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The field of Translation Studies has expanded rapidly in the twenty-first century, largely due to the growing demand for translation and interpreting professionals. This study provides a scientometric review of Translation Studies to identify its developmental trends and patterns over the past two decades. Document co-citation analysis was conducted on 6007 journal articles published in the fifteen translation studies journals indexed in the Web of Science between January 2001 and December 2020. Twelve document co-citation analysis networks were generated and compared. Quantitative analyses, including temporal and structural metrics, confirmed the robustness and reliability of a network comprising ten discrete research clusters. A timeline view was generated to visualize how these clusters have evolved over time. Ten clusters were identified as major research subdomains in Translation Studies, namely translation competence, translation in conflict zones, translator training, collaborative translation, translation and society, language policy, post-editing and revision, media translation, the translation profession, and web localization. In addition, burst detection analysis identified the twenty most influential publications in this sample. Based on these findings, we discuss how the observed trends in each cluster contribute to further developments in Translation Studies. The implications for teaching, research, and theory are discussed and some methodological guidelines are proposed for future research.

Our previous trial demonstrated that tirofiban was effective and safe in acute ischemic stroke (AIS) patients who were not undergoing early recanalization treatments. We aimed to further evaluate the structural MRI characteristics and their clinical significance to better predict and guide tirofiban treatment. In this post hoc analysis of imaging features, the location of infarcts (anterior circulation stroke [ACS] vs posterior circulation stroke [PCS]), degree of cerebral artery stenosis (≤ 69% vs ≥ 70% or occlusion), total infarct volume and ASPECTS score were used to predict the treatment response of tirofiban, defined as a proportion of excellent functional outcome (modified Rankin Scale (mRS) score of 0–1) and favorable functional outcome (mRS score of 0–2) at 90 days. Patients with ACS were more likely to achieve excellent functional outcome (p = 0.004) and favorable functional outcome (p = 0.008) when treated with tirofiban. However, there were no significant differences between the two groups for patients with PCS. For patients due to severe stenosis (≥ 70% or occlusion), there were significant differences between the two groups (p = 0.002 for mRS 0–1; p = 0.011 for mRS 0–2). Meanwhile, we found that tirofiban treatment improved clinical outcome only in patients with ASPECTS (8–10) (p = 0.016). In addition, we found that the effect of tirofiban treatment was independent of total infarct volume. The neuroimaging data supported that patients with ACS and severe stenosis were recommended for the application of tirofiban, and better treatment response could be predicted independent of total infarct volume.

This study was aimed at exploring the efficacy of morphine combined with mechanical ventilation in the treatment of heart failure with artificial intelligence algorithms. The cardiac magnetic resonance imaging (MRI) under the watershed segmentation algorithm was proposed, and the local grayscale clustering watershed (LGCW) model was designed in this study. A total of 136 patients with acute left heart failure were taken as the research objects and randomly divided into the control group (conventional treatment) and the experimental group (morphine combined with mechanical ventilation), with 68 cases in each group. The left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-proBNP), arterial partial pressure of oxygen (PaO2), and arterial partial pressure of carbon dioxide (PaCO2) were observed. The results showed that the mean absolute deviation (MAD) and maximum mean absolute deviation (max-MAD) of the LGCW model were lower than those of the fuzzy k-nearest neighbor (FKNN) algorithm and local gray-scale clustering model (LGSCm). The Dice metric was also significantly higher than that of other algorithms with statistically significant differences ( P < 0.05 ). After treatment, LVEDD, LVESD, and NT-proBNP of patients in the experimental group were significantly lower than those in the control group, and LVEF in the experimental group was higher than that in the control group ( P < 0.05 ). PaO2 of patients in the experimental group was also significantly higher than that in the control group ( P < 0.05 ). It suggested that the LGCW model had a better segmentation effect, and morphine combined with mechanical ventilation gave a better clinical efficacy in the treatment of acute left heart failure, improving the patients’ cardiac function and arterial blood gas effectively.

