Publications by authors named "Kun Huang"

800 Publications

What limits limits?

Natl Sci Rev 2021 Jan 28;8(1):nwaa210. Epub 2020 Aug 28.

Department of Electrical and Computer Engineering, National University of Singapore, Singapore.

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http://dx.doi.org/10.1093/nsr/nwaa210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288363PMC
January 2021

TPSC: a module detection method based on topology potential and spectral clustering in weighted networks and its application in gene co-expression module discovery.

BMC Bioinformatics 2021 Oct 25;22(Suppl 4):111. Epub 2021 Oct 25.

Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Background: Gene co-expression networks are widely studied in the biomedical field, with algorithms such as WGCNA and lmQCM having been developed to detect co-expressed modules. However, these algorithms have limitations such as insufficient granularity and unbalanced module size, which prevent full acquisition of knowledge from data mining. In addition, it is difficult to incorporate prior knowledge in current co-expression module detection algorithms.

Results: In this paper, we propose a novel module detection algorithm based on topology potential and spectral clustering algorithm to detect co-expressed modules in gene co-expression networks. By testing on TCGA data, our novel method can provide more complete coverage of genes, more balanced module size and finer granularity than current methods in detecting modules with significant overall survival difference. In addition, the proposed algorithm can identify modules by incorporating prior knowledge.

Conclusion: In summary, we developed a method to obtain as much as possible information from networks with increased input coverage and the ability to detect more size-balanced and granular modules. In addition, our method can integrate data from different sources. Our proposed method performs better than current methods with complete coverage of input genes and finer granularity. Moreover, this method is designed not only for gene co-expression networks but can also be applied to any general fully connected weighted network.
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http://dx.doi.org/10.1186/s12859-021-03964-5DOI Listing
October 2021

Expanding the clinicopathological-genetic spectrum of GNE myopathy by a Chinese neuromuscular centre.

J Cell Mol Med 2021 Oct 22. Epub 2021 Oct 22.

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

GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological-genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy.
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http://dx.doi.org/10.1111/jcmm.16978DOI Listing
October 2021

Gestational diabetes mellitus, autistic traits and ADHD symptoms in toddlers: Placental inflammatory and oxidative stress cytokines do not play an intermediary role.

Psychoneuroendocrinology 2021 Oct 2;134:105435. Epub 2021 Oct 2.

School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No. 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University; No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Objective: To evaluate whether gestational diabetes mellitus (GDM) is associated with increased risks of autistic traits and attention deficit/hyperactivity disorder (ADHD) among offspring and whether placental inflammatory and oxidative stress cytokines play an intermediary role.

Methods: Based on a prospective cohort study from China, namely, the Ma'anshan Birth Cohort study (MABC), 3260 mother-child pairs were included. Autistic traits and ADHD symptoms among children were assessed at 18 months and 36 months, respectively. The mRNA expression levels of fourteen placental cytokines were determined using PCR. Logistic regression analysis was used to examine the associations between GDM and the risks of autistic traits or ADHD symptoms. Mediation analysis was used to assess the potential mediation effects of certain placental inflammatory factors.

Results: Of the 3260 children, 419 (12.85%) were exposed to GDM. The prevalence rates of autistic traits and ADHD symptoms were 13.86% and 6.4%, respectively. A 48.6% increased risk of autistic traits was observed among offspring born to mothers with GDM [odds ratio (OR) = 1.49, 95% confidence interval (95%CI): 1.11-2.00)], while no significant association was found in terms of ADHD symptoms. There were significant positive associations between GDM and IL-10 expression and between HIF1-α and CRP mRNA expression and a significant negative association between GDM and CD206 mRNA expression. The expression of MCP-1 mRNA was negatively associated with the risk of autistic traits [adjusted OR = 0.73 (95%CI: 0.73-0.55)]. The levels of TNF-α were positively associated with the risk of ADHD symptoms [OR = 2.11 (95%CI: 1.39-3.21)], while GRP78 was inversely associated with it [OR = 0.64 (95%CI: 0.44-0.94)]. However, none of the 14 placental cytokines was involved as a key mediator.

Conclusion: Our findings suggest that GDM may act as a risk factor for autistic traits in offspring, while the biological mechanisms may not involve the 14 placental cytokines studied. No significant association between GDM and ADHD symptoms was observed.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105435DOI Listing
October 2021

Hallstatt miners consumed blue cheese and beer during the Iron Age and retained a non-Westernized gut microbiome until the Baroque period.

Curr Biol 2021 Oct 8. Epub 2021 Oct 8.

Prehistoric Department, Museum of Natural History Vienna, Burgring 7, 1010 Vienna, Austria. Electronic address:

We subjected human paleofeces dating from the Bronze Age to the Baroque period (18 century AD) to in-depth microscopic, metagenomic, and proteomic analyses. The paleofeces were preserved in the underground salt mines of the UNESCO World Heritage site of Hallstatt in Austria. This allowed us to reconstruct the diet of the former population and gain insights into their ancient gut microbiome composition. Our dietary survey identified bran and glumes of different cereals as some of the most prevalent plant fragments. This highly fibrous, carbohydrate-rich diet was supplemented with proteins from broad beans and occasionally with fruits, nuts, or animal food products. Due to these traditional dietary habits, all ancient miners up to the Baroque period have gut microbiome structures akin to modern non-Westernized individuals whose diets are also mainly composed of unprocessed foods and fresh fruits and vegetables. This may indicate a shift in the gut community composition of modern Westernized populations due to quite recent dietary and lifestyle changes. When we extended our microbial survey to fungi present in the paleofeces, in one of the Iron Age samples, we observed a high abundance of Penicillium roqueforti and Saccharomyces cerevisiae DNA. Genome-wide analysis indicates that both fungi were involved in food fermentation and provides the first molecular evidence for blue cheese and beer consumption in Iron Age Europe.
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http://dx.doi.org/10.1016/j.cub.2021.09.031DOI Listing
October 2021

A Computational Framework to Analyze the Associations between Symptoms and Cancer Patient Attributes Post Chemotherapy using EHR data.

