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Objective: Stroke is a well-known and devastating complication during the perioperative period. However, detailed stroke risk profiles within 90 days in patients discharged without stroke after inpatient surgery are not fully understood. Using the case-crossover design, we aimed to evaluate the risk of ischemic stroke in these patients. Methods: We included adult patients with the first hospitalization for ischemic stroke between 2011 and 2012 from 23 million enrollees in the National Health Insurance Research Database. Admission date of the hospitalization was defined as the case day and exactly 365 days before the admission date as the control day. The exposure was the last hospitalization for surgery within 1–30, 31–60, or 61–90 days (case period) before the case day or similar time intervals (control period) before the control day. Surgical types were grouped based on the International Classification of Diseases procedure codes. We performed conditional logistic regression adjusting for time-varying variables to determine the relationship between surgery and subsequent stroke, and case-time-control analyses to examine whether the results were confounded by the time-trend in surgery. Results: A total of 56596 adult patients (41% female, mean age 69 years) comprised the study population. After adjustment was made for confounding variables, an association between stroke and prior inpatient surgery within 30 days was observed (adjusted odds ratio 1.44; 95% confidence interval 1.29–1.61). Cardiothoracic, vascular, digestive surgery, and musculoskeletal surgery within 30 days independently predicted ischemic stroke in the case-crossover analysis. In the case-time-control analysis, inpatient surgery remained an independent risk factor for ischemic stroke, whereas only cardiothoracic, vascular, and digestive surgery independently predicted ischemic stroke. Conclusions: Surgery as a whole independently increased the risk of ischemic stroke within 30 days. Among various types of surgery, cardiothoracic, vascular, and digestive surgery significantly increased the risk of ischemic stroke. [ABSTRACT FROM AUTHOR]

The advanced manufacturing industry is located at the top of the manufacturing value chain. Its development is restricted by supply chain collaboration (SCC), the level of which is affected by many factors. Few studies comprehensively summarize what influences SCC and distinguish the impact level of each factor. Practitioners have difficulty isolating the primary factors that affect SCC and managing them effectively. Therefore, based on synergetics and the theory of comparative advantage, this study analyzes what influences SCC in the advanced manufacturing industry and how these influencing factors work, using data from 94 manufacturing enterprises and the Haken model to identify the influencing factors. The results show that China's advanced manufacturing supply chain underwent a phase change and entered a new stage during 2017–2018. In the new stage, the competitive advantages of enterprises are one order parameter (slow variable) and are primary factors affecting SCC. The interest demands of enterprises are a fast variable and are secondary factors affecting SCC. The competitive advantages of enterprises dominate the interests of enterprises in affecting the collaboration level of China's advanced manufacturing supply chain. In addition, in the process of influencing SCC, there is a positive correlation between the competitive advantages of enterprises and the interest demands of enterprises, and the two factors have a positive feedback mechanism. Finally, when the enterprises in the supply chain cooperate based on their differential advantages, the collaboration capability of the supply chain is at the highest level, and the overall operation of the supply chain is orderly. In terms of theoretical contribution, this study is the first to propose a collaborative motivation framework that conforms to the characteristics of sequential parameters, which provides a theoretical reference for subsequent studies on SCC. In addition, the theory of comparative advantage and synergetics are linked for the first time in this study, and both of them are enriched and developed. Equally importantly, this study compares the bidirectional influence between firms' competitive advantages and firms' interest demands and the ability of both to influence SCC, enriching previous validation studies of unidirectional influence. In terms of practical implications, this study guides top managers to focus on the management practice of collaborative innovation in the supply chain and advises purchasing managers and sales managers on selecting supply chain partnerships. [ABSTRACT FROM AUTHOR]

Background: The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. Methods: A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Results: Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. Conclusions: The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted. [ABSTRACT FROM AUTHOR]

