bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetic analysis of dutogliptin, a selective dipeptidyl peptidase‐4 inhibitor
Authors: Marier Jean‐Francois , Mouksassi Mohamad‐Samer , Gosselin Nathalie H. , Li Jianke 
Published: October 2013

AbstractDutogliptin is a selective dipeptidyl peptidase‐4 inhibitor shown to be efficacious and safe in patients with type 2 diabetes mellitus (T2DM). Population pharmacokinetic (PK) analysis of dutogliptin was performed based on data collected in 561 healthy subjects and patients with T2DM enrolled in Phase I and II studies to assess sources of variability and support dosing rationale. The effect of extrinsic (formulations, fed/fasting conditions, potential drug–drug interaction with metformin) and intrinsic (baseline characteristics, markers of renal function, renal impairment category, and disease status) covariates was evaluated using non‐linear mixed effect modeling. Plasma concentrations of dutogliptin were best fitted with a two‐compartment model with a first‐order rate constant of absorption (Ka) and a lag time. No differences were observed between healthy subjects and patients with T2DM. Apparent clearance (CL/F) and terminal elimination half‐life of dutogliptin were 176 L/h and 12.2 hours, respectively. Typical CL/F values in patients with mild and moderate renal impairment were 121 and 79 L/h, respectively. No drug–drug interaction was observed with metformin. These results suggest that a reduction in dosing from 400 to 200 mg daily is warranted in T2DM patients with moderate renal impairment. No dose adjustments were deemed necessary for other evaluated patient characteristics and coadministration with metformin.
Passive sampling in contaminated sediment assessment: Building consensus to improve decision making
Authors: Parkerton Thomas F , Maruya Keith A 
Published: October 2013

Abstract
Contaminated sediments pose an ongoing, pervasive, global challenge to environmental managers, because sediments can reflect a legacy of pollution that can impair the beneficial uses of water bodies. A formidable challenge in assessing the risks of contaminated sediments has been the elucidation and measurement of contaminant bioavailability, expressed as the freely dissolved concentration (Cfree) in interstitial water, which serves as a surrogate measure of the substances' chemical activity. Recent advances in passive sampling methods (PSMs) enable Cfree of sediment-associated contaminants to be quantified at trace levels, thereby overcoming current limitations of predictive models. As a result, PSMs afford the opportunity for a paradigm shift from traditional practice that can effectively reduce uncertainty in risk assessment and bolster confidence in the science used to support management of contaminated sediments. This paper provides a brief overview of the 5 subsequent papers in this series that review literature on PSM use in sediments for both organic and metal(loid) contaminants, outline the technical rationale for using PSMs as a preferred basis for risk assessment over conventional chemical analyses, describe practical considerations for and uncertainties associated with laboratory and field deployment of PSMs, discuss management application of PSMs, including illustrative case studies in which PSMs have been used in decision making, and highlight future research and communication needs. Integr Environ Assess Manag 2014;10:163–166. © 2013 SETAC
Key Points
Forty-five experts from around the world reached consensus on the utility and application of passive sampling methods that target Cfree for improved management of contaminated sediments. The objectives and highlights of subsequent papers included in this series that support this conclusion are briefly summarized.
A specific groove design for individualized healing in a canine partial sternal defect model by a polycaprolactone/hydroxyapatite scaffold coated with bone marrow stromal cells
Authors: Xuan Yiwen , Tang Hua , Wu Bin , Ding Xinyu , Lu Zhongyuan , Li Wei , Xu Zhifei 
Published: October 2013

AbstractThe reconstruction of sternal defects remains clinically challenging for thoracic surgeons. Here we aimed to explore the individualized reconstruction of partial sternal defects with new biodegradable material in a large animal model. We used the fused deposition modeling (FDM) technique to manufacture polycaprolactone/hydroxyapatite (PCL/HA) tissue scaffolds with individualized grooves to repair the sternal defect. The defects were surgically created in a sternocostal joint of eighteen Beagle dogs. The animals were separated into three groups (n = 6): Blank group, PCL/HA group, and PCL/HA/BMSCs group. Radiographic examination, histological, and histomorphometric analyses were performed to evaluate the result. In the blank group, the defect site couldn't maintain its original integrity due to no bone union. In the PCL/HA group and PCL/HA/BMSCs group, it was observed that the scaffolds retained their shapes without significant degradation at 12 weeks. Both groups could observe new bone‐union by radiographic and histological examination. And PCL/HA/BMSCs would be more mineralized tissue area at implant sites (p < 0.05). These results reveal that using the FDM technique to manufacture the PCL/HA scaffolds with specific grooves could repair the sternal defect satisfactorily. Furthermore the scaffolds with BMSCs‐seeded could enhance the amount of bone ingrowth and seemed to be more promising. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3401–3408, 2014.
Polymeric cryogels are biocompatible, and their biodegradation is independent of oxidative radicals
Authors: Shakya Akhilesh Kumar , Holmdahl Rikard , Nandakumar Kutty Selva , Kumar Ashok 
Published: October 2013

