bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine profile, Treg/Th17 cell frequency changes during different posttransplantational time points in patients undergoing renal transplantation
Authors: Mortazavi Hamid , Soltani‐Zangbar Mohammad Sadegh , Eghbal‐Fard Shadi , Mehdizadeh Amir , Kamrani Amin , Chakeri‐Khiavi Forough , Kafil Hossein Samadi , Jadidi‐Niaragh Farhad , Rahimifar Shahrzad , Khosroshahi Hamid Tayebi , Yousefi Mehdi 
Published: April 2019

AbstractRenal transplantation is the best therapeutic approach for end stage renal dysfunction patients. There are direct relationships between proportions of Treg cells, Treg/Th17 cells ratio and secreted immunosuppressive cytokines with increased survival rate of the transplanted organ. The aim of this study was the measurement of Treg and Th17 cells frequency and their secreted cytokines. Ninety renal‐transplanted patients were divided in three groups based on times after transplantation (1–6 month, 6–36 month, and more than 3 years). Treg and Th17 cells frequency, expression level of their transcription factors and cytokines, and their secreted cytokines level were measured in these groups. Higher expression level of Interleukin (IL)‐10 and FoxP3 mRNA were observed in patients who had longer posttransplantation time. In contrast, lower mRNA expressions of IL‐6, IL‐17, IL‐23, and TGF‐β were observed in this group. Receptor γt showed no significant changes in studied groups. In addition IL‐10 level was increased and IL‐6, IL‐17, IL‐23, and TGF‐β level were decreased in patients who had longer posttransplantation time. Treg cells frequency was raised in mentioned group whereas no remarkable changes were observed in Th17 cell frequency. The present study declared that in stable renal transplantation, over time, the percentage of Treg cells and Treg/Th17 ration is increased. This increase in ratio induces a change in cytokine profile, resulting in an increased immunosuppressive cytokines such as IL‐10 leading to increase in the survival rate of the transplanted organ.
Biology of MarR family transcription factors and implications for targets of antibiotics against tuberculosis
Authors: Gong Zhen , Li Hui , Cai Yuhua , Stojkoska Andrea , Xie Jianping 
Published: April 2019

AbstractThe emergence of multidrug resistant (MDR) Mycobacterium tuberculosis strains and increased incidence of HIV coinfection fueled the difficulty in controlling tuberculosis (TB). MarR (multiple antibiotic resistance regulator) family transcription factors can regulate marRAB operon and are involved in resistance to multiple environmental stresses. We have summarized the structure, function, distribution, and regulation of the MarR family proteins, as well as their implications for novel targets for antibiotics, especially for tuberculosis.
Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials
Authors: van der Aar Ellen , Desrivot Julie , Dupont Sonia , Heckmann Bertrand , Fieuw Ann , Stutvoet Simone , Fagard Liesbeth , Van de Wal Karen , Helmer Eric 
Published: April 2019

AbstractGLPG1690 is a novel autotaxin inhibitor in development for the treatment of idiopathic pulmonary fibrosis (IPF). We report phase 1 studies investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GLPG1690 in healthy subjects. We performed a first‐in‐human randomized, double‐blind, placebo‐controlled trial of single (20, 60, 150, 300, 600, 1000, 1500 mg) and multiple (14 days: 150 mg twice daily; 600 and 1000 mg once daily) ascending oral doses of GLPG1690 (NCT02179502), and a randomized, open‐label, crossover relative bioavailability study to compare the PK of tablet and capsule formulations of GLPG1690 600 mg and to assess the effect of food on PK of the tablet formulation (NCT03143712). Forty and 13 subjects were randomized in the first‐in‐human and relative bioavailability studies, respectively. GLPG1690 was well tolerated, with no dose‐limiting toxicity at all single and multiple doses. GLPG1690 was rapidly absorbed and eliminated, with a median tmax and mean t1/2 of approximately 2 and 5 hours, respectively. GLPG1690 exposure increased with increasing dose (mean Cmax, 0.09‐19.01 µg/mL; mean AUC0‐inf, 0.501‐168 µg·h/mL, following single doses of GLPG1690 20‐1500 mg). PD response, evidenced by rapid reduction in plasma lysophosphatidic acid (LPA) C18:2 levels, increased with increasing GLPG1690 plasma levels, plateauing at approximately 80% reduction in LPA C18:2 at around 0.6 µg/mL GLPG1690. Tablet and capsule formulations had similar PK profiles, and no clinically significant food effect was observed when comparing tablets taken in fed and fasted states. The safety, tolerability, and PK/PD profiles of GLPG1690 support continued clinical development for IPF.
Comparative analysis of polyester hydrolysis activity among three lipolytic enzymes
Authors: Lin Hong , Mu Xiangduo , Huang Jianzhong , Jiang Hong , Niu Jinghong , Shu Zhengyu 
Published: April 2019

