Search

We aimed to compare the clinical outcomes of pre-emptive angioplasty versus post-thrombotic percutaneous endovascular restoration of dysfunctional arteriovenous fistula (AVF).This retrospective study reviewed the data from 80 patients who underwent 114 endovascular interventions for a malfunctioning AVF from July 2016 to August 2019. Stenotic AVFs were treated with pre-emptive angioplasty. Thrombosed AVFs were treated with percutaneous pharmacomechanical fibrinolysis with urokinase used only during the operation or continuously infused. The differences in patency rates were evaluated using the Kaplan-Meier method. In addition, univariate and multivariate regression Cox models were used to determine influential factors on the postintervention primary patency.Post-thrombotic interventions and pre-emptive angioplasty yielded statistically similar rates in clinical success (100 vs. 100%), anatomic success (94 vs. 89%; P = 0.52), complication (4 vs. 11%; P = 0.29), as well as postintervention primary, assisted primary and secondary patency (P = 0.80; 0.57; 0.57). The use of pre-emptive angioplasty was associated with reduced total cost (¥25,108 vs. ¥30,833, P 0.001). The patients who used urokinase only during the operation prolonged both the primary and assisted primary patency (P = 0.02; 0.002), while those with continuous infusion of urokinase had worst patency rates and high costs (¥39,275 vs. ¥25,108 vs. ¥27,140, P 0.001). Compared with the other locations, dysfunction in the anastomotic or juxta-anastomotic segment (HR = 0.41, P = 0.001) was associated with prolonged postintervention primary patency.No clinical outcome differences were found between the post-thrombotic percutaneous endovascular interventions and pre-emptive angioplasty. However, pre-emptive angioplasty decreased access expenditure.

Using temporal and spatial correlations to predict wind speed is still one of the most challenging and least-researched fields in wind speed prediction. How to make full use of the spatial correlation of wind speed between adjacent wind turbines to improve the accuracy of wind speed prediction is significant. Therefore, to address the challenges of making multi-location, short-term wind speed predictions, we propose a multi-location wind speed prediction model based on spatiotemporal joint learning, which called Mixed-SqueezeNet-BiGRU. By designing the SqueezeNet model with a deformable convolutional network, the spatial correlation of a multi-location time series is learned by using the spatial wind speed matrix; by introducing the Channel Shuffle operation of ShuffleNet, the characteristics of multi-location and multi-channel are output to ensure the orderly flow of information among the channels. To describe the dynamic information of the time series, a time series dynamic network model based on the bi-directional gating cycle unit, BiGRU, is introduced to model the long-term and nonlinear dependence of the time series. Experiments were carried out on three wind farm's wind speed dataset to verify that the Mixed-SqueezeNet-BiGRU short-term wind speed prediction model has a better prediction performance than some advanced methods.

The study aimed to develop a machine learning (ML)-coupled interpretable radiomics signature to predict the pathological status of non-palpable suspicious breast microcalcifications (MCs). We enrolled 463 digital mammographical view images from 260 consecutive patients detected with non-palpable MCs and BI-RADS scored at 4 (training cohort, n = 428; independent testing cohort, n = 35). Subsequently, 837 textures and 9 shape features were subsequently extracted from each view and finally selected by an XGBoost-embedded recursive feature elimination technique (RFE), followed by four machine learning-based classifiers to build the radiomics signature. As a result, 10 radiomic features constituted a malignancy-related signature for breast MCs as logistic regression (LR) and support vector machine (SVM) yielded better positive predictive value (PPV)/sensitivity (SE), i.e., 0.904 (95% CI, 0.865–0.949)/0.946 (95% CI, 0.929–0.977) and 0.891 (95% CI, 0.822–0.939)/0.939 (95% CI, 0.907–0.973) respectively, outperforming their negative predictive value (NPV)/specificity (SP) from 10-fold cross-validation (10FCV) of the training cohort. Our optimal prognostic model was obtained by SVM with an area under the curve (AUC) of 0.906 (95% CI, 0.834–0.969) and accuracy (ACC) 0.787 (95% CI, 0.680–0.855) from 10FCV against AUC 0.810 (95% CI, 0.760–0.960) and ACC 0.800 from the testing cohort. The proposed radiomics signature dependens on a set of ML-based advanced computational algorithms and is expected to identify pathologically cancerous cases from mammographically undecipherable MCs and thus offer prospective clinical diagnostic guidance.

