Publications by authors named "Tao Huang"

1,961 Publications

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Identifying COVID-19 Severity-Related SARS-CoV-2 Mutation Using a Machine Learning Method.

Life (Basel) 2022 May 28;12(6). Epub 2022 May 28.

School of Life Sciences, Shanghai University, Shanghai 200444, China.

SARS-CoV-2 shows great evolutionary capacity through a high frequency of genomic variation during transmission. Evolved SARS-CoV-2 often demonstrates resistance to previous vaccines and can cause poor clinical status in patients. Mutations in the SARS-CoV-2 genome involve mutations in structural and nonstructural proteins, and some of these proteins such as spike proteins have been shown to be directly associated with the clinical status of patients with severe COVID-19 pneumonia. In this study, we collected genome-wide mutation information of virulent strains and the severity of COVID-19 pneumonia in patients varying depending on their clinical status. Important protein mutations and untranslated region mutations were extracted using machine learning methods. First, through Boruta and four ranking algorithms (least absolute shrinkage and selection operator, light gradient boosting machine, max-relevance and min-redundancy, and Monte Carlo feature selection), mutations that were highly correlated with the clinical status of the patients were screened out and sorted in four feature lists. Some mutations such as D614G and V1176F were shown to be associated with viral infectivity. Moreover, previously unreported mutations such as A320V of nsp14 and I164ILV of nsp14 were also identified, which suggests their potential roles. We then applied the incremental feature selection method to each feature list to construct efficient classifiers, which can be directly used to distinguish the clinical status of COVID-19 patients. Meanwhile, four sets of quantitative rules were set up, which can help us to more intuitively understand the role of each mutation in differentiating the clinical status of COVID-19 patients. Identified key mutations linked to virologic properties will help better understand the mechanisms of infection and will aid in the development of antiviral treatments.
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http://dx.doi.org/10.3390/life12060806DOI Listing
May 2022

Coal combustion facilitating faster burial of char than soot in a plateau lake of southwest China.

J Hazard Mater 2022 Aug 21;436:129209. Epub 2022 May 21.

Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application, Nanjing Normal University, Nanjing 210023, China; School of Geography Science, Nanjing Normal University, Nanjing 210023, China.

Black carbon (BC) is a retarder in carbon cycle, and the proportion of char and soot in BC restricts the significance of BC as a sink in carbon cycle. Tracing the sources of char and soot is helpful for in-depth understanding the anthropogenic-driven burial and pattern of BC, and is crucial for regulating emissions of BC and impact of BC on carbon cycle/climate change. This study investigated source-driven BC via the concentration and δC of BC (char and soot) in a Plateau lake sediment. The burial rate of BC (mean: 6.42 ± 5.09 g m yr) showed an increasing trend (3.7 times after 1977 compared with before), and the growth rate of char (4.1 times) was faster than soot (2.5 times). The source trace results, showing faster growth of coal combustion ratio in char (increased 21% after 1980 compared with before) than soot (13%), proved that coal combustion promoted faster growth of char in BC. Redundancy analysis confirmed that more low-temperature utilization of coal urged a stronger driving force for char than soot, which caused BC to have lower aromatic content and higher reactivity in organic carbon pool from the past to present, further impact the effects of BC on carbon cycle.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129209DOI Listing
August 2022

The transcription factor RFX5 coordinates antigen-presenting function and resistance to nutrient stress in synovial macrophages.

Nat Metab 2022 Jun 23. Epub 2022 Jun 23.

Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

Tissue macrophages (Mϕ) are essential effector cells in rheumatoid arthritis (RA), contributing to autoimmune tissue inflammation through diverse effector functions. Their arthritogenic potential depends on their proficiency to survive in the glucose-depleted environment of the inflamed joint. Here, we identify a mechanism that links metabolic adaptation to nutrient stress with the efficacy of tissue Mϕ to activate adaptive immunity by presenting antigen to tissue-invading T cells. Specifically, Mϕ populating the rheumatoid joint produce and respond to the small cytokine CCL18, which protects against cell death induced by glucose withdrawal. Mechanistically, CCL18 induces the transcription factor RFX5 that selectively upregulates glutamate dehydrogenase 1 (GLUD1), thus enabling glutamate utilization to support energy production. In parallel, RFX5 enhances surface expression of HLA-DR molecules, promoting Mϕ-dependent expansion of antigen-specific T cells. These data place CCL18 at the top of a RFX5-GLUD1 survival pathway and couple adaptability to nutrient conditions in the tissue environment to antigen-presenting function in autoimmune tissue inflammation.
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http://dx.doi.org/10.1038/s42255-022-00585-xDOI Listing
June 2022

Assessing Safety of Market-Sold Fresh Fish: Tracking Fish Origins and Toxic Chemical Origins.

Environ Sci Technol 2022 Jun 22. Epub 2022 Jun 22.

Key Laboratory for Environmental Pollution Prediction and Control, Gansu Province, Key Laboratory of Western China's Environmental Systems Stems (Ministry of Education), College of Earth and Environmental Sciences, Lanzhou University, Lanzhou 730000, P. R. China.

Increasing global and domestic food trade and required logistics create uncertainties in food safety inspection due to uncertainties in food origins and extensive trade activities. Modern blockchain techniques have been developed to inform consumers of food origins but do not provide food safety information in many cases. A novel food safety tracking and modeling framework for quantifying toxic chemical levels in the food and the food origins was developed. By integrating chemicals' multimedia environment exchange, food web, and source tracking systems, the framework was implemented to identify short-chain chlorinated paraffin (SCCP) contamination of fresh hairtail fish sold by a Walmart supermarket in Xi'an, northwestern China, and sourced in Eastern China Sea coastal waters. The framework was shown to successfully predict SCCP level with a mean of 17.8 ng g in Walmart-sold hairtails, which was comparable to lab-analyzed 21.9 ng g in Walmart-sold hairtails. The framework provides an alternative and cost-effective approach for safe food inspection compared to traditional food safety inspection techniques. These encouraging results suggest that the approach and rationale reported here could add additional information to the food origin tracking system to enhance transparency and consumers' confidence in the traded food they consumed.
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http://dx.doi.org/10.1021/acs.est.2c00495DOI Listing
June 2022

A security-aware service function chain deployment method for load balance and delay optimization.

