bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eosinophil protein X and childhood asthma: A systematic review and meta‐analysis
Authors: Klonoff‐Cohen Hillary , Polavarapu Mounika 
Published: April 2016

AbstractBackground: There are no reference guidelines for health care providers regarding appropriate use and interpretation of urine eosinophil protein X (u‐EPX) in clinical practice. Currently, there are no clear‐cut clinical or laboratory parameters to diagnose asthma in young children. Objective: In this study, we (1) systematically reviewed and qualitatively appraised the epidemiological evidence to determine diagnostic u‐EPX cut points for pediatric asthma, and (2) performed a meta‐analysis to provide u‐EPX estimates for diagnosing pediatric asthma. Methods: Research articles in literature were identified from PubMed/Medline and Web of Science databases from 1966 to August 2015. Children <18 years of age were included. Both serum and urine EPX were included. Twenty‐seven studies met the inclusion criteria for the systematic review and nine studies for the meta‐analysis. Details regarding EPX analyses, treatment efficacy, and outcomes were assessed. For meta‐analyses, effect estimates were abstracted using standardized means. Results: Over 70% of studies found a significant relationship between u‐EPX and childhood asthma. There was 1.94 times higher standardized means of u‐EPX among acute asthmatics compared to healthy controls (confidence interval [CI]: 1.67–2.22). Similarly, the difference in standardized means between asymptomatic asthmatics and healthy controls was 1.58 times higher (CI: 1.27–1.88). Conclusions and Clinical Relevance: Despite differences in sample sizes, EPX processing and measurement, and ages of children, a consistent trend of higher EPX levels with childhood asthma was revealed.
Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates
Authors: Weeratna Risini D. , Chikh Ghania , Zhang Lu , Fraser James D. , Thorn Jennifer M. , Merson James R. , McCluskie Michael J. , Champion Brian R. , Davis Heather L. 
Published: April 2016

AbstractThe anti‐human immunoglobulin E (IgE) monoclonal antibody, omalizumab (Xolair®, Genentech, South San Fransisco, CA), is effective in the treatment of poorly controlled moderate to severe allergic asthma and chronic idiopathic urticaria. It acts by specifically binding to the constant domain (Cϵ3) of free human IgE in the blood and interstitial fluid. Although efficacious, use of omalizumab is limited due to restrictions on patient weight and pre‐existing IgE levels, and frequent dosing (q2–4 weeks). A vaccine inducing anti‐IgE antibodies has the potential for similar clinical benefits with less frequent dosing and relatively lower cost of goods. We developed a vaccine containing two IgE peptide‐conjugates targeting the Cϵ3 domain of human IgE. As part of preclinical evaluation of the vaccine to optimize formulation and dose prior to initiating clinical studies, we evaluated the vaccine in non‐human primates, and demonstrate the induction of anti‐peptide antibodies that can bind to conformationally intact human IgE and are capable, at least in some animals, of substantial lowering circulating IgE levels.
In Search of the Transmission Mechanism of Fiscal Policy in the Euro Area
Authors: Fève Patrick , Sahuc Jean‐Guillaume 
Published: April 2016

SummaryThis paper applies the DSGE‐VAR methodology to assess the size of fiscal multipliers in the data and the relative contributions of two transmission mechanisms of government spending shocks, namely hand‐to‐mouth consumers and Edgeworth complementarity. Econometric experiments show that a DSGE model with Edgeworth complementarity is a better representation of the transmission mechanism of fiscal policy as it yields dynamic responses close to those obtained with the flexible DSGE‐VAR model (i.e. an impact output multiplier larger than one and a crowding‐in of private consumption). The estimated share of hand‐to‐mouth consumers is too small to replicate the positive response of private consumption. Copyright © 2016 John Wiley & Sons, Ltd.
DMSO‐ and Serum‐Free Cryopreservation of Wharton's Jelly Tissue Isolated From Human Umbilical Cord
Authors: Shivakumar Sharath Belame , Bharti Dinesh , Subbarao Raghavendra Baregundi , Jang Si‐Jung , Park Ji‐Sung , Ullah Imran , Park Ji‐Kwon , Byun June‐Ho , Park Bong‐Wook , Rho Gyu‐Jin 
Published: April 2016