AbstractBiocompatibility and in vivo degradation are two important characteristics of cell scaffolds. We evaluated these properties for four different polymeric macroporous cryogels, polyvinylcaprolactam, polyvinyl alcohol‐alginate‐bioactive glass composite, polyhydroxyethylmethacrylate–gelatin (pHEMA–gelatin), and chitosan–agarose–gelatin in mice. All the cryogels were synthesized at subzero temperature and were implanted subcutaneously in C57Bl/10.Q inbred mice. Both local and systemic toxicities were negligible as determined by serum tumor necrosis factor α analysis and histology of surrounding tissues nearby the implants. Complete integration of cryogels into the surrounding tissues with neovascular formation was evident in all the mice. At the implantation site, massive infiltration of macrophages and few dendritic cells were observed but neutrophils and mast cells were clearly absent. Macrophage infiltrations were observed even inside the pores of cryogel implants. To ascertain whether oxidative radicals are involved in the cryogel degradation, we implanted these gels in mice deficient for reactive oxygen species (ROS) production. Rapid gel degradation was observed in the absence of ROS, and there was no significant difference in the biodegradation of these cryogels between ROS sufficient and deficient mice thereby excluding any major role for ROS in this process. Thus, we demonstrate the biocompatibility and ROS‐independent biodegradable properties of cryogels that could be useful for tissue‐specific tissue engineering applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3409–3418, 2014.
Comparison of Nestin‐Expressing Multipotent Stem Cells in the Tongue Fungiform Papilla and Vibrissa Hair Follicle
Authors: Mii Sumiyuki , Amoh Yasuyuki , Katsuoka Kensei , Hoffman Robert M. 
Published: October 2013

ABSTRACTWe have previously reported that hair follicles contain multipotent stem cells, which express nestin and participate in follicle growth at anagen as well as in the extension of the follicle sensory nerve. The nestin‐driven green fluorescent protein (ND‐GFP) transgenic mouse labels all nestin‐expressing cells with GFP. The hair follicle nestin‐GFP cells can differentiate into neurons, Schwann cells, and other cell types. In this study, we describe nestin‐expressing multipotent stem cells in the fungiform papilla in the tongue. The nestin‐expressing multipotent stem cells in the fungiform papilla are located around a peripheral sensory nerve immediately below the taste bud and co‐express the neural crest cell marker p75NTR. The fungiform papilla cells formed spheres in suspension culture in DMEM‐F12 medium supplemented with basic fibroblast growth factor (bFGF). The spheres consisted of nestin‐expressing cells that co‐expressed the neural crest marker p75NTR and which developed expression of the stem cell marker CD34. P75NTR, CD34 and nestin co‐expression suggested that nestin‐expressing cells comprising the fungiform papilla spheres were in a relatively undifferentiated state. The nestin‐expressing cells of these spheres acquired the following markers: β III tubulin typical of nerve cells; GFAP typical of glial cells; K15 typical of keratinocytes; and smooth‐muscle antigen (SMA), after transfer to RPMI 1640 medium with 10% fetal bovine serum (FBS), suggesting they differentiated into multiple cell types. The results of the current study indicate nestin‐expressing fungiform papilla cells and the nestin‐expressing hair follicle stem cells have common features of cell morphology and ability to differentiate into multiple cell types, suggesting their remarkable similarity. J. Cell. Biochem. 115: 1070–1076, 2014. © 2013 Wiley Periodicals, Inc.
Pyk2 and Src Mediate Signaling to CCL18‐Induced Breast Cancer Metastasis
Authors: Li Hai‐Yan , Cui Xiu‐Ying , Wu Wei , Yu Feng‐Yan , Yao He‐Rui , Liu Qiang , Song Er‐Wei , Chen Jing‐Qi 
Published: October 2013