Purpose The aim of this study is to establish a rapid antibody-free diagnostic method of malaria infection with Plasmodium falciparum and Plasmodium vivax in whole blood with Surface-enhanced Raman Spectroscopy using Nanostructured Gold Substrate. Materials and methods The blood samples collected from patients were first lysed and centrifuged before dropping on the gold nano-structure (AuNS) substrate. Malaria diagnosis was performed by detecting Raman peaks from Surface Enhanced Raman Spectroscopy (SERS) with a 532 nm laser excitation. Results Raman peaks at 1370 cm−1, 1570 cm−1, and 1627 cm−1, known to have high specificity against interference from other mosquito-borne diseases such as Dengue and West Nile virus infection, were selected as the fingerprint markers associated with P. falciparum and P. vivax infection. The limit of detection was 10−5 dilution, corresponding to the concentration of parasitized blood cells of 100/mL. A total number of 25 clinical samples, including 5 from patients with P. falciparum infection, 10 with P. vivax infection and 10 from healthy volunteers, were evaluated to support its clinical practical use. The whole assay on malaria detection took 30 min to complete. Conclusions While the samples analyzed in this work have strong clinical relevance, we have clearly demonstrated that sensitive malaria detection using AuNS-SERS is a practical direction for rapid in-field diagnosis of malaria infection.

Objective: The nucleic acid-based polymerase chain reaction (PCR) assay is commonly applied to detect infection with Zika virus (ZIKV). However, the time- and labor-intensive sample pretreatment required to remove inhibitors that cause false-negative results in clinical samples is impractical for use in resource-limited areas. The aim was to develop a direct reverse-transcription quantitative PCR (dirRT-qPCR) assay for ZIKV diagnosis directly from clinical samples. Methods: The combination of inhibitor-tolerant polymerases, polymerase enhancers, and dirRT-qPCR conditions was optimized for various clinical samples including blood and serum. Sensitivity was evaluated with standard DNA spiked in simulated samples. Specificity was evaluated using clinical specimens of other infections such as dengue virus and chikungunya virus. Results: High specificity and sensitivity were achieved, and the limit of detection (LOD) of the assay was 9.5 × 101 ZIKV RNA copies/reaction. The on-site clinical diagnosis of ZIKV required a 5 μl sample and the diagnosis could be completed within 2 h. Conclusions: This robust dirRT-qPCR assay shows a high potential for point-of-care diagnosis, and the primer–probe combinations can also be extended for other viral detection. It realizes the goal of large-scale on-site screening for viral infections and could be used for early diagnosis and the prevention and control of viral outbreaks. Keywords: Clinical Zika diagnostics, Direct sample detection, dirRT-qPCR, Molecular diagnostics

Third-party library (TPL) detection in Android has been a hot topic to security researchers for a long time. A precise yet scalable detection of TPLs in applications can greatly facilitate other security activities such as TPL integrity checking, malware detection, and privacy leakage detection. Since TPLs of specific versions may exhibit their own security issues, the identification of TPL as well as its concrete version, can help assess the security of Android APPs. However in reality, existing approaches of TPL detection suffer from low efficiency for their detection algorithm to impracticable and low accuracy due to insufficient analysis data, inappropriate features, or the disturbance from code obfuscation, shrinkage, and optimization. In this paper, we present an automated approach, named PanGuard , to detect TPLs from an enormous number of Android APPs. We propose a novel combination of features including both structural and content information for packages in APPs to characterize TPLs. In order to address the difficulties caused by code obfuscation, shrinkage, and optimization, we identify the invariants that are unchanged during mutation, separate TPLs from the primary code in APPs, and use these invariants to determine the contained TPLs as well as their versions. The extensive experiments show that PanGuard achieves a high accuracy and scalability simultaneously in TPL detection. In order to accommodate to optimized TPL detection, which has not been mentioned by previous work, we adopt set analysis, which speed up the detection as a side effect. PanGuard is implemented and applied on an industrial edge computing platform, and powers the identification of TPL. Beside fast detection algorithm, the edge computing deployment architecture make the detection scalable to real-time detection on a large volume of emerging APPs. Based on the detection results from millions of Android APPs, we successfully identify over 800 TPLs with 12 versions on average. By investigating the differences amongst these versions, we identify over 10 security issues in TPLs, and shed light on the significance of TPL detection with the caused harmful impacts on the Android ecosystem.

