Text mining of CHO bioprocess bibliome: Topic modeling and document classification.

Chinese hamster ovary (CHO) cells are widely used for mass production of therapeutic proteins in the pharmaceutical industry. With the growing need in optimizing the performance of producer CHO cell lines, research on CHO cell line development and bioprocess continues to increase in recent decades. Bibliographic mapping and classification of relevant research studies will be essential for identifying research gaps and trends in literature. To qualitatively and quantitatively understand the CHO literature, we have conducted topic modeling using a CHO bioprocess bibliome manually compiled in 2016, and compared the topics uncovered by the Latent Dirichlet Allocation (LDA) models with the human labels of the CHO bibliome. The results show a significant overlap between the manually selected categories and computationally generated topics, and reveal the machine-generated topic-specific characteristics. To identify relevant CHO bioprocessing papers from new scientific literature, we have developed supervized models using Logistic Regression to identify specific article topics and evaluated the results using three CHO bibliome datasets, Bioprocessing set, Glycosylation set, and Phenotype set. The use of top terms as features supports the explainability of document classification results to yield insights on new CHO bioprocessing papers.

The Glycan Structure Dictionary-a dictionary describing commonly used glycan structure terms.

Recent technological advances in glycobiology have resulted in a large influx of data and the publication of many papers describing discoveries in glycoscience. However, the terms used in describing glycan structural features are not standardized, making it difficult to harmonize data across biomolecular databases, hampering the harvesting of information across studies and hindering text mining and curation efforts. To address this shortcoming, the Glycan Structure Dictionary has been developed as a reference dictionary to provide a standardized list of widely used glycan terms that can help in the curation and mapping of glycan structures described in publications. Currently, the dictionary has 190 glycan structure terms with 297 synonyms linked to 3,332 publications. For a term to be included in the dictionary, it must be present in at least 2 peer-reviewed publications. Synonyms, annotations, and cross-references to GlyTouCan, GlycoMotif, and other relevant databases and resources are also provided when available. The purpose of this effort is to facilitate biocuration, assist in the development of text mining tools, improve the harmonization of search, and browse capabilities in glycoinformatics resources and help to map glycan structures to function and disease. It is also expected that authors will use these terms to describe glycan structures in their manuscripts over time. A mechanism is also provided for researchers to submit terms for potential incorporation. The dictionary is available at https://wiki.glygen.org/Glycan_structure_dictionary.

Investigation of improving the pre-training and fine-tuning of BERT model for biomedical relation extraction.

BACKGROUND: Recently, automatically extracting biomedical relations has been a significant subject in biomedical research due to the rapid growth of biomedical literature. Since the adaptation to the biomedical domain, the transformer-based BERT models have produced leading results on many biomedical natural language processing tasks. In this work, we will explore the approaches to improve the BERT model for relation extraction tasks in both the pre-training and fine-tuning stages of its applications. In the pre-training stage, we add another level of BERT adaptation on sub-domain data to bridge the gap between domain knowledge and task-specific knowledge. Also, we propose methods to incorporate the ignored knowledge in the last layer of BERT to improve its fine-tuning. RESULTS: The experiment results demonstrate that our approaches for pre-training and fine-tuning can improve the BERT model performance. After combining the two proposed techniques, our approach outperforms the original BERT models with averaged F1 score improvement of 2.1% on relation extraction tasks. Moreover, our approach achieves state-of-the-art performance on three relation extraction benchmark datasets. CONCLUSIONS: The extra pre-training step on sub-domain data can help the BERT model generalization on specific tasks, and our proposed fine-tuning mechanism could utilize the knowledge in the last layer of BERT to boost the model performance. Furthermore, the combination of these two approaches further improves the performance of BERT model on the relation extraction tasks.

Therapeutic effects of oral fluralaner in pet rabbits with severe sarcoptic mange (Sarcoptes scabiei).