AbstractBackgroundBacillus subtilis lipase (BSL), Burkholderia sp. lipase (BCL) and Ophiostoma piceae sterol esterase (OPE) represent three typical structural features of lipolytic enzyme active sites. In this research, enzymatic characterization, especially polyester degradation activity, of these lipolytic enzymes was conducted, which might give clues to enzymatic degradation of polyester plastics in the future.ResultsThe optimum temperatures of BSL, BCL and OPE were 40, 40 and 35 °C, respectively. The optimum pH of BSL, BCL and OPE were 8.0, 8.0 and 7.5, respectively. All three lipolytic enzymes displayed a preference for esters with medium acyl chain length (C8–C10). The initiation reaction rates towards poly(ϵ‐caprolactone) hydrolysis catalyzed by BSL and BCL were 57 and 80 μg min−1 U−1, respectively. However, OPE showed very low activity towards poly(ϵ‐caprolactone) degradation. In contrast, OPE displayed high activity towards poly(vinyl acetate) degradation.ConclusionsPoly(ϵ‐caprolactone) could be enzymatically hydrolyzed using BSL and BCL, while poly(vinyl acetate) could only be enzymatically hydrolyzed using OPE. © 2019 Society of Chemical Industry
Probing demyelination and remyelination of the cuprizone mouse model using multimodality MRI
Authors: Wang Nian , Zhuang Jie , Wei Hongjiang , Dibb Russell , Qi Yi , Liu Chunlei 
Published: April 2019

BackgroundVarious studies by MRI exhibit that the corpus callosum (CC) is the most vulnerable to cuprizone administration, detecting the demyelination and remyelination process using different MRI parameters are, however, lacking.PurposeTo investigate the sensitivity of multiparametric MRI both in vivo and ex vivo for demyelination and remyelination.Study TypeProspective.Animal ModelA cuprizone mice model with an age‐matched control group (n = 5), 4‐week cuprizone exposure group followed by 9‐week on a normal diet (n = 6), and a 13‐week cuprizone exposure group (n = 6).Field Strength/Sequence3D gradient recalled echo, T2‐weighted, and diffusion tensor imaging (DTI) at 7.0T and 9.4T.AssessmentQuantification of DTI metrics, quantitative susceptibility mapping (QSM), and T2‐weighted imaging intensity in major white matter bundles.Statistical TestsNonparametric permutation tests were used with a cluster‐forming threshold as 3.09 (equivalent to P = 0.001), and the significant level as P = 0.05 with family‐wise correction.ResultsIn vivo susceptibility values increased from –11.7 to –0.7 ppb (P < 0.001) in CC and from –13.7 to –5.1 ppb (P < 0.001) in the anterior commissure (AC) after the 13‐week cuprizone exposure. Ex vivo susceptibility values increased from –25.4 to 7.4 ppb (P < 0.001) in CC and from –41.6 to –15.8 ppb (P < 0.001) in AC. Susceptibility values showed high variations to demyelination for in vivo studies (94.0% in CC, 62.8% in AC). Susceptibility values exhibited higher variations than radial diffusivity for ex vivo studies (129.1% vs. 28.3% in CC, 62.0% vs. 25.0% in AC). In addition to the differential susceptibility variations in different white matter tracts, intraregional demyelination variation was also present not only in CC but also in the AC area by voxel‐based analysis.Data ConclusionQSM is sensitive to the demyelination process of cuprizone exposure, which can be a complementary technique to conventional T2‐weighted images and DTI metrics.Level of Evidence: 2Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2019;50:1852–1865.
Seroepidemiology of respiratory syncytial virus in western India with special reference to appropriate age for infant vaccination
Authors: Arankalle Vidya A. , Kulkarni Ruta , Malshe Nandini , Palkar Sonali , Lalwani Sanjay , Mishra Akhilesh Chandra 
Published: April 2019