ABSTRACTPyk2 and Src phosphorylation is initiated by CCL18, which promotes breast cancer metastasis via its functional G protein‐coupled receptor PITPNM3. However, the function of Pyk2 and Src in CCL18‐induced breast cancer metastasis is poorly understood. Quantitative reverse‐transcription polymerase chain reactions (qRT‐PCRs), Western blot, boyden chamber assay, and adherence assay were performed to delineate the consequences of Pyk2/Src in CCL18‐induced breast cancer cells. Co‐immunoprecipitation and immunofluorescence were performed to analyze the interaction of proteins. Upon the binding of CCL18 to PITPNM3, Pyk2 translocates from the cytoplasm to the plasma membrane to form a stable complex with PITPNM3, subsequently activating Src kinase. Moreover, upon stimulation with CCL18, Pyk2 and Src become essential for integrin alpha5/beta1 clustering‐dependent adherence, migration, and invasion. Pyk2 and Src are important in CCL18‐induced breast cancer metastasis. J. Cell. Biochem. 115: 596–603, 2014. © 2013 Wiley Periodicals, Inc.
An Unconventional Role of BMP‐Smad1 Signaling in DNA Damage Response: A Mechanism for Tumor Suppression
Authors: Liu Huijuan , Bao Dandan , Xia Xuechun , Chau Jenny Fung Ling , Li Baojie 
Published: October 2013

ABSTRACTThe genome is under constant attack by self‐produced reactive oxygen species and genotoxic reagents in the environment. Cells have evolved a DNA damage response (DDR) system to sense DNA damage, to halt cell cycle progression and repair the lesions, or to induce apoptosis if encountering irreparable damage. The best studied DDR pathways are the PIKK‐p53 and PIKK‐Chk1/2. Mutations in these genes encoding DDR molecules usually lead to genome instability and tumorigenesis. It is worth noting that there exist unconventional pathways that facilitate the canonical pathways or take over in the absence of the canonical pathways in DDR. This review will summarize on several unconventional pathways that participate in DDR with an emphasis on the BMP‐Smad1 pathway, a known regulator of mouse development and bone remodeling. J. Cell. Biochem. 115: 450–456, 2014. © 2013 Wiley Periodicals, Inc.
Population pharmacogenetic‐based pharmacokinetic modeling of efavirenz, 7‐hydroxy‐ and 8‐hydroxyefavirenz
Authors: Abdelhady A.M. , Desta Z. , Jiang F. , Yeo C.W. , Shin J.G. , Overholser B.R. 
Published: October 2013

AbstractThe purpose of this study was to determine the demographic and pharmacogenetic covariates that influence the disposition of efavirenz (EFV) and its major metabolites. A population pharmacokinetic (PK) model was developed from a randomized, cross‐over, drug‐interaction study in healthy male Korean subjects (n = 17). Plasma concentrations of EFV and its hydroxy‐metabolites (0–120 hours) were measured by LC/MS/MS. Genomic DNA was genotyped for variants in the cytochrome P450 (CYP) 2A6, 2B6, 3A5, and MDR1 genes. A PK model was built in a stepwise procedure using nonlinear mixed effect modeling in NONMEM 7. The covariate model was built using the generalized additive modeling and forward selection‐backward elimination. Model‐based simulations were performed to predict EFV steady‐state concentrations following 200, 400, and 600 mg daily oral dose among different CYP2B6 genotypes. The final model included only CYP2B6 genotype as a covariate that predicts EFV clearance through the formation of 8‐OH EFV that represented 65% to 80% of EFV clearance. The total clearance of EFV in CYP2B6*6/*6 genotype was ∼30% lower than CYP2B6*1/*1 or CYP2B6*1/*6 alleles (P < .001). Clopidogrel reduced both formation and elimination clearances of 8‐OH EFV by 22% and 19%, respectively (P = .033 and .041). Other demographics and genotype of accessory CYP pathways did not predict EFV or metabolites PK. CYP2B6 genotype was the only significant predictor of EFV disposition. The developed model may serve as the foundation for further exploration of pharmacogenetic‐based dosing of EFV.
Analysis of risk factors for recurrence after curative resection of well‐differentiated pancreatic neuroendocrine tumors based on the new grading classification
Authors: Tsutsumi Kosuke , Ohtsuka Takao , Fujino Minoru , Nakashima Hiroshi , Aishima Shinichi , Ueda Junji , Takahata Shunichi , Nakamura Masafumi , Oda Yoshinao , Tanaka Masao 
Published: October 2013

