Combining Early Ischemic Change and Collateral Extent for Functional Outcomes After Endovascular Therapy: An Analysis From AcT Trial.

BACKGROUND: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. METHODS: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. RESULTS: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). CONCLUSIONS: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.

Identification of immune-associated prognostic biomarkers in lung adenocarcinoma on the basis of gene co-expression network.

Objective: We aimed to explore immune-related prognosis genes of lung adenocarcinoma (LUAD).Materials and methods: TCGA-LUAD and GSE31210 data sets were accessed from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) respectively. By using "WGCNA" R package, we established a gene co-expression network and clustered genes into various modules. The correlation between immune scores and module eigengenes by using Pearson analysis. Screened hub genes and constructed prognostic model by using LASSO and Cox regression analysis. Evaluated model by survival analysis and receiver operating characteristic (ROC) curves. Hub genes expression in clinical tissues of LUAD patients by qRT-PCR analysis. ssGSEA and TIMER (a website tool for examination of different immune cells in different cancers) analyzed immune correlation of hub genes. Gene set variation analysis (GSVA) uncovered difference of signal pathway between high- and low-risk score group.Results: We found that brown module significantly correlated with the immune scores of immune cells. Therefore, we constructed a 7-gene prognostic model based on brown module genes, and indicated that this model possessed good predictive performance. Patients in training and validation sets were stratified into the high- and low-risk group using this model. Also, hub genes CDCP1, PLSCR1 and CD79A were highly expressed in clinical tissues of LUAD patients, while ID1, CLEC7A, KIAA1324 and CMTM7 were lowly expressed. Both ssGSEA and TIMER revealed a significant negative correlation between risk score and B cell infiltration. Additionally, some signal pathways were suppressed in the high-risk group.Conclusion: We identified 7 immune-associated prognostic markers, which may play vital roles in LUAD and could be used as hopeful targets for immunotherapy of LUAD.

Melamine induced changes in histopathology of the main organs and transcriptional levels of MAPK signaling genes in kidneys of female mice.

Melamine is an important chemical raw material used in industries, which has potential health risks to animals and humans. Current research mainly focuses on the toxic effects of high-dose melamine ingestion. However, there are few reports on whether melamine at the current limited standard dose has adverse effects on various tissues and organs, and whether there are sensitive target genes for risk evaluation. For this, 24 female Kunming mice were fed 0, 1.8-, 3.6-, and 7.2- mg/kg/d melamine via drinking water for consecutive 28 days, respectively. The morphological changes of the ovarian, hepatic, and renal tissues were firstly observed. The results demonstrated that the histopathology of ovary, liver, and especially in kidney had been altered by melamine intake in female. And then, the transcriptional levels of MAPK signaling genes including p38, ERK1, ERK2, JNK1, and JNK2 in kidneys were investigated by real-time PCR. The data showed that ERK1 and p38 mRNAs expressions were up-regulated significantly by melamine, suggesting that ERK1 and p38 transcriptional levels in the kidney might to be considered as candidate targets for lower-dose melamine toxicity. This study not only provides potential targets for the diagnosis and prevention of melamine damage, but also helps to assess the health risks of the current minimum allowable levels of melamine in food and environment.

Dual-Branch Discrimination Network Using Multiple Sparse Priors for Image Deblurring.

Blind image deblurring is a challenging problem in computer vision, aiming to restore the sharp image from blurred observation. Due to the incompatibility between the complex unknown degradation and the simple synthetic model, directly training a deep convolutional neural network (CNN) usually cannot sufficiently handle real-world blurry images. An existed generative adversarial network (GAN) can generate more detailed and realistic images, but the game between generator and discriminator is unbalancing, which leads to the training parameters not being able to converge to the ideal Nash equilibrium points. In this paper, we propose a GAN with a dual-branch discriminator using multiple sparse priors for image deblurring (DBSGAN) to overcome this limitation. By adding the multiple sparse priors into the other branch of the discriminator, the task of the discriminator is more complex. It can balance the game between the generator and the discriminator. Extensive experimental results on both synthetic and real-world blurry image datasets demonstrate the superior performance of our method over the state of the art in terms of quantitative metrics and visual quality. Especially for the GOPRO dataset, the averaged PSNR improves 1.7% over others.

