bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental occupational exposure to engine exhausts and childhood brain tumors
Authors: Peters Susan , Glass Deborah C. , Reid Alison , de Klerk Nicholas , Armstrong Bruce K. , Kellie Stewart , Ashton Lesley J. , Milne Elizabeth , Fritschi Lin 
Published: November 2012

AbstractChildhood brain tumors (CBT) are the leading cause of cancer death in children; their risk factors are still largely unknown. Since most CBTs are diagnosed before five years of age, prenatal exposure and early postnatal factors may be involved in their etiology. We investigated the association between CBT and parental occupational exposure to engine exhausts in an Australian population‐based case–control study. Parents of 306 cases and 950 controls completed detailed occupational histories. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for both maternal and paternal exposure in key time periods. Increased risks were observed for maternal exposure to diesel exhaust any time before the child's birth (OR 2.03, 95% CI 1.09–3.81) and paternal exposure around the time of the child's conception (OR 1.62, 95% CI 1.12–2.34). No clear associations with other engine exhausts were found. Our results suggest that parental occupational exposure to diesel exhaust may increase the risk of CBT.
Blockade of Myd88 signaling induces antitumor effects by skewing the immunosuppressive function of myeloid‐derived suppressor cells
Authors: Hong Eun‐Hye , Chang Sun‐Young , Lee Bo‐Ra , Kim Yun‐Sun , Lee Jeong‐Mi , Kang Chang‐Yuil , Kweon Mi‐Na , Ko Hyun‐Jeong 
Published: November 2012

AbstractMyd88 is an important adaptor molecule for the activation of NADPH oxidase and arginase‐1, which are responsible for the suppressive function of myeloid‐derived suppressor cells (MDSCs). When wild‐type and Myd88−/− mice were subcutaneously injected with CT26 colon cancer cells expressing human Her‐2/neu, tumor growth was retarded in Myd88−/− mice than in wild‐type mice. Although the generation of CD11b+Gr‐1+ MDSCs was less in Myd88−/− mice than in wild‐type mice, Myd88−/− mice having tumor masses still had significant quantities of MDSCs, suggesting that MDSC generation might be independent of Myd88 signaling. However, MDSCs obtained from tumor‐bearing Myd88−/− mice failed to suppress antigen‐specific proliferation of CD8+ T cells and CD4+ T cells, whereas MDSCs from wild‐type mice significantly suppressed both types of T cells. Consistent with this, we found that the levels of costimulatory molecules and MHC class II were significantly increased in MDSCs obtained from Myd88−/− mice compared with wild‐type mice after tumor challenge. Furthermore, CD4+ T cells residing in tumor‐draining lymph nodes of Myd88−/− mice secreted more TNF‐α than those of wild‐type mice. Finally, the blockade of Myd88 signaling by treatment with Myd88 inhibitory peptide, during later tumor stages, significantly inhibited the growth of immunogenic tumors. Overall, these data suggest that signaling through the Myd88 adaptor molecule is critical for the direct suppressive function of MDSCs and approaches to block Myd88‐mediated signaling in MDSCs might be effective to inhibit the immunosuppressive function of MDSCs.
2.5D constructs for characterizing phase separated polymer blend surface morphology in tissue engineering scaffolds
Authors: Marszalek Jolanta E. , Simon Carl G. , Thodeti Charles , Adapala Ravi Kumar , Murthy Ananth , Karim Alamgir 
Published: November 2012

