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https://www.readbyqxmd.com/read/29028616/simultaneous-determination-of-a-novel-c-met-axl-dual-target-small-molecule-inhibitor-bpi-9016m-and-its-metabolites-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry-application-in-a-pharmacokinetic-study-in-chinese-advanced-solid-tumor-patients
#1
Xinge Cui, Xin Zheng, Ji Jiang, Fenlai Tan, Lieming Ding, Pei Hu
BPI-9016M is a novel dual-target small-molecule inhibitor targeting c-Met and AXL, which was developed by Betta Pharmaceuticals Co., Ltd (Hangzhou, China). It has great potential in the treatment of advanced cancer. A high throughput quantitation method, based on liquid chromatography-tandem mass spectrometry, was developed and validated for the simultaneous determination of BPI-9016M and its main metabolite, M1 and M2-2, in human plasma with a sample preparation method of precipitation of protein. Liquid chromatographic separation was performed with a gradient elution of formic acid-10mM ammonium acetate aqueous solution (1:1000, v/v) and acetonitrile at a flow rate of 0...
October 8, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29018070/hypothermic-oxygenated-machine-perfusion-hope-for-orthotopic-liver-transplantation-of-human-liver-allografts-from-extended-criteria-donors-ecd-in-donation-after-brain-death-dbd-a-prospective-multicentre-randomised-controlled-trial-hope-ecd-dbd
#2
Zoltan Czigany, Wenzel Schöning, Tom Florian Ulmer, Jan Bednarsch, Iakovos Amygdalos, Thorsten Cramer, Xavier Rogiers, Irinel Popescu, Florin Botea, Jiří Froněk, Daniela Kroy, Alexander Koch, Frank Tacke, Christian Trautwein, Rene H Tolba, Marc Hein, Ger H Koek, Cornelis H C Dejong, Ulf Peter Neumann, Georg Lurje
INTRODUCTION: Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts...
October 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28988860/theta-phase-synchronization-is-the-glue-that-binds-human-associative-memory
#3
Andrew Clouter, Kimron L Shapiro, Simon Hanslmayr
Episodic memories are information-rich, often multisensory events that rely on binding different elements [1]. The elements that will constitute a memory episode are processed in specialized but distinct brain modules. The binding of these elements is most likely mediated by fast-acting long-term potentiation (LTP), which relies on the precise timing of neural activity [2]. Theta oscillations in the hippocampus orchestrate such timing as demonstrated by animal studies in vitro [3, 4] and in vivo [5, 6], suggesting a causal role of theta activity for the formation of complex memory episodes, but direct evidence from humans is missing...
October 4, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28984053/ten-year-immune-persistence-and-safety-of-the-hpv-16-18-as04-adjuvanted-vaccine-in-females-vaccinated-at-15-55%C3%A2-years-of-age
#4
Tino F Schwarz, Andrzej Galaj, Marek Spaczynski, Jacek Wysocki, Andreas M Kaufmann, Sylviane Poncelet, Pemmaraju V Suryakiran, Nicolas Folschweiller, Florence Thomas, Lan Lin, Frank Struyf
Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety...
October 5, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28977026/infants-predict-expressers-cooperative-behavior-through-facial-expressions
#5
Toshinori Kaneshige, Etsuko Haryu
This study investigated infants' ability to use facial expressions to predict the expressers' subsequent cooperative behavior. To explore this problem, Experiment 1 tested 10- and 14-month-olds (N = 16, respectively) by using a violation-of-expectation procedure. In the experiment, all infants were first familiarized with two models, one with a happy facial expression and the other with an angry expression. They were also familiarized with an event in which a duck puppet tried to open a box but failed. During the test phase, infants in the helping condition saw two test scenes; one in which the happy model helped the duck open the box, and the other in which the angry model helped the duck...
2017: PloS One
https://www.readbyqxmd.com/read/28972130/the-role-of-oscillatory-phase-in-determining-the-temporal-organization-of-perception-evidence-from-sensory-entrainment
#6
Luca Ronconi, David Melcher
Recent behavioural, neuroimaging and neurophysiological studies have renewed the idea that the information processing within different temporal windows is linked to the phase and/or frequency of the ongoing oscillation, predominantly in the theta/alpha band (∼4-7 and 8-12 Hz). However, being correlational in nature, this evidence might reflect a non-functional by-product rather than a causal role. A more direct link can be shown with methods that manipulate oscillatory activity. Here, we used audio-visual entrainment at different frequencies in the pre-stimulus period of a temporal integration/segregation task...