Predicting prognosis of heart failure using common malnutrition assessment tools: A systematic review and meta-analysis.

BACKGROUND AND AIMS: COUNT score, PNI score, and GNRI scores are associated with cardiovascular events. This review identifies the most accurate malnutrition assessment tools based on these scores in predicting mortality and readmission outcomes in HF patients. MATERIAL AND METHODS: PubMed via MEDLINE, EMBASE were searched to identify studies assessing malnutrition using CONUT, PNI and GNRI. A meta-analysis was carried out to pool the hazard ratios on mortality and readmission rates. The methodological quality was assessed using the Newcastle-Ottawa Scale. RESULTS: The mortality in HF patients with malnutrition assessed by CONUT showed pooled HR of 1.23. HF patients with all severe, moderate, and mild risk of malnutrition showed mortality with HR 3.56, 2.71 and 1.57 respectively. For malnutrition assessed with GNRI, HF patients with all severe, moderate, and mild risk of malnutrition showed mortality with HR 4.17, 2.73 and 1.73 respectively. No significance difference in association of CONUT score with pooled HR of readmission rate was observed HR 0.99. With PNI, HF patients with all severe and moderate risk of malnutrition showed mortality with HR 2.14 and HR 1.68 respectively, although they failed to achieve significance. CONCLUSION: CONUT and GNRI are the superior prognostic indicator than PNI in prediction of mortality associated with risk of malnutrition.

Relationship between common eNOS gene polymorphisms and predisposition to coronary artery disease: Evidence from a meta-analysis of 155 published association studies.

BACKGROUND: Relationship between endothelial nitric oxide synthase (eNOS) polymorphisms and predisposition to coronary artery disease (CAD) are still controversial and ambiguous. So we performed this meta-analysis to more precisely estimate relationship between eNOS polymorphisms and CAD by pooling the results of already published studies. METHODS: We searched Pubmed, Embase, Web of Science and CNKI for eligible studies. We used Review Manager to pool the results of eligible studies. RESULTS: One hundred and fifty-five studies were included in this meta-analysis. We found that eNOS rs1799983, rs2070744 and rs869109213 polymorphisms were all significantly associated with CAD in the general population. We also detected similar significant results for eNOS rs1799983, rs2070744 and rs869109213 polymorphisms in both Caucasians and Asians in further subgroup analyses. CONCLUSIONS: This meta-analysis demonstrated that eNOS rs1799983, rs2070744 and rs869109213 polymorphisms might influence predisposition to CAD in both Caucasians and Asians.

EEG-Based Sleep Staging Analysis with Functional Connectivity.

Sleep staging is important in sleep research since it is the basis for sleep evaluation and disease diagnosis. Related works have acquired many desirable outcomes. However, most of current studies focus on time-domain or frequency-domain measures as classification features using single or very few channels, which only obtain the local features but ignore the global information exchanging between different brain regions. Meanwhile, brain functional connectivity is considered to be closely related to brain activity and can be used to study the interaction relationship between brain areas. To explore the electroencephalography (EEG)-based brain mechanisms of sleep stages through functional connectivity, especially from different frequency bands, we applied phase-locked value (PLV) to build the functional connectivity network and analyze the brain interaction during sleep stages for different frequency bands. Then, we performed the feature-level, decision-level and hybrid fusion methods to discuss the performance of different frequency bands for sleep stages. The results show that (1) PLV increases in the lower frequency band (delta and alpha bands) and vice versa during different stages of non-rapid eye movement (NREM); (2) alpha band shows a better discriminative ability for sleeping stages; (3) the classification accuracy of feature-level fusion (six frequency bands) reaches 96.91% and 96.14% for intra-subject and inter-subjects respectively, which outperforms decision-level and hybrid fusion methods.

The role of dorsal root ganglia alpha-7 nicotinic acetylcholine receptor in complete Freund's adjuvant-induced chronic inflammatory pain.