AbstractPreviously, we used 2D films to identify an annealed PCL‐PDLLA phase‐separated blend morphology which provided nanoscale surface texture and patterning that stimulated osteoblast differentiation. In order to translate these 2D surface nanopatterning effects to the walls of 3D salt‐leached scaffolds, the blend phase morphology of scaffold walls must be characterized. For salt‐leached scaffolds, NaCl is used as a porogen, which may affect phase separation in PCL‐PDLLA blends. However, it is not possible to characterize the surface blend morphology of 3D scaffold walls using standard approaches such as AFM or optical microscopy, since scaffolds are too rough for AFM and do not transmit light for optical microscopy. We introduce a 2.5D approach that mimics the processing conditions of 3D salt‐leached scaffolds, but has a geometry amenable to surface characterization by AFM and optical microscopy. For the 2.5D approach, PCL‐PDLLA blend films were covered with NaCl crystals prior to annealing. The presence of NaCl significantly influenced blend morphology in PCL‐PDLLA 2.5D constructs causing increased surface roughness, higher percent PCL area on the surface and a smaller PCL domain size. During cell culture on 2.5D constructs, osteoblast (MC3T3‐E1) and dermal endothelial cell (MDEC) adhesion were enhanced on PCL‐PDLLA blends that were annealed with NaCl while chondrogenic cell (ATDC5) adhesion was diminished. This work introduces a 2.5D approach that mimicked 3D salt‐leached scaffold processing, but enabled characterization of scaffold surface properties by AFM and light microscopy, to demonstrate that the presence of NaCl during annealing strongly influenced polymer blend surface morphology and cell adhesion. Published 2012 Wiley Periodicals, Inc.† J Biomed Mater Res Part A, 2013.
Chondrogenic differentiation of bone marrow‐derived mesenchymal stromal cells via biomimetic and bioactive poly‐ε‐caprolactone scaffolds
Authors: Schagemann J. C. , Paul S. , Casper M. E. , Rohwedel J. , Kramer J. , Kaps C. , Mittelstaedt H. , Fehr M. , Reinholz G. G. 
Published: November 2012

AbstractThe objective of this study was to develop a scaffold for mesenchymal stromal cell (MSC) recruitment, proliferation, and chondrogenic differentiation. The concept behind the design is to mimic the cartilage matrix and contain stimulatory agents that make continuous supply of inductive factors redundant. Nanofibrous (N: ∼400 nm) and microfibrous (M: ∼10 μm) poly‐ε‐caprolactone (PCL) scaffolds were combined with 1% high‐molecular‐weight sodium hyaluronate (NHA/MHA), 1% hyaluronan (HA) and 200 ng transforming growth factor‐beta 1 (TGF‐β1; NTGF/MTGF), or 0.1% bovine serum albumin (N/M). Scaffolds were seeded with MSCs from bone marrow and cultured without growth factors in vitro. Cultures with chondrogenic medium supplemented with TGF‐β1 served as controls. Proliferation, migration, and release of TGF‐β1 were investigated. Cell differentiation was evaluated by polymerase chain reaction (PCR) and real‐time PCR. NTGF and MTGF exhibited primarily an initial release of TGF‐β1. None of the factors released by the scaffolds recruited MSCs. The expression of aggrecan was dependent on the scaffold ultrastructure with nanofibers promoting increasing and microfibers decreasing expression levels. Composites containing HA demonstrated elevated seeding efficiency and lower type I collagen expression. Expression of type II collagen was dependent on continuous or late supply of TGF‐β1, which was not provided by our scaffold design. The initial release of TGF‐β1 induced an expression of type I collagen and osteogenic marker genes. In conclusion, nanofibrous PCL scaffolds with or without augmentation are suitable for chondrogenic initiation of MSCs. Initial release of HA is sufficient in terms of directing the implanted MSCs toward a chondrogenic end, whereas a late release of TGF‐β1 is preferred to foster type II and avoid type I collagen expression. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH‐sensitive units with a bioactive compound
Authors: Fundueanu Gheorghe , Constantin Marieta , Asmarandei Ionela , Harabagiu Valeria , Ascenzi Paolo , Simionescu Bogdan C. 
Published: November 2012