ABSTRACTThe facile nature of mesenchymal stem cell (MSC) acquisition in relatively large numbers has made Wharton's jelly (WJ) tissue an alternative source of MSCs for regenerative medicine. However, freezing of such tissue using dimethyl sulfoxide (DMSO) for future use impedes its clinical utility. In this study, we compared the effect of two different cryoprotectants (DMSO and cocktail solution) on post‐thaw cell behavior upon freezing of WJ tissue following two different freezing protocols (Conventional [−1°C/min] and programmed). The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO. Post‐thaw growth characteristics and stem cell behavior of Wharton's jelly mesenchymal stem cells (WJMSCs) from WJ tissue cryopreserved with a cocktail solution in conjunction with programmed method (Prog‐Cock) were comparable with WJMSCs from fresh WJ tissue. They preserved their expression of surface markers, pluripotent factors, and successfully differentiated in vitro into osteocytes, adipocytes, chondrocytes, and hepatocytes. They also produced lesser annexin‐V‐positive cells compared to cells from WJ tissue stored using cocktail solution in conjunction with the conventional method (Conv‐Cock). Real‐time PCR and Western blot analysis of post‐thaw WJMSCs from Conv‐Cock group showed significantly increased expression of pro‐apoptotic factors (BAX, p53, and p21) and reduced expression of anti‐apoptotic factor (BCL2) compared to WJMSCs from the fresh and Prog‐Cock group. Therefore, we conclude that freezing of fresh WJ tissue using cocktail solution in conjunction with programmed freezing method allows for an efficient WJ tissue banking for future MSC‐based regenerative therapies. J. Cell. Biochem. 117: 2397–2412, 2016. © 2016 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.
Molecular Dynamics Simulations of Ligand‐Induced Flap Conformational Changes in Cathepsin‐D—A Comparative Study
Authors: Arodola Olayide A. , Soliman Mahmoud E.S. 
Published: April 2016

ABSTRACTThe flap region in aspartic proteases is a unique structural feature to this class of enzymes, and found to have a profound impact on protein overall structure, function, and dynamics. Understanding the structure and dynamic behavior of the flap regions is crucial in the design of selective inhibitors against aspartic proteases. Cathepsin‐D, an aspartic protease enzyme, has been implicated in a long list of degenerative diseases as well as breast cancer progression. Presented herein, for the first time, is a comprehensive description of the conformational flap dynamics of cathepsin‐D using a comparative 50 ns “multiple” molecular dynamics simulations. Diverse collective metrics were proposed to accurately define flap dynamics. These are distance d1 between the flap tips residues (Gly79 and Met301); dihedral angle ϕ; in addition to TriCα angles Gly79‐Asp33‐Asp223, θ1, and Gly79‐Asp223‐Met301, θ2. The maximum distance attained throughout the simulation was 17.42 and 11.47 Å for apo and bound cathepsin‐D, respectively, while the minimum distance observed was 8.75 and 6.32 Å for apo and bound cathepsin‐D, respectively. The movement of the flap as well as the twist of the active pocket can properly be explained by measuring the angle, θ1, between Gly79‐Asp33‐Met301 and correlating it with the distance Cα of the flap tip residues. The asymmetrical opening of the binding cavity was best described by the large shift of −6.26° to +20.94° in the dihedral angle, ϕ, corresponding to the full opening of the flap at a range of 31–33 ns. A wide‐range of post‐dynamic analyses was also applied in this report to supplement our findings. We believe that this report would augment current efforts in designing potent structure‐based inhibitors against cathepsin‐D in the treatment of breast cancer and other degenerative diseases. J. Cell. Biochem. 117: 2643–2657, 2016. © 2016 Wiley Periodicals, Inc.
Effect of Combined Action of Extracellular ATP and Elevated Calcium on Osteogenic Differentiation of Primary Cultures From Rat Calvaria
Authors: Laiuppa Juan A. , Santillán Graciela E. 
Published: April 2016