Sarcoptic mange is one of the most severe, highly contagious, and fatal ectoparasitic infestations of rabbits. Fluralaner, an isoxazoline class of oral ectoparasiticide, is considered as a very potent acaricide. The present study aimed to evaluate the therapeutic efficacy of oral fluralaner in pet rabbits with severe spontaneous Sarcoptes scabiei infestation. A total of eight un-neutered pet rabbits, tested positive for S. scabiei by microscopy of skin scrapings, were enrolled. Seven rabbits had severe clinical infestation (score 5), while remaining one rabbit had moderate disease clinical signs (score <3). A single oral dose equivalent to 25 mg/kg of fluralaner was administered to each rabbit. On day 14 post-therapy, marked improvements in the skin lesions were observed; severely infested rabbits had a clinical score of 3, while the moderately infested rabbit had a score of 1. However, none of the rabbits tested negative for S. scabiei. On day 30 post-therapy, complete clinical recovery was recorded in all rabbits (Score 0), but, a complete parasitological clearance was not recorded except to the moderately infested rabbit. All rabbits were tested negative for S. scabiei on day 45 post-therapy. Therefore, a single oral dose of fluralaner at a 25 mg/kg was found to be effective in the treatment of severe sarcoptic mange in pet rabbits and no additional topical or systemic medications were needed. Further studies in a larger number of individuals with a bigger spectrum of disease severities (i.e. more moderate/mild) are needed to comprehensively document the safety and efficacy of this drug in mangy rabbits.

The phenotypic and haemato-biochemical appraisal of tropical theileriosis in newborn calves.

Tropical theileriosis is one of the major causes of newborn calves mortality. Observation of clinical manifestations is important while making the presumptive/tentative diagnosis of tropical theileriosis in newborn calves. The phenotypic and haemato-biochemical appraisals of tropical theileriosis could be of great help to make a holistic therapeutic plan for diseased newborn calves. Therefore, the present study aimed to evaluate the haemato-biochemical and phenotypic diagnostic markers of tropical theileriosis in newborn calves. A total of 43 newborn calves naturally infected with Theileria annulata and 16 age-matched healthy calves were enrolled. The percentage distribution of clinical markers was generalized lymph nodes enlargement (100%), pyrexia (97.67%), respiratory distress (95.34%), tick infestation (90.69%), anorexia (88.37%), pica (81.39%), pallor mucous membrane (67.44%), hyperlacrimation (58.13%) and exophthalmia (30.22%). Haemograms including TEC, Hb and HCT were found to be significantly (P ≤ 0.001) lowered in diseased calves. Remarkable alterations in the leukogram panels were not observed. Serum glucose, total protein, albumin and globulin concentrations of calves with theileriosis were significantly (P ≤ 0.001) lower than healthy ones, whereas triglycerides and total cholesterol levels of diseased calves were significantly (P ≤ 0.001) higher. Significantly (P ≤ 0.001) elevated activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzymes were observed in diseased calves. An evaluation of clinical phenotypes could be helpful to initiate quick treatment of diseased calves in field conditions and save the lives of sick calves of economically poor farmers. Altered haemato-biochemical panels to be appraised by veterinary clinicians while making a therapeutic plan of tropical theileriosis.

Expression of barrier proteins in the skin lesions and inflammatory cytokines in peripheral blood mononuclear cells of atopic dogs.

Atopic dermatitis (AD) is one of the most common skin diseases of dogs. Defects in the skin barrier and overproduction of inflammatory cytokines may be the pathogenesis of canine AD. Therefore, the present study was aimed to quantify the gene expression of certain skin barrier proteins and inflammatory cytokines in dogs with AD. Eleven dogs with AD and three healthy dogs were included in the present study. The skin barrier proteins, namely Filaggrin (FLG) and Involucrin (IVL), gene expression was quantified by Real-time PCR in the lesional skin tissues of the atopic dogs and normal skin of the healthy dogs. In addition to the skin proteins, the gene expressions of the interleukin (IL)-13, IL-31, and tumour necrosis factor (TNF)-α were also quantified in the peripheral blood mononuclear cells (PBMCs) of these dogs. Compared to the healthy dogs, significantly higher (P ≤ 0.01) FLG gene expression and significantly (P ≤ 0.05) lower expression of the IVL gene were quantified in the skin of atopic dogs. Further, the dogs with AD revealed significantly higher expression of TNF-α (P ≤ 0.01), IL-31 (P ≤ 0.05), and IL-13 (P ≤ 0.05) as compared to the healthy dogs. The findings of our present study evidently suggest significantly increased and decreased expressions of FLG and IVL genes, respectively, which may be responsible for disruption of the skin barrier in dogs with AD. While, the over-expressions of TNF-α, IL-31, and IL-13 genes might be attributed to the clinical pathology and manifestations of AD in dogs. However, further studies are warranted to substantiate our hypothesis about pathogenesis and clinical manifestation of AD in dogs by including a large number of animals.