AbstractpH/thermosensitive hydrogels whose thermosensitivity is activated by the electrostatic interaction of the pH‐sensitive units with a hydrophobic bioactive compound are proposed here as sensor‐based self‐regulated drug delivery systems. Poly(N‐isopropylacrylamide‐co‐acrylamide‐co‐aminoethylacrylamide) (poly(NIPAAm‐co‐AAm‐co‐AEAAm)) was prepared as a new pH/thermoresponsive polymer by hydrolysis of poly(N‐isopropylacrylamide‐co‐acrylamide (poly(NIPAAm‐co‐AAm)) at high temperature (120°C) in the presence of ethylenediamine. Owing to the hydrophilicity of the inserted amine, the copolymers lose the thermosensitivity at physiological temperature and have a slow‐phase transition at temperatures much higher than that of the human body. However, when the positively charged amine groups of the pH‐sensitive units bind electrostatically with the negatively charged drug diclofenac, the copolymers retrieve the thermosensitivity. Poly(NIPAAm‐co‐AAm‐co‐AEAAm) was transformed into pH/thermoresponsive stable microspheres by an original approach based on crosslinking of the amine groups of aminoethylacrylamide (AEAAm) with glutaraldehyde at a temperature slightly below the lower critical solution temperature. The swelling/deswelling processes of microspheres occur only after the interaction of poly(NIPAAm‐co‐AAm‐co‐AEAAm) with the negatively charged drug diclofenac. The pH/temperature‐sensitive microgels and dicofenac act as sensors and as the triggering agent, respectively. Conductometric titration reveals that the thermosensitivity of poly(NIPAAm‐co‐AAm‐co‐AEAAm) is retrieved when just half of its amino groups are complexed with diclofenac. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Development of vapor deposited silica sol–gel particles for use as a bioactive materials system
Authors: Snyder Katherine L. , Holmes Hallie R. , VanWagner Michael J. , Hartman Natalie J. , Rajachar Rupak M. 
Published: November 2012

AbstractSilica‐based sol–gel and bioglass materials are used in a variety of biomedical applications including the surface modification of orthopedic implants and tissue engineering scaffolds. In this work, a simple system for vapor depositing silica sol–gel nano‐ and micro‐particles onto substrates using nebulizer technology has been developed and characterized. Particle morphology, size distribution, and degradation can easily be controlled through key formulation and manufacturing parameters including water:alkoxide molar ratio, pH, deposition time, and substrate character. These particles can be used as a means to rapidly modify substrate surface properties, including surface hydrophobicity (contact angle changes >15°) and roughness (RMS roughness changes of up to 300 nm), creating unique surface topography. Ions (calcium and phosphate) were successfully incorporated into particles, and induced apatitie‐like mineral formation upon exposure to simulated body fluid Preosteoblasts (MC3T3) cultured with these particles showed up to twice the adhesivity within 48 h when compared to controls, potentially indicating an increase in cell proliferation, with the effect likely due to both the modified substrate properties as well as the release of silica ions. This novel method has the potential to be used with implants and tissue engineering materials to influence cell behavior including attachment, proliferation, and differentiation via cell–material interactions to promote osteogenesis. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Use of a poly(ether imide) coating to improve corrosion resistance and biocompatibility of magnesium (Mg) implant for orthopedic applications
Authors: Kim Sang‐Bok , Jo Ji‐Hoon , Lee Sung‐Mi , Kim Hyoun‐Ee , Shin Kwan‐Ha , Koh Young‐Hag 
Published: November 2012

AbstractThis study investigated the utility of poly(ether imide) (PEI) coating for improving the corrosion resistance and biocompatibility of magnesium (Mg) implants for orthopedic application. In particular, the microstructure of the PEI coating layers was controlled by the adjustment of the temperature used to dry the spin‐coated wet PEI films. When a wet PEI film was dried at 4°C, a relatively thick and porous coating layer was achieved as a result of an extensive exchange of the solvent with water in a moist environment. In contrast, when a wet PEI film was dried at 70°C, a relatively thin and dense layer was created due to the faster evaporation of the solvent with a negligible exchange of the solvent with water. The porous PEI coating layer showed higher stability than did the dense one when immersed in a simulated body fluid (SBF), which was presumably attributed to the formation of chemical bonding between the PEI and the Mg substrate. Both the porous and the dense PEI coated Mg specimens showed significantly improved in vitro biocompatibility, which were assessed in terms of cell attachment, proliferation and differentiation. However, interestingly, the dense PEI coating layer showed greater cell proliferation and differentiation than did the porous layer. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Compression‐induced alignment and elongation of human mesenchymal stem cell (hMSC) in 3D collagen constructs is collagen concentration dependent
Authors: Kwok C. B. , Ho F. C. , Li C. W. , Ngan A. H. W. , Chan D. , Chan B. P. 
Published: November 2012

