement is attributed to the sub-nanometer scale near-field coupling between the Ag NPs and the photo-generated Ag clusters in the surface oxide layer of Ag NPs. This model is verified through the finite-difference time-domain (FDTD) simulations.
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http://dx.doi.org/10.1016/j.saa.2021.120372DOI Listing
September 2021

Magnetic resonance-guided thermal ablation for small liver malignant tumor located on segment II or IVa abutting the heart: a retrospective cohort study.

Int J Hyperthermia 2021 ;38(1):1359-1365

Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University; Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.

Objective: This study aimed to evaluate the clinical safety and efficacy magnetic resonance (MR)-guided percutaneous thermal ablation for the treatment of small liver malignant tumors of segment II and IVa (≤3.0 cm) abutting the heart.

Method: The enrollment of 24 patients with 25 malignant liver lesions located on the II or IVa segment abutting the heart who underwent MRI-guided thermal ablation between August 2010 and February 2020 were retrospectively analyzed. Follow-up MRI was performed to evaluate the curative effect. Local tumor progression-free survival and overall survival rates were also calculated.

Results: The procedures including radiofrequency ablation (RFA) for 15 patients and microwave ablation (MWA) for 9 patients were successfully accomplished (technical success rate of 100%) without major complications. The mean duration time was 78.4 ± 29.4 min (40-140 min), and mean follow-up time was 31.5 ± 22.2 months (6-92 months). The technical efficacy was 100% following one ablation session with MRI assessment after one month. Local tumor progression was observed in one patient with a metastatic lesion located in segment II at 18 months follow-up. The progression-free survival time was 20.1 ± 16.9 months (median: 15 months). The 1-, 3-, and 5-year local tumor progression-free survival rates of this patient were 100%, 94.7%, and 94.7%, respectively. With regards to all the patients, the 1-, 3-, and 5-year estimated overall survival rates were 91.7%, 80.6%, and 50.1%, respectively.

Conclusion: MR-guided thermal ablation is safe and effective for the treatment of small liver malignant tumors located on the II or IVa segment abutting the heart.
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http://dx.doi.org/10.1080/02656736.2021.1976851DOI Listing
September 2021

The Impact of an Authoritarian Personality on Pro-Environmental Behaviour for Air Pollution Mitigation through Interactions with Social Norms.

Authors:
Jiawen Cao Jin Chen

Int J Environ Res Public Health 2021 Sep 3;18(17). Epub 2021 Sep 3.

CAS Key Laboratory of Tropical Forest Ecology, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla 666303, China.

This study examines how risk perception and authoritarian personality affect public engagement in mitigating air pollution. Data were collected ( = 2010) from 13 Chinese cities with varying air pollution gradients using questionnaires. The results demonstrated that air pollution was significantly correlated with people's risk perception and concern about air pollution, which significantly affected their pro-environmental behaviour (PEB). However, high-risk perceptions undermine the public's self-efficacy and reduce people's PEB in the private sphere. People with high scores of the authoritarian personality type were reluctant to engage in PEB in the private sphere; interestingly, it can also be transformed into a stronger PEB in the public sphere via social norms. Thus, this study suggests that educational activities can break the negative link between authoritarianism and environmentalism, leading to behavioural change. Hence, it is essential for education programs to harvest positive outcomes via adaptive approaches for varying authoritarian personalities.
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http://dx.doi.org/10.3390/ijerph18179301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431633PMC
September 2021

Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis.

Acta Cir Bras 2021 3;36(7):e360705. Epub 2021 Sep 3.

MM. Department of Pharmacy - Zhejiang Pharmaceutical College - Ningbo, China.

Purpose: To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms.

Methods: Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis.

Results: The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant.

Conclusions: FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.
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http://dx.doi.org/10.1590/ACB360705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428671PMC
September 2021

Tetrandrine suppresses the growth of human osteosarcoma cells by regulating multiple signaling pathways.

Bioengineered 2021 12;12(1):5870-5882

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.