emiRIT: a text-mining-based resource for microRNA information.

microRNAs (miRNAs) are essential gene regulators, and their dysregulation often leads to diseases. Easy access to miRNA information is crucial for interpreting generated experimental data, connecting facts across publications and developing new hypotheses built on previous knowledge. Here, we present extracting miRNA Information from Text (emiRIT), a text-miningbased resource, which presents miRNA information mined from the literature through a user-friendly interface. We collected 149 ,233 miRNA -PubMed ID pairs from Medline between January 1997 and May 2020. emiRIT currently contains 'miRNA -gene regulation' (69 ,152 relations), 'miRNA disease (cancer)' (12 ,300 relations), 'miRNA -biological process and pathways' (23, 390 relations) and circulatory 'miRNAs in extracellular locations' (3782 relations). Biological entities and their relation to miRNAs were extracted from Medline abstracts using publicly available and in-house developed text-mining tools, and the entities were normalized to facilitate querying and integration. We built a database and an interface to store and access the integrated data, respectively. We provide an up-to-date and user-friendly resource to facilitate access to comprehensive miRNA information from the literature on a large scale, enabling users to navigate through different roles of miRNA and examine them in a context specific to their information needs. To assess our resource's information coverage, we have conducted two case studies focusing on the target and differential expression information of miRNAs in the context of cancer and a third case study to assess the usage of emiRIT in the curation of miRNA information. Database URL: https://research.bioinformatics.udel.edu/emirit/.

Effects of Injectable Trace Minerals (ITMs) on Th1/Th2 Cytokine Balance of Newborn Calves with Tropical Theileriosis.

Injectable trace minerals (ITMs) could provide a potential alternative way of trace mineral delivery for sick animals. Therefore, evaluation of ameliorative potentials of ITMs (copper, manganese, selenium, and zinc) on the circulating Th1/Th2 cytokine misbalance in Theileria annulata-infected calves was aimed. Forty-three T. annulata-infected newborn calves were randomly allocated into four groups: buparvaquone alone-treated group (BUPA), buparvaquone + oxytetracycline (BUPA + OXY)-treated group, buparvaquone + injectable trace minerals (BUPA + ITMs)-treated group, and BUPA + OXY + ITM-treated group. Blood samples were collected from each of the calves before the start of therapy (day 0) and on day 14 post-therapy. Serum contents of pro- and anti-inflammatory cytokines were estimated by bovine specific ELISA kits. On day 14 post-therapy, significant amelioration in the circulating levels of the studied cytokines was not observed in the calves treated with BUPA, while the calves treated with BUPA + OXY revealed significant (P ≤ 0.04) amelioration in the circulating tumour necrosis factor-α (TNF-α) level. The calves treated with BUPA + ITMs revealed significant (P ≤ 0.041) elevation in the circulating interferon-γ (IFN-γ) and significant (P ≤ 0.011) reduction in the interleukin-10 (IL-10) levels. Moreover, the calves treated with BUPA + OXY + ITMs revealed significant reduction in TNF-α (P ≤ 0.0001) and IL-10 (P ≤ 0.012) contents, and significant elevation in IFN-γ (P ≤ 0.0002) content on day 14 post-therapy. None of the treated calve group revealed significant alteration in the circulating level of transforming growth factor-ß (TGF-ß) on day 14 post-therapy. In conclusion, administration of ITMs to the therapeutic regimen of newborn calves with tropical theileriosis could be a promising therapeutic strategy. ITMs can be recommended for the amelioration of immunological misbalance due to tropical theileriosis in newborn calves.