BACKGROUND: Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) was reported to have a critical role in the regulation of pain sensitivity and neuroinflammation. However, the expression level of α7 nAChR in dorsal root ganglion (DRG) and the underlying neuroinflammatory mechanisms associated with hyperalgesia are still unknown. METHODS: In the present study, the expression and mechanism of α7 nAChR in chronic inflammatory pain was investigated using a complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model. Subsequently, a series of assays including immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. RESULTS: α7 nAChR was mostly colocalized with NeuN in DRG and upregulated after CFA injection. Microinjection of α7 nAChR siRNA into ipsilateral L4/5 DRGs aggravated the CFA-induced pain hypersensitivity. Intrathecal α7 nAChR agonist GTS-21 attenuated the development of CFA-induced mechanical and temperature-related pain hypersensitivities. In neuronal the SH-SY5Y cell line, the knockdown of α7 nAChRs triggered the upregulation of TRAF6 and NF-κB under CFA-induced inflammatory conditions, while agitation of α7 nAChR suppressed the TRAF6/NF-κB activation. α7 nAChR siRNA also exacerbated the secretion of pro-inflammatory mediators from LPS-induced SH-SY5Y cells. Conversely, α7 nAChR-specific agonist GTS-21 diminished the release of interleukin-1beta (IL-1ß), IL-6, IL-8, and tumor necrosis factor-α (TNFα) in SH-SY5Y cells under inflammatory conditions. Mechanistically, the modulation of pain sensitivity and neuroinflammatory action of α7 nAChR may be mediated by the TRAF6/NF-κB signaling pathway. CONCLUSIONS: The findings of this study suggest that α7 nAChR may be potentially utilized as a therapeutic target for therapeutics of chronic inflammatory pain.

The Relationship between Sparseness and Energy Consumption of Neural Networks.

About 50-80% of total energy is consumed by signaling in neural networks. A neural network consumes much energy if there are many active neurons in the network. If there are few active neurons in a neural network, the network consumes very little energy. The ratio of active neurons to all neurons of a neural network, that is, the sparseness, affects the energy consumption of a neural network. Laughlin's studies show that the sparseness of an energy-efficient code depends on the balance between signaling and fixed costs. Laughlin did not give an exact ratio of signaling to fixed costs, nor did they give the ratio of active neurons to all neurons in most energy-efficient neural networks. In this paper, we calculated the ratio of signaling costs to fixed costs by the data from physiology experiments. The ratio of signaling costs to fixed costs is between 1.3 and 2.1. We calculated the ratio of active neurons to all neurons in most energy-efficient neural networks. The ratio of active neurons to all neurons in neural networks is between 0.3 and 0.4. Our results are consistent with the data from many relevant physiological experiments, indicating that the model used in this paper may meet neural coding under real conditions. The calculation results of this paper may be helpful to the study of neural coding.

A Hybrid System for Distinguishing between Brain Death and Coma Using Diverse EEG Features.

Electroencephalography (EEG) signals may provide abundant information reflecting the developmental changes in brain status. It usually takes a long time to finally judge whether a brain is dead, so an effective pre-test of brain states method is needed. In this paper, we present a hybrid processing pipeline to differentiate brain death and coma patients based on canonical correlation analysis (CCA) of power spectral density, complexity features, and feature fusion for group analysis. In addition, time-varying power spectrum and complexity were observed based on the analysis of individual patients, which can be used to monitor the change of brain status over time. Results showed three major differences between brain death and coma groups of EEG signal: slowing, increased complexity, and the improvement on classification accuracy with feature fusion. To the best of our knowledge, this is the first scheme for joint general analysis and time-varying state monitoring. Delta-band relative power spectrum density and permutation entropy could effectively be regarded as potential features of discrimination analysis on brain death and coma patients.

Combination of Fluoride and SO2 Induce DNA Damage and Morphological Alterations in Male Rat Kidney.