Background Patients with multiple sclerosis (MS) experience relapses and sustained disability progression. Since 2004, the number of disease-modifying therapies (DMTs) for MS has grown substantially. As a result, patients, healthcare providers, and insurers are increasingly interested in comparative efficacy and safety evaluations to distinguish between treatment options, but head-to-head studies between DMTs are limited. Objective The aim of the current study was to compare efficacy and safety outcomes with the DMTs ozanimod and dimethyl fumarate (DMF) using a matching-adjusted indirect comparison (MAIC) to adjust for cross-trial differences in study design and population. Methods A systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod compared with DMF. Individual patient-level data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate-level patient data (APD) for DMF were obtained from CONFIRM and DEFINE. A MAIC is used to weight IPD to APD based on important baseline patient characteristics considered to be effect modifiers or prognostic factors in order to balance the covariate distribution to establish more homogenous trial populations. Once trial populations are determined to be sufficiently homogenous, outcomes of interest are estimated and used to generate treatment effects between the weighted IPD and APD. We used MAIC methodology to compare efficacy and safety outcomes of interest between ozanimod 1.0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. Results After matching patient data, baseline patient characteristics were balanced between patients receiving ozanimod and those receiving DMF. Compared with DMF, ozanimod demonstrated significantly improved CDP at 3 months (hazard ratio 0.67; 95% confidence interval [CI] 0.53–0.86), ARR (rate ratio [RR] 0.80; 95% CI 0.67–0.97), proportion of patients relapsed (odds ratio [OR] 0.66; 95% CI 0.52–0.83), overall AEs (OR 0.11; 95% CI 0.08–0.16), SAEs (OR 0.27; 95% CI 0.19–0.39), and discontinuations (OR 0.11; 95% CI 0.07–0.17). CDP at 6 months did not differ significantly between the two agents (RR 0.89; 95% CI 0.62–1.26). Conclusions After adjustment of baseline patient characteristics, the MAIC demonstrated that the efficacy and safety of ozanimod 1.0 mg OD was superior to that of DMF 240 mg BID. Although a MAIC is less likely to produce biased estimates than a naïve or a standard indirect treatment comparison via a common comparator, limitations include potential confounding due to unobserved and thus unaccounted for baseline differences., Plain Language Summary Ozanimod and dimethyl fumarate (DMF) are disease-modifying therapies used to treat relapsing-remitting multiple sclerosis (MS). Comparative efficacy and safety evaluation is important to key patients, healthcare providers, and health insurers; however, head-to-head studies between MS therapies are limited. In this analysis, we used an indirect treatment comparison method, specifically a matching-adjusted indirect comparison (MAIC), to compare results of clinical trials of ozanimod and DMF. In this MAIC, findings suggested that ozanimod was associated with greater reductions of relapses, a lowered risk of disability progression at 3 months, and improved safety outcomes compared with DMF. Although MAICs were conducted while adjusting for important treatment-effect modifiers and/or prognostic factors, the possibility of confounding as a result of unobserved baseline differences remains. Such an issue can be resolved only by conducting a head-to-head treatment comparison in a randomized clinical trial.

Introduction To compare all-cause and endometriosis-related healthcare resource utilization (HCRU) and healthcare costs by service categories (outpatient, inpatient, emergency room [ER], pharmacy) among patients with newly diagnosed endometriosis using opioids compared to patients with endometriosis not using opioids. Methods A retrospective analysis of IBM® MarketScan® Commercial Claims data from 2009 to 2018 was performed for women aged 18–49 with newly diagnosed endometriosis (International Classification of Diseases (ICD)-9 code 617.xx; ICD-10 code N80.xx) over 24 months follow-up. Patients were stratified on the basis of opioid use within 12 months post first endometriosis diagnosis date. Patients with opioid use were 1:1 matched to patients without opioid use using propensity score matching. Results A total of 85,329 female patients with a new endometriosis diagnosis were identified and 48,470 patients (24,235 opioid and 24,235 non-opioid users) remained after inclusion–exclusion criteria and matching. Opioid patients had an estimated mean 30.33 outpatient visits, 29.59 pharmacy fills, 0.28 inpatient visits, 0.65 ER visits, and total length of stay (LOS) was 1.01 days. Non-opioid patients had an estimated mean 27.94 outpatient visits, 22.06 pharmacy fills, 0.23 inpatient visits, 0.42 ER visits, and total LOS was 0.82 days. On average, opioid patients had significantly greater all-cause HCRU compared to non-opioid patients (all p