IEEE J Biomed Health Inform 2021 Oct 6;PP. Epub 2021 Oct 6.

Patients with cancer, such as breast and col-orectal cancer, often experience different symptoms post-chemotherapy. The symptoms could be fatigue, gastroin-testinal (nausea, vomiting, lack of appetite), psychoneuro-logical symptoms (depressive symptoms, anxiety), or other types. Previous research focused on understanding the symptoms using survey data. In this research, we propose to utilize the data within the Electronic Health Record (EHR). A computational framework is developed to use a natural language processing (NLP) pipeline to extract the clinician-documented symptoms from clinical notes. Then, a patient clustering method is based on the symptom severity levels to group the patient in clusters. The association rule mining is used to analyze the associations between symptoms and patient attributes (smoking history, number of comor-bidities, diabetes status, age at diagnosis) in the patient clusters. The results show that the various symptom types and severity levels have different associations between breast and colorectal cancers and different timeframes post-chemotherapy. The results also show that patients with breast or colorectal cancers, who smoke and have severe fatigue, likely have severe gastrointestinal symptoms six months after the chemotherapy. Our framework can be generalized to analyze symptoms or symptom clusters of other chronic diseases where symptom management is critical.
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http://dx.doi.org/10.1109/JBHI.2021.3117238DOI Listing
October 2021

Metagenomic analysis of ancient dental calculus reveals unexplored diversity of oral archaeal Methanobrevibacter.

Microbiome 2021 09 30;9(1):197. Epub 2021 Sep 30.

Institute for Mummy Studies, Eurac Research, 39100, Bolzano, Italy.

Background: Dental calculus (mineralised dental plaque) preserves many types of microfossils and biomolecules, including microbial and host DNA, and ancient calculus are thus an important source of information regarding our ancestral human oral microbiome. In this study, we taxonomically characterised the dental calculus microbiome from 20 ancient human skeletal remains originating from Trentino-South Tyrol, Italy, dating from the Neolithic (6000-3500 BCE) to the Early Middle Ages (400-1000 CE).

Results: We found a high abundance of the archaeal genus Methanobrevibacter in the calculus. However, only a fraction of the sequences showed high similarity to Methanobrevibacter oralis, the only described Methanobrevibacter species in the human oral microbiome so far. To further investigate the diversity of this genus, we used de novo metagenome assembly to reconstruct 11 Methanobrevibacter genomes from the ancient calculus samples. Besides the presence of M. oralis in one of the samples, our phylogenetic analysis revealed two hitherto uncharacterised and unnamed oral Methanobrevibacter species that are prevalent in ancient calculus samples sampled from a broad range of geographical locations and time periods.

Conclusions: We have shown the potential of using de novo metagenomic assembly on ancient samples to explore microbial diversity and evolution. Our study suggests that there has been a possible shift in the human oral microbiome member Methanobrevibacter over the last millennia. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01132-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485483PMC
September 2021

PGRMC1 Exerts Its Function of Anti-Influenza Virus in the Central Nervous System.

Microbiol Spectr 2021 Sep 29:e0073421. Epub 2021 Sep 29.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural Universitygrid.35155.37, Wuhan, People's Republic of China.

The influenza A virus (IAV) infection is usually restricted to the respiratory tract and only rarely enters the central nervous system (CNS) and causes neurological symptoms. However, the roles of host factors involved in IAV infection in the CNS remain largely undetermined. Therefore, we aimed to characterize the host responses to IAV infection in the brain. We isolated a strain of IAV H5N6, which is neurotoxic and highly pathogenic to mice. High-throughput RNA sequencing (RNA-seq) revealed 240 differentially expressed genes in IAV-infected brains. Among the significantly downregulated genes, we focused on the gene encoding progesterone receptor membrane component-1 () and observed that IAV H5N6 infection clearly inhibited in both neuroblastoma and glioma cells. Furthermore, treatment with AG205, a -specific inhibitor, or knockout promoted H5N6 multiplication , while overexpression of resulted in opposite effects. Furthermore, AG205 treatment or knockout significantly inhibited the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-β) signaling pathway and reduced the levels of several antiviral proteins (Mx1 and ISG15). In addition, -mediated regulation of IFN signaling relied on inhibition of the expression and ubiquitination of RIG-I. The loss of leads to an increased susceptibility of mice (brain and lung) to influenza A virus infection. Conclusively, our results show for the first time that IAV H5N6 downregulates expression to contribute to virus proliferation by inhibiting RIG-I-mediated IFN-β production in the brain. These findings may offer new insights regarding the interplay between IAV and host factors that may impact IAV pathogenicity in the brain. Central nervous system (CNS) disease is one of the most common extra-respiratory tract complications of influenza A virus (IAV) infections. However, there is still little knowledge about IAV regulating host responses in brain. In this study, we identified progesterone receptor membrane component-1 (PGRMC1) as a novel host factor involved in the replication and propagation of IAV H5N6 in the host brain. We also observed that PGRMC1 antagonism was required for viral evasion from the host immune response during IAV infection via inhibition of the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-β) signaling pathway and downstream antiviral gene expression. This study revealed a newly identified regulatory mechanism used by IAV H5N6 to ensure its life cycle in the CNS.
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http://dx.doi.org/10.1128/Spectrum.00734-21DOI Listing
September 2021

Sex-specific mediation of placental inflammatory biomarkers in the effects of prenatal phthalate coexposure on preschooler cognitive development.

Environ Sci Pollut Res Int 2021 Sep 28. Epub 2021 Sep 28.

MOE Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, People's Republic of China.