BACKGROUND/AIMS: We investigated the combined toxic effect of sodium fluoride (NaF) and sulfur dioxide (SO2) on kidney morphological changes and DNA damage in male Wistar rats. METHODS: In this study we selected totally 96 male Wistar rats (12-week-old) then randomly group-housed them into four cages, treated with deionized water, NaF, SO2 and co-treatment of NaF and SO2 respectively. Morphological changes of kidney were detected by hematoxylin and eosin (H&E) staining at 2, 4, 6 and 8 weeks. Correspondingly, tailing ratio and comet length were measured by BAB Bs Comet Assay System, including DNA damage special unit were calculated to evaluate the grades of kidney DNA damage at the same time. RESULTS: Treated groups showed a body weight decrease when compared to control group. However, no significant difference in the relative weight of kidney was found in all four groups. It is noteworthy that at 2, 4, 6 and 8 weeks after exposure, the morphological alteration of renal tubules were observed in all treated groups, especially in group-IV. Also, at 4 and 6 weeks, notable DNA damage was found in all treated groups, as assessed by significantly increasing trend of comet length tailing ratio. CONCLUSION: The study manifests that presence of NaF and SO2 will not only induce renal tissue lesions but also impact DNA integrity. In addition, this combined exposure exhibits a synergistic effect, characterizing a dose-dependence and time correlation. These findings may provide novel insights regarding perturbations of DNA damage and its functions as a potential new mechanism, by which cautious interpretation of NaF and SO2 co-exposure evolved in both animals and human beings is necessary.

Co-exposure to fluoride and sulfur dioxide on histological alteration and DNA damage in rat brain.

Fluoride (F) and sulfur dioxide (SO2 ) are the two common environmental contaminants that are associated with neurotoxicity. The present study was conducted to explore individual and combined exposure effects of F and SO2 on histological alteration and DNA damage in rat brain. For this, male Wistar albino rats were exposed to sodium fluoride (100 mg/L NaF) and sulfur dioxide (39.3 mg/m3 ) individually and in combination for 8 weeks. Histological alteration in brain is evaluated by hematoxylin-eosin staining, showed shrunken neurons, darkly stained small nucleus and decreased cell numbers in F and SO2 exposed groups. The effect of F and SO2 on DNA damage was assessed by comet assay. The results showed an increase in ratio of tailing and tail length in F or/and SO2 administered rats. In addition, the proportion of grade II and III were also increased in individual and combined exposed groups. Compared with the individual exposure, the proportion the grade III was significantly high in combined exposure, suggesting a synergistic effect of F and SO2 . These results indicate that the brain was more susceptible to the toxic effects of F and SO2 . And combined exposure to these pollutants can lead more pronounced toxic effects on brain.

Arsenic induces autophagy in developmental mouse cerebral cortex and hippocampus by inhibiting PI3K/Akt/mTOR signaling pathway: involvement of blood-brain barrier's tight junction proteins.

For the past decade, there has been an increased concern about the health risks from arsenic (As) exposure, because of its neurotoxic effects on the developing brain. The exact mechanism underlying As-induced neurotoxicity during sensitive periods of brain development remains unclear, especially the role of blood-brain barrier's (BBB) tight junction (TJ) proteins during As-induced neurotoxicity. Here, we highlight the involvement of TJ proteins in As-induced autophagy in cerebral cortex and hippocampus during developmental periods [postnatal day (PND) 21, 28, 35 and 42]. Here, the administration of arsenic trioxide (As2O3) at doses of 0.15 mg or 1.5 mg or 15 mg As2O3/L in drinking water from gestational to lactational and continued to the pups till PND42 resulted in a significant decrease in the mRNA expression levels of TJ proteins (Occludin, Claudin, ZO-1 and ZO-2) and Occludin protein expression level. In addition, As exposure significantly decreased PI3K, Akt, mTOR, and p62 with a concomitant increase in Beclin1, LC3I, LC3II, Atg5 and Atg12. Moreover, As exposure also significantly downregulated the protein expression levels of mTOR with a concomitant upregulation of Beclin 1, LC3 and Atg12 in all the developmental age points. However, no significant alterations were observed in low and medium dose-exposed groups of PND42. Histopathological analysis in As-exposed mice revealed decreased number of pyramidal neurons in hippocampus; and neurons with degenerating axons, shrinkage of cells, remarkable vacuolar degeneration in cytoplasm, karyolysis and pyknosis in cerebral cortex. Ultrastructural analysis by transmission electron microscopy revealed the occurrence of autophagosomes and vacuolated axons in the cerebral cortex and hippocampus of the mice exposed to high dose As at PND21 and 42. The severities of changes were found to more persist in the cerebral cortex than in the hippocampus of As-exposed mice. Finally, we conclude that the leaky BBB in cerebral cortex and hippocampus may facilitate the transfer of As and induces autophagy by inhibiting PI3K/Akt/mTOR signaling pathway in an age-dependent manner, i.e., among the four different developmental age points, PND21 animals were found to be more vulnerable to the As-induced neurotoxicity than the other three age points.