Purpose: To study the effect of dexmedetomidine on myocardial ischemia-reperfusion injury (MI/RI)- induced imbalance on oxidant-prooxidant status and apoptotic changes in rats. Methods: Ninety (90) male Wistar rats were randomly divided into three groups – sham, model and post-treatment. In model rats, the anterior descending branch of the left coronary artery was ligated for 25 min, prior to their being subjected to reperfusion for 2 h. Rats in the post-treatment group were subjected to ligation at the anterior descending branch of the left coronary artery for 25 min, but they were intravenously injected with dexmedetomidine at a dose of 10 μg/kg prior to reperfusion. There was no ligation in the sham group. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were assayed. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) levels were also evaluated. Apoptosis was measured with TdT-mediated dUTP nick end labeling (TUNEL) assay. Results: Compared with the sham group, MDA level in the model group was significantly rose, while SOD and GSH-Px activities were markedly decreased (p < 0.05). Moreover, there were higher LDH and CK-MB activities in model rats than in the sham rats, but they were significantly lower in the posttreatment group than in the model group (p < 0.05). Apoptosis was higher in model rats than in sham operation rats, but was markedly decreased in post-treatment rats than in model rats (p < 0.05). Conclusion: Post-treatment with dexmedetomidine exerts myocardial protective effect via significant reduction in oxidative stress-induced myocardial injury and apoptosis. Keywords: Dexmedetomidine, Myocardial ischemia-reperfusion injury, Antioxidant status, Programmed cell death

A fundamental requirement of language assessments which is underresearched in computerized assessments is impartiality (fairness) or equal treatment of test takers regardless of background. The pre...

The present study, which involved 10 GEO datasets and 3 ArrayExpress datasets, comprehensively characterized the potential effects of CMGs in sepsis. Based on machine learning algorithms (Lasso, SVM and ANN), the CMG classifier was constructed by integrating 6 hub CMGs (CD28, CD40, LTB, TMIGD2, TNFRSF13C and TNFSF4). The CMG classifier exhibit excellent diagnostic values across multiple datasets and time points, and was able to distinguish sepsis from other critical diseases. The CMG classifier performed better in predicting mortality than other clinical characteristics or endotypes. More importantly, from clinical specimens, the CMG classifier showed more superior diagnostic values than PCT and CRP. Alternatively, the CMG classifier/hub CMGs is significantly correlated with immune cells infiltration (B cells, T cells, Tregs, and MDSC), pivotal immune and molecular pathways (inflammation-promoting, complement and coagulation cascades), and several cytokines. Collectively, CMG classifier was a robust tool for diagnosis, prognosis and recognition of immune microenvironment features in sepsis.

As an important characteristic information in incipient fault diagnosis of rotating machinery, the fault impulse signal is hard to be monitored due to the low signal amplitude and system disturbance/noise. Based on bilateral spectrum and precession energy difference density spectrum for the incipient fault diagnosis of rotating machinery, a novel diagnosis method is proposed in this paper to overcome this key problem. Compared with the existing methods to extract transient impulses from the vibrate signals, this paper designs a new fault feature parameter-precession energy difference density to characterize the feature of transient impulse. Furthermore, the complex signal and the negative frequency are introduced into the spectrum analysis and the forward and backward precession characteristics, which can be directly gained through the bilateral spectrum and relieves the problems not to be overlooked, such as high calculation, high error and time consuming. Finally, the feasibility and effectiveness of the proposed methods are demonstrated via a case study of a vertical mill reducer.