Sci Rep 2022 Jun 21;12(1):10442. Epub 2022 Jun 21.

Information and Navigation College, Air Force Engineering University, Xi'an, 710077, China.

Network function virtualization (NFV) decouples network functions from hardware devices. However, it introduces security challenges due to its reliance on software, which facilitates attacks. This security problem has a significant negative impact on the interests of users. Existing deployment methods are not suitable for SFC requests with a security demand, causing the use of substrate resources unreasonable and lower acceptance ratio. Moreover, a strict delay requirement is another challenge for NFV. To make the use of the substrate resources more reasonable and reduce the transmission delay, this paper proposes a security-constraint and function-mutex-constraint consolidation (SFMC) method for virtual network function (VNF) to reduce resource consumption and transmission delay. In addition, a security-aware service function chain (SASFC) deployment method for load balance and delay optimization is presented, which deploys service function chains according to the consolidated results of the SFMC method. The SASFC method first obtains a candidate server node set using resource, hosting capacity, security and node load constraints. It then obtains candidate paths according to the metric of the minimum transmission delay and link load constraint using the Viterbi algorithm. Finally, the path with the highest VNF security level match degree among the candidate paths is adopted to deploy virtual links, and the corresponding server nodes are employed to deploy VNFs. As a result, the SASFC method makes the use of substrate resources more reasonable. It improves the acceptance ratio and long-term average revenue to cost ratio, reduces transmission delay, and achieves load balancing. Experiment results show that when the number of VNFs is five, the acceptance ratio and long-term average revenue to cost ratio of the SASFC method are close to 0.75 and 0.88, which are higher than those of the compared methods. Its transmission delay and proportion of bottleneck nodes are 7.71 and 0.024, which are lower than those of the compared methods. The simulations demonstrate the effectiveness of the SASFC method.
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http://dx.doi.org/10.1038/s41598-022-14494-2DOI Listing
June 2022

Stable carbon isotopes trace the effect of fossil fuels on fractions of particulate black carbon in a large urban lake in China.

J Environ Manage 2022 Jun 17;318:115528. Epub 2022 Jun 17.

Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application, Nanjing Normal University, Nanjing, 210023, China; School of Geography Science, Nanjing Normal University, Nanjing, 210023, China.

Black carbon (BC), the highly recalcitrant aromatic carbonaceous from the incomplete combustion of fossil fuel and biomass, is an important carbon sink in carbon cycle. Char and soot, the main components of BC, have significantly different origin and physicochemical characteristics (particle sizes and resultant transportability). The limited understanding of char and soot sources leads to poor insight into the effect of BC on carbon cycle. Sources of char and soot were investigated in this study using stable carbon isotopes to study the effect of BC on the organic carbon pool in a lake, thereby improving the knowledge of lacustrine carbon cycling. The concentration of BC in Taihu Lake ranged from 0.0 to 0.7 mg·Land accounted for 10.9 ± 4.7% of the particulate organic carbon. The spatial-mean δC values of BC, char, and soot were -23.2 ± 2.0‰, -23.5 ± 2.2‰, and -22.9 ± 1.6‰, respectively. The BC in water was primarily derived from fossil fuels (66.0 ± 9.3%), with liquid fossil fuel accounting for 48.2 ± 13.2% of the BC. The contribution of liquid fossil fuel to soot (49.3%) was much higher than that to char (36.1%); correspondingly, the contributions of biomass and coal to soot (29.2% and 21.5%) were lower than those to char (38.1% and 25.8%). The contribution of liquid fossil fuel combustion to organic carbon (OC), char, and soot gradually increased from 31.9% to 49.3%. Biomass and coal combustion primarily contributed to char (38.1% and 25.8%) and OC (37.5% and 30.6%). The source apportionment of BC, char, and soot revealed the influence of anthropogenically driven BC, char, and soot on the lake and, by extension, to the global carbon cycle.
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http://dx.doi.org/10.1016/j.jenvman.2022.115528DOI Listing
June 2022

Identifying In Vitro Cultured Human Hepatocytes Markers with Machine Learning Methods Based on Single-Cell RNA-Seq Data.

Front Bioeng Biotechnol 2022 30;10:916309. Epub 2022 May 30.

School of Life Sciences, Shanghai University, Shanghai, China.

Cell transplantation is an effective method for compensating for the loss of liver function and improve patient survival. However, given that hepatocytes cultivated have diverse developmental processes and physiological features, obtaining hepatocytes that can properly function is difficult. In the present study, we present an advanced computational analysis on single-cell transcriptional profiling to resolve the heterogeneity of the hepatocyte differentiation process and to mine biomarkers at different periods of differentiation. We obtained a batch of compressed and effective classification features with the Boruta method and ranked them using the Max-Relevance and Min-Redundancy method. Some key genes were identified during the culture of hepatocytes, including , which not only regulates terminally differentiated cells in the liver but also affects cell differentiation. , which encodes a CD147 ligand, also appeared in the identified gene list, and the combination of the two proteins mediated multiple biological pathways. Other genes, such as , , and , which are involved in the maturation and differentiation of hepatocytes and assist different hepatic cell types in performing their roles were also identified. Then, several classifiers were trained and evaluated to obtain optimal classifiers and optimal feature subsets, using three classification algorithms (random forest, k-nearest neighbor, and decision tree) and the incremental feature selection method. The best random forest classifier with a 0.940 Matthews correlation coefficient was constructed to distinguish different hepatic cell types. Finally, classification rules were created for quantitatively describing hepatic cell types. In summary, This study provided potential targets for cell transplantation associated liver disease treatment strategies by elucidating the process and mechanism of hepatocyte development at both qualitative and quantitative levels.
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http://dx.doi.org/10.3389/fbioe.2022.916309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189284PMC
May 2022

Simvastatin inhibits prostatic hyperplasia in rats with metabolic syndrome.

Int Urol Nephrol 2022 Jun 13. Epub 2022 Jun 13.

Department of Urology, Anhui Provincial Hospital, First Affiliated Hospital of University of Science and Technology of China, 17#, Lujiang Rd, Hefei, 230001, China.

Objects: To evaluate the influence of metabolic syndrome (MetS) induced by high fat diet (HFD) on prostate tissue and local inflammatory factors in rats model, and the protective efficacy of statins against pathological changes of prostate.

