bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxoplasma gondii excreted‐secreted antigens suppress Foxp3 via PI3K‐AKT‐mTOR signaling pathway
Authors: Chen Jinling , Hu Liang , Wang Jingjing , Cao Yangqing , Zhu Dandan , Chen Liuting , Duan Yinong 
Published: May 2019

AbstractToxoplasma gondii excreted‐secreted antigens (ESA) cause spontaneous abortion or fetal teratogenesis during the pregnancy in mice, especially in the early stage. Those adverse pregnancy outcomes are due to the deficit in regulatory T cells (Tregs). Forkhead box P3 (Foxp3), a critical transcription factor, modulates Tregs differentiation and its function. Besides, phosphatidylinositol 3‐kinase‐protein kinase B‐mammalian target of rapamycin (PI3K‐AKT‐mTOR) signaling network is implicated in interfering with Foxp3 induction. We previously demonstrated that ESA diminished the number of Tregs and inhibited its function. And ESA suppressed Foxp3 expression via the attenuation of transforming growth factor β RII/Smad2/Smad3/Smad4 pathway. The current study aimed to investigate whether the PI3K‐AKT‐mTOR signaling network is involved in Foxp3 downregulation induced by ESA. We found that ESA upregulated PI3K, P‐AKT, mTOR, and P‐mTOR. Knockdown of PI3K cooperated with ESA to restore Foxp3 expression mediated by ESA. This suppressive role of ESA on Foxp3 expression was abrogated by AKT inhibitor. In addition, neutralization of Toll‐like receptor 4 could restore the expression of Foxp3, PI3K, and its downstream effectors induced by ESA. Collectively, the findings indicated that ESA inhibited Foxp3 expression via the upregulation of PI3K‐AKT‐mTOR signaling pathway.
MRI‐based radiomics signature for tumor grading of rectal carcinoma using random forest model
Authors: He Bo , Ji Tao , Zhang Hong , Zhu Yun , Shu Ruo , Zhao Wei , Wang Kunhua 
Published: May 2019

AbstractThe present study aimed to construct prospective models for tumor grading of rectal carcinoma by using magnetic resonance (MR)‐based radiomics features. A set of 118 patients with rectal carcinoma was analyzed. After imbalance‐adjustments of the data using Synthetic Minority Oversampling Technique (SMOTE), the final data set was randomized into the training set and validation set at the ratio of 3:1. The radiomics features were captured from manually segmented lesion of magnetic resonance imaging (MRI). The most related radiomics features were selected using the random forest model by calculating the Gini importance of initial extracted characteristics. A random forest classifier model was constructed using the top important features. The classifier model performance was evaluated via receive operator characteristic curve and area under the curve (AUC). A total of 1,131 radiomics features were extracted from segmented lesion. The top 50 most important features were selected to construct a random forest classifier model. The AUC values of grade 1, 2, 3, and 4 for training set were 0.918, 0.822, 0.775, and 1.000, respectively, and the corresponding AUC values for testing set were 0.717, 0.683, 0.690, and 0.827 separately. The developed feature selection method and machine learning‐based prediction models using radiomics features of MRI show a relatively acceptable performance in tumor grading of rectal carcinoma and could distinguish the tumor subjects from the healthy ones, which is important for the prognosis of cancer patients.
Upregulation of AKT1 and downregulation of AKT3 caused by dysregulation of microRNAs contributes to pathogenesis of hemangioma by promoting proliferation of endothelial cells
Authors: Lu Shuo , Chen Lingling , Tang Li 
Published: May 2019