ABSTRACTThe in vitro osteogenic differentiation has been intensively studied. However, it is not yet clear precisely how osteogenesis can be optimized. Changes in extracellular Ca2+ concentration ([Ca2+]e), as well as modulation of purinergic receptors play an important role in the regulation of osteoblasts differentiation and bone formation. In this study, we investigated the effects of a combined treatment of ATPγ‐S and high [Ca2+]e (5.35 mM) on osteogenic differentiation and function of primary cell cultures from rat calvaria. Our results indicate that ATPγ‐S stimulates cell transition from the G0 to S phase of cell cycle, involving the PI3K signaling pathway. Treatment with 10 or 100 µM ATPγ‐S and [Ca2+]e (ATP‐[Ca2+]e) for 48 h increases cell number significantly above the control. ATPγ‐S treatment in osteogenic medium containing [Ca2+]e stimulates the gene expression of BMP‐4, BMP‐5, and OPN at 16, 48, and 72 h, respectively, above control. In same conditions, treatment for 6 days with 10 µM UTP or 100 µM UDP significantly increased the ALP activity respect to control. Cells grown in osteogenic medium showed a statistically significant increase in calcium deposits at 15 and 18 days, for 10 µM ATPγ‐S treatment, and at 18 and 22 days, for [Ca2+]e treatment, respect to control but ATP‐[Ca2+]e treatment shown a significant greater mineralization at 15 days respect to ATPγ‐S, and at 18 days respect to both agonists. In conclusion, we demonstrated that an osteogenic medium containing 10 µM ATPγ‐S and 5.35 mM [Ca2+]e enhance osteogenesis and mineralization by rat primary calvarial cells cultures. J. Cell. Biochem. 117: 2658–2668, 2016. © 2016 Wiley Periodicals, Inc.
Impact of Braun anastomosis on reducing delayed gastric emptying following pancreaticoduodenectomy: a prospective, randomized controlled trial
Authors: Hwang Ho Kyoung , Lee Sung Hwan , Han Dai Hoon , Choi Sung Hoon , Kang Chang Moo , Lee Woo Jung 
Published: April 2016

AbstractBackgroundThe present study investigates the clinical impact of Braun anastomosis on delayed gastric emptying (DGE) after pylorus‐preserving pancreaticoduodenectomy (PPPD).MethodsFrom February 2013 to June 2014, 60 patients were recruited for this randomized controlled trial. The incidence of DGE and its risk factors were analyzed according to whether or not Braun anastomosis was used after PPPD.ResultsThirty patients were respectively enrolled in No‐Braun group and Braun group. A comparative analysis between the two groups showed no differences in sex, diagnosis, operation time, hospital stay, or postoperative complications, including pancreatic fistula. Overall DGE developed in eight patients (26.7%) in the Braun group and in 14 patients (46.7%) in the No‐Braun group (P = 0.108). However, clinically relevant DGE (grades B and C) was marginally more frequent in the No‐Braun group (23.3% vs. 3.3%, P = 0.052). In a multivariable analysis, No‐Braun anastomosis was an independent risk factor for developing clinically relevant DGE (odds ratio = 16.489; 95% confidence interval: 1.287–211.195; P = 0.031).ConclusionThe overall DGE occurrence was not different between the two groups. However, No‐Braun anastomosis was an independent risk factor for developing clinically relevant DGE.
Influence of body habitus on feasibility and outcome of laparoscopic liver resections: a prospective study
Authors: Ratti Francesca , D'Alessandro Valentina , Cipriani Federica , Giannone Fabio , Catena Marco , Aldrighetti Luca 
Published: April 2016

AbstractBackgroundThe aim of the present study was to prospectively investigate whether the anthropometric measures of A Body Shape Index (ABSI, taking into account waist circumference adjusted for height and weight) affects feasibility and outcome of laparoscopic liver resections.MethodsOne hundred patients undergoing laparoscopic liver resection were prospectively included in the study (2014–2015). Preoperative clinical parameters, including body mass index (BMI) and ABSI were evaluated for associations with intraoperative outcome and postoperative results (morbidity, mortality and functional recovery).ResultsTwenty‐two and 78 patients underwent major and minor hepatectomies, respectively. Conversion rate was 9%, mean blood loss was 210 ± 115 ml. Postoperative morbidity was 15% and mortality was nil. Mean length of stay was 4 days. When considering the entire series, ABSI was not associated with intra and postoperative outcome. After stratification of patients according to difficulty score, Pearson's correlation demonstrated an association between ABSI and intraoperative blood loss (P = 0.03) and time for functional recovery (P = 0.05) in patients undergoing resections with high score of difficulty.ConclusionBody habitus has an influence on outcome of laparoscopic liver resections with high degree of difficulty, while feasibility and outcome of low difficulty resections seem not to be affected by anthropometric measures.
Value of severe liver iron overload for assessing heart iron levels in thalassemia major patients
Authors: Chen Xiaodong , Zhang Hui , Yang Qihua , Luo Zebin , Zhang Zuoquan , Cheng Ziliang , Mao Jiaji , Chan Queenie , Xu Honggui , Liang Biling , Guo Hua 
Published: April 2016