Background Delirium is a brain dysfunction syndrome, which children have a higher incidence. At present, there have been more and more studies and reports on delirium in paediatric intensive care unit, but there are some differences in the risk factor results among different studies. To better manage delirium, this study was performed. Objective To integrate and clarify the risk factors for delirium in paediatric intensive care unit. Methods CNKI, CBMdisc, Wanfang Data Knowledge Service Platform, VIP, PubMed, Embase, Cochrane Library, JBI and PsycInfo were searched for relevant literature. The study subjects were patients in PICU and literature was included according to the PICOS principle. Literature screening and risk of bias assessment were mainly completed by two researchers, and RevMan 5.3 software and Stata software were used for data analysis. The GRADE systerm was used to assess the quality of evidence. Results A total of 10 studies were included, all in English, involving 4343 children. Within the GRADE system, 4 indicators were scored A, 1 indicators were scored B, and 3 indicators were scored C regarding evidence levels. Three studies analysed the influence of developmental delay on the occurrence of delirium in PICU, total sample size of which was 1823, and the results showed that the combined effect was statistically significant [OR = 3.34, 95%CI(2.46–4.53), Z = 7.75, PP Conclusion Developmental delay, mechanical ventilation, benzodiazepine use, anticholinergic use, age and PICU length of stay are independent risk factors for delirium in children in PICU. However, only a few articles were included in this study, which may lead to a certain bias and affect the analysing results. More large-sample, multicentre studies should be conducted to further explore and clarify the independent influencing factors of delirium in children in PICU and to provide guidance for clinical practice.

Objectives:Evaluate all-cause and endometriosis-related health care resource utilization and costs among newly diagnosed endometriosis patients with high-risk versus low-risk opioid use or patients with chronic versus non-chronic opioid use.Methods:A retrospective analysis of IBM MarketScan®Commercial Claims data from 2009 to 2018 was performed for females aged 18 to 49 with newly diagnosed endometriosis (International Classification of Diseases, Ninth Edition code: 617.xx; International Classification of Diseases, Tenth Edition code: N80.xx). Two sub-cohorts were identified: high-risk (⩾1 day with ⩾90 morphine milligram equivalents per day or ⩾1-day concomitant benzodiazepine use) or chronic opioid utilization (⩾90-day supply prescribed or ⩾10 opioid prescriptions). High-risk or chronic utilization was evaluated during the 12-month assessment period after the index date. Index date was the first opioid prescription within 12 months following endometriosis diagnosis. All outcomes were assessed over 12-month post-assessment period while adjusting for demographic and clinical characteristics.Results:Out of 61,019 patients identified, 18,239 had high-risk opioid use and 5001 chronic opioid use. Health care resource utilization drivers were outpatient visits and pharmacy fills, which were higher among high-risk versus low-risk patients (outpatient visits: 17.49 vs 15.51; pharmacy fills: 19.58 vs 16.88, p Conclusion:This analysis demonstrates significantly higher all-cause and endometriosis-related health care resource utilization and total costs for high-risk opioid users compared to low-risk opioid users among newly diagnosed endometriosis patients over 1 year. Similar trends were observed for comparing chronic opioid users with non-chronic opioid users, except for endometriosis-related pharmacy fills and associated costs.