Although osteosarcoma (OS) is the most common malignant tumor among juvenile bone tumors, its treatment plan and clinical outcome have not improved significantly in recent decades. Tetrandrine (TET), a Chinese medicine that is usually used in the therapy of silicosis, hypertension and arthritis, has been confirmed by many studies to possess potent antitumour growth properties, but there are different limitations when describing specific mechanisms. Here, we found that TET can obviously prevent the proliferation, migration and invasion of both 143B and MG63 cells and promote their apoptosis in vitro. Our results for luciferase reporter and Western blotting assays show that TET may exert its antitumour activity by regulating multiplex signaling pathways, including the MAPK/Erk, PTEN/Akt, Juk and Wnt signaling pathways. Furthermore, the regulatory effect of TET on OS cells and related signaling pathways was verified again in vivo. Our findings suggest that the anticancer function of TET on human OS may be mediated by its targeting of multiple signaling pathways and that TET may be used as a single drug or in combination with other drugs during the treatment of OS.
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http://dx.doi.org/10.1080/21655979.2021.1967034DOI Listing
December 2021

Coating Polyelectrolyte Multilayers Loaded with Quercetin on Titanium Surfaces by Layer-By-Layer Assembly Technique to Improve Surface Osteogenesis Under Osteoporotic Condition.

J Biomed Nanotechnol 2021 Jul;17(7):1392-1403

Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Lucheng District, Wenzhou 325000, Zhejiang Province, People's Republic of China.

Titanium (Ti) and its alloy implants are widely used in the field of orthopedics, and osteoporosis is an important reason for implantation failure. This study aimed to establish a quercetin (QTN) controlled release system on the surface of titanium implants and to study its effects on osteogenesis and osseointegration on the surface of implants. Polyethylenimine (PEI) was first immobilized on a titanium substrate as the base layer, and then, hyaluronic acid/chitosan-quercetin (HA/CS-QTN) multilayer films were assembled on the PEI layer by a self-assembly technique. Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and contact angle measurements were used to characterize and analyze the samples. The release characteristics of QTN were studied by release assays. The osteogenic ability of the samples was evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The FTIR, SEM, and contact angle measurements all showed that the PEI substrate layer and HA/CS-QTN multilayer film were successfully immobilized on the titanium matrix. The drug release test showed the successful establishment of a QTN controlled release system. The results showed that osteoblasts exhibited higher adhesion, proliferation and differentiation ability on the coated titanium matrix than on the pure titanium surface. In addition, the results showed that the HA/CS-QTN coating significantly increased the new bone mass around the implant. By depositing a PEI matrix layer and HA/CS-QTN multilayer films on titanium implants, a controlled release system of QTN was established, which improved implant surface osseointegration under osteoporotic conditions. This study proposes a new implant therapy strategy for patients with osteoporosis.
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http://dx.doi.org/10.1166/jbn.2021.3115DOI Listing
July 2021

Structured elements drive extensive circular RNA translation.

Mol Cell 2021 Aug 19. Epub 2021 Aug 19.

Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA; Departments of Dermatology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

The human genome encodes tens of thousands circular RNAs (circRNAs) with mostly unknown functions. Circular RNAs require internal ribosome entry sites (IRES) if they are to undergo translation without a 5' cap. Here, we develop a high-throughput screen to systematically discover RNA sequences that can direct circRNA translation in human cells. We identify more than 17,000 endogenous and synthetic sequences as candidate circRNA IRES. 18S rRNA complementarity and a structured RNA element positioned on the IRES are important for driving circRNA translation. Ribosome profiling and peptidomic analyses show extensive IRES-ribosome association, hundreds of circRNA-encoded proteins with tissue-specific distribution, and antigen presentation. We find that circFGFR1p, a protein encoded by circFGFR1 that is downregulated in cancer, functions as a negative regulator of FGFR1 oncoprotein to suppress cell growth during stress. Systematic identification of circRNA IRES elements may provide important links among circRNA regulation, biological function, and disease.
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http://dx.doi.org/10.1016/j.molcel.2021.07.042DOI Listing
August 2021

The biomechanical effect of preexisting different types of disc herniation in cervical hyperextension injury.