AbstractControlling cell organization is important in tissue engineering. Guidance by aligned features on scaffolds or stimulation by physical signals can be used to induce cell alignment. We have previously demonstrated a preferred alignment of human MSCs (hMSCs) along the compression loading axis in 3D collagen construct. In this study, we aim to investigate the collagen concentration dependence of the compression‐induced hMSC organization. Results demonstrated that the compression‐induced alignment and elongation of hMSCs exhibited a biphasic dose‐dependent relationship with collagen concentration, and associated well with both collagen ligand density and elastic modulus of the constructs. Moreover, collagen concentration and compression loading significantly affected the expression level of integrin beta 1 and antibody neutralization against this molecule aborted the compression‐induced alignment and elongation responses. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
A 3D‐matrigel/microbead assay for the visualization of mechanical tractive forces at the neurite–substrate interface of cultured neurons
Authors: Meseke Maurice , Förster Eckart 
Published: November 2012

AbstractMechanical properties of neuronal processes contribute to neuronal function, to resistance of fiber tracts against mechanical trauma, and to morphological changes during development and neurodegeneration. Conventional in vitro cell culture systems on inflexible substrates do not allow for the visualization of changing mechanical stress between neurites and their substrate. To solve this problem, we adapted a three‐dimensional gel matrix assay to visualize mechanical traction forces at the neurite–substrate interface. We chose matrigel as substrate because in this matrix various types of neurons initially adapt a bipolar morphology while migrating, similar to migrating neurons in vivo. To visualize emerging traction forces between neurites and their substrate, microbeads were embedded into the matrix as visible landmarks. We first analyzed mechanical distortion of matrigel by stepwise movements of a glass pipette tip under control of a micromanipulator to ensure reproducibility of induced bead displacement. The assay was then used to study the effect of the microtubule disrupting drug nocodazole on neuronal processes. By monitoring displacement of matrigel‐embedded microbeads, we visualized here for the first time emerging mechanical traction forces between the leading process and the substrate during nocodazole‐induced soma translocation. We did not observe bead displacement by processes of aged neurons. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Polyethylene glycol–grafted polyethylenimine used to enhance adenovirus gene delivery
Authors: Singarapu Kumar , Pal Ivy , Ramsey Joshua D. 
Published: November 2012

AbstractAn improved adenoviral‐based gene delivery vector was developed by complexing adenovirus (Ad) with a biocompatible, grafted copolymer PEG‐g‐PEI composed of polyethylene glycol (PEG) and polyethylenimine (PEI). Although an Ad‐based gene vector is considered relatively safe, its native tropism, tendency to elicit an immune response, and susceptibility to inactivating antibodies makes the virus less than ideal. The goal of the current study was to determine whether Ad could be complexed with a PEG‐g‐PEI copolymer that would enable the virus to transduce cells lacking the Ad receptor, while avoiding the issues commonly associated with PEI. A copolymer library was synthesized using 2 kDa PEG and either linear or branched PEI (25 kDa) with a PEG to PEI grafting ratio of 10, 20, or 30. The results of the study indicate that PEG‐g‐PEI/Ad complexes are indeed able to transduce CAR‐negative NIH 3T3 cells. The results also demonstrate that the PEG‐g‐PEI/Ad complexes are less toxic, less hemolytic, and more appropriately sized than PEI/Ad complexes. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Development of a bone reconstruction technique using a solid free‐form fabrication (SFF)‐based drug releasing scaffold and adipose‐derived stem cells
Authors: Lee Jin Woo , Kim Ki‐Joo , Kang Kyung Shin , Chen Shaochen , Rhie Jong‐Won , Cho Dong‐Woo 
Published: November 2012

AbstractFor tissue regeneration, three essential components of scaffolds, signals (biomolecules), and cells are required. Moreover, because bony defects are three‐dimensional in many clinical circumstances, an exact 3D scaffold is important. Therefore, we proposed an effective reconstruction tool for cranial defects using human adipose‐derived stem cells (hADSCs) and a 3D functional scaffold fabricated by solid free‐form fabrication (SFF) technology that secretes biomolecules. We fabricated poly(propylene fumarate)‐based 3D scaffolds with embedded microsphere‐deliverable bone morphogenetic protein‐2 (BMP‐2) by microstereolithography. BMP‐2‐loaded SFF scaffolds with/without hADSCs (SFF/BMP/hADSCs scaffolds and SFF/BMP scaffolds, respectively) and BMP‐2‐unloaded SFF scaffolds (SFF scaffolds) were then implanted in rat crania, and in vivo bone formation was observed. Analyses of bone formation areas using micro‐computed tomography (micro‐CT) showed the superiority of SFF/BMP/hADSCs scaffolds. Hematoxylin and eosin stain, Masson's trichrome stain, and collagen type‐I stain supported the results of the micro‐CT scan. And human leukocyte antigen‐ABC showed that seeded, differentiated hADSCs were well grown and changed to the bone tissue at the inside of the scaffold. Results showed that our combination of a functional 3D scaffold and hADSCs may be a useful tool for improving the reconstruction quality of severe bony defects in which thick bone is required. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans
Authors: Warraich Sumeeta , Bone Derek BJ , Quinonez Diana , Ii Hisataka , Choi Doo-Sup , Holdsworth David W , Drangova Maria , Dixon S Jeffrey , Séguin Cheryle A , Hammond James R 
Published: November 2012