AbstractRespiratory syncytial virus (RSV) causes significant infant mortality worldwide and a vaccine may be available soon. This study determined age‐stratified anti‐RSV antibody positivity (enzyme‐linked immunosorbent assay [ELISA]) at Pune, India (cord blood‐85 years). Antibody positivity declined from 100% at birth to 71.3% (3 months), and 0.7% (6 months). A significant rise was noted at 15 months (16%), 16 to 24 months (64.5%) and 4 years (95.2%) with concomitant IgM‐anti‐RSV positivity indicative of recent infection. Antibody decline was higher in infants born preterm than full‐term. Across subsequent age groups including the elderly, antibody positivity was similar and comparable, suggestive of repeated exposure to the virus. Early protection/vaccination is essential for the infant population.
Carbamate Chemistry at Interfaces: Practical Considerations and Challenges of Studying Amine Surfactants
Authors: Hellström Anna‐Karin , Nordstierna Lars , Bordes Romain 
Published: April 2019

AbstractIt is well known that CO2 reacts with primary and secondary amines in aqueous solutions and forms carbamates. This reaction can have consequences when studying the self‐assembly of amines. In this article, we discuss the practical challenges when working with an alkyl Y‐shaped amine (Y12‐amine) and demonstrate how the formation of carbamate species influences the physicochemistry of the amine‐based surfactant. A drift in dynamic surface tension was observed for Y12‐amine at pH above pKa due to the reaction with the naturally occurring CO2 from the atmosphere. The drift in dynamic surface tension was more pronounced at pH above pKa, than at and below pKa. Furthermore, the drift in dynamic surface tension of Y12‐amine at pH 12 also affected the surfactant's critical micelle concentration (CMC). CMC of Y12‐amine determined by the pendant drop at the air/water interface was almost five times higher than at the N2/water interface. The latter result was in agreement with the one determined by monitoring the change in chemical shift of 1H NMR in a N2 atmosphere. Moreover, it was also shown that the adsorption of the amine at different interfaces influences carbamate formation.
Preparative isolation and purification of steroidal glycoalkaloid from the ripe berries of Solanum nigrum L. by preparative HPLC–MS and UHPLC–TOF‐MS/MS and its anti‐non‐small cell lung tumors effects in vitro and in vivo
Authors: Shi Fengqiang , Wang Caifang , Wang Lixue , Song Xueying , Yang Hua , Fu Qi , Zhao Wenhua 
Published: April 2019

