Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical concept extraction using transformers

OBJECTIVE The goal of this study is to explore transformer-based models (eg, Bidirectional Encoder Representations from Transformers [BERT]) for clinical concept extraction and develop an open-source package with pretrained clinical models to facilitate concept extraction and other downstream natural language processing (NLP) tasks in the medical domain. METHODS We systematically explored 4 widely used transformer-based architectures, including BERT, RoBERTa, ALBERT, and ELECTRA, for extracting various types of clinical concepts using 3 public datasets from the 2010 and 2012 i2b2 challenges and the 2018 n2c2 challenge. We examined general transformer models pretrained using general English corpora as well as clinical transformer models pretrained using a clinical corpus and compared them with a long short-term memory conditional random fields (LSTM-CRFs) mode as a baseline. Furthermore, we integrated the 4 clinical transformer-based models into an open-source package. RESULTS AND CONCLUSION The RoBERTa-MIMIC model achieved state-of-the-art performance on 3 public clinical concept extraction datasets with F1-scores of 0.8994, 0.8053, and 0.8907, respectively. Compared to the baseline LSTM-CRFs model, RoBERTa-MIMIC remarkably improved the F1-score by approximately 4% and 6% on the 2010 and 2012 i2b2 datasets. This study demonstrated the efficiency of transformer-based models for clinical concept extraction. Our methods and systems can be applied to other clinical tasks. The clinical transformer package with 4 pretrained clinical models is publicly available at https://github.com/uf-hobi-informatics-lab/ClinicalTransformerNER. We believe this package will improve current practice on clinical concept extraction and other tasks in the medical domain.
Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets

Evolving information has identified disease mechanisms and dysregulation of host biology that might be targeted therapeutically in COVID-19. Thrombosis and coagulopathy, associated with pulmonary injury and inflammation, are emerging clinical features of COVID-19. We present a framework for mechanisms of thrombosis in COVID-19 that initially derive from interaction of SARS-CoV-2 with ACE2, resulting in dysregulation of angiotensin signaling and subsequent inflammation and tissue injury. These responses result in increased signaling by thrombin (proteinase-activated) and purinergic receptors, which promote platelet activation and exert pathological effects on other cell types (e.g., endothelial cells, epithelial cells, fibroblasts), further enhancing inflammation and injury. Inhibitors of thrombin and purinergic receptors may thus have therapeutic effects by blunting platelet-mediated thromboinflammation and dysfunction in other cell types. Such inhibitors include agents (e.g., anti-platelet drugs) approved for other indications and that could be repurposed to treat, and potentially improve the outcome of, COVID-19 patients.
Effect of polyphenol-rich extra-virgin olive oil on lipid profile and inflammatory biomarkers in patients undergoing coronary angiography: a randomised, controlled, clinical trial

Abstract The present study was conducted to compare the effects of high polyphenol extra-virgin olive oil (EVOO) with low polyphenol refined olive oil (ROO) on some cardiovascular risk factors in patients undergoing coronary angiography. In a randomised, controlled, parallel-arm, clinical trial, 40 patients with at least one classic cardiovascular risk factor who referred to coronary angiography were randomly allocated to two groups and receied 25 mL EVOO or ROO daily for 6 weeks. Plasma LDL-cholesterol significantly reduced in EVOO group (–9.52 ± 20.44 vs 8.68 ± 18.77 mg/dL, p = .007 for EVOO and ROO respectively). EVOO resulted in a significant reduction in plasma CRP (–0.40 ± 0.52 vs 0.007 ± 0.42 mg/L, p = .01 for EVOO and ROO respectively) and increased ex-vivo whole blood LPS-stimulated IL-10 production (12.13 ± 33.64 vs −17.47 ± 49.04 pg/mL, p = .035 for EVOO and ROO respectively). Daily consumption of polyphenol-rich EVOO in subjects who have been under medical treatment with risk-reducing agents could additionally improve LDL-C and selected inflammatory markers. Trial Registration Number: NCT03796780
Exosomal long non-coding RNA UCA1 functions as growth inhibitor in esophageal cancer