October 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28971257/nitrogen-doped-carbon-quantum-dots-as-a-fluorescence-probe-combined-with-magnetic-solid-phase-extraction-purification-for-analysis-of-folic-acid-in-human-serum
#7
Meng Wang, Yang Jiao, Chunsheng Cheng, Jianhao Hua, Yaling Yang
A novel and sensitive method based on nitrogen-doped carbon quantum dots as a fluorescence probe coupled with magnetic solid-phase extraction (MSPE) purification for analysis of folic acid (FA) in human serum samples has been established for the first time. In the developed system, magnetic nanoparticles coated with hexanoic acid (Fe3O4@C6) were synthesized by a one-step chemical co-precipitation method with good magnetic properties and dispersibility for sample purification, and it is better to be separated from the sample...
October 2, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28967708/assessment-of-safety-tolerability-pharmacokinetics-and-pharmacological-effect-of-orally-administered-cort125134-an-adaptive-double-blind-randomized-placebo-controlled-phase-1-clinical-study
#8
Hazel Hunt, Kirsteen Donaldson, Mark Strem, Vanessa Zann, Pui Leung, Suzanne Sweet, Alyson Connor, Dan Combs, Joseph Belanoff
CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts...
October 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28967640/endometrial-stromal-cells-isolation-expansion-morphological-and-functional-properties
#9
A V Zlatska, A E Rodnichenko, O S Gubar, D O Zubov, S N Novikova, R G Vasyliev
AIM: We aimed to study biological properties of human endometrial stromal cells in vitro. MATERIALS AND METHODS: The endometrium samples (n = 5) were obtained by biopsy at the first phase of the menstrual cycle from women with endometrial hypoplasia. In all cases, a voluntary written informed consent was obtained from the patients. Endometrial fragments were dissociated by enzymatic treatment. The cells were cultured in DMEM/F12 supplemented with 10% FBS, 2 mМ L-glutamine and 1 ng/ml FGF-2 in a multi-gas incubator at 5% CO2 and 5% O2...
September 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28963724/the-anti-cd6-antibody-itolizumab-provides-clinical-benefit-without-lymphopenia-in-rheumatoid-arthritis-patients-results-from-a-6-month-open-label-phase-i-clinical-trial
#10
Pedro C Rodríguez, Dinorah M Prada, Ernesto Moreno, Lazaro E Aira, Claudino Molinero, Ana M Lopez, Jorge A Gómez, Isabel M Hernandez, Jose P Martinez, Yusimi Reyes, Joel M Milera, Maria V Hernandez, Roberto Torres, Yisel Avila, Yinet Barrese, Carmen Viada, Enrique Montero, Patricia Hernández
Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in RA patients. The current phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous DMARD therapy. Twenty one subjects were enrolled in four dose groups (0.1, 0.2, 0.4 and 0.8 mg/kg). Efficacy endpoints including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and Disease Activity Score in 28 joints (DAS28) were monitored at baseline and at specific time points over a 10-week follow-up period...
September 30, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28958504/rilotumumab-plus-epirubicin-cisplatin-and-capecitabine-as-first-line-therapy-in-advanced-met-positive-gastric-or-gastro-oesophageal-junction-cancer-rilomet-1-a-randomised-double-blind-placebo-controlled-phase-3-trial
#11
Daniel V T Catenacci, Niall C Tebbutt, Irina Davidenko, André M Murad, Salah-Eddin Al-Batran, David H Ilson, Sergei Tjulandin, Evengy Gotovkin, Boguslawa Karaszewska, Igor Bondarenko, Mohamedtaki A Tejani, Anghel A Udrea, Mustapha Tehfe, Ferdinando De Vita, Cheryl Turkington, Rui Tang, Agnes Ang, Yilong Zhang, Tien Hoang, Roger Sidhu, David Cunningham
BACKGROUND: Rilotumumab is a fully human monoclonal antibody that selectively targets the ligand of the MET receptor, hepatocyte growth factor (HGF). We aimed to assess the efficacy, safety, and pharmacokinetics of rilotumumab combined with epirubicin, cisplatin, and capecitabine, and to assess potential biomarkers, in patients with advanced MET-positive gastric or gastro-oesophageal junction adenocarcinoma. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study was done at 152 centres in 27 countries...
