An evaluation model for children's foot & ankle deformity severity using sparse multi-objective feature selection algorithm.

Foot & ankle deformity is a chronic disease with high incidence and is best treated in childhood. However, the current diagnostic procedures rely on doctor's consultation and empirical judgment, and lack objective and quantitative evaluation methods, resulting in low screening rates. To solve this problem, this paper aims to construct an evaluation model for children's foot & ankle deformity through data mining and machine learning technologies. Firstly, it proposes the grading rules for children's foot & ankle deformity severity based on analyzing the existing quantitative indexes and expert experience. Then the 3D foot scanner is used to collect the sample data including 30 foot structure indexes. Finally, an advanced sparse multi-objective evolutionary algorithm (sparse MO-FS) is present for feature selection. The effectiveness of the proposed sparse MO-FS and its search efficiency are proved by comparing 8 feature selection methods and 7 search strategies. Using sparse MO-FS, foot length, arch index, ankle index, and hallux valgus index are selected, which not only simplifies the evaluation model but also improves the average classification accuracy of random forest to more than 98%.

Sustained activation of interferon regulatory factor 3 during infection by paramyxoviruses requires MDA5.

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are the main cytosolic sensors of single-stranded RNA viruses, including paramyxoviruses, and are required to initiate a quick and robust innate antiviral response. Despite different ligand-binding properties, the consensus view is that RIG-I and MDA5 trigger common signal(s) to activate interferon regulatory factor 3 (IRF-3) and NF-κB, and downstream antiviral and proinflammatory cytokine expression. Here, we performed a thorough analysis of the temporal involvement of RIG-I and MDA5 in the regulation of IRF-3 during respiratory syncytial virus (RSV) infection. Based on specific RNA interference-mediated knockdown of RIG-I and MDA5 in A549 cells, we confirmed that RIG-I is critical for the initiation of IRF-3 phosphorylation, dimerization and downstream gene expression. On the other hand, our experiments yielded the first evidence that knockdown of MDA5 leads to early ubiquitination and proteasomal degradation of active IRF-3. Conversely, ectopic expression of MDA5 prolonged RIG-I-induced IRF-3 activation. Altogether, we provide novel mechanistic insight into the temporal involvement of RIG-I and MDA5 in the innate antiviral response. While RIG-I is essential for initial IRF-3 activation, engagement of induced MDA5 is essential to prevent early degradation of IRF-3, thereby sustaining IRF-3-dependent antiviral gene expression. MDA5 plays a similar role during Sendai virus infection suggesting that this model is not restricted to RSV amongst paramyxoviruses.

Feasibility of infrared and Raman spectroscopies for identification of juvenile black seabream (Sparus macrocephalus) intoxicated by heavy metals.

The potential application of infrared and Raman spectroscopies was explored as rapid and nondestructive tools for the identification of juvenile black seabream samples intoxicated by heavy metals (Zn, Cu, and Cd). Discrimination models were established on the basis of the infrared and Raman spectral data using three calibration methods, namely, partial least-squares discriminant analysis, least-squares support vector machines, and random forest. The combination of two spectroscopies was studied, in which three combination strategies were proposed and compared. Discrimination models achieved overall correct discriminations of 100% for identifying the fish intoxicated by one heavy metal or the heavy metal mixture. When samples intoxicated by different heavy metals were analyzed together, the discrimination accuracy remained >90%. Results confirmed the possibility of developing fast and reliable systems for the identification of juvenile black seabream intoxicated by heavy metals based on infrared and Raman spectroscopies.

2-Arachidonoyl-glycerol- and arachidonic acid-stimulated neutrophils release antimicrobial effectors against E. coli, S. aureus, HSV-1, and RSV.

The endocannabinoid 2-AG is highly susceptible to its hydrolysis into AA, which activates neutrophils through de novo LTB(4) biosynthesis, independently of CB activation. In this study, we show that 2-AG and AA stimulate neutrophils to release antimicrobial effectors. Supernatants of neutrophils activated with nanomolar concentrations of 2-AG and AA indeed inhibited the infectivity of HSV-1 and RSV. Additionally, the supernatants of 2-AG- and AA-stimulated neutrophils strongly impaired the growth of Escherichia coli and Staphylococcus aureus. This correlated with the release of a large amount (micrograms) of α-defensins, as well as a limited amount (nanograms) of LL-37. All the effects of AA and 2-AG mentioned above were prevented by inhibiting LTB(4) biosynthesis or by blocking BLT(1). Importantly, neither CB(2) receptor agonists nor antagonists could mimic nor prevent the effects of 2-AG, respectively. In fact, qPCR data show that contaminating eosinophils express ∼100-fold more CB(2) receptor mRNA than purified neutrophils, suggesting that CB(2) receptor expression by human neutrophils is limited and that contaminating eosinophils are likely responsible for the previously documented CB(2) expression by freshly isolated human neutrophils. The rapid conversion of 2-AG to AA and their subsequent metabolism into LTB(4) promote 2-AG and AA as multifunctional activators of neutrophils, mainly exerting their effects by activating the BLT(1). Considering that nanomolar concentrations of AA or 2-AG were sufficient to impair viral infectivity, this suggests potential physiological roles for 2-AG and AA as regulators of host defense in vivo.