Purpose: Esophageal cancer is a highly lethal and broad-spreading malignant tumor worldwide. Exosome-carrying lncRNAs play an essential role in the pathogenesis of various cancers. Results: The results revealed that the expression of UCA1 was decreased in esophageal cancer tissues and plasma exosomes. UCA1 was enriched in exosomes, and exosomal UCA1 was a promising biomarker for the diagnosis of esophageal cancer with 86.7% sensitivity and 70.2% specificity. Overexpression of UCA1 played anticancer roles in esophageal cancer cells through inhibiting cell proliferation, invasion and migration, and colony formation. Also, exosomal UCA1 was taken up by esophageal cancer cells and inhibited the progression of esophageal cancer in vitro and tumor growth in vivo. Furthermore, exosomal UCA1 could directly target miRNA-613 in esophageal cancer cells. Conclusions: The results suggested that exosomal UCA1 inhibits tumorigenesis and progression of esophageal cancer in vitro and in vivo, and might be a promising biomarker for esophageal cancer. Patient and Methods: In this study, we determined the expression of UCA1 in esophageal cancer tissues, plasma exosomes of patients with esophageal cancer. We determined the potential of exosomal UCA1 as a biomarker and its effect on the pathogenesis and progression of esophageal cancer in vitro and in vivo.
Fully automated dried blood spot sample handling and extraction for serological testing of human anti-SARS-COV-2 antibodies.

At the beginning of 2020, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reached pandemic dimensions. Throughout the event diagnostic tests function as an essential tool for understanding, mitigating and implement strategies to curb and receduce infections. Here, we present a novel method for the fully automated dried blood spot (DBS) sample handling and extraction for serological testing of human IgG antibodies against SARS-CoV-2 using a commercial ELISA testing kit. This proof-of-principle pilot study successfully demonstrates the recovery of antibodies in their intact form from DBS using automated, direct sample elution within 100 μL of extraction buffer. The use of minimally invasive DBS sampling provides an alternative to existing analytical procedures such as sampling by venipuncture or nasal swabs. Due to the ease of DBS collection, no third party need be involved, making at-home sampling possible(e.g. during quarantine).
Data-Driven and Knowledge-Based Algorithms for Gene Network Reconstruction on High-Dimensional Data

Previous efforts in gene network reconstruction have mainly focused on data-driven modeling, with little attention paid to knowledge-based approaches. Leveraging prior knowledge, however, is a promising paradigm that has been gaining momentum in network reconstruction and computational biology research communities. This paper proposes two new algorithms for reconstructing a gene network from expression profiles with and without prior knowledge in small sample and high-dimensional settings. First, using tools from the statistical estimation theory, particularly the empirical Bayesian approach, the current research estimates a covariance matrix via the shrinkage method. Second, estimated covariance matrix is employed in the penalized normal likelihood method to select the Gaussian graphical model. This formulation allows the application of prior knowledge in the covariance estimation, as well as in the Gaussian graphical model selection. Experimental results on simulated and real datasets show that, compared to state-of-the-art methods, the proposed algorithms achieve better results in terms of both PR and ROC curves. Finally, the present work applies its method on the RNA-seq data of human gastric atrophy patients, which was obtained from the EMBL-EBI database. The source codes and relevant data can be downloaded from: https://github.com/AbbaszadehO/DKGN.
Genotype-Specific Antioxidant Responses and Assessment of Resistance Against Sclerotinia sclerotiorum Causing Sclerotinia Rot in Indian Mustard

Productivity of Indian mustard, an important oilseed crop of India, is affected by several pathogens. Among them, the hemibiotroph Sclerotinia sclerotiorum, which causes sclerotinia rot disease, is the most devastating fungal pathogen causing up to 90% yield losses. The availability of host resistance is the only efficient approach to control and understand the host–pathogen interaction. Therefore, the present investigation was carried out using six Indian mustard genotypes with contrasting behavior towards sclerotinia rot to study the antioxidant resistance mechanism against S. sclerotiorum. The plants at post-flowering stage were inoculated with five-day-old pure culture of S. sclerotiorum using artificial stem inoculation method. Disease evaluation revealed significant genotypic differences for mean lesion length among the tested genotypes, where genotype DRMR 2035 was found highly resistant, while genotypes RH 1569 and RH 1633 were found highly susceptible. The resistant genotypes had more phenolics and higher activities of peroxidase, catalase and polyphenol oxidase which provide them more efficient and strong antioxidant systems as compared with susceptible genotypes. Studies of antioxidative mechanisms validate the results of disease responses.
Does audit regulation improve the underlying information used by managers? Evidence from PCAOB inspection access and management forecast accuracy