September 25, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28954784/a-first-in-human-phase-1-study-of-the-anti-cancer-stem-cell-agent-ipafricept-omp-54f28-a-decoy-receptor-for-wnt-ligands-in-patients-with-advanced-solid-tumors
#12
Antonio Jimeno, Michael S Gordon, Rashmi Chugh, Wells Messersmith, David S Mendelson, Jakob Dupont, Robert J Stagg, Ann M Kapoun, Lu Xu, Shailaja Uttamsingh, Rainer Brachmann, David C Smith
PURPOSE: Wnt signaling is implicated in tumor cell de-differentiation and cancer stem cell function. Ipafricept (OMP-54F28) is a first-in-class recombinant fusion protein with the extracellular part of human Frizzled 8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands. This trial evaluated ipafricept in patients with solid tumors. EXPERIMENTAL DESIGN: A 3+3 design was used; ipafricept was given intravenously every 3 weeks. Objectives were determination of dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy...
September 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28951841/study-on-pharmacokinetics-and-tissue-distribution-of-single-dose-oral-tryptanthrin-in-kunming-mice-by-validated-reversed-phase-high-performance-liquid-chromatography-with-ultraviolet-detection
#13
Xiaoyan Zhang, Jie Xia, Wenjing Zhang, Yao Luo, Wenbo Sun, Wei Zhou
BACKGROUND: Tryptanthrin is a major active constituent of several Chinese herbal plants, such as Isatidis radix. Tryptanthrin had been demonstrated to have several beneficial pharmacological effects in vitro for human diseases, including antitumor, anti-inflammatory and antibacteria activities. In contrast to the extensive in vitro investigations, the in vivo disposition process of tryptanthrin was explored limitedly. METHODS: In this study, the pharmacokinetics (PK) and tissue distribution of tryptanthrin in Kunming mice following a single oral dose of 80 mg/kg tryptanthrin were investigated for the first time...
September 2017: Integrative medicine research
https://www.readbyqxmd.com/read/28951551/detecting-a-surprisingly-low-transmission-distance-in-the-early-phase-of-the-2009-influenza-pandemic
#14
Valentina Marziano, Andrea Pugliese, Stefano Merler, Marco Ajelli
The spread of the 2009 H1N1 influenza pandemic in England was characterized by two major waves of infections: the first one was highly spatially localized (mainly in the London area), while the second one spread homogeneously through the entire country. The reasons behind this complex spatiotemporal dynamics have yet to be clarified. In this study, we perform a Bayesian analysis of five models entailing different hypotheses on the possible determinants of the observed pattern. We find a consensus among all models in showing a surprisingly low transmission distance (defined as the geographic distance between the place of residence of the infectors and her/his infectees) during the first wave: about 1...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28950833/alphavbeta3-integrin-expression-within-uterine-endometrium-in-unexplained-infertility-a-prospective-cohort-study
#15
Ahmed Elnaggar, Amr H Farag, Mohamed E Gaber, Mohamed Abdel Hafeez, Mohamed S Ali, Alaa M Atef
BACKGROUND: Implantation defect is one of these contributing factors for unexplained infertility. In the mid-luteal phase, when implantation is expected to happen, Integrins expression is remarkably increased. So, Integrins could potentially serve as markers for the frame of the window of implantation. αVβ3 integrin could have a role as a potential receptor for embryonic attachment. The aim of the current study is to investigate whether the women with unexplained infertility have a pattern of expression of endometrial αvβ3 integrin that could differ from those who have normal fertility or not...