Methods: 40 Sprague-Dawley rats were divided into 4 subgroups of normal diet (ND), HFD blank, HFD + saline and HFD + simvastatin. After the establishment of models, all subjects were killed to obtain body weight serum lipid, FBG level, FINS and HOMA-IR level. Hyperplasia level of prostate, as well as expression level of interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-α) were also measured.

Results: Models have been successfully established. Level of serum lipid, prostatic weight, hyperplasia as well as expressions of IL-6, TNF-α and IGF-1 in the blank and saline subgroups of HFD group were higher than that of ND group (P < 0.05). While simvastatin has significantly resisted the former effects of HFD on serum lipid and prostate (P < 0.05). No significant difference in serum FBG level was found between groups and subunits. FINS levels of ND group was lower than other groups (P < 0.05). In addition, There is no significant difference in FPG and HOMA-IR levels in blank control subunit, saline control subunit, simvastatin subunit (P > 0.05).

Conclusions: MetS induced by HFD is an important factor in the induction of BPH. Simvastatin can alleviate the hyperplasia of prostate through the relief of local inflammation in prostatic tissue.
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http://dx.doi.org/10.1007/s11255-022-03227-zDOI Listing
June 2022

Solution structure of c-FLIP death effector domains.

Biochem Biophys Res Commun 2022 Aug 29;617(Pt 2):1-6. Epub 2022 May 29.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 132 Lanhei Road, Heilongtan, Kunming, 650201, Yunnan, China; Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

The formation of death-inducing signaling complex (DISC) and death effector domain (DED) filament initiates extrinsic apoptosis. Recruitment and activation of procaspase-8 at the DISC are regulated by c-FLIP. The interaction between c-FLIP and procaspase-8 is mediated by their tandem DEDs (tDED). However, the structure of c-FLIP and how c-FLIP interferes with procaspase-8 activation at the DISC remain elusive. Here, we solved the monomeric structure of c-FLIP (F114G) at near physiological pH by solution nuclear magnetic resonance (NMR). Structural superimposition reveals c-FLIP (F114G) adopts a structural topology similar to that of procaspase-8. Our results provide a structural basis for understanding how c-FLIP interacts with procaspase-8 and the molecular mechanisms of c-FLIP in regulating cell death.
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http://dx.doi.org/10.1016/j.bbrc.2022.05.086DOI Listing
August 2022

Accurate Adjusting the Lattice Strain of Triple-Cation and Mixed-Halide Perovskites for High-Performance Photodetector.

ACS Appl Mater Interfaces 2022 Jun 10;14(24):28154-28162. Epub 2022 Jun 10.

GPL Photonics Laboratory, State Key Laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, P. R. China.

The instability of perovskite optoelectronic devices remains a big barrier to their commercialization. The instability caused by external stimuli has been addressed by encapsulation, such as humidity, oxygen, heat, and ultraviolet light. However, the intrinsic instability of perovskite materials due to the lattice strain has not been fully addressed, which affects the physical properties and device performance to a great extent. Tuning the lattice strain by controlling the perovskite composition and ratio is an effective way to further develop efficient and stable devices. Herein, we prepare a series of triple-cation and mixed-halide (FAPbI)(MAPbBr)(CsPbI) perovskite single-crystal thin films and study the effect of lattice strain on the perovskite optoelectronic properties. Especially, the perovskite photodetector with a horizontal structure based on (FAPbI)(MAPbBr)(CsPbI) single-crystal thin films exhibits excellent performance with an enhanced responsivity of 40 A/W, high detectivity of 1.9 × 10 Jones, external quantum efficiency of 9100%, and superior stability. This can be explained by the fact that the optimal coordination between each element leads to the release of lattice strain and further produces low defect density and long carrier lifetime in (FAPbI)(MAPbBr)(CsPbI) single-crystal thin films. This research shows the significance of ion ratios in tuning lattice strain and determining the intrinsic device performance and makes the perovskite (FAPbI)(MAPbBr)(CsPbI) a promising candidate for the next generation of optoelectronic devices.
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http://dx.doi.org/10.1021/acsami.2c02427DOI Listing
June 2022

A Novel Risk-Prediction Scoring System for Sepsis among Patients with Acute Pancreatitis: A Retrospective Analysis of a Large Clinical Database.

Int J Clin Pract 2022 22;2022:5435656. Epub 2022 Feb 22.

Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, China.

Background: The prognosis is poor when acute pancreatitis (AP) progresses to sepsis; therefore, it is necessary to accurately predict the probability of sepsis and develop a personalized treatment plan to reduce the disease burden of AP patients.

Methods: A total of 1295 patients with AP and 43 variables were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV database. The included patients were randomly assigned to the training set and to the validation set at a ratio of 7 : 3. The chi-square test or Fisher's exact test was used to test the distribution of categorical variables, and Student's -test was used for continuous variables. Multivariate logistic regression was used to establish a prognostic model for predicting the occurrence of sepsis in AP patients. The indicators to verify the overall performance of the model included the area under the receiver operating characteristic curve (AUC), calibration curves, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA).

Results: The multifactor analysis results showed that temperature, phosphate, calcium, lactate, the mean blood pressure (MBP), urinary output, Glasgow Coma Scale (GCS), Charlson Comorbidity Index (CCI), sodium, platelet count, and albumin were independent risk factors. All of the indicators proved that the prediction performance and clinical profitability of the newly established nomogram were better than those of other common indicators (including SIRS, BISAP, SOFA, and qSOFA).

Conclusions: The new risk-prediction system that was established in this research can accurately predict the probability of sepsis in patients with acute pancreatitis, and this helps clinicians formulate personalized treatment plans for patients. The new model can reduce the disease burden of patients and can contribute to the reasonable allocation of medical resources, which is significant for tertiary prevention.
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http://dx.doi.org/10.1155/2022/5435656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159144PMC
June 2022

Observational and Genetic Associations of Modifiable Risk Factors with Aortic Valve Stenosis: A Prospective Cohort Study of 0.5 Million Participants.

Nutrients 2022 May 28;14(11). Epub 2022 May 28.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Background: Observational studies have shown that modifiable risk factors are associated with aortic valve stenosis (AVS). However, the causality behind these associations remains largely unknown.

Objectives: To explore the associations of modifiable risk factors, including metabolic factors, biochemical measures, education, and lifestyles with AVS and their potential causal associations.