Survey evidence and academic research raises the possibility that audit regulation can impact not only the information contained in external financial reports but also the internal information used by management (International Federation of Accountants, 2018; Libby, Rennekamp, & Seybert, 2015). We investigate this issue by examining the improvement in management forecast accuracy around initiation of the Public Company Accounting Oversight Board’s (PCAOB) international inspection program. Consistent with managers having improved information, we find that managers issue more accurate forecasts following PCAOB inspection access. Further, this improvement in forecast accuracy is more pronounced in countries with stronger legal institutions, supporting the intended effect of legal institutions to facilitate enacted regulations. Our study uses a multi-country setting to provide evidence that audit regulation benefits an important internal stakeholder—managers.
Temperature affects the host hematological and cytokine response following experimental ranavirus infection in red-eared sliders (Trachemys scripta elegans)

Pathogen-host interactions are important components of epidemiological research, but are scarcely investigated in chelonians. Red-eared sliders (Trachemys scripta elegans), are recognized as a model for frog virus-3 infection (FV3), a ranavirus in the family Iridoviridae that infects multiple classes of ectothermic vertebrates. Previous challenge studies observed differences in disease outcome based on environmental temperature in this species, but the host response was minimally evaluated. We challenged red-eared sliders with an FV3-like ranavirus at both 28°C and 22°C. We monitored several host response variables for 30 days, including: survival (binary outcome and duration), clinical signs, total and differential leukocytes, and select cytokine transcription in the buffy coat (IL-1β, TNFα, IFYg, IL-10). After 30 days, 17% of challenged turtles survived at 28°C (Median survival time [MST]: 15 days, range: 10–30 days) and 50% survived (MST: 28.5 days, range: 23–30 days) at 22°C (range 23–30 days). The most common clinical signs were injection site swelling, palpebral swelling, and lethargy. The heterophil/lymphocyte ratio at 22°C and interleukin-1 beta (IL1β) transcription at both 22°C and 28°C were significantly greater on days 9, 16, and 23 in FV3 challenged groups. Tumor necrosis factor alpha and interleukin-10 were transcribed at detectable levels, but did not display significant differences in mean relative transcription quantity over time. Overall, evidence indicates an over-robust immune response leading to death in the challenged turtles. FV3 remains a risk for captive and free-ranging chelonian populations, and insight to host/pathogen interaction through this model helps to elucidate the timing and intensity of the host response that contribute to mortality.
Environmental tolerance of three gammarid species with and without invasion record under current and future global warming scenarios

Numerous regions worldwide are highly impacted by anthropogenic activities and globalization, with climate change and species introductions being among the greatest stressors to biodiversity and ecosystems. A main donor region of non‐indigenous species (NIS) for numerous European water bodies, as well as in the North American Great Lakes is the Ponto‐Caspian region (i.e., Black, Azov and Caspian Seas), with some of those species having significant impact on local communities and ecosystem functioning.
Relationships between Abelson tyrosine kinase (c-abl) and spindle during meiotic division in mouse oocyte in vitro

The c-Abl gene is a nonreceptor tyrosine kinase that has roles in cell growth, control of the cell cycle, initiation of pronuclear movement and actin cytoskeleton dynamics. The present study has examined the localization of c-Abl protein during oocyte activation in mouse in vitro . Confocal immunofluorescence analysis showed that c-Abl originates at the cortex with a crescent shape before the activation and continues up along both sides of the cortex after activation during meiotic division until pronuclear stage. These results demonstrate that c-Abl may play role in asymmetric division of the egg to produce polar body, positioning of the spindle, and may regulate the microtubule cytoskeleton or have some roles in this process.
MRI Radiomic Features to Predict IDH1 Mutation Status in Gliomas: A Machine Learning Approach using Gradient Tree Boosting