Background A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS. Methods A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. Results After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62–0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44–0.70), overall AEs (OR: 0.35; 95% CI: 0.29–0.43), SAEs (OR: 0.53; 95% CI: 0.37–0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09–0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66–0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60–1.01) compared with TERI. Conclusion In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit–risk profile over TERI.

e16252 Background: Treatment options remain limited for pts newly diagnosed with mPDAC. NCCN and ASCO guidelines both recommend treatment with FOLFIRINOX or gemcitabine plus nab-paclitaxel in the first line (1L) setting for pts with mPDAC and good performance status. Over 80% of randomized clinical trials (RCTs) studying treatments for mPDAC have failed to meet their primary endpoints. Recently published analyses have utilized real-world (RW) data to compare outcomes between pts enrolled in clinical trials and RW pts. This study sought to identify the eligible population of pts with mPDAC treated with FOLFIRINOX in the 1L setting who would meet RCT eligibility criteria for the phase 1/2 study (NCT02551991) evaluating NALIRIFOX for pts with previously untreated locally advanced or mPDAC, and to assess their survival outcomes. Methods: This retrospective observational study utilized the Flatiron Health EHR database. Data were analyzed for adult pts diagnosed with mPDAC between January 2016 and February 2020 who initiated treatment with FOLFIRNOX in 1L within 90 days of their diagnosis for metastatic disease. Eligibility criteria from the phase 1/2 trial were applied to select a population of RW pts who may have been eligible to enter the RCT. Pts meeting the following criteria were included: good performance scores (ECOG 0-1), adequate hematological, hepatic, and renal function, were recovered from the effects of surgery, were untreated in the year prior to initiating 1L, and had no evidence of a different cancer in the last three years. Kaplan-Meier analyses were used to assess the median overall survival (mOS) from the start of 1L FOLFIRNOX treatment. Results: Of the 1,210 pts treated with 1L FOLFIRINOX, 652 pts (53.8%) met less stringent versions of the RCT eligibility criteria in which missing values were deemed to indicate normal function/performance; 244 pts (20.2%) met the more stringent criteria and had complete data. The most restrictive selection criteria were the requirements for adequate hematological, hepatic, and renal function and having received prior therapy. The median age at treatment initiation among the 244 pts was 64 years (IQR: 58 – 70). 153 pts were male (62.7%), 158 were White (64.8%), and ECOG scores of 0 and 1 were split among the cohort 50%/50%. The mOS observed for the 244 pts was 10.1 months (95% CI: 9.1 – 11.3). The reported mOS from the phase 1/2 trial of NALIRIFOX was 12.6 months (8.7 – 18.7). Conclusions: This study demonstrates that RW data may be used to select a comparator cohort for a clinical trial. Initial estimates suggest NALIRIFOX pts from the RCT experienced longer survival than those receiving 1L FOLFIRINOX in the RW setting. Further analysis is necessary to minimize the effects of confounding and the differences in data collection between the RW and the RCT settings.

In order to explore the reasons that affect the flow of material and energy in the river, the Longji terraces are used as the research area, and the methods of field investigation and geospatial information technology are used to carry out research. The results show that human activities, vegetation coverage and the establishment of reservoirs are all factors that affect the flow of material and energy in the river.

Longji Terrace, one of the three ancient terraces in China, is a comprehensive tourist scenic spot with agricultural terraces as the main body and integrating natural landscape, cultural landscape and ethnic customs. In this paper, taking Longji Terrace in Guilin as the research object, using geographic information technology to study its ecosystem structure from the aspects of space, components, etc., to explore the material and energy flow patterns of the ecosystem, and to analyze the service functions of the ecosystem, so as to provide basic information for the healthy and sustainable development of the local ecological environment.

This paper presents improvements in performance, power, and area (PPA) obtained by optimizing the gear ratio (GR) between the Gate and vertical metal layer pitches in standard cells in sub-10nm node CMOS SoC designs. Changing the GR from 1:1 to 3:2 leads to better pin accessibility, routability, and higher cell density. This in turn enables a gate pitch relaxation and associated improvements in cell delay. Implementation of 3:2 GR ultra-dense cells in an SoC CPU block results in up to 17% higher performance, 4% smaller logic size, and 8% lower dynamic power at typical PVT conditions.