Methods: We enrolled 361,930 British white people with genetic data in the UK biobank. Cox proportional risk regression models were used to estimate the hazard ratios between 28 modifiable risk factors and AVS. We used genetic instruments for modifiable risk factors to determine the potential causal relationships using a one-sample Mendelian randomization (MR) approach.

Results: A total of 1602 participants developed AVS during an 8.4-year follow-up. Observational analyses showed higher adiposity, blood pressure, heart rate, low-density lipoprotein, urate, C-reactive protein, creatinine, albumin, and glycated hemoglobin, but lower serum vitamin D, and education, unhealthy lifestyle, and poor sleep quality were related to a higher risk of AVS after adjusting for the Bonferroni correction ( < 0.0013). Genetically predicted 1-SD higher levels of body mass index [HR: 1.09, 95% CI: 1.03 to 1.16], body fat percentage (1.17, 1.03 to 1.33), triglyceride (TG) [1.08, 1.00 to 1.16], low-density lipoprotein (LDL) (1.15, 1.08 to 1.21) and serum total cholesterol (TC) (1.13, 1.02 to 1.25) were associated with a higher risk of AVS, respectively. Genetically determined per category higher insomnia (1.32, 1.13 to 1.55) was also associated with AVS. The abovementioned genetic associations with the incident AVS showed an increasing relationship pattern.

Conclusions: This study provides strong evidence for the potential causal roles of cardiometabolic factors in developing AVS, highlighting that an idea of metabolic status through a healthy lifestyle may help prevent AVS.
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http://dx.doi.org/10.3390/nu14112273DOI Listing
May 2022

Neighbor2Neighbor: A Self-Supervised Framework for Deep Image Denoising.

IEEE Trans Image Process 2022 14;31:4023-4038. Epub 2022 Jun 14.

In recent years, image denoising has benefited a lot from deep neural networks. However, these models need large amounts of noisy-clean image pairs for supervision. Although there have been attempts in training denoising networks with only noisy images, existing self-supervised algorithms suffer from inefficient network training, heavy computational burden, or dependence on noise modeling. In this paper, we proposed a self-supervised framework named Neighbor2Neighbor for deep image denoising. We develop a theoretical motivation and prove that by designing specific samplers for training image pairs generation from only noisy images, we can train a self-supervised denoising network similar to the network trained with clean images supervision. Besides, we propose a regularizer in the perspective of optimization to narrow the optimization gap between the self-supervised denoiser and the supervised denoiser. We present a very simple yet effective self-supervised training scheme based on the theoretical understandings: training image pairs are generated by random neighbor sub-samplers, and denoising networks are trained with a regularized loss. Moreover, we propose a training strategy named BayerEnsemble to adapt the Neighbor2Neighbor framework in raw image denoising. The proposed Neighbor2Neighbor framework can enjoy the progress of state-of-the-art supervised denoising networks in network architecture design. It also avoids heavy dependence on the assumption of the noise distribution. We evaluate the Neighbor2Neighbor framework through extensive experiments, including synthetic experiments with different noise distributions and real-world experiments under various scenarios. The code is available online: https://github.com/TaoHuang2018/Neighbor2Neighbor.
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http://dx.doi.org/10.1109/TIP.2022.3176533DOI Listing
June 2022

EMDLP: Ensemble multiscale deep learning model for RNA methylation site prediction.

BMC Bioinformatics 2022 Jun 8;23(1):221. Epub 2022 Jun 8.

Engineering Research Center of Intelligent Control for Underground Space, Ministry of Education, China University of Mining and Technology, Xuzhou, 221116, China.

Background: Recent research recommends that epi-transcriptome regulation through post-transcriptional RNA modifications is essential for all sorts of RNA. Exact identification of RNA modification is vital for understanding their purposes and regulatory mechanisms. However, traditional experimental methods of identifying RNA modification sites are relatively complicated, time-consuming, and laborious. Machine learning approaches have been applied in the procedures of RNA sequence features extraction and classification in a computational way, which may supplement experimental approaches more efficiently. Recently, convolutional neural network (CNN) and long short-term memory (LSTM) have been demonstrated achievements in modification site prediction on account of their powerful functions in representation learning. However, CNN can learn the local response from the spatial data but cannot learn sequential correlations. And LSTM is specialized for sequential modeling and can access both the contextual representation but lacks spatial data extraction compared with CNN. There is strong motivation to construct a prediction framework using natural language processing (NLP), deep learning (DL) for these reasons.

Results: This study presents an ensemble multiscale deep learning predictor (EMDLP) to identify RNA methylation sites in an NLP and DL way. It organically combines the dilated convolution and Bidirectional LSTM (BiLSTM), which helps to take better advantage of the local and global information for site prediction. The first step of EMDLP is to represent the RNA sequences in an NLP way. Thus, three encodings, e.g., RNA word embedding, One-hot encoding, and RGloVe, which is an improved learning method of word vector representation based on GloVe, are adopted to decipher sites from the viewpoints of the local and global information. Then, a dilated convolutional Bidirectional LSTM network (DCB) model is constructed with the dilated convolutional neural network (DCNN) followed by BiLSTM to extract potential contributing features for methylation site prediction. Finally, these three encoding methods are integrated by a soft vote to obtain better predictive performance. Experiment results on mA and mA reveal that the area under the receiver operating characteristic(AUROC) of EMDLP obtains respectively 95.56%, 85.24%, and outperforms the state-of-the-art models. To maximize user convenience, a user-friendly webserver for EMDLP was publicly available at http://www.labiip.net/EMDLP/index.php ( http://47.104.130.81/EMDLP/index.php ).

Conclusions: We developed a predictor for mA and mA methylation sites.
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http://dx.doi.org/10.1186/s12859-022-04756-1DOI Listing
June 2022

GATA1 regulates the microRNA‑328‑3p/PIM1 axis via circular RNA ITGB1 to promote renal ischemia/reperfusion injury in HK‑2 cells.

Int J Mol Med 2022 Aug 8;50(2). Epub 2022 Jun 8.

Department of Kidney Transplantation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.