In patients with gliomas, isocitrate dehydrogenase 1 (IDH1) mutation status has been studied as a prognostic indicator. Recent advances in machine learning (ML) have demonstrated promise in utilizing radiomic features to study disease processes in the brain. We investigate whether ML analysis of multiparametric radiomic features from preoperative Magnetic Resonance Imaging (MRI) can predict IDH1 mutation status in patients with glioma. This retrospective study included patients with glioma with known IDH1 status and preoperative MRI. Radiomic features were extracted from Fluid-Attenuated Inversion Recovery (FLAIR) and Diffusion-Weighted-Imaging (DWI). The dataset was split into training, validation, and testing sets by stratified sampling. Synthetic Minority Oversampling Technique (SMOTE) was applied to the training sets. eXtreme Gradient Boosting (XGBoost) classifiers were trained, and the hyperparameters were tuned. Receiver operating characteristic curve (ROC), accuracy, and f1-scores were collected. A total of 100 patients (age: 55 ± 15, M/F 60/40); with IDH1 mutant (n = 22) and IDH1 wildtype (n = 78) were included. The best performance was seen with a DWI-trained XGBoost model, which achieved ROC with Area Under the Curve (AUC) of 0.97, accuracy of 0.90, and f1-score of 0.75 on the test set. The FLAIR-trained XGBoost model achieved ROC with AUC of 0.95, accuracy of 0.90, f1-score of 0.75 on the test set. A model that was trained on combined FLAIR-DWI radiomic features did not provide incremental accuracy. The results show that a XGBoost classifier using multiparametric radiomic features derived from preoperative MRI can predict IDH1 mutation status with > 90% accuracy.
Lactococcus lactis subsp. Cremoris C60 restores T Cell Population in Small Intestinal Lamina Propria in Aged Interleukin-18 Deficient Mice

Lactic acid bacteria (LAB), a major commensal bacterium in the small intestine, are well known beneficial bacteria which promote establishment of gut-centric immunity, such as anti-inflammation and anti-infection. In this report, we show that a LAB strain Lactococcus lactis subsp. Cremoris C60 possess an ability to activate antigen presenting cells, such as dendritic cells (DCs), and intestinal T cells which possibly support to maintain healthy intestinal immunological environment in aging process. We found that CD4+ T cells in the small intestine are dramatically decreased in aged Interleukin-18 knock out (IL-18KO) mice, associated with the impairment of IFN-γ production in the CD4+ T cells, especially in small intestinal lamina propria (LP). Surprisingly, heat killed-C60 (HK-C60) diet completely recovered the CD4+ T cells population and activity in SI-LP and over activated the population in Peyer’s patches (PPs) of IL-18KO mice. The HK-C60 diet was effective approach not only to restore the number of cells, but also to recover IFN-γ production in the CD4+ T cell population in the small intestine of IL-18-deficient mice. As a possible cause in the age-associated impairment of CD4+ T cells activity in IL-18KO mice, we found that the immunological activity was downregulated in the IL-18-deficient DCs. The cytokines production and cellular activation markers expression were downregulated in the IL-18-deficient bone marrow derived dendritic cells (BMDCs) at the basal level, however, both activities were highly upregulated in HK-C60 stimulation as compared to those of WT cells. Antigen uptake was also attenuated in the IL-18-deficient BMDCs, and it was significantly enhanced in the cells as compared to WT cells in HK-60 stimulation. An in vitro antigen presentation assay showed that IFN-γ production in the CD4+ T cells was significantly enhanced in the culture of IL-18-deficient BMDCs compared with WT cells in the presence of HK-C60. Thus, we conclude that HK-C60 diet possesses an ability to restore T cells impairment in the small intestine of IL-18-deficient environment. In addition, the positive effect is based on the immunological modification of DCs function which directory influences into the promotion of effector CD4+ T cells generation in the small intestine.
Profiling Chinese EFL students’ technology-based self-regulated English learning strategies