The objective of this study is to investigate the mediating effect of placental inflammatory biomarkers on the relationship between prenatal phthalate coexposure and cognitive development in preschoolers. A subgroup of 1660 mother-child pairs from the Ma'anshan Birth Cohort study were included. We measured the levels of phthalate metabolites of dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP) in all the women included in the study from three urine samples collected in each of the trimesters. A potency-weighted sum of coexposure to DBP, BBzP, and DEHP (indicator: ∑PAE) was calculated. The mRNA of the proinflammatory cytokine IL-6 and the classically activated macrophage (M1) biomarker CD68 was analyzed using placental tissues. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition-Chinese was used to evaluate the full-scale intelligence quotient (FSIQ) of children aged 2.5-6 years. Average ∑PAEs and ∑PAEs in each trimester were associated with IL-6 and CD68. ∑PAE in the first trimester was positively associated with IL-6 (β = 0.11, 95% CIs = 0.03-0.19) and CD68 (β = 0.16, 95% CIs = 0.04-0.28), and negatively associated with FSIQ (β =-0.06, 95% CIs = -0.11 to -0.02), verbal comprehension (β =-0.06, 95% CIs = -0.11 to -0.01), and processing speed (β =-0.07, 95% CIs = -0.12 to -0.01). Additionally, sex discrepancies were observed for the mediating effects of placental inflammation on the relationships between ∑PAE and children's cognitive development. For instance, the association between ∑PAE in early pregnancy and FSIQ was partially mediated by IL-6 (estimated proportion mediated: 21.85%) and CD68 (estimated proportion mediated: 16.2%). Gender-specific associations and trimester-specific relationships of prenatal multiple phthalate coexposure were revealed. ∑PAE in the first trimester of pregnancy was associated with increased of placental inflammation, and a decrease in preschoolers' cognitive development. In boys, placental IL-6 and CD68 elevation resulting from phthalates might be potential mechanisms of poor cognitive development.
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http://dx.doi.org/10.1007/s11356-021-16695-0DOI Listing
September 2021

Gut microbiota: An emerging biological diagnostic and treatment approach for gastrointestinal diseases.

JGH Open 2021 Sep 21;5(9):973-975. Epub 2021 Sep 21.

Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center Chinese PLA General Hospital Beijing China.

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http://dx.doi.org/10.1002/jgh3.12659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454480PMC
September 2021

In vivo structure and dynamics of the SARS-CoV-2 RNA genome.

Nat Commun 2021 09 28;12(1):5695. Epub 2021 Sep 28.

Beijing institute of Biotechnology, Beijing, China.

The dynamics of SARS-CoV-2 RNA structure and their functional relevance are largely unknown. Here we develop a simplified SPLASH assay and comprehensively map the in vivo RNA-RNA interactome of SARS-CoV-2 genome across viral life cycle. We report canonical and alternative structures including 5'-UTR and 3'-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in both cells and virions. We provide direct evidence of interactions between Transcription Regulating Sequences, which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE. More importantly, we find that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome domains remain stable but with strengthened demarcation of local domains and weakened global cyclization. Taken together, our analysis reveals the structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, the alternative conformations and the maintenance of global genome organization during the whole life cycle of SARS-CoV-2, which we anticipate will help develop better antiviral strategies.
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http://dx.doi.org/10.1038/s41467-021-25999-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478942PMC
September 2021

Combined LXR and RXR Agonist Therapy Increases ABCA1 Protein Expression and Enhances ApoAI-Mediated Cholesterol Efflux in Cultured Endothelial Cells.

Metabolites 2021 Sep 18;11(9). Epub 2021 Sep 18.

Department of Food, Nutrition, and Packaging Sciences, Clemson University, Clemson, SC 29634, USA.

Endothelial ABCA1 expression protects against atherosclerosis and this atheroprotective effect is partially attributed to enhancing apoAI-mediated cholesterol efflux. ABCA1 is a target gene for LXR and RXR; therefore, treating endothelial cells with LXR and/or RXR agonists may increase ABCA1 expression. We tested whether treating cultured immortalized mouse aortic endothelial cells (iMAEC) with the endogenous LXR agonist 22(R)-hydroxycholesterol, synthetic LXR agonist GW3965, endogenous RXR agonist 9-cis-retinoic acid, or synthetic RXR agonist SR11237 increases ABCA1 protein expression. We observed a significant increase in ABCA1 protein expression in iMAEC treated with either GW3965 or SR11237 alone, but no significant increase in ABCA1 protein was observed in iMAEC treated with either 22(R)-hydroxycholesterol or 9-cis-retionic acid alone. However, we observed significant increases in both ABCA1 protein expression and apoAI-mediated cholesterol efflux when iMAEC were treated with a combination of either 22(R)-hydroxycholesterol and 9-cis-retinoic acid or GW3965 and SR11237. Furthermore, treating iMAEC with either 22(R)-hydroxycholesterol and 9-cis-retinoic acid or GW3965 and SR11237 did not trigger an inflammatory response, based on VCAM-1, ICAM-1, CCL2, and IL-6 mRNA expression. Based on our findings, delivering LXR and RXR agonists precisely to endothelial cells may be a promising atheroprotective approach.
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http://dx.doi.org/10.3390/metabo11090640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466889PMC
September 2021

Clinicopathological features of titinopathy from a Chinese neuromuscular center.

Neuropathology 2021 Oct 22;41(5):349-356. Epub 2021 Sep 22.