Acute kidney injury (AKI) is caused by renal ischemia/reperfusion injury (IRI) during kidney transplantation. The levels of both circular RNAs (circRNAs) and microRNAs (miRNAs/miR) appear to be critical for AKI detection. While several RNA interactions in AKI have been found, the regulatory mechanisms between the molecules remain to be fully elucidated. In the present study, miRNA expression profiling analysis was conducted using an online dataset to identify the differentially expressed miRNAs in rats with IRI. miR‑328‑3p was also found to be downregulated in human kidney‑2 (HK‑2) cells subjected to hypoxia/reperfusion (H/R), and its overexpression targeting pim‑1 proto‑oncogene (PIM1) resulted in an increased viability and a reduced apoptosis, as well as in the decreased expression of inflammatory factors upon H/R exposure. Putative targets and circRNAs of miR‑328‑3p were identified using publically available databases. The inhibition of circRNA integrin beta 1 (ITGB1; circITGB1) suppressed the inflammatory response induced by H/R by sponging miR‑328‑3p in HK‑2 cells. Furthermore, a sequence of the functional ITGB1 promoter was studied for transcription factor GATA binding protein 1 (GATA1) binding sites. GATA1 binds to the ITGB1 promoter, leading to the expression of circITGB1. On the whole, the findings of the present study revealed a regulatory pathway modulating miR‑328‑3p in IRI, demonstrating that the GATA1‑mediated regulation of circITGB1 enhanced the H/R‑induced inflammatory response via the miR‑328‑3p/PIM1 axis.
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http://dx.doi.org/10.3892/ijmm.2022.5156DOI Listing
August 2022

Sleep and Late-Onset Alzheimer's Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects.

Front Genet 2022 17;13:794202. Epub 2022 May 17.

Department of Biostatistics, School of Public Health, Peking University, Beijing, China.

Late-onset Alzheimer's disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD ( = 455,258) and summary-level data for seven SRPs (sample size ranges from 359,916 to 1,331,010). AD shared a strong genetic basis with insomnia ( = 0.20; = 9.70 × 10), snoring ( = 0.13; = 2.45 × 10), and sleep duration ( = -0.11; = 1.18 × 10). The CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and the TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues and highlighted the regulatory roles of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance, and positive regulation of T-cell-mediated cytotoxicity pathways. Protein-protein interaction analysis identified three potential drug target genes (, , and ) that interacted with known FDA-approved drug target genes. The CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3, and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed insomnia had a causal effect on AD (OR = 1.02, = 6.7 × 10), and multivariate MR suggested a potential role of sleep duration and major depression in this association. Our findings provide strong evidence of shared genetics and causation between AD and sleep abnormalities and advance our understanding of the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial for treating AD and sleep disorders more efficiently.
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http://dx.doi.org/10.3389/fgene.2022.794202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152224PMC
May 2022

Lipids, Apolipoproteins, Statins, and Intracerebral Hemorrhage: A Mendelian Randomization Study.

Ann Neurol 2022 Jun 2. Epub 2022 Jun 2.

Department of Neurology, Peking, University Third Hospital, Beijing, China.

Objective: To investigate the causal role of lipid or apolipoprotein traits in intracerebral hemorrhage (ICH) and determine the effect of lipid-lowering interventions on the disease.

Methods: Two-sample Mendelian randomization (MR) analyses were conducted to evaluate the associations of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein (Apo)B and ApoA1 levels with risks for ICH, and those of LDL-C- (HMGCR, PCSK9, and NPC1L1) and TG-lowering targets (LPL and APOC3) with ICH.

Results: Increased levels of ApoB was associated with a decreased risk of overall ICH (OR 0.623, 95% CI 0.413-0.940; p = 0.024) and lobar ICH (OR 0.579, 95% CI 0.342-0.979; p = 0.042). The inverse relationship remained stable in multivariable MR. In addition, elevated TGs showed a causal effect on lobar ICH in multivariable MR (OR 1.600, 95% CI 1.009-2.537; p = 0.046). The LDL-C-reducing genetic variation alleles at or near the HMGCR gene (mimicking the effect of statins) were predicted to increase the overall and deep ICH risk. Additionally, genetic variation at or near the APOC3 gene suggested that genetically reducing the activity of APOC3 (mimicking antisense anti-apoC3 agents) was predicted to decrease lobar ICH.

Interpretation: Genetically predicted elevated ApoB may have a protective effect on overall ICH and lobar ICH, whereas elevated TG was associated with a higher risk of lobar ICH conditional on LDL-C and ApoB. MR analysis supports the conclusion that statins may increase the risk of overall and deep ICH independent of their lipid-lowering effect. More specific lipid-lowering targets may end up being the future. ANN NEUROL 2022.
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http://dx.doi.org/10.1002/ana.26426DOI Listing
June 2022

Source apportionment of polycyclic aromatic hydrocarbons (PAHs) in a sediment core from Lake Dagze Co, Tibetan Plateau, China: Comparison of three receptor models.

J Environ Sci (China) 2022 Nov 9;121:224-233. Epub 2022 Feb 9.

School of Geography, Nanjing Normal University, Nanjing 210023, China; Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application, Nanjing Normal University, Nanjing 210023, China; Key Laboratory of Virtual Geographic Environment (Nanjing Normal University), Ministry of Education, Nanjing 210023, China; State Key Laboratory Cultivation Base of Geographical Environment Evolution (Jiangsu Province), Nanjing 210023, China. Electronic address:

Receptor models are a useful tool for identifying sources of polycyclic aromatic hydrocarbons (PAHs) in multiple environmental media. In this study, three different receptor models (including the principal component analysis-multiple linear regression (PCA-MLR), positive matrix factorization (PMF), and Unmix models) were used to apportion the sources of 16 priority PAHs in a sediment core of Lake Dagze Co. The ∑PAHs (sum of all 16 measured PAHs) concentrations ranged from 51.89 to 132.82 ng/g with an average of 80.39 ng/g. The ∑PAHs were dominated by 2-3 ring PAHs, accounting for 80.12% on average, thereby indicating that they mainly originated from biomass and coal combustion and/or from long-range atmospheric transportation. The three models produced consistent source apportionment results. The greatest contributor to ∑PAHs was biomass combustion, followed by coal combustion, vehicle emissions, and petrogenic sources. Moreover, the temporal variation of the common sources was well-correlated among models. The multi-method comparison and evaluation results showed that all three models were useful tools for source apportionment of PAHs, with the PMF model providing better results than the PCA-MLR and Unmix models. The temporal trends of factor contributions were verified by PAHs with different ring numbers. Significant correlations were found between the simulated concentrations of each source factor and the PAHs with different ring numbers (P<0.01), except for the petrogenic source identified by the Unmix model (P>0.05). This study can provide useful information for further investigation of source apportionment of PAHs in the sediment cores.
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http://dx.doi.org/10.1016/j.jes.2022.01.043DOI Listing
November 2022

Identifying Functions of Proteins in Mice With Functional Embedding Features.