As pitch scaling is becoming constrained not only by lithographic resolution limits but alos by fundamental device and interconnect challenges the semiconductor industry has turned to cell-height reduction as a means of achieving competitive area scaling. The risk in using cell-height reduction to compensate for insufficient pitch scaling is that place- and-route inefficiencies caused by wiring congestion at the block level of the design can easily eliminate any area scaling gains made at the cell level of the design. This paper shows how careful cell-architecture optimization, physical design methodology changes, and place-and-route innovations have led to competitive block level area scaling for 7nm technology nodes and beyond. Data is presented to show that an entire node’s worth of scaling can be achieved through these comprehensive design-technology co-optimization efforts.

Acetohydroxyacid synthase (AHAS) has been regarded as a promising drug target against Mycobacterium tuberculosis (MTB) as it catalyzes the biosynthesis of branched-chain amino acids. In this study, 23 novel AHAS inhibitors were identified through molecular docking followed by similarity search. The determined IC(50) values range from 0.385 ± 0.026 μM to200 μM against bacterium AHAS. Five of the identified compounds show significant in vitro activity against H37Rv strains (MICs in the range of 2.5-80 mg/L) and clinical MTB strains, including MDR and XDR isolates. More impressively, compounds 5 and 7 can enhance the killing ability against macrophages infected pathogen remarkably. This study suggests our discovered inhibitors can be further developed as novel anti-MTB therapeutics targeting AHAS.

In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound 9f exerts the most potency, with IC(50) value of 0.013, 0.001, and 0.09 μM against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC(50) = 0.0014 μM, H5N1 IC(50) = 0.012 μM, H1N1 IC(50) = 0.001 μM). Pharmacokinetic studies of compound 9f in rats showed a much longer plasma half-life (t(1/2)) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents.

Design technology co-optimization (DTCO) is the term used to describe the process of deriving a competitive technology definition out of a number of increasingly complex trade-offs. DTCO is not a specific approach or methodology, but rather a commitment to closer collaboration between designers and process engineers born out of necessity to maintain value in semiconductor scaling. This paper aims to clarify this abstract concept through a series of examples encountered in scaling a logic cell from the N14 to the N3 technology node.

The fabrication of three-dimensional (3D) diamond photonic crystals with controllable nanoroughness (≤120 nm) on the surface from epoxy-functionalized cyclohexyl polyhedral oligomeric silsesquioxanes (POSS) is reported. The nanoroughness is generated on the 3D network due to microphase separation of the polymer chain segments in a nonsolvent during the rinsing step in holographic lithography process. The degree of roughness can be tuned by the crosslinking density of the polymer network, which is dependent on the loading of photoacid generators, the exposure dosage, and the choice of developer and rinsing solvent. Because the nanoroughness size is small, it does not affect the photonic band gap position of the photonic crystal in the infrared region. The combination of periodic microstructure and nanoroughness, however, offers new opportunities to realize superhydrophobicity and enhanced dye adsorption in addition to the photon management in the 3D photonic crystal.

To construct a reliable computational model for the classification of agonists and antagonists of 5-HT(1A) receptor.Support vector machine (SVM), a well-known machine learning method, was employed to build a prediction model, and genetic algorithm (GA) was used to select the most relevant descriptors and to optimize two important parameters, C and r of the SVM model. The overall dataset used in this study comprised 284 ligands of the 5-HT(1A) receptor with diverse structures reported in the literatures.A SVM model was successfully developed that could be used to predict the probability of a ligand being an agonist or antagonist of the 5-HT(1A) receptor. The predictive accuracy for training and test sets was 0.942 and 0.865, respectively. For compounds with probability estimate higher than 0.7, the predictive accuracy of the model for training and test sets was 0.954 and 0.927, respectively. To further validate our model, the receiver operating characteristic (ROC) curve was plotted, and the Area-Under-the-ROC- Curve (AUC) value was calculated to be 0.883 for training set and 0.906 for test set.A reliable SVM model was successfully developed that could effectively distinguish agonists and antagonists among the ligands of the 5-HT(1A) receptor. To our knowledge, this is the first effort for the classification of 5-HT(1A) receptor agonists and antagonists based on a diverse dataset. This method may be used to classify the ligands of other members of the GPCR family.