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

Titin, one of the largest proteins in humans, is a major component of muscle sarcomeres. Pathogenic variants in the titin gene (TTN) have been reported to cause a range of skeletal muscle diseases, collectively known as titinopathy. Titinopathy is a heterogeneous group of disabling diseases characterized by muscle weakness. In our study, we aimed to establish the clinicopathological-genetic spectrum of titinopathy from a single neuromuscular center. Three patients were diagnosed as having definite titinopathy, and additional three patients were diagnosed as having possible titinopathy according to the diagnostic criteria. All the patients showed initial symptoms from age one to 40 years. Physical examination revealed that five patients had muscle weakness, and that one patient experienced behavioral changes. Muscle biopsy specimens obtained from all six patients demonstrated multiple myopathological changes, including increased fiber size variation, muscle fiber hypertrophy or atrophy, formation of centralized cell nuclei, necklace cytoplasmic bodies, and formation of rimmed vacuoles and cores. Genetic testing revealed 11 different TTN alterations, including missense (6/11), nonsense (2/11), frameshift (2/11), and splicing (1/11) mutations. Our study provides further evidence that TTN mutations are more likely to be responsible for an increasing proportion of various myopathies, such as hereditary myopathy with early respiratory failure (HMERF), core myopathy, and distal myopathy with rimmed vacuoles, than currently recognized mutations. Our findings expand the clinical, pathohistological and genetic spectrum of titinopathy.
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http://dx.doi.org/10.1111/neup.12761DOI Listing
October 2021

A Novel Method to Map Small RNAs with High Resolution.

Bio Protoc 2021 Aug 20;11(16):e4128. Epub 2021 Aug 20.

Department of Plant and Soil Sciences, University of Delaware, Newark, DE, USA.

Analyzing cellular structures and the relative location of molecules is essential for addressing biological questions. Super-resolution microscopy techniques that bypass the light diffraction limit have become increasingly popular to study cellular molecule dynamics . However, the application of super-resolution imaging techniques to detect small RNAs (sRNAs) is limited by the choice of proper fluorophores, autofluorescence of samples, and failure to multiplex. Here, we describe an sRNA-PAINT protocol for the detection of sRNAs at nanometer resolution. The method combines the specificity of locked nucleic acid probes and the low background, precise quantitation, and multiplexable characteristics of DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT). Using this method, we successfully located sRNA targets that are important for development in maize anthers at sub-20 nm resolution and quantitated their exact copy numbers. Graphic abstract: Multiple Vetting and Analysis of RNA for Hybridization (VARNISH) probes with different docking strands (, a, b, …) will be hybridized to samples. The first probe will be imaged with the a* imager. The a* imager will be washed off with buffer C, and then the sample will be imaged with b* imager. The wash and image steps can be repeated sequentially for multiplexing.
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http://dx.doi.org/10.21769/BioProtoc.4128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413618PMC
August 2021

Applying interpretable deep learning models to identify chronic cough patients using EHR data.

Comput Methods Programs Biomed 2021 Oct 4;210:106395. Epub 2021 Sep 4.

Indiana University School of Medicine, 340W 10th St #6200, Indianapolis, IN 46202, United States; Regenstrief Institute, 1101W 10th Street, Indianapolis, IN, 46202, United States. Electronic address:

Background And Objective: Chronic cough (CC) affects approximately 10% of adults. Many disease states are associated with chronic cough, such as asthma, upper airway cough syndrome, bronchitis, and gastroesophageal reflux disease. The lack of an ICD code specific for chronic cough makes it challenging to identify such patients from electronic health records (EHRs). For clinical and research purposes, computational methods using EHR data are urgently needed to identify chronic cough cases. This research aims to investigate the data representations and deep learning algorithms for chronic cough prediction.

Methods: Utilizing real-world EHR data from a large academic healthcare system from October 2005 to September 2015, we investigated Natural Language Representation of the EHR data and systematically evaluated deep learning and traditional machine learning models to predict chronic cough patients. We built these machine learning models using structured data (medication and diagnosis) and unstructured data (clinical notes).

Results: The sensitivity and specificity of a transformer-based deep learning algorithm, specifically BERT with attention model, was 0.856 and 0.866, respectively, using structured data (medication and diagnosis). Sensitivity and specificity improved to 0.952 and 0.930 when we combined structured data with symptoms extracted from clinical notes. We further found that the attention mechanism of deep learning models can be used to extract important features that drive the prediction decisions. Compared with our previously published rule-based algorithm, the deep learning algorithm can identify more chronic cough patients with structured data.

Conclusions: By applying deep learning models, chronic cough patients can be reliably identified for prospective or retrospective research through medication and diagnosis data, widely available in EHR and electronic claims data, thus improving the generalizability of the patient identification algorithm. Deep learning models can identify chronic cough patients with even higher sensitivity and specificity when structured and unstructured EHR data are utilized. We anticipate language-based data representation and deep learning models developed in this research could also be productively used for other disease prediction and case identification.
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http://dx.doi.org/10.1016/j.cmpb.2021.106395DOI Listing
October 2021

Intron retention-induced neoantigen load correlates with unfavorable prognosis in multiple myeloma.

Oncogene 2021 Oct 9;40(42):6130-6138. Epub 2021 Sep 9.

Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

Neoantigen peptides arising from genetic alterations may serve as targets for personalized cancer vaccines and as positive predictors of response to immune checkpoint therapy. Mutations in genes regulating RNA splicing are common in hematological malignancies leading to dysregulated splicing and intron retention (IR). In this study, we investigated IR as a potential source of tumor neoantigens in multiple myeloma (MM) patients and the relationship of IR-induced neoantigens (IR-neoAg) with clinical outcomes. MM-specific IR events were identified in RNA-sequencing data from the Multiple Myeloma Research Foundation CoMMpass study after removing IR events that also occurred in normal plasma cells. We quantified the IR-neoAg load by assessing IR-induced novel peptides that were predicted to bind to major histocompatibility complex (MHC) molecules. We found that high IR-neoAg load was associated with poor overall survival in both newly diagnosed and relapsed MM patients. Further analyses revealed that poor outcome in MM patients with high IR-neoAg load was associated with high expression levels of T-cell co-inhibitory molecules and elevated interferon signaling activity. We also found that MM cells exhibiting high IR levels had lower MHC-II protein abundance and treatment of MM cells with a spliceosome inhibitor resulted in increased MHC-I protein abundance. Our findings suggest that IR-neoAg may represent a novel biomarker of MM patient clinical outcome and further that targeting RNA splicing may serve as a potential therapeutic strategy to prevent MM immune escape and promote response to checkpoint blockade.
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http://dx.doi.org/10.1038/s41388-021-02005-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426332PMC
October 2021

Prenatal low-dose antibiotic exposure and children allergic diseases at 4 years of age: A prospective birth cohort study.