The effects of the preovulatory luteinizing hormone (LH) surge on the ovulatory process are mediated by prostaglandins (PGs), the synthesis of which involves prostaglandin synthetase and cytosolic phospholipase A2 (cPLA2). In our previous study, we systematically investigated the function of prostaglandin endoperoxide synthase (ptgs) genes on ovulation in zebrafish. However, the role of cPLA2 in ovulation was not determined in zebrafish. In this study, we investigated the function of cpla2α in PGs production and ovulation in periovulatory follicles. Our data showed that the expression of pla2g4aa increased during zebrafish folliculogenesis and the follicular layer was the primary region with expression of pla2g4aa. In addition, the expression of pla2g4aa was regulated by LH in vitro and in vivo. Furthermore, injection of AACOCF3, a specific inhibitor of cPLA2, significantly reduced ovarian PGs level and blocked hCG-induced ovulation. Collectively, these findings suggest that pla2g4aa is related to the ovulation process in zebrafish.

A novel non-noble metal catalyst towards the hydrolysis of ammonia borane, Mo-doped Cu0.5Ni0.5Co2O4 nanowires, are designed and prepared. For the sample with the optimized doping amount of Mo, the turnover frequency value can reach 195.25 molhydrogen min−1 molcat−1. This value is much higher than those of all the other non-noble metal catalysts ever reported in the literature. In addition, there is nearly no activity loss for that catalyst after 6 catalytic cycles. Considering its high performance and low cost, our catalyst can be a strong substitute for noble-metal-based catalysts in AB hydrolysis for hydrogen production.

Toll-like receptors (TLRs) are important innate immune receptors that recognize multiple pathogen-associated molecular patterns (PAMPs) and activate the immune responses to resist the invasion of pathogens. Many TLRs need assistance from trafficking chaperones to transport to the specific cell compartments and then are processed before they are activated. In this study, we identified an important trafficking chaperone, Unc-93 homolog B1 (unc93b1), from the Epinephelus coioides (orange-spotted grouper). The deduced protein sequence of Eco.unc93b1 was 632 amino acids, containing 12 transmembrane domains, consistent with other UNC93B1 proteins from other species. Phylogenetic analysis showed that Eco.Unc93b1 was clustered with teleost Unc93b1 and had the closest relationship with Larimichthys crocea (large yellow croaker) Unc93b1. Eco.unc93b1 was expressed the highest in the spleen, and its protein was co-localized with the endoplasmic reticulum and early endosomes in both human embryonic kidney 293T cells and grouper spleen cells (GS cells). Moreover, the stimulation of lipopolysaccharide (LPS), high-molecular-weight poly (I:C) (HMW), imidazoquinoline (R848), polyadenylic-polyuridylic acid (poly AU), and 19-mer Staphylococcus aureus 23S rRNA-derived oligoribonucleotide (ORN Sa 19) promoted the mRNA expression of unc93b1 in GS cells with different patterns. Furthermore, the cytokine expression induced by these PAMPs was suppressed, while Eco.unc93b1 was knocked down, by small interfering RNA. In conclusion, these results suggest that Eco.unc93b1 plays an essential role in several PAMP-induced immune responses.

Toll-like receptors (TLRs) are one of the most important innate immune receptors, which recognize various pathogen-associated molecular patterns and activate the downstream immune response. Mouse TLR13 has been found to recognize a highly conserved sequence from bacterial or viral RNA and activate the myeloid differentiation primary response gene 88-dependent signaling response. The function of teleost tlr13 is still not fully understood, especially its relationship with bacterial RNA. In our study, we identified and characterized a tlr13 from Epinephelus coioides (orange-spotted grouper). The full-length cDNA of Eco. tlr13 contained a 2844 bp open reading frame, encoding 947 amino acids. The polypeptide was constitutive of a signal peptide, 13 leucine-rich repeats domains, a C-terminal leucine-rich repeats, a transmembrane domain and a conserved Toll/interleukin (IL)-1 receptor domain, indicating that Eco. Tlr13 exhibited a typical TLR structure. Multiple alignments showed that the Toll/IL-1 receptor domain of Eco. Tlr13 was identical with other homologues, and the phylogenetic tree suggested that Eco. Tlr13 was clustered with other TLR13s and had the closest relationship with predicted Lates calcarifer (sea bass) Tlr13. Subcellular localization analysis revealed that Eco. Tlr13 colocalized with the endoplasmic reticulum and early endosome. Moreover, Eco. tlr13 was broadly observed in all tested tissues with the relatively high expressions in the brain and immune-related tissues. After challenged with 19-mer Staphylococcus aureus 23S ribosomal RNA-derived oligoribonucleotide (ORN Sa19), the expression of Eco. tlr13 was significantly up-regulated in grouper spleen cells. Also, the luciferase assay further revealed that with the overexpression of Eco. Tlr13 in human embryonic kidney 293T cells, ORN Sa19 activated the promoter activity of interferon-β in a dose-dependent pattern. These results indicate that Eco. tlr13 may involve in the recognition of bacterial RNA.