Front Genet 2022 16;13:909040. Epub 2022 May 16.

School of Life Sciences, Shanghai University, Shanghai, China.

In current biology, exploring the biological functions of proteins is important. Given the large number of proteins in some organisms, exploring their functions one by one through traditional experiments is impossible. Therefore, developing quick and reliable methods for identifying protein functions is necessary. Considerable accumulation of protein knowledge and recent developments on computer science provide an alternative way to complete this task, that is, designing computational methods. Several efforts have been made in this field. Most previous methods have adopted the protein sequence features or directly used the linkage from a protein-protein interaction (PPI) network. In this study, we proposed some novel multi-label classifiers, which adopted new embedding features to represent proteins. These features were derived from functional domains and a PPI network via word embedding and network embedding, respectively. The minimum redundancy maximum relevance method was used to assess the features, generating a feature list. Incremental feature selection, incorporating RAndom k-labELsets to construct multi-label classifiers, used such list to construct two optimum classifiers, corresponding to two key measurements: accuracy and exact match. These two classifiers had good performance, and they were superior to classifiers that used features extracted by traditional methods.
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http://dx.doi.org/10.3389/fgene.2022.909040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149260PMC
May 2022

Pan-Cancer Analysis, Reveals COVID-19-Related BSG as a Novel Marker for Treatment and Identification of Multiple Human Cancers.

Front Cell Dev Biol 2022 13;10:876180. Epub 2022 May 13.

The First Clinical Medical College, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Coronavirus disease 2019 (COVID-19) has been a public threat and healthcare concern caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the period of the pandemic of COVID-19, cancer patients should be paid more attention as more severe events are found in cancer patients infected with SARS-CoV-2. Basigin () is an essential factor for the infection and progression of COVID-19 and tumorigenesis of multiple tumors, which may serve as a novel target for the effective treatment against COVID-19 and multiple human cancers. A total of 19,020 samples from multiple centers were included in our research for the comprehensive investigation of the differences in BSG expression among human organs, cancer cells, cancer tissues, and normal tissues. Cox regression analysis and Kaplan-Meier curves were utilized to explore the prognosis factor of in cancers. Correlation analyses were used to determine associations of expression with tumor mutational burden, the immune microenvironment, etc. Gene set enrichment analysis was applied to explore the underlying mechanisms of in cancers. Compared with normal tissues, expression was high in 13 types of cancers (cholangiocarcinoma, etc.) and low in colon adenocarcinoma and rectum adenocarcinoma. expression was related to the prognosis of eight cancers (e.g., invasive breast carcinoma) ( < 0.05). The gene also demonstrated a pronounced effect in identifying 12 cancers (cholangiocarcinoma, etc.) from their control samples (AUC >0.7). The expression was associated with DNA methyltransferases, mismatch repair genes, immune infiltration levels, tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoints, suggesting the potential of as an exciting target for cancer treatment. may play its role in several cancers by affecting several signaling pathways such as drug cytochrome metabolism P450 and JAK-STAT. may be a novel biomarker for treating and identifying multiple human cancers.
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http://dx.doi.org/10.3389/fcell.2022.876180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136262PMC
May 2022

Case Report: Intravascular Large B-Cell Lymphoma: A Clinicopathologic Study of Four Cases With Review of Additional 331 Cases in the Literature.

Front Oncol 2022 13;12:883141. Epub 2022 May 13.

Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and highly malignant non-Hodgkin B-cell lymphoma with uncommon clinical presentation and poor prognosis. The diagnostic pitfall of IVLBCL is mainly due to the fact that subtle histological changes could be easily overlooked, in addition to its rare occurrence, non-specific and variable clinical presentations, and the absence of significant mass lesions. The purpose of this study is to further explore the clinicopathologic and molecular features of IVLBCL to ensure an accurate diagnosis of this entity. Here, we retrospectively present the data of the four new cases and the literature cases. The age ranged from 23 to 92, with a medium age of 67 and a male-to-female ratio of 1:1. The clinical manifestations are extremely variable, including fever, night sweats, weight loss, anemia, thrombocytopenia, unexplained hypoxemia, impaired consciousness, and skin lesions, as well as the extremely low levels of serum albumin, high levels of serum lactate dehydrogenase (LDH), soluble interleukin-2 receptor (sIL2R), and ferritin. Morphologically, 99.9% of cases showed a selective growth pattern with large, atypical lymphocytes within the lumen of small blood vessels. In addition, vast majority of cases were positive for CD20, CD79a, PAX5, MUM1, and BCL6, and a subset of cases expressed BCL2 and CD5, whereas CD3 and CD10 were typically negative. Ki-67 proliferative index ranged from 20% to 100%. To sum up, we have conducted comprehensive case reports, to the best of our knowledge, this is the largest reported cohort of IVLBCL cases. Comprehensive assessments and more IVLBCL cases are required for early diagnosis and prompt treatment.
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http://dx.doi.org/10.3389/fonc.2022.883141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135977PMC
May 2022

Feasibility and efficacy of superconducting open-configuration magnetic resonance-guided microwave ablation of malignant liver tumors with real-time imaging sequences.

J Cancer Res Ther 2022 Apr;18(2):384-390

Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.

Objective: To evaluate the safety and effectiveness of open superconducting magnetic resonance (MR)-guided microwave ablation of liver tumors and explore feasibility of real-time imaging sequence-guided needle insertion technique.

Materials And Methods: Medical records of December 2019-May 2021 of microwave ablations of liver tumors under MR guidance in XX University Cancer Center were reviewed. Real-time imaging-guided puncture technique refers to real-time insertion and adjusting the position of a microwave applicator under a fast imaging sequence. The safety and efficacy of the procedure among the enrolled patients were assessed.