Ecotoxicol Environ Saf 2021 Dec 1;225:112736. Epub 2021 Sep 1.

School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China. Electronic address:

Background: Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing.

Objectives: This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age.

Methods: The current study including 2453 mother-child pairs was based on the Ma'anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children.

Results: The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children.

Conclusions: Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112736DOI Listing
December 2021

Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice.

BMC Gastroenterol 2021 Aug 28;21(1):335. Epub 2021 Aug 28.

Department of Gastroenterology, Civil Aviation General Hospital, No. 1, Gaojingjia, Chaoyang District, China.

Background: Although salt plays an important role in maintaining the normal physiological metabolism of the human body, many abnormalities in the liver caused by a high-salt diet, especially with normal pathological results, are not well characterized.

Methods: Eight-week-old female C57BL/6 mice were randomly divided into a normal group and a high salt group. These groups were then fed with normal or sodium-rich chow (containing 6% NaCl) for 6 weeks. Liver injury was evaluated, and the influences of a high-salt diet on the liver were analyzed by transcriptome sequencing at the end of week 6.

Results: We found that although no liver parenchymal injury could be found after high-salt feeding, many metabolic abnormalities had formed based on transcriptome sequencing results. GO and KEGG enrichment analyses of differentially expressed genes revealed that at least 15 enzymatic activities and the metabolism of multiple substances were affected by a high-salt diet. Moreover, a variety of signaling and metabolic pathways, as well as numerous biological functions, were involved in liver dysfunction due to a high-salt diet. This included some known pathways and many novel ones, such as retinol metabolism, linoleic acid metabolism, steroid hormone biosynthesis, and signaling pathways.

Conclusions: A high-salt diet can induce serious abnormal liver metabolic activities in mice at the transcriptional level, although substantial physical damage may not yet be visible. This study, to our knowledge, was the first to reveal the impact of a high-salt diet on the liver at the omics level, and provides theoretical support for potential clinical risk evaluation, pathogenic mechanisms, and drug design for combating liver dysfunction. This study also provides a serious candidate direction for further research on the physiological impacts of high-salt diets.
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http://dx.doi.org/10.1186/s12876-021-01912-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397858PMC
August 2021

3-Indoleacetonitrile Is Highly Effective in Treating Influenza A Virus Infection In Vitro and In Vivo.

Viruses 2021 Jul 23;13(8). Epub 2021 Jul 23.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.

Influenza A viruses are serious zoonotic pathogens that continuously cause pandemics in several animal hosts, including birds, pigs, and humans. Indole derivatives containing an indole core framework have been extensively studied and developed to prevent and/or treat viral infection. This study evaluated the anti-influenza activity of several indole derivatives, including 3-indoleacetonitrile, indole-3-carboxaldehyde, 3-carboxyindole, and gramine, in A549 and MDCK cells. Among these compounds, 3-indoleacetonitrile exerts profound antiviral activity against a broad spectrum of influenza A viruses, as tested in A549 cells. Importantly, in a mouse model, 3-indoleacetonitrile with a non-toxic concentration of 20 mg/kg effectively reduced the mortality and weight loss, diminished lung virus titers, and alleviated lung lesions of mice lethally challenged with A/duck/Hubei/WH18/2015 H5N6 and A/Puerto Rico/8/1934 H1N1 influenza A viruses. The antiviral properties enable the potential use of 3-indoleacetonitrile for the treatment of IAV infection.
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http://dx.doi.org/10.3390/v13081433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402863PMC
July 2021

Prediction of dispositional dialectical thinking from resting-state electroencephalography.

Brain Behav 2021 Sep 22;11(9):e2327. Epub 2021 Aug 22.

Center for Statistical Science and Department of Industrial Engineering, Tsinghua University, Beijing, China.

This study aims to explore the possibility of predicting the dispositional level of dialectical thinking using resting-state electroencephalography signals. Thirty-four participants completed a self-reported measure of dialectical thinking, and their resting-state electroencephalography was recorded. After wave filtration and eye movement removal, time-frequency electroencephalography signals were converted into four frequency domains: delta (1-4 Hz), theta (4-7 Hz), alpha (7-13 Hz), and beta (13-30 Hz). Functional principal component analysis with B-spline approximation was then applied for feature reduction. Five machine learning methods (support vector regression, least absolute shrinkage and selection operator, K-nearest neighbors, random forest, and gradient boosting decision tree) were applied to the reduced features for prediction. The model ensemble technique was used to create the best performing final model. The results showed that the alpha wave of the electroencephalography signal in the early period (12-15 s) contributed most to the prediction of dialectical thinking. With data-driven electrode selection (FC1, FCz, Fz, FC3, Cz, AFz), the prediction model achieved an average coefficient of determination of 0.45 on 200 random test sets. Furthermore, a significant positive correlation was found between the alpha value of standardized low-resolution electromagnetic tomography activity in the right dorsal anterior cingulate cortex and dialectical self-scale score. The prefrontal and midline alpha oscillations of resting electroencephalography are good predictors of the dispositional level of dialectical thinking, possibly reflecting these brain structures' involvement in dialectical thinking.
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http://dx.doi.org/10.1002/brb3.2327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442598PMC
September 2021

Pre-meiotic 21-nucleotide reproductive phasiRNAs emerged in seed plants and diversified in flowering plants.