J Orthop Surg Res 2021 Aug 24;16(1):527. Epub 2021 Aug 24.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, 200065, Shanghai, People's Republic of China.

Objective: Preexisting severe cervical spinal cord compression is a significant risk factor in cervical hyperextension injury, and the neurological function may deteriorate after a slight force to the forehead. There are few biomechanical studies regarding the influence of pathological factors in hyperextension loading condition. The aim of this study is to analyze the effects of preexisting different types of cervical disc herniation and different degrees of compression on the spinal cord in cervical hyperextension.

Method: A 3D finite element (FE) model of cervical spinal cord was modeled. Local type with median herniation, local type with lateral herniation, diffuse type with median herniation, and diffuse type with lateral herniation were simulated in neutral and extention positions. The compressions which were equivalent to 10%, 20%, 30%, and 40% of the sagittal diameter of the spinal cord were modeled.

Results: The results of normal FE model were consistent with those of previous studies. The maximum von Mises stresses appeared in the pia mater for all 32 loading conditions. The maximum von Mises stresses in extension position were much higher than in neutral position. In most cases, the maximum von Mises stresses in diffuse type were higher than in local type.

Conclusion: Cervical spinal cord with preexisting disc herniation is more likely to be compressed in hyperextension situation than in neutral position. Diffuse type with median herniation may cause more severe compression with higher von Mises stresses concentrated at the anterior horn and the peripheral white matter, resulting in acute central cord syndrome from biomechanical point of view.
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http://dx.doi.org/10.1186/s13018-021-02677-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383414PMC
August 2021

Comparative Proteomics of Rat Olfactory Bulb Reveal Insights into Susceptibility and Resiliency to Chronic-stress-induced Depression or Anxiety.

Neuroscience 2021 10 21;473:29-43. Epub 2021 Aug 21.

Institute of Neuroscience, Basic Medical College, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Chronic stress causes the abnormality of olfactory bulb (OB) in both anxiety and depression, however, the unique and common neurobiological underpinnings are still poorly understood. Previously, we built the three groups by chronic mild stress (CMS), depression-susceptible (Dep-Sus): with depression-like behavior, anxiety-susceptible (Anx-Sus): with anxiety-like behavior and insusceptible (Insus): without depression- and anxiety-like behaviors. To continuously explore the protein expression changes in these three groups, comparative quantitative proteomics analysis was conducted on the rat OB as crucial part of the olfactory system. Next, bioinformatics analyses were implemented whereas protein expressions were independently analyzed by parallel reaction monitoring (PRM) or Western blot (WB). The OB-proteome analysis identified totally 133 differentially expressed proteins as a CMS response. These deregulated proteins were involved in multiple functions and significant pathways potentially correlated with phenotypes of maladaptive behavior of depression or anxiety as well as adaptive behavior, and hence might act as potential candidate protein targets. The subsequent PRM-based or WB-based analyses showed that changes in Nefl, Mtmr7 and Tk2; Prkaca, Coa3, Cox6c2, Lamc1 and Tubal3; and Pabpn1, Nme3, Sos1 and Lum were uniquely associated with Dep-Sus, Anx-Sus, and Insus groups, respectively. These phenotype-specific deregulated proteins were primarily involved in multiple metabolic and signaling pathways, suggesting that the identical CMS differently impacted the olfactory protein regulation system and biological processes. To sum up, our present data as a useful proteomics underpinning provided the common and distinct molecular insights into the biochemical understanding of OB dysfunction underlying susceptibility and resiliency to chronic-stress-induced anxiety or depression.
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http://dx.doi.org/10.1016/j.neuroscience.2021.08.012DOI Listing
October 2021

Nanobody-based immunosensing methods for safeguarding public health.

J Biomed Res 2021 Jul;35(4):318-326

Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.