Abstract
Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy, characterized by ectopic calcification of spinal tissues. Symptoms include spine pain and stiffness, and in severe cases dysphagia and spinal cord compression. The etiology of DISH is unknown and there are no specific treatments. Recent studies have suggested a role for purine metabolism in the regulation of biomineralization. Equilibrative nucleoside transporter 1 (ENT1) transfers hydrophilic nucleosides, such as adenosine, across the plasma membrane. In mice lacking ENT1, we observed the development of calcified lesions resembling DISH. By 12 months of age, ENT1–/– mice exhibited signs of spine stiffness, hind limb dysfunction, and paralysis. Micro–computed tomography (µCT) revealed ectopic mineralization of paraspinal tissues in the cervical-thoracic region at 2 months of age, which extended to the lumbar and caudal regions with advancing age. Energy-dispersive X-ray microanalysis of lesions revealed a high content of calcium and phosphorus with a ratio similar to that of cortical bone. At 12 months of age, histological examination of ENT1–/– mice revealed large, irregular accumulations of eosinophilic material in paraspinal ligaments and entheses, intervertebral discs, and sternocostal articulations. There was no evidence of mineralization in appendicular joints or blood vessels, indicating specificity for the axial skeleton. Plasma adenosine levels were significantly greater in ENT1–/– mice than in wild-type, consistent with loss of ENT1—a primary adenosine uptake pathway. There was a significant reduction in the expression of Enpp1, Ank, and Alpl in intervertebral discs from ENT1–/– mice compared to wild-type mice. Elevated plasma levels of inorganic pyrophosphate in ENT1–/– mice indicated generalized disruption of pyrophosphate homeostasis. This is the first report of a role for ENT1 in regulating the calcification of soft tissues. Moreover, ENT1–/– mice may be a useful model for investigating pathogenesis and evaluating therapeutics for the prevention of mineralization in DISH and related disorders. © 2013 American Society for Bone and Mineral Research.
Serum 25-hydroxyvitamin D and risk of major osteoporotic fractures in older U.S. adults
Authors: Looker Anne C 
Published: November 2012

Abstract
Results from previous prospective studies linking serum 25-hydroxyvitamin D (25OHD) with fracture risk have been inconsistent. The present study examined the relationship between serum 25OHD and risk of incident major osteoporotic fracture (hip, spine, radius, and humerus) in older U.S. adults. The study used a pooled cohort of 4749 men and women ages 65 years and older from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and NHANES 2000–2004. Incident fractures were identified using linked mortality and Medicare records that were obtained for participants from both surveys. Serum 25OHD values were measured by radioimmunoassay in both surveys. Cox proportional hazards models were used to estimate the relative risk (RR) of fracture by serum 25OHD level. There were 525 incident major osteoporotic fractures (287 hip fractures) in the sample. Serum 25OHD was a significant linear predictor of major osteoporotic fracture and significant quadratic predictor of hip fracture in the total sample and among those with less than 10 years of follow-up, but it was not related to risk of either fracture type among those with ≥10 years of follow-up. Major osteoporotic fracture risk was increased by 26% to 27% for each SD decrease in serum 25OHD among those with less than 10 years of follow-up. Serum 25OHD was significantly related to risk of major osteoporotic fractures as a group and to hip fracture alone in this cohort of older U.S. adults from NHANES III and NHANES 2000–2004. However, the predictive utility of serum 25OHD diminished after 10 years. In addition, the relationship appeared to be linear when major osteoporotic fracture risk was considered but quadratic when hip fracture risk was assessed. © 2013 American Society for Bone and Mineral Research.