Nat Commun 2021 08 16;12(1):4941. Epub 2021 Aug 16.

Donald Danforth Plant Science Center, Saint Louis, MO, USA.

Plant small RNAs are important regulatory elements that fine-tune gene expression and maintain genome integrity by silencing transposons. Reproductive organs of monocots produce abundant phased, small interfering RNAs (phasiRNAs). The 21-nt reproductive phasiRNAs triggered by miR2118 are highly enriched in pre-meiotic anthers, and have been found in multiple eudicot species, in contrast with prior reports of monocot specificity. The 24-nt reproductive phasiRNAs are triggered by miR2275, and are highly enriched during meiosis in many angiosperms. Here, we report the widespread presence of the 21-nt reproductive phasiRNA pathway in eudicots including canonical and non-canonical microRNA (miRNA) triggers of this pathway. In eudicots, these 21-nt phasiRNAs are enriched in pre-meiotic stages, a spatiotemporal distribution consistent with that of monocots and suggesting a role in anther development. Although this pathway is apparently absent in well-studied eudicot families including the Brassicaceae, Solanaceae and Fabaceae, our work in eudicots supports an earlier singular finding in spruce, a gymnosperm, indicating that the pathway of 21-nt reproductive phasiRNAs emerged in seed plants and was lost in some lineages.
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http://dx.doi.org/10.1038/s41467-021-25128-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368212PMC
August 2021

Evaluation of outcome measures for myasthenia gravis subgroups.

J Clin Neurosci 2021 Sep 27;91:270-275. Epub 2021 Jul 27.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, PR China. Electronic address:

Introduction: Disease evaluation and long-term follow-up of myasthenia gravis (MG) patients rely on disease-specific measures. We evaluated four widely used MG-specific assessments, and compared the response to disease change in different MG subgroups.

Methods: We used the Cronbach's α coefficient to test reliability, Pearson correlation coefficients to test construct validity, as well as one-way ANOVA and independent-sample t-tests to access discriminant validity. Analyses of similar items between QMG and MG-ADL included paired-sample t-tests and mean score comparisons. Pearson correlation coefficients were used to describe the correlation between changes of QMG, MG-ADL, MG-QOL15r and MGC. The Wilcoxon matched-pairs signed-ranks test was performed to compare the outcomes.

Results: 872 MG patients were enrolled. QMG, MG-ADL, MG-QOL15r, and MGC all exhibited high reliability. All four scales displayed good discriminant validity according to the MGFA classification and MGC score. MG-ADL showed significant differences between patients grouped by age and gender, and MG-QOL15r showed significant differences between patients grouped by age. Analyses of similar items showed that MG-ADL achieved higher scores in bulbar items, whereas QMG produced higher scores in limb items. For patients in remission or minimal manifestation status, QMG exhibited significantly greater improvement than MG-QOL15r. In patients of MGFA I, II, III, and IV, QMG showed significantly greater improvement than MG-ADL.

Conclusions: Patient-reported scale is an important supplement for a given period. MG-ADL has a better response to severe disease, and MG-QOL15r is more comprehensive for patients in remission or minimal manifestation status.
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http://dx.doi.org/10.1016/j.jocn.2021.07.020DOI Listing
September 2021

Risk factors related to postoperative recurrence of dermatofibrosarcoma protuberans: A retrospective study and literature review.

World J Clin Cases 2021 Jul;9(20):5442-5452

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade malignant soft tissue tumor characterized by rosette-like infiltrative growth. Postoperative recurrence of this tumor is very common.

Aim: To evaluate the risk factors related to recurrence after wide local excision (WLE) of DFSP and to guide clinical diagnosis and treatment.

Methods: The medical records of 44 DFSP patients confirmed by pathology at our hospital from 2012 to 2019 were retrospectively reviewed. The relationship between clinical features, tumor characteristics, treatment, and recurrence risk were analyzed, and the possible risk factors for postoperative tumor recurrence were evaluated.

Results: There were 44 patients in total, including 21 males and 23 females. The median progression free survival was 36 mo (range, 1-240 mo). Twenty patients were treated for the first time, while 24 had previous treatment experience. Forty-two cases were followed for 25.76 ± 22.0 mo, among whom four (9.52%) experienced recurrence after WLE (rate was 9.52%). The recurrence rate in the recurrent group was higher than that in the patients with primary tumor (19.05% 0%, = 0.028). Eighteen cases had a history of misdiagnosis (rate was 40.91%). The recurrence rate among patients with previous experience of misdiagnosis was significantly higher than in patients without (68% 36.84%, = 0.04). The tumor diameter in patients with a history of treatment was larger than in patients treated for the first time (4.75 ± 0.70 cm 2.25 ± 0.36 cm, = 0.004).

Conclusion: To sum up, the clinical manifestations of DFSP are not specific and are easily misdiagnosed, thus commonly causing the recurrence of DFSP. After incomplete resection, the tumor may rapidly grow. Previous recurrence history may be a risk factor for postoperative recurrence, and tumor location may have an indirect effect on postoperative recurrence; however, we found no significant correlation between sex, age, course of the disease, or tumor size and postoperative recurrence.
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http://dx.doi.org/10.12998/wjcc.v9.i20.5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281415PMC
July 2021

Emerging roles of angiopoietin-like proteins in inflammation: Mechanisms and potential as pharmacological targets.

J Cell Physiol 2021 Jul 21. Epub 2021 Jul 21.

Department of Biopharmacy, Tongji School of Pharmacy, Huazhong University of Science & Technology, Wuhan, China.