AbstractThis study aimed to verify the differentially expressed miRNAs (microRNAs) in hemangioma, and explore their roles in the pathogenesis of hemangioma in vivo and ex vivo. Real‐time polymerase chain reaction (PCR) and western blot were used to measure reported differentially expressed miRNAs and their potential targets. In‐silicon analysis and luciferase assay were conducted to find the target of miR‐15a and miR‐205. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay and flowcytometry were performed to examine the effect of dysregulation of miR‐15a and miR‐205 on the proliferation and apoptosis of endothelial cells. Among all candidate miRNAs, only miR‐205 level was significantly downregulated whereas miR‐15a was evidently upregulated in the hemangioma group. Accordingly, AKT3 was validated to be the direct target of miR‐15a and miR‐205. Using real‐time PCR, the level of AKT1 was much higher in hemangioma group, whereas level of AKT3 was much lower in the hemangioma group, and in general expression level of ATK was upregulated in the hemangioma group. Furthermore, the ATK1 level of cells transfected with miR‐205 mimics and ATK1 siRNA was substantially downregulated, and anti‐miR‐205 mimic significantly improved the level of AKT1, and meanwhile the level of ATK3 and PTEN were remarkably suppressed after transfection with miR‐15a mimics and ATK3 siRNA, whereas notably overexpressed after introduction of anti‐miR‐15a. And miR‐15a, AKT3 siRNA and anti‐miR‐205 evidently induced viability, and miR‐205, AKT1 siRNA, and anti‐miR‐15a obviously promoted apoptosis of cells.ConclusionmiR‐15a and miR‐205 had different expression in hemangioma, may be novel therapeutic targets in the treatment of hemangioma by targeting AKT3 and AKT1.
RECK suppresses interleukin‐17/TRAF3IP2‐mediated MMP‐13 activation and human aortic smooth muscle cell migration and proliferation
Authors: Mummidi Srinivas , Das Nitin A. , Carpenter Andrea J. , Yoshida Tadashi , Yariswamy Manjunath , Mostany Ricardo , Izadpanah Reza , Higashi Yusuke , Sukhanov Sergiy , Noda Makoto , Siebenlist Ulrich , Rector Randy S. , Chandrasekar Bysani 
Published: May 2019

AbstractSustained inflammation and matrix metalloproteinase (MMP) activation contribute to vascular occlusive/proliferative disorders. Interleukin‐17 (IL‐17) is a proinflammatory cytokine that signals mainly via TRAF3 Interacting Protein 2 (TRAF3IP2), an upstream regulator of various critical transcription factors, including AP‐1 and NF‐κB. Reversion inducing cysteine rich protein with kazal motifs (RECK) is a membrane‐anchored MMP inhibitor. Here we investigated whether IL‐17A/TRAF3IP2 signaling promotes MMP‐13‐dependent human aortic smooth muscle cell (SMC) proliferation and migration, and determined whether RECK overexpression blunts these responses. Indeed, IL‐17A treatment induced (a) JNK, p38 MAPK, AP‐1, NF‐κB, and CREB activation, (b) miR‐21 induction, (c) miR‐27b and miR‐320 inhibition, (d) MMP‐13 expression and activation, (e) RECK suppression, and (f) SMC migration and proliferation, all in a TRAF3IP2‐dependent manner. In fact, gain of TRAG3IP2 function, by itself, induced MMP‐13 expression and activation, and RECK suppression. Furthermore, treatment with recombinant MMP‐13 stimulated SMC migration in part via ERK activation. Importantly, RECK gain‐of‐function attenuated MMP‐13 activity without affecting its mRNA or protein levels, and inhibited IL‐17A‐ and MMP‐13‐induced SMC migration. These results indicate that increased MMP‐13 and decreased RECK contribute to IL‐17A‐induced TRAF3IP2‐dependent SMC migration and proliferation, and suggest that TRAF3IP2 inhibitors or RECK inducers have the potential to block the progression of neointimal thickening in hyperplastic vascular diseases.
Genome‐wide analysis reveals alcohol dehydrogenase 1C and secreted phosphoprotein 1 for prognostic biomarkers in lung adenocarcinoma
Authors: Shen Xiao‐Yan , Liu Xiao‐Ping , Song Cong‐Kuan , Wang Yu‐Jin , Li Sheng , Hu Wei‐Dong 
Published: May 2019

AbstractTo seek out novel promising biomarkers for predicting lung adenocarcinoma (LUAD) prognosis, we conducted this study. First, 279 upregulated and 37 downregulated differentially expressed genes were obtained from LUAD and para‐carcinoma tissues by the Affymetrix GeneChip Human Transcriptome Array. Then, we randomly classified samples of LUAD data set GSE31210 as training and testing sets in a 1:1 ratio. Alcohol dehydrogenase 1C (ADH1C) and secreted phosphoprotein 1 (SPP1) were finally identified correlating with the LUAD survival through least absolute shrinkage and selection operator penalized Cox proportion hazards regression model, and applied to build a 2‐gene signature related to prognosis in training set. Univariate and multivariable survival analyses suggested that overall survival (OS) and relapse‐free survival (RFS) in the 2‐gene signature low‐risk group were better than the high‐risk group. Kaplan–Meier curves proved that elevated ADH1C expression and reduced SPP1 expression were related to better OS and RFS. Besides, the SPP1 expressed higher in LUAD than para‐carcinoma tissues using quantitative reverse transcription polymerase chain reaction assay. Finally, the association between the two genes and clinicopathological parameters in 80 LUAD were analyzed, it is suggested that SPP1 was relevant to epidermal growth factor receptor mutation. These findings indicated that ADH1C and SPP1 might be novel promising biomarkers for predicting LUAD prognosis.
Pharmacokinetics of Lapatinib, a Nonrenally Cleared Drug, in Patients With End‐Stage Renal Disease on Maintenance Hemodialysis
Authors: Pai Sudhakar M. , Chaikin Philip , Berg Jolene Kay 
Published: May 2019