Dihydropyrimidinase is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. These metalloenzymes possess very similar active sites and may use a similar mechanism for catalysis. However, whether the substrates and inhibitors of other cyclic amidohydrolases can inhibit dihydropyrimidinase remains unclear. This study investigated the inhibition of dihydropyrimidinase by flavonoids and substrates of other cyclic amidohydrolases. Allantoin, dihydroorotate, 5-hydantoin acetic acid, acetohydroxamate, orotic acid, and 3-amino-1,2,4-triazole could slightly inhibit dihydropyrimidinase, and the IC50 values of these compounds were within the millimolar range. The inhibition of dihydropyrimidinase by flavonoids, such as myricetin, quercetin, kaempferol, galangin, dihydromyricetin, and myricitrin, was also investigated. Some of these compounds are known as inhibitors of allantoinase and dihydroorotase. Although the inhibitory effects of these flavonoids on dihydropyrimidinase were substrate-dependent, dihydromyricetin significantly inhibited dihydropyrimidinase with IC50 values of 48 and 40 μM for the substrates dihydrouracil and 5-propyl-hydantoin, respectively. The results from the Lineweaver−Burk plot indicated that dihydromyricetin was a competitive inhibitor. Results from fluorescence quenching analysis indicated that dihydromyricetin could form a stable complex with dihydropyrimidinase with the Kd value of 22.6 μM. A structural study using PatchDock showed that dihydromyricetin was docked in the active site pocket of dihydropyrimidinase, which was consistent with the findings from kinetic and fluorescence studies. This study was the first to demonstrate that naturally occurring product dihydromyricetin inhibited dihydropyrimidinase, even more than the substrate analogs (>3 orders of magnitude). These flavonols, particularly myricetin, may serve as drug leads and dirty drugs (for multiple targets) for designing compounds that target several cyclic amidohydrolases. [ABSTRACT FROM AUTHOR]

In Plasmodium, the membrane of intracellular parasites is initially formed during invasion as an invagination of the red blood cell surface, which forms a barrier between the parasite and infected red blood cells in asexual blood stage parasites. The membrane proteins of intracellular parasites of Plasmodium species have been identified such as early-transcribed membrane proteins (ETRAMPs) and exported proteins (EXPs). However, there is little or no information regarding the intracellular parasite membrane in Plasmodium vivax. In the present study, recombinant PvETRAMP11.2 (PVX_003565) and PvEXP1 (PVX_091700) were expressed and evaluated antigenicity tests using sera from P. vivax-infected patients. A large proportion of infected individuals presented with IgG antibody responses against PvETRAMP11.2 (76.8%) and PvEXP1 (69.6%). Both of the recombinant proteins elicited high antibody titers capable of recognizing parasites of vivax malaria patients. PvETRAMP11.2 partially co-localized with PvEXP1 on the intracellular membranes of immature schizont. Moreover, they were also detected at the apical organelles of newly formed merozoites of mature schizont. We first proposed that these proteins might be synthesized in the preceding schizont stage, localized on the parasite membranes and apical organelles of infected erythrocytes, and induced high IgG antibody responses in patients. [ABSTRACT FROM AUTHOR]

Background: This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention. Methods: We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives. Results: Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention. Conclusions: Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient’s condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes. [ABSTRACT FROM AUTHOR]

Bombyx mori nucleopolyhedrovirus (BmNPV) is a primary pathogen of silkworm (B. mori) that causes severe economic losses each year. However, the molecular mechanisms of silkworm-BmNPV interactions, especially the silkworm proteins that can interact with the virus, are still largely unknown. In this study, the total and membrane proteins of silkworm midguts were displayed using one- and two-dimensional electrophoresis. A virus overlay assay was used to detect B. mori proteins that specifically bind to BmNPV particles. Twelve proteins were located and identified using mass spectrometry, and the different expression of the corresponding genes in BmNPV susceptible and resistant silkworm strains also indicated their involvement in BmNPV infection. The 12 proteins are grouped based on their potential roles in viral infection, for example, endocytosis, intracellular transportation, and host responses. Based on these results, we hypothesize the following: I) vacuolar ATP synthase catalytic subunit A and subunit B may be implicated in the process of the membrane fusion of virus and the release of the nucleocapsid into cytoplasm; II) actin, enolase and phosphoglycerate kinase are cytoskeleton associated proteins and may play an important role in BmNPV intracellular transportation; III) mitochondrial prohibitin complex protein 2, ganglioside-induced differentiation-associated protein, calreticulin, regucalcin-like isoform X1 and 60 kDa heat shock protein are involved in cell apoptosis regulation during BmNPV infection in larvae midguts; IV) ribosomal P0 may be associated with BmNPV infection by regulating gene expression of BmNPV; V) arginine kinase has a role in the antiviral activities against BmNPV. Our work should prove informative by providing multiple protein targets and a novel direction to investigate the molecular mechanisms of the interactions between silkworms and BmNPV. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects. Materials and Methods: Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias. Results: A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46–2.06) and hyperprolactinemia (12.04; 1.59–91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment. Conclusions: We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological, dermatological, and musculoskeletal or joint side effects, constipation, and pneumonia. [ABSTRACT FROM AUTHOR]