The Dynamic EEG Microstates in Mental Rotation.

Mental rotation is generally analyzed based on event-related potential (ERP) in a time domain with several characteristic electrodes, but neglects the whole spatial-temporal brain pattern in the cognitive process which may reflect the underlying cognitive mechanism. In this paper, we mainly proposed an approach based on microstates to examine the encoding of mental rotation from the spatial-temporal changes of EEG signals. In particular, we collected EEG data from 11 healthy subjects in a mental rotation cognitive task using 12 different stimulus pictures representing left and right hands at various rotational angles. We applied the microstate method to investigate the microstates conveyed by the event-related potential extracted from EEG data during mental rotation, and obtained four microstate modes (referred to as modes A, B, C, D, respectively). Subsequently, we defined several measures, including microstate sequences, topographical map, hemispheric lateralization, and duration of microstate, to characterize the dynamics of microstates during mental rotation. We observed that (1) the microstates sequence had a specified progressing mode, i.e., A → B → A ; (2) the activation of the right parietal occipital region was stronger than that of the left parietal occipital region according to the hemispheric lateralization of the microstates mode A; and (3) the duration of the second microstates mode A showed the shorter duration in the vertical stimuli, named "angle effect".

Riemannian Spatio-Temporal Features of Locomotion for Individual Recognition.

Individual recognition based on skeletal sequence is a challenging computer vision task with multiple important applications, such as public security, human⁻computer interaction, and surveillance. However, much of the existing work usually fails to provide any explicit quantitative differences between different individuals. In this paper, we propose a novel 3D spatio-temporal geometric feature representation of locomotion on Riemannian manifold, which explicitly reveals the intrinsic differences between individuals. To this end, we construct mean sequence by aligning related motion sequences on the Riemannian manifold. The differences in respect to this mean sequence are modeled as spatial state descriptors. Subsequently, a temporal hierarchy of covariance are imposed on the state descriptors, making it a higher-order statistical spatio-temporal feature representation, showing unique biometric characteristics for individuals. Finally, we introduce a kernel metric learning method to improve the classification accuracy. We evaluated our method on two public databases: the CMU Mocap database and the UPCV Gait database. Furthermore, we also constructed a new database for evaluating running and analyzing two major influence factors of walking. As a result, the proposed approach achieves promising results in all experiments.

[Transport characteristics of Shuxiong prescription across Caco-2 cell monolayer model].

Shuxiong prescription (Notoginseng Radix et Rhizoma, Chuanxiong Rhizome and Carthami Flos) has the function of activating blood circulation to dissipate blood stasis, activating meridians to stop pain. This paper was mainly aimed to discuss the transport characteristics of Shuxiong prescription across Caco-2 cell monolayer. Safe concentration range of Shuxiong prescription against Caco-2 cell monolayer model was determined by MTT assay. The mechanism of Shuxiong prescription bidirectional transport was investigated by Caco-2 cell monolayer model. The apparent permeability coefficient Papp of digoxin was determined by high performance liquid chromatography (HPLC). The test results showed that the Papp of extract from Notoginseng Radix et Rhizoma, Chuanxiong Rhizome, Carthami Flos, Chuanxiong Rhizome+Carthami Flos and Shuxiong prescription transport from apical (AP) side to basolateral (BL) side was (3.12±0.73)×10⁻6, (2.58±0.41)×10⁻6, (4.97±0.64)×10⁻6, (4.63±0.57)×10⁻6, (5.79±0.68)×10⁻6 cm·s⁻¹, respectively, indicating that the transport of digoxin across Caco-2 cell monolayer model was active absorption, and the P-gp protein took part in the process. Chuanxiong Rhizome could significantly decrease the transport of digoxin from BL→AP(P<0.01) and increase its transport from AP→BL(P<0.05) significantiy. After the addition of Shuxiong prescription, the transport of digoxin from BL→AP was significantly inhibited(P<0.01). The results suggested that the extract of safflower had no effect on P-gp transport, nor on the independence diffusion of digoxin. The transport of digoxin could be degraded by the extract of Chuanxiong Rhizome and the extract of Shuxiong prescription from BL→AP(P<0.01), significantly; pseudo-ginseng had no effect on the independence diffusion of digoxin; the extract of safflower+Chuanxiong Rhizome had the same experimental result as Chuanxiong Rhizome extract.