This article reports the development and validation of an instrument, the Technology-Based Self-Regulated English Learning Strategies Scale (TSELSS), in terms of its multifaceted structure of self-directed use of technology in English learning among Chinese university EFL students. TSELSS was developed through a three-phase process, focusing on the domain of self-regulated English learning in technology-assisted conditions. The first phase involved the generation of an item pool, the second a pilot study (N = 164) aimed at identifying the factor structure of TSELSS using exploratory factor analysis, and the third an examination of the psychometric properties of the revised TSELSS using confirmatory factor analysis with another independent sample of students (N = 525). Furthermore, the concurrent validity of TSELSS was investigated through correlations with students’ English language self-efficacy and English learning outcomes. The final version of the scale is made up of five types of technology-based self-regulated English learning strategies: motivational regulation strategies, goal setting and learning evaluation, social strategies, technology-based English song and movie learning, and technology-based vocabulary learning. The TSELSS can be used as an evaluation tool to appraise EFL students’ technology-based self-regulated English learning experience, and as a research tool to investigate more associations between technology-based self-regulated strategic English learning and other contextual and learner individual factors.
Renewal of goal direction with a context change after habit learning.

An instrumental action can be goal-directed after a moderate amount of practice and then convert to habit after more extensive practice. Recent evidence suggests, however, that habits can return to action status after different environmental manipulations. The present experiments therefore asked whether habit learning interferes with goal direction in a context-dependent manner like other types of retroactive interference (e.g., extinction, punishment, counterconditioning). In Experiment 1, rats were given a moderate amount of instrumental training to form an action in one context (Context A) and then more extended training of the same response to form a habit in another context (Context B). We then performed reinforcer devaluation with taste aversion conditioning in both contexts, and tested the response in both contexts. The response remained habitual in Context B, but was goal-directed in Context A, indicating renewal of goal direction after habit learning. Experiment 2 expanded on Experiment 1 by testing the response in a third context (Context C). It found that the habitual response also renewed as action in this context. Together, the results establish a parallel between habit and extinction learning: Conversion to habit does not destroy action knowledge, but interferes with it in a context-specific way. They are also consistent with other results suggesting that habit is specific to the context in which it is learned, whereas goal-direction can transfer between contexts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation

CXCL12, also known as stromal cell-derived factor-1, is a chemokine classified into CXC families, which exerts its function by binding to specific receptors called CXCR4 and CXCR7. Human platelets express CXCR4 and CXCR7 on the plasma membrane. It has been reported that CXCL12 potentiates to induce platelet aggregation in cooperation with agonists including collagen. However, the precise roles and mechanisms of CXCL12 in human platelet activation are not fully elucidated. In the present study, we investigated the effect of simultaneous stimulation with low doses of collagen and CXCL12 on the activation of human platelets. The simultaneous stimulation with collagen and CXCL12 induced the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble CD40 ligand (sCD40L) from human platelets in addition to their aggregation, despite the fact that the simultaneous stimulation with thrombin receptor-activating peptide (TRAP) or adenosine diphosphate (ADP), and CXCL12 had little effects on the platelet aggregation. The agonist of Glycoprotein (GP) Ⅵ convulxin and CXCL12 also induced platelet aggregation synergistically. The monoclonal antibody against CXCR4 but not CXCR7 suppressed the platelet aggregation induced by simultaneous stimulation with collagen and CXCL12. The phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not p44/p42 MAPK, was induced by the simultaneous stimulation. In addition, the simultaneous stimulation with collagen and CXCL12 induced the phosphorylation of HSP27 and the subsequent release of phosphorylated-HSP27 from human platelets. SB203580, a specific inhibitor of p38 MAPK, attenuated the platelet aggregation, the phosphorylation of p38 MAPK and HSP27, the PDGF-AB secretion, the sCD40L release and the phosphorylated-HSP27 release induced by the simultaneous stimulation with collagen and CXCL12. These results strongly suggest that collagen and CXCL12 in low doses synergistically act to induce PDGF-AB secretion, sCD40L release and phosphorylated-HSP27 release from activated human platelets via p38 MAPK activation.