The residue of imidacloprid in the nectar and pollens of the plants is toxic not only to adult honeybees but also the larvae. Our understanding of the risk of imidacloprid to larvae of the honeybees is still in a very early stage. In this study, the capped-brood, pupation and eclosion rates of the honeybee larvae were recorded after treating them directly in the hive with different dosages of imidacloprid. The brood-capped rates of the larvae decreased significantly when the dosages increased from 24 to 8000 ng/larva. However, there were no significant effects of DMSO or 0.4 ng of imidacloprid per larva on the brood-capped, pupation and eclosion rates. Although the sublethal dosage of imidacloprid had no effect on the eclosion rate, we found that the olfactory associative behavior of the adult bees was impaired if they had been treated with 0.04 ng/larva imidacloprid in the larval stage. These results demonstrate that a sublethal dosage of imidacloprid given to the larvae affects the subsequent associative ability of the adult honeybee workers. Thus, a low dose of imidacloprid may affect the survival condition of the entire colony, even though the larvae survive to adulthood. [ABSTRACT FROM AUTHOR]

Single-stranded DNA-binding protein (SSB) and PriA helicase play important roles in bacterial DNA replication restart process. The mechanism by which PriA helicase is bound and stimulated by SSB in Escherichia coli (Ec) has been established, but information on this process in Gram-positive bacteria are limited. We characterized the properties of SSB from Staphylococcus aureus (SaSsbA, a counterpart of EcSSB) and analyzed its interaction with SaPriA. The gel filtration chromatography analysis of purified SaSsbA showed a stable tetramer in solution. The crystal structure of SaSsbA determined at 1.82 Å resolution (PDB entry 5XGT) reveals that the classic oligonucleotide/oligosaccharide-binding folds are formed in the N-terminal DNA-binding domain, but the entire C-terminal domain is disordered. Unlike EcSSB, which can stimulate EcPriA via a physical interaction between EcPriA and the C-terminus of EcSSB (SSB-Ct), SaSsbA does not affect the activity of SaPriA. We also found that SaPriA can be bound by SaSsbA, but not by SaSsbA-Ct. Although no effect was found with SaSsbA, SaPriA can be significantly stimulated by the Gram-negative Klebsiella pneumoniae SSB (KpSSB). In addition, we found that the conserved SSB-Ct binding site of KpPriA (Trp82, Tyr86, Lys370, Arg697, and Gln701) is not present in SaPriA. Arg697 in KpPriA is known to play a critical role in altering the SSB35/SSB65 distribution, but this corresponding residue in SaPriA is Glu767 instead, which has an opposite charge to Arg. SaPriA E767R mutant was constructed and analyzed; however, it still cannot be stimulated by SaSsbA. Finally, we found that the conserved MDFDDDIPF motif in the Gram-negative bacterial SSB is DISDDDLPF in SaSsbA, i.e., F172 in EcSSB and F168 in KpSSB is S161 in SaSsbA, not F. When acting with SaSsbA S161F mutant, the activity of SaPriA was dramatically enhanced elevenfold. Overall, the conserved binding sites, both in EcPriA and EcSSB, are not present in SaPriA and SaSsbA, thereby no stimulation occurs. Our observations through structure-sequence comparison and mutational analyses indicate that the case of EcPriA-EcSSB is not applicable to SaPriA-SaSsbA because of inherent differences among the species. [ABSTRACT FROM AUTHOR]

Traffic state estimation from the floating car system is a challenging problem. The low penetration rate and random distribution make available floating car samples usually cover part space and time points of the road networks. To obtain a wide range of traffic state from the floating car system, many methods have been proposed to estimate the traffic state for the uncovered links. However, these methods cannot provide traffic state of the entire road networks. In this paper, the traffic state estimation is transformed to solve a missing data imputation problem, and the tensor completion framework is proposed to estimate missing traffic state. A tensor is constructed to model traffic state in which observed entries are directly derived from floating car system and unobserved traffic states are modeled as missing entries of constructed tensor. The constructed traffic state tensor can represent spatial and temporal correlations of traffic data and encode the multi-way properties of traffic state. The advantage of the proposed approach is that it can fully mine and utilize the multi-dimensional inherent correlations of traffic state. We tested the proposed approach on a well calibrated simulation network. Experimental results demonstrated that the proposed approach yield reliable traffic state estimation from very sparse floating car data, particularly when dealing with the floating car penetration rate is below 1%. [ABSTRACT FROM AUTHOR]