Synthesis and biological evaluation of imidazoline derivatives as potential CNS and CVS agents.

A series of substituted imidazoline derivatives were synthesized and characterized. Compounds were tested in-vivo for their antihypertensive, analgesic, antiaggressive, depressant, antidepressant, and ALD50 activities. The compounds 3a, 3c, 4c, 5a, and 6c showed cardiovascular as well as central nervous system activities and are potential candidate as drug among all fifteen compounds tested. All these compounds have shown better activity for antihypertensive, analgesic, antiaggressive, and depressant-antidepressant, properties than reference compounds clonidine, morphine, diazepam, and imipramine respectively. Most of the compounds have shown ALD50 > 500 mg/kg with maximum in 4a and 5a (>1000 mg/kg).

Role of cytokines in the clinical manifestation of exophthalmia in newborn calves with tropical theileriosis.

The present study aimed to evaluate the pathology of the exophthalmia and the host-immune response in naturally Theileria annulata-infected calves. The newborn calves detected positive for theileriosis were grouped into calves with theileriosis and absence of exophthalmia (n = 30), and calves with theileriosis and the presence of exophthalmia (n = 13). Sixteen healthy calves, free from any haemoprotozoal infection, were kept as healthy controls. A significantly (P ≤ .001) higher circulating levels of tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were estimated in diseased calves with and without exophthalmia as compared to healthy controls. Contrarily, significantly (P ≤ .01) lower interferon-γ (IFN-γ) level was estimated in diseased calves. The diseased calves with exophthalmia revealed significantly higher levels of TNF-α (P ≤ .001) and IL-10 (P ≤ .006) as compared to the diseased calves without exophthalmia. The diseased calves were not found to have an elevated intraocular pressure; rather they had significantly (P ≤ .001) lower intraocular pressure compared to the healthy controls. An elevated systemic TNF-α level might be attributed to the exophthalmia in calves with tropical theileriosis. The elevated circulatory IL-10 and reduced IFN-γ levels could be one of the strategies of Theileria annulata to escape the host immunity.

OncoMX: A Knowledgebase for Exploring Cancer Biomarkers in the Context of Related Cancer and Healthy Data.

PURPOSE: The purpose of OncoMX1 knowledgebase development was to integrate cancer biomarker and relevant data types into a meta-portal, enabling the research of cancer biomarkers side by side with other pertinent multidimensional data types. METHODS: Cancer mutation, cancer differential expression, cancer expression specificity, healthy gene expression from human and mouse, literature mining for cancer mutation and cancer expression, and biomarker data were integrated, unified by relevant biomedical ontologies, and subjected to rule-based automated quality control before ingestion into the database. RESULTS: OncoMX provides integrated data encompassing more than 1,000 unique biomarker entries (939 from the Early Detection Research Network [EDRN] and 96 from the US Food and Drug Administration) mapped to 20,576 genes that have either mutation or differential expression in cancer. Sentences reporting mutation or differential expression in cancer were extracted from more than 40,000 publications, and healthy gene expression data with samples mapped to organs are available for both human genes and their mouse orthologs. CONCLUSION: OncoMX has prioritized user feedback as a means of guiding development priorities. By mapping to and integrating data from several cancer genomics resources, it is hoped that OncoMX will foster a dynamic engagement between bioinformaticians and cancer biomarker researchers. This engagement should culminate in a community resource that substantially improves the ability and efficiency of exploring cancer biomarker data and related multidimensional data.

Quantification of immuno-regulatory cytokine and toll-like receptors gene expression in dogs with generalized demodicosis.