AbstractOvercoming epidermal growth factor receptor resistance is a critical problem that needs to be solved in clinical practice. Drugs that downregulate the fatty acid synthase‐epidermal growth factor receptor will become novel treatments for non‐small cell lung cancer. Solanum nigrum, extracted with water at 4°C, shows strong cytotoxic activity and inhibits tumor growth in Lewis tumor bearing‐mice in a dose‐dependent manner. A novel active compound in S. nigrum, solaoiacid, was successfully separated and purified from S. nigrum by preparative high‐performance liquid chromatography with mass spectrometry and ultra high performance liquid chromatography with time‐of‐flight tandem mass spectrometry. The IC50 of solaoiacid on lung cancer cells was 2.3 µmol/L, which was significantly lower than that of the known steroidal glycoalkaloid. Label‐free proteomics and STRING Network analysis were used to identify significantly deregulated proteins in lung cancer cells that were treated with the fresh ripe fruit extracts of S. nigrum. S. nigrum regulates multiple signal pathways, including the epidermal growth factor receptor pathway. S. nigrum downregulated 24 main proteins with direct roles in fatty acid biosynthesis. Both S. nigrum and solaoiacid showed strong downregulation of the fatty acid synthase‐epidermal growth factor receptor and anti‐non‐small cell lung cancer effects, and thus will become a novel drug for the treatment of non‐small cell lung cancer.
Fast determination of 14 mycotoxins in chestnut by dispersive solid‐phase extraction coupled with ultra high performance liquid chromatography‐tandem mass spectrometry
Authors: Liang Jingyun , Dong Yanjie , Yuan Xuexia , Fan Lixia , Zhao Shancang , Wang Lei 
Published: April 2019

AbstractA dispersive solid‐phase extraction coupled with ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of T‐2 toxin, penicillic acid, fumonisins B1, B2, and B3, aflatoxins B1, B2, G1, and G2, ochratoxin A, deoxynivalenol, 3‐acetyldeoxynivalenol, 15‐acetyldeoxynivalenol, and zearalenone in chestnut samples. The method was used to analyze 136 samples obtained from Shandong province in China. The mycotoxins were extracted using a dispersive solid‐phase extraction method and cleaned using an improved quick, easy, cheap, effective, rugged, and safe approach. The mycotoxins were then detected using a triple‐quadrupole mass spectrometer. The limits of detection and quantification ranged from 0.02 to 1 and 0.1 to 2 μg/kg, respectively. The recovery rates ranged from 74.2 to 109.5%, with relative standard deviations below 15%. A total of 71 samples were contaminated with seven mycotoxins at concentrations ranging from 1.2 to 105.5 μg/kg, with a number of samples exceeding the maximum limits set in the European regulations for mycotoxins in unprocessed chestnuts.
Preparation and Gas Separation Properties of Triptycene‐Based Microporous Polyimide
Authors: Li Fenfen , Zhang Caili , Weng Yunxuan 
Published: April 2019

AbstractPolyimides with intrinsic microporosity (PIM‐PIs) are widely regarded as one of the most promising next‐generation membrane materials to simultaneously achieve high permeability and selectivity. Despite the fact that tremendous microporous polyimides have been synthesized, only cost‐efﬁcient PIM‐PIs have the potential to be used in industrial applications. In this work, a PIM‐PI is prepared by using the commercial and inexpensive planar pyromellitic dianhydride (PMDA) as the dianhydride monomer, and 2,6‐diaminotriptycene as the diamine monomer. The CO2 permeability of PMDA‐DAT is ≈23‐fold higher than that of Kapton, one of the commercially available polyimide membranes also made from PMDA, and with almost the same CO2/CH4 selectivity. In addition, no plasticization phenomenon is observed for PMDA‐DAT membrane even at a CO2 pressure up to 15 atm. The good plasticization resistance performance of PMDA‐DAT can be mainly attributed to the formation of pseudo‐physical crosslinking by interlocking and π–π interactions in triptycene moieties.
Solution‐Processable Conductive Organics via Anion‐Induced n‐Doping and Their Applications in Organic and Perovskite Solar Cells
Authors: Yan Kangrong , Li Chang‐Zhi 
Published: April 2019

AbstractThe essential challenge for accessing high‐performance organic optoelectronics strongly relies on how to enable organic materials with high charge transport capabilities. This short review gives an elucidation of the mild n‐doping that occurs between Lewis base anions and n‐semiconductors, as well as their extension to develop solution‐processable conductive interlayers for organic and perovskite solar cells.
Deletion of Prl7d1 causes placental defects at mid‐pregnancy in mice
Authors: Zhang Qiong , Hao Jie , Li Gang 
Published: April 2019