Immunosensing methods are biosensing techniques based on specific recognition of an antigen-antibody immunocomplex, which have become commonly used in safeguarding public health. Taking advantage of antibody-related biotechnological advances, the utilization of an antigen-binding fragment of a heavy-chain-only antibody termed as 'nanobody' holds significant biomedical potential. Compared with the conventional full-length antibody, a single-domain nanobody retaining cognate antigen specificity possesses remarkable physicochemical stability and structural adaptability, which enables a flexible and efficient molecular design of the immunosensing strategy. This minireview aims to summarize the recent progress in immunosensing methods using nanobody targeting tumor markers, environmental pollutants, and foodborne microbes.
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http://dx.doi.org/10.7555/JBR.35.20210108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383166PMC
July 2021

Regulation nature of water-choline amino acid ionic liquid mixtures on the disaggregation behavior of starch.

Carbohydr Polym 2021 Nov 22;272:118474. Epub 2021 Jul 22.

School of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, Engineering Research Center of Starch and Vegetable Protein Processing Ministry of Education, South China University of Technology, Guangzhou 510640, China. Electronic address:

Fully green and renewable choline amino acid (choline glycine, [Cho][Gly]) ionic liquid (IL) was firstly explored and evaluated as a solvent for starch. By a thorough investigation of microstructure evolution of water-[Cho][Gly] (w:IL) mixtures, its regulation mechanism on disaggregation behaviors of starch was revealed and illuminated. Compared with pure water, existed hydrated free ions in w:IL-9:1 and w:IL-7:3 restrict starch-water interactions to disaggregate of starch, thus hampering gelatinization of starch. While the gelatinization temperatures decreased at w:IL-5:5 and w:IL-4:6 mixtures with a result of homogeneous starch solutions. The tight and water-separated ion pairs existed at w:IL-5:5 and w:IL-4:6 mixtures allow adequate ions to interact with starch to facilitate the disaggregation of starch. At w:IL-2:8 and w:IL-0:10 mixtures, an exothermic dissolution of starch was observed at high temperatures as a result of predominant starch-ion interactions. These results provide the possibility of using [Cho][Gly] solvent to meet various application requirements of starch.
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http://dx.doi.org/10.1016/j.carbpol.2021.118474DOI Listing
November 2021

The qualitative accuracy of clinical dermatophytes via matrix-assisted laser desorption ionization-time of flight mass spectrometry: a meta-analysis.

Med Mycol 2021 Aug 20. Epub 2021 Aug 20.

Department of Respiratory Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.

Dermatophytes are an important part of superficial fungal infections, and accurate diagnosis is paramount for successful treatment. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a powerful tool to identify clinical pathogens; its advantages are cost-effectiveness, rapid detection, and high accuracy. However, as the accurate identification of clinical dermatophytes via MALDI-TOF MS has still not been fully evaluated, we performed a meta-analysis for systematic evaluation it. Fifteen eligible studies were involved and showed high accuracy with an identification ratio of 0.96 (95%CI = 0.92─1.01) and 0.91 (95%CI = 0.86─0.96) at the genus and species levels, respectively. The results showed higher accuracy ratio of Vitek MS (91%) than MALDI Biotyper (85%). Dermatophytes such as Trichophyton interdigitale (0.99, 95%CI = 0.97─1.02), T. mentagrophytes var interdigitale (1.00, 95%CI = 0.98─1.02), and Microsporum canis (0.97, 95%CI = 0.89─1.04) showed high accuracy in detected clinical dermatophytes. Moreover, a library with self-built database set up by laboratories showed higher accuracy than commercial database, and 15-day cultivation for dermatophytes showed highest accuracy considering culture time. High heterogeneity was observed and decreased only with the subgroup analysis of species. The subgroup analysis of mass spectrometry, library database, and culture time also exhibited high heterogeneity. In summary, our results showed that MALDI-TOF MS could be used for highly accurate detection of clinically pathogenic dermatophytes, which could be an alternative diagnostic method in addition to morphological and molecular methods.

Lay Abstract: This meta-analysis comprehensively investigated the qualitative accuracy of clinical dermatophytes through MALDI-TOF MS. Owing to the high accuracy observed at both genus and species levels, this approach could be an alternative diagnostic method in addition to morphological and molecular methods.
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http://dx.doi.org/10.1093/mmy/myab049DOI Listing
August 2021
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