Background Sepsis management guidelines endorse use of biomarkers to support clinical assessment and treatment decisions in septic patients. The impact of biomarkers on improving patient outcomes remains uncertain. Methods Retrospective observational study of adult sepsis discharges between January 1, 2012, and December 31, 2015, from Premier Healthcare Database hospitals. Sepsis was defined by an All Patients Refined Diagnosis-Related Group code of 720 (septicemia and disseminated infections). Use of four biomarker strategies was evaluated based on hospital records: (i) >1 procalcitonin (PCT), (ii) 1 PCT, (iii) no PCT but ≥1 C-reactive protein (CRP) and/or lactate and (iv) no sepsis biomarkers. Associations between biomarker use and clinical and cost outcomes were examined. The primary outcome was impact of biomarker strategy on hospital costs per day. Results Among 933,591 adult sepsis discharges during the study period, 731,392 (78%) had biomarker tests ordered. In multivariable analyses, discharges with >1 PCT had higher hospital costs per day ($1,904; 95% confidence interval [CI] $1,896–$1,911) compared with discharges with no sepsis biomarkers ($1,606; 95% CI $1,658–$1,664). Discharges with >1 PCT also had greater illness severity and antimicrobial exposure compared with other biomarker-use groups. The adjusted odds of dying during hospital stay compared with being discharged were significantly lower for sepsis discharges with >1 PCT (0.64; 95% CI 0.61–0.67) and 1 PCT (0.88; 95% CI 0.85–0.91) compared with no sepsis biomarker use. The proportion of discharges with ≥1 PCT increased almost six-fold during the study; use of other biomarkers remained constant. Conclusions Between 2012 and 2015, PCT use among sepsis discharges increased six-fold while lactate and CRP use remained unchanged. PCT use was associated with decreased odds of in-hospital mortality but increased hospital costs per day. Serial biomarker monitoring may be associated with improved patient outcomes in the most critically ill septic patients.

The fabrication of 3D diamond-like silicon-oxycarbide and silicon-carbide high-temperature ceramic photonic crystals has been achieved by a strategy involving (1) the use of four-beam interference lithography (IL) to construct a patterned silsesquioxane (POSS) template and (2) infiltration of the polymeric allylhydridopolycarbosilane (AHPCS) silicon-carbide precursor into the patterned POSS template followed by high temperature ceramic conversion and HF etching. Energy-dispersive X-ray mapping analysis and Fourier transform infrared (FT-IR) studies suggested that the 3D ceramic photonic crystals formed at 1100 °C were SiC-like silicon oxycarbide. Additional thermal treatment at 1300 °C in vacuo resulted in the carbothermic reduction of the 3D silicon-oxycarbide to form 3D β-SiC with less than 10% shrinkage in the (111) plane and [111] direction, respectively. The reflectivities of the inverse 3D ceramic photonic crystals obtained at different stages were characterized by FT-IR in the [111] direction. Both...

We fabricated diamond-like microstructures from epoxy-functionalized cyclohexyl polyhedral oligomeric silsesquioxanes (POSS) through four-beam interference lithography. The 3D structure was maintained when calcined at a temperature up to 1100 degrees C, and crack-free samples over a large area ( approximately 5 mm in diameter) were obtained when the POSS films were heated at 500 degrees C under an Ar environment or treated with a low intensity oxygen plasma. In the latter, the volume fraction of the 3D porous structures could be fine-tuned by plasma etching time and power. Both Fourier transform infrared (FT-IR) spectroscopy and energy-dispersive X-ray (EDX) spectroscopy analysis suggested that the presence of carbon materials in the films enhanced the crack resistance of 3D POSS structures treated under Ar or oxygen plasma. Since POSS and its derivatives could be easily removed by HF solution at room temperature, we demonstrated high fidelity replication of the 3D porous structures to biocompatible poly(glycidyl methacrylate) (PGMA) and elastomeric poly(dimethylsiloxane) (PDMS). Importantly, the whole fabrication process (template fabrication, infiltration, and removal) was carried out at room temperature. Finally, we illustrated the application of 3D PDMS film as a reversible and repeatable color-changing, flexible photonic crystal.