AbstractLapatinib, a tyrosine kinase inhibitor, is approved for the treatment of breast cancer. The literature shows that it is metabolized by CYP3A4 and eliminated predominantly (>90%) by the fecal route, with minimal (<2%) renal elimination in healthy subjects (dose of 250 mg); in cancer patients, renal elimination is minimal at therapeutic doses. For nonrenally cleared drugs, while there is ample evidence of pharmacokinetic alterations secondary to renal impairment‐induced effects on drug metabolizing enzymes and/or transporters, the effect of end‐stage renal disease (ESRD) on lapatinib pharmacokinetics has not been determined. Rather, as stated in the drug's label, the expectation is lack of effect of renal impairment on lapatinib pharmacokinetics based on its minimal renal elimination. The current report addresses this gap with pharmacokinetic data (obtained in a 1‐way drug interaction study) in ESRD patients (n = 11) on maintenance hemodialysis and compared with published data in 37 healthy subjects in 3 separate studies. Following a 250‐mg oral dose in ESRD patients, the median tmax was 3.0 hours, and geometric mean (95%CI) values for Cmax, AUCinf, and t1/2 were 349 ng/mL (245–499 ng/mL), 4410 ng·h/mL (2960–6580 ng·h/mL), and 14.8 hours (9.7–22.5 hours), respectively. These parameters approximated published values in healthy subjects and demonstrated that renal impairment and hemodialysis did not affect lapatinib pharmacokinetics. The results of the present study in this renally impaired population, the only such information available to date, support the drug's label and are valuable in view of the recognized difficulties in enrolling organ‐impaired patients in oncology trials.
Dapivirine vaginal ring for HIV prevention: modelling health outcomes, drug resistance and cost‐effectiveness
Authors: Glaubius Robert , Ding Yajun , Penrose Kerri J , Hood Greg , Engquist Erik , Mellors John W , Parikh Urvi M , Abbas Ume L 
Published: May 2019

AbstractIntroductionA vaginal ring containing dapivirine is effective for HIV prevention as pre‐exposure prophylaxis (PrEP). We evaluated the potential epidemiological impact and cost‐effectiveness of dapivirine vaginal ring PrEP among 22‐ to 45‐year‐old women in KwaZulu‐Natal, South Africa.MethodsUsing mathematical modelling, we studied dapivirine vaginal ring PrEP implementation, either unprioritized, or prioritized based on HIV incidence (≥3% per year), age (22 to 29 years) or female sex worker status, alongside the implementation of voluntary medical male circumcision and antiretroviral therapy scaled‐up to UNAIDS Fast‐Track targets. Outcomes over the intervention (2019 to 2030) and lifetime horizons included cumulative HIV infections, life‐years lived, costs and cost‐effectiveness. We assessed the incremental cost‐effectiveness ratios against the revealed willingness to pay ($500) and the standard (2017 per capita gross domestic product; $6161) cost‐effectiveness thresholds for South Africa.ResultsCompared to a reference scenario without PrEP, implementation of dapivirine vaginal ring PrEP, assuming 56% effectiveness and covering 50% of 22 to 29‐year‐old or high‐incidence women, prevented 10% or 11% of infections by 2030 respectively. Equivalent, unprioritized coverage (30%) prevented fewer infections (7%), whereas 50% coverage of female sex workers had the least impact (4%). Drug resistance attributable to PrEP was modest (2% to 4% of people living with drug‐resistant HIV). Over the lifetime horizon, dapivirine PrEP implementation among female sex workers was cost‐saving, whereas incidence‐based PrEP cost $1898 per life‐year gained, relative to PrEP among female sex workers and $989 versus the reference scenario. In a scenario of 37% PrEP effectiveness, PrEP had less impact, but prioritization to female sex workers remained cost‐saving. In uncertainty analysis, female sex worker PrEP was consistently cost‐saving; and over the lifetime horizon, PrEP cost less than $6161 per life‐year gained in over 99% of simulations, whereas incidence‐ and age‐based PrEP cost below $500 per life‐year gained in 61% and 49% of simulations respectively. PrEP adherence and efficacy, and the effectiveness of antiretroviral therapy for HIV prevention, were the principal drivers of uncertainty in the cost‐effectiveness of PrEP.ConclusionsDapivirine vaginal ring PrEP would be cost‐saving in KwaZulu‐Natal if prioritized to female sex workers. PrEP's impact on HIV prevention would be increased, with potential affordability, if prioritized to women by age or incidence.
Subversion of host immune responses by otopathogens during otitis media
Authors: Parrish James M , Soni Manasi , Mittal Rahul 
Published: May 2019