The proliferation of Demodex mites is mainly controlled by host immunity; however, the precised mechanism of host-mite interplay and host immune response in the cutaneous microenvironment of dogs with generalized demodicosis (GD) are not yet established. In the present study, we envisaged the alterations in the expression of toll-like receptors (TLRs) and immuno-regulatory cytokine gene in the skin lesions and peripheral blood mononuclear cells (PBMCs) of dogs with GD. The expression of TLR2, TLR6, IFN-γ, TGF-ß and IL-10 genes in the skin lesions and PBMCs of 15 dogs with GD was quantified by qRT-PCR. Compared to healthy dogs, significantly elevated expression of TLR2 (P = 0.048), TGF-ß (P = 0.04) and IL-10 (P = 0.012) were found in the PBMCs of dogs with GD. Conversely, there was significantly reduced expression of TLR6 gene (P = 0.021) in the PBMCs of these dogs. The infested dogs also revealed significantly elevated expression of TLR2 gene (P = 0.034) in the skin lesions, while, the expression of the TLR6 gene was found to be significantly (P = 0.004) reduced. Interestingly, significant alterations in TGF-ß (P = 0.105) and IL-10 (P = 0.162) genes expression were not observed in the skin lesions of diseased dogs. Our findings suggest that Demodex mites contribute to a different systemic and cutaneous immune response in dogs for their proliferation, and consequently the development of GD. Therefore, Demodex mites might be inducing the immunosuppression through activating the systemic over-expression of immunosuppressive cytokines; however, in the cutaneous lesions, the expression of immunosuppressive cytokines remained unaltered. Both systemic and local over-expression of TLR2 and reduced expression of TLR6 genes might be responsible for the inflammatory signs of canine demodicosis and helping to the mite to escape the host immunity.

Endophytes enhance the production of root alkaloids ajmalicine and serpentine by modulating the terpenoid indole alkaloid pathway in Catharanthus roseus roots.

AIM: The aim of this study was to identify and characterize promising endophytes capable of enhancing the content of root alkaloids ajmalicine and serpentine in low alkaloid yielding genotype of Catharanthus roseus cultivar Prabal and the possible mechanisms involved. METHOD AND RESULT: Of the four strains isolated from alkaloid-rich genotype of C. roseus cultivar Dhawal, endophytic strains CATDLF5 (Curvularia sp.) and CATDLF6 (Choanephora infundibulifera) enhanced serpentine content by 211·7-337·6%, while CATDRF2 (Aspergillus japonicus) and CATDS5 (Pseudomonas sp.) increased the content of ajmalicine by 123·4-203·8% in cultivar Prabal. Upregulated expression of key genes, geraniol 10-hydroxylase, tryptophan decarboxylase and strictosidine synthase involved in terpenoid indole alkaloid (TIA) biosynthetic pathway was observed in endophyte inoculated plants. Upregulated Octadecanoid-derivative Responsive Catharanthus AP2/ERF domain transcription activators like ORCA3 while, and downregulation of transcriptional repressor, ZCTs (Cys2/His2-type zinc finger protein family) enhanced the expression of genes for secondary metabolite production in endophyte-inoculated plants. CONCLUSION: The present work concluded that the selected endophytes of C. roseus can enhance the ajmalicine and serpentine contents by modulating the expression of structural and regulatory genes of TIA biosynthetic pathway in root. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytes can play an important role to enhance in planta content of pharmaceutically important alkaloids in C. roseus and can therefore be useful in reducing the cost of production of important alkaloids.

Superglue slide impression (SSI) method: a novel diagnostic application for canine demodicosis.

The conventional gold standard diagnostic method for canine demodicosis, the deep skin scrapings (DSS), is traumatic to the animal and appears aggressive in the eyes of the owner. A less invasive, sensitive, easy-to-perform and field-oriented diagnostic method for the rapid diagnosis of canine demodicosis is warranted. The present study aimed to develop a rapid less invasive diagnostic method using superglue (cyanoacrylate adhesive) slide impression (SSI). Ninety-seven client-owned dogs presented with clinical symptoms and signs suggestive of demodicosis were examined using SSI for detection of Demodex mites. A clean microscope slide was taken and a drop of superglue was placed on the slide. Immediately, the superglue-bearing slide surface was applied to the previously squeezed selected skin lesion with gentle pressure for 30 s. The slide was removed from the skin lesion and a drop of immersion oil was placed over the SSI. Another clean cover slide was applied and examined under the microscope at low-power magnification (× 10 lens). Of the 97 dogs, 90 dogs (92.8%) were detected positive for demodectic mites using the SSI method, whereas 86 (88.7%) dogs were found positive using the DSS technique. The SSI method was found to be equally sensitive to the DSS method. In summary, the SSI method is a new quick, sensitive, easy-to-perform, owner- and animal-friendly, less traumatic and field-oriented diagnostic application for demodicosis in dogs. It can be used for harvesting the live demodectic mites and monitoring miticidal therapies.