AbstractBackgroundIt is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs.MethodsData of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni‐ and multivariate analyses. Histopathological findings were re‐reviewed by experienced pathologists. NET G1 was defined as mitotic count <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index, and NET G2 as 2–20 mitosis per 10 HPF and/or 3–20% Ki67 index.ResultsThere were 58 patients with NET G1 and 12 with NET G2. Incidence of recurrence was 11.4%. Univariate analysis demonstrated significant risk factors for recurrence including NET G2 of histological grade (P = 0.0089), male gender (P = 0.0333), tumor size ≥ 20 mm (P = 0.0117), lymph node metastasis (P = 0.0004), liver metastasis (P < 0.0001), lymphatic invasion (P = 0.046), and neural invasion (P = 0.0002). By multivariate analysis, histological grade (hazard ratio; 59.76, P = 0.0022) and neural invasion (hazard ratio; 147.49, P = 0.0016) were significantly associated with recurrence of PNETs.ConclusionsThis study confirmed the prognostic relevance of the new grading classification and that evaluation of perineural invasion and histological grade should be considered as prognostic predictors in well‐differentiated PNETs (NET G1 and G2).
Climatology, annual cycle and interannual variability of precipitation and temperature in CORDEX simulations over West Africa
Authors: Gbobaniyi Emiola , Sarr Abdoulaye , Sylla Mouhamadou Bamba , Diallo Ismaila , Lennard Chris , Dosio Alessandro , Dhiédiou Arona , Kamga Andre , Klutse Nana Ama Browne , Hewitson Bruce , Nikulin Grigory , Lamptey Benjamin 
Published: October 2013

ABSTRACTWe examine the ability of an ensemble of 10 Regional Climate Models (RCMs), driven by ERA‐Interim reanalysis, in skillfully reproducing key features of present‐day precipitation and temperature (1990–2008) over West Africa. We explore a wide range of time scales spanning seasonal climatologies, annual cycles and interannual variability, and a number of spatial scales covering the Sahel, the Gulf of Guinea and the entire West Africa. We find that the RCMs show acceptable performance in simulating the spatial distribution of the main precipitation and temperature features. The occurrence of the West African Monsoon jump, the intensification and northward shift of the Saharan Heat Low (SHL), during the course of the year, are shown to be realistic in most RCMs. They also capture the mean annual cycle of precipitation and temperature, including, single and double‐peaked rainy seasons, in terms of timing and amplitude over the homogeneous sub‐regions. However, we should emphasize that the RCMs exhibit some biases, which vary considerably in both magnitude and spatial extent from model to model. The interannual variability of seasonal anomalies is best reproduced in temperature rather than precipitation. The ensemble mean considerably improves the skill of most of the individual RCMs. This highlights the importance of performing multi‐model assessment in properly estimating the response of the West African climate to global warming at seasonal, annual and interannual time scales.
The change of cherry first‐flowering date over South Korea projected from downscaled IPCC AR5 simulation
Authors: Hur Jina , Ahn Joong‐Bae , Shim Kyo‐Moon 
Published: October 2013

ABSTRACTSimulations from six global climate models participating in Coupled Model Intercomparison Project 5 are used to project future changes in regional early spring (February–April) temperature and in cherry (Prunus yedoensis) first‐flowering date (FFD) over South Korea in order to investigate a potential plant growth response to local climate change. For the study, we statistically downscale daily Historical (1986–2005), RCP4.5 (2071–2090), and RCP8.5 (2071–2090) gridded model data to 59 cherry FFD observation sites over South Korea. In order to reduce the uncertainties in the model simulation produced by a single model, multi‐model ensemble (MME) is performed after eliminating the mean systematic bias of each model. A shift of cherry FFD under global warming is estimated and compared with the observation and Historical simulation by applying the downscaled data to a DTS phenological model. The analysis reveals a projected advance in cherry FFD over South Korea by 2090 of 6.3 and 11.2 days compared to the current dates due to a rising mean temperature of about 2.0 and 3.5 K under the RCP4.5 and RCP8.5 scenarios, which approximately correspond to moving north at a speed of 0.01 and 0.03oN year−1, respectively. These average yearly advances (0.07 and 0.13 days year−1) of cherry FFD in the RCP4.5 and RCP8.5 simulations are 0.22 and 0.16 days year−1 lower, respectively, than the value of 0.29 days year−1 derived in previous studies with the SRES A2 scenario. Regardless of the difference between the SRES A2 and RCP8.5 scenarios, the discrepancy in the advancement tendency was primarily attributed to the inability of the previous studies to eliminate the systematic model biases, which led to overestimation of both the temperature and the FFD changes.
Application of an electronic nose in the diagnosis of head and neck cancer
Authors: Leunis Nicoline , Boumans Marie‐Louise , Kremer Bernd , Din Sinh , Stobberingh Ellen , Kessels Alfons G. H. , Kross Kenneth W. 
Published: October 2013