Cu2O–ZnO composite opal was fabricated by electrodeposition using ZnO inverse opal as template. The photonic stop band of the composite opal can be observed from the UV–Vis spectrum, which indicates that the Cu2O filled into ZnO inverse opal did not destroy its three-dimensional (3D) ordered structure. Due to the multiple scattering in the 3D ordered structure, the absorption and photoluminescence (PL) are stronger in Cu2O–ZnO composite opal than those in a Cu2O/ZnO bilayer film and a Cu2O/ITO film without 3D ordered structure. The remaining ZnO inverse opal in Cu2O–ZnO composite opal enhances the photoluminescence measured in back geometry while it suppresses that in front geometry.

To fabricate a photonic crystal with large and complete photonic bandgap, it often requires backfilling of high index inorganic materials into a 3D polymer template. However, the pore network may become disconnected before the template is completely filled in a conformal coating process, which, therefore, limits the achievable maximum bandgap in the 3D photonic crystals. Here, we demonstrate nearly complete filling of the holographically patterned, diamond-like polymer templates with titania sol−gel through the electrodeposition method. The deposition proceeded in two stages: a thin titania seed layer (∼55 nm thick) was conformally coated on the surface of the polymer template at the early stage of electrodeposition, after which the deposition occurred preferentially from the template bottom layer at a rate of ∼0.4 µm/min. After preannealing and a slow ramping rate to 500 °C to remove the polymer template, an inverse 3D anatase titania crystal was obtained without pattern collapse. The measurement of film...

Mathematical and computational multiscale models are becoming increasingly important investigative tools in developmental biological research. During certain developmental processes cells that start out as independent entities interact to form multicellular structures. Cells of the embryonic vertebrate limb in high-density culture undergo chondrogenic pattern formation, which results in the formation of regularly-spaced "islands" of cartilage analogous to the cartilage primordia of the developing limb skeleton. In this article we describe a discrete, agent-based stochastic model for studying the behavior of limb bud precartilage mesenchymal cells in vitro. This model, like an earlier one, employs a biologically motivated reaction-diffusion process and cell-matrix adhesion as the basis of self-organizing pattern formation, but constitutes an improvement in biological fidelity over previous descriptions in that it is multiscale (i.e., cell and molecular dynamics occur on distinct scales), and the cells are represented as spatially extended objects. The improved model reproduces a broader set of results of the micromass culture system than the previous one and discloses multiple dynamical regimes that suggest new biological experiments.

Zn1−xCoxO (x = 0.05, 0.10) thin films are formed on silicon (100) substrates using pulsed laser deposition (PLD). The as-deposited films show ferromagnetic behaviors with Curie temperature higher than room temperature. Homogeneous film with a wurtzite structure has been formed when x = 0.05, whereas inhomogeneous film with a wurtzite phase mixed with cubic Co phase has been formed when x = 0.10. A significant increase in the magnetism is observed for the Zn0.90Co0.10O film because of the presence of Co clusters. After thermal annealing in O2, the carrier concentration of the Zn0.95Co0.05O film decreased three orders of magnitude from 1020 to 1017 cm− 3 and the film became paramagnetic. The electronic structure of Zn1−xCoxO (x = 0.125) was studied using full-potential linearized augmented plane-wave (FP-LAPW) method. Both the annealing experiments and calculation suggest that the double-exchange mechanism is the possible origin of the ferromagnetism in the Zn0.95Co0.05O film.