Pre- and post-therapy circulating immuno-stimulatory and immuno-suppressive cytokines in dogs with juvenile-onset generalized demodecosis.

Overproliferation of Demodex mites in dogs with compromised immunity attributed to the development of canine demodecosis. Whether clinical signs of canine demodecosis are triggered by genetically-mediated specific immunodeficiency in dogs or the Demodex mites induce lesions in hair follicles and result in compromised immunity is yet to be fully explored. To unravel the concealments of immunosuppression in canine demodecosis the present study was aimed to estimate the levels of circulating cytokines, pre- and post-therapy in nine dogs with juvenile-onset generalized demodecosis. At day 60 post-therapy of recommended amitraz rinse, significant (p ≤ 0.02) reduction in circulating IL-10 level was observed compared to its level before the start of the therapy (day 0). However, significant alterations in circulating levels of TNF-α and IFN-γ were not observed in these dogs at day 60 post-therapy as compared to their day 0 levels. A strong positive correlation between circulating level of IL-10 and mites population was observed both on day 0 (r2 = 0.656; p ≤ 0.005) and day 60 post-therapy (r2 = 0.575; p ≤ 0.018). Therefore, our findings suggest that Demodex mites induce immunosuppression in dogs during clinical disease and mites burden seems to be responsible for the development of generalized demodecosis.

Using distant supervision to augment manually annotated data for relation extraction.

Significant progress has been made in applying deep learning on natural language processing tasks recently. However, deep learning models typically require a large amount of annotated training data while often only small labeled datasets are available for many natural language processing tasks in biomedical literature. Building large-size datasets for deep learning is expensive since it involves considerable human effort and usually requires domain expertise in specialized fields. In this work, we consider augmenting manually annotated data with large amounts of data using distant supervision. However, data obtained by distant supervision is often noisy, we first apply some heuristics to remove some of the incorrect annotations. Then using methods inspired from transfer learning, we show that the resulting models outperform models trained on the original manually annotated sets.

Alterations in circulating concentrations of IL-17, IL-31 and total IgE in dogs with atopic dermatitis.

BACKGROUND: The pathogenesis of canine atopic dermatitis (AD) is complex. Dysregulation of the cutaneous immune system is considered an important regulator of the allergic response. Exploration of association of interleukin-17 (IL-17), IL-31, IgE and leukogram attributes with canine AD could provide novel insights into its immunopathology. HYPOTHESIS/OBJECTIVES: To investigate possible associations of IL-17, IL-3, IgE and leukogram attributes of canine AD. ANIMALS: 17 dogs diagnosed with AD and six healthy dogs. METHODS AND MATERIALS: Circulating concentrations of IL-17, IL-31 and total IgE from sera samples were determined using commercial canine-specific quantitative immunoassay kits. Complete blood cell counts were analysed by an automated haematology analyser. Statistical differences between the two groups were determined using an unpaired t-test. The degree of relationship between the IL-17, IL-31, IgE, total leukocyte count (TLC) values and clinical signs scores (Canine Atopic Dermatitis Lesion Index and pruritus Visual Analog Scale pVAS) was determined by Pearson's r correlation statistic. RESULTS: Dogs with AD had significantly (P < 0.0001) higher circulating concentrations of IL-17, IL-31 and total IgE compared with healthy dogs. Dogs with AD also had significantly higher TLC (P < 0.0002), absolute neutrophils (P < 0.0001) and absolute eosinophils (P < 0.0001) counts, and percentage of neutrophils (P < 0.03) and eosinophils (P < 0.0001) compared with healthy controls. A significant positive correlation (r2  = 0.396; P < 0.007) between the pVAS and IL-31 was observed in dogs with AD. CONCLUSIONS AND CLINICAL IMPORTANCE: Marked elevation in circulating IL-17, IL-31 and total IgE along with the abnormalities in leukogram may be associated with canine AD and could be possible targets in the therapeutic management of canine AD.