Angiopoietin-like proteins (ANGPTLs), a family of eight secreted glycoproteins termed ANGTPL1-8, are involved in angiogenesis, lipid metabolism, cancer progression, and inflammation. Their roles in regulating lipid metabolism have been intensively studied, as some ANGPTLs are promising pharmacological targets for hypertriglyceridemia and associated cardiovascular disease. Recently, the emerging roles of ANGPTLs in inflammation have attracted great attention. First, elevated levels of multiple circulating ANGPTLs in inflammatory diseases make them potential disease biomarkers. Second, multiple ANGPTLs regulate acute or chronic inflammation via various mechanisms, including triggering inflammatory signaling through their action as ligands for integrin or forming homo- /hetero-oligomers to regulate signal transduction via extra- or intracellular mechanisms. As dysregulation of the inflammatory response is a critical trigger in many diseases, understanding the roles of ANGPTLs in inflammation will aid in drug/therapy development. Here, we summarize the roles, mechanisms, and potential therapeutic values for ANGPTLs in inflammation and inflammatory diseases.
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http://dx.doi.org/10.1002/jcp.30534DOI Listing
July 2021

BrcaSeg: A Deep Learning Approach for Tissue Quantification and Genomic Correlations of Histopathological Images.

Genomics Proteomics Bioinformatics 2021 Jul 16. Epub 2021 Jul 16.

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Regenstrief Institute, Indianapolis, IN 46202, USA. Electronic address:

Epithelial and stromal tissues are components of the tumor microenvironment and play a major role in tumor initiation and progression. Distinguishing stroma from epithelial tissues is critically important for spatial characterization of the tumor microenvironment. We propose BrcaSeg, an image analysis pipeline based on a convolutional neural network (CNN) model to classify epithelial and stromal regions in whole-slide hematoxylin and eosin (H&E) stained histopathological images. The CNN model was trained using well-annotated breast cancer tissue microarrays and validated with images from The Cancer Genome Atlas (TCGA) Program. BrcaSeg achieves a classification accuracy of 91.02%, which outperforms other state-of-the-art methods. Using this model, we generated pixel-level epithelial/stromal tissue maps for 1000 TCGA breast cancer slide images that are paired with gene expression data. We subsequently estimated the epithelial and stromal ratios and performed correlation analysis to model the relationship between gene expression and tissue ratios. Gene Ontology (GO) enrichment analyses of genes that were highly correlated with tissue ratios suggest that the same tissue was associated with similar biological processes in different breast cancer subtypes, whereas each subtype also had its own idiosyncratic biological processes governing the development of these tissues. Taken all together, our approach can lead to new insights in exploring relationships between image-based phenotypes and their underlying genomic events and biological processes for all types of solid tumors. BrcaSeg can be accessed at https://github.com/Serian1992/ImgBio.
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http://dx.doi.org/10.1016/j.gpb.2020.06.026DOI Listing
July 2021

Low-dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors.

Res Pract Thromb Haemost 2021 Jul 14;5(5):e12562. Epub 2021 Jul 14.

Hemophilia Comprehensive Care Center Hematology Center Beijing Key Laboratory of Pediatric Hematology Oncology National Key Discipline of Pediatrics (Capital Medical University) Key Laboratory of Major Diseases in Children Ministry of Education Beijing Children's Hospital National Center for Children's Health Capital Medical University Beijing China.

Background: In developing countries, children with hemophilia A (HA) with high-titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high- or intermediate-dose ITI.

Objectives: To determine the efficacy of low-dose ITI (plasma-derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI-alone) or combined with immunosuppressants rituximab and prednisone (ITI-IS) in children with HA with high-titer inhibitor.

Methods: All enrolled patients had pre-ITI inhibitor ≥10 BU. We used ITI-alone if inhibitor titer was <40 BU pre-ITI and during ITI, and ITI-IS if titer was ≥100 BU (historic) or ≥40 BU (pre- or during ITI) or if the patient was nonresponsive on ITI-alone.

Results: Fifty-six children were analyzable, with median historic peak inhibitor titer 48.0 BU and followed for median 31.4 months. Overall, 35 (62.5%) achieved phase 2 success with negative inhibitor and normal FVIII recovery. The phase 2 success rate was 95% for the 20 patients receiving ITI-alone. For the 36 patients receiving ITI-IS, the phase 2 success rate was 44.4%, but would increase to 63.6% if the 14 patients with historic peak inhibitor titer ≥100 BU (and having phase 2 success rate of only 14.3%) were excluded. One patient developed repeated infection after IS treatment. Relapse occurred in 11.4% (4/35) patients with phase 2 success associated with rapid ITI dose reduction or irregular post-ITI FVIII prophylaxis. Our strategy reduced the cost from high-dose ITI by 74% to 90%.

Conclusion: The use of low-dose ITI with or without immunosuppressants according to ITI prognostic risk(s) is a clinically and economically feasible strategy for eradicating inhibitors in children with HA, particularly for those with historic peak inhibitor titer <100 BU.
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http://dx.doi.org/10.1002/rth2.12562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279128PMC
July 2021

Clinical value of contrast-enhanced ultrasonography in focal hypoechogenic lesions of thyroid.

Eur Arch Otorhinolaryngol 2021 Jul 18. Epub 2021 Jul 18.

Department of Ultrasonic Diagnosis, The First Affiliated Hospital of China Medical University, Nanjingbei Street 155#, Shenyang, Liaoning, People's Republic of China.

Objective: The objectives of this study were to analyze the accuracy of contrast-enhanced ultrasonography (CE-US) in diagnosing focal hypoechogenic lesions of the thyroid (FHLT), and to explore the clinical value of CE-US in the diagnosis of FHLT.

Methods: Patients undergoing CE-US and ultrasound-guided fine needle aspiration (US-FNA) of FHLT at First Hospital of China Medical University between January 2017 and December 2018 were selected for the study; this included patients with papillary thyroid carcinoma (PTC), subacute thyroiditis (SAT) and focal Hashimoto thyroiditis (FHT). All patients underwent color Doppler ultrasonography (CD-US) after which thyroid image reporting and data system (TI-RADS) grading were done. Then, each patient underwent CE-US and US-FNA. The results of the CE-US were analyzed using descriptive statistics. The cytopathological results from the US-FNAs were the gold standard used to confirm the diagnoses.