Results: Twenty-six patients underwent 27 procedures, with 30 lesions ablated (long diameter: 1.51 ± 0.81 cm, short diameter: 1.30 ± 0.61 cm). There were 20 cases of primary liver cancer and 10 of liver metastases. All lesions were identified by MR imaging (MRI), and all procedures were successfully performed using the finger positioning method for puncture sites. Five patients underwent real-time guided needle insertion techniques. Further, the microwave applicators reached the target position at once, and the entire insertion process was completed within 3 min. The completion rate of the real-time guided needle insertion technology was 100%, and 25 (92.6%) patients had minor complications. No severe complications were observed, and the technical success rate of 30 MRI-guided lesions was 100%. Finally, the complete ablation rate of the MRI-guided ablation after the first procedure was 93.1%.

Conclusion: Open MR-guided microwave ablation is safe and effective in treating liver tumors. Furthermore, real-time imaging sequence-guided puncture technique under MRI is feasible and efficient.
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http://dx.doi.org/10.4103/jcrt.jcrt_1659_21DOI Listing
April 2022

Multiple recurrent cystic hydatid disease of abdominal cavity.

Asian J Surg 2022 May 25. Epub 2022 May 25.

Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, PR China.

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http://dx.doi.org/10.1016/j.asjsur.2022.05.074DOI Listing
May 2022

CD20CD22ADAM28 B Cells in Tertiary Lymphoid Structures Promote Immunotherapy Response.

Front Immunol 2022 11;13:865596. Epub 2022 May 11.

Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: As the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells' roles in the anti-tumor response are far from clear.

Methods: Based on single-cell transcriptomic data for ICI-treated patients, we identified a B-cell cluster [B (ICI-Responsive B) cells] and described the phenotype, cell-cell communication, biological processes, gene signature, and prognosis value of B cells through bioinformatic analysis, tissue immunofluorescence, and animal experiments. Surgery samples from 12 non-small cell lung carcinoma (NSCLC) patients with adjuvant checkpoint blockade were evaluated as external validation.

Results: B cells were identified as a subset of CD20CD22ADAM28 B cells with a memory phenotype. Bioinformatic analysis revealed that B cells had enhanced cell viability and epigenetic regulation, and that ALOX5AP, MIF, and PTPRC/CD45 expressed by myeloid cells may be critical coordinators of diverse biological processes of B cells. Immunofluorescence confirmed the presence of B cells in tertiary lymphoid structures (TLSs) in skin SCC, RCC, CRC, and breast cancer. B-associated gene signatures correlate with positive outcomes in patients with melanoma, glioblastoma, NSCLC, HNSCC, or RCC treated with ICI therapy, and B-cell density predicted NSCLC patients' response to checkpoint immunotherapy. In line with this, melanoma-bearing mice depleted of B cells were resistant to ICIs.

Conclusions: CD20CD22ADAM28 B cells were present in cancer-associated TLS and promoted the response to ICI therapy.
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http://dx.doi.org/10.3389/fimmu.2022.865596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130862PMC
June 2022

Research Progress of Alumina-Forming Austenitic Stainless Steels: A Review.

Materials (Basel) 2022 May 13;15(10). Epub 2022 May 13.

School of Materials Science and Engineering, Henan University of Science and Technology, Luoyang 471000, China.

The development of Alumina-Forming Austenitic (AFA) stainless steel is reviewed in this paper. As a new type of heat-resistant steel, AFA steel forms an alumina protective scale instead of chromia in a corrosive environment. This work summarizes the types of developed AFA steels and introduces the methods of composition design. Various precipitates appear in the microstructure that directly determine the performance at high temperatures. It was found that alloy elements and the heat treatment process have an important influence on precipitates. In addition, the corrosion resistance of AFA steel in different corrosive environments is systematically analyzed, and the beneficial or harmful effects of different elements on the formation of alumina protective scale are discussed. In this paper, the short-term mechanical properties, creep properties and influencing factors of AFA steel are also analyzed. This work aims to summarize the research status on this subject, analyze the current research results, and explore future research directions.
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http://dx.doi.org/10.3390/ma15103515DOI Listing
May 2022

Hsa_circ_0006692 Promotes Lung Cancer Progression via miR-205-5p/CDK19 Axis.

Genes (Basel) 2022 May 10;13(5). Epub 2022 May 10.

Laboratory of Radiation Oncology and Radiobiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China.

Circular RNA (CircRNA) is related to tumor development. Nevertheless, the regulation and function of hsa_circ_0006692 and its interactions with miR-205-5p and in the development of non-small-cell lung cancer (NSCLC) were un-explored. The correlations of expression levels of hsa_circ_0006692 in NSCLC specimens and cells with pathological characteristics were studied. The interactions of hsa_circ_0006692 with miR-205-5p and were assessed with real-time PCR, RNA-binding protein immunoprecipitation (RIP), luciferase reporter, RNA pull-down, and fluorescence in situ hybridization (FISH). The roles of hsa_circ_0006692 on cell growth, invasion, and migration in vitro and metastasis in vivo were evaluated. Hsa_circ_0006692 was over-expressed in 60 cases of NSCLC specimens and cells, which was positively correlated with TNM stage, tumor size, and invasion of the lung basal layer. The results of the in vitro and in vivo studies revealed that the over-expression of hsa_circ_0006692 facilitated NSCLC cell growth, migration, and invasion, cell cycle arrest at the S phase, and the activation of , , and . The results of the dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that hsa_circ_0006692 sponged miR-205-5p, which targeted and facilitated the malignant behaviors of lung cancer cells. Hsa_circ_0006692 modulated EMT of lung cancer cells via the stimulation of , , , and . This study revealed that hsa_circ_0006692 promoted NSCLC progression via enhancing cell growth, invasion, and metastasis through sponging mir-205-5p, up-regulating the downstream oncogene and modulating EMT of lung cancer cells. The circ-0006692/mir-205-5p/ axis might serve as a prognosis biomarker and target for drugs aimed against NSCLC.
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http://dx.doi.org/10.3390/genes13050846DOI Listing
May 2022

Deep transfer learning to quantify pleural effusion severity in chest X-rays.

BMC Med Imaging 2022 May 27;22(1):100. Epub 2022 May 27.

Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.

Purpose: The detection of pleural effusion in chest radiography is crucial for doctors to make timely treatment decisions for patients with chronic obstructive pulmonary disease. We used the MIMIC-CXR database to develop a deep learning model to quantify pleural effusion severity in chest radiographs.