The role of DnaD in the recruitment of replicative helicase has been identified. However, knowledge of the DNA, PriA, and DnaA binding mechanism of this protein for the DnaA- and PriA-directed replication primosome assemblies is limited. We characterized the DNA-binding properties of DnaD from Staphylococcus aureus (SaDnaD) and analyzed its interactions with SaPriA and SaDnaA. The gel filtration chromatography analysis of purified SaDnaD and its deletion mutant proteins (SaDnaD1-195, SaDnaD1-200 and SaDnaD1-204) showed a stable tetramer in solution. This finding indicates that the C-terminal region aa 196–228 is not crucial for SaDnaD oligomerization. SaDnaD forms distinct complexes with ssDNA of different lengths. In fluorescence titrations, SaDnaD bound to ssDNA with a binding-site size of approximately 32 nt. A stable complex of SaDnaD1-195, SaDnaD1-200, and SaDnaD1-204 with ssDNA dT40 was undetectable, indicating that the C-terminal region of SaDnaD (particularly aa 205–228) is crucial for ssDNA binding. The SPR results revealed that SaDnaD1-195 can interact with SaDnaA but not with SaPriA, which may indicate that DnaD has different binding sites for PriA and DnaA. Both SaDnaD and SaDnaDY176A mutant proteins, but not SaDnaD1-195, can significantly stimulate the ATPase activity of SaPriA. Hence, the stimulation effect mainly resulted from direct contact within the protein—protein interaction, not via the DNA—protein interaction. Kinetic studies revealed that the SaDnaD-SaPriA interaction increases the Vmax of the SaPriA ATPase fivefold without significantly affecting the Km. These results indicate that the conserved C-terminal region is crucial for ssDNA and PriA helicase binding, but not for DnaA protein-binding and self-tetramerization. [ABSTRACT FROM AUTHOR]

The net photosynthetic rate, chlorophyll content, chlorophyll fluorescence and 820 nm transmission were investigated to explore the behavior of the photosynthetic apparatus, including light absorption, energy transformation and the photoactivities of photosystem II (PSII) and photosystem I (PSI) during senescence in the stay-green inbred line of maize (Zea mays) Q319 and the quick- leaf-senescence inbred line of maize HZ4. The relationship between the photosynthetic performance and the decrease in chlorophyll content in the two inbred lines was also studied. Both the field and laboratory data indicated that the chlorophyll content, net photosynthetic rate, and the photoactivities of PSII and PSI decreased later and slower in Q319 than in HZ4, indicating that Q319 is a functional stay-green inbred line. In order to avoid the influence of different development stages and environmental factors on senescence, age- matched detached leaf segments from the two inbred lines were treated with ethephon under controlled conditions to induce senescence. The net photosynthetic rate, light absorption, energy transformation, the activities of PSII acceptor side and donor side and the PSI activities decreased much slower in Q319 than in HZ4 during the ethephon-induced senescence. These results suggest that the retention of light absorption, energy transformation and activity of electron transfer contribute to the extended duration of active photosynthesis in Q319. Although the chlorophyll content decreased faster in HZ4, with decrease of chlorophyll content induced by ethephon, photosynthetic performance of Q319 deteriorated much more severely than that of HZ4, indicating that, compared with Q319, HZ4 has an advantage at maintaining higher photosynthetic activity with decrease of chlorophyll although HZ4 is a quick- leaf-senescence inbred line. We conclude that attention should be paid to two favorable characteristics in breeding long duration of active photosynthesis hybrids: 1) maintaining more chlorophyll content during senescence and 2) maintaining higher photosynthetic activity during the loss of chlorophyll. [ABSTRACT FROM AUTHOR]

Background: Ras is frequently mutated in a variety of human cancers, including lung cancer, leading to constitutive activation of MAPK signaling. Despite decades of research focused on the Ras oncogene, Ras-targeted phosphorylation events and signaling pathways have not been described on a proteome-wide scale. Methodology/Principal Findings: By functional phosphoproteomics, we studied the molecular mechanics of oncogenic Ras signaling using a pathway-based approach. We identified Ras-regulated phosphorylation events (n = 77) using label-free comparative proteomics analysis of immortalized human bronchial epithelial cells with and without the expression of oncogenic Ras. Many were newly identified as potential targets of the Ras signaling pathway. A majority (∼60%) of the Rastargeted events consisted of a [pSer/Thr]-Pro motif, indicating the involvement of proline-directed kinases. By integrating the phosphorylated signatures into the Pathway Interaction Database, we further inferred Ras-regulated pathways, including MAPK signaling and other novel cascades, in governing diverse functions such as gene expression, apoptosis, cell growth, and RNA processing. Comparisons of Ras-regulated phosphorylation events, pathways, and related kinases in lung cancer-derived cells supported a role of oncogenic Ras signaling in lung adenocarcinoma A549 and H322 cells, but not in large cell carcinoma H1299 cells. Conclusions/Significance: This study reveals phosphorylation events, signaling networks, and molecular functions that are regulated by oncogenic Ras. The results observed in this study may aid to extend our knowledge on Ras signaling in lung cancer. [ABSTRACT FROM AUTHOR]

By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC. [ABSTRACT FROM AUTHOR]