AbstractProlactin family 7, subfamily d, member 1 (Prl7d1), a member of the expanding prolactin family, is mainly expressed in the placental junctional zone (including trophoblast giant cells and spongiotrophoblast cells) with peak expression observed at 12 days postcoitum (dpc) in mice. Previous studies have shown that PRL7D1 is a key mediator of angiogenesis in vitro; however, its physiological roles in placental development in vivo have not been characterized. To address this issue, we deleted Prl7d1 in mice and demonstrated that its absence results in reduced litter size and fertility. Histologically, Prl7d1 mutants exhibited striking placental abnormalities at 12.5 dpc, including a reduction in the proportion of labyrinth layers and a significant increase in decidual natural killer cells, glycogen trophoblasts, and trophoblast giant cells in the junctional zone. Moreover, placentas from Prl7d1‐null mice displayed a thickened decidual spiral artery. Notably, these negative effects were more pronounced in male fetuses. Further RNA‐sequencing analysis showed that Prl7d1 deletion results in significant differences in the placental transcriptome profile between the two sexes of fetuses. Together, this study demonstrates that Prl7d1 possesses antiangiogenic properties in deciduas and inhibits the development of junctional zone, which potentially alters the functional capacity of the placenta to support optimal fetal growth. Moreover, of note, the role of Prl7d1 in the placenta is regulated in a fetal sex‐specific manner.
Abnormal Metabolic Phenotypes Among Urban Chinese Children: Epidemiology and the Impact of DXA‐Measured Body Composition
Authors: Chen Fangfang , Liu Junting , Yan Yinkun , Mi Jie ,   the China Child and Adolescent Cardiovascular Health (CCACH) Study Group
Published: April 2019

ObjectiveThis study aimed to describe the prevalence rates of abnormal metabolic phenotypes among urban Chinese children and to explore the impact of body composition as measured by dual‐energy x‐ray absorptiometry (DXA) on metabolic disorders.MethodsA total of 7,926 children aged 6 to 17 years from seven cities across China were involved. Metabolically unhealthy was defined as having ≥ 2 risk factors (elevated blood pressure, high triglyceride levels, low levels of high‐density lipoprotein cholesterol, and impaired fasting glucose [IFG]). Abnormal metabolic phenotypes were defined as metabolically unhealthy with normal weight (MUNW) and metabolically healthy with overweight or obesity (MHO).ResultsOverall prevalence rates of MUNW and MHO were 10.6% and 15.3%, respectively. The prevalence of MUNW increased with age in boys, whereas the prevalence in girls was statistically higher in 11‐ to 15‐year‐olds than in other age groups. The prevalence of MHO decreased with age in both genders. Among children with normal weight, the levels of body composition indices were positively correlated with metabolically unhealthy phenotype. Fat‐free mass had a protective effect on IFG in children with normal weight. Among children with overweight or obesity, body composition was related to elevated blood pressure and dyslipidemia but not to IFG.ConclusionsThe prevalence rates of abnormal metabolic phenotypes differed between genders and ages. Body composition could partly explain the different metabolic phenotypes at the same BMI status among children.
Curative‐intent radiotherapy for pediatric osteosarcoma: The St. Jude experience
Authors: Tinkle Christopher L. , Lu Jason , Han Yuanyuan , Li Yimei , McCarville Beth M. , Neel Michael D. , Bishop Michael W. , Krasin Matthew J. 
Published: April 2019