Perfluorooctanoic acid exposure disturbs glucose metabolism in mouse liver.

Environmental pollutants such as perfluorooctanoic acid (PFOA) can influence human metabolism processes and are associated with certain metabolic diseases. To investigate the effect of PFOA on liver glucose homeostasis, adult male Balb/c mice were orally administered 1.25mg/kg of PFOA for 28d consecutively. Compared with the control mice, the body weights of the PFOA-treated mice were unchanged following exposure. However, PFOA exposure increased fasting blood glucose levels and decreased glycogen and glucose content in the liver of treated mice, but did not influence blood insulin significantly. The increased blood glucagon might contribute to the hyperglycemia observed in the PFOA-treated group compared with the control group. In addition, pyruvate tolerance tests supported enhanced glucose production ability in PFOA-exposed mice. Consistent with the increase in blood glucose and decrease in hepatic glucose and glycogen, PFOA exposure decreased the protein level of glycogen synthase in the mouse liver, but increased the level of glucokinase. Furthermore, liver pyruvate, as well as mRNA levels of enzymes involved in the Krebs cycle, such as citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, increased in the PFOA-treated group. PFOA exposure did not affect muscle glucose or glycogen levels. Indirect calorimetry showed higher VO2 consumption and respiratory quotient values in the PFOA-treated group compared with the control group, implying that PFOA treatment might promote energy consumption in mice, with a reliance on carbohydrates as a primary source of energy. Thus, our findings indicate that subacute exposure to PFOA might enhance glycogenolysis and gluconeogenesis and promote carbohydrate consumption.

A multiple distributed representation method based on neural network for biomedical event extraction.

BACKGROUND: Biomedical event extraction is one of the most frontier domains in biomedical research. The two main subtasks of biomedical event extraction are trigger identification and arguments detection which can both be considered as classification problems. However, traditional state-of-the-art methods are based on support vector machine (SVM) with massive manually designed one-hot represented features, which require enormous work but lack semantic relation among words. METHODS: In this paper, we propose a multiple distributed representation method for biomedical event extraction. The method combines context consisting of dependency-based word embedding, and task-based features represented in a distributed way as the input of deep learning models to train deep learning models. Finally, we used softmax classifier to label the example candidates. RESULTS: The experimental results on Multi-Level Event Extraction (MLEE) corpus show higher F-scores of 77.97% in trigger identification and 58.31% in overall compared to the state-of-the-art SVM method. CONCLUSIONS: Our distributed representation method for biomedical event extraction avoids the problems of semantic gap and dimension disaster from traditional one-hot representation methods. The promising results demonstrate that our proposed method is effective for biomedical event extraction.

Analysis of the roles of dietary protein and calcium in fluoride-induced changes in T-lymphocyte subsets in rat.

The roles of dietary protein (Pr) and calcium (Ca) levels on the changes in T-lymphocyte subsets induced by excessive fluoride (F) intake were assessed using rats that were malnourished for 120 days as a model. The CD4+ and CD8+ T-lymphocytes in the spleen tissue were determined by flow cytometry and immunofluorescence assay. The percentages of CD3+ , CD4+ , and CD8+ T-lymphocytes were reduced in the spleen of rats exposed to excessive F, and malnutrition aggravated these changes in the T-lymphocytes. In addition, the mRNA expression levels of IL-1ß, IL-2, IL-6, TNF-α, and IFN-γ in the spleen were downregulated significantly. We also reported herein the increased apoptosis ratio following caspase-9 and caspase-3 upregulation in the spleen of rats exposed to excessive amount of F. Light and transmisison electron microscopy revealed the irregularly arranged lymphocytes, few lymph nodules and the apoptotic characteristic of lymphocytes, which are caused by the increased expression of caspase. In addition, Pr and Ca supplementation reversed the morphologic and T-lymphocytic changes in spleen under malnutrition. Taken together, our results revealed an endogenous caspase-mediated mechanism of regulating the apoptosis of the T-lymphocyte subsets, as well as the immune-related cytokine secretion, which reduces the immune function in F-induced rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1587-1595, 2017.