Results: A total of 56 patients were selected for the study. In the PTC group (n = 16), grading was as follows: TI-RADS4a, n = 3; TI-RADS4b, n = 12; and TI-RADS4c, n = 1. More patients with PTC showed heterogeneous hypoenhancement (n = 15) than heterogeneous isoenhancement (n = 1) on CE-US. In the SAT group (n = 24), grading was as follows: TI-RADS3, n = 1; TI-RADS4a, n = 18; TI-RADS4b, n = 5. Fewer patients with SAT showed heterogeneous hypoenhancement (n = 2) than heterogeneous isoenhancement (n = 22) on CE-US. In the FHT group (n = 16), grading was as follows: TI-RADS3, n = 1; TI-RADS4a, n = 11; TI-RADS4b, n = 4. Of those in the FHT group, one patient showed heterogeneous isoenhancement, one patient showed heterogeneous hypoenhancement, and 14 showed uniform isoenhancement on CE-US. The diagnostic accuracy of CD-US alone differed significantly from that of CD-US + CE-US (p < 0.05).

Conclusion: CE-US has a high diagnostic accuracy for FHLT and can be used to identify PTC, SAT, and FHT.
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http://dx.doi.org/10.1007/s00405-021-06982-4DOI Listing
July 2021

High-precision passive stabilization of repetition rate for a mode-locked fiber laser based on optical pulse injection.

Opt Express 2021 Jun;29(13):20930-20940

We have proposed and implemented a novel scheme to obtain high-precision repetition rate stabilization for a polarization-maintaining mode-locked fiber laser. The essential technique lies in the periodic injection of electronically modulated optical pulses into a nonlinear amplifying loop mirror within the laser resonator. Thanks to the nonlinear cross-phase modulation effect, the injected pulses referenced to an external clock serves as a stable and precise timing trigger for an effective intensity modulator. Consequently, synchronous mode-locking can be initiated to output ultrafast pulses with a passively stabilized repetition rate. The capture range of the locking system reaches to a record of 1 mm, which enables a long-term stable operation over 15 hours without the need of temperature stabilization and vibration isolation. Meanwhile, the achieved standard deviation is as low as 100 μHz with a 1-s sample time, corresponding to a fluctuation instability of 5.0×10. Additionally, the repetition rate stabilization performance based on the passive synchronization has been systematically investigated by varying the average power, central wavelength and pulse duration of the optical injection.
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http://dx.doi.org/10.1364/OE.425435DOI Listing
June 2021

Weakly Supervised Deep Ordinal Cox Model for Survival Prediction from Whole-slide Pathological Images.

IEEE Trans Med Imaging 2021 Jul 15;PP. Epub 2021 Jul 15.

Whole-Slide Histopathology Image (WSI) is generally considered the gold standard for cancer diagnosis and prognosis. Given the large inter-operator variation among pathologists, there is an imperative need to develop machine learning models based on WSIs for consistently predicting patient prognosis. The existing WSI-based prediction methods do not utilize the ordinal ranking loss to train the prognosis model, and thus cannot model the strong ordinal information among different patients in an efficient way. Another challenge is that a WSI is of large size (e.g., 100,000-by-100,000 pixels) with heterogeneous patterns but often only annotated with a single WSI-level label, which further complicates the training process. To address these challenges, we consider the ordinal characteristic of the survival process by adding a ranking-based regularization term on the Cox model and propose a weakly supervised deep ordinal Cox model (BDOCOX) for survival prediction from WSIs. Here, we generate amounts of bags from WSIs, and each bag is comprised of the image patches representing the heterogeneous patterns of WSIs, which is assumed to match the WSI-level labels for training the proposed model. The effectiveness of the proposed method is well validated by theoretical analysis as well as the prognosis and patient stratification results on three cancer datasets from The Cancer Genome Atlas (TCGA).
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http://dx.doi.org/10.1109/TMI.2021.3097319DOI Listing
July 2021

Tetraphenylpyrazine-Based Manganese Metal-Organic Framework as a Multifunctional Sensor for Cu, Cr, MnO, and 2,4,6-Trinitrophenol and the Construction of a Molecular Logical Gate.

Inorg Chem 2021 Aug 14;60(15):11222-11230. Epub 2021 Jul 14.

Key Laboratory of Chemical Synthesis and Pollution Control of Sichuan Province, School of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002, P. R. China.

A tetraimidazole-decorating tetraphenylpyrazine has been designed and utilized for the fabrication of a novel metal-organic framework (MOF), denoted as {Mn(Tipp)(A)}·2HO (TippMn, where Tipp = 2,3,5,6-tetrakis[4-[(1-imidazol-1-yl)methyl]phenyl]pyrazine and A = deprotonation of 1,4-naphthalenedicarboxylic acid), through hydrothermal synthesis. Structural analysis reveals that TippMn possesses a 2-fold-interpenetrated 4,8-connected three-dimensional (3D) network with an unprecedented {4·6}{4·6} topology. Fluorescent spectral investigations indicate that TippMn shows discriminative fluorescence when treated by Cr and Cu, giving an INHIBIT logical gate performance. Meanwhile, TippMn can be further used as a sensor for MnO and 2,4,6-trinitrophenol (TNP) by fluorescence quenching. Notably, the sensing processes toward Cu, Cr, MnO, and TNP are labeled with high selectivity and sensitivity, quick response, and good recyclability. It is anticipated that this MOF-based versatile sensor could shed light on the exploration of MOFs for fluorescent sensors, optical switches, etc.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01226DOI Listing
August 2021
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