Zika virus (ZIKV) is an important emerging human pathogen associated with microcephaly, Guillain-Barre syndrome and meningoencephalitis. Developing rapid and reliable HTS assay is important for ZIKV drug discovery. Here, we constructed a dicistronic ZIKV replicon (ZIKV-Pac-Rluc-Rep) that contained the Renilla luciferase (Rluc) reporter gene separated from the puromycin N-acetyl-transferase (Pac) selectable marker by a short peptide cleavage site. A clonal replicon cell line stably expressing high level of ZIKV replicon was established by selection with puromycin. By optimizing cell number, compound concentration and incubation time, a robust replicon cell-based HTS assay was developed with a calculated Z' value of >0.5. The fully optimized assay was further validated using several known flavivirus replication inhibitors. Altogether, the replicon cell-based HTS assay developed in this study will facilitate the discovery of antiviral compounds against ZIKV.

The NOD-like receptors (NLRs) are an important part of the innate immune system, capable of recognizing or sensing pathogens or cell homeostasis imbalance, and play an important role in pathogen removal and body protection. NOD2 is one of the important members in NLR family. In present study, NOD2 was cloned and identified from Nile tilapia (Oreochromis niloticus). The Nile tilapia NOD2 ORF was 2961 bp in length encoding a peptide of 986 amino acid residues with a typical structure of CARD-CARD-NACHT-LRRs. Phylogenetic and synteny analysis illustrated that NOD2 was highly conserved between different species. Tissue distribution of NOD2 mRNA showed that it was widely expressed and highly expressed in immune-related tissues (blood, head kidney, liver and spleen). Post Streptococcus agalactiae challenge, NOD2 mRNA expression levels were altered in immune organs or tissues (liver, head kidney, spleen and blood). Subcellular localization of Nile tilapia NOD2 illuminated that it was an intracellular PRR like mammalian counterparts, most of which was co-localized with mitochondria, and a few of which was co-localized with endosome and endoplasmic reticulum. In addition, Nile tilapia NOD2-mediated signaling pathway and ligand recognition were also studied, it illuminated that Nile tilapia NOD2 could recognize MDP intracellularly and activate NF-κB signaling pathway. In conclusion, this study indicated that the Nile tilapia NOD2 was conservative and had a significant role in innate immune defense against bacterial infection.

Pyruvate kinase M2 isoform (PKM2) plays a key role in cancer progression through both metabolic and non-metabolic functions, thus it is recognized as a potential target for cancer diagnosis and treatment. In this study, we discovered a sulfonamide-dithiocarbamate compound 8a as a novel PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8a analogs were designed and synthesized for screening as potent PKM2 activators. Among them, compound 8b (AC50 = 0.136 µM) and 8k (AC50 = 0.056 µM) showed higher PKM2 activation activities than positive control NZT (AC50 = 0.228 µM), and they (IC50 10 µM). Especially, compound 8k inhibited the proliferation of multiple cancer cells, but showed little toxicity on normal cells. In addition, we found that compound 8k inhibit the colony formation of MCF7 cells. Western blot analysis demonstrated that 8k could reduce PKM2 nuclear localization and block the downstream signaling pathway of PKM2, resulting in suppression of tumor cell proliferation. Overall, compound 8k may be a promising candidate for further mechanistic investigation of PKM2 and cancer therapy.

Here, we describe a cell culture-based procedure for isolating the infectious ZIKV (GenBank KU963796) from a human serum sample (ca. 50 μL) with an extremely low viral load (Ct value = 32).