Abstract
Otitis media (OM) is one of the most common ear diseases affecting humans. Children are at greater risk and suffer most frequently from OM, which can cause serious deterioration in the quality of life. OM is generally classified into two main types: acute and chronic OM (AOM and COM). AOM is characterized by tympanic membrane swelling or otorrhea and is accompanied by signs or symptoms of ear infection. In COM, there is a tympanic membrane perforation and purulent discharge. The most common pathogens that cause AOM are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis whereas Pseudomonas aeruginosa and Staphylococcus aureus are commonly associated with COM. Innate and adaptive immune responses provide protection against OM. However, pathogens employ a wide arsenal of weapons to evade potent immune responses and these mechanisms likely contribute to AOM and COM. Immunologic evasion is multifactorial, and involves damage to host mucociliary tract, genetic polymorphisms within otopathogens, the number and variety of different otopathogens in the nasopharynx as well as the interaction between the host's innate and adaptive immune responses. Otopathogens utilize host mucin production, phase variation, biofilm production, glycans, as well as neutrophil and eosinophilic extracellular traps to induce OM. The objective of this review article is to discuss our current understanding about the mechanisms through which otopathogens escape host immunity to induce OM. A better knowledge about the molecular mechanisms leading to subversion of host immune responses will provide novel clues to develop effective treatment modalities for OM.
Survey of quality of life, phenotypic expression, and response to treatment in Krabbe leukodystrophy
Authors: Langan Thomas J. , Barczykowski Amy , Jalal Kabir , Sherwood Laura , Allewelt Heather , Kurtzberg Joanne , Carter Randy L. 
Published: May 2019

AbstractObjectivesTo develop a quality of life (QOL) survey for Krabbe disease (KD), and to thereby improve understanding of its phenotypic expression and response to treatment.MethodsThe survey, the Leukodystrophy Quality of Life Assessment (LQLA) and the Vineland Adaptive Behavior Scales were co‐administered to 33 patients or their caretakers. These included the phenotypes of early infantile KD (EIKD; 0‐6 months old at onset), late infantile cases (LIKD; 7‐12 months old at onset), and cases that emerged after 12 months old, late onset (LOKD). The sample included cases with and without stem cell transplantation (SCT). Reliability and concurrent validity were assessed for overall and subscale scores. Analysis of variance tested differences in QOL between phenotypes and transplant groups (none, pre‐, post‐symptom).ResultsGood concurrent validity with the Vineland was shown for total, communication, daily activity, social, and motor scales and good reliability was observed. LOKD cases had better communication skills than either EIKD or LIKD and better overall QOL than EIKD. Analyses of individual items showed that communication items, mostly, contributed significantly to phenotype differences. Presymptomatic SCT significantly improved QOL compared to postsymptomatic SCT or no treatment. Presymptomatically treated patients had near‐normal total scores.ConclusionsThe LQLA is valid and reliable. Despite small sample size, phenotypic demarcation was determined to be due mainly to differences in communication skills. There was a relative enhancement of QOL in LOKD patients, and in those who had presymptomatic SCT. These results apply to the current controversy about recommendations for newborn screening for this condition.
Prevalence, risk factors and clinical characteristics of respiratory syncytial virus–associated lower respiratory tract infections in Kelantan, Malaysia
Authors: Teck Kew Seih , Mac Guad Rhanye , Van Rostenberghe Amin Hans , Hua Gan Siew 
Published: May 2019