PurposeThe relationship between severe liver iron overload (LIO) and heart iron overload (HIO) in transfusion‐dependent patients with thalassemia major (TM) is uncertain. Whether severe LIO can serve as an index for assessing heart iron deposition has vital clinical significance. Therefore, our aim is to determine if a close relationship exists between severe LIO and HIO.Materials and MethodsWe examined 110 TM patients who underwent T2* measurement in the liver and heart on a 1.5 Tesla MRI scanner. Various statistical analysis methods were used to assess the relationship.ResultsMost of these patients suffered from severe LIO (58.18%, liver T2* < 1.4 ms). Both Pearson's and Spearman's tests showed a significant correlation between liver T2* and heart T2* values (with a correlation coefficient of 0.408 and 0.550, respectively, both P < 0.0001). A nonlinear model, with the equation of Heart T2* = 37.974–17.684 / Liver T2*, was found to be the best model to indicate the relationship between liver T2* and heart T2*. Receiver operating characteristic (ROC) analysis showed the area under the ROC curve of liver T2* and serum ferritin for predicting HIO was 0.812 (95% confidence interval [CI]: 0.731–0.892; P < 0.0001) and 0.69 (95% CI: 0.585–0.795; P = 0.001), respectively.ConclusionOur preliminary data suggest the existence of a close relationship between severe LIO and HIO. High liver iron levels appear to increase the risk of heart iron deposition. This further supports the concept of critical liver iron concentration, above which elevated heart iron is present. J. MAGN. RESON. IMAGING 2016;44:880–889.
Preliminary investigation of multiparametric strain Z‐score (MPZS) computation using displacement encoding with simulated echoes (DENSE) and radial point interpretation method (RPIM)
Authors: Kar Julia , Cupps Brian , Zhong Xiaodong , Koerner Danielle , Kulshrestha Kevin , Neudecker Samuel , Bell Jennifer , Craddock Heidi , Pasque Michael 
Published: April 2016

PurposeTo describe and assess an automated normalization method for identifying sentinel (septal) regions of myocardial dysfunction in nonischemic, nonvalvular dilated cardiomyopathy (DCM), using an unprecedented combination of the navigator‐gated 3D spiral displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI), radial point interpolation (RPIM) and multiparametric strain z‐score (MPZS).Materials and MethodsNavigator‐gated 3D spiral DENSE, in a 1.5T MRI machine, was used for acquiring the displacement encoded complex images, MR Analytical Software System (MASS) for automated boundary detection and automated meshfree RPIM for left‐ventricular (LV) myocardial strain computation to analyze MPZS in 36 subjects (with n = 17 DCM patients). Pearson's r correlation established relations between global/sentinel MPZS and ejection fraction (EF). The time taken for combined RPIM‐MPZS computations was recorded.ResultsMaximum MPZS differences were seen between anteroseptal and posterolateral regions in the base (2.0 ± 0.3 vs. 0.9 ± 0.5) and the mid‐wall (2.1 ± 0.4 vs. 1.0 ± 0.4). These regional differences were found to be consistent with historically documented septal injury in nonischemic DCM. Correlations were 0.6 between global MPZS and EF, and 0.7 between sentinel MPZS and EF. The time taken for combined RPIM‐MPZS computations per subject was 18.9 ± 5.9 seconds.ConclusionHeterogeneous contractility found in the sentinel regions with the current automated MPZS computation scheme and the correlation found between MPZS and EF may lead to the creation of a new clinical metric in LV DCM surveillance. J. MAGN. RESON. IMAGING 2016;44:993–1002.
Nonsurgical treatment and early return to activity leads to improved Achilles tendon fatigue mechanics and functional outcomes during early healing in an animal model
Authors: Freedman Benjamin R. , Gordon Joshua A. , Bhatt Pankti R. , Pardes Adam M. , Thomas Stephen J. , Sarver Joseph J. , Riggin Corinne N. , Tucker Jennica J. , Williams Alexis W. , Zanes Robert C. , Hast Michael W. , Farber Daniel C. , Silbernagel Karin G. , Soslowsky Louis J. 
Published: April 2016

ABSTRACTAchilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3 weeks of healing. Sprague–Dawley rats (N = 100) received unilateral blunt transection of their Achilles tendon. Animals were then randomized into repaired or non‐repaired treatments, and further randomized into groups that returned to activity after 1 week (RTA1) or after 3 weeks (RTA3) of limb casting in plantarflexion. Limb function, passive joint mechanics, and tendon properties (mechanical, organizational using high frequency ultrasound, histological, and compositional) were evaluated. Results showed that both treatment and return to activity collectively affected limb function, passive joint mechanics, and tendon properties. Functionally, RTA1 animals had increased dorsiflexion ROM and weight bearing of the injured limb compared to RTA3 animals 3‐weeks post‐injury. Such functional improvements in RTA1 tendons were evidenced in their mechanical fatigue properties and increased cross sectional area compared to RTA3 tendons. When RTA1 was coupled with nonsurgical treatment, superior fatigue properties were achieved compared to repaired tendons. No differences in cell shape, cellularity, GAG, collagen type I, or TGF‐β staining were identified between groups, but collagen type III was elevated in RTA3 repaired tendons. The larger tissue area and increased fatigue resistance created in RTA1 tendons may prove critical for optimized outcomes in early Achilles tendon healing following complete rupture. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2172–2180, 2016.
N‐acetyl cysteine protects cells from chondrocyte death induced by local anesthetics
Authors: Kim Ra Jeong , Kang Jae‐Ran , Hah Young‐Sool , Park Hyung Bin 
Published: April 2016

ABSTRACTLocal anesthetics (LA) are among the drugs most frequently used for musculoskeletal problems, in procedures ranging from diagnosis to postoperative pain control. Chondrocyte toxicity induced by LA is an emerging area of concern. The purpose of this study was to determine whether N‐acetyl cysteine (NAC), an antioxidant, will exert cytoprotective effects against chondrocyte death induced by LA. Primary cultured human chondrocytes were used for this study. This study used control, NAC, LA, and NAC‐LA groups. Cytotoxicity was induced in the LA subgroups and their paired NAC‐LA subgroups through exposure to ropivacaine (0.075%), bupivacaine (0.05%), or lidocaine (0.2%) for 24 h. The NAC‐LA subgroups were exposed to 10 mM NAC for 1 h, before LA exposure. These study groups were evaluated for rates of cell viability, apoptosis, necrosis, intracellular ROS production, and caspase‐3/7 activity. Cell viability in all LA subgroups was significantly lower than in the control group (p < 0.001). Cell viability in the NAC‐LA subgroups was significantly higher than in their paired LA subgroups (p < 0.001). In the LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase‐3/7 activity were significantly higher than in the control group (p ≤ 0.029). In the NAC‐LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase‐3/7 activity were significantly lower than in their paired LA subgroups (p ≤ 0.023). These results indicate that N‐acetyl cysteine, an antioxidant, has cytoprotective effects against LA‐induced toxicity to chondrocytes in vitro. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:297–303, 2017.
Interaction between living bone particles and rhBMP‐2 in large segmental defect healing in the rat femur
Authors: Liu Fangjun , Wells James W. , Porter Ryan M. , Glatt Vaida , Shen Zhenxin , Schinhan Martina , Ivkovic Alan , Vrahas Mark S. , Evans Christopher H. , Ferreira Elisabeth 
Published: April 2016

ABSTRACTOrthopedic surgeons sometimes combine recombinant, human BMP‐2 with autograft bone when dealing with problematic osseous fractures. Although some case reports indicate success with this off‐label strategy, there have been no randomized controlled trials. Moreover, a literature search revealed only one pre‐clinical study and this was in a cranial defect model. The present project examined the consequences of combining BMP‐2 with particles of living bone in a rat femoral defect model. Human bone particles were recovered with a reamer‐irrigator‐aspirator (RIA). To allow acceptance of the xenograft as surrogate autograft, rats were administered an immunosuppressive cocktail that does not interfere with bone healing. Implantation of 200 µg living bone particles generated a small amount of new bone and defects did not heal. Graded amounts of BMP‐2 that alone provoked no healing (1.1 µg), borderline healing (5.5 µg), or full healing (11 µg) were added to this amount of bone particles. Addition of BMP‐2 (1.1 µg) increased osteogenesis, and produced bridging in 2 of 7 defects. The combination of BMP‐2 (5.5 µg) and bone particles made healing more reliable and advanced the maturation of the regenerate. Bone formation with BMP‐2 (11 µg) and bone particles showed improved maturation. Thus, the combination of autograft and BMP‐2 may be helpful clinically under conditions where the healing response is suboptimal. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2137–2145, 2016.Clinical significanceThese data support the clinical use of recombinant, human BMP‐2 with autograft bone when treating large segmental osseous defects. The combination leads to greater bone formation and accelerates the maturation of the regenerate.