Objectives/HypothesisElectronic nose (E‐nose) technology has various applications such as the monitoring of air quality and the detection of explosive and chemical agents. We studied the diagnostic accuracy of volatile organic compounds (VOC) pattern analysis in exhaled breath by means of an E‐nose in patients with head and neck squamous cell carcinoma (HNSCC).Study DesignCohort study. Exhaled breath samples from patients with HNSCC were analyzed by using an E‐Nose.MethodsThirty‐six patients diagnosed with HNSCC exhaled into a 5‐litre Tedlar bag. The control group consisted of 23 patients visiting the outpatient clinic for other (benign) conditions. Air samples were analyzed using an E‐nose.ResultsLogistic regression showed a significant difference (P < 0.05) in VOC resistance patterns between patients diagnosed with HNSCC and the control group, with a sensitivity of 90% and a corresponding specificity of 80%.ConclusionsE‐nose application holds a promising potential for application in the diagnosis of HNSCC due to its rapid, simple, and noninvasive nature.Level of Evidence3b. Laryngoscope, 124:1377–1381, 2014
Vibroplasty in mixed and conductive hearing loss: Comparison of different coupling methods
Authors: Vyskocil Erich , Riss Dominik , Honeder Clemens , Arnoldner Christoph , Hamzavi Jafar‐Sasan , Baumgartner Wolf‐Dieter , Flak Stefan , Gstoettner Wolfgang 
Published: October 2013

Objectives/HypothesisTo evaluate modified coupling techniques of the Vibrant Soundbridge system in patients with mixed and conductive hearing loss and to compare it with conventional vibroplasty.Study DesignRetrospective study.MethodsTwo different groups were evaluated: 1) nine cases of conventional incus vibroplasty in comparison with 2) nine patients with modified coupling of the floating mass transducer. In the modified coupling approach, the vibrant floating mass transducer was attached to 1) the stapes/oval window, 2) the round window, or 3) the drilled promontory bone (promontory fenestration window). In three patients, an additional ossiculoplasty was performed. Preoperative and postoperative aided and unaided pure‐tone and free‐field audiometry and Freiburg monosyllabic word test were used to assess hearing outcome.ResultsFunctional hearing gain obtained in patients with mixed and conductive hearing loss who underwent modified coupling was 39 dB. Patients with pure sensorineural hearing loss who received conventional incus coupling showed a functional hearing gain of 25 dB. Average functional gain was 41 dB in the oval window group, 45 dB in the round window group, and 30 dB in the promontory fenestration window group. Word recognition test revealed an average improvement of 51% and 21% in the modified and in the conventional approach, respectively.ConclusionsModified vibroplasty is a safe and effective treatment for patients with conductive and mixed hearing loss. Coupling the floating mass transducer to the promontory bone (promontory fenestration window) is a viable option in chronically disabled ears if oval and round window coupling is not possible.Level of Evidence4. Laryngoscope, 124:1436–1443, 2014
Oleic acid increases hepatic sex hormone binding globulin production in men
Authors: Sáez‐López Cristina , Soriguer Federico , Hernandez Cristina , Rojo‐Martinez Gemma , Rubio‐Martín Elehazara , Simó Rafael , Selva David M. 
Published: October 2013

ScopeLow circulating sex hormone‐binding globulin (SHBG) is an independent risk factor for cardiovascular disease. Mediterranean diet has been associated with a decreased risk of cardiovascular disease. We aimed to test the hypothesis that the increase of circulating MUFA associated with olive oil consumption (primary fat source in Mediterranean diet) increases SHBG serum levels.Methods and resultsA total of 315 men were included. In these patients, nutrition data and plasma samples for SHBG assessment were obtained. In vitro studies to examine the effects of oleic and linoleic acid on SHBG production using HepG2 cells were performed. We provided evidence that SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil. The SHBG levels correlated positively with MUFA (p < 0.001) and negatively with saturated fatty acids (p = 0.003). In the multiple regression analysis, MUFA were independently associated with SHBG levels and accounted for the 20.4% of SHBG variance. In vitro studies revealed that oleoyl‐CoA increases SHBG production by downregulating PPAR‐γ levels in HepG2 cells.ConclusionOlive oil consumption is associated with elevated SHBG serum levels. PPAR‐γ downregulation induced by oleoyl‐CoA is an important underlying mechanism of such regulation.