AbstractBackgroundRadiation therapy (RT) confers local tumor control and survival advantages in some patients with osteosarcoma, yet pediatric and adolescent and young adult (AYA) population studies are limited.MethodsTwenty‐eight patients treated with curative‐intent RT (median dose, 59.4 Gy; range, 40‐76 Gy) at our institution from 1990 to 2017 were retrospectively identified. Cumulative incidence (CIN) of local failure (LF) was estimated by Gray's method and overall survival (OS) by the Kaplan‐Meier method. Competing‐risk regression and Cox proportional hazards models determined predictors of outcome. Toxicity was reported according to CTCAE v4.0.ResultsWith a median follow‐up of 99.1 months in living patients, nine patients (32.1%) developed LF. Estimated CINs of LF with competing risk of death at 5 years for the entire cohort, patients at initial diagnosis (n = 16), and recurrent/refractory patients (n = 12) were 32.7% (95% CI, 16.0‐50.5%), 25.0% (95% CI, 7.3‐48.0%), and 43.8% (95% CI, 13.6‐71.0%), respectively (P  =  0.31). Estimated 5‐year OS was 42.6% (95% CI, 23.2‐62.0%), 54.6% (95% CI, 29.5‐79.6%), and 24.3% (95% CI, 0‐52.2%), respectively (P  =  0.15). No clinicopathologic features were significantly associated with LF, yet lack of chemotherapy or metastasis at the time of RT was independent significant prognostic factors of decreased OS. Eleven patients experienced RT‐related morbidity, with two grade 3 toxicities and no grade 4/5 events.ConclusionsCurative‐intent RT in pediatric and AYA patients was well tolerated and achieved a local tumor control rate of 75% in patients with primary disease. Local control rates were similar to those in primarily adult studies, with similar or lower doses.
Treatment of advanced pediatric renal cell carcinoma
Authors: Ambalavanan Manoj , Geller James I. 
Published: April 2019

AbstractBackgroundPediatric renal cell carcinoma (pRCC) is the second most common renal malignancy of childhood; however, treatment data for advanced disease is lacking.MethodsA retrospective analysis of pRCC patients (age < 21 years at diagnosis) treated between 2000 and 2015 at Cincinnati Children's Hospital Medical Center was undertaken, with specific focus on medical therapies, accompanied by a detailed literature review.ResultsTwenty‐four patients (median age = 15 years) were identified; 11 were female. Past history of kidney pathology (4) and prior hematologic/oncologic diagnoses (5) were common associated findings. Translocation morphology RCC (tRCC) was the most common subtype (16; 64%), followed by papillary (6; 24%), clear cell renal cell carcinoma (ccRCC) (1), and chromophobe (1). The TNM stage distribution was I (8; 33%), II (2; 8%), III (3; 13%), and IV (11; 46%). Eleven patients with stage IV disease all had tRCC and received medicinal anticancer therapies, the most common being antiangiogenic (10), conventional chemotherapy (8), mTOR inhibition (7), and immunotherapy (3). Four patients also received small‐port radiotherapy. The mean time to progression (TTP) was longest for axitinib (n = 2; TTP = 7.8 m; range 5.5‐10 m) and sunitinib (n = 6; TTP = 4.7 m; range 0.3–12 m). Overall, 20 cases of pediatric RCC who received RCC‐directed medicinal therapy with outcome data have been previously reported.ConclusionsFor patients with unresectable pRCC requiring systemic therapy, available data are scarce. Data herein support an increased TTP with antiangiogenic therapy in tRCC supporting a formal study of antiangiogenic therapies through multicooperative‐group collaboration.
IRF4 translocation status in pediatric follicular and diffuse large B‐cell lymphoma patients enrolled in Children's Oncology Group trials
Authors: Chisholm Karen M. , Mohlman Jeffrey , Liew Michael , Termuhlen Amanda , Cairo Mitchell S. , Gross Thomas G. , Perkins Sherrie L. , Miles Rodney R. 
Published: April 2019

AbstractLarge B‐cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Both cases had strong, diffuse IRF4/MUM1 immunohistochemical staining, which may be a pathologic clue to the diagnosis. Reclassification of these cases may have prognostic and therapeutic implications.