Methods: The Medical Information Mart for Intensive Care Chest X-ray (MIMIC-CXR) dataset was divided into patients 'with' or 'without' chronic obstructive pulmonary disease (COPD). The label of pleural effusion severity was obtained from the extracted COPD radiology reports and classified into four categories: no effusion, small effusion, moderate effusion, and large effusion. A total of 200 datasets were randomly sampled to manually check each item and determine whether the tags are correct. A professional doctor re-tagged these items as a verification cohort without knowing their previous tags. The learning models include eight common network structures including Resnet, DenseNet, and GoogleNET. Three data processing methods (no sampling, downsampling, and upsampling) and two loss algorithms (focal loss and cross-entropy loss) were used for unbalanced data. The Neural Network Intelligence tool was applied to train the model. Receiver operating characteristic curves, Area under the curve, and confusion matrix were employed to evaluate the model results. Grad-CAM was used for model interpretation.

Results: Among the 8533 patients, 15,620 chest X-rays with clearly marked pleural effusion severity were obtained (no effusion, 5685; small effusion, 4877; moderate effusion, 3657; and large effusion, 1401). The error rate of the manual check label was 6.5%, and the error rate of the doctor's relabeling was 11.0%. The highest accuracy rate of the optimized model was 73.07. The micro-average AUCs of the testing and validation cohorts was 0.89 and 0.90, respectively, and their macro-average AUCs were 0.86 and 0.89, respectively. The AUC of the distinguishing results of each class and the other three classes were 0.95 and 0.94, 0.76 and 0.83, 0.85 and 0.83, and 0.87 and 0.93.

Conclusion: The deep transfer learning model can grade the severity of pleural effusion.
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http://dx.doi.org/10.1186/s12880-022-00827-0DOI Listing
May 2022

Identifying Methylation Signatures and Rules for COVID-19 With Machine Learning Methods.

Front Mol Biosci 2022 10;9:908080. Epub 2022 May 10.

School of Life Sciences, Shanghai University, Shanghai, China.

The occurrence of coronavirus disease 2019 (COVID-19) has become a serious challenge to global public health. Definitive and effective treatments for COVID-19 are still lacking, and targeted antiviral drugs are not available. In addition, viruses can regulate host innate immunity and antiviral processes through the epigenome to promote viral self-replication and disease progression. In this study, we first analyzed the methylation dataset of COVID-19 using the Monte Carlo feature selection method to obtain a feature list. This feature list was subjected to the incremental feature selection method combined with a decision tree algorithm to extract key biomarkers, build effective classification models and classification rules that can remarkably distinguish patients with or without COVID-19. EPSTI1, NACAP1, SHROOM3, C19ORF35, and MX1 as the essential features play important roles in the infection and immune response to novel coronavirus. The six significant rules extracted from the optimal classifier quantitatively explained the expression pattern of COVID-19. Therefore, these findings validated that our method can distinguish COVID-19 at the methylation level and provide guidance for the diagnosis and treatment of COVID-19.
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http://dx.doi.org/10.3389/fmolb.2022.908080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127386PMC
May 2022

Importance of ideal cardiovascular health metrics in the risk of colorectal cancer among people aged 50 years or older: a UK Biobank cohort study.

BMJ Open 2022 05 24;12(5):e059642. Epub 2022 May 24.

School of Public Administration and Policy, Renmin University of China, Beijing, China

Objective: To explore the correlation between the ideal cardiovascular health metrics (ICVHMs) and the incidence of colorectal cancer (CRC) among people aged 50 years or older.

Design: Prospective cohort study.

Setting: The UK Biobank, a prospective cohort of middle-aged participants recruited between 2006 and 2010.

Participants: The study included 342 226 participants from the UK Biobank aged 50 years or older without prevalent cancer.

Exposure: The ICVHMs consist of four behavioural factors (abstinence from smoking, ideal body mass index (BMI), physical activity at goal and consumption of healthy diet) and three cardiometabolic factors (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/80 mm Hg and untreated fasting plasma glucose <100 mg/dL).

Main Outcomes: The outcome was ascertained by linkage to cancer and death registries using the International Classification of Diseases, Tenth codes C18-C20.

Results: During a median follow-up time of 8.72 years, 3060 CRC cases were identified. Compared with the reference (participants with ICVHMs ≤2), the multivariable-adjusted HRs for subgroups with 3, 4, 5 and ≥6 ICVHM factors were 0.98 (95% CI 0.85 to 1.12), 0.90 (95% CI 0.77 to 1.02), 0.85 (95% CI 0.71 to 0.98) and 0.69 (95% CI 0.48 to 0.90), respectively. Among the seven ICVHM factors, lower BMI, healthier diet and ideal fasting plasma glucose were significantly associated with lower risk of CRC (HR: 0.86, 95% CI 0.78 to 0.95; HR: 0.92, 95% CI 0.84 to 0.99; HR: 0.90, 95% CI 0.80 to 0.99).

Conclusions: Adherence to the ICVHMs was associated with a lower risk of CRC among people aged 50 years or older. Among the seven ICVHM factors, BMI, diet and fasting plasma glucose played a more critical role in the prevention of CRC. These findings imply that adherence to ICVHMs should be encouraged to reduce the burden of cardiovascular disease as well as CRC.
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http://dx.doi.org/10.1136/bmjopen-2021-059642DOI Listing
May 2022

Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors.

J Med Chem 2022 Jun 24;65(11):7656-7681. Epub 2022 May 24.

Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24060, United States.

Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homologue 2 (Spns2). While mouse genetic studies suggest that Spns2 functions to maintain lymph S1P, Spns2 inhibitors are necessary to understand its biology and to learn whether Spns2 is a viable drug target. Herein, we report a structure-activity relationship study that identified the first Spns2 inhibitor (SLF1081851). In vitro studies in HeLa cells demonstrated that inhibited S1P release with an IC of 1.93 μM. Administration of to mice and rats drove significant decreases in circulating lymphocyte counts and plasma S1P concentrations, recapitulating the phenotype observed in mice made deficient in Spns2. Thus, has the potential for development and use as a probe to investigate Spns2 biology and to determine the potential of Spns2 as a drug target.
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http://dx.doi.org/10.1021/acs.jmedchem.1c02171DOI Listing
June 2022
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