September 26, 2017: BMC Women's Health
https://www.readbyqxmd.com/read/28947682/assessment-of-a-combined-gas-chromatography-mass-spectrometer-sensor-gc-mss-system-for-detecting-biologically-relevant-volatile-compounds-vcs
#16
Oliver Gould, Tomas Wieczorek, Ben P J de Lacy Costello, Raj Persad, Norman Ratcliffe
There have been a number of studies in which metal oxide sensors (MOS) have replaced conventional analytical detectors in gas chromatography systems. However, despite the use of these instruments in a range of applications including breath research the sensor responses (i.e. resistance changes w.r.t. concentration of VCs) remain largely unreported. This paper addresses that issue by comparing the response of a metal oxide sensor directly with a mass spectrometer (MS), whereby both detectors are interfaced to the same GC column using an s-swafer...
September 26, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28940154/elsulfavirine-first-global-approval
#17
Zaina T Al-Salama
Elsulfavirine (Elpida(®)) is a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) being developed by Viriom for the treatment and prevention of human immunodeficiency virus (HIV) infections. It is the prodrug of the active compound VM-1500A, a small molecule selective NNRTI, which prevents HIV replication. In June 2017, elsulfavirine received its first global approval in Russia for the treatment of HIV-1 infections in combination with other antiretroviral medicines. Other formulations of this drug are also being evaluated in preclinical and phase II studies for the treatment of HIV infections and/or pre-exposure and post-exposure prophylaxis...
September 23, 2017: Drugs
https://www.readbyqxmd.com/read/28929209/upper-urinary-tract-effects-after-irreversible-electroporation-ire-of-human-localised-renal-cell-carcinoma-rcc-in-the-irene-pilot-phase-2a-ablate-and-resect-study
#18
J J Wendler, M Pech, J Köllermann, B Friebe, S Siedentopf, S Blaschke, D Schindele, M Porsch, D Baumunk, J Jürgens, F Fischbach, J Ricke, M Schostak, M Böhm, U B Liehr
PURPOSE: Irreversible electroporation (IRE) is a new potential ablation modality for small renal masses. Animal experiments have shown preservation of the urine-collecting system (UCS). The purpose of this clinical study was to perform the first evaluation and comparison of IRE's effects on the renal UCS by using urinary cytology, magnetic-resonance imaging, and resection histology in men after IRE of pT1a renal-cell carcinoma (RCC). METHODS: Seven patients with biopsy-proven RCC pT1a cN0cM0 underwent IRE in a phase 2a pilot ablate-and-resect study (IRENE trial)...
September 19, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28927490/development-and-validation-of-an-analytical-method-readily-applicable-for-quality-control-of-tabebuia-impetiginosa-taheebo-ethanolic-extract
#19
Yan Jin, Kyung Min Jeong, Jeongmi Lee, Jing Zhao, Su-Young Choi, Kwang-Soo Baek
The dried inner bark of Tabebuia impetiginosa, known as taheebo or red lapacho, has numerous beneficial effects on human health. This study presents the first simple and reliable quantitative method that could serve for the QC of taheebo. The method uses LC–UV spectroscopy to determine the veratric acid (VA; 3,4-dimethoxybenzoic acid) content of taheebo extracts (TEs). Sample preparation entailed the dissolution of TE in methanol (MeOH), facilitated by ultrasonic radiation for 10 min. The optimized conditions included chromatographic separation on an Agilent Eclipse Plus C18 column (4...
September 19, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28926579/cervical-screening-with-primary-hpv-testing-or-cytology-in-a-population-of-women-in-which-those-aged-33-years-or-younger-had-previously-been-offered-hpv-vaccination-results-of-the-compass-pilot-randomised-trial
#20
RANDOMIZED CONTROLLED TRIAL
Karen Canfell, Michael Caruana, Val Gebski, Jessica Darlington-Brown, Stella Heley, Julia Brotherton, Dorota Gertig, Chloe J Jennett, Annabelle Farnsworth, Jeffrey Tan, C David Wrede, Philip E Castle, Marion Saville
BACKGROUND: Using primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplastic lesions and invasive cancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) compared to cytology, but no evaluation has been conducted in a population previously offered HPV vaccination. We aimed to assess colposcopy referral and CIN2+ detection rates for HPV-screened versus cytology-screened women in Australia's HPV-vaccinated population (by 2014, resident women ≤33 years had been age-eligible for HPV vaccination, with 3-dose uptake across age cohorts being about 50%-77%)...
September 2017: PLoS Medicine
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