AbstractRespiratory syncytial virus (RSV) is a common pathogen affecting the respiratory tract in infants. To date, there is limited data on RSV occurrence in Malaysia especially in the northeast of Peninsular Malaysia which is significantly affected by the rainy (monsoon) season. This study aimed to determine the prevalence, risk factors (the presence of a male sibling and older school‐age siblings, parental education level, monthly income, chronic lung disease, immunocompromised, being a passive smoker, multipara, breastfeeding, prematurity, congenital heart disease, nursery attendance, and rainy season) as well as clinical manifestations of RSV in hospitalized infants and children with lower respiratory tract infection (LRTI). Patients' nasopharyngeal aspirates were tested for RSV antigen, questionnaires, and seasonal variations were used to assess RSV infection. Approximately 22.6% of children were infected with RSV; mean age 7.68 ± 5.45 months. The peak incidence of RSV as a causative agent for LRTI in infants was less than or equal to 1‐year old (83%) with approximately 50.5% of the affected children in the younger age group (6 months amd below). RSV infection was significantly but independently associated with the rainy season (odds ratio, 3.307; 95% confidence interval, 1.443‐3.688; P < 0.001). The infection was also associated (
P < 0.05) with a higher number of severe clinical courses, poor feeding, vomiting, increased need for medical care and a shorter mean duration of symptoms before hospital admission. Our study suggested administration of the passive prophylaxis for RSV to high‐risk infants during the rainy season in the months of October to January.
Synthesis and Properties of Novel Phenylenediamine Gemini Surfactants
Authors: Xu Hujun , Wang Chen , Lin Liangliang , Xu Jin 
Published: May 2019

AbstractIn the present work, a two‐step method was adopted to synthesize a series of novel Gemini surfactants using N,N‐dimethylalkyl amines (alkyl length = C12, C16 and C18), epichlorohydrin, and n‐phenyllenediamine as starting materials. The products were characterized using mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (1H NMR). Systematic experiments were conducted to evaluate their surface activity, foaming properties, and antibacterial performance. Results showed the critical micelle concentrations (CMC) of the C12‐based, C16‐based, and C18‐based phenylenediamine surfactants were 3.295 × 10−3, 2.532 × 10−4, and 3.140 × 10−4 mol L−1 at 298 K, respectively, with corresponding surface tension (γcmc) values of 28.24, 31.95, and 35.06 mN m−1 under the same conditions. The Gemini surfactants showed not only good surface activity and foaming properties, but also demonstrated good antimicrobial performance against Gram‐positive and Gram‐negative bacteria and fungi.
Optimization of heteroatom doped graphene oxide by deep eutectic solvents and the application for pipette‐tip solid‐phase extraction of flavonoids
Authors: Sun Liping , Deng Qilin , Zhu Tao 
Published: May 2019

AbstractIn order to improve the permeation and adsorption properties of graphene oxide, heteroatoms and deep eutectic solvent were introduced in this study. After being modified, the structural properties of graphene oxide were improved and the materials were applied to the determination of myricetin and rutin in tea sample by pipette‐tip solid‐phase extraction method. The materials were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X‐Ray diffractomer, energy dispersive spectroscopy, atomic force microscope, and specific surface area by Brunauer–Emmett–Teller N2 adsorption desorption analysis. Meanwhile, they were tested by static and dynamic adsorption. The result showed that the materials after modifying had better adsorption amount for myricetin and rutin than graphene oxide. The calibration graphs of myricetin and rutin in MeOH were linear over 0.10–500.00 µg/mL, and the limits of detection and quantification were in the range of 0.00546–0.0182 µg/mL and 0.00741–0.0247 µg/mL, respectively. A reliable analytical method was developed for recognition targets in tea sample by DES modified nitrogen‐doped graphene oxide with satisfactory extraction recoveries (myricetin 99.77%, rutin 98.14%). It was potential for the rapid purification of myricetin and rutin in tea sample combined with the pipette‐tip solid‐phase extraction.
Enhancing the hospitality customer experience of families with children on the autism spectrum disorder
Authors: Freund Daniela , Cerdan Chiscano Monica , Hernandez-Maskivker Gilda , Guix Mireia , Iñesta Ana , Castelló Montserrat 
Published: May 2019

AbstractThe purpose of this study is to examine intention to travel to accessible accommodations by families of children diagnosed with autism spectrum disorder (ASD), the influence of travel constraints (intrinsic, interactive, and environmental), the severity of disorder, and the families' strategies for coping with such constraints. A structured survey targeted at Spanish families (N = 117) indicated that the intrinsic dimension and the severity of disorder positively influence their intention to travel. The study contributes to extend knowledge about travel constraints related to accessible tourism and provides insights to accommodation providers on how to better enhance the customer experience of families travelling with a child diagnosed with ASD.