Potential of di-aldehyde cellulose for sustained release of oxytetracycline: A pharmacokinetic study.

This study focused on the in-vivo sustained release of oxytetracycline (OTC) loaded on di-aldehyde cellulose (DAC). The periodate oxidation method was used for the synthesis of DAC. The prepared DAC-OTC material was characterized by different techniques such as Scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Transmission electron microscopy (TEM) and particle size analyzer. The pharmacokinetic studies were performed on DAC-OTC composite system and commercial tablet (COTA). The results of pharmacokinetic studies demonstrated that DAC-OTC exhibited higher area under the curve (AUC) (482.8 µghmL-1) as compared to COTA (90.72 µghmL-1). DAC-OTC composite system has double compartment pattern with improvement in mean residing time (MRT) and area under moment curve (AUMC0-∞) than the commercial tablet (2.8 and 15.13 folds higher, respectively). Swelling index of DAC-OTC at different pH and pKa of OTC release imply that controlled in-vivo release in DAC-OTC composite system could be due to the simultaneous occurrence of the covalent and hydrogen bond between OTC and di-aldehyde cellulose. These results indicate that di-aldehyde cellulose may improve the in-vivo bioavailability of OTC.

iTextMine: integrated text-mining system for large-scale knowledge extraction from the literature.

Numerous efforts have been made for developing text-mining tools to extract information from biomedical text automatically. They have assisted in many biological tasks, such as database curation and hypothesis generation. Text-mining tools are usually different from each other in terms of programming language, system dependency and input/output format. There are few previous works that concern the integration of different text-mining tools and their results from large-scale text processing. In this paper, we describe the iTextMine system with an automated workflow to run multiple text-mining tools on large-scale text for knowledge extraction. We employ parallel processing with dockerized text-mining tools with a standardized JSON output format and implement a text alignment algorithm to solve the text discrepancy for result integration. iTextMine presently integrates four relation extraction tools, which have been used to process all the Medline abstracts and PMC open access full-length articles. The website allows users to browse the text evidence and view integrated results for knowledge discovery through a network view. We demonstrate the utilities of iTextMine with two use cases involving the gene PTEN and breast cancer and the gene SATB1.

Automatic gene annotation using GO terms from cellular component domain.

BACKGROUND: The Gene Ontology (GO) is a resource that supplies information about gene product function using ontologies to represent biological knowledge. These ontologies cover three domains: Cellular Component (CC), Molecular Function (MF), and Biological Process (BP). GO annotation is a process which assigns gene functional information using GO terms to relevant genes in the literature. It is a common task among the Model Organism Database (MOD) groups. Manual GO annotation relies on human curators assigning gene functional information using GO terms by reading the biomedical literature. This process is very time-consuming and labor-intensive. As a result, many MODs can afford to curate only a fraction of relevant articles. METHODS: GO terms from the CC domain can be essentially divided into two sub-hierarchies: subcellular location terms, and protein complex terms. We cast the task of gene annotation using GO terms from the CC domain as relation extraction between gene and other entities: (1) extract cases where a protein is found to be in a subcellular location, and (2) extract cases where a protein is a subunit of a protein complex. For each relation extraction task, we use an approach based on triggers and syntactic dependencies to extract the desired relations among entities. RESULTS: We tested our approach on the BC4GO test set, a publicly available corpus for GO annotation. Our approach obtains a F1-score of 71%, a precision of 91% and a recall of 58% for predicting GO terms from CC Domain for given genes. CONCLUSIONS: We have described a novel approach of treating gene annotation with GO terms from CC domain as two relation extraction subtasks. Evaluation results show that our approach achieves a F1-score of 71% for predicting GO terms for given genes. Thereby our approach can be used to accelerate the process of GO annotation for the bio-annotators.